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Sample records for anti human herpes

  1. Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals, improved with anti-human herpes virus treatment

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    María Lilia Diaz Betancourth

    2012-12-01

    Full Text Available 14.00 Normal 0 21 false false false ES-CO X-NONE X-NONE Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immu­nodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lym­phocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diag­nosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings’ health.

  2. Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals, improved with anti-human herpes virus treatment

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    Díaz Betancourt, María Lilia

    2012-12-01

    Full Text Available Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immunodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lymphocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient ymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient ymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diagnosis of profoundly CD4+ T lymphocytopenia etiology, when human mmunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings’ health

  3. Herpes

    Science.gov (United States)

    ... of this website will be limited. Home Visit Global Sites Search Help? Herpes Testing Share this page: Was this page helpful? Also known as: Herpes Culture; Herpes Simplex Viral Culture; HSV DNA; HSV by ...

  4. 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"...

  5. 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 ...

  6. Prevalence of Anti Human Herpes Virus-6 IgG and its Receptor in Acute Leukemia (Membrane Cofactor Protein: MCP, CD46)

    International Nuclear Information System (INIS)

    CD46 is a membrane cofactor protein, which acts as a cofactor for factor I proteolytic cleavage of C3, so it protects the cells expressing it on their surface from autologous complement attack. It has been recently described as a receptor for HHV-6. Also, it has been shown to be highly expressed on malignant cells as compared to normal cells, thus playing a major role by which these cells, either cells of haematological malignancy or cells of other body cancers, can protect themselves against complement attack so they can survive and metastasize. Patients and methods: This study has been done to detect the sero prevalence of HHV-6 among 47 Egyptian adult cases of acute leukemia using the anti-HHV-6 IgG ELISA serological technique. CD46 receptor expression and immuno phenotyping technique were performed using FCM. Twenty nine of the cases were ANLL, while 18 were ALL cases. Sixteen age- and sex-matched control cases were also studied for both anti-HHV-6 IgG and CD46 receptor expression. HHV-6 IgG antibodies were encountered in 29 (100%), 14 (77.8%) and 12 (75%) of the ANLL, ALL and the control group, cases, respectively. CD46 expression was encountered in 21 (72.4%) of the ANLL cases and in 10 (55.6%) of the ALL cases. Concordance between HHV6 sero positivity and CD46 expression was encountered in 31 cases (29 positive and 2 negative). Dis concordance was encountered in 16 cases with 14 showing HHV-6 IgG sero positivity with no CD46 expression and 2 showing the reverse. The lack of significant correlation between CD46 expression and sero positivity would exclude CD46 expression as a cause of contracting HHV-6 infection in leukemic patients

  7. Human herpes virus 6 and endogenous biotin in salivary glands.

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    Green, M.; Sviland, L; Taylor, C. E.; Peiris, M.; McCarthy, A. L.; Pearson, A. D.; Malcolm, A. J.

    1992-01-01

    AIMS: To detect the presence of human herpes virus 6 (HHV6) and endogenous biotin in paraffin wax embedded and frozen salivary glands. METHODS: Two stage indirect and streptavidin-biotin immunoperoxidase techniques were used to visualise the antigens. RESULTS: HHV6 could not be shown in any of the tissues. However, considerable endogenous biotin antigenicity was detected in the glandular elements of the paraffin wax embedded material. CONCLUSIONS: Results obtained with avidin-biotin detection...

  8. Evidence for herpes simplex viral latency in the human cornea.

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    Kaye, S. B.; Lynas, C.; Patterson, A.; Risk, J. M.; McCarthy, K.; Hart, C. A.

    1991-01-01

    Patients undergoing penetrating keratoplasty for prior herpes simplex keratitis (group A) and corneal disease unrelated to herpes simplex (group B) were investigated to assess whether the cornea is a site for herpes simplex viral latency. All patients were seropositive for herpes simplex viral antibody. Virus was isolated from the tear film postoperatively in one patient and on cocultivation from the cornea of another patient. Herpes simplex viral DNA, however, was detected in the corneas of ...

  9. Expression of varicella-zoster virus and herpes simplex virus in normal human trigeminal ganglia

    International Nuclear Information System (INIS)

    Lysates of radiolabeled explants from four human trigeminal ganglia were immunoprecipitated with antibodies to varicella-zoster virus (VZV) and to herpes simplex virus. Both herpes simplex virus- and VZV-specific proteins were detected in lysates of all four ganglia. Absence of reactivity in ganglion explants with monoclonal antibodies suggested that herpes simplex virus and VZV were not reactivated during the culture period. In situ hybridization studies demonstrated the presence of RNA transcripts from the VZV immediate early gene 63. This approach to the detection of herpes simplex virus and VZV expression in human ganglia should facilitate analysis of viral RNA and proteins in human sensory ganglia

  10. Human Herpes Virus Type 6 and Febrile Convulsion

    OpenAIRE

    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...

  11. 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.

  12. Imunoprofilaxia anti-herpética utilizando vírus geneticamente modificado: vacina DISC

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    Lupi Omar

    2003-01-01

    Full Text Available As vacinas anti-herpéticas podem atuar de forma profilática ou terapêutica contra a infecção pelo herpes simples. Diversos tipos de vacinas foram avaliados no passado com resultados pouco efetivos, tais como aquelas que utilizaram vírus vivos, porém atenuados, e as que utilizaram subunidades glicoprotéicas. As novas vacinas do tipo DISC, com partículas infectivas incapacitadas para mais de um ciclo replicativo, são desenhadas para combinar a segurança e as vantagens das vacinas que utilizam vírus atenuados com a imunogenicidade das que usam vírus vivos. Nas vacinas DISC utiliza-se um vírus cujo gene para a glicoproteína H foi removido. Torna-se, assim, capaz de infectar células humanas, exatamente como o vírus natural, mas sua progênie não pode mais completar o ciclo replicativo. São partículas virais não patogênicas, capazes de induzir ampla resposta de linfócitos T citotóxicos e da imunidade humoral contra antígenos herpéticos.

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

    OpenAIRE

    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...

  14. 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.

  15. 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.

  16. Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model

    International Nuclear Information System (INIS)

    Infection with herpes simplex virus often results in a latent infection of local sensory ganglia and a disease characterized by periodic viral reactivation and mucocutaneous lesions. The factors that trigger reactivation in humans are still poorly defined. In our study, five patients with documented histories of recurrent herpes simplex virus infection on the buttocks or sacrum were exposed to three times their minimal erythema dose of ultraviolet light. Site-specific cutaneous herpes simplex virus infection occurred at 4.4 +/- 0.4 days after exposure to ultraviolet light in 8 of 13 attempts at reactivation. We conclude that ultraviolet light can reactivate herpes simplex virus under experimentally defined conditions. This model in humans should prove useful in evaluating the pathophysiology and prevention of viral reactivation

  17. Indirect micro-immunofluorescence test for detecting type-specific antibodies to herpes simplex virus.

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    Forsey, T; Darougar, S

    1980-01-01

    A rapid indirect micro-immunofluorescence test capable of detecting and differentiating type-specific antibodies to herpes simplex virus is described. The test proved highly sensitive and, in 80 patients with active herpes ocular infection, antibody was detected in 94%. No anti-herpes antibody was detected in a control group of 20 patients with adenovirus infections. Testing of animal sera prepared against herpes simplex virus types 1 and 2 and of human sera from cases of ocular and genital h...

  18. 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.

  19. 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...

  20. 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...

  1. 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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    Gutiérrez-Fernández J

    2015-03-01

    Full Text Available José Gutiérrez-Fernández,1 Juan de Dios Luna del Castillo,2 Sara Mañanes-González,1 José Antonio Carrillo-Ávila,1 Blanca Gutiérrez,3 Jorge A Cervilla,3 Antonio Sorlózano-Puerto1 1Department of Microbiology, 2Department of Statistics and Operation Research, 3Department of Psychiatry, Institute of Neurosciences and CIBERSAM, School of Medicine and Biohealth Research Institute (Instituto de Investigación Biosanitaria IBS-Granada, University of Granada, Granada, Spain Abstract: 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 DNA in total peripheral blood was performed by nested polymerase chain reaction. The meta-analysis showed that: 1 C. pneumoniae DNA in blood and brain are more common in schizophrenic patients; 2 there is association with parasitism by T. gondii, despite the existence of publication bias; and 3 herpes viruses were not more common in schizophrenic patients. In our sample only anti-Toxoplasma immunoglobulin G was more prevalent and may be a risk factor related to schizophrenia, with potential value for prevention. Keywords: meta-analysis, analytical study, Chlamydia pneumoniae, herpes simplex virus type 1, human herpes virus 6, Toxoplasma gondii, schizophrenia

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

    Science.gov (United States)

    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

  3. 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.

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

    OpenAIRE

    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...

  5. The interplay between human herpes simplex virus infection and the apoptosis and necroptosis cell death pathways.

    Science.gov (United States)

    Yu, Xiaoliang; He, Sudan

    2016-01-01

    Human herpes simplex virus (HSV) is a ubiquitous human pathogen that establishes a lifelong latent infection and is associated with mucocutaneous lesions. In multicellular organisms, cell death is a crucial host defense mechanism that eliminates pathogen-infected cells. Apoptosis is a well-defined form of programmed cell death executed by a group of cysteine proteases, called caspases. Studies have shown that HSV has evolved strategies to counteract caspase activation and apoptosis by encoding anti-apoptotic viral proteins such as gD, gJ, Us3, LAT, and the ribonucleotide reductase large subunit (R1). Recently, necroptosis has been identified as a regulated form of necrosis that can be invoked in the absence of caspase activity. Receptor-interacting kinase 3 (RIP3 or RIPK3) has emerged as a central signaling molecule in necroptosis; it is activated via interaction with other RIP homotypic interaction motif (RHIM)-containing proteins such as RIP1 (or RIPK1). There is increasing evidence that HSV R1 manipulates necroptosis via the RHIM-dependent inactivation or activation ofRIP3 in a species-specific manner. This review summarizes the current understanding of the interplay between HSV infection and cell death pathways, with an emphasis on apoptosis and necroptosis. PMID:27154074

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

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    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

  7. 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.

  8. 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

  9. Griffithsin and Carrageenan Combination To Target Herpes Simplex Virus 2 and Human Papillomavirus.

    Science.gov (United States)

    Levendosky, Keith; Mizenina, Olga; Martinelli, Elena; Jean-Pierre, Ninochka; Kizima, Larisa; Rodriguez, Aixa; Kleinbeck, Kyle; Bonnaire, Thierry; Robbiani, Melissa; Zydowsky, Thomas M; O'Keefe, Barry R; Fernández-Romero, José A

    2015-12-01

    Extensive preclinical evaluation of griffithsin (GRFT) has identified this lectin to be a promising broad-spectrum microbicide. We set out to explore the antiviral properties of a GRFT and carrageenan (CG) combination product against herpes simplex virus 2 (HSV-2) and human papillomavirus (HPV) as well as determine the mechanism of action (MOA) of GRFT against both viruses. We performed the experiments in different cell lines, using time-of-addition and temperature dependence experiments to differentiate inhibition of viral attachment from entry and viral receptor internalization. Surface plasmon resonance (SPR) was used to assess GRFT binding to viral glycoproteins, and immunoprecipitation and immunohistochemistry were used to identify the specific glycoprotein involved. We determined the antiviral activity of GRFT against HSV-2 to be a 50% effective concentration (EC50) of 230 nM and provide the first evidence that GRFT has moderate anti-HPV activity (EC50 = 0.429 to 1.39 μM). GRFT blocks the entry of HSV-2 and HPV into target cells but not the adsorption of HSV-2 and HPV onto target cells. The results of the SPR, immunoprecipitation, and immunohistochemistry analyses of HSV-2 combined suggest that GRFT may block viral entry by binding to HSV-2 glycoprotein D. Cell-based assays suggest anti-HPV activity through α6 integrin internalization. The GRFT-CG combination product but not GRFT or CG alone reduced HSV-2 vaginal infection in mice when given an hour before challenge (P = 0.0352). While GRFT significantly protected mice against vaginal HPV infection when dosed during and after HPV16 pseudovirus challenge (P < 0.026), greater CG-mediated protection was afforded by the GRFT-CG combination for up to 8 h (P < 0.0022). These findings support the development of the GRFT-CG combination as a broad-spectrum microbicide. PMID:26369967

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

    OpenAIRE

    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 ...

  11. 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.

  12. 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.

  13. 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...

  14. 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.

  15. 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...

  16. Evaluation of Cynanchum otophyllum glucan sulfate against human immunodeficiency virus and herpes simplex virus as a microbicide agent

    Directory of Open Access Journals (Sweden)

    Jian Tao

    2011-01-01

    Full Text Available Objective : The root ofCynanchum otophyllum -also known as Qing Yang Sheng-is a traditional ethnical Chinese medicine. The objective of this study was to evaluate in vitro activities and safety of C. otophyllum glucan sulfate (PS20 against Human Immunodeficiency Virus (HIV and Herpes Simplex Virus (HSV. Materials and Methods : Anti-HIV activity was detected with syncytial formation assay and quantitative P24 Enzyme-Linked Immunosorbent Assay (ELISA. Anti-HSV activity was detected with plaque reduction assay; cytotoxicity was tested with MTT colorimetric assay; and anti-bacterial activity was tested with microdilution method. Anti-HIV mechanism was investigated with fusion inhibition, time of addition, and pretreatment. Results : The 50% Inhibition Concentration (IC 50 of PS20 for HIV-1 IIIB , HIV- Ada-M , HIV-1 Bal , HSV-I, and -II were 0.26 ± 0.02 mM, 0.46 ± 0.02 mM, 0.90 ± 0.04 mM, 3.45 ± 0.85 mM, and 0.70 ± 0.22 mM, respectively. Selectivity Indices (SI were 653, 50, 39, 85, and 362, respectively. Studies on anti-HIV mechanism of PS20 showed that the target molecule should be the envelope protein. The 50% Cytotoxicity Concentrations (CC 50 of PS20 for HeLa and ME-180 cell lines and human foreskin fibroblast cells was more than 70 mM. The Minimum Inhibitory Concentration (MIC for vaginal lactobacilli was more than 1000 mM. Conclusion : PS20 possesses anti-HIV and HSV effect and low cytotoxicity to epithelium cells and vaginal lactobacilli. It may be considered as a potential microbicide agent for further investigation.

  17. 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

  18. 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...

  19. 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.

  20. 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

  1. [PCR study of the human herpes virus type 6 and other viruses of the herpes group in eye diseases].

    Science.gov (United States)

    Slepowa, O S; Svetlova, E V; Kovaleva, L A; Makarov, P V; Kugusheva, A E; Denisova, E V; Vahova, E S; Zaharova, G Yu; Kondrat'eva, Yu A; Andryushin, A E; Demkin, V V

    2015-01-01

    To study the role of the HHV-6 type in the development of eye diseases PCR tests of blood (152), cornea biopsies (61), and intraocular fluids (11) for HHV-6 and other viruses of the herpes group (HSV type 1 and 2, CMV, EBV) were conducted. It was found that the HHV-6, along with other representatives of the Herpesviridae, can be detected in patients with different clinical forms of ophthalmopathology (174 patients were surveyed). Viral DNA was detected in blood, cornea, and in the anterior chamber fluid. The obtained data allow that the HHV-6 to be suggested as a possible cause of the ophthalmic herpes along with the other viruses of this group. It makes finding the virus DNA an essential step towards setting the etiologic diagnosis of the ophthalmological patients. PMID:27024918

  2. 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 ...

  3. 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.

  4. 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...

  5. 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......-like phenotype and that down-regulation of vGPCR expression results in reduced expression of angiogenic factors and regression of the lesions. Together, these findings implicate vGPCR as a key element in KS pathogenesis and suggest that strategies to block its function may represent a novel approach for the...

  6. Anti-herpes simplex virus activities of Eugenia caryophyllus (Spreng.) Bullock & S. G. Harrison and essential oil, eugenol.

    Science.gov (United States)

    Tragoolpua, Y; Jatisatienr, A

    2007-12-01

    In this study, an extract from the flower buds of Eugenia caryophyllus (Spreng.) Bullock & S. G. Harrison and the essential oil, eugenol, were evaluated for their anti-herpes simplex virus properties on standard HSV-1(F), standard HSV-2(G) and ten HSV isolates. The plaque reduction assay showed that HSV-1(F), HSV-2(G), two HSV-1 isolates (2, 30) and four HSV-2 isolates (1, 2, 3, 21) were inhibited by E. caryophyllus. Only HSV-1 isolates 1 and 30 were inhibited by eugenol. Thus, strains or isolates of viruses may affect the range of inhibition. Moreover, particles of HSV standard strains were directly inactivated by E. caryophyllus and eugenol. The total virus yield of HSV standard strains and isolates at 30 h also declined after treatment with E. caryophyllus and eugenol. The E. caryophyllus extract exerted higher antiviral replication on HSV-2(G) than on HSV-1(F). The inhibition of the viral yield of HSV-1 isolates was higher than standard HSV-1(F) and standard HSV-2(G) was also inhibited more than most of the HSV-2 isolates. The anti-HSV activity of eugenol against HSV-1(F) and HSV isolates was stronger than with the E. caryophyllus crude extract. However, the percentage inhibition was more pronounced on HSV-1(F) than on HSV-2(G). Moreover, HSV-1(1) and HSV-2(1, 32) could not replicate when eugenol was included in the assay. PMID:17628885

  7. Herpes Simplex (Cold Sores and Genital Herpes)

    Science.gov (United States)

    ... 2014 Select a Language: Fact Sheet 508 Herpes Simplex (Cold Sores and Genital Herpes) WHAT IS HERPES? ... PREVENTED? THE BOTTOM LINE WHAT IS HERPES? Herpes simplex refers to a group of viruses that infect ...

  8. 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

  9. 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.

  10. 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.

  11. 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 ...

  12. 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...

  13. 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.

  14. 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 ...

  15. Elimination of Fc receptor binding of human immunoglobulin G in immunofluorescence assays for herpes simplex virus antibodies.

    OpenAIRE

    Gallo, D

    1986-01-01

    The binding of human immunoglobulin G by Fc receptors in herpes simplex virus (HSV)-infected cells can cause false-positive interpretations in the immunofluorescence test for HSV antibody. When the infected cell smears were treated with 10% glacial acetic acid for 5 min and rinsed in phosphate-buffered saline before the immunofluorescence test was performed, the Fc receptors were completely inactivated, resulting in a reliable method for HSV antibody detection.

  16. Entry of Oncolytic Herpes Simplex Virus into Human Squamous Cell Carcinoma Cells by Ultrasound

    Directory of Open Access Journals (Sweden)

    Shusuke Okunaga

    2015-10-01

    Full Text Available Low-intensity ultrasound is a useful method to introduce materials into cells due to the transient formation of micropores, called sonoporations, on the cell membrane. Whether oncolytic herpes simplex virus type 1 (HSV-1 can be introduced into oral squamous cell carcinoma (SCC cells through membrane pores remains undetermined. Human SCC cell line SAS and oncolytic HSV-1 RH2, which was deficient in the 134.5 gene and fusogenic, were used. Cells were exposed to ultrasound in the presence or absence of microbubbles. The increase of virus entry was estimated by plaque numbers. Viral infection was hardly established without the adsorption step, but plaque number was increased by the exposure of HSV-1-inoculated cells to ultrasound. Plaque number was also increased even if SAS cells were exposed to ultrasound and inoculated with RH2 without the adsorption step. This effect was abolished when the interval from ultrasound exposure to virus inoculation was prolonged. Scanning electron microscopy revealed depressed spots on the cell surface after exposure to ultrasound. These results suggest that oncolytic HSV-1 RH2 can be introduced into SAS cells through ultrasound-mediated pores of the cell membrane that are resealed after an interval.

  17. Ganciclovir uptake in human mammary carcinoma cells expressing herpes simplex virus thymidine kinase

    International Nuclear Information System (INIS)

    Assessment of suicide enzyme activity would have considerable impact on the planning and the individualization of suicide gene therapy of malignant tumors. This may be done by determining the pharmacokinetics of specific substrates. We generated ganciclovir (GCV)-sensitive human mammary carcinoma cell lines after transfection with a retroviral vector bearing the herpes simplex virus thymidine kinase (HSV-tk) gene. Thereafter, uptake measurements and HPLC analyses were performed up to 48 h in an HSV-tk-expressing cell line and in a wild-type cell line using tritiated GCV. HSV-tk-expressing cells showed higher GCV uptake and phosphorylation than control cells, whereas in wild-type MCF7 cells no phosphorylated GCV was detected. In bystander experiments the total GCV uptake was related to the amount of HSV-tk-expressing cells. Furthermore, the uptake of GCV correlated closely with the growth inhibition (r=0.92). Therefore, the accumulation of specific substrates may serve as an indicator of the HSV-tk activity and of therapy outcome. Inhibition and competition experiments demonstrated slow transport of GCV by the nucleoside carriers. The slow uptake and low affinity to HSV-tk indicate that GCV is not an ideal substrate for the nucleoside transport systems or for HSV-tk. This may be the limiting factor for therapy success, necessitating the search for better substrates of HSV-tk

  18. Enhanced replication of herpes simplex virus type 1 in human cells

    International Nuclear Information System (INIS)

    The effects of DNA-damaging agents on the replication of herpes simplex virus type 1 (HSV-1) were assessed in vitro. Monolayers of human lung fibroblast cell lines were exposed to DNA-damaging agents (methyl methanesulfonate [MMS], methyl methanethiosulfonate [MMTS], ultraviolet light [UV], or gamma radiation [GR]) at specific intervals, before or after inoculation with low levels of HSV-1. The ability of cell monolayers to support HSV-1 replication was measured by direct plaque assay and was compared with that of untreated control samples. In this system, monolayers of different cell lines infected with identical HSV-1 strains demonstrated dissimilar levels of recovery of the infectious virus. Exposure of DNA-repair-competent cell cultures to DNA-damaging agents produced time-dependent enhanced virus replication. Treatment with agent before virus inoculation significantly (p less than 0.025) increased the number of plaques by 10 to 68%, compared with untreated control cultures, while treatment with agent after virus adsorption significantly increased (p less than 0.025) the number of plaques by 7 to 15%. In a parallel series of experiments, cells deficient in DNA repair (xeroderma pigmentosum) failed to support enhanced virus replication. These results suggest that after exposure to DNA-damaging agents, fibroblasts competent in DNA repair amplify the replication of HSV-1, and that DNA-repair mechanisms that act on a variety of chromosomal lesions may be involved in the repair and biological activation of HSV-1 genomes

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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...

  4. 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...

  5. 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.

  6. 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...

  7. 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

  8. 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 ...

  9. 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

  10. 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

  11. Herpes simplex virus type-1 and human lymphocytes: virus expression and the response to infection of adult and foetal cells

    International Nuclear Information System (INIS)

    The growth of Herpes simplex virus type 1 (HSV-1) in human lymphocytes of adult and foetal origin was studied. Virus DNA synthesis, antigen and particle production and the yield of infectious progeny were determined in cultured lymphocytes with or without exposure to stimulating concentrations of the mitogen phytohaemagglutinin and pokeweed mitogen. Separated subpopulations of cells were examined and the conclusion reached that only the stimulated T-lymphoblast was permissive for full virus expression. Stimulation of cell DNA synthesis in response to infection was observed in cultures of adult and foetal lymphocytes under conditions which were non-permissive for virus growth. Morphological change and prolonged culture survival were a feature of foetal lymphocytes exposed to u.v. irradiated HSV-1. (author)

  12. Neonatal herpes simplex pneumonia.

    OpenAIRE

    Lissauer, T J; Shaw, P. J.; Underhill, G

    1984-01-01

    A neonate with herpes simplex pneumonia is described. Herpes simplex infection should be considered in the differential diagnosis of pneumonia in newborn infants, even in the absence of clinically apparent herpes in the mother.

  13. 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 ...

  14. 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 ...

  15. A subset of human plasmacytoid dendritic cells expresses CD8α upon exposure to herpes simplex virus type 1.

    Science.gov (United States)

    Schuster, Philipp; Thomann, Sabrina; Werner, Maren; Vollmer, Jörg; Schmidt, Barbara

    2015-01-01

    Classical and plasmacytoid dendritic cells (DC) play important roles in the defense against murine and human infections with herpes simplex virus (HSV). So far, CD8α expression has only been reported for murine DC. CD8α(+) DC have prominent cross-presenting activities, which are enhanced by murine CD8α(+) PDC. The human orthologue of murine CD8α(+) DC, the CD141 (BDCA3)(+) DC, mainly cross-present after TLR3 ligation. We report here the serendipitous finding that a subset of human PDC upregulates CD8α upon HSV-1 stimulation, as shown by gene array and flow cytometry analyses. CD8α, not CD8ß, was expressed upon exposure. Markers of activation, migration, and costimulation were upregulated on CD8α-expressing human PDC. In these cells, increased cytokine and chemokine levels were detected that enhance development and function of T, B, and NK cells, and recruit immature DC, monocytes, and Th1 cells, respectively. Altogether, human CD8α(+) PDC exhibit a highly activated phenotype and appear to recruit other immune cells to the site of inflammation. Further studies will show whether CD8α-expressing PDC contribute to antigen cross-presentation, which may be important for immune defenses against HSV infections in vitro and in vivo. PMID:26082771

  16. Human Rights and Cohen's Anti-Statism

    DEFF Research Database (Denmark)

    Lippert-Rasmussen, Kasper

    2014-01-01

    , 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 than it would have been had a police officer done it on behalf of the state. To this extent the standard liberal understanding of human rights is statist. This parallel between liberal understandings of distributive justice and human rights raises two questions: (1) Is the statist...

  17. A lymphoblastoid response of human foetal lymphocytes to ultraviolet-irradiated herpes simplex virus

    International Nuclear Information System (INIS)

    Cultures of foetal lymphocytes were exposed to u.v.-irradiated herpes simplex virus (HSV). The cells responded with increased 6-3H-thymidine incorporation, the formation of clumps of enlarged lymphoblastoid cells and cell division. This response was first detected 3 to 4 days after exposure to virus material and was shown to be virus-dose dependent. The ability to stimulate foetal cells was considerably more u.v. resistant than infectivity. Two isolates of HSV type 2 (4663 and 37174), which had a high 'transforming' ability, produced large numbers of non-infectious particles (particle: infectivity ratios in excess of 104). The cells, which responded to u.v.-irradiated HSV with blastoid transformation, were associated with the non-E-rosetting (T-cell-depleted) subpopulation. (author)

  18. 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.

  19. Prevalência do herpes-vírus humano tipo 1 em neoplasias cutâneas epiteliais malignas Prevalence of human herpes virus type 1 in epithelial skin cancer

    Directory of Open Access Journals (Sweden)

    Sylvia Ypiranga

    2009-04-01

    Full Text Available FUNDAMENTOS - O DNA viral pode atuar como oncogene, favorecendo o desenvolvimento de neoplasias, como as linfoides e da pele. Entre esses vírus, encontram-se alguns herpes-vírus humanos. OBJETIVO - Identificar a presença de DNA do herpes-vírus humano tipo 1 em neoplasias epiteliais pré-malignas,malignas e pele normal de indivíduos controle, avaliando seu papel na carcinogênese. MÉTODOS - Identificação, por reação em cadeia da polimerase, do DNA viral do tumor e pele sã de 41 pacientes e comparação com grupo controle, sem neoplasia. Análise estatística: Testes de Fisher e de McNemar. RESULTADOS - O vírus foi identificado em 20 indivíduos sem e em 21 com neoplasia. Destes últimos, 11 o expessaram apenas nas células tumorais. A diferença, entretanto, não foi estatisticamente significante. CONCLUSÕES - Parece não haver relação direta entre o encontro do DNA viral na pele sã e na pele tumoral. Sua presença pode facilitar o desenvolvimento da neoplasia ou apenas coincidir de se localizar onde esta já ocorreu.BACKGROUND - Viral DNA may act as an oncogene, especially in skin and lymphoid organs. This group includes some human herpes virus. OBJECTIVE - To identify human herpes virus type 1 DNA in pre-malignant and malignant skin samples of epithelial tumors comparing to normal skin to determine its role in carcinogenesis. METHODS - Forty-one patients with epithelial tumors were submitted to biopsies from tumor and normal skin. The control group comprised 41 biopsies from patients with other dermatoses than cancer. After DNA extraction, polymerase chain reaction was performed to identify 199-bp band. The results were statistically evaluated by Fisher and McNemar tests. RESULTS - The virus was identified in 20 subjects without cancer and in 21 with skin cancer. From these, 11 expressed it only in tumor cells. This difference was not significant. CONCLUSION - There seem to be no direct relation between viral findings in normal

  20. 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...

  1. 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...

  2. 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...

  3. 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)

  4. 5-(1-Substituted) alkyl pyrimidine nucleosides as antiviral (herpes) agents.

    Science.gov (United States)

    Kumar, Rakesh

    2004-10-01

    The treatment of viral diseases remains one of the major challenges to modern medicine. During the past two decades there has been increased recognition of the consequences of serious viral illnesses that are not controlled by vaccination. These illnesses include human immunodeficiency virus, human herpes viruses, and viruses that cause hepatitis. There are now eight pathogens recognized in the herpes virus family that cause infections in humans. Infections by the herpes viruses are opportunistic and often life-threatening, leading to significant morbidity and mortality in the increasing number of chronically immune compromised individuals such as AIDS patients, cancer patients and transplant recipients on immunosuppressive therapy. Nearly all individuals with AIDS are infected with one or more of the herpes viruses. Antiviral therapy with guanosine nucleoside analogs acyclovir and ganciclovir has had a major impact on diseases caused by herpes simplex virus type-1 and type-2 (HSV-1, HSV-2), Varicella zoster virus (VZV), and human cytomegalovirus (HCMV) but development of resistant virus strains and the absence of any effective treatment for other members of the herpes family provide a stimulus for increased search of new agents effective against various herpes viruses. Pyrimidine nucleosides have taken up an important role in the therapy of virus infection. Significant progress in the study of anti-herpes nucleosides has been made by the advent of 5-substituted pyrimidine nucleosides such as 5-iodo-, 5-ethyl-, 5-(2-chloroethyl)-, and (E)-5-(2-bromovinyl)- derivatives of 2'-deoxyuridine. These are highly specific inhibitors of HSV-1, HSV-2, and/or VZV infections. However, Epstein Barr virus (EBV) and HCMV are much less sensitive to these agents. In 5-substituted pyrimidine nucleosides the nature of substituents, particularly at the C-5 position, has been found to be an important determinant of anti-herpes activity. Structural requirements at the C-2 carbon of the 5

  5. 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

  6. 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.

  7. 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

  8. 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%)

  9. Suppression of human papillomavirus gene expression in vitro and in vivo by herpes simplex virus type 2 infection

    International Nuclear Information System (INIS)

    Recent epidemiological studies have found that women infected with both herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) type 16 or HPV-18 are at greater risk of developing cervical carcinoma compared to women infected with only one virus. However, it remains unclear if HSV-2 is a cofactor for cervical cancer or if HPV and HSV-2 interact in any way. We have studied the effect of HSV-2 infection on HPV-11 gene expression in an in vitro double-infection assay. HPV transcripts were down-regulated in response to HSV-2 infection. Two HSV-2 vhs mutants failed to reduce HPV-16 E1-circumflexE4 transcripts. We also studied the effect of HSV-2 infection on preexisting experimental papillomas in a vaginal epithelial xenograft model. Doubly infected grafts demonstrated papillomatous transformation and the classical cytopathic effect from HSV-2 infection. HPV and HSV DNA signals were mutually exclusive. These studies may have therapeutic applications for HPV infections and related neoplasms

  10. Human rights orientation and modern anti-Semitism

    OpenAIRE

    Johannes Kopf-Beck

    2011-01-01

    The manifestations of anti-Semitism in Germany have changed since the end of WWII. Whereas in the past German anti-Semitism was overtly racist, today it is characterized more by subtle and latent facets. How are these modern facets, such as secondary anti-Semitism, latent anti-Semitism and anti-Semitic criticism of Israel, related to human rights orientations? A survey of experts and a pre-study provided the basis for developing the Human Rights Orientation Scale, which includes the four s...

  11. Herpes simplex virus infections of women and their offspring: implications for a developed society.

    OpenAIRE

    Whitley, R J

    1994-01-01

    Herpes simplex virus infections of humans have been known since ancient times. Contemporary society has witnessed a series of devastating manifestations of herpes simplex virus infections--namely, genital herpes simplex virus infection and neonatal herpes simplex virus infection. With the evolution of society, particularly advances in birth control and increasing promiscuity, the seroprevalence of herpes simplex virus type 2 infections has increased worldwide, however, more so in developed so...

  12. The High Prevalence of Herpes Simplex Virus Type 1 DNA in Human Trigeminal Ganglia Is Not a Function of Age or Gender▿

    OpenAIRE

    Hill, James M.; Ball, Melvyn J.; Neumann, Donna M.; Azcuy, Ann M.; Bhattacharjee, Partha S.; Bouhanik, Saadallah; Clement, Christian; Lukiw, Walter J.; Foster, Timothy P.; Kumar, Manish; Kaufman, Herbert E.; Hilary W. Thompson

    2008-01-01

    The purpose of this study was to determine the presence and copy numbers of herpes simplex virus type 1 (HSV-1) DNA in human trigeminal ganglia (TG) with respect to age, gender, and postmortem interval (PMI). Human TG (n = 174, obtained from the Oregon Brain Bank, with data on age, gender, and PMI) were analyzed for HSV-1 DNA copies (HSV-1 DNA polymerase gene) by using real-time PCR. We found that 89.1% (131/147) of subjects and 90.1% (155/174) of TG contained HSV-1 DNA. The copy numbers of H...

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

    OpenAIRE

    Rajasekaran S; Abhiskek Chatterjee; Gopalkrishna Rao

    2012-01-01

    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 ...

  14. 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 ...

  15. Inducible gene expression of the human immunodeficiency virus LTR in a replication-incompetent herpes simplex virus vector.

    Science.gov (United States)

    Warden, M P; Weir, J P

    1996-12-01

    Although replication-incompetent herpes simplex virus (HSV) vectors have the capability to express foreign genes, successful development of these vectors for gene delivery would require that expression of the foreign gene be regulated. To investigate the feasibility of obtaining inducible expression of a foreign gene in such a vector, a replication-incompetent HSV vector, vd120/LTR beta, was developed that used the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) to express the Escherichia coli lacZ gene. Examination of lacZ expression from the HIV-1 LTR in vd120/LTR beta-infected cells indicated that the LTR was active as a promoter under both replicating and nonreplicating conditions, although expression of lacZ under nonreplicating conditions was approximately 4-fold lower. In addition, the LTR expressed lacZ in a manner distinct from that of well-characterized HSV-1 promoters of each temporal class. The effect of the HIV-1 regulatory protein Tat on expression from the LTR in vd120/LTR beta was examined by infection of two different HeLa-derived cell lines that constitutively expressed Tat, HL2/3, and HLtat. Compared to infection of HeLa cells, lacZ expression from vd120/LTR beta-infected HL2/3 and HLtat cells increased from 4- to 24-fold, depending on the multiplicity of vector infection. Sustained expression of lacZ from the LTR in vd120/LTR beta-infected cells was not observed even in the continuous presence of Tat, although vector could be recovered for up to 5 days after infection. However, the amount of recoverable vector decreased during this time, suggesting that cellular cytotoxicity may account for some of the decrease in Tat-mediated expression from the LTR. PMID:8941330

  16. Human rights orientation and modern anti-Semitism

    Directory of Open Access Journals (Sweden)

    Johannes Kopf-Beck

    2011-04-01

    Full Text Available The manifestations of anti-Semitism in Germany have changed since the end of WWII. Whereas in the past German anti-Semitism was overtly racist, today it is characterized more by subtle and latent facets. How are these modern facets, such as secondary anti-Semitism, latent anti-Semitism and anti-Semitic criticism of Israel, related to human rights orientations? A survey of experts and a pre-study provided the basis for developing the Human Rights Orientation Scale, which includes the four subscales of Endorsement, Application, Restriction and Willingness to engage in human rights activity. In a study of 304 German subjects, data was collected on human rights orientations and facets of modern anti-Semitism. The present paper introduces the questionnaire, discusses the relevance of the study for determining the relationships between human rights orientations and facets of modern anti-Semitism and summarizes the study's implications for viewing secondary anti-Semitism and prejudicial criticism of Israel as facets of modern anti-Semitism.

  17. Use of multiplex PCR and real-time PCR to detect human herpes virus genome in ocular fluids of patients with uveitis

    OpenAIRE

    Sugita, S.; Shimizu, N; Watanabe, K.; Mizukami, M; Morio, T.; Sugamoto, Y; Mochizuki, M.

    2008-01-01

    Aim: To measure the genomic DNA of human herpes viruses (HHV) in the ocular fluids and to analyse the clinical relevance of HHV in uveitis. Methods: After informed consent was obtained, a total of 111 ocular fluid samples (68 aqueous humour and 43 vitreous fluid samples) were collected from 100 patients with uveitis. The samples were assayed for HHV-DNA (HHV1–8) by using two different polymerase chain reaction (PCR) assays, qualitative PCR (multiplex PCR) and quantitative PCR (real-time PCR)....

  18. 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 ...

  19. 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.

  20. Evidence for an involvement of thymidine kinase in the excision repair of ultraviolet-irradiated herpes simplex virus in human cells

    International Nuclear Information System (INIS)

    A wild-type strain of herpes simplex virus type 1 (HSV-1:KOS) encoding a functional thymidine kinase (tk+) and a tk- mutant strain (HSV-1:PTK3B) were used to study the role of the viral tk in the repair of UV-irradiated HSV-1 in human cells. UV survival of HSV-1:PTK3B was substantially reduced compared with that of HSV-1:KOS when infecting normal human cells. In contrast, the UV survival of HSV-1:PTK3B was similar to that of HSV-1:KOS when infecting excision repair-deficient cells from a xeroderma pigmentosum patient from complementation group A. These results suggest that the repair of UV-irradiated HSV-1 in human cells depends, in part at least, on expression of the viral tk and that the repair process influenced by tk activity is excision repair or a process dependent on excision repair

  1. Human Rights and Anti-Semitism after Gaza

    OpenAIRE

    Ramón Grosfoguel

    2009-01-01

    This article analyzes the consequences of the latest Israel massacres in Gaza in relation to their global consequences in reference to human rights and global Anti-Semitism in actuality. The first part examines the consequences of Gaza in light of human rights. The second part is an analysis of the consequences of Gaza in reference to global Anti- Semitism. The last part analyzes global fundamentalism in the current world.

  2. 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.

  3. 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 ...

  4. [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

  5. Determination of suitable housekeeping genes for normalisation of quantitative real time PCR analysis of cells infected with human immunodeficiency virus and herpes viruses

    Directory of Open Access Journals (Sweden)

    Wilkinson John

    2007-12-01

    Full Text Available Abstract The choice of an appropriate housekeeping gene for normalisation purposes has now become an essential requirement when designing QPCR experiments. This is of particular importance when using QPCR to measure viral and cellular gene transcription levels in the context of viral infections as viruses can significantly interfere with host cell pathways, the components of which traditional housekeeping genes often encode. In this study we have determined the reliability of 10 housekeeping genes in context of four heavily studied viral infections; human immunodeficiency virus type 1, herpes simplex virus type 1, cytomegalovirus and varicella zoster virus infections using a variety of cell types and virus strains. This provides researchers of these viruses with a shortlist of potential housekeeping genes to use as normalisers for QPCR experiments.

  6. 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

  7. 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

  8. Herpes simplex encephalitis

    International Nuclear Information System (INIS)

    Early institution of therapy with acyclovir is essential for the successful outcome in herpes simplex encephalitis. Brain biopsy remains the only conclusive means of establishing the diagnosis, but many fear possible biobsy complications. Thus, therapy is often instituted when the diagnosis is clinically suspected, even though cerebral computed tomography and other diagnostic studies may be inconclusive. Nuclear magnetic resonance imaging (NMR) has proven to be a sensitive tool for diagnosing presumptive herpes simplex encephalitis. This case presentation demonstrates the superiority of cerebral NMR over computerized tomography for detecting early temporal lobe changes consistent with acute herpes simplex encephalitis

  9. 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 ...

  10. 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 ...

  11. 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...

  12. Herpes –zoster: An update

    Directory of Open Access Journals (Sweden)

    Bansal Puja, Bhargava Deepak, Ali Sheeba

    2013-10-01

    Full Text Available Herpes zoster (HZ is the reactivated form of the Varicella zoster virus (VZV, the same virus responsible for chickenpox. The condition produces a striking picture, with a blistering, crusting rash confined to well demarcated areas of the body. Latency is typically life long, and Herpes Zoster is caused by viral reactivation from the latent state. The survival of Varicella Zoster Virus in human for several million years attests to its success. Present review provides an overview of the natural history, epidemiology and possible complications of varicella zoster virus along with diagnosis, prophylaxis and different treatment modalities.

  13. Activation of human immunodeficiency virus by herpesvirus infection: identification of a region within the long terminal repeat that responds to a trans-acting factor encoded by herpes simplex virus 1.

    OpenAIRE

    Mosca, J D; Bednarik, D P; Raj, N B; Rosen, C A; Sodroski, J G; Haseltine, W A; Hayward, G S; Pitha, P. M.

    1987-01-01

    Herpes simplex virus 1 (HSV-1) infection induces transcription of the chloramphenicol acetyltransferase (CAT) gene directed by the long terminal repeat (LTR) of human immunodeficiency virus (HIV) in both transiently and permanently transfected cells containing the HIV-LTR/CAT hybrid gene. To define the mechanism by which HSV-1 stimulates the HIV LTR, we examined the effects of isolated regulatory genes from HSV-1. The results of cotransfection assays with the immediate-early (IE) genes of HSV...

  14. [{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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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...

  20. 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.

  1. 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

  2. Human telomerase reverse-transcriptase promoter-controlled and herpes simplex virus thymidine kinase-armed adenoviruses for renal cell carcinoma treatment

    Directory of Open Access Journals (Sweden)

    Tian DW

    2013-04-01

    Full Text Available Dawei Tian,1–4 Yan Sun,3 Yang Yang,2,3 Mingde Lei,3 Na Ding,3 Ruifa Han2,31Tianjin Medical University, Tianjin, People's Republic of China; 2Department of Urinary Surgery, 3Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin, People's Republic of China; 4Tianjin Nankai Hospital, Tianjin, People's Republic of ChinaAbstract: New treatment strategies are required for renal cell carcinoma (RCC due to its relative insensitivity to conventional radio- and chemotherapies. The promising strategy of tumor inhibition using human telomerase reverse transcriptase (hTERT-controlled herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV in the hTERT promoter-driven HSV-TK/GCV suicide gene system was investigated. Tumor volume, weight, relative proliferation rate, and cell-apoptosis levels were examined in mice injected with adenovirus (Ad-hTERT-HSV-TK and GCV. Increased cell death occurred following treatment with Ads carrying hTERT-HSV-TK/GCV or cytomegalovirus promoter-controlled (CMV-HSV-TK/GCV for human RCC 786-0 and fibroblast MRC-5 cells. In mice, Ad-hTERT-HSV-TK/GCV more specifically inhibited tumor and RCC xenograft growth than Ad-CMV-HSV-TK/GCV (P < 0.05. Furthermore, Ad-hTERT-HSV-TK/GCV did not significantly damage normal fibroblasts or organ systems (heart, lung, liver, brain, kidney, and spleen. Thus, Ad-hTERT-HSV-TK/GCV is an effective RCC inhibitor in human cells in vitro and in vivo mouse models, indicating potential usefulness in RCC-targeted gene therapy.Keywords: hTERT promoter, HSV-TK/GCV, renal cell carcinoma, adenovirus

  3. 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

  4. Herpes zoster infection

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    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.

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

    OpenAIRE

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

    2014-01-01

    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 endot...

  6. TXU (Anti-CD7)-Pokeweed Antiviral Protein as a Potent Inhibitor of Human Immunodeficiency Virus

    OpenAIRE

    Uckun, Fatih M.; Chelstrom, Lisa M.; Tuel-Ahlgren, Lisa; Dibirdik, Ilker; Irvin, James D.; Langlie, Mridula-Chandan; Myers, Dorothea E.

    1998-01-01

    We have evaluated the clinical potential of TXU (anti-CD7)-pokeweed antiviral protein (PAP) immunoconjugate (TXU-PAP) as a new biotherapeutic anti-human immunodeficiency virus (anti-HIV) agent by evaluating its anti-HIV type 1 (anti-HIV-1) activity in vitro, as well as in a surrogate human peripheral blood lymphocyte-severe combined immunodeficient (Hu-PBL-SCID) mouse model of human AIDS. The present report documents in a side-by-side comparison the superior in vitro anti-HIV-1 activity of TX...

  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. Virus-specific HLA-restricted lysis of herpes simplex virus-infected human monocytes and macrophages mediated by cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    Freshly-isolated peripheral blood human monocytes and 5 day in vitro cultured macrophages were infected with herpes simplex virus type 1 (HSV-1), labeled with 51Cr, and used as target cells in a 12-14 hour cell-mediated cytotoxicity assay. Mononuclear leukocytes (MNL) from HSV-1 non-immune individuals, whether unstimulated or stimulated with HSV-1 antigen, did not mediate significant lysis of either target cell. HSV-immune MNL, both freshly-isolated and cultured for 5 days without antigen, demonstrated only low levels of natural killer (NK) cell-mediate lysis. MNL from HSV-immune individuals incubated for 5 days in vitro with HSV-1 antigen mediated significant virus-specific lysis of both target cells. Mean virus-specific lysis of autologous monocytes was 8.5(/+-/2.0)% compared to a three-fold greater virus-specific lysis of autologous macrophages. Greater than 70% of this lytic activity was mediated by Leu-11-negative, T3-positive cytotoxic T lymphocytes (CTL). Allogeneic target cells lacking a common HLA determinant were not significantly lysed while T8-positive CTL mediated infrequent lysis of target cells sharing a common HLA-A and/or HLA-B determinant. T4-positive lymphocytes were demonstrated to be the predominant cell mediating lysis of autologous target cells and allogeneic target cells sharing both HLA-A and/or HLA-B plus HLA-DR determinants with the CTL; the T4-positive cell was the sole CTL mediator of lysis of allogeneic target cells having a common HLA-DR determinant

  10. Herpes simplex virus 2 modulates apoptosis and stimulates NF-κB nuclear translocation during infection in human epithelial HEp-2 cells

    International Nuclear Information System (INIS)

    Virus-mediated apoptosis is well documented in various systems, including herpes simplex virus 1 (HSV-1). HSV-2 is closely related to HSV-1 but its apoptotic potential during infection has not been extensively scrutinized. We report that (i) HEp-2 cells infected with HSV-2(G) triggered apoptosis, assessed by apoptotic cellular morphologies, oligosomal DNA laddering, chromatin condensation, and death factor processing when a translational inhibitor (CHX) was added at 3 hpi. Thus, HSV-2 induced apoptosis but was unable to prevent the process from killing cells. (ii) Results from a time course of CHX addition experiment indicated that infected cell protein produced between 3 and 5 hpi, termed the apoptosis prevention window, are required for blocking virus-induced apoptosis. This corresponds to the same prevention time frame as reported for HSV-1. (iii) Importantly, CHX addition prior to 3 hpi led to less apoptosis than that at 3 hpi. This suggests that proteins produced immediately upon infection are needed for efficient apoptosis induction by HSV-2. This finding is different from that observed previously with HSV-1. (iv) Infected cell factors produced during the HSV-2(G) prevention window inhibited apoptosis induced by external TNFα plus cycloheximide treatment. (v) NF-κB translocated to nuclei and its presence in nuclei correlated with apoptosis prevention during HSV-2(G) infection. (vi) Finally, clinical HSV-2 isolates induced and prevented apoptosis in HEp-2 cells in a manner similar to that of laboratory strains. Thus, while laboratory and clinical HSV-2 strains are capable of modulating apoptosis in human HEp-2 cells, the mechanism of HSV-2 induction of apoptosis differs from that of HSV-1

  11. 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

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    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

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

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    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.

  13. 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.)

  14. 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...

  15. Coinfection of Epstein-Barr virus, cytomegalovirus, herpes simplex virus, human papillomavirus and anal intraepithelial neoplasia in HIV patients in Amazon, Brazil

    Directory of Open Access Journals (Sweden)

    Adriana Gonçalves Daumas Pinheiro Guimarães

    2012-03-01

    Full Text Available OBJECTIVE: The prevention of anal cancer is a goal of worldwide Aids support centers. Despite the efforts that have been made and progress in the antiretroviral therapy, effective disease control remains elusive. Difficulty in preventing anal cancer may result from the ineffectiveness of highly active antiretroviral therapy on the human papillomavirus (HPV since the coinfection with HIV and HPV appears to increase the risk of HPV-infected cells, becoming cancerous. METHODS: We evaluated 69 HIV-positive and 30 HIV-negative male patients who underwent cytological evaluation by RT-PCR for the presence of HPV, Epstein-Barr virus, cytomegalovirus and herpes virus types (HSV 1 and 2, and histopathology analysis of the anal canal. RESULTS: The prevalence of anal intraepithelial neoplasia was 35% and it was restricted to HIV-positive patients. Patients infected with high-risk HPV and with fewer than 50 TCD4 cells/µL showed an anal intraepithelial neoplasia rate of 85.7% compared to those with TCD4 cells >200 cells/µL (pOBJETIVO: A prevenção do câncer anal tem sido aplicada pelos centros de apoio a pacientes com Aids em todo o mundo. Apesar dos esforços empregados, o eficaz controle da doença permanece distante. A dificuldade na prevenção do câncer anal pode resultar, em parte, da ineficácia da ação da terapia antirretroviral sobre o papilomavírus humano (HPV, pois a coinfecção com HIV e HPV parece aumentar o risco das células infectadas pelo HPV em tornarem-se cancerosas. MÉTODOS: Foram avaliados 69 HIV-positivos e 30 pacientes HIV-negativos do sexo masculino, que foram submetidos à avaliação citológica anal por real time-PCR para a presença de HPV, vírus Epstein-Barr, citomegalovírus e herpes vírus tipos (HSV 1 e 2 além da análise histopatológica de fragmento de mucosa do canal anal. RESULTADOS: A prevalência de neoplasia intraepitelial anal foi de 35% e foi restrita a pacientes HIV-positivos. Os pacientes infectados com o

  16. 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 ...

  17. [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

  18. Clinical application of antibody monoclonal humanized anti-EGFrnimotuzumab labeled

    International Nuclear Information System (INIS)

    Most malignant tumors are of epithelial origin. These are characterized by overexpression of the receptor of epidermal growth factor (EGFR), which the neoplastic cells escape the regulatory mechanisms are allowed, so its high concentration of membrane is generally associated with a poor prognosis . By binding an antibody specifically to this receptor, preventing binding of EGF latter and activation mechanism tyrosine kinase inhibiting cell mitosis and apoptosis causing tumor cell. For this reason, the EGFr has been considered as an attractive target for anti-tumor therapy. The humanized monoclonal antibody anti-EGFr nimotuzumab was developed by the Center of Molecular Immunology (Havana, Cuba). Numerous clinical trials have been developed in the Department of Clinical Research Center Isotopes (Cuba), in which it has been applied this antibody, both labeled with 99mTc for immuno gammagraphic detection of tumors, as labeled with 188Re for radioimmunotherapy of gliomas high degree of malignancy. The aim of this paper is to show the experience of the Department of Clinical Research of CENTIS in various clinical trials with marking for both immuno gammagraphics detection of tumors, such as for radioimmunotherapy nimotuzumab. (author)

  19. 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.

  20. 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.

  1. Anti-oxidative and anti-genotoxic effects of methanolic extract of Mentha pulegium on human lymphocyte culture.

    Science.gov (United States)

    Alpsoy, Lokman; Sahin, Hilal; Karaman, Seyda

    2011-08-01

    In the present work, methanolic extract of Mentha pulegium from Erzurum, Turkey, was used in order to report the results of anti-oxidant capacity, anti-oxidant activity and anti-genotoxic effects. The total antioxidant capacity and total phenolic content were measured by using CUPRAC, ABTS and Folin-Ciocalteu colorimetric methods. The total phenolic content was higher than the total antioxidant capacity (for the results of both the CUPRAC and ABTS methods) of methanolic extract of M pulegium (ME). Also, we evaluated the anti-oxidant enzyme activity such as superoxide dismutase (SOD) and glutation peroxidase, total glutation (GSH) and malondialdehyde (MDA) in human lymphocyte culture. In CCl₄-treated group, the activity of SOD, glutathione peroxidase (GPx) and GSH decreased significantly and the level of MDA increased significantly. A significant increase in the activity of SOD, GPx and the level of GSH were seen when supplemented with ME to CCl₄-treated group. Furthermore, a significant decrease in the level of MDA was observed when compared with CCl₄ alone treated group. In addition, anti-genotoxic effect of ME was studied by using sister chromatid exchange (SCE) method. As a result, ME has shown anti-genotoxic effect depend on anti-oxidative effect on human lymphocyte culture. PMID:21511894

  2. Anti-idiotypic antisera in man. I. Production and immunochemical characterization of anti-idiotypic antisera to human antitetanus antibodies

    International Nuclear Information System (INIS)

    Antisera were raised in rabbits against immunosorbent-purified F(ab')2 fragments of IgG antitetanus toxoid (TT) antibodies obtained from three different donors. The antisera were rendered idiotype specific by absorption with insolubilized TT-nontreactive F(ab')2. The resulting anti-idiotypic antisera precipitated more than 85% of 125I-radiolabeled F(ab')2 anti-TT and were shown to be individual specific in that they reacted only with the immunizing F(ab')2 anti-TT and not with F(ab')2 anti-TT derived from other donors. Anti-idiotypic antiserum inhibited binding of 125I-TT but not of 125I-DT to IgG derived from the donor of the immunizing F(ab')2 anti-TT, but did not inhibit 125I-TT binding to IgG derived from other donors. Finally, binding of 125I-F(ab')2 anti-TT to the anti-idiotypic antiserum was completely inhibited by IgG derived from the same donor but only partially inhibited by a great excess of TT antigen, suggesting that the anti-idiotypic antiserum is recognizing nonantigen-binding idiotypic determinants on F(ab')2 anti-TT. The data presented demonstrate that anti-idiotypic heteroantisera can be successfully raised against human antibodies to TT, indicate minimal cross-reactivity of idiotypic determinants between unrelated individuals, and suggest the presence of nonantigen binding-idiotypic determinants on the antibody molecule

  3. Production, isolation, and characterization of rabbit anti-idiotypic antibodies directed against human antithyrotrophin receptor antibodies.

    OpenAIRE

    Baker, J. R.; Lukes, Y G; Burman, K. D.

    1984-01-01

    Previous studies have shown that anti-idiotypic antibodies can be developed in vivo through animal immunization with idiotype, and that these antibodies can be isolated from other anti-immunoglobulin antibodies by affinity purification. These techniques have relied on large amounts of idiotype, which were produced either by hyperimmunization or by monoclonal antibodies, to serve as the affinity adsorbent. In the present study, we produced anti-idiotypic antibodies to human anti-thyroid-stimul...

  4. 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

  5. Anti-Staphylococcal Biofilm Effects of Human Cathelicidin Peptides.

    Science.gov (United States)

    Mishra, Biswajit; Golla, Radha M; Lau, Kyle; Lushnikova, Tamara; Wang, Guangshun

    2016-01-14

    Staphylococcus aureus can live together in the form of biofilms to avoid elimination by the host. Thus, a useful strategy to counteract bacterial biofilms is to re-engineer human antimicrobial peptide LL-37 so that it can be used as a remedy for preventing and removing biofilms. This study reports antibiofilm effects of four human cathelicidin LL-37 peptides against community-associated and hospital isolated methicillin-resistant Staphylococcus aureus (MRSA) strains. Although the intact molecule LL-37 inhibited biofilm formation at low concentrations, it did not inhibit bacterial attachment nor disrupt preformed biofilms. However, two 17-residue peptides, GF-17 and 17BIPHE2, inhibited bacterial attachment, biofilm growth, and disrupted established biofilms. An inactive peptide RI-10 was used as a negative control. Our results obtained using the S. aureus mutants in a static biofilm model are consistent with the literature obtained in a flow cell biofilm model. Because 17BIPHE2 is the most effective biofilm disruptor with desired stability to proteases, it is a promising lead for developing new anti-MRSA biofilm agents. PMID:26819677

  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

    2015-07-28

    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

  7. Chronic urticaria associated with recurrent genital herpes simplex infection and success of antiviral therapy--a report of two cases.

    Science.gov (United States)

    Zawar, Vijay; Godse, Kiran; Sankalecha, Sudhir

    2010-06-01

    The role of infectious agents as a cause of chronic idiopathic urticaria (CIU) is uncertain. The objective of this study was to investigate whether genital herpes simplex infection is causally related to CIU. We identified two patients with recurrent genital herpes simplex infections associated with CIU. Episodes of genital herpes were especially associated with acute exacerbation of urticaria. Anti-herpes simplex 2 antibodies and Tzanck smears were done in both patients, along with other relevant investigations for CIU. Acyclovir was added to antihistamine therapy. Both patients were apparently in good health and appeared clinically immunologically stable, though one of them was found to be diabetic. Clinical and laboratory investigations for genital lesions supported a diagnosis of herpes simplex. Anti-herpes simplex 2 antibodies were markedly raised in both patients. The Tzanck smear was positive in one case and negative in the other, despite a definitive clinical diagnosis of herpes progenitalis. CIU, which was inadequately controlled with antihistamines alone, responded dramatically to the addition of acyclovir therapy. Our results may not be applicable to other patients with CIU, especially when there is inadequate evidence of an association with genital herpes. CIU may be associated with recurrent genital herpes simplex infection. In such situations, the addition of acyclovir to therapy may be beneficial. PMID:19699670

  8. 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.

  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. Possible enhancement of BP180 autoantibody production by herpes zoster.

    Science.gov (United States)

    Kamiya, Koji; Aoyama, Yumi; Suzuki, Takahiro; Niwa, Haruo; Horio, Ai; Nishio, Eiichi; Tokura, Yoshiki

    2016-02-01

    Bullous pemphigoid (BP) is an autoimmune blistering disease caused by autoantibodies against type XVII collagen/BP180 (BP180). Although the mechanisms of autoantibody production remain to be elucidated, herpes virus infections have been identified as a possible triggering factor for pemphigus. We report a case of herpes zoster (HZ) having anti-BP180 serum antibodies. The patient developed sudden-onset, tense blisters and edematous erythema on the right anterior chest, shoulder and upper back. Histopathology showed remarkable degeneration of keratinocytes, acantholysis and blister formation with ballooning cells, indicating herpes virus infection. A polymerase chain reaction analysis of varicella zoster virus (VZV) was positive in crusts and effusions from the skin lesions, confirming the definitive diagnosis of HZ. Notably, we found that the patient had anti-BP180 serum antibodies in association with the occurrence of HZ. After successful treatment with valacyclovir hydrochloride for 7 days, the serum levels of anti-BP180 antibodies decreased in accordance with the improvement of skin lesions. These findings suggest that the production of anti-BP180 antibodies could be triggered by the reactivation of VZV. PMID:26212492

  11. 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.

  12. 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

  13. 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

  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. Binding specificity of antiidiotypic autoantibodies to anti-DNA antibodies in humans.

    OpenAIRE

    Sasaki, T; Muryoi, T; Takai, O; Tamate, E; Saito, H.; Yoshinaga, K

    1988-01-01

    Human antiidiotypic antibodies to anti-DNA antibodies can be separated into at least two categories based on their binding to anti-DNA, antiidiotypic antibodies, and antigens. One type was found mainly in inactive stage of SLE. The antiidiotypic antibodies appear to be directed towards idiotype (Id) determinants in the antigen-binding sites of anti-DNA antibodies. Antibody from patient T.K. acted like a mirror image of anti-single-stranded DNA antibodies, O-81, as determined by a competitive ...

  16. 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

  17. 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...

  18. 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)

  19. 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

  20. 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.

  1. 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

  2. EPIDEMIOLOGY OF THE HERPES SIMPLEX VIRUS INFECTION

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    Ljiljana Kostadinović

    2002-07-01

    Full Text Available Over 150 sorts of viruses are capable of causing diseases of the respiratory ways. The virus infections have become the cost to be paid for urbanization and industrialization. The acute virus infections jeopardize mankind by their complications with numerous consequences. They open up the way to super infections, they provoke endogenous infections and lead to insufficiency of the vital organs. The viruses penetrate the organism mainly through the respiratory ways, digestive and urinary-sexual organs and skin. Some viruses immediately at the place of their entrance into the organism find receptive cells in which they can multiply (herpes virus and etc.. Some viruses must get through the blood, through the lymph or the nerve fibers to the target organs that they have affinity for.The changes that primarily occur in the mouth with manifest lymphadenopathy of the surrounding area emerge with respect to the type of the acute infection dis-ease.The human herpes viruses are responsible for a great number of diseases in people; that is why it can be said that the infections they induce are a very frequent cause of people's diseases in the world. Man is natural and the only host for the types I and II of the herpes simplex virus (HSV; that is why the infected person is regarded as the source of infection. The infection transmission can be by direct contact or over the contaminated secretions during the sexual intercourse. The age and the socioeconomic status (living conditions, level of medical culture, habits, etc. affect to agreat extent epidemiology of the HSV infection. The HSV distribution in the region of Niš in the five-year period (from 1987 to 1992 was the highest in the early and late summer (June and September.

  3. 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

  4. 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...

  5. MRI of herpes simplex encephalitis

    International Nuclear Information System (INIS)

    The magnetic resonance imaging (MRI) findings in eight patients with herpes simplex meningoence phalitis were reviewed: 14 examinations were analysed. The most striking finding was high signal intensity in the temporal lobe(s) with the typical configuration known from CT. Meningeal enhancement after Gd-DTPA administration was clearly seen in four patients. Haemorrhagic changes are much better seen on MRI than on CT. When adequate motion control can be achieved, MRI becomes the examination of choice in the diagnosis and follow-up of herpes simplex encephalitis. Localized 1H MR spectroscopy also proved promising in the study of neuronal loss. (orig.)

  6. 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.

  7. 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

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

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    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.

  9. 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...

  10. 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.

  11. 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.

  12. Polyneuritis cranialis following herpes zoster

    OpenAIRE

    Radhakrishna H; Malakondaiah T; Reddy I; Saheb D

    2000-01-01

    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.

  13. 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)

  14. 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.

  15. Update On Emerging Antivirals For The Management Of Herpes Simplex Virus Infections: A Patenting Perspective

    OpenAIRE

    Vadlapudi, Aswani D.; Vadlapatla, Ramya K.; Ashim K. Mitra

    2013-01-01

    Herpes simplex virus (HSV) infections can be treated efficiently by the application of antiviral drugs. The herpes family of viruses is responsible for causing a wide variety of diseases in humans. The standard therapy for the management of such infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valaciclovir and famciclovir. Though effective, long term prophylaxis with the current drugs leads to development of drug-resistant viral isolates, particularly i...

  16. 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

  17. 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

  18. 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.......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....

  19. Chimpanzees Immunized with Recombinant Soluble CD4 Develop Anti-Self CD4 Antibody Responses with Anti-Human Immunodeficiency Virus Activity

    Science.gov (United States)

    Watanabe, Mamoru; Boyson, Jonathan E.; Lord, Carol I.; Letvin, Norman L.

    1992-06-01

    In view of the efficiency with which human immunodeficiency virus replication can be blocked in vitro with anti-CD4 antibodies, the elicitation of an anti-CD4 antibody response through active immunization might represent a useful therapeutic strategy for AIDS. Here we demonstrate that immunization of chimpanzees with recombinant soluble human CD4 elicited an anti-CD4 antibody response. The elicited antibody bound self CD4 on digitonin-treated but not freshly isolated lymphocytes. Nevertheless, this antibody blocked human immunodeficiency virus replication in chimpanzee and human lymphocytes. These observations suggest that immunization with recombinant soluble CD4 from human immunodeficiency virus-infected humans may be feasible and therapeutically beneficial.

  20. Role of anti-human lymphocyte culture cytotoxic antibodies in recurrent spontaneous pregnancy loss women

    Directory of Open Access Journals (Sweden)

    Shankarkumar Umapathy

    2011-01-01

    Full Text Available Background : Recurrent spontaneous pregnancy (RSA is defined as a sequence of three or more consecutive spontaneous abortions. One of the major causes of RSA is immunological where alloimmune antibodies develop towards human leucocyte antigen (HLA antigens. Earlier research had suggested that anti-HLA antibodies are produced in normal women; studies have been reported that normal pregnant women develop anti-HLA antibodies, mostly after 20-28 weeks of gestation. Aim : To evaluate the role of anti-HLA antibodies in RSA patients Materials and Methods : A total of 80 randomly selected couples with unexplained three or more RSA and control group of 50 normal pregnant women were screened for anti-HLA A and B antibodies. The anti-HLA antibodies were analyzed following the standard two-stage NIH microlymphocytotoxicity assay. Results : In our study group a high frequency of anti-HLA antibodies among women with RSA (26.25% was detected compared to normal pregnant women (8.0%. Most of the sera showed HLA-A and HLA-B antibodies which had high titer, up to a dilution of 1: 4096. Conclusion : This incidence of high anti-HLA antibodies in RSA women during early weeks of gestation may explain the recurrent pregnancy loss.

  1. Human serum-derived hydroxy long-chain fatty acids exhibit anti-inflammatory and anti-proliferative activity

    Directory of Open Access Journals (Sweden)

    Ahiahonu Pearson

    2011-05-01

    Full Text Available Abstract Background Circulating levels of novel long-chain hydroxy fatty acids (called GTAs were recently discovered in the serum of healthy subjects which were shown to be reduced in subjects with colorectal cancer (CRC, independent of tumor burden or disease stage. The levels of GTAs were subsequently observed to exhibit an inverse association with age in the general population. The current work investigates the biological activity of these fatty acids by evaluating the effects of enriched human serum extracts on cell growth and inflammation. Methods GTAs were extracted from commercially available bulk human serum and then chromatographically separated into enriched (GTA-positive and depleted (GTA-negative fractions. SW620, MCF7 and LPS stimulated RAW264.7 cells were treated with various concentrations of the GTA-positive and GTA-negative extracts, and the effects on cell growth and inflammation determined. Results Enriched fractions resulted in poly-ADP ribose polymerase (PARP cleavage, suppression of NFκB, induction of IκBα, and reduction in NOS2 mRNA transcript levels. In RAW264.7 mouse macrophage cells, incubation with enriched fractions prior to treatment with LPS blocked the induction of several pro-inflammatory markers including nitric oxide, TNFα, IL-1β, NOS2 and COX2. Conclusions Our results show that human serum extracts enriched with endogenous long-chain hydroxy fatty acids possess anti-inflammatory and anti-proliferative activity. These findings support a hypothesis that the reduction of these metabolites with age may result in a compromised ability to defend against uncontrolled cell growth and inflammation, and could therefore represent a significant risk for the development of CRC.

  2. 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.

  3. 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

  4. The phosphoproteome of human Jurkat T cell clones upon costimulation with anti-CD3/anti-CD28 antibodies.

    Science.gov (United States)

    Nguyen, Tien Dung; Carrascal, Montserrat; Vidal-Cortes, Oriol; Gallardo, Oscar; Casas, Vanessa; Gay, Marina; Phan, Van Chi; Abian, Joaquin

    2016-01-10

    Phosphorylation is a reversible post-translational modification, playing a vital role in protein function. In T cells, protein phosphorylation is the key mechanism regulating T cell receptor-driven signaling pathways. In order to gain insights into the phosphoproteome evolution of T cell activation, we performed a large-scale quantitative phosphoproteomics study of Jurkat E6.1 (wild type) and Jurkat gamma1 (Phospholipase gamma1 null) cell clones upon costimulation with anti-CD3 and anti-CD28 antibodies at times ranging from 15min to as long as 120min. In total, we identified 5585 phosphopeptides belonging to 2008 phosphoproteins from both cell clones. We detected 130 and 114 novel phosphopeptides in Jurkat E6.1 and Jurkat gamma1 clones, respectively. A significantly lower number of proteins containing regulated phosphorylation sites were identified in Jurkat gamma1 in comparison to Jurkat E6.1, reflecting the vital role of Phospholipase gamma1 in T cell signaling. Several new phosphorylation sites from lymphocyte-specific protein tyrosine kinase (Lck) were identified. Of these, serine-121 showed significant changes in JE6.1 while only small changes in the Jgamma1 clone. Our data may contribute to the current human T cell phosphoproteome and provide a better understanding on T cell receptor signaling. Data are available via ProteomeXchange with identifier PXD002871. PMID:26546556

  5. 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...

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. A new sialyloligosaccharide from human milk: isolation and characterization using anti-oligosaccharide antibodies

    International Nuclear Information System (INIS)

    A previously undescribed sialyloligosaccharide has been isolated from human milk using a specific anti-sialyloligosaccharide antibody. Structural studies of the radiolabeled oligosaccharide by enzyme degradation and binding by specific anti-oligosaccharide sera are consistent with the following structure: (sequence in text) The oligosaccharide is present only in milk from donors who secrete A, B, or H blood group substances; this is consistent with the requirement of at least one copy of the Se (Secretor) gene necessary for the synthesis of oligosaccharides with Fuc alpha 1-2Gal . . . linkages

  11. Production, isolation, and characterization of rabbit anti-idiotypic antibodies directed against human antithyrotrophin receptor antibodies.

    Science.gov (United States)

    Baker, J R; Lukes, Y G; Burman, K D

    1984-01-01

    Previous studies have shown that anti-idiotypic antibodies can be developed in vivo through animal immunization with idiotype, and that these antibodies can be isolated from other anti-immunoglobulin antibodies by affinity purification. These techniques have relied on large amounts of idiotype, which were produced either by hyperimmunization or by monoclonal antibodies, to serve as the affinity adsorbent. In the present study, we produced anti-idiotypic antibodies to human anti-thyroid-stimulating hormone (TSH) receptor antibodies by first injecting rabbits with (TSH receptor purified) IgG from Graves' patients. The resulting antiserum was then adsorbed with Sepharose-coupled TSH in an attempt to specifically bind and isolate the anti-idiotype. The antibody obtained from this process was shown to bind specifically to TSH receptor-binding antibodies from Graves' patients, and this binding could be inhibited by 56% with the addition of 10(-4) M TSH but not by HCG (10(-2) M). The anti-idiotype also bound to TSH, and this binding could be specifically inhibited by receptor-purified Graves' IgG (60% inhibition at 10 micrograms/ml IgG), but not by IgG from normal subjects (no inhibition at 50 micrograms/ml IgG). In a TSH receptor binding assay, the anti-idiotype could inhibit TSH receptor binding in Graves' sera at a 1,000-fold lower concentration than could anti-kappa/lambda antiserum; the anti-idiotypic antiserum also inhibited in vitro TSH-mediated adenylate cyclase stimulation at an IgG concentration of 5 micrograms/ml, while heterologous anti-TSH antisera and normal IgG at similar concentrations had no effect. Finally, despite being generated against a single patient's TSH receptor binding antibody, the anti-idiotype was able to block TSH receptor binding in the serum of six other Graves' patients, thus suggesting that there may be conformational conservation in the antigen that is recognized by different individuals' TSH receptor-binding immunoglobulins. PMID

  12. 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)

  13. 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

  14. 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.

  15. 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

  16. Lactation associated with herpes zoster pectoralis.

    Science.gov (United States)

    Bhattacharya, S K; Girgla, H S

    1976-05-01

    The phenomenon of lactation associated with herpes zoster is unexpected. To our knowledge such an association has been reported only once. A case is reported in whom spontaneous lactation occurred in the ipsilateral breast following herpes zoster. It is believed to have resulted from stimulation of the intercostal nerve endings supplying the overlying skin of the breast. PMID:945354

  17. 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.

  18. 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

  19. 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

  20. Anti-Angiogenic Activity of Ficus carica Latex Extract on Human Umbilical Vein Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Ali Mostafaie

    2011-01-01

    Full Text Available Angiogenesis, the formation of new blood vessels, is a key process in cancer developmentand metastasis. In this study, the anti-angiogenic and anti-proliferative potentials of Ficuscarica latex extract have been investigated using human umbilical vein endothelial cells(HUVECs.Different doses of latex extract were prepared and added to a three-dimensional culture ofHUVEC in a collagen matrix. After 3-5 days of treatment, the anti-angiogenic effects of theextracts were monitored microscopically. For the anti-proliferation assay, different dosesof the extracts were examined on HUVECs.The results clearly indicated that latex extract could inhibit proliferation and capillary tubeformation of HUVECs in a dose-dependent manner at the range of 100-400 μg/ml. In addition,the extract was not cytotoxic up to 450 μg/ml as assessed by trypan blue and lactatedehydrogenase (LDH cytotoxicity assays.It is concluded that latex extracts of F. carica contain strong anti-angiogenic andanti-proliferative activities. Our data indicates that latex extract could be a candidateas a potential agent for the prevention of angiogenesis in cancer and other chronicdisorders.

  1. 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

  2. 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.

  3. 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... simplex virus serological assays. (a) Identification. Herpes simplex virus serological assays are devices... herpes simplex virus in serum. Additionally, some of the assays consist of herpes simplex virus...

  4. 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

  5. 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. The aim of this work was to investigate the epidemiological profile of Herpes simplex at Stomatology Division of Hospital São Lucas-PUCRS. Records of 167 patients were reviewed: 98 (58,68% of them were primary herpetic gingivostomatitis patients and 69 (41,32% were recurrent herpes patients. Age, sex, symptoms, anatomical sites affected, complications, lymphadenopathy and treatment were analyzed. Results showed that 69,38% of primary herpetic gingivostomatitis patients were under age of 21 years, while 41,42% of recurrent herpes patients were between 21 and 40 years of age. Females were more affected than males by both primary and secondary disease. The most commonly involved anatomical sites were tongue and gums in primary herpetic gingivostomatitis and lip vermilion in recurrent herpes. Fever

  6. 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

  7. Infected cell protein 0 functional domains and their coordination in herpes simplex virus replication.

    Science.gov (United States)

    Gu, Haidong

    2016-02-12

    Herpes simplex virus 1 (HSV-1) is a ubiquitous human pathogen that establishes latent infection in ganglia neurons. Its unique life cycle requires a balanced "conquer and compromise" strategy to deal with the host anti-viral defenses. One of HSV-1 α (immediate early) gene products, infected cell protein 0 (ICP0), is a multifunctional protein that interacts with and modulates a wide range of cellular defensive pathways. These pathways may locate in different cell compartments, which then migrate or exchange factors upon stimulation, for the purpose of a concerted and effective defense. ICP0 is able to simultaneously attack multiple host pathways by either degrading key restrictive factors or modifying repressive complexes. This is a viral protein that contains an E3 ubiquitin ligase, translocates among different cell compartments and interacts with major defensive complexes. The multiple functional domains of ICP0 can work independently and at the same time coordinate with each other. Dissecting the functional domains of ICP0 and delineating the coordination of these domains will help us understand HSV-1 pathogenicity as well as host defense mechanisms. This article focuses on describing individual ICP0 domains, their biochemical properties and their implication in HSV-1 infection. By putting individual domain functions back into the picture of host anti-viral defense network, this review seeks to elaborate the complex interactions between HSV-1 and its host. PMID:26870669

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

    DEFF Research Database (Denmark)

    Bouquin, Thomas; Thomsen, Mads; Nielsen, Leif Kofoed; Green, Trine Hefsgaard; Mundy, John; Dziegiel, Morten Hanefeld

    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...... properties to CHO cell-produced anti-RhD antibody, indicating its potential usefulness in diagnostic and therapeutic programs....

  9. 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

    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. Improved radioimmunoscintigraphy of human mammary carcinoma xenografts after injection of an anti-antibody

    International Nuclear Information System (INIS)

    The low tumor-to-background ratio obtained after administration of radiolabeled whole monoclonal antibodies (MAbs) is one of the major problems in immunoscintigraphy and -therapy. To reduce the blood pool label caused by the circulation of radiolabeled MAb we have investigated the advantage of injecting an anti-antibody after administration of tumor-specific MAb in nude mice bearing human mammary carcinoma xenografts. The MAb MA 10-11 of rat origin, used in these studies, had shown a high affinity to human mammary carcinoma tissue on frozen sections and low cross-reactivity with various normal human tissues. 24 h after injection of 1.5 MBq 131I-labeled MAb containing 10 μg IgG2a one group of mice received an additional injection of 100 μg anti-rat antibody. Blood taken 2 min after the second antibody injection showed nearly the whole activity bound to antibody aggregates, that cleared very rapidly from the circulation and accumulated in liver and spleen. The transitory high liver activity decreased within several hours because of rapid deiodination of the antibody-complex in this organ. The release of radioactivity from the spleen, however, was found to be much slower. The rapid excretion of the radioactivity from the blood pool combined with a nearly constant tumor activity allowed early tumor detection with tumor-to-blood ratios of 250:1 at 48 h after anti-antibody injection compared to 1.1:1 obtained for the control animals. In addition the results may explain the reported reduction of imaging quality and high uptake of radioactivity in the spleen of patients having repeated injections of mouse MAbs due to complex formation after development of human anti-mouse antibodies. (orig.)

  11. Cationic polypeptides contribute to the anti-HIV-1 activity of human seminal plasma

    OpenAIRE

    Martellini, Julie A.; Amy L Cole; Venkataraman, Nitya; Quinn, Gerry A.; Svoboda, Pavel; Bhushan K Gangrade; Pohl, Jan; Sørensen, Ole E.; Cole, Alexander M.

    2009-01-01

    Mucosal surfaces of the reproductive tract as well as their secretions have important roles in preventing sexual transmission of HIV-1. In the current study, the majority of the intrinsic anti-HIV-1 activity of human seminal plasma (SP) was determined to reside in the cationic polypeptide fraction. Antiviral assays utilizing luciferase reporter cells and lymphocytic cells revealed the ability of whole SP to prevent HIV-1 infection, even when SP was diluted 3200-fold. Subsequent fractionation ...

  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. 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 ...

  14. 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...

  15. Herpes simplex keratitis in children.

    OpenAIRE

    Beigi, B; Algawi, K; Foley-Nolan, A; O'Keefe, M.

    1994-01-01

    Ophthalmic findings are reported in 31 eyes of 28 children with herpes simplex keratitis. Twenty two had dendritic ulcers, and nine had geographic ulcers or disciform stromal keratitis. After resolution of keratitis, 80% (19/22) of children with dendritic ulcers achieved corrected visual acuity of 6/9 or better, 50% (11/22) had induced astigmatism, 45% (9/22) had one to five recurrences. In the group with geographic or disciform lesions, 89% (8/9) had reduced corrected vision, 78% (7/9) had i...

  16. 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

  17. 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...

  18. Anti-inflammatory effects of methoxyphenolic compounds on human airway cells

    Directory of Open Access Journals (Sweden)

    Houser Kenneth R

    2012-03-01

    Full Text Available Abstract Background The respiratory epithelium plays a central role in the inflammatory response in asthma and other diseases. Methoxyphenolic compounds are purported to be effective anti-inflammatory agents, but their effects on the airway epithelium have not been well characterized. Methods Human airway cells were stimulated with TNF-α in the presence or absence of 4-substituted methoxyphenols and resveratrol. The expression of various cytokines was measured by qPCR, ELISAs, and protein arrays. Reactive oxygen species (ROS production was measured with a reactive fluorescent probe (3',6'-diacetate-2',7'-dichlorofluorescein. Activation of NF-κB was measured by nuclear translocation and phosphorylation. Ribonuclear protein association with mRNA was assessed with a biotin-RNA affinity isolation assay. Results Multiple inflammatory mediators were inhibited by methoxyphenols, including: CCL2, CCL5, IL-6, IL-8, ICAM-1, MIF, CXCL1, CXCL10, and Serpin E1. IC50 values were obtained for each compound that showed significant anti-inflammatory activity: diapocynin (20.3 μM, resveratrol (42.7 μM, 2-methoxyhydroquinone (64.3 μM, apocynin (146.6 μM, and 4-amino-2-methoxyphenol (410 μM. The anti-inflammatory activity did not correlate with inhibition of reactive oxygen species production or NF-κB activation. However, methoxyphenols inhibited binding of the RNA-binding protein HuR to mRNA, indicating that they may act post-transcriptionally. Conclusions Methoxyphenols demonstrate anti-inflammatory activity in human airway cells. More potent compounds that act via similar mechanisms may have therapeutic potential as novel anti-inflammatory agents.

  19. Preparation and in vivo evaluation of linkers for 211At labeling of humanized anti-Tac

    International Nuclear Information System (INIS)

    The syntheses, radiolabeling, antibody conjugation, and in vivo evaluation of new linkers for 211At labeling of humanized anti-Tac (Hu-anti-Tac), an antibody to the α-chain of the IL-2 receptor (IL-2Rα) shown to be a useful target for radioimmunotherapy are described. Synthesis of the organometallic linker precursors is accomplished by reaction of the corresponding bromo- or iodoaryl esters with bis(tributyltin) in the presence of a palladium catalyst. Subsequent conversion to the corresponding N-succinimidyl ester and labeling with 211At of two new linkers, N-succinimidyl 4-[211At]astato-3-methylbenzoate and N-succinimidyl N-(4-[211At]astatophenethyl)succinamate (SAPS), together with the previously reported N-succinimidyl 4-[211At]astatobenzoate and N-succinimidyl 3-[211At]astato-4-methylbenzoate, are each conjugated to Hu-anti-Tac. The plasma survival times of these conjugates are compared to those of directly iodinated (125I) Hu-anti-Tac. The N-succinimidyl N-(4-[211At]astatophenethyl)succinamate compound (SAPS) emerged from this assay as the most viable candidate for 211At-labeling of Hu-anti-Tac. SAPS, along with the directly analogous radio-iodinated reagent, N-succinimidyl N-(4-[125I]astatophenethyl)succinamate (SIPS), are evaluated in a biodistribution study along with directly iodinated (125I) Hu-anti-Tac. Blood clearance and biological accretion results indicate that SAPS is a viable candidate for further evaluation for radioimmunotherapy of cancer

  20. 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

  1. Novel human anti-claudin 1 mAbs inhibit hepatitis C virus infection and may synergize with anti-SRB1 mAb.

    Science.gov (United States)

    Paciello, Rolando; Urbanowicz, Richard A; Riccio, Gennaro; Sasso, Emanuele; McClure, C Patrick; Zambrano, Nicola; Ball, Jonathan K; Cortese, Riccardo; Nicosia, Alfredo; De Lorenzo, Claudia

    2016-01-01

    Hepatitis C virus (HCV) is a major cause of chronic hepatitis and liver carcinoma and new therapies based on novel targets are needed. The tight junction protein claudin 1 (CLDN-1) is essential for HCV cell entry and spread, and anti-CLDN-1 rat and mouse mAbs are safe and effective in preventing and treating HCV infection in a human liver chimeric mouse model. To accelerate translation of these observations into a novel approach to treat HCV infection and disease in humans, we screened a phage display library of human single-chain antibody fragments by using a panel of CLDN-1-positive and -negative cell lines and identified phage specifically binding to CLDN-1. The 12 clones showing the highest levels of binding were converted into human IgG4. Some of these mAbs displayed low-nanomolar affinity, and inhibited infection of human hepatoma Huh7.5 cells by different HCV isolates in a dose-dependent manner. Cross-competition experiments identified six inhibitory mAbs that recognized distinct epitopes. Combination of the human anti-SRB1 mAb C-1671 with these anti-CLDN-1 mAbs could either increase or reduce inhibition of cell culture-derived HCV infection in vitro. These novel human anti-CLDN-1 mAbs are potentially useful to develop a new strategy for anti-HCV therapy and lend support to the combined use of antibodies targeting the HCV receptors CLDN-1 and SRB1, but indicate that care must be taken in selecting the proper combination. PMID:26519290

  2. 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 specificity of a panel of five novel high-affinity AMH monoclonal antibodies. Two recognize the mature C-terminal form of AMH, whereas three recognize the active pro-mature form of AMH in human tissue. The antibodies were tested on fetal male testicular and mesonephric tissue aged 8-19 weeks post conception...... (pc), fetal male serum aged 16-26 weeks pc and human immature GCs by immunofluorescence, immunohistochemistry, ELISA and western blotting. The active pro-mature forms of AMH were expressed in both Sertoli cells from human fetal testis and human immature GCs. In contrast, the mature C-terminal form...

  3. Structural basis for the antibody neutralization of Herpes simplex virus

    International Nuclear Information System (INIS)

    The gD–E317-Fab complex crystal revealed the conformational epitope of human mAb E317 on HSV gD, providing a molecular basis for understanding the viral neutralization mechanism. Glycoprotein D (gD) of Herpes simplex virus (HSV) binds to a host cell surface receptor, which is required to trigger membrane fusion for virion entry into the host cell. gD has become a validated anti-HSV target for therapeutic antibody development. The highly inhibitory human monoclonal antibody E317 (mAb E317) was previously raised against HSV gD for viral neutralization. To understand the structural basis of antibody neutralization, crystals of the gD ectodomain bound to the E317 Fab domain were obtained. The structure of the complex reveals that E317 interacts with gD mainly through the heavy chain, which covers a large area for epitope recognition on gD, with a flexible N-terminal and C-terminal conformation. The epitope core structure maps to the external surface of gD, corresponding to the binding sites of two receptors, herpesvirus entry mediator (HVEM) and nectin-1, which mediate HSV infection. E317 directly recognizes the gD–nectin-1 interface and occludes the HVEM contact site of gD to block its binding to either receptor. The binding of E317 to gD also prohibits the formation of the N-terminal hairpin of gD for HVEM recognition. The major E317-binding site on gD overlaps with either the nectin-1-binding residues or the neutralizing antigenic sites identified thus far (Tyr38, Asp215, Arg222 and Phe223). The epitopes of gD for E317 binding are highly conserved between two types of human herpesvirus (HSV-1 and HSV-2). This study enables the virus-neutralizing epitopes to be correlated with the receptor-binding regions. The results further strengthen the previously demonstrated therapeutic and diagnostic potential of the E317 antibody

  4. Structural basis for the antibody neutralization of Herpes simplex virus

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Cheng-Chung; Lin, Li-Ling [Academia Sinica, Taipei 115, Taiwan (China); Academia Sinica, Taipei 115, Taiwan (China); Chan, Woan-Eng [Development Center for Biotechnology, New Taipei City 221, Taiwan (China); Ko, Tzu-Ping [Academia Sinica, Taipei 115, Taiwan (China); Academia Sinica, Taipei 115, Taiwan (China); Lai, Jiann-Shiun [Development Center for Biotechnology, New Taipei City 221, Taiwan (China); Ministry of Economic Affairs, Taipei 100, Taiwan (China); Wang, Andrew H.-J., E-mail: ahjwang@gate.sinica.edu.tw [Academia Sinica, Taipei 115, Taiwan (China); Academia Sinica, Taipei 115, Taiwan (China); Taipei Medical University, Taipei 110, Taiwan (China)

    2013-10-01

    The gD–E317-Fab complex crystal revealed the conformational epitope of human mAb E317 on HSV gD, providing a molecular basis for understanding the viral neutralization mechanism. Glycoprotein D (gD) of Herpes simplex virus (HSV) binds to a host cell surface receptor, which is required to trigger membrane fusion for virion entry into the host cell. gD has become a validated anti-HSV target for therapeutic antibody development. The highly inhibitory human monoclonal antibody E317 (mAb E317) was previously raised against HSV gD for viral neutralization. To understand the structural basis of antibody neutralization, crystals of the gD ectodomain bound to the E317 Fab domain were obtained. The structure of the complex reveals that E317 interacts with gD mainly through the heavy chain, which covers a large area for epitope recognition on gD, with a flexible N-terminal and C-terminal conformation. The epitope core structure maps to the external surface of gD, corresponding to the binding sites of two receptors, herpesvirus entry mediator (HVEM) and nectin-1, which mediate HSV infection. E317 directly recognizes the gD–nectin-1 interface and occludes the HVEM contact site of gD to block its binding to either receptor. The binding of E317 to gD also prohibits the formation of the N-terminal hairpin of gD for HVEM recognition. The major E317-binding site on gD overlaps with either the nectin-1-binding residues or the neutralizing antigenic sites identified thus far (Tyr38, Asp215, Arg222 and Phe223). The epitopes of gD for E317 binding are highly conserved between two types of human herpesvirus (HSV-1 and HSV-2). This study enables the virus-neutralizing epitopes to be correlated with the receptor-binding regions. The results further strengthen the previously demonstrated therapeutic and diagnostic potential of the E317 antibody.

  5. 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

    OpenAIRE

    Sílvia Regina Ferreira Gonçalves Pereira; Fernando Portela Câmara; Maria Angélica Arpon Marandino Guimarães; Leonardo Vieira Neto; Daniel Segenreich; Antônio Carlos da Costa Guimarães; Vera Lucia Antunes Chagas

    2007-01-01

    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 acet...

  6. 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

  7. 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)

  8. Serum antibodies to herpes simplex virus type 1 during active oral herpes infection.

    OpenAIRE

    Ratner, J J; Smith, K O

    1980-01-01

    Subjects with oral herpes lesions at the time of serum sampling had higher-efficiency antibody (higher proportion of neutralizing antibody as determined by plaque reduction, compared with total antibody as detected by radioimmunoassay) to herpes simplex virus type 1 (HSV-1) than did subjects with no lesions at the time of serum sampling. These higher-efficiency sera also had higher antibody titers to structural components of herpes simplex virus type 1 than did the low-efficiency sera. Absorp...

  9. Case of herpes zoster duplex bilateralis.

    Science.gov (United States)

    Shin, Bong Seok; Seo, Hyun Deok; Na, Chan Ho; Choi, Kyu Chul

    2009-02-01

    Non-contiguously simultaneous development of herpes zoster is very rare. It is named either herpes zoster duplex unilateralis or bilaterarlis, depending on whether one or both sides of the body are involved. Herein, we report a 21-year-old man, who had been treated for ulcerative colitis with prednisolone, and presented with painful grouped vesicles of the lower abdomen and back in a relatively symmetrical distribution. A Tzanck smear and punch biopsy were performed on the vesicles of the back. We report a rare case of symmetrical herpes zoster duplex bilateralis. PMID:19284453

  10. 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.

  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. Anti-Human VEGF Repebody Effectively Suppresses Choroidal Neovascularization and Vascular Leakage

    Science.gov (United States)

    Hwang, Da-Eun; Ryou, Jeong-Hyun; Oh, Jong Rok; Han, Jung Woo; Park, Tae Kwann; Kim, Hak-Sung

    2016-01-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness among people over the age of 60. Vascular endothelial growth factor (VEGF) plays a major role in pathological angiogenesis in AMD. Herein, we present the development of an anti- human VEGF repebody, which is a small-sized protein binder consisting of leucine-rich repeat (LRR) modules. The anti-VEGF repebody selected through a phage-display was shown to have a high affinity and specificity for human VEGF. We demonstrate that this repebody effectively inhibits in vitro angiogenic cellular processes, such as proliferation and migration, by blocking the VEGF-mediated signaling pathway. The repebody was also shown to have a strong suppression effect on choroidal neovascularization (CNV) and vascular leakage in vivo. Our results indicate that the anti-VEGF repebody has a therapeutic potential for treating neovascular AMD as well as other VEGF-involved diseases including diabetic retinopathy and metastatic cancers. PMID:27015541

  13. 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

  14. 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...

  15. 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...

  16. Development of a Fully Human Anti-PDGFRβ Antibody That Suppresses Growth of Human Tumor Xenografts and Enhances Antitumor Activity of an Anti-VEGFR2 Antibody

    Directory of Open Access Journals (Sweden)

    Juqun Shen

    2009-06-01

    Full Text Available Platelet-derived growth factor receptor β (PDGFRβ is upregulated in most of solid tumors. It is expressed by pericytes/smooth muscle cells, fibroblast, macrophage, and certain tumor cells. Several PDGF receptor-related antagonists are being developed as potential antitumor agents and have demonstrated promising antitumor activity in both preclinical and clinical settings. Here, we produced a fully human neutralizing antibody, IMC-2C5, directed against PDGFRβ from an antibody phage display library. IMC-2C5 binds to both human and mouse PDGFRβ and blocks PDGF-B from binding to the receptor. IMC-2C5 also blocks ligand-stimulated activation of PDGFRβ and downstream signaling molecules in tumor cells. In animal studies, IMC-2C5 significantly delayed the growth of OVCAR-8 and NCI-H460 human tumor xenografts in nude mice but failed to show antitumor activities in OVCAR-5 and Caki-1 xenografts. Our results indicate that the antitumor efficacy of IMC-2C5 is primarily due to its effects on tumor stroma, rather than on tumor cells directly. Combination of IMC-2C5 and DC101, an anti-mouse vascular endothelial growth factor receptor 2 antibody, resulted in significantly enhanced antitumor activity in BxPC-3, NCI-H460, and HCT-116 xenografts, compared with DC101 alone, and the trend of additive effects to DC101 treatment in several other tumor models. ELISA analysis of NCI-H460 tumor homogenates showed that IMC-2C5 attenuated protein level of vascular endothelial growth factor and basic fibroblast growth factor elevated by DC101 treatment. Finally, IMC-2C5 showed a trend of additive effects when combined with DC101/chemotherapy in MIA-PaCa-2 and NCI-H460 models. Taken together, these results lend great support to the use of PDGFRβ antagonists in combination with other antiangiogenic agents in the treatment of a broad range of human cancers.

  17. Comparison of anti-CD3 and anti-CD28-coated beads with soluble anti-CD3 for expanding human T cells: Differing impact on CD8 T cell phenotype and responsiveness to restimulation

    Directory of Open Access Journals (Sweden)

    Kurlander Roger J

    2010-10-01

    Full Text Available Abstract Background The ability to expand virus- or tumor-specific T cells without damaging their functional capabilities is critical for success adoptive transfer immunotherapy of patients with opportunistic infection or tumor. Careful comparisons can help identify expansion methods better suited for particular clinical settings and identify recurrent deficiencies requiring new innovation. Methods We compared the efficacy of magnetic beads coated with anti-CD3 and anti-CD28 (anti-CD3/CD28 beads, and soluble anti-CD3 plus mixed mononuclear cells (designated a rapid expansion protocol or REP in expanding normal human T cells. Results Both anti-CD3/CD28 beads and soluble anti-CD3 promoted extensive expansion. Beads stimulated greater CD4 cell growth (geometric mean of 56- versus 27-fold (p Conclusions Anti-CD3/CD28 beads are highly effective for expanding CD4 cells, but soluble anti-CD3 has significant potential advantages for expanding CD8 T cells, particularly where preservation of phenotypically "young" CD8 cells would be desirable, or where the T cells of interest have been antigen-stimulated in vitro or in vivo in the recent past.

  18. How computer simulations of the human heart can improve anti-arrhythmia therapy.

    Science.gov (United States)

    Trayanova, Natalia A; Chang, Kelly C

    2016-05-01

    Over the last decade, the state-of-the-art in cardiac computational modelling has progressed rapidly. The electrophysiological function of the heart can now be simulated with a high degree of detail and accuracy, opening the doors for simulation-guided approaches to anti-arrhythmic drug development and patient-specific therapeutic interventions. In this review, we outline the basic methodology for cardiac modelling, which has been developed and validated over decades of research. In addition, we present several recent examples of how computational models of the human heart have been used to address current clinical problems in cardiac electrophysiology. We will explore the use of simulations to improve anti-arrhythmic pacing and defibrillation interventions; to predict optimal sites for clinical ablation procedures; and to aid in the understanding and selection of arrhythmia risk markers. Together, these studies illustrate how the tremendous advances in cardiac modelling are poised to revolutionize medical treatment and prevention of arrhythmia. PMID:26621489

  19. 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.

  20. 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......-reactive antibody reacted with lymphocytes from mink. The anti-C3b-R antibody reacted with lymphocytes from horse, swine, dog, and cat, and the anti-HLA-DR reacted with lymphocytes from cow, goat, sheep, horse, dog, cat, and mink....... antibodies bound to lymphocytes from some of the animals. These were the antibodies against CD8 and CD4 antigen, the antibody to C3b-receptor, and the antibody to the HLA-DR antigen. The CD8 antigen-reactive antibody reacted with lymphocytes from mink, cat, dog, and sheep, while the CD4 antigen...

  1. 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.

  2. 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

  3. 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

  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. 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.

  7. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kaner, R.J.; Iozzo, R.V.; Ziaie, Z.; Kefalides, N.A.

    1987-05-01

    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 (/sup 35/S)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.

  9. 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

  10. Induction of anti-phospholipid syndrome in naive mice with mouse lupus monoclonal and human polyclonal anti-cardiolipin antibodies.

    OpenAIRE

    Blank, M.; Cohen, J.; Toder, V.; Y. Shoenfeld

    1991-01-01

    The primary anti-phospholipid syndrome is characterized by recurrent venous and arterial thromboembolic phenomena, recurrent fetal loss, thrombocytopenia, and serological evidence of anti-cardiolipin (aCL) antibodies or/and the presence of lupus anticoagulant (prolonged activated partial thromboplastin time). The exact role of aCL antibodies in pathogenesis is not clear and the mechanism by which the antibodies may induce the various manifestations is unknown. In the current study we evaluate...

  11. Psychological factors in recurrent genital herpes.

    OpenAIRE

    Green, J; Kocsis, A

    1997-01-01

    OBJECTIVES: To review recent research into psychological aspects of genital herpes and assess possible implications for clinical practice. METHODS: Review of all papers in the field on Medline 1985-96. RESULTS: Much attention has been paid to possible links between stress and recurrent genital herpes. There is no convincing evidence that stress in itself causes recurrences. It may be that recurrences are preceded by a prodromal period of altered mood. Patients with recurrences show considerab...

  12. 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...

  13. 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

    longevity. The involvement of heat shock protein 70 (Hsp70) in cellular maintenance and repair mechanisms, including its role as an anti-inflammatory protein, makes it a suitable candidate for studying such associations. We have studied the association of three single nucleotide polymorphisms, HSPA1A (-110A......>C), HSPA1B (1267A>G), and HSPA1L (2437T>C), present in the three HSP70 genes, with human survival, in a cohort of individuals born in the year 1905. This population cohort is a part of the longitudinal study of Danish nonagenarians. Since DNA samples were already collected in 1998, this gave us the...

  14. Efficacy and safety of dendrimer nanoparticles with coexpression of tumor necrosis factor-α and herpes simplex virus thymidine kinase in gene radiotherapy of the human uveal melanoma OCM-1 cell line

    Directory of Open Access Journals (Sweden)

    Wang YC

    2013-10-01

    Full Text Available Yingchih Wang,1,* Li Mo,2,* Wenbin Wei,1 Xuehui Shi1 1Beijing Tongren Eye Center, Capital Medical University, Beijing, People's Republic of China; 2Department of Ophthalmology, The 180th Hospital of PLA, Quanzhou, People's Republic of China *These authors contributed equally to this work Abstract: Human uveal melanoma is the most common primary intraocular tumor, and brachytherapy is one of the most common and effective treatment strategies. In order to find a safer and more effective way to increase the radio sensitivity of the tumor, we tried to use the dendrimer nanoparticle performing coexpression gene radiotherapy. In this study, we constructed recombinant DNA plasmids (early growth response-1 tumor necrosis factor-α [pEgr1-TNFα], pEgr1 thymidine kinase [TK], and pEgr1-TNFα -TK according to the Egr1 promoter sequence. The sequences of human TNFα and herpes simplex virus (HSV TK that were published by GenBank. Agarose gel electrophoresis and DNA sequencing had proven that we constructed the double-gene recombined plasmids pEgr1-TNF-TK correctly, as well as the plasmids pEgr1-TNFα and pEgr1-TK. The dendrimer nanoparticles combined with plasmid DNA as dendriplexes were verified with agarose gel electrophoresis and observed by transmission electron microscopy (TEM and scanning electron microscopy to define size and shape. Zeta potential was measured using a Zetasizer analyzer. Optimal size and neutral zeta-potential characteristics of dendriplexes were achieved for the transfection studies. DNase I examination proved that the dendriplexes could protect plasmid DNA for at least 6 hours. The recombinant plasmids were transfected with dendrimer nanoparticles into the human choroidal melanoma OCM-1 cell line, followed by exposure to iodine-125 (125I after transfection. After transfection with dendrimer nanoparticles and the irradiation of 125I, the gene expressions of TNFα and HSV1-TK were significantly increased at the protein level by

  15. 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.

  16. Low risk of anti-human leukocyte antigen antibody sensitization after combined kidney and islet transplantation.

    Science.gov (United States)

    Ferrari-Lacraz, Sylvie; Berney, Thierry; Morel, Philippe; Marangon, Nicola; Hadaya, Karine; Demuylder-Mischler, Sandrine; Pongratz, Gilles; Pernin, Nadine; Villard, Jean

    2008-07-27

    Anti-human leukocyte antigen (HLA) antibody could lead to humoral rejection and a decrease in graft survival after kidney transplantation. A recent report has suggested that islet transplantation alone is associated with a high rate of sensitization. The withdrawal of the immunosuppressive therapy because of the progressive nonfunction of the islets could explain the high rate of sensitization. Because the specific risk of immunization of multiple islet infusions remains unknown, we studied the immunization rate in our cohort of multiple islet infusions transplant recipients. De novo anti-HLA antibodies were analyzed in 37 patients after islets alone (n=8), islet-after-kidney (n=13), and simultaneous islet-kidney (n=16) transplantation by solid phase assays over time. The rate of immunization was 10.8% that is comparable with the risk of immunization after kidney transplantation alone. Multiple islet infusions do not represent a specific risk for the development of anti-HLA antibodies after combined kidney-islets transplantation. PMID:18645502

  17. Anti-human-cytomegalovirus immunoglobulin G levels in glioma risk and prognosis

    International Nuclear Information System (INIS)

    The role of human cytomegalovirus (HCMV) in glioma development and progression remains controversial. The purpose of our study was to assess the potential associations between anti-HCMV antibodies (immunoglobulin G [IgG] and immunoglobulin M [IgM]) and glioma risk and prognosis using data from the Harris County Case–Control Study. Multivariable logistic regression models were utilized to estimate odds ratios and 95% confidence intervals (CI) for the associations between glioma status and antibody levels among glioma cases (n = 362) and cancer-free controls (n = 462). Hazard ratios and 95% CIs were calculated using Cox proportional hazards regression, adjusting for age, race, and sex, to determine if antibody levels were associated with survival over time among cases. Among IgG-positive participants, increasing anti-HCMV IgG levels were associated with decreasing glioma risk (P for trend = 0.0008), and those with the lowest level of anti-HCMV IgG (<10 U/mL) had the highest glioma risk, controlling for age, sex, and race/ethnicity (OR: 2.51, 95% CI: 1.42–4.43). Antibody levels were not associated with survival among glioma cases. Our study contributes new evidence toward the potential importance of the direct and indirect effects of HCMV infection in gliomagenesis

  18. 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.

  19. Herpes simplex-virus type 1 påvist hos patient med herpes zoster

    DEFF Research Database (Denmark)

    Larsen, Helle Kiellberg; Schønning, Kristian; Danielsen, Patricia Louise

    2012-01-01

    In this case report we present an otherwise healthy 63 year-old male patient with herpes zoster corresponding to the 2nd left branch of the trigeminal nerve. Real time-polymerase chain reaction analyses were positive for both herpes simplex virus (HSV) type 1 and varicella zoster virus (VZV). The...

  20. 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

    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...... 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...... antimetabolites using two cell lines with different phenotypic origins, and found that it is effective in inhibiting the growth of these cell lines. Using immunohistochemistry, we also showed high or moderate expression levels of proteins targeted by the validated antimetabolite. Identified anti-growth factors...

  1. Targeting colorectal cancer with human anti-EGFR monoclonocal antibodies: focus on panitumumab

    Directory of Open Access Journals (Sweden)

    George P Kim

    2008-06-01

    Full Text Available George P Kim, Axel GrotheyCollege of Medicine, Mayo ClinicAbstract: The human anti-epidermal growth factor receptor (EGFR monoclonal antibody, panitumumab, represents a significant advance in the treatment of colorectal cancer. The strategy to target this receptor is based on sound cancer biology demonstrating its essential role in colorectal carcinogenesis. Panitumumab, unlike its predecessor, cetuximab, is fully human and thus reduces the incidence of hypersensitivity reactions. But, in several clinical trials, unexpected toxicities have become more apparent, raising concerns of how readily panitumumab can succeed cetuximab. This paper reviews the development of this agent and the pivotal clinical trials that help our understanding of its optimal use in colorectal cancer treatment.Keywords: colorectal cancer, chemotherapy, panitumumab, oxaliplatin, irinotecan, bevacizumab, cetuximab

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

    Directory of Open Access Journals (Sweden)

    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.

  4. A radioimmunoassay for the quantitative evaluation of anti-human acetylcholine receptor antibodies in myasthenia gravis

    International Nuclear Information System (INIS)

    A radioimmunoassay was developed for the quantitative evaluation of antibodies to the acetylcholine receptor in the serum of myasthenic patients. AcChR was extracted from human muscle. A detailed preparation of the 125I-labelled α-Bgt-AcChR complex used as antigen is reported. Usually, an average of 20 pmol were obtained from 100 g muscle. This preparation is stable for 1 month in presence of an inhibitor of proteolysis and sufficient for performing about fifteen assays. The labelled complex was incubated with increasing amounts of sera and precipitated with anti-human IgG serum. Titres were expressed in pmol 125I-labelled α-Bgt-AcChR complex precipitated per ml serum. Out of thirty-nine sera tested thirty-six had positive titres ranging from 0.1 to 46 pmol/ml. No anti-AcChR were detected in the sera from twenty-seven patients used as controls. (author)

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

    Directory of Open Access Journals (Sweden)

    Chung Myung

    2008-10-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

  6. 77 FR 41792 - Prospective Grant of Co-Exclusive License: The Development of Human Anti-CD22 Monoclonal...

    Science.gov (United States)

    2012-07-16

    ... hematological malignancies such as hairy cell leukemia, chronic lymphocytic leukemia and pediatric acute 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...

  7. 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

  8. Docking of anti-HIV-1 oxoquinoline-acylhydrazone derivatives as potential HSV-1 DNA polymerase inhibitors

    Science.gov (United States)

    Yoneda, Julliane Diniz; Albuquerque, Magaly Girão; Leal, Kátia Zaccur; Santos, Fernanda da Costa; Batalha, Pedro Netto; Brozeguini, Leonardo; Seidl, Peter R.; de Alencastro, Ricardo Bicca; Cunha, Anna Cláudia; de Souza, Maria Cecília B. V.; Ferreira, Vitor F.; Giongo, Viveca A.; Cirne-Santos, Cláudio; Paixão, Izabel C. P.

    2014-09-01

    Although there are many antiviral drugs available for the treatment of herpes simplex virus (HSV) infections, still the synthesis of new anti-HSV candidates is an important strategy to be pursued, due to the emergency of resistant HSV strains mainly in human immunodeficiency virus (HIV) co-infected patients. Some 1,4-dihydro-4-oxoquinolines, such as PNU-183792 (1), show a broad spectrum antiviral activity against human herpes viruses, inhibiting the viral DNA polymerase (POL) without affecting the human POLs. Thus, on an ongoing antiviral research project, our group has synthesized ribonucleosides containing the 1,4-dihydro-4-oxoquinoline (quinolone) heterocyclic moiety, such as the 6-Cl derivative (2), which is a dual antiviral agent (HSV-1 and HIV-1). Molecular dynamics simulations of the complexes of 1 and 2 with the HSV-1 POL suggest that structural modifications of 2 should increase its experimental anti-HSV-1 activity, since its ribosyl and carboxyl groups are highly hydrophilic to interact with a hydrophobic pocket of this enzyme. Therefore, in this work, comparative molecular docking simulations of 1 and three new synthesized oxoquinoline-acylhydrazone HIV-1 inhibitors (3-5), which do not contain those hydrophilic groups, were carried out, in order to access these modifications in the proposition of new potential anti-HSV-1 agents, but maintaining the anti-HIV-1 activity. Among the docked compounds, the oxoquinoline-acylhydrazone 3 is the best candidate for an anti-HSV-1 agent, and, in addition, it showed anti-HIV-1 activity (EC50 = 3.4 ± 0.3 μM). Compounds 2 and 3 were used as templates in the design of four new oxoquinoline-acylhydrazones (6-9) as potential anti-HSV-1 agents to increase the antiviral activity of 2. Among the docked compounds, oxoquinoline-acylhydrazone 7 was selected as the best candidate for further development of dual anti-HIV/HSV activity.

  9. 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.

  10. A case of transfusion-related acute lung injury induced by anti-human leukocyte antigen antibodies in acute leukemia

    OpenAIRE

    Jin, Sun Mi; Jang, Moon Ju; Huh, Ji Young; Park, Myoung Hee; Song, Eun Young; Oh, Doyeun

    2012-01-01

    Transfusion-related acute lung injury (TRALI) is a noncardiogenic pulmonary edema that occurs during or within 6 hours after transfusion. Risk factors for TRALI, which is relatively common in critically ill patients, include recent surgery, hematologic malignancy, and sepsis. Here, we report a case of TRALI induced by anti-human leukocyte antigen (anti-HLA) class II antibodies (HLA-DR) occurring after transfusion of platelet concentrates in a patient with acute leukemia. Although most patient...

  11. 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...

  12. Curcumin conjugated with PLGA potentiates sustainability, anti-proliferative activity and apoptosis in human colon carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Bhargav N Waghela

    Full Text Available Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116. The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy.

  13. 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.

  14. Understanding the conversation between machines: Heidegger's ontology of presence versus Lacan's anti-humanism

    Directory of Open Access Journals (Sweden)

    Katarina Peović Vuković

    2015-12-01

    Full Text Available This paper addresses the question of machine intelligence, a cybernetic problem closely related to the questions of subjectivity, human intelligence and the constitution of human communication. The example of chatterbots and their (movie representations will be used in order to reexamine their similarities and differences, as well as their relation to subjectivity in the broadest sense. Reversing the thesis on the instrumentalisation of the subject by means of a cybernetic framework, which is, as Martin Heidegger claimed, established as a paradigmatic framework of contemporary sciences, the paper will point to the closest relation between the subject and the mechanical or digital quasi-intelligent machine. Jacques Lacan's applied psychoanalysis provides a theoretical framework for this paper since it is in a position to point out the inadequacies of understanding communication as a means of conveying information. Such critique will prove to be fruitful not only for describing communication and the difference between the machinal and the human, but also for indicating the problems of identity politics. Lacan's anti-humanism and ethics of separation appear as tools of contemporary critique of political economy.

  15. 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

  16. Local production of donkey anti-rabbit's sera for human prolactin radioimmunoassay

    International Nuclear Information System (INIS)

    Pure Rabbit's IgG was used in this study to raise donkey anti rabbit's sera to be used as separating agent in radioimmunoassay. Two healthy donkeys have been immunized. The anti rabbit's sera have been titrated as (i) crude, (ii) purified and dialysed coupled to magnetic particles. Then this antibody was used as separating agent in a radioimmunoassay for measurement of human prolactin (PRL). Coupled Sudanese donkey and rabbit's sera (Sud-DARS) was used as 1/8 titre using chelsea RIA kit for human prolactin while 1/200 of liquid Sud-DARS was found to be the best titre using the Chinese kit. The best condition for estimation of the prolactin were optimized by determining the suitable incubation time and temperature. The assay can be done at room temperature but it should be incubated for 6 hours as recommended by the Chinese kit. Validity tests were done. The regression coefficients were 0.994 and 0.999 for linearity and recovery tests respectively. Measurement of human PRL wa found to be reproducible using Sud-DARS as separating agent since the coefficient of variation (C.V. %) was found to be less than 15% for both within batch and between assays. Comparing SudDARS to the Chinese kit, separating agent as reference agent, regression coefficient was found to be 0.977 which indicate that Sud-DARS can be used as separating agent. Prolactin in Sudanese subject was determined using the Chinese kit the Sud-DARS as separating agent. The ranges were 74-398 mIU/L in males and 102-414 mI/L in the preovulatory phase for the females while in the post ovulatory phase it was 114-442 mIU/L. Ovulation was confirmed by measurement of progesterone level 7 days before the next suspected mensuration. (Author)

  17. 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.

  18. Latency of herpes simplex virus in ocular tissue of mice.

    OpenAIRE

    Openshaw, H

    1983-01-01

    At 5 to 7 months after corneal inoculation of herpes simplex virus type 1 in mice, explants of ocular tissue yielded virus. Immunoperoxidase study of explants undergoing reactivation revealed herpes simplex virus antigens in retinal tissue. These results indicate that herpes simplex virus can establish and maintain latency in ocular tissue, most probably in the retina.

  19. 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.

  20. 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.

  1. 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...

  2. 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....

  3. A Study of the Antiviral Effect of the Essential oil of Zataria Multiflora Boiss on Herpes Simplex Type 1 in Vero Cell Culture

    Directory of Open Access Journals (Sweden)

    Mardani M.

    2012-02-01

    Full Text Available Statement of Problems: Herpes Simplex type 1 (HSV-1 is associated with different human infections including oral infection. Acyclovir is used for the treatment of such herpetic infections. However, acyclovir resistant HSVs are increasing nowadays due to the lack of thymidine kinase activity in HSV mutants. So, researchon alternative treatment is urgently required. Purpose: The aim of this study was to examine the effect of essential oil of Zataria multiflora Boiss on herpes simplex type 1 in Vero cell culture.Materials and Method: The essence of Zataria multiflora was prepared by the clevenger apparatus and used for the experiments in Vero cell culture. Cytotoxic effect of increasing concentrations of the essence from 0.001-0.02% was assessed on Vero cell line and antiviral effect of the essence was studied in Vero cells, using plaque reduction method. The data were analyzed by one way ANOVA using SPSS, version 17.Results: The 50% cytotoxic concentration (CC50 of Zataria multiflora essential oil for Vero cells and 50% inhibitory concentration (IC50 were 0.067% and 0.0059%, respectively. Compared to the controls, all the above used concentrations had the inhibitory effect on HSV-1 ( p <0.05. Concentrations of 0.1- 0.2% showed a complete anti-HSV-1 inhibitory effect. Conclusion: The results of this study showed that essential oil of Zataria multiflora Boiss has a significant inhibitory effect on HSV-1, so it may be used as an anti-herpetic mouthwash candidate for the control of oral HSV infections. However, in vivo studies might be necessary for determining its exact toxic effects on human cells.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. Anti-proliferative effects of protein kinase C inhibitors in human keratinocytes.

    Science.gov (United States)

    Hegemann, L; Bonnekoh, B; van Rooijen, L A; Mahrle, G

    1992-07-01

    Various lines of evidence indicate that protein kinase C, a key enzyme in transmembraneous signal transduction, is involved in the regulation of keratinocyte proliferation. In the present study we have investigated the effects of various structurally unrelated protein kinase C inhibitors on the proliferation of HaCa T cells, a non-tumorigenic human keratinocyte cell line. All protein kinase C inhibitors dose-dependently inhibited cell proliferation as assessed by the incorporation of radioactively labelled thymidine and amino acids as well as the increase in total protein content in keratinocytes. The potencies of the drugs to inhibit cell proliferation were strongly correlated to their inhibitory potency on purified protein kinase C, displaying a correlation coefficient of 0.97. Methotrexate, an anti-proliferative drug, was found not to inhibit protein kinase C. Therefore, our data provide evidence that protein kinase C is crucially involved in the regulation of keratinocyte proliferation but is not the only target of anti-proliferative drug action. PMID:1390454

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

    Science.gov (United States)

    Jadoon, Saima; Karim, Sabiha; Asad, Muhammad Hassham Hassan Bin; Akram, Muhammad Rouf; Kalsoom Khan, Abida; 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

  10. Anti-Oxidative Stress Activity of Stachys lavandulifolia Aqueous Extract in Human

    Directory of Open Access Journals (Sweden)

    Naser Hosseini

    2013-01-01

    Full Text Available Medicinal plants are presumed to be natural sources of antioxidants that protect organisms from oxidative stresses. The present investigation aims to study the anti-oxidative stress activity of the Stachys lavandulifolia (S. lavandulifolia plant. This trial was conducted on 26 healthy human subjects. The study was done in a before after fashion. The included subjects were asked to consume the prepared infusion from 3 g aerial parts of S. lavandulifolia on a daily basis. Doses were administered in every morning and evening for 14 days. At the beginning and the end of the study, blood samples were acquired to determine the level of cellular lipid peroxidation and the total content of serum antioxidants. Biomarkers analyzed from samples obtained before start of treatment and 14 days post treatment, were subjected to paired t test analysis. Total blood antioxidants increased and reached from 2.3 ± 0.84 μmol/ml to 3.3 ± 0.54 μmol/ml. The lipid peroxidation reduced and reached from 8.38 ± 1.78 to 11.6 ± 2.64 nmol/ml. The results suggest that S. lavandulifolia possesses marked anti-oxidative stress activity and it can be useful as a supplement in the management of diseases related to oxidative stress (Registration Number: IRCT2013012210003N2.

  11. 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

  12. 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.

  13. [Epidemiologic profile of human anti-rabies treatment in Porto Alegre, RS, brazil].

    Science.gov (United States)

    Veloso, Rejane Dias; Aerts, Denise Rangel Ganzo de Castro; Fetzer, Liane Oliveira; Anjos, Celso Bittencourt Dos; Sangiovanni, José Carlos

    2011-12-01

    Animal bites are injuries that carry the risk of rabies transmission, a disease with a 100% mortality rate. The purpose of this study was to determine the epidemiologic profiles of post exposure human anti-rabies treatments and to analyze whether prescriptions were appropriate. This cross-sectional study collected data from the forms of the Brazilian Notification System (Sistema Nacional Agravos de Notificação - SINAN), which were filled out by the professionals responsible for treatment in healthcare services in the second semester of 2006. Of the 2,223 cases identified, 50.3% of the individuals were male, the age group with the greatest number of cases was 20 to 59 years (47.6%); the type of injury responsible for the largest number of medical consultations was animal bite (87.4%), and 35.3% of the injuries were in the lower extremities. Dogs were the animals that caused the most injuries (91.7%). The analysis of type of treatment showed that vaccination was prescribed for 78.1% of the individuals, and anti-rabies serum, for 6.4%. Of the all treatments, 96.2% were classified as correctly prescribed. Although treatments were classified as necessary, the option of keeping animals that cause aggressions under observation should be considered so that the number of treatments administered can be reduced. PMID:22124927

  14. Anti-human CD138 monoclonal antibodies and their bispecific formats: generation and characterization.

    Science.gov (United States)

    Chen, Dan; Zou, Jianxuan; Zong, Yunhui; Meng, Huimin; An, Gangli; Yang, Lin

    2016-06-01

    Syndecan-1 (CD138), a heparan sulfate proteoglycan, acts as a co-receptor for growth factors and chemokines and is a molecular marker associated with the epithelial-mesenchymal transition during development and carcinogenesis. In this study, we generated two specific mouse anti-human CD138 monoclonal antibodies (mAbs, clone ID: 480CT5.4.3, 587CT7.3.6.5) using hybridoma technology and identified their immunological characteristics. After hybridoma sequencing, the single-chain variable fragments (ScFvs) cloned from two hybridoma cells were combined with anti-CD3 OKT-3 ScFv to generate two recombinant bispecific antibodies (h-STL002, m-STL002) against CD138 and CD3 molecules, respectively. The bispecific antibodies were able to specifically target CD138 + multiple myeloma (MM) cells and CD3 + T cells, and showed the potent cytotoxicity against MM RPMI-8226 cell line through T cell activation. However, these bispecific antibodies without T cells did not cause toxic side effect on MM cells. Overall, the two hybridoma clones and their bispecific formats have great potential to promote diagnosis and immunotherapy of plasma cell malignancy. PMID:26954291

  15. Herpes Zoster Ophthalmicus With Oculomotor Nerve Palsy

    Directory of Open Access Journals (Sweden)

    Viroj WIWANITKIT

    2010-03-01

    Full Text Available Editor, I read the recent publication on a case of herpes zoster ophthalmicus with oculomotor nerve palsy by Yildiz et al with a great interest(4. As Yildiz et al noted, this is a rare neurological complication of herpes zoster(4. Haargaard et al proposed that “Central nervous system involvement after varicella zoster virus infection is an uncommon, but potentially life-threatening, complication. (2” This complication is usually acute(1 and the early antiviral treatment is not proved useful on the prevention(3. There is still no present recommended effective mean for prevention and treatment of this condition. Further research to assess the pathogenesis and natural history of oculomotor nerve palsy in herpes zoster ophthalmicus is recommended.

  16. Herpes Zoster-Induced Ogilvie's Syndrome

    Science.gov (United States)

    Masood, Irfan; Majid, Zain; Rind, Waqas; Zia, Aisha; Riaz, Haris; Raza, Sajjad

    2015-01-01

    Ogilvie's syndrome due to herpes zoster infection is a rare manifestation of VZV reactivation. The onset of rash of herpes zoster and the symptoms of intestinal obstruction can occur at different time intervals posing a significant diagnostic challenge resulting in avoidable surgical interventions. Herein, we describe a case of 35-year-old male who presented with 6-day history of constipation and colicky abdominal pain along with an exquisitely tender and vesicular skin eruption involving the T8–T11 dermatome. Abdominal X-ray and ultrasound revealed generalized gaseous distention of the large intestine with air up to the rectum consistent with paralytic ileus. Colonoscopy did not show any obstructing lesion. A diagnosis of Ogilvie's syndrome associated with herpes zoster was made. He was conservatively managed with nasogastric decompression, IV fluids, and acyclovir. The patient had an uneventful recovery and was later discharged. PMID:26664758

  17. 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)

  18. Radiolabelled anti-human fibrin antibody: a new thrombus-detecting agent

    International Nuclear Information System (INIS)

    Rabbit anti-human fibrin globulin (A.F.G.) was labelled with iodine (131I) and used as a thrombus-detecting agent. 131I-A.F.G. labelled thrombi were displayed by means of a gamma scintillation camera. Normal subjects and patients with thrombo-phlebitis of legs, acute fibrin depositions other than thrombi, and chronic varicosities were examined. The 131I-A.F.G. technique detected both formed thrombi and those that were forming and could discriminate between acute thrombosis and chronic varicosities. Thrombo-phlebitis and extravascular fibrin depositions were best demonstrated between 24 and 72 hours after 131I-A.F.G. injection. Radiolabelled A.F.G. in normal veins and chronic varicosities was best displayed within 6 hours of injection. (author)

  19. Which follicles make the most anti-Mullerian hormone in humans?

    DEFF Research Database (Denmark)

    Jeppesen, J V; Anderson, R A; Kelsey, T W;

    2013-01-01

    Anti-Müllerian hormone (AMH) is exclusively produced by granulosa cells (GC) of the developing pre-antral and antral follicles, and AMH is increasingly used to assess ovarian function. It is unclear which size follicles make the most AMH (total content) and are the main contributors to circulating...... AMH concentrations. To determine AMH gene expression in GC (q-RT-PCR) and follicular AMH production (Elisa and RIA) in relation to follicular development, 87 follicles (3-13 mm diameter) including both GC and the corresponding follicular fluid (FF) were collected in connection with fertility...... preservation of human ovaries. Further, follicle number and diameter, graded in 1 mm increments, were determined by 3D ultrasound in 113 women in their natural menstrual cycle to determine follicle number and diameter in relation to circulating AMH levels. This study demonstrates for the first time a positive...

  20. 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...... at the levels of maintenance of stress protein profile; reduction in the accumulation of oxidatively and glycoxidatively damaged proteins; stimulation of the proteasomal activities for the degradation of abnormal proteins; improved cellular resistance to ethanol, hydrogenperoxide, and ultraviolet-B rays......; and enhanced levels of various antioxidant enzymes. We are now undertaking a detailed analysis of the signal transduction pathways to determine alterations in the phosphorylation and dephosphorylation states of extracellular signal-related kinase, c-Jun terminal kinase and p38 MAP-kinases as a measure...

  1. Properties of a glycopeptide isolated from human Tamm-Horsfall glycoprotein. Interaction with leucoagglutinin and anti-(human Tamm-Horsfall glycoprotein) antibodies.

    Science.gov (United States)

    Abbondanza, A; Franceschi, C; Licastro, F; Serafini-Cessi, F

    1980-01-01

    A sialylated glycopeptide isolated after Pronase digestion of human Tamm-Horsfall glycoprotein behaves as a powerful monovalent hapten in the precipitin reaction between human Tamm-Horsfall glycoprotein and leucoagglutinin, but fails to inhibit the interaction of the glycoprotein with rabbit anti-(human Tamm-Horsfall glycoprotein) antibodies. The glycopeptide is much less active than the intact glycoprotein as an inhibitor of lymphocyte transformation induced by leucoagglutinin. PMID:6967312

  2. 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

  3. Radionuclide imaging in herpes simplex encephalitis

    International Nuclear Information System (INIS)

    Eight patients with herpes simplex encephalitis among the 10 cases diagnosed at the University of Kansas Medical Center from 1966 to 1976 were studied with /sup 99m/Tc early in their diagnostic work-up. The images were unilaterally positive in the temporal lobe area in all 8 patients. Radionuclide studies can suggest herpes simplex as the specific etiology in cases of encephalitis and can also indicate the best site for brain biopsy to confirm the diagnosis by fluorescent antibody techniques. Appropriate antiviral therapy should be instituted as soon as possible to alter the course of this destructive form of viral encephalitis

  4. Benzalkonium Chloride Intoxication Mimicking Herpes Zoster Encephalitis

    Directory of Open Access Journals (Sweden)

    Ekrem Güler

    2011-06-01

    Full Text Available Benzalkonium chloride (BAC is a frequently used disinfectant and its most well-known side effect is contact dermatitis. In this report, two children who had vesicular dermatitis, headache, lethargy, fever and encephalopathy mimicking Herpes zoster encephalitis were presented. Their consciousness level improved on the second day. From the medical history it was understood that the mother had applied 20% BAC solution to the scalps of two children. The aim of the presentation of this report is to draw attention to the fact that BAC application to the scalp for treating pediculosis capitis may resemble the herpes encephalitis clinical picture.

  5. Acute lymphocytic crisis following herpes simplex type 1 virus hepatitis in a nonimmunocompromised man: a case report

    Directory of Open Access Journals (Sweden)

    Plastiras Sotiris

    2009-08-01

    Full Text Available Abstract Introduction An increase in circulating lymphocytes can be seen following infections such as infectious mononucleosis and pertussis, or in lymphoproliferative disorders such as acute and chronic lymphocytic leukemia. Acute lymphocytic crisis following herpes simplex virus hepatitis has not been described in the literature. Case presentation A 52-year-old man was admitted to our hospital reporting low-grade fever for the previous seven days, and fatigue. During the fifth day of hospitalization, the patient developed a lymphocytic crisis and, after further tests the patient was diagnosed as having herpes simplex virus hepatitis. Conclusion This case report shows that herpes simplex virus type 1 is a possible cause of an acute lymphocytic crisis similar to other well known infectious agents such as Epstein–Barr virus, cytomegalovirus, human immunodeficiency virus, human herpes virus type 6, adenovirus, toxoplasma and human T-cell lymphotropic virus. Furthermore, this case report expands the clinical spectrum of herpes simplex virus hepatitis, since it is reported in a nonimmunocompromised patient presenting with atypical acute lymphocytic syndrome.

  6. 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.

  7. 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

  8. 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.

  9. 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 consumptio...

  10. 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...

  11. 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.

  12. Herpes zoster ophthalmicus with total ophthalmoplegia

    Directory of Open Access Journals (Sweden)

    Talwar S

    1990-01-01

    Full Text Available A case of unilateral herpes zoster ophthalmicus (HZO is reported with ipsilateral involvement of III, IV and VI cranial nerves which led to extra ocular muscles palsy presenting as total ophthalmopegia along with ptosis, cycloplegia and dilated non reactive pupil.

  13. Oropharyngeal herpes simplex in an adult

    OpenAIRE

    Yelankar, Haritosh K.; Paul, Sharmila P.

    2003-01-01

    Herpis simplex 1 infection involving the orophaiynx in an adult is a rare entity, as, primary infection with type I herpes simplex is commonly seen in children and c auses a severe vesicular and ulcertive stomatitis and occasionally spreads to the oropharynx

  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. Anorexia nervosa with herpes simplex encephalitis

    OpenAIRE

    George, G. C. W.

    1981-01-01

    Studies of patients suffering from anorexia nervosa appear to show an increased immunity to certain infections, as well as immunological deficiencies. This is the report of a patient with anorexia nervosa who developed herpes simplex encephalitis, a condition associated with lowered immunological defence mechanisms.

  16. 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

  17. 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...

  18. A Study of the Antiviral Effect of the Essential oil of Zataria Multiflora Boiss on Herpes Simplex Type 1 in Vero Cell Culture

    OpenAIRE

    Mardani M; Motamedifar M.; Hoseinipour R.

    2012-01-01

    Statement of Problems: Herpes Simplex type 1 (HSV-1) is associated with different human infections including oral infection. Acyclovir is used for the treatment of such herpetic infections. However, acyclovir resistant HSVs are increasing nowadays due to the lack of thymidine kinase activity in HSV mutants. So, researchon alternative treatment is urgently required. Purpose: The aim of this study was to examine the effect of essential oil of Zataria multiflora Boiss on herpes simplex type 1 in...

  19. Dermatitis herpetiformis sera or goat anti-transglutaminase-3 transferred to human skin-grafted mice mimics dermatitis herpetiformis immunopathology.

    Science.gov (United States)

    Zone, John J; Schmidt, Linda A; Taylor, Ted B; Hull, Christopher M; Sotiriou, Michael C; Jaskowski, Troy D; Hill, Harry R; Meyer, Laurence J

    2011-04-01

    Dermatitis herpetiformis (DH) is characterized by deposition of IgA in the papillary dermis. However, indirect immunofluorescence is routinely negative, raising the question of the mechanism of formation of these immune deposits. Sárdy et al. (2002. J. Exp. Med. 195: 747-757) reported that transglutaminase-3 (TG3) colocalizes with the IgA. We sought to create such deposits using passive transfer of Ab to SCID mice bearing human skin grafts. IgG fraction of goat anti-TG3 or control IgG were administered i.p. to 20 mice. Separately, sera from seven DH patients and seven controls were injected intradermally. Biopsies were removed and processed for routine histology as well as direct immunofluorescence. All mice that received goat anti-TG3 produced papillary dermal immune deposits, and these deposits reacted with both rabbit anti-TG3 and DH patient sera. Three DH sera high in IgA anti-TG3 also produced deposits of granular IgA and TG3. We hypothesize that the IgA class anti-TG3 Abs are directly responsible for the immune deposits and that the TG3 is from human epidermis, as this is its only source in our model. These deposits seem to form over weeks in a process similar to an Ouchterlony immunodiffusion precipitate. This process of deposition explains the negative indirect immunofluorescence results with DH serum. PMID:21335491

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus

    OpenAIRE

    Dörner, Thomas; Kaufmann, Joerg; Wegener, William A.; Teoh, Nick; David M Goldenberg; Burmester, Gerd R

    2006-01-01

    B cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE), so the safety and activity of anti-B cell immunotherapy with the humanized anti-CD22 antibody epratuzumab was evaluated in SLE patients. An open-label, single-center study of 14 patients with moderately active SLE (total British Isles Lupus Assessment Group (BILAG) score 6 to 12) was conducted. Patients received 360 mg/m2 epratuzumab intravenously every 2 weeks for 4 doses with analgesic/antihistamine pr...

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Trefoil Factor 3 Is Oncogenic and Mediates Anti-Estrogen Resistance in Human Mammary Carcinoma

    Directory of Open Access Journals (Sweden)

    Nagarajan Kannan

    2010-12-01

    Full Text Available 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.

  11. Anti-proliferative action of silibinin on human colon adenomatous cancer HT-29 cells

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    Reyhan Akhtar

    2014-02-01

    Full Text Available Background: Silibinin a flavonoid from milk thistle (Silybum marianum exhibit a variety of pharmacological actions, including anti-proliferative and apoptotic activities against various types of cancers in intact animals and cancer cell lines. In the present study, the effect of silibinin on human colon cancer HT-29 cells was studied. Method: Incubations of cells with different silibinin concentrations (0.783-1,600 μg/ml for 24, 48 or 72 h showed a progressive decline in cell viability. Results: Loss of cell viability was time dependent and optimum inhibition of cell growth (78% was observed at 72 h. Under inverted microscope, the dead cells were seen as cell aggregates. IC50 (silibinin concentration killing 50% cells values were 180, 110 and 40μg/ml at 24, 48 and 72 h respectively. Conclusion: These findings re-enforce the anticancer potential of silibinin, as reported earlier for various other cancer cell lines (Ramasamy and Agarwal (2008, Cancer Letters, 269: 352-62.

  12. 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

  13. 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

  14. 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

  15. 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...

  16. 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

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

    International Nuclear Information System (INIS)

    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 β-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 H2O/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: → LDL cholesterol is a risk factor in the development of coronary heart diseases. → Antibodies against LDL are used for the selective extracorporeal removal of LDL. → Protein A is used for the oriented immobilization of anti LDL onto PHEMA cryogel. → PHEMA cryogels are biocompatible, exhibit a low pressure drop, lack diffusion resistance and viscous samples can be

  18. 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

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

    International Nuclear Information System (INIS)

    Highlights: ► Chemerin is a novel adipocytokine with almost unknown function in vasculature. ► Chemerin activates Akt/eNOS/NO pathways in endothelial cells. ► Chemerin inhibits TNF-α-induced monocyte adhesion to endothelial cells. ► Chemerin inhibits TNF-induced VCAM-1 via suppressing NF-κB and p38 signal. ► 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)-κB p65 (Ser536) and p38 as well as vascular cell adhesion molecule (VCAM)-1 expression induced by tumor necrosis factor (TNF)-α (5 ng/ml, 20 min–6 h). Inhibitor of NF-κB or p38 significantly inhibited the TNF-α-induced VCAM-1 expression. Chemerin also inhibited TNF-α-induced VCAM-1 expression in rat isolated aorta. Moreover, chemerin significantly inhibited monocytes adhesion to TNF-α-stimulated endothelial cells. The inhibitory effect of chemerin on TNF-α-induced VCAM-1 was reversed by a NOS inhibitor. Conversely, an NO donor, sodium nitroprusside significantly inhibited TNF-α-induced VCAM-1. The present results for the first time demonstrate that chemerin plays anti-inflammatory roles by preventing TNF-α-induced VCAM-1 expression and monocytes adhesion in vascular endothelial cells. The effect is mediated via inhibiting activation of NF-κB and p38 through stimulation of Akt/eNOS signaling and NO production.

  20. Herpes zoster duplex bilateralis in an immunocompetent host

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    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.

  1. 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.

  2. 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

  3. 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

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

    Directory of Open Access Journals (Sweden)

    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

  5. 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.

  6. Serological analysis of human anti-human antibody responses in colon cancer patients treated with repeated doses of humanized monoclonal antibody A33.

    Science.gov (United States)

    Ritter, G; Cohen, L S; Williams, C; Richards, E C; Old, L J; Welt, S

    2001-09-15

    Mouse monoclonal antibody A33 (mAb A33) recognizes a M(r) 43,000 cell surface glycoprotein (designated A33) expressed in human colonic epithelium and colon cancer but absent from most other normal tissues. In patients, mAb A33 localizes with high specificity to colon cancer and is retained for up to 6 weeks in the cancer but cleared rapidly from normal colon (5-6 days). As a carrier of (125)I or (131)I, mAb A33 has shown antitumor activity. Induction of strong human anti-mouse antibody (immunoglobulin; HAMA) responses in patients, however, limits the use of the murine mAb A33 to very few injections. A humanized version of this antibody (huAb A33) has been prepared for Phase I and II clinical studies in patients with colon cancer. In those studies, immunogenicity of huAb A33 has been monitored using a novel, highly sensitive BIACORE method, which allows measurement of human anti-human antibodies (HAHAs) without the use of secondary reagents. We found that 63% (26 of 41) of the patients treated with repeated doses of huAb A33 developed HAHAs against a conformational antigenic determinant located in the V(L) and V(H) regions of huAb A33. Detailed serological analysis showed two distinct types of HAHAs. HAHA of type I (49% of patients) was characterized by an early onset with peak HAHA levels after 2 weeks of treatment, which declined with ongoing huAb A33 treatment. HAHA of type II (17% of patients) was characterized by a typically later onset of HAHA than in type I and by progressively increasing HAHA levels with each subsequent huAb A33 administration. Colon cancer patients with type I HAHAs did not develop infusion-related adverse events. In contrast, HAHA of type II was indicative of infusion-related adverse events. By using this new method, we were able to distinguish these two types of HAHAs in patients while on antibody treatment, allowing patients to be removed from study prior to the onset of severe infusion-related adverse events. PMID:11559561

  7. 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.

  8. Human parvovirus B19, varicella zoster virus, and human herpes virus 6 in temporal artery biopsy specimens of patients with giant cell arteritis: analysis with quantitative real time polymerase chain reaction

    OpenAIRE

    Alvarez-Lafuente, R.; Fernandez-Gutierr..., B; Jover, J; Judez, E; Loza, E; Clemente, D; Garcia-Asenjo, J; Lamas, J

    2005-01-01

    Methods: Temporal artery biopsy specimens from 57 patients with GCA and 56 controls were investigated. DNA was obtained by biopsy, and quantitative real time polymerase chain reaction assay performed to establish the prevalence and viral load of B19, VZV, and HHV-6. Amplification of the human ß-globin gene was used as internal positive control.

  9. 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

  10. 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.

  11. 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.

  12. 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 ...

  13. Age-Related Changes in the Mechanical Properties of Human Fibroblasts and Its Prospective Reversal After Anti-Wrinkle Tripeptide Treatment

    OpenAIRE

    Dulińska-Molak, Ida; Pasikowska, Monika; Pogoda, Katarzyna; Lewandowska, Małgorzata; Eris, Irena; Lekka, Małgorzata

    2013-01-01

    One of an essential characteristic of human skin are time dependent mechanical properties. Here, we demonstrate that stiffness of human dermal fibroblast correlates with age and it can be restored after anti-wrinkle tripeptide treatment. The stiffness of human fibroblasts isolated from donors of 30-, 40- and 60 years old were examined. Additionally the effect of anti- wrinkle tripeptide of latter cells was investigated. The atomic force microscopy measurements were performed on untreated fibr...

  14. 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.

  15. 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

  16. Light Microscopy, Culture, Molecular, and Serologic Methods for Detection of Herpes Simplex Virus

    OpenAIRE

    Anderson, Neil W.; Buchan, Blake W.; Ledeboer, Nathan A.

    2014-01-01

    Herpes simplex virus 1 (HSV-1) and 2 (HSV-2) cause a variety of human diseases, ranging from acute to chronic and mild to severe. The absence of curative therapy results in lifelong carriage marked by recurrent outbreaks and allows transmission of the virus to uninfected individuals. Nonspecific lesions, variable presentation, and chronic carriage necessitate the use of different laboratory testing methods appropriate for each presentation. A thorough understanding of the performance characte...

  17. 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.

  18. In vivo reactivation of herpes simplex virus in rabbit trigeminal ganglia: electrode model.

    OpenAIRE

    Green, M T; Rosborough, J. P.; Dunkel, E C

    1981-01-01

    The rabbit provides an excellent model for the study of ocular herpes because herpetic keratitis in the rabbit eye resembles human disease in its clinical features and in its propensity for spontaneous recurrence. This paper presents a method for the electrical induction of multiple episodes of in vivo reactivation of latent HSV-1 infection with peripheral shedding of virus. Physiological levels of current delivered via an electrode implanted over the trigeminal ganglion of latently infected ...

  19. 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.

  20. Herpes zoster: Burden of disease in France.

    OpenAIRE

    Gonzalez Chiappe, Solange; Sarazin, Marianne; Turbelin, Clément; Lasserre, Andrea; Pelat, Camille; Bonmarin, Isabelle; Chosidow, Olivier; Blanchon, Thierry; Hanslik, Thomas

    2010-01-01

    This work provides estimates of HZ incidence and HZ-related hospitalization and mortality rates in France, where no immunization programme has been implemented. Herpes zoster data was obtained from the Sentinelles surveillance general practitioners (GPs) network, the PMSI Data processing centre for hospital discharges and from the French National Mortality Database (INSERM CépiDC). The yearly HZ incidence rate averaged 382 cases per 100,000 inhabitants (95% CI 364-405) and exponentially incre...

  1. Computed tomography of herpes simplex encephalitis

    International Nuclear Information System (INIS)

    Referring to 9 patients of our own material we report on the pattern of distribution and the development of CT-changes in herpes simplex encephalitis (HSE). Our cases include the outstanding findings of a primarily hemorrhagic HSE and an extensive calcification at the residual stage on the borderline of widespread tissue necrosis on a baby. With respect to literature we receive a quite homogenous picture, reflecting the crucial characteristics of the disease as known from neuropathology. (orig.)

  2. Serial CT scannings in herpes simplex encephalitis

    International Nuclear Information System (INIS)

    Two patients with serologically confirmed herpes simplex encephalitis were studied by serial CT scannings. Case 1, a 60-year-old woman, was admitted to National Cardiovascular Center because of headache, fever, and attacks of Jacksonian seizure. Case 2, a 54-year-old man, was admitted because of fever, consciousness disturbance and right hemipare sis. Pleocytosis (mainly lymphocytes) and elevation of protein content in cerebrospinal fluid were observed in both cases. Both patients presented ''das apallische Syndrom'' one month after admission. The diagnosis of herpes simplex encephalitis was confirmed by typical clinical courses and by greater than fourfold rises in serum antibody titer for herpes simplex virus as well as that in cerebrospinal fluid in case 1. Characteristic CT findings observed in these two cases were summarized as follows: Within a week after the onset, no obvious abnormalities could be detected on CT scans (Case 1). Two weeks after the onset, a large low-density area appeared in the left temporal lobe and in the contralateral insular cortex with midline shift toward the right side (Case 2). One month later, an ill-defined linear and ring-like high-density area (Case 1), or a well-defined high-density area (Case 2), that was enhanced after contrast administration, was observed in the large low-density area in the temporal lobe. These findings were considered as characteristic for hemorrhagic encephalitis. These high-density areas disappeared two months later, however, widespread and intensified low-density areas still remained. In both cases, the basal ganglia and thalamus were completely spared on CT scans. From these observations, it can be concluded that serial CT scannings are quite useful for diagnosis of herpes simplex encephalitis. (author)

  3. Granuloma annulare in herpes zoster scars.

    Science.gov (United States)

    Ohata, C; Shirabe, H; Takagi, K; Kawatsu, T

    2000-03-01

    A 54-year-old Japanese female developed granuloma annulare twice in herpes zoster scars. Soon after the second event, she developed ulcerative colitis, which was well controlled by sulfonamides and corticosteroid suppository. She had no history of diabetes mellitus. There was no recurrence of granuloma annulare by June of 1999. Granuloma annulare might have contributed to the complications of ulcerative colitis, although this had not been noticed before. PMID:10774142

  4. Herpes simplex virus colitis in a neonate.

    Science.gov (United States)

    Daley, Andrew J; Craven, Paul; Holland, Andrew J A; Jones, Cheryl A; Badawi, Nadia; Isaacs, David

    2002-09-01

    Involvement of the gastrointestinal tract in neonates with congenital herpes simplex virus (HSV) infection is rarely described. We report a case of a newborn with disseminated HSV infection associated with profuse hematochezia and late sigmoid colon perforation. Histologic examination showed patchy areas of ulceration with multinucleated giant cells and HSV nucleic acid was detected by polymerase chain reaction in colonic tissue. No clinically apparent episodes of recurrent colitis occurred in the first year of life. PMID:12380594

  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. Potent Inhibition of Human Immunodeficiency Virus Type 1 Replication by an Intracellular Anti-Rev Single-Chain Antibody

    Science.gov (United States)

    Duan, Lingxun; Bagasra, Omar; Laughlin, Mark A.; Oakes, Joseph W.; Pomerantz, Roger J.

    1994-05-01

    Human immunodeficiency virus type 1 (HIV-1) has a complex life cycle, which has made it a difficult target for conventional therapeutic modalities. A single-chain antibody moiety, directed against the HIV-1 regulatory protein Rev, which rescues unspliced viral RNA from the nucleus of infected cells, has now been developed. This anti-Rev single-chain construct (SFv) consists of both light and heavy chain variable regions of an anti-Rev monoclonal antibody, which, when expressed intracellularly within human cells, potently inhibits HIV-1 replication. This intracellular SFv molecule is demonstrated to specifically antagonize Rev function. Thus, intracellular SFv expression, against a retroviral regulatory protein, may be useful as a gene therapeutic approach to combat HIV-1 infections.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    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

  13. Interaction of anti-phospholipid antibodies with late endosomes of human endothelial cells.

    Science.gov (United States)

    Galve-de Rochemonteix, B; Kobayashi, T; Rosnoblet, C; Lindsay, M; Parton, R G; Reber, G; de Maistre, E; Wahl, D; Kruithof, E K; Gruenberg, J; de Moerloose, P

    2000-02-01

    Anti-phospholipid antibodies (APLAs) are associated with thrombosis and/or recurrent pregnancy loss. APLAs bind to anionic phospholipids directly or indirectly via a cofactor such as beta(2)-glycoprotein 1 (beta(2)GPI). The lipid target of APLA is not yet established. Recently, we observed that APLAs in vitro can bind lysobisphosphatidic acid (LBPA). The internal membranes of late endosomes are enriched in this phospholipid. The current study was undertaken to determine to what extent binding of APLA to LBPA is correlated with binding to cardiolipin and to beta(2)GPI and to determine whether patient antibodies interact with late endosomes of human umbilical vein endothelial cells (HUVECs) and thus modify the intracellular trafficking of proteins. Binding of patient immunoglobulin G (n=37) to LBPA was correlated significantly with binding to cardiolipin. Although LBPA binding was correlated to a lesser extent with beta(2)GPI binding, we observed that beta(2)GPI binds with high affinity to LBPA. Immunofluorescence studies showed that late endosomes of HUVECs contain LBPA. Patient but not control antibodies recognized late endosomes, but not cardiolipin-rich mitochondria, even when we used antibodies that were immunopurified on cardiolipin. Incubation of HUVECs with patient plasma samples immunoreactive toward LBPA resulted in an accumulation of the antibodies in late endosomes and led to a redistribution of the insulinlike growth factor 2/mannose-6-phosphate receptor from the Golgi apparatus to late endosomes. Our results suggest that LBPA is an important lipid target of APLA in HUVECs. These antibodies are internalized by the cells and accumulate in late endosomes. By modifying the intracellular trafficking of proteins, APLA could contribute to several of the proposed pathogenic mechanisms leading to the antiphospholipid syndrome. PMID:10669657

  14. 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...

  15. Performance enhancement, elite athletes and anti doping governance: comparing human guinea pigs in pharmaceutical research and professional sports

    OpenAIRE

    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 ...

  16. 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...

  17. Hantavirus Infection Prevalence in Wild Rodents and Human Anti-Hantavirus Serological Profiles from Different Geographic Areas of South Brazil

    OpenAIRE

    Sonia M. Raboni; Delfraro, Adriana; de Borba, Luana; Teixeira, Bernardo R.; Stella, Vanessa; de Araujo, Marina R.; Carstensen, Suzana; Rubio, Giselia; Maron, Angela; Elba R.S. Lemos; D'Andrea, Paulo S.; Duarte dos Santos, Claudia N.

    2012-01-01

    Paraná state presents the fourth highest number of accumulated cases of hantavirus pulmonary syndrome in Brazil. To map the risk areas for hantavirus transmission we carried out a study based on rodent trapping and determined the anti-hantavirus seroprevalence in these animals and in the inhabitants of these localities. Overall seroprevalence in rodents and humans were 2.5% and 2.4%, respectively. Eighty-two percent of the seropositive rodents were genetically analyzed. Phylogenetic analyses ...

  18. Localization of the discontinous immunodominant region recognized by human anti-thyroperoxidase autoantibodies in autoimmune thyroid diseases

    OpenAIRE

    Bresson, Damien; Cerutti, Martine; Devauchelle, Gerard; Pugnière, Martine; Roquet, Françoise; Bès, Cédric; Bossard, Carine; Chardès, Thierry; Péraldi-Roux, Sylvie

    2003-01-01

    The discontinuous immunodominant region (IDR) recognized by autoantibodies directed against the thyroperoxidase (TPO) molecule, a major autoantigen in autoimmune thyroid diseases, has not yet been completely localized. By using peptide phage-displayed technology, we identified three critical motifs, LXPEXD, QSYP, and EX(E/D)PPV, within selected mimotopes which interacted with the human recombinant anti-TPO autoantibody (aAb) T13, derived from an antibody phage-displayed library obtained from ...

  19. Pretargeting of human mammary carcinoma xenografts with bispecific anti-MUC1/anti-Ga chelate antibodies and immunoscintigraphy with PET

    International Nuclear Information System (INIS)

    We recently demonstrated the feasibility of combining enhanced tumor-to-tissue contrast and PET imaging for immunoscintigraphic tumor localization in pancreas and colon carcinoma bearing nude mice. Contrast enhancement was obtained with a multistep targeting technique that consists of the sequential administration of an antitumor/antihapten bispecific antibody (BS-MAb), a blocker to saturate the antihapten binding sites of the BS-MAb that remains in circulation, and a low molecular weight Ga chelate, labeled with the positron emitter 68Ga, which serves as the hapten. To evaluate the efficacy of this pretargeting technique for breast cancer localization, we synthesized a BS-MAb from the F(ab')2 fragments of the anti-MUC1 MAb 12H12 which reacts with the vast majority of human breast carcinomas, and the F(ab') fragment of an anti-Ga chelate MAb using a bifunctional chemical linker. The BS-MAb was tested for its affinity and its biokinetics in nude mice bearing a human mammary carcinoma. Equilibrium binding of the BS-MAb for mammary carcinoma cells was low (1.2 x 107 M-1) while the binding capacity of cells was high (8.4 x 106 BS-MAbs per cell). Tumor uptake of the 67Ga labeled chelate in pretargeted animals was to 5.8 ± 0.8% iD/g resulting in a tumor-to-blood ratio of 2.6 at 1h postinjection. This compares with a ratio of 0.65 and 0.85 obtained with 125I-labeled native 12H12 at 24h and 48h postinjection. No difference in the tumor uptake of both the 68Ga and 67Ga labeled chelate was observed. PET imaging of mice, started 1h postinjection of the 68Ga chelate, clearly visualized all tumors

  20. 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.

  1. 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

  2. Presence of anti-Toxoplasma antibodies in humans and their cats in the urban zone of Guadalajara

    Directory of Open Access Journals (Sweden)

    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.

  3. A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words.

    Science.gov (United States)

    Mirick, G R; Bradt, B M; Denardo, S J; Denardo, G L

    2004-12-01

    The United States Food and Drug Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ((90)yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ((131)I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) anti-CD20 MAbs for use in radioimmunotherapy (RIT) of non-Hodgkin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, assays were developed to determine HAGA (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to ''humanize'' MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades. PMID:15640788

  4. A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words

    Energy Technology Data Exchange (ETDEWEB)

    Mirick, G. R.; Bradt, B. M.; Denardo, S. J.; Denardo, G. L. [Calfornia Univ., Sacramento (United States). Davis Medical Center

    2004-12-01

    The United States Food and Drugs Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM ({sup 9}0yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM ({sup 1}31I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) antiCD20 MAns for use in radioimmunotherapy (RIT) of non-Hodgikin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, essays were developed to determine HAGE (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to humanize MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades.

  5. A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words

    International Nuclear Information System (INIS)

    The United States Food and Drugs Administration (FDA) has approved unconjugated monoclonal antibodies (MAbs) for immunotherapy (IT) of B-cell lymphoma, breast cancer and acute myeloid leukemia. More recently, approval has been given for conjugated ZevalinTM (90yttrium ibritumomab tiuxetan, IDEC-Y2B8, Biogen Idec, Cambridge, MA) and BexxarTM (131I-tositumomab, Corixa, Corp., Seattle, WA and GlaxoSmithKline, Philadelphia, PA) antiCD20 MAns for use in radioimmunotherapy (RIT) of non-Hodgikin's lymphoma (NHL), thus redefining the standard care of cancer patients. Because of, and despite a lack of basis for concern about allergic reactions due to human antibody responses to these foreign proteins, essays were developed to determine HAGE (human anti-globulin antibody) levels that developed in patient sera following treatment with MAbs. Strategies were also devised to humanize MAbs and to temporarily block patient immune function with drugs in order to decrease the seroconversion rates, with considerable success. On the other hand, a survival advantage has been observed in some patients who developed a HAGA following treatment. This correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients. What follows is a selective review of HAGA and its effect on cancer treatment over the past 2 decades

  6. Electrochemical Detection of Anti-Breast-Cancer Agents in Human Serum by Cytochrome P450-Coated Carbon Nanotubes

    Directory of Open Access Journals (Sweden)

    Camilla Baj-Rossi

    2012-05-01

    Full Text Available We report on the electrochemical detection of anti-cancer drugs in human serum with sensitivity values in the range of 8–925 nA/µM. Multi-walled carbon nanotubes were functionalized with three different cytochrome P450 isoforms (CYP1A2, CYP2B6, and CYP3A4. A model used to effectively describe the cytochrome P450 deposition onto carbon nanotubes was confirmed by Monte Carlo simulations. Voltammetric measurements were performed in phosphate buffer saline (PBS as well as in human serum, giving well-defined current responses upon addition of increasing concentrations of anti-cancer drugs. The results assert the capability to measure concentration of drugs in the pharmacological ranges in human serum. Another important result is the possibility to detect pairs of drugs present in the same sample, which is highly required in case of therapies with high side-effects risk and in anti-cancer pharmacological treatments based on mixtures of different drugs. Our technology holds potentials for inexpensive multi-panel drug-monitoring in personalized therapy.

  7. 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

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

    OpenAIRE

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

    2014-01-01

    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 m...

  9. Human recombinant anti-thyroperoxidase autoantibodies: in vitro cytotoxic activity on papillary thyroid cancer expressing TPO

    OpenAIRE

    Rebuffat, S A; MORIN, M; Nguyen, B; Castex, F; Robert, B.; Péraldi-Roux, S.

    2010-01-01

    Background: Thyroid cancers are difficult to treat due to their limited responsiveness to chemo- and radiotherapy. There is thus a great interest in and a need for alternative therapeutic approaches. Results: We studied the cytotoxic activity of anti-thyroperoxidase autoantibodies (anti-TPO aAbs, expressed in baculovirus/insect cell (B4) and CHO cells (B4′) or purified from patients' sera) against a papillary thyroid cancer (NPA) cell line. Anti-TPO aAbs from patients' sera led to a partial d...

  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. Benzene-Poly-Carboxylic Acid Complex, a Novel Anti-Cancer Agent Induces Apoptosis in Human Breast Cancer Cells

    OpenAIRE

    Fares, Fuad; Azzam, Naiel; Fares, Basem; Larsen, Stig; Lindkaer-Jensen, Steen

    2014-01-01

    Some cases of breast cancer are composed of clones of hormonal-independent growing cells, which do not respond to therapy. In the present study, the effect of Benzene-Poly-Carboxylic Acid Complex (BP-C1) on growth of human breast-cancer cells was tested. BP-C1 is a novel anti-cancer complex of benzene-poly-carboxylic acids with a very low concentration of cis-diammineplatinum (II) dichloride. Human breast cancer cells, MCF-7 and T47D, were used. Cell viability was detected by XTT assay and ap...

  12. 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...

  13. 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.

  14. 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

  15. 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.

  16. 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...

  17. Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumor cells

    International Nuclear Information System (INIS)

    The authors have used polyclonal anti-synthetic peptide serum to study the role of retinoblastoma gene (RB) inactivation in a variety of human tumor cell lines. The analysis indicates that inactivation of the RB protein, p105-Rb, is universal in retinoblastoma cells, vindicating the predictions of the Knudson two-hit hypothesis. In addition, the analysis has shown that inactivations of the RB gene are nearly as frequent in a more common human tumor, small cell lung carcinoma. One-third of bladder carcinomas surveyed also carry altered or absent p105-Rb. Other human tumors by contrast demonstrate only infrequent inactivation of the RB gene. These results suggest that inactivation of the RB gene is a critical step in the pathogenesis of a subset of human tumors

  18. High throughput screening of natural products for anti-mitotic effects in MDA-MB-231 human breast carcinoma cells.

    Science.gov (United States)

    Mazzio, E; Badisa, R; Mack, N; Deiab, S; Soliman, K F A

    2014-06-01

    Some of the most effective anti-mitotic microtubule-binding agents, such as paclitaxel (Taxus brevifolia) were originally discovered through robust National Cancer Institute botanical screenings. In this study, a high-through put microarray format was utilized to screen 897 aqueous extracts of commonly used natural products (0.00015-0.5 mg/mL) relative to paclitaxel for anti-mitotic effects (independent of toxicity) on proliferation of MDA-MB-231 cells. The data obtained showed that less than 1.34 % of the extracts tested showed inhibitory growth (IG50 ) properties Phoradendron flavescens), Tou Gu Cao [symbol: see text] Speranskia herb (Speranskia tuberculata), Bentonite clay, Bunge root (Pulsatilla chinensis), Brucea fruit (Brucea javanica), Madder root (Rubia tinctorum), Gallnut of Chinese Sumac (Melaphis chinensis), Elecampane root (Inula Helenium), Yuan Zhi [symbol: see text] root (Polygala tenuifolia), Pagoda Tree fruit (Melia Toosendan), Stone root (Collinsonia Canadensis), and others such as American Witchhazel, Arjun, and Bladderwrack. The strongest tumoricidal herbs identified from amongst the subset evaluated for anti-mitotic properties were wild yam (Dioscorea villosa), beth root (Trillium Pendulum), and alkanet root (Lithospermum canescens). Additional data was obtained on a lesser-recognized herb: (S. tuberculata), which showed growth inhibition on BT-474 (human ductal breast carcinoma) and Ishikawa (human endometrial adenocarcinoma) cells with ability to block replicative DNA synthesis, leading to G2 arrest in MDA-MB-231 cells. In conclusion, these findings present relative potency of anti-mitotic natural plants that are effective against human breast carcinoma MDA-MB-231 cell division. PMID:24105850

  19. Herpes Zoster Duplex Symmetricus in an immunocompetent 70-year female

    Directory of Open Access Journals (Sweden)

    Mankesh Lal Gambhir

    2014-07-01

    Full Text Available Herpes zoster is a neuroectodermal viral infection which afflicts one or more closely grouped, spinal or cranial nerves, resulting in unilateral radicular pain and vesicular eruption limited to a dermatome innervated by that nerve [1]. Bilateral involvement is rare, bilaterally symmetrical involvement is extremely rare. We hereby report a case of bilaterally symmetrical herpes zoster in an old immunocompetent female.

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

    Directory of Open Access Journals (Sweden)

    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. 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.

  2. 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

  3. The Anti-tumour Agent, Cisplatin, and its Clinically Ineffective Isomer, Transplatin, Produce Unique Gene Expression Profiles in Human Cells

    Directory of Open Access Journals (Sweden)

    Anne M. Galea

    2008-01-01

    Full Text Available Cisplatin is a DNA-damaging anti-cancer agent that is widely used to treat a range of tumour types. Despite its clinical success, cisplatin treatment is still associated with a number of dose-limiting toxic side effects. The purpose of this study was to clarify the molecular events that are important in the anti-tumour activity of cisplatin, using gene expression profi ling techniques. Currently, our incomplete understanding of this drug’s mechanism of action hinders the development of more efficient and less harmful cisplatin-based chemotherapeutics. In this study the effect of cisplatin on gene expression in human foreskin fibroblasts has been investigated using human 19K oligonucleotide microarrays. In addition its clinically inactive isomer, transplatin, was also tested. Dual-fluor microarray experiments comparing treated and untreated cells were performed in quadruplicate. Cisplatin treatment was shown to significantly up- or down-regulate a consistent subset of genes. Many of these genes responded similarly to treatment with transplatin, the therapeutically inactive isomer of cisplatin. However, a smaller proportion of these transcripts underwent differential expression changes in response to the two isomers. Some of these genes may constitute part of the DNA damage response induced by cisplatin that is critical for its anti-tumour activity. Ultimately, the identification of gene expression responses unique to clinically active compounds, like cisplatin, could thus greatly benefit the design and development of improved chemotherapeutics.

  4. The Anti-Inflammatory Effect of Algae-Derived Lipid Extracts on Lipopolysaccharide (LPS)-Stimulated Human THP-1 Macrophages.

    Science.gov (United States)

    Robertson, Ruairi C; Guihéneuf, Freddy; Bahar, Bojlul; Schmid, Matthias; Stengel, Dagmar B; Fitzgerald, Gerald F; Ross, R Paul; Stanton, Catherine

    2015-08-01

    Algae contain a number of anti-inflammatory bioactive compounds such as omega-3 polyunsaturated fatty acids (n-3 PUFA) and chlorophyll a, hence as dietary ingredients, their extracts may be effective in chronic inflammation-linked metabolic diseases such as cardiovascular disease. In this study, anti-inflammatory potential of lipid extracts from three red seaweeds (Porphyra dioica, Palmaria palmata and Chondrus crispus) and one microalga (Pavlova lutheri) were assessed in lipopolysaccharide (LPS)-stimulated human THP-1 macrophages. Extracts contained 34%-42% total fatty acids as n-3 PUFA and 5%-7% crude extract as pigments, including chlorophyll a, β-carotene and fucoxanthin. Pretreatment of the THP-1 cells with lipid extract from P. palmata inhibited production of the pro-inflammatory cytokines interleukin (IL)-6 (p effectively inhibited the LPS-induced pro-inflammatory signaling pathways mediated via toll-like receptors, chemokines and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling molecules. These results suggest that lipid extracts from P. lutheri, P. palmata, P. dioica and C. crispus can inhibit LPS-induced inflammatory pathways in human macrophages. Therefore, algal lipid extracts should be further explored as anti-inflammatory ingredients for chronic inflammation-linked metabolic diseases. PMID:26308008

  5. Recidiverende erythema multiforme udløst af herpes simplex-virus

    DEFF Research Database (Denmark)

    Vestergård Grejsen, Dorthe; Henningsen, Emil

    2012-01-01

    We describe two cases of recurrent erythema multiforme, both associated to infection with herpes simplex virus. The importance of subclinical herpes is illustrated. Antiviral and additional treatment is described.......We describe two cases of recurrent erythema multiforme, both associated to infection with herpes simplex virus. The importance of subclinical herpes is illustrated. Antiviral and additional treatment is described....

  6. Uptake of radiolabeled anti-CEA antibodies in human colorectal primary tumors as a function of tumor mass

    International Nuclear Information System (INIS)

    An inverse correlation has been demonstrated between tumor uptake (u, in units of % injected dose/kg) of monoclonal antibody (Mab) and tumor mass (m, in units of g) for colorectal carcinoma in a series of 19 consecutive patients. The correlation (ρ=-0.510), developed using surgical samples was of the form u=abb and was significant at the 2% level of confidence. All tumors were positive for carcinoembryonic antigen (CEA) and the radiopharmaceutical was in iodine-131 labeled anti-CEA Mab. Such correlations have been predicted earlier from murine and rat tumor uptake data. The slope parameter (b) was -0.362, a number consistent with the previous value (-0.382) found in anti-CEA experiments in mice bearing human xenograft LS174T tumors. (orig.)

  7. Treatment of Herpes simplex virus infections with topical antiviral agents.

    Science.gov (United States)

    Hamuy, R; Berman, B

    1998-01-01

    Clinical studies of topical therapy against Herpes simplex virus (HSV) infections have been reviewed. Idoxuridine (IDU) 15% in dimethyl sulfoxide (DMSO), interferons, and penciclovir result in significant clinical benefit against this virus. IDU reduced pain duration and decreased time to loss of crust in a study of 301 patients. Alpha-interferon has shown synergism with other anti-HSV drugs such as caffeine, trifluorothymidine (TFT), DMSO, and nonoxynol-9. Finally, in a study of over 2,000 patients, application of penciclovir cream, both early and late in the course of HSV infection, decreased the duration of lesions, pain, and viral shedding. Acyclovir (ACV)-resistant strains of HSV are susceptible to (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC), and ascorbic acid shows promising effects against HSV. Using a vehicle that enhances skin penetration of a drug or possibly further exploring combination therapy may result in efficacious treatment of HSV. The possibility of topical vaccination or topical gene therapy may also prove beneficial in the future. PMID:9683881

  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-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 metallopro-teinase-1 (TIMP-1) and decreasing elastase activity, thus exerting anti-aging and anti-wrinkle effects by increasing collagen synthesis and promoting skin fibroblast proliferation

  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. Herpes simplex encephalitis -A case series

    OpenAIRE

    MANJU, Jyotir; Patil, Shruti; RAU, ATK

    2012-01-01

    The prognosis of Herpes simplex encephalitis (HSE) depends on the early and appropriate administration of specific antiviral therapy. We retrospectively reviewed 42 children with acute CNS infection, over a period of 18 months, of which 4 were positive for HSV antibodies. All four showed CSF pleocytosis, with mildly elevated protein and rising titers of antibodies to HSV in the CSF. All the 4 cases were started on i.v. acyclovir on day 1 and continued for a total duration of 14 days. The pati...

  12. Forebyggelse af herpes zoster med vaccination

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Rønholt, Finn; Gerstoft, Jan; Sand, Carsten

    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...

  13. 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....

  14. 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

  15. Immunoscintigraphy of human tumors transplanted in nude mice with radiolabeled anti-ras p21 monoclonal antibodies

    International Nuclear Information System (INIS)

    Anti-ras p21 monoclonal antibody (RASK-3) was used for immunoscintigraphy of human cancer cell lines in nude mice. Iodine-125-labeled RASK-3 was injected into nude mice with either human colon cancers (FCC-1 or BM-314) or lung cancer (KNS-62). Clear images were obtained in all three cancers 7 days after the injection of antibody. No localization of 125I-labeled control monoclonal antibody was observed. The ratio of tissue/blood radioactivity and % ID/g in the tumor were significantly higher than other organs by Day 8. The specific localization index examined by 131I-RASK-3 and 125I-control monoclonal antibody was also higher in the tumor than in other tissues. In the in vitro study, binding of RASK-3 to tumor cells increased significantly by treatment of cells with either lysolecithin or periodate-lysine-paraformaldehyde, which confirmed the intracellular localization of ras p21. The mechanism by which anti-ras p21 antibodies accumulate in tumor sites could be the necrotic changes in tumor cells or changes in membrane permeability of non-necrotic cells. These results provide a strong rationale for the utilization of ras p21 as a target antigen in the imaging of a variety of human cancers

  16. 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

  17. 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...

  18. In vivo tumor localization and biodistribution in the human tumor xenografts models of an anti-CD71 mouse/human chimeric antibody

    International Nuclear Information System (INIS)

    Objective: In order to investigate the tumor localization and biodistribution of the anti-CD71 mouse/human chimeric antibody (D2C). Methods: The tumor localization and biodistribution of the chimeric antibody (D2C) were observed by labeling the chimeric Ab with radioiodine (131I) and injecting it into nude mice (Balb/c nu/nu) transplanted with human hepatocellular carcinoma cells (SMMC-7721). Results: The labeled chimeric Ab (D2C), with intraperitoneal as well as tumor regional administration, was significantly localized in the tumor and the location of the tumor was successfully visualized by SPECT. The in vivo D2C Ab's biodistribution of organs and tissues showed that non-specific binding in the tumor regional administration was lower than those in the intraperitoneal. Conclusion: The human/mouse chimeric antibody (D2C) can exert in specific tumor localization in vivo and can be utilized for radio-immunoimaging

  19. 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...

  20. Update on emerging antivirals for the management of herpes simplex virus infections: a patenting perspective.

    Science.gov (United States)

    Vadlapudi, Aswani D; Vadlapatla, Ramya K; Mitra, Ashim K

    2013-04-01

    Herpes simplex virus (HSV) infections can be treated efficiently by the application of antiviral drugs. The herpes family of viruses is responsible for causing a wide variety of diseases in humans. The standard therapy for the management of such infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valaciclovir and famciclovir. Though effective, long term prophylaxis with the current drugs leads to development of drug-resistant viral isolates, particularly in immunocompromised patients. Moreover, some drugs are associated with dose-limiting toxicities which limit their further utility. Therefore, there is a need to develop new antiherpetic compounds with different mechanisms of action which will be safe and effective against emerging drug resistant viral isolates. Significant advances have been made towards the design and development of novel antiviral therapeutics during the last decade. As evident by their excellent antiviral activities, pharmaceutical companies are moving forward with several new compounds into various phases of clinical trials. This review provides an overview of structure and life cycle of HSV, progress in the development of new therapies, update on the advances in emerging therapeutics under clinical development and related recent patents for the treatment of Herpes simplex virus infections. PMID:23331181

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. Abdominal muscle paralysis associated with herpes zoster.

    Science.gov (United States)

    Gottschau, P; Trojaborg, W

    1991-10-01

    We describe a 77-year-old women with cutaneous herpes zoster in the area of the right T9-T11 dermatomes complicated by abdominal muscle paralysis. Four months after onset of paralysis, stimulation of appropriate intercostal nerves failed to evoke responses from the corresponding segments of the rectus abdominis muscle. Three months later EMG of these muscle segments revealed profuse denervation activity and spontaneous long-lasting burst of high frequency discharges. Magnetic stimulation applied transcranially and peripherally at T10 evoked responses from the left, but not from the right paralytic rectus abdominis muscle. Electric stimulation of right T10 elicited a markedly delayed, prolonged and polyphasic response in the transverse abdominis muscle and EMG revealed polyphasia and increased motor unit potential duration in muscle segments underlying herpes zoster eruption. One and a half years after onset, the paralysis of the rectus abdominis muscle was still present. A survey of the literature concerning this rare type of zoster paralysis is presented. PMID:1837649

  6. Anti-aging effects of vitamin C on human pluripotent stem cell-derived cardiomyocytes

    OpenAIRE

    Kim, Yoon Young; Ku, Seung-Yup; Huh, Yul; Liu, Hung-Ching; Kim, Seok Hyun; Choi, Young Min; Moon, Shin Yong

    2012-01-01

    Human pluripotent stem cells (hPSCs) have arisen as a source of cells for biomedical research due to their developmental potential. Stem cells possess the promise of providing clinicians with novel treatments for disease as well as allowing researchers to generate human-specific cellular metabolism models. Aging is a natural process of living organisms, yet aging in human heart cells is difficult to study due to the ethical considerations regarding human experimentation as well as a current l...

  7. 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

  8. 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...

  9. 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

  10. 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...

  11. 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

  12. 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

  13. Radioimmunoimaging of 131I-anti human colon carcinoma monoclonal antibodies in nude mice with tumor xenografts

    International Nuclear Information System (INIS)

    The paired labeled antibodies, 131-labeled anti-human colon carcinoma monoclonal antibody 2C10 and 125I-labeled mice IgG, were used in the radioimmunolocalization study in nude mice with human colon carcinoma xenograft. The antibodies were radioiodinated with Iodogen method, and the incroporation efficiency and immune activity of the labeled antibodies were satisfactory. 96 hours after injection of the antibodies, good tumor localization was observed. Tumor/L. intestinal ratio was 7.08, tumor/S. intestinal 6.02, tumor/muscle 7.53, tumor/blood 1.10. Tumor imaging with camera was clear. The entrance of the antibodies into tumor tissues is a slow passive process and the accumulation of the antibodies in tumor is a combined result of specific immune reactivity and nonspecific deposition

  14. Molecularly Targeted Therapy of Human Hepatocellular Carcinoma Xenografts with Radio-iodinated Anti-VEGFR2 Murine-Human Chimeric Fab

    OpenAIRE

    Jianfei Huang; Qi Tang; Changjun Wang; Huixin Yu; Zhenqing Feng; Jin Zhu

    2015-01-01

    Vascular endothelial growth factor receptor 2 (VEGFR2) is traditionally regarded as an important therapeutic target in a wide variety of malignancies, such as hepatocellular carcinoma (HCC). We previously generated a murine-human anti-VEGFR2 chimeric Fab (cFab), named FA8H1, which has the potential to treat VEGFR2-overexpressing solid tumors. Here, we investigated whether FA8H1 can be used as a carrier in molecularly targeted therapy in HCC xenograft models. FA8H1 was labeled with 131I, and t...

  15. 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....

  16. In vivo neutralization of hepatitis B virus infection by an anti-preS1 humanized antibody in chimpanzees

    International Nuclear Information System (INIS)

    Previously, we generated a murine monoclonal antibody (mAb), KR127, that recognizes amino acids (aa) 37-45 of the preS1 of hepatitis B virus (HBV). In this study, we have constructed a humanized version of KR127 and evaluated its HBV-neutralizing activity in chimpanzees. A study chimpanzee was given a single intravenous dose of the humanized antibody, followed by intravenous challenge with adr subtype of wild type HBV, while a control chimpanzee was only challenged with the virus. The result showed that the study chimpanzee did not develop HBV infection during 1 year, while the control chimpanzee was infected, indicating that the humanized antibody exhibited in vivo virus-neutralizing activity and thus protected the chimpanzee from HBV infection. In addition, the humanized antibody bound to the preS1 of all subtypes of HBV. We first demonstrate that an anti-preS1 mAb can neutralize HBV infection in vivo. This humanized antibody will be useful for the immunoprophylaxis of HBV infection

  17. 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.

  18. The Anti-Inflammatory Effect of Algae-Derived Lipid Extracts on Lipopolysaccharide (LPS-Stimulated Human THP-1 Macrophages

    Directory of Open Access Journals (Sweden)

    Ruairi C. Robertson

    2015-08-01

    Full Text Available Algae contain a number of anti-inflammatory bioactive compounds such as omega-3 polyunsaturated fatty acids (n-3 PUFA and chlorophyll a, hence as dietary ingredients, their extracts may be effective in chronic inflammation-linked metabolic diseases such as cardiovascular disease. In this study, anti-inflammatory potential of lipid extracts from three red seaweeds (Porphyra dioica, Palmaria palmata and Chondrus crispus and one microalga (Pavlova lutheri were assessed in lipopolysaccharide (LPS-stimulated human THP-1 macrophages. Extracts contained 34%–42% total fatty acids as n-3 PUFA and 5%–7% crude extract as pigments, including chlorophyll a, β-carotene and fucoxanthin. Pretreatment of the THP-1 cells with lipid extract from P. palmata inhibited production of the pro-inflammatory cytokines interleukin (IL-6 (p < 0.05 and IL-8 (p < 0.05 while that of P. lutheri inhibited IL-6 (p < 0.01 production. Quantitative gene expression analysis of a panel of 92 genes linked to inflammatory signaling pathway revealed down-regulation of the expression of 14 pro-inflammatory genes (TLR1, TLR2, TLR4, TLR8, TRAF5, TRAF6, TNFSF18, IL6R, IL23, CCR1, CCR4, CCL17, STAT3, MAP3K1 by the lipid extracts. The lipid extracts effectively inhibited the LPS-induced pro-inflammatory signaling pathways mediated via toll-like receptors, chemokines and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB signaling molecules. These results suggest that lipid extracts from P. lutheri, P. palmata, P. dioica and C. crispus can inhibit LPS-induced inflammatory pathways in human macrophages. Therefore, algal lipid extracts should be further explored as anti-inflammatory ingredients for chronic inflammation-linked metabolic diseases.

  19. 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.

  20. 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.

  1. 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.

  2. Pharmacokinetics, biodistribution and dosimetry of 99mTc-labeled anti-human epidermal growth factor receptor humanized monoclonal antibody R3 in rats

    International Nuclear Information System (INIS)

    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(2α))) of 0.250 h and a mean elimination (t(1(2β))) 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

  3. Latency in vitro using irradiated Herpes simplex virus

    International Nuclear Information System (INIS)

    Human embryonic fibroblasts infected with u.v.-irradiated herpes simplex virus type 2 (HSV-2, strain 186) and maintained at 40.5 0C did not yield detectable virus. Virus synthesis was induced by temperature shift-down to 36.5 0C. The induced virus grew very poorly and was inactivated very rapidly at 40.5 0C. Non-irradiated virus failed to establish latency at 40.5 0C in infected cells. Enhanced reactivation of HSV-2 was observed when latently infected cultures were superinfected with human cytomegalovirus (HCMV) or irradiated with a small dose of u.v. light at the time of temperature shift-down. HCMV did not enhance synthesis of HSV-2 during a normal growth cycle but did enhance synthesis of u.v.-irradiated HSV-2. These observations suggest that in this in vitro latency system, some HSV genomes damaged by u.v. irradiation were maintained in a non-replicating state without being destroyed or significantly repaired. (author)

  4. Evaluation of two commercially available anti human immunodeficiency virus antibody Elisa Kits using clinical samples

    OpenAIRE

    Anuradha K; Ponamgi S; Lakshmi V

    2002-01-01

    Laboratory diagnosis is the mainstay in the diagnosis of HIV infection in an individual. The wide range of diagnostic kits available, for the detection of anti HIV antibodies, makes it mandatory that the kits are evaluated before they are made available in the market. We evaluated the performance of a Microlisa HIV kit (J.Mitra & Co.)† using a panel of HIV reactive and non reactive clinical specimens. The sensitivity and specificity of the kit were found to be 100% as com...

  5. 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

  6. 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.

  7. 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…

  8. 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

  9. Crystallization and preliminary X-ray diffraction analysis of the complex between a human anti-interferon antibody fragment and human interferon α-2A

    International Nuclear Information System (INIS)

    Crystals of the complex between the Fab fragment of a human anti-interferon α therapeutic antibody and human interferon α-2A have been obtained and diffracted to 3.0 Å resolution. Recombinant human interferon α-2A (rhIFN-α-2A) has been crystallized in complex with the recombinantly produced Fab fragment of a therapeutic monoclonal antibody (MEDI545; IgG1/κ) which targets several human interferon α subtypes. This constitutes the first reported crystals of a human type I interferon bound to an antibody. The orthorhombic crystals belonged to either space group I222 or I212121, with unit-cell parameters a = 134.82, b = 153.26, c = 163.49 Å. The diffraction of the crystals extended to 3.0 Å resolution. The asymmetric unit contained two Fab–rhIFN-α-2A complexes. This corresponded to a crystal volume per protein weight (VM) of 3.02 Å3 Da−1 and a solvent content of 59.3%. The corresponding three-dimensional structure is expected to shed light on the mechanism of action of MEDI545 and the molecular basis of its specificity

  10. 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...

  11. Structure-Based Design and Engineering of a Nontoxic Recombinant Pokeweed Antiviral Protein with Potent Anti-Human Immunodeficiency Virus Activity

    OpenAIRE

    Uckun, Fatih M.; Rajamohan, Francis; Pendergrass, Sharon; Ozer, Zahide; Waurzyniak, Barbara; Mao, Chen

    2003-01-01

    A molecular model of pokeweed antiviral protein (PAP)-RNA interactions was used to rationally engineer FLP-102(151AA152) and FLP-105(191AA192) as nontoxic PAPs with potent anti-human immunodeficiency virus (anti-HIV) activities. FLP-102 and FLP-105 have been produced in Escherichia coli and tested both in vitro and in vivo. These proteins depurinate HIV type 1 (HIV-1) RNA much better than rRNA and are more potent anti-HIV agents than native PAP or recombinant wild-type PAP. They are substanti...

  12. 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.

  13. 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.

  14. 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)

  15. 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

  16. Identification and typing of herpes simplex viruses with monoclonal antibodies.

    OpenAIRE

    Balachandran, N; Frame, B; Chernesky, M; Kraiselburd, E; Kouri, Y; Garcia, D.; Lavery, C; Rawls, W. E.

    1982-01-01

    Monoclonal antibodies which reacted with type-specific antigens of herpes simplex virus type 2 or with antigens shared by herpes simplex virus types 1 and 2 were used in an indirect immunofluorescence assay to type virus isolates and to detect viral antigens in cells obtained from herpetic lesions. Complete concordance was obtained for 42 isolates typed by endonuclease restriction analysis of viral DNA and by indirect immunofluorescence with monoclonal antibodies. Examination of a limited num...

  17. 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...

  18. 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...

  19. Herpes Zoster and Postherpetic Neuralgia: An Examination of Psychological Antecedents

    OpenAIRE

    Sansone, Randy A.; Sansone, Lori A.

    2014-01-01

    Herpes zoster and an associated complication, postherpetic neuralgia, are both attributable to the varicella zoster virus. This virus, which lies dormant within the affected sensory ganglia after an initial infection, appears to be triggered in part by a decrease in immunity. According to available research, stress, stressful life events, and depressive symptoms are identified antecedents to outbreaks of herpes zoster. Likewise, the development of postherpetic neuralgia has been associated wi...

  20. A case report of abdominal distention caused by herpes zoster

    OpenAIRE

    Su-Rong Zhou; Chuan-Yu Liu

    2012-01-01

    Gastrointestinal complications caused by herpes zoster are extremely rare. Here, we described a case of abdominal distention caused by herpes zoster. The patient was a 59-year-old female who suffered from unexplained paroxysmal and a burning pain on the right part of her waist and abdomen, accompanied by abdominal distention. Intestinal pseudo-obstruction was diagnosed by abdominal radiography. Distention of the right abdominal wall was still apparent after one month. In this report, we found...

  1. [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

  2. Herpes simplex virus encephalitis: neuroradiological diagnosis

    International Nuclear Information System (INIS)

    Herpes simplex virus encephalitis (HSE) is the most frequent viral encephalitis, as a rule with the starting point and centre within the temporal lobe. If untreated, HSE is usually fatal, thus diagnosis has to be established rapidly. Treatment with Acyclovir should begin as soon possible. As MRI is extremely sensitive in detecting the early inflammatory changes, it should be initially performed, especially as in the early stadium CT may be unspecific. We recommend the following examination protocol: coronar T1-weighted MR imaging before and after administration of gadopentetate dimeglumine, coronar FLAIR sequence and axial T2-weighted imaging. The diagnostic proof is to show the evidence of viral DNA by polymerase chain reaction (PCR) in cerebrospinal liquor. (orig.)

  3. MRI findings of herpes simplex encephalitis

    International Nuclear Information System (INIS)

    We retrospectively analyzed the MR findings of 12 patients with herpes simplex encephalitis (HSE) (8 months - 64 years old). MR imaging was performed on either a 0.5T (6 patients) or 2.0T (6 patients) superconducting unit with spin echo pulse sequences. The most common and characteristic MR finding consisted of non-hemorrhagic lesions in the cortices of the temporal lobes(12), and insular(6), either bilateral(7) or unilateral(5). The frontal lobe and cingulate gyrus were involved in 4 and 2 patients respectively. Petechial hemorrhage was found in 3 patients. Non-hemorrhagic lesions were shown as high signal intensities on proton and T2WI, and iso- or low signal intensities on T1WI. In conclusion, MR imaging findings described above appear to be characteristic of HSE and were found to be extremely valuable in the diagnosis of HSE

  4. 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

  5. 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.

  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. Neonatal herpes in Serbia: Is it a problem or not?

    Directory of Open Access Journals (Sweden)

    Knežević Aleksandra

    2014-01-01

    Full Text Available With 20-80% mortality, neonatal infection caused by herpes simplex virus (HSV or neonatal herpes is among the most severe of all perinatal infections. The majority of neonatal HSV infections are acquired during delivery, although in utero and postnatal infections do occur. Primary maternal infection is associated with a high rate of transmission (~50%, compared to <3% in infants of women with reactivated disease. Other factors that influence transmission include HSV type, premature delivery, etc. Clinical manifestations have been classified into three forms: skin-eye-mouth disease, CNS and disseminated disease. The diagnosis of neonatal HSV infection includes the detection of HSV DNA by PCR in samples from neonate and mother. The incidence of neonatal herpes differs widely between different countries. In Serbia, the data about neonatal herpes incidence are scarce. The results of our pilot study showed that the minimal estimation of the national incidence of neonatal herpes is 7.5 per 100 000. Therefore, the set up and implementation of a national neonatal herpes surveillance system might provide valuable information for the accurate assessment of disease burden and development of an effective prevention strategy in Serbia. [Projekat Ministarstva nauke Republike Srbije, br. 175073

  8. 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...

  9. 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...

  10. 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...

  11. Anti-bacterial effects of the essential oil of Teucrium polium L. on human pathogenic bacteria

    OpenAIRE

    Mohammad Mohammad; Hassan Salari; Armita Farahmand

    2013-01-01

    Background: Pathogenic bacteria are important causes of disease in humans and agricultural products contamination. Side effects of chemical preservatives necessitate research on the use of a special blend of natural oils to prevent the growth of bacteria. The aim of this study was elucidating the antibacterial effect of the essential oil of Teucrium polium on human pathogenic bacteria in the Kerman province. Materials and Methods: In order to investigate the chemical composition and antiba...

  12. Human RIF1 encodes an anti-apoptotic factor required for DNA repair

    OpenAIRE

    Wang, Haibo; Zhao, Ailian; Chen, Lin; Zhong, Xueyan; Liao, Ji; Gao, Min; Cai, Minghua; Lee, Dong-Hyun; Jing LI; Chowdhury, Dipanjan; Yang, Yun-Gui; Pfeifer, Gerd P.; Yen, Yun; Xu, Xingzhi

    2009-01-01

    Human Rap1-interacting protein 1 (RIF1) contributes to the ataxia telangiectasia, mutated-mediated DNA damage response against the dexterous effect of DNA lesions and plays a critical role in the S-phase checkpoint. However, the molecular mechanisms by which human RIF1 conquers DNA aberrations remain largely unknown. We here showed that inhibition of RIF1 expression by small interfering RNA led to defective homologous recombination-mediated DNA double-strand break repair and sensitized cancer...

  13. 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

  14. 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

  15. Production of pro- and anti-inflammatory cytokines in human monocytes: regulation and signaling

    OpenAIRE

    Molnarfi, Nicolas; Dayer, Jean-Michel; Gruenberg, Jean; Burger, Danielle

    2006-01-01

    Les tissus vivants répondent aux agressions par l'inflammation qui élimine les agents préjudiciables et initie la guérison des tissus lésés. Les dérèglements de l'inflammation entraînent des pathologies (polyarthrite rhumatoïde (PR), sclérose en plaques (SEP)). Les cytokines pro- (TNF, IL-1β) et anti-inflammatoires (sIL-1Ra), peuvent jouer des rôles salutaires ou délétères dans l'inflammation aiguë/physiologique ou chronique/pathologique. Dans l'inflammation chronique (PR, SEP) les cytokines ...

  16. Production of pro- and anti-inflammatory cytokines in human monocytes : regulation and signaling

    OpenAIRE

    Molnarfi, Nicolas

    2005-01-01

    Les tissus vivants répondent aux agressions par l'inflammation qui élimine les agents préjudiciables et initie la guérison des tissus lésés. Les dérèglements de l'inflammation entraînent des pathologies (polyarthrite rhumatoïde (PR), sclérose en plaques (SEP)). Les cytokines pro- (TNF, IL-1β) et anti-inflammatoires (sIL-1Ra), peuvent jouer des rôles salutaires ou délétères dans l'inflammation aiguë/physiologique ou chronique/pathologique. Dans l'inflammation chronique (PR, SEP) les cytokines ...

  17. A possible role for polymorphonuclear leucocytes in the defence against recrudescent herpes simplex virus infection in man

    International Nuclear Information System (INIS)

    A 51Cr release assay has been used to demonstrate that human polymorphonuclear leucocytes (PMNL) can damage herpes simplex infected target cells sensitized with antiviral antibody. Effective sensitizing antibodies were found in both serum and saliva of all those persons tested who were subject to recurrent cold sores. PMNL were much less effective as killer cells than peripheral blood mononuclear cells, but as they are the predominant inflammatory cell within the HSVl lesion they may be, quantitatively, more important. The cytotoxic effects of both PMNL and mononuclear cells were significantly reduced by prostaglandin El as well as by several drugs that were tested. It is suggested that antibody dependent PMNL-mediated cytotoxicity may play a role in the human host defences against recrudescent herpes simplex infection. (author)

  18. 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

  19. 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.

  20. Anti-estrogen Resistance in Human Breast Tumors Is Driven by JAG1-NOTCH4-Dependent Cancer Stem Cell Activity

    Directory of Open Access Journals (Sweden)

    Bruno M. Simões

    2015-09-01

    Full Text Available Breast cancers (BCs typically express estrogen receptors (ERs but frequently exhibit de novo or acquired resistance to hormonal therapies. Here, we show that short-term treatment with the anti-estrogens tamoxifen or fulvestrant decrease cell proliferation but increase BC stem cell (BCSC activity through JAG1-NOTCH4 receptor activation both in patient-derived samples and xenograft (PDX tumors. In support of this mechanism, we demonstrate that high ALDH1 predicts resistance in women treated with tamoxifen and that a NOTCH4/HES/HEY gene signature predicts for a poor response/prognosis in 2 ER+ patient cohorts. Targeting of NOTCH4 reverses the increase in Notch and BCSC activity induced by anti-estrogens. Importantly, in PDX tumors with acquired tamoxifen resistance, NOTCH4 inhibition reduced BCSC activity. Thus, we establish that BCSC and NOTCH4 activities predict both de novo and acquired tamoxifen resistance and that combining endocrine therapy with targeting JAG1-NOTCH4 overcomes resistance in human breast cancers.

  1. 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

  2. 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...

  3. Disseminated cutaneous herpes simplex infection in a patient with Crohn's disease under azathioprine and steroids: First case report and literature review.

    Science.gov (United States)

    Santos-Antunes, João; Abreu, Cândida; Magro, Fernando; Coelho, Rosa; Vilas-Boas, Filipe; Andrade, Patrícia; Lopes, Susana; Macedo, Guilherme

    2014-04-01

    Immunosuppressive treatments used in the management of Inflammatory Bowel Disease, namely steroids, thiopurines and anti-TNF drugs, raise the risk of acquiring opportunistic infections. However, most of these infections are mild and self-limited, not requiring specific therapy or suspension of the immunosuppressors. We report a case of disseminated cutaneous herpes simplex infection in a patient with Crohn's disease under steroids and azathioprine. PMID:24257435

  4. Benzene-Poly-Carboxylic Acid Complex, a Novel Anti-Cancer Agent Induces Apoptosis in Human Breast Cancer Cells

    Science.gov (United States)

    Fares, Fuad; Azzam, Naiel; Fares, Basem; Larsen, Stig; Lindkaer-Jensen, Steen

    2014-01-01

    Some cases of breast cancer are composed of clones of hormonal-independent growing cells, which do not respond to therapy. In the present study, the effect of Benzene-Poly-Carboxylic Acid Complex (BP-C1) on growth of human breast-cancer cells was tested. BP-C1 is a novel anti-cancer complex of benzene-poly-carboxylic acids with a very low concentration of cis-diammineplatinum (II) dichloride. Human breast cancer cells, MCF-7 and T47D, were used. Cell viability was detected by XTT assay and apoptosis was detected by Flow Cytometry and by annexin V/FITC/PI assay. Caspases were detected by western blot analysis and gene expression was measured by using the Applied Biosystems® TaqMan® Array Plates. The results showed that exposure of the cells to BP-C1 for 48 h, significantly (P<0.001) reduced cell viability, induced apoptosis and activated caspase 8 and caspace 9. Moreover, gene expression experiments indicated that BP-C1 increased the expression of pro-apoptotic genes (CASP8AP1, TNFRSF21, NFkB2, FADD, BCL10 and CASP8) and lowered the level of mRNA transcripts of inhibitory apoptotic genes (BCL2L11, BCL2L2 and XIAP. These findings may lead to the development of new therapeutic strategies for treatment of human cancer using BP-C1 analog. PMID:24523856

  5. 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.

  6. 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.

  7. Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► Protocatechualdehyde (PCA) suppressed cell proliferation and induced apoptosis in human colorectal cancer cells. ► PCA enhanced transcriptional downregulation of cyclin D1 gene. ► PCA suppressed HDAC2 expression and activity. ► 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.

  8. 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

  9. 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.

  10. Optimization of Azoles as Anti-Human Immunodeficiency Virus Agents Guided by Free-Energy Calculations

    OpenAIRE

    Zeevaart, Jacob G.; Wang, Ligong; Thakur, Vinay V.; Leung, Cheryl S.; Tirado-Rives, Julian; Bailey, Christopher M; Domaoal, Robert A.; Anderson, Karen S.; Jorgensen, William L.

    2008-01-01

    Efficient optimization of an inactive 2-anilinyl-5-benzyloxadiazole core has been guided by free energy perturbation (FEP) calculations to provide potent non-nucleoside inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (NNRTIs). An FEP “chlorine scan” was performed to identify the most promising sites for substitution of aryl hydrogens. This yielded NNRTIs 8 and 10 with activities (EC50) of 820 and 310 nM for protection of human T-cells from infection by wild-type HIV-1. ...

  11. 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.

  12. 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.

  13. 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.

  14. Touched by Injury: Toward an Educational Theory of Anti-Racist Humanism

    Science.gov (United States)

    Georgis, Dina; Kennedy, R. M.

    2009-01-01

    Informed by the critical humanisms of Hannah Arendt, Frantz Fanon, and Paul Gilroy, the authors argue for an orientation to teaching and learning that troubles the continuing effects of dehumanizing race logic. Reflecting on Paul Haggis's Oscar award winning film "Crash" from 2004, they suggest that the metaphor of racial "crashing" captures what…

  15. Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus.

    Science.gov (United States)

    Dörner, Thomas; Kaufmann, Joerg; Wegener, William A; Teoh, Nick; Goldenberg, David M; Burmester, Gerd R

    2006-01-01

    B cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE), so the safety and activity of anti-B cell immunotherapy with the humanized anti-CD22 antibody epratuzumab was evaluated in SLE patients. An open-label, single-center study of 14 patients with moderately active SLE (total British Isles Lupus Assessment Group (BILAG) score 6 to 12) was conducted. Patients received 360 mg/m2 epratuzumab intravenously every 2 weeks for 4 doses with analgesic/antihistamine premedication (but no steroids) prior to each dose. Evaluations at 6, 10, 18 and 32 weeks (6 months post-treatment) follow-up included safety, SLE activity (BILAG score), blood levels of epratuzumab, B and T cells, immunoglobulins, and human anti-epratuzumab antibody (HAHA) titers. Total BILAG scores decreased by > or = 50% in all 14 patients at some point during the study (including 77% with a > or = 50% decrease at 6 weeks), with 92% having decreases of various amounts continuing to at least 18 weeks (where 38% showed a >/= 50% decrease). Almost all patients (93%) experienced improvements in at least one BILAG B- or C-level disease activity at 6, 10 and 18 weeks. Additionally, 3 patients with multiple BILAG B involvement at baseline had completely resolved all B-level disease activities by 18 weeks. Epratuzumab was well tolerated, with a median infusion time of 32 minutes. Drug serum levels were measurable for at least 4 weeks post-treatment and detectable in most samples at 18 weeks. B cell levels decreased by an average of 35% at 18 weeks and remained depressed at 6 months post-treatment. Changes in routine safety laboratory tests were infrequent and without any consistent pattern, and there was no evidence of immunogenicity or significant changes in T cells, immunoglobulins, or autoantibody levels. In patients with mild to moderate active lupus, 360 mg/m2 epratuzumab was well tolerated, with evidence of clinical improvement after the first infusion and durable clinical

  16. 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

  17. 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

  18. 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

  19. Anti-bacterial effects of the essential oil of Teucrium polium L. on human pathogenic bacteria

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    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

  20. 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.