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  1. Kaposi sarcoma associated with lipoedema.

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    Ekmekci, T R; Ayabakan, O; Sakiz, D; Koslu, A

    2005-05-01

    Lipoedema is a form of lipodistrophy, which consists of abnormal accumulation of fat in subcutaneous tissue of the lower limbs. It does not cause any disease and it has not been reported association with malignity. We describe a 63-year-old woman occurring of Kaposi sarcoma on the lipoedema base.

  2. Molecular piracy of Kaposi's sarcoma associated herpesvirus.

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    Choi, J; Means, R E; Damania, B; Jung, J U

    2001-01-01

    Kaposi's Sarcoma associated Herpesvirus (KSHV) is the most recently discovered human tumor virus and is associated with the pathogenesis of Kaposi's sarcoma, primary effusion lymphoma, and Multicentric Casttleman's disease. KSHV contains numerous open reading frames with striking homology to cellular genes. These viral gene products play a variety of roles in KSHV-associated pathogenesis by disrupting cellular signal transduction pathways, which include interferon-mediated anti-viral responses, cytokine-regulated cell growth, apoptosis, and cell cycle control. In this review, we will attempt to cover our understanding of how viral proteins deregulate cellular signaling pathways, which ultimately contribute to the conversion of normal cells to cancerous cells.

  3. Pathogenesis and Associated Diseases of Kaposi's Sarcoma-associated Herpesvirus

    Institute of Scientific and Technical Information of China (English)

    Lin-ding WANG

    2007-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the primary etiological agent of Kaposi's sarcoma, primary effusion lymphoma and muticentric Castleman's disease. In common with the other herpesviruses, KSHV exhibits both latent and lytic life cycles, both of which are characterized by distinct gene expression profiles and programs. KSHV encodes proteins which play essential roles in the inhibition of host adaptive and innate immunity, the inhibition of apoptosis, and the regulation of the cell cycle. KSHV also encodes several proteins which have transforming and intrcellular signalling activity.

  4. Kaposi Sarcoma-associated Herpesvirus: mechanisms of oncogenesis.

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    Schulz, Thomas F; Cesarman, Ethel

    2015-10-01

    Kaposi Sarcoma-associated Herpesvirus (KSHV, HHV8) causes three human malignancies, Kaposi Sarcoma (KS), an endothelial tumor, as well as Primary Effusion Lymphoma (PEL) and the plasma cell variant of Multicentric Castleman's Disease (MCD), two B-cell lymphoproliferative diseases. All three cancers occur primarily in the context of immune deficiency and/or HIV infection, but their pathogenesis differs. KS most likely results from the combined effects of an endotheliotropic virus with angiogenic properties and inflammatory stimuli and thus represents an interesting example of a cancer that arises in an inflammatory context. Viral and cellular angiogenic and inflammatory factors also play an important role in the pathogenesis of MCD. In contrast, PEL represents an autonomously growing malignancy that is, however, still dependent on the continuous presence of KSHV and the action of several KSHV proteins.

  5. Mechanisms of Kaposi's Sarcoma-Associated Herpesvirus Latency and Reactivation

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    Fengchun Ye

    2011-01-01

    Full Text Available The life cycle of Kaposi's sarcoma-associated herpesvirus (KSHV consists of latent and lytic replication phases. During latent infection, only a limited number of KSHV genes are expressed. However, this phase of replication is essential for persistent infection, evasion of host immune response, and induction of KSHV-related malignancies. KSHV reactivation from latency produces a wide range of viral products and infectious virions. The resulting de novo infection and viral lytic products modulate diverse cellular pathways and stromal microenvironment, which promote the development of Kaposi's sarcoma (KS. The mechanisms controlling KSHV latency and reactivation are complex, involving both viral and host factors, and are modulated by diverse environmental factors. Here, we review the cellular and molecular basis of KSHV latency and reactivation with a focus on the most recent advancements in the field.

  6. The role of Kaposi sarcoma-associated herpesvirus in the pathogenesis of Kaposi sarcoma.

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    Gramolelli, Silvia; Schulz, Thomas F

    2015-01-01

    Kaposi sarcoma (KS) is an unusual vascular tumour caused by an oncogenic-herpesvirus, Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV 8). KS lesions are characterized by an abundant inflammatory infiltrate, the presence of KSHV-infected endothelial cells that show signs of aberrant differentiation, as well as faulty angiogenesis/ vascularization. Here we discuss the molecular mechanisms that lead to the development of these histological features of KS, with an emphasis on the viral proteins that are responsible for their development.

  7. Kinetics of Kaposi's sarcoma-associated herpesvirus gene expression.

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    Sun, R; Lin, S F; Staskus, K; Gradoville, L; Grogan, E; Haase, A; Miller, G

    1999-03-01

    Herpesvirus gene expression can be classified into four distinct kinetic stages: latent, immediate early, early, and late. Here we characterize the kinetic class of a group of 16 Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 genes in a cultured primary effusion cell line and examine the expression of a subset of these genes in KS biopsies. Expression of two latent genes, LANA and vFLIP, was constitutive and was not induced by chemicals that induce the lytic cycle in primary effusion lymphoma (PEL) cell lines. An immediate-early gene, Rta (open reading frame 50 [ORF50]), was induced within 4 h of the addition of n-butyrate, and its 3.6-kb mRNA was resistant to inhibition by cycloheximide. Early genes, including K3 and K5 that are homologues of the "immediate-early" gene of bovine herpesvirus 4, K8 that is a positional homologue of Epstein-Barr virus BZLF1, vMIP II, vIL-6, and polyadenylated nuclear (PAN) RNA, appeared 8 to 13 h after chemical induction. A second group of early genes that were slightly delayed in their appearance included viral DHFR, thymidylate synthase, vMIP I, G protein-coupled receptor, K12, vBcl2, and a lytic transcript that overlapped LANA. The transcript of sVCA (ORF65), a late gene whose expression was abolished by Phosphonoacetic acid, an inhibitor of KSHV DNA replication, did not appear until 30 h after induction. Single-cell assays indicated that the induction of lytic cycle transcripts resulted from the recruitment of additional cells into the lytic cycle. In situ hybridization of KS biopsies showed that about 3% of spindle-shaped tumor cells expressed Rta, ORF K8, vIL-6, vMIP I, vBcl-2, PAN RNA, and sVCA. Our study shows that several KSHV-encoded homologues of cellular cytokines, chemokines, and antiapoptotic factors are expressed during the viral lytic cycle in PEL cell lines and in KS biopsies. The lytic cycle of KSHV, probably under the initial control of the KSHV/Rta gene, may directly contribute to tumor

  8. Epigenetic Landscape of Kaposi's Sarcoma-Associated Herpesvirus Genome in Classic Kaposi's Sarcoma Tissues

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    Wang, Xiaodong; Yang, Lei; Robertson, Erle S.; Lan, Ke

    2017-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically related to Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). It typically displays two different phases in its life cycle, the default latency and occasional lytic replication. The epigenetic modifications are thought to determine the fate of KSHV infection. Previous studies elegantly depicted epigenetic landscape of latent viral genome in in vitro cell culture systems. However, the physiologically relevant scenario in clinical KS tissue samples is unclear. In the present study, we established a protocol of ChIP-Seq for clinical KS tissue samples and mapped out the epigenetic landscape of KSHV genome in classic KS tissues. We examined AcH3 and H3K27me3 histone modifications on KSHV genome, as well as the genome-wide binding sites of latency associated nuclear antigen (LANA). Our results demonstrated that the enriched AcH3 was mainly restricted at latent locus while H3K27me3 was widespread on KSHV genome in classic KS tissues. The epigenetic landscape at the region of vIRF3 gene confirmed its silenced state in KS tissues. Meanwhile, the abundant enrichment of LANA at the terminal repeat (TR) region was also validated in the classic KS tissues, however, different LANA binding sites were observed on the host genome. Furthermore, we verified the histone modifications by ChIP-qPCR and found the dominant repressive H3K27me3 at the promoter region of replication and transcription activator (RTA) in classic KS tissues. Intriguingly, we found that the TR region in classic KS tissues was lacking in AcH3 histone modifications. These data now established the epigenetic landscape of KSHV genome in classic KS tissues, which provides new insights for understanding KSHV epigenetics and pathogenesis. PMID:28118409

  9. Kaposi's sarcoma-associated herpesvirus infection and Kaposi's sarcoma in Brazil

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    S. Ramos-da-Silva

    2006-05-01

    Full Text Available Kaposi's sarcoma (KS became a critical health issue with the emergence of acquired immunodeficiency syndrome (AIDS in the 1980s. Four clinical-epidemiological forms of KS have been described: classical KS, endemic KS, iatrogenic KS, and AIDS-associated KS. In 1994, Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus type 8 was identified by Chang and colleagues, and has been detected worldwide at frequencies ranging from 80 to 100%. The aim of the present study was to evaluate the frequency of KSHV infection in KS lesions from HIV-positive and HIV-negative patients in Brazil, as well as to review the current knowledge about KS transmission and detection. For these purposes, DNA from 51 cases of KS was assessed by PCR: 20 (39.2% cases of classical KS, 29 (56.9% of AIDS-associated KS and 2 (3.9% of iatrogenic KS. Most patients were males (7.5:1, M/F, and mean age was 47.9 years (SD = ± 18.7 years. As expected, HIV-positive KS patients were younger than patients with classical KS. On the other hand, patients with AIDS-associated KS have early lesions (patch and plaque compared to classical KS patients (predominantly nodular lesions. This is assumed to be the result of the early diagnose of KS in the HIV-positive setting. KSHV infection was detected by PCR in almost all cases (48/51; 94.1%, irrespectively of the clinical-epidemiological form of KS. These results show that KSHV is associated with all forms of KS in Brazilian patients, a fact that supports the role of this virus in KS pathogenesis.

  10. Kaposi's sarcoma associated herpesvirus infection%Kaposi's肉瘤相关疱疹病毒感染

    Institute of Scientific and Technical Information of China (English)

    荣义辉; 游绍莉

    2004-01-01

    @@ 1994年Chang等[1]应用代表性差异分析方法从1例AIDS患者的Kaposi's肉瘤(KS)组织中分离到2段独立的核酸片段,经进一步研究确认为一种新的人类疱疹病毒,研究者称之Kaposi肉瘤相关疱疹病毒(Kaposi's sarcoma-associated herpesvirus,KSHV),也被称为人类疱疹病毒8型(Humanherpesvirus 8,HHV-8).

  11. Treatment of Kaposi sarcoma-associated herpesvirus (KSHV-associated cancers

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    Dirk P Dittmer

    2012-04-01

    Full Text Available Kaposi sarcoma (KS is the most frequent AIDS-defining cancer worldwide. Kaposi sarcoma associated herpesvirus (KSHV is the etiological agent of KS, and the virus is also associated with two lymphoproliferative diseases. Both KS and KSHV-associated lymphomas, are cancers of unique molecular composition. They represent a challenge for cancer treatment and an opportunity to identify new mechanisms of transformation. Here, we review the current clinical insights into KSHV-associated cancers and discuss scientific insights into the pathobiology of KS, primary effusion lymphoma and multicentric Castleman’s disease.

  12. Kaposi's sarcoma associated herpesvirus (KSHV entry into target cells

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    Sayan eChakraborty

    2012-01-01

    Full Text Available Herpesvirus infection of target cells is a complex process involving multiple host cell surface molecules (receptors and multiple viral envelope glycoproteins. Kaposi’s sarcoma associated herpesvirus (KSHV or HHV-8 infects a variety of in vivo target cells such as endothelial cells, B cells, monocytes, epithelial cells, and keratinocytes. KSHV also infects a diversity of in vitro target cells and establishes in vitro latency in many of these cell types. KSHV interactions with the host cell surface molecules and its mode of entry in the various target cells are critical for the understanding of KSHV pathogenesis. KSHV is the first herpesvirus shown to interact with adherent target cell integrins and this interaction initiates the host cell pre-existing signal pathways that are utilized for successful infection. This chapter discusses the various aspects of the early stage of KSHV infection of target cells, receptors used and issues that need to be clarified and future directions. The various signaling events triggered by KSHV infection and the potential role of signaling events in the different stages of infection are summarized providing the framework and starting point for further detailed studies essential to fully comprehend the pathogenesis of KSHV.

  13. Pathology of Kaposi's sarcoma-associated herpesvirus infection

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    Hitomi eFukumoto

    2011-08-01

    Full Text Available Kaposi’s sarcoma-associated herpesvirus (KSHV, human herpesvirus 8, HHV-8 is a human herpesvirus, classified as a gamma-herpesvirus. KSHV is detected in Kaposi’s sarcoma (KS, primary effusion lymphoma (PEL, and some cases of multicentric Castleman’s disease (MCD. Similar to other herpes viruses, there are two phases of infection, latent and lytic. In KSHV-associated malignancies such as KS and PEL, KSHV latently infects almost all tumor cells. Quantitative PCR analysis revealed that each tumor cell contains one copy of KSHV in KS lesions. The oncogenesis by KSHV has remained unclear. Latency-associated nuclear antigen (LANA-1 plays an important role in the pathogenesis of KSHV-associated malignancies through inhibition of apoptosis and maintenance of latency. Because all KSHV-infected cells express LANA-1, LANA-1 immunohistochemistry is a useful tool for diagnosis of KSHV infection. KSHV encodes some homologs of cellular proteins including cell-cycle regulators, cytokines and chemokines, such as cyclin D, G-protein coupled protein, interleukin-6, and macrophage inflammatory protein-1 and -2. These viral proteins mimic or disrupt host cytokine signals, resulting in microenvironments amenable to tumor growth. Lytic infection is frequently seen in MCD tissues, suggesting a different pathogenesis from KS and lymphoma.

  14. Distinct p53, p53:LANA, and LANA Complexes in Kaposi's Sarcoma-Associated Herpesvirus Lymphomas▿

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    Chen, Wuguo; Hilton, Isaac B.; Staudt, Michelle R; Burd, Christin E.; Dittmer, Dirk P

    2010-01-01

    The role of p53 in primary effusion lymphoma (PEL) is complicated. The latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) binds p53. Despite this interaction, we had found that p53 was functional in PEL, i.e., able to induce apoptosis in response to DNA damage (C. E. Petre, S. H. Sin, and D. P. Dittmer, J. Virol. 81:1912-1922, 2007), and that hdm2 was overexpressed. To further elucidate the relationship between LANA, p53, and hdm2, we purified LANA com...

  15. The Biology of Kaposi's Sarcoma-Associated Herpesvirus and the Infection of Human Immunodeficiency Virus

    Institute of Scientific and Technical Information of China (English)

    Di QIN; Chun LU

    2008-01-01

    Kaposi sarcoma-associated herpesvirus (KSHV),also known as human herpesvirus 8 (HHV-8),is discovered in 1994 from Kaposi's sarcoma (KS) lesion of an acquired immunodeficiency syndrome (AIDS)patient.In addition to its association with KS,KSHV has also been implicated as the causative agent of two other AIDS-associated malignancies:primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD).KSHV is a complex DNA virus that not only has the ability to promote cellular growth and survival for tumor development,but also can provoke deregulated angiogenesis,inflammation,and modulate the patient's immune system in favor of tumor growth.As KSHV is a necessary but not sufficient etiological factor for KS,human immunodeficiency virus (HIV) is a very important cofactor.Here we review the basic information about the biology of KSHV,development of pathogenesis and interaction between KSHV and HIV.

  16. Kaposi's Sarcoma-Associated Herpesvirus-Related Solid Lymphoma Involving the Heart and Brain

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    Jason R. Andrews

    2011-01-01

    Full Text Available Since its discovery in 1994, Kaposi's sarcoma-associated herpesvirus (KSHV has been associated with lymphoproliferative disorders, particularly in patients infected with human immunodeficiency virus (HIV. The disorders most strongly linked to KSHV are multicentric Castleman's Disease (MCD, primary effusion lymphoma, and diffuse large B-cell lymphomas. We report an unusual case of KSHV-associated lymphoma in an HIV-infected patient manifesting with myocardial and central nervous system involvement. We discuss this case in the context of increasing array of KSHV-associated lymphomas. In the HIV-infected patient with a mass lesion, a history of cutaneous Kaposi's sarcoma and prolonged immunosuppression should alert clinicians as to the possibility of KSHV-associated lymphoproliferative disorders, in order to establish a timely diagnosis.

  17. Association between malaria exposure and Kaposi's sarcoma-associated herpes virus seropositivity in Uganda

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    Nalwoga, Angela; Cose, Stephen; Wakeham, Katie; Miley, Wendell; Ndibazza, Juliet; Drakeley, Christopher; Elliott, Alison; Whitby, Denise; Newton, Robert

    2015-01-01

    Objective Unlike other herpes viruses, Kaposi's sarcoma-associated herpes virus (KSHV) is not ubiquitous worldwide and is most prevalent in sub-Saharan Africa. The reasons for this are unclear. As part of a wider investigation of factors that facilitate transmission in Uganda, a high prevalence country, we examined the association between antimalaria antibodies and seropositivity against KSHV. Methods Antibodies against P. falciparum merozoite surface protein (PfMSP)-1, P. falciparum apical membrane antigen (PfAMA)-1 and KSHV antigens (ORF73 and K8.1) were measured in samples from 1164 mothers and 1227 children. Results Kaposi's sarcoma-associated herpes virus seroprevalence was 69% among mothers and 15% children. Among mothers, KSHV seroprevalence increased with malaria antibody titres: from 60% to 82% and from 54% to 77%, comparing those with the lowest and highest titres for PfMSP-1 and PfAMA-1, respectively (P < 0.0001). Among children, only antibodies to PfAMA-1 were significantly associated with KSHV seropositivity, (P < 0.0001). In both mothers and children, anti-ORF73 antibodies were more strongly associated with malaria antibodies than anti-K8.1 antibodies. Conclusion The association between malaria exposure and KSHV seropositivity suggests that malaria is a cofactor for KSHV infection or reactivation. PMID:25611008

  18. Cancer angiogenesis induced by Kaposi sarcoma-associated herpesvirus is mediated by EZH2.

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    He, Meilan; Zhang, Wei; Bakken, Thomas; Schutten, Melissa; Toth, Zsolt; Jung, Jae U; Gill, Parkash; Cannon, Mark; Gao, Shou-Jiang

    2012-07-15

    EZH2 is a component of the epigenetic regulator PRC2 that suppresses gene expression. Elevated expression of EZH2 is common in human cancers and is associated with tumor progression and poor prognosis. In this study, we show that EZH2 elevation is associated with epigenetic modifications of Kaposi sarcoma-associated herpesvirus (KSHV), an oncogenic virus that promotes the development of Kaposi sarcoma and other malignancies that occur in patients with chronic HIV infections. KSHV induction of EZH2 expression was essential for KSHV-induced angiogenesis. High expression of EZH2 was observed in Kaposi sarcoma tumors. In cell culture, latent KSHV infection upregulated the expression of EZH2 in human endothelial cells through the expression of vFLIP and LANA, two KSHV-latent genes that activate the NF-κB pathway. KSHV-mediated upregulation of EZH2 was required for the induction of Ephrin-B2, an essential proangiogenic factor that drives endothelial cell tubule formation. Taken together, our findings indicate that KSHV regulates the host epigenetic modifier EZH2 to promote angiogenesis.

  19. [Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV, HHV-8)].

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    Katano, Harutaka

    2010-12-01

    Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8, HHV-8) are members of gamma-herpes virus family. Both viruses infect to B cells and cause malignancies such as lymphoma. Since EBV and HHV-8 are so-called 'oncovirus', their oncogenecities have been focused in the researches on EBV and KSHV for a long time. EBV was discovered in 1964, whereas KSHV was identified in 1994. However, KSHV was analyzed rapidly in these fifteen years. One of the recent progresses in the research on EBV and KSHV is that virus-encoded small RNAs were identified in their genomes and characterized. EBV is the first human virus in whose genome microRNA was identified. The oncogenecity of EBV and KSHV remains unclear. Here, I discuss the pathogenesis by EBV and KSHV with special reference to recent progress in this field.

  20. Molecular piracy: manipulation of the ubiquitin system by Kaposi's sarcoma-associated herpesvirus.

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    Fujimuro, Masahiro; Hayward, S Diane; Yokosawa, Hideyoshi

    2007-01-01

    Ubiquitination, one of several post-translational protein modifications, plays a key role in the regulation of cellular events, including protein degradation, signal transduction, endocytosis, protein trafficking, apoptosis and immune responses. Ubiquitin attachment at the lysine residue of cellular factors acts as a signal for endocytosis and rapid degradation by the 26S proteasome. It has recently been observed that viruses, especially oncogenic herpesviruses, utilise molecular piracy by encoding their own proteins to interfere with regulation of cell signalling. Kaposi's sarcoma- associated herpesvirus (KSHV) manipulates the ubiquitin system to facilitate cell proliferation, anti-apoptosis and evasion from immunity. In this review, we will describe the strategies used by KSHV at distinct stages of the viral life-cycle to control the ubiquitin system and promote oncogenesis and viral persistence.

  1. Multiplexed colorimetric detection of Kaposi's sarcoma associated herpesvirus and Bartonella DNA using gold and silver nanoparticles

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    Mancuso, Matthew; Jiang, Li; Cesarman, Ethel; Erickson, David

    2013-01-01

    Kaposi's sarcoma (KS) is an infectious cancer occurring most commonly in human immunodeficiency virus (HIV) positive patients and in endemic regions, such as Sub-Saharan Africa, where KS is among the top four most prevalent cancers. The cause of KS is the Kaposi's sarcoma-associated herpesvirus (KSHV, also called HHV-8), an oncogenic herpesvirus that while routinely diagnosed in developed nations, provides challenges to developing world medical providers and point-of-care detection. A major challenge in the diagnosis of KS is the existence of a number of other diseases with similar clinical presentation and histopathological features, requiring the detection of KSHV in a biopsy sample. In this work we develop an answer to this challenge by creating a multiplexed one-pot detection system for KSHV DNA and DNA from a frequently confounding disease, bacillary angiomatosis. Gold and silver nanoparticle aggregation reactions are tuned for each target and a multi-color change system is developed capable of detecting both targets down to levels between 1 nM and 2 nM. The system developed here could later be integrated with microfluidic sample processing to create a final device capable of solving the two major challenges in point-of-care KS detection.

  2. Kaposi sarcoma-associated herpesvirus promotes tumorigenesis by modulating the Hippo pathway.

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    Liu, G; Yu, F-X; Kim, Y C; Meng, Z; Naipauer, J; Looney, D J; Liu, X; Gutkind, J S; Mesri, E A; Guan, K-L

    2015-07-01

    Kaposi sarcoma-associated herpesvirus (KSHV) is an oncogenic virus and the culprit behind the human disease Kaposi sarcoma (KS), an AIDS-defining malignancy. KSHV encodes a viral G-protein-coupled receptor (vGPCR) critical for the initiation and progression of KS. In this study, we identified that YAP/TAZ, two homologous oncoproteins inhibited by the Hippo tumor suppressor pathway, are activated in KSHV-infected cells in vitro, KS-like mouse tumors and clinical human KS specimens. The KSHV-encoded vGPCR acts through Gq/11 and G12/13 to inhibit the Hippo pathway kinases Lats1/2, promoting the activation of YAP/TAZ. Furthermore, depletion of YAP/TAZ blocks vGPCR-induced cell proliferation and tumorigenesis in a xenograft mouse model. The vGPCR-transformed cells are sensitive to pharmacologic inhibition of YAP. Our study establishes a pivotal role of the Hippo pathway in mediating the oncogenic activity of KSHV and development of KS, and also suggests a potential of using YAP inhibitors for KS intervention.

  3. Regional prevalence and transmission route of Kaposi's sarcoma-associated herpes virus in Zhejiang, China

    Institute of Scientific and Technical Information of China (English)

    JU Hong-zhen; ZHU Biao; WANG Ying-jie; SHENG Zi-ke; SHENG Ji-fang

    2012-01-01

    Background The infection of Kaposi's sarcoma-associated herpes virus (KSHV) is most likely the cause of clinical Kaposi's sarcoma,primary effusion lymphoma,and multi-center Castleman's disease.KSHV infection has very limited epidemiological survey data in China,and its definite mode of transmission remains controversial.This study aimed to determine the infection status and the main transmission route of KSHV in Chinese population.Methods An enzyme-linked immunosorbent assay (ELISA) utilizing KSHV ORF65 recombinant protein was employed to analyze the antibody response to KSHV ORF65 in sera from 122 healthy physical examination people,107intravenous drug users,135 non-intravenous drug users,211 hepatitis B (HBV) patients infected via blood transmission,107 kidney transplant recipients,and 72 female sex workers in Zhejiang Province in Southeast China.Results KSHV infection occurred relatively common (13.1%) in healthy population in Zhejiang,China.Infection rate was 16.7% in female sex workers,but significantly elevated in intravenous drug addicts (58.9%),blood-transmitted HBV patients (28.0%) and kidney transplant patients (41.1%).Conclusion Blood borne transmission of KSHV is probably the main route of infection in Zhejiang Province.

  4. Non-human primate model of Kaposi's sarcoma-associated herpesvirus infection.

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    Heesoon Chang

    2009-10-01

    Full Text Available Since Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8 was first identified in Kaposi's sarcoma (KS lesions of HIV-infected individuals with AIDS, the basic biological understanding of KSHV has progressed remarkably. However, the absence of a proper animal model for KSHV continues to impede direct in vivo studies of viral replication, persistence, and pathogenesis. In response to this need for an animal model of KSHV infection, we have explored whether common marmosets can be experimentally infected with human KSHV. Here, we report the successful zoonotic transmission of KSHV into common marmosets (Callithrix jacchus, Cj, a New World primate. Marmosets infected with recombinant KSHV rapidly seroconverted and maintained a vigorous anti-KSHV antibody response. KSHV DNA and latent nuclear antigen (LANA were readily detected in the peripheral blood mononuclear cells (PBMCs and various tissues of infected marmosets. Remarkably, one orally infected marmoset developed a KS-like skin lesion with the characteristic infiltration of leukocytes by spindle cells positive for KSHV DNA and proteins. These results demonstrate that human KSHV infects common marmosets, establishes an efficient persistent infection, and occasionally leads to a KS-like skin lesion. This is the first animal model to significantly elaborate the important aspects of KSHV infection in humans and will aid in the future design of vaccines against KSHV and anti-viral therapies targeting KSHV coinfected tumor cells.

  5. Characterization of Kaposi's Sarcoma-Associated Herpesvirus-Related Lymphomas by DNA Microarray Analysis

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    Keiji Ueda

    2011-01-01

    Full Text Available Among herpesviruses, γ-herpesviruses are supposed to have typical oncogenic activities. Two human γ-herpesviruses, Epstein-Barr virus (EBV and Kaposi's sarcoma-associated herpesvirus (KSHV, are putative etiologic agents for Burkitt lymphoma, nasopharyngeal carcinoma, and some cases of gastric cancers, and Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma (PEL especially in AIDS setting for the latter case, respectively. Since such two viruses mentioned above are highly species specific, it has been quite difficult to prove their oncogenic activities in animal models. Nevertheless, the viral oncogenesis is epidemiologically and/or in vitro experimentally evident. This time, we investigated gene expression profiles of KSHV-oriented lymphoma cell lines, EBV-oriented lymphoma cell lines, and T-cell leukemia cell lines. Both KSHV and EBV cause a B-cell-originated lymphoma, but the gene expression profiles were typically classified. Furthermore, KSHV could govern gene expression profiles, although PELs are usually coinfected with KSHV and EBV.

  6. The HIV protease inhibitor nelfinavir inhibits Kaposi's sarcoma-associated herpesvirus replication in vitro.

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    Gantt, Soren; Carlsson, Jacquelyn; Ikoma, Minako; Gachelet, Eliora; Gray, Matthew; Geballe, Adam P; Corey, Lawrence; Casper, Corey; Lagunoff, Michael; Vieira, Jeffrey

    2011-06-01

    Kaposi's sarcoma (KS) is the most common HIV-associated cancer worldwide and is associated with high levels of morbidity and mortality in some regions. Antiretroviral (ARV) combination regimens have had mixed results for KS progression and resolution. Anecdotal case reports suggest that protease inhibitors (PIs) may have effects against KS that are independent of their effect on HIV infection. As such, we evaluated whether PIs or other ARVs directly inhibit replication of Kaposi's sarcoma-associated herpesvirus (KSHV), the gammaherpesvirus that causes KS. Among a broad panel of ARVs tested, only the PI nelfinavir consistently displayed potent inhibitory activity against KSHV in vitro as demonstrated by an efficient quantitative assay for infectious KSHV using a recombinant virus, rKSHV.294, which expresses the secreted alkaline phosphatase. This inhibitory activity of nelfinavir against KSHV replication was confirmed using virus derived from a second primary effusion lymphoma cell line. Nelfinavir was similarly found to inhibit in vitro replication of an alphaherpesvirus (herpes simplex virus) and a betaherpesvirus (human cytomegalovirus). No activity was observed with nelfinavir against vaccinia virus or adenovirus. Nelfinavir may provide unique benefits for the prevention or treatment of HIV-associated KS and potentially other human herpesviruses by direct inhibition of replication.

  7. Kaposi's Sarcoma-Associated Herpesvirus Infection of Neurons in HIV-Positive Patients.

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    Tso, For Yue; Sawyer, Ashley; Kwon, Eun Hee; Mudenda, Victor; Langford, Dianne; Zhou, You; West, John; Wood, Charles

    2017-06-15

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), one of the leading cancers in human immunodeficiency virus (HIV)-infected patients in Zambia. KSHV was detected in the human central nervous system (CNS) by polymerase chain reaction (PCR) analysis, but tissue location and cell tropism for KSHV infection has not been established. Given the neurotropism exhibited by other herpesviruses and the frequent coinfection of HIV-positive individuals by KSHV, we sought to determine whether the central nervous system (CNS) can be infected by KSHV in HIV-positive Zambian individuals. Postmortem brain tissue specimens were collected from individuals coinfected with KSHV and HIV. PCR and Southern blots were performed on DNA extracted from the brain tissue specimens to verify KSHV infection. Immunohistochemical analysis and immunofluorescent microscopy were used to localize and identify KSHV-infected cells. Tropism was further established by in vitro infection of primary human neurons with rKSHV.219. KSHV DNA was detected in the CNS from 4 of 11 HIV-positive individuals. Immunohistochemical analysis and immunofluorescent microscopy demonstrated that KSHV infected neurons and oligodendrocytes in parenchymal brain tissues. KSHV infection of neurons was confirmed by in vitro infection of primary human neurons with rKSHV.219. Our study showed that KSHV infects human CNS-resident cells, primarily neurons, in HIV-positive Zambian individuals.

  8. Latency-associated nuclear antigen of Kaposi sarcoma-associated herpesvirus promotes angiogenesis through targeting notch signaling effector Hey1.

    Science.gov (United States)

    Wang, Xing; He, Zhiheng; Xia, Tian; Li, Xiaofan; Liang, Deguang; Lin, Xianzhi; Wen, Hao; Lan, Ke

    2014-04-01

    Notch signaling has been implicated in the pathogenesis of Kaposi sarcoma. Kaposi sarcoma is an angioproliferative neoplasm that originates from Kaposi sarcoma-associated herpesvirus (KSHV) infection. Previously, we showed that the KSHV LANA protein can stabilize intracellular Notch in KSHV-infected tumor cells and promote cell proliferation. However, whether Notch signaling functions in pathologic angiogenesis of Kaposi sarcoma remains largely unknown. Hey1, an essential downstream effector of the Notch signaling pathway, has been demonstrated to play a fundamental role in vascular development. In the present study, we performed whole transcriptome, paired-end sequencing on three patient-matched clinical Kaposi sarcoma specimens and their corresponding adjacent stroma samples, with an average depth of 42 million reads per sample. Dll4, Hey1, and HeyL displayed significant upregulation in Kaposi sarcoma. Further verification based on immunohistochemistry analysis demonstrated that Hey1 was indeed highly expressed in Kaposi sarcoma lesions. Using the Matrigel plug assay, we showed that downregulation of Hey1 and γ-secretase inhibitor treatment caused dramatic reduction in the formation of new blood vessels in mice. Interestingly, LANA was responsible for the elevated level of Hey1 through inhibition of its degradation. Importantly, Hey1 stabilized by LANA promoted the neoplastic vasculature. Taken together, our data suggest that hijacking of the proangiogenic property of Hey1 by LANA is an important strategy utilized by KSHV to achieve pathologic angiogenesis and that Hey1 is a potential therapeutic target in Kaposi sarcoma.

  9. Differential Regulation of the Overlapping Kaposi's Sarcoma-Associated Herpesvirus vGCR (orf74) and LANA (orf73) Promoters

    OpenAIRE

    Jeong, Joseph; Papin, James; Dittmer, Dirk

    2001-01-01

    Similar to that of other herpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) lytic replication destroys the host cell, while the virus can persist in a latent state in synchrony with the host. During latency only a few genes are transcribed, and the question becomes one of what determines latent versus lytic gene expression. Here we undertake a detailed analysis of the latency-associated nuclear antigen (LANA [orf73]) promoter (LANAp). We characterized a minimal region that is...

  10. Kaposi's Sarcoma-Associated Herpesvirus Hijacks RNA Polymerase II To Create a Viral Transcriptional Factory.

    Science.gov (United States)

    Chen, Christopher Phillip; Lyu, Yuanzhi; Chuang, Frank; Nakano, Kazushi; Izumiya, Chie; Jin, Di; Campbell, Mel; Izumiya, Yoshihiro

    2017-06-01

    Locally concentrated nuclear factors ensure efficient binding to DNA templates, facilitating RNA polymerase II recruitment and frequent reutilization of stable preinitiation complexes. We have uncovered a mechanism for effective viral transcription by focal assembly of RNA polymerase II around Kaposi's sarcoma-associated herpesvirus (KSHV) genomes in the host cell nucleus. Using immunofluorescence labeling of latent nuclear antigen (LANA) protein, together with fluorescence in situ RNA hybridization (RNA-FISH) of the intron region of immediate early transcripts, we visualized active transcription of viral genomes in naturally infected cells. At the single-cell level, we found that not all episomes were uniformly transcribed following reactivation stimuli. However, those episomes that were being transcribed would spontaneously aggregate to form transcriptional "factories," which recruited a significant fraction of cellular RNA polymerase II. Focal assembly of "viral transcriptional factories" decreased the pool of cellular RNA polymerase II available for cellular gene transcription, which consequently impaired cellular gene expression globally, with the exception of selected ones. The viral transcriptional factories localized with replicating viral genomic DNAs. The observed colocalization of viral transcriptional factories with replicating viral genomic DNA suggests that KSHV assembles an "all-in-one" factory for both gene transcription and DNA replication. We propose that the assembly of RNA polymerase II around viral episomes in the nucleus may be a previously unexplored aspect of KSHV gene regulation by confiscation of a limited supply of RNA polymerase II in infected cells.IMPORTANCE B cells infected with Kaposi's sarcoma-associated herpesvirus (KSHV) harbor multiple copies of the KSHV genome in the form of episomes. Three-dimensional imaging of viral gene expression in the nucleus allows us to study interactions and changes in the physical distribution of

  11. The epigenetic landscape of latent Kaposi sarcoma-associated herpesvirus genomes.

    Directory of Open Access Journals (Sweden)

    Thomas Günther

    Full Text Available Herpesvirus latency is generally thought to be governed by epigenetic modifications, but the dynamics of viral chromatin at early timepoints of latent infection are poorly understood. Here, we report a comprehensive spatial and temporal analysis of DNA methylation and histone modifications during latent infection with Kaposi Sarcoma-associated herpesvirus (KSHV, the etiologic agent of Kaposi Sarcoma and primary effusion lymphoma (PEL. By use of high resolution tiling microarrays in conjunction with immunoprecipitation of methylated DNA (MeDIP or modified histones (chromatin IP, ChIP, our study revealed highly distinct landscapes of epigenetic modifications associated with latent KSHV infection in several tumor-derived cell lines as well as de novo infected endothelial cells. We find that KSHV genomes are subject to profound methylation at CpG dinucleotides, leading to the establishment of characteristic global DNA methylation patterns. However, such patterns evolve slowly and thus are unlikely to control early latency. In contrast, we observed that latency-specific histone modification patterns were rapidly established upon a de novo infection. Our analysis furthermore demonstrates that such patterns are not characterized by the absence of activating histone modifications, as H3K9/K14-ac and H3K4-me3 marks were prominently detected at several loci, including the promoter of the lytic cycle transactivator Rta. While these regions were furthermore largely devoid of the constitutive heterochromatin marker H3K9-me3, we observed rapid and widespread deposition of H3K27-me3 across latent KSHV genomes, a bivalent modification which is able to repress transcription in spite of the simultaneous presence of activating marks. Our findings suggest that the modification patterns identified here induce a poised state of repression during viral latency, which can be rapidly reversed once the lytic cycle is induced.

  12. Kaposi's sarcoma-associated herpesvirus contains G protein-coupled receptor and cyclin D homologs which are expressed in Kaposi's sarcoma and malignant lymphoma.

    OpenAIRE

    1996-01-01

    A new human herpesvirus was recently identified in all forms of Kaposi's sarcoma (Kaposi's sarcoma-associated herpesvirus [KSHV] or human herpesvirus 8), as well as in primary effusion (body cavity-based) lymphomas (PELs). A 12.3-kb-long KSHV clone was obtained from a PEL genomic library. Sequencing of this clone revealed extensive homology and colinearity with the right end of the herpesvirus saimiri (HVS) genome and more limited homology to the left end of the Epstein-Barr virus genome. Fou...

  13. Expression of Kaposi's Sarcoma-associated Herpesvirus ORFK8.1 and Its Preliminary Diagnostic Application

    Institute of Scientific and Technical Information of China (English)

    Bi-shi FU; Bao-lin LI; Xin-xing OUYANG; Yan ZENG; Fan-hong XU; Lin-ding WANG

    2009-01-01

    The ORFK8.1 of Kaposi's sarcoma associated-herpesvirus (KSHV) was expressed in a prokaryotic expression system. The expression of recombinant E.coli containing pQE-80L-orf K8.1 was induced by isopropyl-b-D-thiogalactopyranoside (IPTG). The fusion protein was purified by chromatyography. The expressed protein and its purified product were identified by sodium dodecyl sulfate-polyacrylamide gel eletrophoresis (SDS-PAGE). SDS-PAGE showed that a protein of 26 kDa was visualized as expected. A western blot assay was established to analyze the immunogenicity of purified recombinant 0RFK8.1 protein. The optimal condition of the recombinant ORFK8.1 ELISA assay was confirmed: the concentration of antigen was 5 ug/mL, the dilution of serum was 1:200. We used the ELISA method to investigate the recombinant ORF K8.1 protein's specificity, the data showed that the specificity of ORF K8.1 to detect KSHV was 100%. At the same time, 560 sera samples from Hubei province were detected by using ORFK8.1 ELISA to investigate KSHV seroprevalence in this region. The KSHV seroprevalence in Hubei province is shown to be 6.80%.

  14. RNA Sequencing Reveals that Kaposi Sarcoma-Associated Herpesvirus Infection Mimics Hypoxia Gene Expression Signature

    Science.gov (United States)

    Viollet, Coralie; Davis, David A.; Tekeste, Shewit S.; Reczko, Martin; Pezzella, Francesco; Ragoussis, Jiannis

    2017-01-01

    Kaposi sarcoma-associated herpesvirus (KSHV) causes several tumors and hyperproliferative disorders. Hypoxia and hypoxia-inducible factors (HIFs) activate latent and lytic KSHV genes, and several KSHV proteins increase the cellular levels of HIF. Here, we used RNA sequencing, qRT-PCR, Taqman assays, and pathway analysis to explore the miRNA and mRNA response of uninfected and KSHV-infected cells to hypoxia, to compare this with the genetic changes seen in chronic latent KSHV infection, and to explore the degree to which hypoxia and KSHV infection interact in modulating mRNA and miRNA expression. We found that the gene expression signatures for KSHV infection and hypoxia have a 34% overlap. Moreover, there were considerable similarities between the genes up-regulated by hypoxia in uninfected (SLK) and in KSHV-infected (SLKK) cells. hsa-miR-210, a HIF-target known to have pro-angiogenic and anti-apoptotic properties, was significantly up-regulated by both KSHV infection and hypoxia using Taqman assays. Interestingly, expression of KSHV-encoded miRNAs was not affected by hypoxia. These results demonstrate that KSHV harnesses a part of the hypoxic cellular response and that a substantial portion of hypoxia-induced changes in cellular gene expression are induced by KSHV infection. Therefore, targeting hypoxic pathways may be a useful way to develop therapeutic strategies for KSHV-related diseases. PMID:28046107

  15. Immunogenicity Analysis of Prokaryotic Expression Products of Kaposi's Sarcoma Associated Herpesvirus orf65

    Institute of Scientific and Technical Information of China (English)

    Bi-shi FU; Bao-lin LI; Lin-ding WANG

    2008-01-01

    To purify the protein encoding the small capsid protein (SCP) of KSHV and analyze its immunogenicity, the carboxyl terminus of orf65 of Kaposi's sarcoma associated-herpesvirus (KSHV) was expressed in a prokaryotic expression system. The expression of recombinant E. coli containing pQE-80L-orf65 was induced by isopropyl-β-D-thiogalactopyranoside (IPTG) and the fusion protein was purified by chromatography. The expressed protein and its purified product were identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and showed that 9 kDa was the expected size of the purified orf65 protein. The antiserum was produced in rabbit which was immunized by purified orf65 protein. An ELISA assay was established to analyze the immunogenicity of the purified orf65 protein. The ELISA analysis demonstrated that orf65 protein has strong immune activity, and the immune activity of polyclonal antibody against orf65 was more than 4 fold higher than that in the serum of the non-immunized rabbit. These results demonstrate that purified orf65 protein has very strong immunogenicity and can be used in screening KSHV infection in the general population using ELISA.

  16. Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus.

    Directory of Open Access Journals (Sweden)

    Fuqu Yu

    2007-03-01

    Full Text Available The herpesvirus life cycle has two distinct phases: latency and lytic replication. The balance between these two phases is critical for viral pathogenesis. It is believed that cellular signals regulate the switch from latency to lytic replication. To systematically evaluate the cellular signals regulating this reactivation process in Kaposi sarcoma-associated herpesvirus, the effects of 26,000 full-length cDNA expression constructs on viral reactivation were individually assessed in primary effusion lymphoma-derived cells that harbor the latent virus. A group of diverse cellular signaling proteins were identified and validated in their effect of inducing viral lytic gene expression from the latent viral genome. The results suggest that multiple cellular signaling pathways can reactivate the virus in a genetically homogeneous cell population. Further analysis revealed that the Raf/MEK/ERK/Ets-1 pathway mediates Ras-induced reactivation. The same pathway also mediates spontaneous reactivation, which sets the first example to our knowledge of a specific cellular pathway being studied in the spontaneous reactivation process. Our study provides a functional genomic approach to systematically identify the cellular signals regulating the herpesvirus life cycle, thus facilitating better understanding of a fundamental issue in virology and identifying novel therapeutic targets.

  17. Preparation and characterization of polyclonal antibody against Kaposi's sarcoma-associated herpesvirus lytic gene encoding RTA.

    Science.gov (United States)

    Fan, Weifei; Tang, Qiao; Shen, Chenyou; Qin, Di; Lu, Chun; Yan, Qin

    2015-11-01

    Replication and transcription activator (RTA) is a critical lytic protein encoded by Kaposi's sarcoma-associated herpesvirus (KSHV). To prepare rabbit polyclonal antibody against RTA, three antigenic polypeptides of KSHV RTA were initially synthesized. The fragment of RTA was cloned into p3FlagBsd to construct the recombinant plasmid, pRTA-Flag. 293 T and EA.hy926 cells were transfected with pRTA-Flag to obtain RTA-Flag fusion protein, which was detected using anti-Flag antibody. Next, New Zealand white rabbits were immunized with keyhole limpet hemocyanin-conjugated peptides to generate polyclonal antibodies against RTA. Enzyme-linked immunosorbent assays were performed to characterize the polyclonal antibodies, and the titers of the polyclonal antibodies against RTA were greater than 1:11,000. Western blotting and immunofluorescence assay revealed that the prepared antibody reacted specifically with the RTA-Flag fusion protein as well as the native viral protein in KSHV-infected primary effusion lymphoma cells. Collectively, our work successfully constructed the recombinant expression vector, pRTA-Flag, and prepared the polyclonal antibody against RTA, which was valuable for investigating the biochemical and biological functions of the critical KSHV lytic gene.

  18. Antagonism of host antiviral responses by Kaposi's sarcoma-associated herpesvirus tegument protein ORF45.

    Directory of Open Access Journals (Sweden)

    Fan Xiu Zhu

    Full Text Available Virus infection of a cell generally evokes an immune response by the host to defeat the intruder in its effort. Many viruses have developed an array of strategies to evade or antagonize host antiviral responses. Kaposi's sarcoma-associated herpesvirus (KSHV is demonstrated in this report to be able to prevent activation of host antiviral defense mechanisms upon infection. Cells infected with wild-type KSHV were permissive for superinfection with vesicular stomatitis virus (VSV, suggesting that KSHV virions fail to induce host antiviral responses. We previously showed that ORF45, a KSHV immediate-early protein as well as a tegument protein of virions, interacts with IRF-7 and inhibits virus-mediated type I interferon induction by blocking IRF-7 phosphorylation and nuclear translocation (Zhu et al., Proc. Natl. Acad. Sci. USA. 99:5573-5578, 2002. Here, using an ORF45-null recombinant virus, we demonstrate a profound role of ORF45 in inhibiting host antiviral responses. Infection of cells with an ORF45-null mutant recombinant KSHV (BAC-stop45 triggered an immune response that resisted VSV super-infection, concomitantly associated with appreciable increases in transcription of type I IFN and downstream anti-viral effector genes. Gain-of-function analysis showed that ectopic expression of ORF45 in human fibroblast cells by a lentivirus vector decreased the antiviral responses of the cells. shRNA-mediated silencing of IRF-7, that predominantly regulates both the early and late phase induction of type I IFNs, clearly indicated its critical contribution to the innate antiviral responses generated against incoming KSHV particles. Thus ORF45 through its targeting of the crucial IRF-7 regulated type I IFN antiviral responses significantly contributes to the KSHV survival immediately following a primary infection allowing for progression onto subsequent stages in its life-cycle.

  19. Kaposi's Sarcoma Associated-Herpes Virus (KSHV Seroprevalence in Pregnant Women in South Africa

    Directory of Open Access Journals (Sweden)

    Malope-Kgokong Babatyi I

    2010-08-01

    Full Text Available Abstract Background Factors previously associated with Kaposi's sarcoma-associated herpesvirus (KSHV transmission in Africa include sexual, familial, and proximity to river water. We measured the seroprevalence of KSHV in relation to HIV, syphilis, and demographic factors among pregnant women attending public antenatal clinics in the Gauteng province of South Africa. Methods We tested for antibodies to KSHV lytic K8.1 and latent Orf73 antigens in 1740 pregnant women attending antenatal clinics who contributed blood to the "National HIV and Syphilis Sero-Prevalence Survey - South Africa, 2001". Information on HIV and syphilis serology, age, education, residential area, gravidity, and parity was anonymously linked to evaluate risk factors for KSHV seropositivity. Clinics were grouped by municipality regions and their proximity to the two main river catchments defined. Results KSHV seropositivity (reactive to either lytic K8.1 and latent Orf73 was nearly twice that of HIV (44.6% vs. 23.1%. HIV and syphilis seropositivity was 12.7% and 14.9% in women without KSHV, and 36.1% and 19.9% respectively in those with KSHV. Women who are KSHV seropositive were 4 times more likely to be HIV positive than those who were KSHV seronegative (AOR 4.1 95%CI: 3.4 - 5.7. Although, women with HIV infection were more likely to be syphilis seropositive (AOR 1.8 95%CI: 1.3 - 2.4, no association between KSHV and syphilis seropositivity was observed. Those with higher levels of education had lower levels of KSHV seropositivity compared to those with lower education levels. KSHV seropositivity showed a heterogeneous pattern of prevalence in some localities. Conclusions The association between KSHV and HIV seropositivity and a lack of common association with syphilis, suggests that KSHV transmission may involve geographical and cultural factors other than sexual transmission.

  20. A novel mechanism inducing genome instability in Kaposi's sarcoma-associated herpesvirus infected cells.

    Directory of Open Access Journals (Sweden)

    Brian R Jackson

    2014-05-01

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is an oncogenic herpesvirus associated with multiple AIDS-related malignancies. Like other herpesviruses, KSHV has a biphasic life cycle and both the lytic and latent phases are required for tumorigenesis. Evidence suggests that KSHV lytic replication can cause genome instability in KSHV-infected cells, although no mechanism has thus far been described. A surprising link has recently been suggested between mRNA export, genome instability and cancer development. Notably, aberrations in the cellular transcription and export complex (hTREX proteins have been identified in high-grade tumours and these defects contribute to genome instability. We have previously shown that the lytically expressed KSHV ORF57 protein interacts with the complete hTREX complex; therefore, we investigated the possible intriguing link between ORF57, hTREX and KSHV-induced genome instability. Herein, we show that lytically active KSHV infected cells induce a DNA damage response and, importantly, we demonstrate directly that this is due to DNA strand breaks. Furthermore, we show that sequestration of the hTREX complex by the KSHV ORF57 protein leads to this double strand break response and significant DNA damage. Moreover, we describe a novel mechanism showing that the genetic instability observed is a consequence of R-loop formation. Importantly, the link between hTREX sequestration and DNA damage may be a common feature in herpesvirus infection, as a similar phenotype was observed with the herpes simplex virus 1 (HSV-1 ICP27 protein. Our data provide a model of R-loop induced DNA damage in KSHV infected cells and describes a novel system for studying genome instability caused by aberrant hTREX.

  1. CD147 and downstream ADAMTSs promote the tumorigenicity of Kaposi's sarcoma-associated herpesvirus infected endothelial cells.

    Science.gov (United States)

    Dai, Lu; Trillo-Tinoco, Jimena; Chen, Yihan; Bonstaff, Karlie; Del Valle, Luis; Parsons, Chris; Ochoa, Augusto C; Zabaleta, Jovanny; Toole, Bryan P; Qin, Zhiqiang

    2016-01-26

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi's sarcoma (KS), which preferentially arise in immunocompromised patients and lack effective therapeutic options. We have previously shown that KSHV or viral protein LANA up-regulates the glycoprotein CD147, thereby inducing primary endothelial cell invasiveness. In the current study, we identify the global network controlled by CD147 in KSHV-infected endothelial cells using Illumina microarray analysis. Among downstream genes, two specific metalloproteases, ADAMTS1 and 9, are strongly expressed in AIDS-KS tissues and contribute to KSHV-infected endothelial cell invasiveness through up-regulation of IL-6 and VEGF. By using a KS-like nude mouse model, we found that targeting CD147 and downstream ADAMTSs significantly suppressed KSHV-induced tumorigenesis in vivo. Taken together, targeting CD147 and associated proteins may represent a promising therapeutic strategy against these KSHV-related malignancies.

  2. Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus.

    Science.gov (United States)

    Nador, R G; Cesarman, E; Chadburn, A; Dawson, D B; Ansari, M Q; Sald, J; Knowles, D M

    1996-07-15

    We recently discovered the Kaposi's sarcoma-associated herpes virus (KSHV/HHV-8) in an uncommon and unusual subset of AIDS-related lymphomas that grow mainly in the body cavities as lymphomatous effusions without an identifiable contiguous tumor mass. The consistent presence of KSHV and certain other distinctive features of these body cavity-based lymphomas suggest that they represent a distinct entity. We tested this hypothesis by investigating 19 malignant lymphomatous effusions occurring in the absence of a contiguous tumor mass for their clinical, morphologic, immunophenotypic, viral, and molecular characteristics, KSHV was present in 15 of 19 lymphomas. All four KSHV-negative lymphomatous effusions exhibited Burkitt or Burkitt-like morphology and c-myc gene rearrangements and, therefore, appeared to be Burkitt-type lymphomas occurring in the body cavities. In contrast, all 15 KSHV-positive lymphomatous effusions exhibited a distinctive morphology bridging large-cell immunoblastic lymphoma and anaplastic large-cell lymphoma, and all 12 cases studied lacked c-myc gene rearrangements. In addition, these lymphomas occurred in men (15/15), frequently but not exclusively in association with HIV infection (13/15), in which homosexuality was a risk factor (13/13), presented initially as a lymphomatous effusion (14/15), remained localized to the body cavity of origin (13/15), expressed CD45 (15/15) and one or more activation-associated antigens (9/10) in the frequent absence of B-cell-associated antigens (11/15), exhibited clonal immunoglobulin gene rearrangements (13/13), contained Epstein-Barr virus (14/15), and lacked bcl-2, bcl-6, ras and p53 gene alterations (13/15). These findings strongly suggest that the KSHV-positive malignant lymphomatous effusions represent a distinct clinicopathologic and biologic entity and should be distinguished from other malignant lymphomas occurring in the body cavities. Therefore, we recommend that these malignant lymphomas be

  3. Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus (KSHV) Upregulates Survivin Expression in KSHV-Associated B-Lymphoma Cells and Contributes to Their Proliferation▿

    OpenAIRE

    Lu, Jie; Verma, Subhash C.; Murakami, Masanao; Cai, Qiliang; KUMAR, Pankaj; Xiao, Bingyi; Robertson, Erle S.

    2009-01-01

    Survivin is a master regulator of cell proliferation and cell viability and is highly expressed in most human tumors. The molecular network linked to survivin expression in tumors has not been completely elucidated. In this study, we show that latency-associated nuclear antigen (LANA), a multifunctional protein of Kaposi's sarcoma-associated herpesvirus (KSHV) that is found in Kaposi's sarcoma tumors, upregulates survivin expression and increases the proliferation of KSHV-infected B cells. An...

  4. Cannabidiol inhibits growth and induces programmed cell death in kaposi sarcoma-associated herpesvirus-infected endothelium.

    Science.gov (United States)

    Maor, Yehoshua; Yu, Jinlong; Kuzontkoski, Paula M; Dezube, Bruce J; Zhang, Xuefeng; Groopman, Jerome E

    2012-07-01

    Kaposi sarcoma is the most common neoplasm caused by Kaposi sarcoma-associated herpesvirus (KSHV). It is prevalent among the elderly in the Mediterranean, inhabitants of sub-Saharan Africa, and immunocompromised individuals such as organ transplant recipients and AIDS patients. Current treatments for Kaposi sarcoma can inhibit tumor growth but are not able to eliminate KSHV from the host. When the host's immune system weakens, KSHV begins to replicate again, and active tumor growth ensues. New therapeutic approaches are needed. Cannabidiol (CBD), a plant-derived cannabinoid, exhibits promising antitumor effects without inducing psychoactive side effects. CBD is emerging as a novel therapeutic for various disorders, including cancer. In this study, we investigated the effects of CBD both on the infection of endothelial cells (ECs) by KSHV and on the growth and apoptosis of KSHV-infected ECs, an in vitro model for the transformation of normal endothelium to Kaposi sarcoma. While CBD did not affect the efficiency with which KSHV infected ECs, it reduced proliferation and induced apoptosis in those infected by the virus. CBD inhibited the expression of KSHV viral G protein-coupled receptor (vGPCR), its agonist, the chemokine growth-regulated protein α (GRO-α), vascular endothelial growth factor receptor 3 (VEGFR-3), and the VEGFR-3 ligand, vascular endothelial growth factor C (VEGF-C). This suggests a potential mechanism by which CBD exerts its effects on KSHV-infected endothelium and supports the further examination of CBD as a novel targeted agent for the treatment of Kaposi sarcoma.

  5. A negative element involved in Kaposi's sarcoma-associated herpesvirus-encoded ORF11 gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Lei [Los Alamos National Laboratory

    2009-01-01

    The ORF11 of the Kaposi's sarcoma-associated herpesvirus (KSHV) is a lytic viral gene with delayed-early expression kinetics. How the ORF11 gene expression is regulated in the KSHV lytic cascade is largely unknown. Here we report that the deletion of the KSHV viral IL-6 gene from the viral genome leads to deregulated ORF11 gene expression. The KSHV-encoded viral IL-6 protein was found not to be essentially involved in the regulation of ORF11, suggesting a potential transcriptional cis-regulation. A negative element was identified downstream of the ORF11 gene, which suppresses the ORF11 basal promoter activity in a position-independent manner.

  6. The Crystal Structure of PF-8, the DNA Polymerase Accessory Subunit from Kaposi's Sarcoma-Associated Herpesvirus

    Energy Technology Data Exchange (ETDEWEB)

    Baltz, Jennifer L.; Filman, David J.; Ciustea, Mihai; Silverman, Janice Elaine Y.; Lautenschlager, Catherine L.; Coen, Donald M.; Ricciardi, Robert P.; Hogle, James M.; (UPENN)

    2009-12-01

    Kaposi's sarcoma-associated herpesvirus is an emerging pathogen whose mechanism of replication is poorly understood. PF-8, the presumed processivity factor of Kaposi's sarcoma-associated herpesvirus DNA polymerase, acts in combination with the catalytic subunit, Pol-8, to synthesize viral DNA. We have solved the crystal structure of residues 1 to 304 of PF-8 at a resolution of 2.8 {angstrom}. This structure reveals that each monomer of PF-8 shares a fold common to processivity factors. Like human cytomegalovirus UL44, PF-8 forms a head-to-head dimer in the form of a C clamp, with its concave face containing a number of basic residues that are predicted to be important for DNA binding. However, there are several differences with related proteins, especially in loops that extend from each monomer into the center of the C clamp and in the loops that connect the two subdomains of each protein, which may be important for determining PF-8's mode of binding to DNA and to Pol-8. Using the crystal structures of PF-8, the herpes simplex virus catalytic subunit, and RB69 bacteriophage DNA polymerase in complex with DNA and initial experiments testing the effects of inhibition of PF-8-stimulated DNA synthesis by peptides derived from Pol-8, we suggest a model for how PF-8 might form a ternary complex with Pol-8 and DNA. The structure and the model suggest interesting similarities and differences in how PF-8 functions relative to structurally similar proteins.

  7. Kaposi's sarcoma-associated herpesvirus-encoded LANA associates with glucocorticoid receptor and enhances its transcriptional activities

    Energy Technology Data Exchange (ETDEWEB)

    Togi, Sumihito; Nakasuji, Misa; Muromoto, Ryuta; Ikeda, Osamu; Okabe, Kanako; Kitai, Yuichi; Kon, Shigeyuki [Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812 (Japan); Oritani, Kenji [Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Matsuda, Tadashi, E-mail: tmatsuda@pharm.hokudai.ac.jp [Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812 (Japan)

    2015-07-31

    Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activated GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. - Highlights: • KSHV-LANA enhances the transcriptional activity of GR in 293T and HeLa cells. • KSHV-LANA physically associates with GR. • KSHV-LANA enhances GR activation and cell growth suppression in human B-lymphocytes. • KSHV-LANA influences the nuclear retention and DNA binding activity of GR.

  8. Kaposi΄s sarcoma-associated herpesvirus ORF36 protein induces chromosome condensation and phosphorylation of histone H3.

    Science.gov (United States)

    Kim, Sunmi; Cha, Seho; Jang, Jun Hyeong; Kim, Yejin; Seo, Taegun

    2013-01-01

    Kaposi΄s sarcoma-associated herpesvirus (KSHV) has been known as an agent causing Kaposi΄s sarcoma, primary effusion lymphoma, and multicentric Castleman΄s disease. In the lytic phase of the virus cycle, various viral genes are expressed, which causes host cell dysregulation. Among the lytic genes, viral protein kinase (vPK) encoded by ORF36 is a member of serine/threonine protein kinase (CHPK) family, which is involved in viral gene expression, viral DNA replication and encapsidation, and nuclear egress of virions. Recent studies have shown that the BGLF4 protein of Epstein-Barr virus (EBV), a member of the CHPK family, alters the host cell chromatin structure through phosphorylation of its key regulators. The role of KSHV ORF36 in cellular mitotic events, however, is not yet understood. In the current study, we showed that KSHV ORF36 induced chromosome condensation and phosphorylation of histone H3 on Ser 10, which are known as cellular mitosis markers. These processes have occurred in a kinase activity-dependent manner.

  9. Regulation and autoregulation of the promoter for the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus.

    Science.gov (United States)

    Jeong, Joseph H; Orvis, Joshua; Kim, Jong Wook; McMurtrey, Curtis P; Renne, Rolf; Dittmer, Dirk P

    2004-04-16

    Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 has been established as the etiological agent of Kaposi's sarcoma and certain AIDS-associated lymphomas. KSHV establishes latent infection in these tumors, invariably expressing high levels of the viral latency-associated nuclear antigen (LANA) protein. LANA is necessary and sufficient to maintain the KSHV episome. It also modulates viral and cellular transcription and has been implicated directly in oncogenesis because of its ability to bind to the p53 and pRb tumor suppressor proteins. Previously, we identified the LANA promoter (LANAp) and showed that it was positively regulated by LANA itself. Here, we present a detailed mutational analysis and define cis-acting elements and trans-acting factors for the core LANAp. We found that a downstream promoter element, TATA box, and GC box/Sp1 site at -29 are all individually required for activity. This architecture places LANAp into the small and unusual group of eukaryotic promoters that contain both the downstream promoter element and TATA element but lack a defined initiation site. Furthermore, we demonstrate that LANA regulates its own promoter via its C-terminal domain and does bind to a defined site within the core promoter.

  10. Trends in Kaposi's sarcoma-associated Herpesvirus antibodies prior to the development of HIV-associated Kaposi's sarcoma: A nested case-control study

    Science.gov (United States)

    Wakeham, Katie; Johnston, W Thomas; Nalwoga, Angela; Webb, Emily L; Mayanja, Billy N; Miley, Wendell; Elliott, Alison M; Whitby, Denise; Newton, Robert

    2015-01-01

    HIV-associated Kaposi's sarcoma (KS) is a public health challenge in sub-Saharan Africa since both the causative agent, Kaposi's sarcoma associated-herpesvirus (KSHV), and the major risk factor, HIV, are prevalent. In a nested case-control study within a long-standing clinical cohort in rural Uganda, we used stored sera to examine the evolution of antibody titres against the KSHV antigens K8.1 and latency-associated nuclear antigen (LANA) among 30 HIV-infected subjects who subsequently developed HIV-related KS (cases) and among 108 matched HIV/KSHV coinfected controls who did not develop KS. Throughout the 6 years prior to diagnosis, antibody titres to K8.1 and LANA were significantly higher among cases than controls (p < 0.0001), and titres increased prior to diagnosis in the cases. K8.1 titres differed more between KS cases and controls, compared to LANA titres. These differences in titre between cases and controls suggest a role for lytic viral replication in the pathogenesis of HIV-related KS in this setting. PMID:25395177

  11. Quantitative determinations of anti-Kaposi sarcoma-associated herpesvirus antibody levels in men who have sex with men.

    Science.gov (United States)

    Gogineni, Emile; Marshall, Vickie; Miley, Wendell; Bayat, Ahmad; Whitby, Denise; Kovacs, Joseph A; Burbelo, Peter D

    2013-05-01

    Infection with Kaposi sarcoma-associated herpesvirus (KSHV; also called human herpesvirus-8) is common among men who have sex with men (MSM). Here, quantitative anti-KSHV antibody levels were measured using luciferase immunoprecipitation systems (LIPS) in an MSM cohort with and without HIV from the NIH Clinical Center. Antibodies were detected using a mixture of 4 KSHV antigens in the MSM cohort and in Kaposi sarcoma (KS) patients. Along with HIV status, these results were compared with K8.1 and ORF73 ELISA, PCR virus detection, and additional LIPS testing. LIPS revealed that 25% (76/307) of the MSM cohort were KSHV seropositive, including 59 HIV+ and 17 HIV- subjects. The anti-KSHV antibody levels detected by LIPS were not statistically different between the KSHV+/HIV+ and KSHV+/HIV- subgroups but were lower than the KS patients (P < 0.0001). ELISA analysis of the MSM cohort detected a 35.5% frequency of KSHV infection and showed agreement with 81% of the samples evaluated by LIPS. Further LIPS testing with v-cyclin, a second ORF73 fragment and ORF38 reconciled some of the differences observed between LIPS and the ELISA immunoassays, and the revised LIPS seroprevalence in the MSM cohort was increased to 31%. Additional quantitative antibody analysis demonstrated statistically lower KSHV antibody levels in MSM compared to KS patients, but no difference was found between KSHV infected with and without HIV coinfection. These findings also suggest that antibodies against v-cyclin and ORF38 are useful for identifying patients with asymptomatic KSHV infection.

  12. Identification, expression, and immunogenicity of Kaposi's sarcoma-associated herpesvirus-encoded small viral capsid antigen.

    OpenAIRE

    Lin, S F; Sun, R; Heston, L; Gradoville, L; Shedd, D; Haglund, K; Rigsby, M; Miller, G.

    1997-01-01

    We describe a recombinant antigen for use in serologic tests for antibodies to Kaposi's sarcoma (KS)-associated herpesvirus (KSHV). The cDNA for a small viral capsid antigen (sVCA) was identified by immunoscreening of a library prepared from the BC-1 body cavity lymphoma cell line induced into KSHV lytic gene expression by sodium butyrate. The cDNA specified a 170-amino-acid peptide with homology to small viral capsid proteins encoded by the BFRF3 gene of Epstein-Barr virus and the ORF65 gene...

  13. Identification and characterization of Kaposi's sarcoma-associated herpesvirus open reading frame 11 promotor activation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Lei [Los Alamos National Laboratory

    2008-01-01

    Open reading frame 11 (ORF11) of Kaposi's sarcoma-associated herpesvirus belongs to a herpesviral homologous protein family shared by some members of the gamma- herpesvirus subfamily. Little is known about this ORF11 homologous protein family. We have characterized an unknown open reading frame, ORF11, located adjacent and in the opposite orientation to a well-characterized viral IL-6 gene. Northern blot analysis reveals that ORF11 is expressed during the KSHV lytic cycle with delayed-early transcription kinetics. We have determined the 5{prime} and 3{prime} untranslated region of the unspliced ORF11 transcript and identified both the transcription start site and the transcription termination site. Core promoter region, representing ORF11 promoter activity, was mapped to a 159nt fragment 5{prime} most proximal to the transcription start site. A functional TATA box was identified in the core promoter region. Interestingly, we found that ORF11 transcriptional activation is not responsive to Rta, the KSHV lytic switch protein. We also discovered that part of the ORF11 promoter region, the 209nt fragment upstream of the transcription start site, was repressed by phorbol esters. Our data help to understand transcription regulation of ORF11 and to elucidate roles of ORF11 in KSHV pathogenesis and life cycle.

  14. A role for MALT1 activity in Kaposi's sarcoma-associated herpes virus latency and growth of primary effusion lymphoma.

    Science.gov (United States)

    Bonsignore, L; Passelli, K; Pelzer, C; Perroud, M; Konrad, A; Thurau, M; Stürzl, M; Dai, L; Trillo-Tinoco, J; Del Valle, L; Qin, Z; Thome, M

    2017-03-01

    Primary effusion lymphoma (PEL) is an incurable malignancy that develops in immunodeficient patients as a consequence of latent infection of B-cells with Kaposi's sarcoma-associated herpes virus (KSHV). Malignant growth of KSHV-infected B cells requires the activity of the transcription factor nuclear factor (NF)-κB, which controls maintenance of viral latency and suppression of the viral lytic program. Here we show that the KSHV proteins K13 and K15 promote NF-κB activation via the protease mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1), a key driver of NF-κB activation in lymphocytes. Inhibition of the MALT1 protease activity induced a switch from the latent to the lytic stage of viral infection, and led to reduced growth and survival of PEL cell lines in vitro and in a xenograft model. These results demonstrate a key role for the proteolytic activity of MALT1 in PEL, and provide a rationale for the pharmacological targeting of MALT1 in PEL therapy.

  15. Expression of Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor monocistronic and bicistronic transcripts in primary effusion lymphomas.

    Science.gov (United States)

    Nador, R G; Milligan, L L; Flore, O; Wang, X; Arvanitakis, L; Knowles, D M; Cesarman, E

    2001-08-15

    Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) encodes a G protein-coupled receptor (vGPCR) in open reading frame (ORF) 74, which is homologous to human chemokine receptors. KSHV vGPCR is constitutively active and induces VEGF-mediated angiogenesis. Previous studies have shown that ORF 74 is transcribed as part of a bicistronic message containing ORF K14 upstream of ORF 74, with an early lytic pattern of expression. We have now extended these studies by analyzing three different KSHV-positive primary effusion lymphoma (PEL) cell lines and three PEL clinical samples. In addition, we have identified another less abundant monocistronic transcript containing only ORF 74. Both transcripts were identified at low but similar levels in two PEL clinical samples. We evaluated the degree of sequence and functional conservation of ORF74 in three additional PELs and two KS clinical specimens, demonstrating complete identity at the amino acid level among all isolates. While it is expressed as an early lytic transcript in PEL cell lines, in primary clinical PEL samples transcription of KSHV vGPCR can be readily detected.

  16. Differential regulation of the overlapping Kaposi's sarcoma-associated herpesvirus vGCR (orf74) and LANA (orf73) promoters.

    Science.gov (United States)

    Jeong, J; Papin, J; Dittmer, D

    2001-02-01

    Similar to that of other herpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) lytic replication destroys the host cell, while the virus can persist in a latent state in synchrony with the host. During latency only a few genes are transcribed, and the question becomes one of what determines latent versus lytic gene expression. Here we undertake a detailed analysis of the latency-associated nuclear antigen (LANA [orf73]) promoter (LANAp). We characterized a minimal region that is necessary and sufficient to maintain high-level transcription in all tissues tested, including primary endothelial cells and B cells, which are the suspected natural host for KSHV. We show that in transient-transfection assays LANAp mimics the expression pattern observed for the authentic promoter in the context of the KSHV episome. Unlike other KSHV promoters tested thus far, LANAp is not affected by tetradecanoyl phorbol acetate or viral lytic cycle functions. It is, however, subject to control by LANA itself and cellular regulatory factors, such as p53. This is in contrast to the K14/vGCR (orf74) promoter, which overlaps LANAp and directs transcription on the opposite strand. We isolated a minimal cis-regulatory region sufficient for K14/vGCR promoter activity and show that it, too, mimics the regulation observed for the authentic viral promoter. In particular, we demonstrate that its activity is absolutely dependent on the immediate-early transactivator orf50, the KSHV homolog of the Epstein-Barr virus Rta transactivator.

  17. Promoter switching allows simultaneous transcription of LANA and K14/vGPCR of Kaposi's sarcoma-associated herpesvirus.

    Science.gov (United States)

    Staudt, Michelle R; Dittmer, Dirk P

    2006-06-20

    Latent transcription of the latency-associated nuclear antigen (LANA/ORF73) of Kaposi's sarcoma-associated herpesvirus is driven by the LANAp-c. Complexity arises during lytic reactivation, however, as the bicistronic K14/vGPCR transcript initiates 32 bp downstream of LANAp-c in the opposite orientation. We identify an Rta/ORF50-inducible LANA promoter (LANAp-i) that is distinct from the LANAp-c. LANAp-c is unaffected by Rta/ORF50. Utilization of the second, downstream LANAp-i explains how LANA and K14/vGPCR are simultaneously transcribed during de novo infection or lytic reactivation. Transactivation of LANAp-i and K14/vGPCRp requires the C-terminal activation domain of Rta/ORF50 and is mediated by DNA-binding-dependent and -independent Rta/ORF50 mechanisms. Transcriptional profiling following viral reactivation support promoter reporter phenotypes. In sum, cis-elements within the LANAp were selected to ensure faithful expression of LANA and other genes regulated by LANAp during all stages of the KSHV lifecycle despite potential interference from K14/vGPCRp activity.

  18. The exonuclease and host shutoff functions of the SOX protein of Kaposi's sarcoma-associated herpesvirus are genetically separable.

    Science.gov (United States)

    Glaunsinger, Britt; Chavez, Leonard; Ganem, Don

    2005-06-01

    The Kaposi's sarcoma-associated herpesvirus (KSHV) SOX protein, encoded by ORF37, promotes shutoff of host cell gene expression during lytic viral replication by dramatically impairing mRNA accumulation. SOX is the KSHV homolog of the alkaline exonuclease of other herpesviruses, which has been shown to function as a DNase involved in processing and packaging the viral genome. Although the exonuclease activity of these proteins is widely conserved across all herpesviruses, the host shutoff activity observed for KSHV SOX is not. We show here that SOX expression sharply reduces the half-life of target mRNAs. Extensive mutational analysis reveals that the DNase and host shutoff activities of SOX are genetically separable. Lesions affecting the DNase activity cluster in conserved regions of the protein, but residues critical for mRNA degradation are not conserved across the viral family. Additionally, we present evidence suggesting that the two different functions of SOX occur within distinct cellular compartments-DNase activity in the nucleus and host shutoff activity in the cytoplasm.

  19. Parasite infection is associated with Kaposi's sarcoma associated herpesvirus (KSHV in Ugandan women

    Directory of Open Access Journals (Sweden)

    Ndibazza Juliet

    2011-09-01

    Full Text Available Abstract Background Immune modulation by parasites may influence susceptibility to bacteria and viruses. We examined the association between current parasite infections, HIV and syphilis (measured in blood or stool samples using standard methods and antibodies against Kaposi's sarcoma herpesvirus (KSHV, measured by ELISA, in 1915 stored plasma samples from pregnant women in Entebbe, Uganda. Results Seroprevalence of KSHV was higher in women with malaria parasitaemia (73% vs 60% p = 0.01, hookworm (67% vs 56% p = 0.001 and Mansonella perstans (69% vs 59% p = 0.05; seroprevalence increased with increasing intensity of hookworm infection (p Conclusions Specific parasite infections are associated with presence of antibodies against KSHV, perhaps mediated via their effect on immune function.

  20. Cellular and Kaposi's sarcoma-associated herpes virus microRNAs in sepsis and surgical trauma.

    Science.gov (United States)

    Tudor, S; Giza, D E; Lin, H Y; Fabris, L; Yoshiaki, K; D'Abundo, L; Toale, K M; Shimizu, M; Ferracin, M; Challagundla, K B; Cortez, M Angelica; Fuentes-Mattei, E; Tulbure, D; Gonzalez, C; Henderson, J; Row, M; Rice, T W; Ivan, C; Negrini, M; Fabbri, M; Morris, J S; Yeung, S-C J; Vasilescu, C; Calin, G A

    2014-12-04

    Once a patient is in septic shock, survival rates drop by 7.6% for every hour of delay in antibiotic therapy. Biomarkers based on the molecular mechanism of sepsis are important for timely diagnosis and triage. Here, we study the potential roles of a panel of cellular and viral miRNAs as sepsis biomarkers. We performed genome-wide microRNA (miRNA) expression profiling in leukocytes from septic patients and nonseptic controls, combined with quantitative RT-PCR in plasmas from two cohorts of septic patients, two cohorts of nonseptic surgical patients and healthy volunteers. Enzyme-linked immunosorbent assay, miRNA transfection and chromatin immunoprecipitation were used to study the effects of Kaposi sarcoma herpes virus (KSHV) miRNAs on interleukin's secretion. Differences related to sepsis etiology were noted for plasma levels of 10 cellular and 2 KSHV miRNAs (miR-K-10b and miR-K-12-12*) between septic and nonseptic patients. All the sepsis groups had high KSHV miRNAs levels compared with controls; Afro-American patients had higher levels of KSHV-miR-K12-12* than non-Afro-American patients. Both KSHV miRNAs were increased on postoperative day 1, but returned to baseline on day 7; they acted as direct agonists of Toll-like receptor 8 (TLR8), which might explain the increased secretion of the IL-6 and IL-10. Cellular and KSHV miRNAs are differentially expressed in sepsis and early postsurgical patients and may be exploited for diagnostic and therapeutic purposes. Increased miR-K-10b and miR-K12-12* are functionally involved in sepsis as agonists of TLR8, forming a positive feedback that may lead to cytokine dysregulation.

  1. Identification, expression, and immunogenicity of Kaposi's sarcoma-associated herpesvirus-encoded small viral capsid antigen.

    Science.gov (United States)

    Lin, S F; Sun, R; Heston, L; Gradoville, L; Shedd, D; Haglund, K; Rigsby, M; Miller, G

    1997-04-01

    We describe a recombinant antigen for use in serologic tests for antibodies to Kaposi's sarcoma (KS)-associated herpesvirus (KSHV). The cDNA for a small viral capsid antigen (sVCA) was identified by immunoscreening of a library prepared from the BC-1 body cavity lymphoma cell line induced into KSHV lytic gene expression by sodium butyrate. The cDNA specified a 170-amino-acid peptide with homology to small viral capsid proteins encoded by the BFRF3 gene of Epstein-Barr virus and the ORF65 gene of herpesvirus saimiri. KSHV sVCA was expressed from a 0.85-kb mRNA present late in lytic KSHV replication in BC-1 cells. This transcript was sensitive to phosphonoacetic acid and phosphonoformic acid, inhibitors of herpesvirus DNA replication. KSHV sVCA expressed in mammalian cells or Escherichia coli or translated in vitro was recognized as an antigen by antisera from KS patients. Rabbit antisera raised to KSHV sVCA expressed in E. coli detected a 22-kDa protein in KSHV-infected human B cells. Overexpressed KSHV sVCA purified from E. coli and used as an antigen in immunoblot screening assay did not cross-react with EBV BFRF3. Antibodies to sVCA were present in 89% of 47 human immunodeficiency virus (HIV)-positive patients with KS, in 20% of 54 HIV-positive patients without KS, but in none of 122 other patients including children born to HIV-seropositive mothers and patients with hemophilia, autoimmune disease, or nasopharyngeal carcinoma. Low-titer antibody was detected in three sera from 28 healthy subjects. Antibodies to recombinant sVCA correlate with KS in high-risk populations. Recombinant sVCA can be used to examine the seroepidemiology of infection with KSHV in the general population.

  2. Epstein-Barr virus (EBV Rta-mediated EBV and Kaposi's sarcoma-associated herpesvirus lytic reactivations in 293 cells.

    Directory of Open Access Journals (Sweden)

    Yen-Ju Chen

    Full Text Available Epstein-Barr virus (EBV Rta belongs to a lytic switch gene family that is evolutionarily conserved in all gamma-herpesviruses. Emerging evidence indicates that cell cycle arrest is a common means by which herpesviral immediate-early protein hijacks the host cell to advance the virus's lytic cycle progression. To examine the role of Rta in cell cycle regulation, we recently established a doxycycline (Dox-inducible Rta system in 293 cells. In this cell background, inducible Rta modulated the levels of signature G1 arrest proteins, followed by induction of the cellular senescence marker, SA-β-Gal. To delineate the relationship between Rta-induced cell growth arrest and EBV reactivation, recombinant viral genomes were transferred into Rta-inducible 293 cells. Somewhat unexpectedly, we found that Dox-inducible Rta reactivated both EBV and Kaposi's sarcoma-associated herpesvirus (KSHV, to similar efficacy. As a consequence, the Rta-mediated EBV and KSHV lytic replication systems, designated as EREV8 and ERKV, respectively, were homogenous, robust, and concurrent with cell death likely due to permissive lytic replication. In addition, the expression kinetics of EBV lytic genes in Dox-treated EREV8 cells was similar to that of their KSHV counterparts in Dox-induced ERKV cells, suggesting that a common pathway is used to disrupt viral latency in both cell systems. When the time course was compared, cell cycle arrest was achieved between 6 and 48 h, EBV or KSHV reactivation was initiated abruptly at 48 h, and the cellular senescence marker was not detected until 120 h after Dox treatment. These results lead us to hypothesize that in 293 cells, Rta-induced G1 cell cycle arrest could provide (1 an ideal environment for virus reactivation if EBV or KSHV coexists and (2 a preparatory milieu for cell senescence if no viral genome is available. The latter is hypothetical in a transient-lytic situation.

  3. Epstein-Barr virus (EBV) Rta-mediated EBV and Kaposi's sarcoma-associated herpesvirus lytic reactivations in 293 cells.

    Science.gov (United States)

    Chen, Yen-Ju; Tsai, Wan-Hua; Chen, Yu-Lian; Ko, Ying-Chieh; Chou, Sheng-Ping; Chen, Jen-Yang; Lin, Su-Fang

    2011-03-10

    Epstein-Barr virus (EBV) Rta belongs to a lytic switch gene family that is evolutionarily conserved in all gamma-herpesviruses. Emerging evidence indicates that cell cycle arrest is a common means by which herpesviral immediate-early protein hijacks the host cell to advance the virus's lytic cycle progression. To examine the role of Rta in cell cycle regulation, we recently established a doxycycline (Dox)-inducible Rta system in 293 cells. In this cell background, inducible Rta modulated the levels of signature G1 arrest proteins, followed by induction of the cellular senescence marker, SA-β-Gal. To delineate the relationship between Rta-induced cell growth arrest and EBV reactivation, recombinant viral genomes were transferred into Rta-inducible 293 cells. Somewhat unexpectedly, we found that Dox-inducible Rta reactivated both EBV and Kaposi's sarcoma-associated herpesvirus (KSHV), to similar efficacy. As a consequence, the Rta-mediated EBV and KSHV lytic replication systems, designated as EREV8 and ERKV, respectively, were homogenous, robust, and concurrent with cell death likely due to permissive lytic replication. In addition, the expression kinetics of EBV lytic genes in Dox-treated EREV8 cells was similar to that of their KSHV counterparts in Dox-induced ERKV cells, suggesting that a common pathway is used to disrupt viral latency in both cell systems. When the time course was compared, cell cycle arrest was achieved between 6 and 48 h, EBV or KSHV reactivation was initiated abruptly at 48 h, and the cellular senescence marker was not detected until 120 h after Dox treatment. These results lead us to hypothesize that in 293 cells, Rta-induced G1 cell cycle arrest could provide (1) an ideal environment for virus reactivation if EBV or KSHV coexists and (2) a preparatory milieu for cell senescence if no viral genome is available. The latter is hypothetical in a transient-lytic situation.

  4. 卡波西肉瘤相关的疱疹病毒致病分子机制%The molecular pathogeny of Kaposi's sarcoma-associated herpesvirus

    Institute of Scientific and Technical Information of China (English)

    朱彪; 陈亚岗; 吴南屏

    2006-01-01

    卡波西肉瘤相关的疱疹病毒(Kaposi's sarcoma-associated herpesvirus,KSHV)自1994年报道以来,近来对其致病性及其分子机制上取得了较大研究进展,此文从该病毒的基因组结构、致病基因、复制调控、宿主受体与免疫差异方面综述了其致病的分子机制研究的最新进展.

  5. Antibodies against lytic and latent Kaposi's sarcoma-associated herpes virus antigens and lymphoma in the European EpiLymph case–control study

    Science.gov (United States)

    Benavente, Y; Mbisa, G; Labo, N; Casabonne, D; Becker, N; Maynadie, M; Foretova, L; Cocco, P L; Nieters, A; Staines, A; Bofetta, P; Brennan, P; Whitby, D; de Sanjosé, S

    2011-01-01

    Background: Kaposi's sarcoma-associated herpes virus is associated with primary effusion lymphoma and multicentric Castleman's disease. Methods: Seropositivity to lytic and latent Kaposi's sarcoma herpes virus (KSHV) antigens were examined in 2083 lymphomas and 2013 controls from six European countries. Results: Antibodies against KSHV latent and lytic antigens were detectable in 4.5% and 3.4% of controls, respectively, and 3.6% of cases (P>0.05). The KSHV seropositivity was associated with splenic marginal zone lymphoma (SMZL) (odds ratio (OR)=4.11, 95% confidence interval (CI)=1.57–10.83) and multiple myeloma (OR=0.31, 95% CI=0.11–0.85). Conclusion: The KSHV is unlikely to contribute importantly to lymphomagenesis among immunocompetent subjects. However, the observed association with SMZL may underline a chronic antigen mechanism in its aetiology. PMID:21952625

  6. A microRNA encoded by Kaposi sarcoma-associated herpesvirus promotes B-cell expansion in vivo.

    Directory of Open Access Journals (Sweden)

    Christine Dahlke

    Full Text Available The human gammaherpesvirus Kaposi sarcoma-associated herpesvirus is strongly linked to neoplasms of endothelial and B-cell origin. The majority of tumor cells in these malignancies are latently infected, and latency genes are consequently thought to play a critical role in virus-induced tumorigenesis. One such factor is kshv-miR-K12-11, a viral microRNA that is constitutively expressed in cell lines derived from KSHV-associated tumors, and that shares perfect homology of its seed sequence with the cellular miR-155. Since miR-155 is overexpressed in a number of human tumors, it is conceivable that mimicry of miR-155 by miR-K12-11 may contribute to cellular transformation in KSHV-associated disease. Here, we have performed a side-by-side study of phenotypic alterations associated with constitutive expression of either human miR-155 or viral miR-K12-11 in bone marrow-derived hematopoietic stem cells. We demonstrate that retroviral-mediated gene transfer and hematopoietic progenitor cell transplantation into C57BL/6 mice leads to increased B-cell fractions in lymphoid organs, as well as to enhanced germinal center formation in both microRNA-expressing mouse cohorts. We furthermore identify Jarid2, a component of Polycomb repressive complex 2, as a novel validated target of miR-K12-11, and confirm its downregulation in miR-K12-11 as well as miR-155 expressing bone marrow cells. Our findings confirm and extend previous observations made in other mouse models, and underscore the notion that miR-K12-11 may have arisen to mimic miR-155 functions in KSHV-infected B-cells. The expression of miR-K12-11 may represent one mechanism by which KSHV presumably aims to reprogram naïve B-cells towards supporting long-term latency, which at the same time is likely to pre-dispose infected lymphocytes to malignant transformation.

  7. Kaposi's Sarcoma-Associated Herpesvirus K-bZIP Protein Is Necessary for Lytic Viral Gene Expression, DNA Replication, and Virion Production in Primary Effusion Lymphoma Cell Lines▿ †

    OpenAIRE

    Lefort, Sylvain; Flamand, Louis

    2009-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of three human proliferative disorders, namely, Kaposi's sarcoma, primary effusion lymphomas (PEL), and multicentric Castleman's disease. Lytic DNA replication of KSHV, which is essential for viral propagation, requires the binding of at least two KSHV proteins, replication and transactivation activator (RTA) and K-bZIP, on the lytic origin of replication. Moreover, K-bZIP physically interacts with RTA and represses its tra...

  8. Reactivation of Kaposi's sarcoma-associated herpesvirus from latency requires MEK/ERK, JNK and p38 multiple mitogen-activated protein kinase pathways.

    Science.gov (United States)

    Xie, Jianping; Ajibade, Adetola Olalekan; Ye, Fengchun; Kuhne, Kurt; Gao, Shou-Jiang

    2008-02-05

    Lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV) promotes the progression of Kaposi's sarcoma (KS), a dominant malignancy in patients with AIDS. While 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced KSHV reactivation from latency is mediated by the protein kinase C delta and MEK/ERK mitogen-activated protein kinase (MAPK) pathways, we have recently shown that the MEK/ERK, JNK and p38 MAPK pathways modulate KSHV lytic replication during productive primary infection of human umbilical vein endothelial cells [Pan, H., Xie, J., Ye, F., Gao, S.J., 2006. Modulation of Kaposi's sarcoma-associated herpesvirus infection and replication by MEK/ERK, JNK, and p38 multiple mitogen-activated protein kinase pathways during primary infection. J. Virol. 80 (11), 5371-5382]. Here, we report that, besides the MEK/ERK pathway, the JNK and p38 MAPK pathways also mediate TPA-induced KSHV reactivation from latency. The MEK/ERK, JNK and p38 MAPK pathways were constitutively activated in latent KSHV-infected BCBL-1 cells. TPA treatment enhanced the levels of activated ERK and p38 but not those of activated JNK. Inhibitors of all three MAPK pathways reduced TPA-induced production of KSHV infectious virions in BCBL-1 cells in a dose-dependent fashion. The inhibitors blocked KSHV lytic replication at the early stage(s) of reactivation, and reduced the expression of viral lytic genes including RTA, a key immediate-early transactivator of viral lytic replication. Activation of MAPK pathways was necessary and sufficient for activating the promoter of RTA. Furthermore, we showed that the activation of RTA promoter by MAPK pathways was mediated by their downstream target AP-1. Together, these findings suggest that MAPK pathways might have general roles in regulating the life cycle of KSHV by mediating both viral infection and switch from viral latency to lytic replication.

  9. DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Seho [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Lim, Chunghun [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Lee, Jae Young [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Song, Yoon-Jae [Department of Life Science, Kyungwon University, Seongnam-Si, Kyeonggi-Do 461-701 (Korea, Republic of); Park, Junsoo [Division of Biological Science and Technology, Yonsei University, Wonju 220-100 (Korea, Republic of); Choe, Joonho [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Seo, Taegun, E-mail: tseo@dongguk.edu [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of)

    2010-04-16

    During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.

  10. Seroprevalence and risk factors of Kaposi's sarcoma-associated herpesvirus infection among the general Uygur population from south and north region of Xinjiang, China

    Directory of Open Access Journals (Sweden)

    Wang Hui

    2011-12-01

    Full Text Available Abstract Background Kaposi sarcoma (KS is a complex multifocal neoplasm and is the major cause of death for about 50% of acquired immunodeficiency syndrome (AIDS patients. Kaposi's sarcoma-associated herpesvirus (KSHV is an oncogenic virus with a causal role in the development of all types of KS. KS is prevalent among the Uygur people in Xinjiang, especially in south area. Here we carried out a cross-sectional study among 1534 general Uygur individuals from south and north region of Xinjiang to assess the seroprevalence of KSHV and to identify the potential correlation between KSHV seroprevalence and KS incidence. Results Seroprevalence of KSHV in South and North Xinjiang was 23.1% and 25.9%, respectively. Older age was independently associated with higher KSHV seroprevalence. In subjects from South Xinjiang, lower educational level and reported drinking were each independently associated with higher KSHV seroprevalence. Furthermore, the antibody titer was significantly lower in both south and north KSHV seropositive individuals compared with KS patients, as analyzed by gradient dilution (P Conclusion KSHV is highly prevalent in the general Uygur population in both South and North Xinjiang. Interestingly, the infection rate of KSHV in these two geographical areas did not correlate well with KS incidence. Perhaps unknown factors exist that promote the progression of KSHV infection to KS development in the local minority groups.

  11. High incidence of Kaposi sarcoma-associated herpesvirus infection in HIV-related solid immunoblastic/plasmablastic diffuse large B-cell lymphoma.

    Science.gov (United States)

    Deloose, S T P; Smit, L A; Pals, F T; Kersten, M-J; van Noesel, C J M; Pals, S T

    2005-05-01

    Kaposi sarcoma-associated herpesvirus (KSHV) is known to be associated with two distinct lymphoproliferative disorders: primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD)/MCD-associated plasmablastic lymphoma. We here report a high incidence of KSHV infection in solid HIV-associated immunoblastic/plasmablastic non-Hodgkin's lymphomas (NHLs), in patients lacking effusions and without evidence of (prior) MCD. Within a cohort of 99 HIV-related NHLs, 10 cases were found to be KSHV positive on the basis of immunostaining for KSHV LNA-1 as well as KSHV-specific polymerase chain reaction. All but one of the tumors coexpressed Epstein-Barr virus. Interestingly, all KSHV-positive cases belonged to a distinctive subgroup of 26 diffuse large B-cell lymphomas characterized by the expression of CD138 (syndecan-1) and plasmablastic/immunoblastic morphology. These KSHV-positive lymphomas were preceded by Kaposi sarcoma in 60% of the patients and involved the gastrointestinal tract in 80%. Our results indicate that KSHV infection is not restricted to PEL and MCD; it is also common (38%) in HIV-related solid immunoblastic/plasmablastic lymphomas.

  12. SIRT1-mediated downregulation of p27Kip1 is essential for overcoming contact inhibition of Kaposi's sarcoma-associated herpesvirus transformed cells.

    Science.gov (United States)

    He, Meilan; Yuan, Hongfeng; Tan, Brandon; Bai, Rosemary; Kim, Heon Seok; Bae, Sangsu; Che, Lu; Kim, Jin-Soo; Gao, Shou-Jiang

    2016-11-15

    Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic virus associated with Kaposi's sarcoma (KS), a malignancy commonly found in AIDS patients. Despite intensive studies in the last two decades, the mechanism of KSHV-induced cellular transformation and tumorigenesis remains unclear. In this study, we found that the expression of SIRT1, a metabolic sensor, was upregulated in a variety of KSHV-infected cells. In a model of KSHV-induced cellular transformation, SIRT1 knockdown with shRNAs or knockout by CRISPR/Cas9 gene editing dramatically suppressed cell proliferation and colony formation in soft agar of KSHV-transformed cells by inducing cell cycle arrest and contact inhibition. SIRT1 knockdown or knockout induced the expression of cyclin-dependent kinase inhibitor 1B (p27Kip1). Consequently, p27 knockdown rescued the inhibitory effect of SIRT1 knockdown or knockout on cell proliferation and colony formation. Furthermore, treatment of KSHV-transformed cells with a SIRT1 inhibitor, nicotinamide (NAM), had the same effect as SIRT1 knockdown and knockout. NAM significantly inhibited cell proliferation in culture and colony formation in soft agar, and induced cell cycle arrest. Significantly, NAM inhibited the progression of tumors and extended the survival of mice in a KSHV-induced tumor model. Collectively, these results demonstrate that SIRT1 suppression of p27 is required for KSHV-induced tumorigenesis and identify a potential therapeutic target for KS.

  13. Screening of the Human Kinome Identifies MSK1/2-CREB1 as an Essential Pathway Mediating Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication during Primary Infection

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    Cheng, Fan; Sawant, Tanvee Vinod; Lan, Ke; Lu, Chun; Jung, Jae U.

    2015-01-01

    ABSTRACT Viruses often hijack cellular pathways to facilitate infection and replication. Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic gammaherpesvirus etiologically associated with Kaposi's sarcoma, a vascular tumor of endothelial cells. Despite intensive studies, cellular pathways mediating KSHV infection and replication are still not well defined. Using an antibody array approach, we examined cellular proteins phosphorylated during primary KSHV infection of primary human umbilical vein endothelial cells. Enrichment analysis identified integrin/mitogen-activated protein kinase (integrin/MAPK), insulin/epidermal growth factor receptor (insulin/EGFR), and JAK/STAT as the activated networks during primary KSHV infection. The transcriptional factor CREB1 (cyclic AMP [cAMP]-responsive element-binding protein 1) had the strongest increase in phosphorylation. While knockdown of CREB1 had no effect on KSHV entry and trafficking, it drastically reduced the expression of lytic transcripts and proteins and the production of infectious virions. Chemical activation of CREB1 significantly enhanced viral lytic replication. In contrast, CREB1 neither influenced the expression of the latent gene LANA nor affected KSHV infectivity. Mechanistically, CREB1 was not activated through the classic cAMP/protein kinase A (cAMP/PKA) pathway or via the AKT, MK2, and RSK pathways. Rather, CREB1 was activated by the mitogen- and stress-activated protein kinases 1 and 2 (MSK1/2). Consequently, chemical inhibition or knockdown of MSKs significantly inhibited the KSHV lytic replication program; however, it had a minimal effect on LANA expression and KSHV infectivity. Together, these results identify the MSK1/2-CREB1 proteins as novel essential effectors of KSHV lytic replication during primary infection. The differential effect of the MSK1/2-CREB1 pathway on the expression of viral latent and lytic genes might control the robustness of viral lytic replication, and therefore the

  14. Radiation therapy for Kaposi's sarcoma associated with acquired immunodeficiency syndrome. Tokyo Metropolitan Komagome Hospital experience

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    Ebara, Takeshi [Municipal Kanbara General Hospital, Fujikawa, Shizuoka (Japan); Karasawa, Katsuyuki; Maebayashi, Katsuya; Kurosaki, Hiromasa; Ishikawa, Hitoshi; Kaizu, Toshihide; Tanaka, Yoshiaki; Akagi, Kumiko; Masuda, Gota

    2000-12-01

    Kaposi's sarcoma is frequently found in association with acquired immunodeficiency syndrome (AIDS). We report on radiotherapy for patients with AIDS-related Kaposi's sarcoma at Tokyo Metropolitan Komagome Hospital. Between April 1991 and May 1997, radiotherapy was given to 11 lesions in eight men with AIDS-related Kaposi's sarcoma to relieve their symptoms. The lesions involved the head and neck region, the legs, and the gastrointestinal tract. Radiotherapy was carried out with 4-MV photon through parallel opposed field or high energy electrons. Total doses ranged from 20 to 38 Gy, with a median of 30 Gy, delivered in 2- to 3-Gy fractions. Four patients were given other treatments prior to the radiotherapy. Acute reaction was evaluated according to the modified acute radiation morbidity scoring criteria of the Radiation Therapy Oncology Group (RTOG). Radiotherapy had relieved the symptoms in all patients at completion of this therapy. Lesions that involved the hard palate and vocal cords had completely disappeared. The lesions that received radiotherapy were controlled without symptoms until the patients died. Patients who had the head and neck region treated exhibited severe acute mucosal reaction (at a dose of 30 Gy, there was grade 2 morbidity by modified RTOG criteria, in two patients, and grade 3 in three patients) although the radiation therapy was completed for these patients. Radiotherapy promises a favorable outcome for symptom relief in AIDS-related Kaposi's sarcoma. (author)

  15. Ets-1 Is Required for the Activation of VEGFR3 during Latent Kaposi's Sarcoma-Associated Herpesvirus Infection of Endothelial Cells

    Science.gov (United States)

    Gutierrez, Kimberley D.; Morris, Valerie A.; Wu, David; Barcy, Serge

    2013-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi's sarcoma (KS), is present in the predominant tumor cells of KS, the spindle cells. Spindle cells express markers of lymphatic endothelium and, interestingly, KSHV infection of blood endothelial cells reprograms them to a lymphatic endothelial cell phenotype. KSHV-induced reprogramming requires the activation of STAT3 and phosphatidylinositol 3 (PI3)/AKT through the activation of cellular receptor gp130. Importantly, KSHV-induced reprogramming is specific to endothelial cells, indicating that there are additional host genes that are differentially regulated during KSHV infection of endothelial cells that contribute to lymphatic reprogramming. We found that the transcription factor Ets-1 is highly expressed in KS spindle cells and is upregulated during KSHV infection of endothelial cells in culture. The KSHV latent vFLIP gene is sufficient to induce Ets-1 expression in an NF-κB-dependent fashion. Ets-1 is required for KSHV-induced expression of VEGFR3, a lymphatic endothelial-cell-specific receptor important for lymphangiogenesis, and Ets-1 activates the promoter of VEGFR3. Ets-1 knockdown does not alter the expression of another lymphatic-specific gene, the podoplanin gene, but does inhibit the expression of VEGFR3 in uninfected lymphatic endothelium, indicating that Ets-1 is a novel cellular regulator of VEGFR3 expression. Knockdown of Ets-1 affects the ability of KSHV-infected cells to display angiogenic phenotypes, indicating that Ets-1 plays a role in KSHV activation of endothelial cells during latent KSHV infection. Thus, Ets-1 is a novel regulator of VEGFR3 and is involved in the induction of angiogenic phenotypes by KSHV. PMID:23552426

  16. CTCF and Rad21 act as host cell restriction factors for Kaposi's sarcoma-associated herpesvirus (KSHV lytic replication by modulating viral gene transcription.

    Directory of Open Access Journals (Sweden)

    Da-Jiang Li

    2014-01-01

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is a human herpesvirus that causes Kaposi's sarcoma and is associated with the development of lymphoproliferative diseases. KSHV reactivation from latency and virion production is dependent on efficient transcription of over eighty lytic cycle genes and viral DNA replication. CTCF and cohesin, cellular proteins that cooperatively regulate gene expression and mediate long-range DNA interactions, have been shown to bind at specific sites in herpesvirus genomes. CTCF and cohesin regulate KSHV gene expression during latency and may also control lytic reactivation, although their role in lytic gene expression remains incompletely characterized. Here, we analyze the dynamic changes in CTCF and cohesin binding that occur during the process of KSHV viral reactivation and virion production by high resolution chromatin immunoprecipitation and deep sequencing (ChIP-Seq and show that both proteins dissociate from viral genomes in kinetically and spatially distinct patterns. By utilizing siRNAs to specifically deplete CTCF and Rad21, a cohesin component, we demonstrate that both proteins are potent restriction factors for KSHV replication, with cohesin knockdown leading to hundred-fold increases in viral yield. High-throughput RNA sequencing was used to characterize the transcriptional effects of CTCF and cohesin depletion, and demonstrated that both proteins have complex and global effects on KSHV lytic transcription. Specifically, both proteins act as positive factors for viral transcription initially but subsequently inhibit KSHV lytic transcription, such that their net effect is to limit KSHV RNA accumulation. Cohesin is a more potent inhibitor of KSHV transcription than CTCF but both proteins are also required for efficient transcription of a subset of KSHV genes. These data reveal novel effects of CTCF and cohesin on transcription from a relatively small genome that resemble their effects on the cellular

  17. Azidothymidine Sensitizes Primary Effusion Lymphoma Cells to Kaposi Sarcoma-Associated Herpesvirus-Specific CD4+ T Cell Control and Inhibits vIRF3 Function

    Science.gov (United States)

    Stürzl, Michael; Sabbah, Shereen

    2016-01-01

    Kaposi sarcoma-associated herpesvirus (KSHV) is linked with the development of Kaposi sarcoma and the B lymphocyte disorders primary effusion lymphoma (PEL) and multi-centric Castleman disease. T cell immunity limits KSHV infection and disease, however the virus employs multiple mechanisms to inhibit efficient control by these effectors. Thus KSHV-specific CD4+ T cells poorly recognize most PEL cells and even where they can, they are unable to kill them. To make KSHV-infected cells more sensitive to T cell control we treated PEL cells with the thymidine analogue azidothymidine (AZT), which sensitizes PEL lines to Fas-ligand and TRAIL challenge; effector mechanisms which T cells use. PELs co-cultured with KSHV-specific CD4+ T cells in the absence of AZT showed no control of PEL outgrowth. However in the presence of AZT PEL outgrowth was controlled in an MHC-restricted manner. To investigate how AZT sensitizes PELs to immune control we first examined BJAB cells transduced with individual KSHV-latent genes for their ability to resist apoptosis mediated by stimuli delivered through Fas and TRAIL receptors. This showed that in addition to the previously described vFLIP protein, expression of vIRF3 also inhibited apoptosis delivered by these stimuli. Importantly vIRF3 mediated protection from these apoptotic stimuli was inhibited in the presence of AZT as was a second vIRF3 associated phenotype, the downregulation of surface MHC class II. Although both vFLIP and vIRF3 are expressed in PELs, we propose that inhibiting vIRF3 function with AZT may be sufficient to restore T cell control of these tumor cells. PMID:27893813

  18. Ets-1 is required for the activation of VEGFR3 during latent Kaposi's sarcoma-associated herpesvirus infection of endothelial cells.

    Science.gov (United States)

    Gutierrez, Kimberley D; Morris, Valerie A; Wu, David; Barcy, Serge; Lagunoff, Michael

    2013-06-01

    Kaposi's sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi's sarcoma (KS), is present in the predominant tumor cells of KS, the spindle cells. Spindle cells express markers of lymphatic endothelium and, interestingly, KSHV infection of blood endothelial cells reprograms them to a lymphatic endothelial cell phenotype. KSHV-induced reprogramming requires the activation of STAT3 and phosphatidylinositol 3 (PI3)/AKT through the activation of cellular receptor gp130. Importantly, KSHV-induced reprogramming is specific to endothelial cells, indicating that there are additional host genes that are differentially regulated during KSHV infection of endothelial cells that contribute to lymphatic reprogramming. We found that the transcription factor Ets-1 is highly expressed in KS spindle cells and is upregulated during KSHV infection of endothelial cells in culture. The KSHV latent vFLIP gene is sufficient to induce Ets-1 expression in an NF-κB-dependent fashion. Ets-1 is required for KSHV-induced expression of VEGFR3, a lymphatic endothelial-cell-specific receptor important for lymphangiogenesis, and Ets-1 activates the promoter of VEGFR3. Ets-1 knockdown does not alter the expression of another lymphatic-specific gene, the podoplanin gene, but does inhibit the expression of VEGFR3 in uninfected lymphatic endothelium, indicating that Ets-1 is a novel cellular regulator of VEGFR3 expression. Knockdown of Ets-1 affects the ability of KSHV-infected cells to display angiogenic phenotypes, indicating that Ets-1 plays a role in KSHV activation of endothelial cells during latent KSHV infection. Thus, Ets-1 is a novel regulator of VEGFR3 and is involved in the induction of angiogenic phenotypes by KSHV.

  19. Kaposi's Sarcoma-Associated Herpesvirus MicroRNAs Target GADD45B To Protect Infected Cells from Cell Cycle Arrest and Apoptosis.

    Science.gov (United States)

    Liu, Xiaoyan; Happel, Christine; Ziegelbauer, Joseph M

    2017-02-01

    Kaposi's sarcoma is one of the most common malignancies in HIV-infected individuals. The responsible agent, Kaposi's sarcoma-associated herpesvirus (KSHV; HHV8), expresses multiple microRNAs (miRNAs), but the targets and functions of these miRNAs are not completely understood. After infection in primary endothelial cells with KSHV, growth arrest DNA damage-inducible gene 45 beta (GADD45B) is one of the most repressed genes using genomic expression profiling. GADD45B was also repressed in mRNA expression profiling experiments when KSHV miRNAs were introduced to uninfected cells. We hypothesized that KSHV miRNAs target human GADD45B to protect cells from consequences of DNA damage, which can be triggered by viral infection. Expression of GADD45B protein is induced by the p53 activator, Nutlin-3, and KSHV miRNA-K9 inhibits this induction. In addition, Nutlin-3 increased apoptosis and cell cycle arrest based on flow cytometry assays. KSHV miR-K9 protected primary endothelial cells from apoptosis and cell cycle arrest following Nutlin-3 treatment. Similar protective phenotypes were seen for targeting GADD45B with short interfering RNAs (siRNAs), as with miR-K9. KSHV miR-K9 also decreased the protein levels of cleaved caspase-3, cleaved caspase-7, and cleaved poly(ADP-ribose) polymerase (PARP). In B lymphocytes latently infected with KSHV, specific inhibitors of KSHV miR-K9 led to increased GADD45B expression and apoptosis, indicating that miR-K9 is important for reducing apoptosis in infected cells. Furthermore, ectopic expression of GADD45B in KSHV-infected cells promoted apoptosis. Together, these results identify a new miRNA target and demonstrate that KSHV miRNAs are important for protecting infected cells from DNA damage responses.

  20. KSHV 2.0: a comprehensive annotation of the Kaposi's sarcoma-associated herpesvirus genome using next-generation sequencing reveals novel genomic and functional features.

    Directory of Open Access Journals (Sweden)

    Carolina Arias

    2014-01-01

    Full Text Available Productive herpesvirus infection requires a profound, time-controlled remodeling of the viral transcriptome and proteome. To gain insights into the genomic architecture and gene expression control in Kaposi's sarcoma-associated herpesvirus (KSHV, we performed a systematic genome-wide survey of viral transcriptional and translational activity throughout the lytic cycle. Using mRNA-sequencing and ribosome profiling, we found that transcripts encoding lytic genes are promptly bound by ribosomes upon lytic reactivation, suggesting their regulation is mainly transcriptional. Our approach also uncovered new genomic features such as ribosome occupancy of viral non-coding RNAs, numerous upstream and small open reading frames (ORFs, and unusual strategies to expand the virus coding repertoire that include alternative splicing, dynamic viral mRNA editing, and the use of alternative translation initiation codons. Furthermore, we provide a refined and expanded annotation of transcription start sites, polyadenylation sites, splice junctions, and initiation/termination codons of known and new viral features in the KSHV genomic space which we have termed KSHV 2.0. Our results represent a comprehensive genome-scale image of gene regulation during lytic KSHV infection that substantially expands our understanding of the genomic architecture and coding capacity of the virus.

  1. Selective peptide inhibitors of antiapoptotic cellular and viral Bcl-2 proteins lead to cytochrome c release during latent Kaposi's sarcoma-associated herpesvirus infection.

    Science.gov (United States)

    Burrer, Christine M; Foight, Glenna W; Keating, Amy E; Chan, Gary C

    2016-01-04

    Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with B-cell lymphomas including primary effusion lymphoma and multicentric Castleman's disease. KSHV establishes latency within B cells by modulating or mimicking the antiapoptotic Bcl-2 family of proteins to promote cell survival. Our previous BH3 profiling analysis, a functional assay that assesses the contribution of Bcl-2 proteins towards cellular survival, identified two Bcl-2 proteins, cellular Mcl-1 and viral KsBcl-2, as potential regulators of mitochondria polarization within a latently infected B-cell line, Bcbl-1. In this study, we used two novel peptide inhibitors identified in a peptide library screen that selectively bind KsBcl-2 (KL6-7_Y4eK) or KsBcl-2 and Mcl-1 (MS1) in order to decipher the relative contribution of Mcl-1 and KsBcl-2 in maintaining mitochondrial membrane potential. We found treatment with KL6-7_Y4eK and MS1 stimulated a similar amount of cytochrome c release from mitochondria isolated from Bcbl-1 cells, indicating that inhibition of KsBcl-2 alone is sufficient for mitochondrial outer membrane permiabilzation (MOMP) and thus apoptosis during a latent B cell infection. In turn, this study also identified and provides a proof-of-concept for the further development of novel KsBcl-2 inhibitors for the treatment of KSHV-associated B-cell lymphomas via the targeting of latently infected B cells.

  2. Wild-type Kaposi's sarcoma-associated herpesvirus isolated from the oropharynx of immune-competent individuals has tropism for cultured oral epithelial cells.

    Science.gov (United States)

    Duus, Karen M; Lentchitsky, Vivian; Wagenaar, Timothy; Grose, Charles; Webster-Cyriaque, Jennifer

    2004-04-01

    Based on the observation that wild-type Kaposi's sarcoma-associated herpesvirus (KSHV) DNA can be detected in the oral cavity of healthy, immunocompetent individuals, we hypothesized that epithelial cells could be infected in vitro by wild-type (WT) KSHV isolated from immunocompetent individuals. Primary oral epithelial (P-EPI) cells and telomerase-immortalized oral epithelial cells were generated from human gingival tissue and were then infected in vitro with WT KSHV isolated from throat wash samples. Markers of lytic and latent KSHV infection were detected in cultures by 24 h postinfection by immunofluorescence confocal microscopic assays. The infectivity of the WT and BCBL virus was blocked by neutralizing antibodies against KSHV gB. The presence of KSHV DNA in these cells was confirmed by real-time PCR amplification of different regions of the viral genome. The significant in vitro viral replication that had occurred was inhibited by ganciclovir and by neutralizing antibodies against gB. When infected cultures were examined by scanning electron microscopy, thousands of KSHV particles were clearly visible across the surfaces of P-EPI cells. The detection of enveloped particles indicated that the infectious cycle had proceeded through assembly and egress. We thus demonstrated that oral WT KSHV isolated from immunocompetent individuals was able to infect and replicate in vitro in a relevant primary cell type. Furthermore, our results provide compelling evidence for KSHV transmission within infected oral epithelial cells derived from healthy, immunocompetent populations.

  3. Binding of cellular export factor REF/Aly by Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 protein is not required for efficient KSHV lytic replication.

    Science.gov (United States)

    Li, Da-Jiang; Verma, Dinesh; Swaminathan, Sankar

    2012-09-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 protein is expressed early during lytic KSHV replication, enhances expression of many KSHV genes, and is essential for virus production. ORF57 is a member of a family of proteins conserved among all human and many animal herpesviruses that are multifunctional regulators of gene expression and act posttranscriptionally to increase accumulation of their target mRNAs. The mechanism of ORF57 action is complex and may involve effects on mRNA transcription, stability, and export. ORF57 directly binds to REF/Aly, a cellular RNA-binding protein component of the TREX complex that mediates RNA transcription and export. We analyzed the effects of an ORF57 mutation known to abrogate REF/Aly binding and demonstrate that the REF-binding mutant is impaired in activation of viral mRNAs and noncoding RNAs confined to the nucleus. Although the inability to bind REF leads to decreased ORF57 activity in enhancing gene expression, there is no demonstrable effect on nuclear export of viral mRNA or the ability of ORF57 to support KSHV replication and virus production. These data indicate that REF/Aly-ORF57 interaction is not essential for KSHV lytic replication but may contribute to target RNA stability independent of effects on RNA export, suggesting a novel role for REF/Aly in viral RNA metabolism.

  4. Attenuation of the suppressive activity of cellular splicing factor SRSF3 by Kaposi sarcoma-associated herpesvirus ORF57 protein is required for RNA splicing.

    Science.gov (United States)

    Majerciak, Vladimir; Lu, Mathew; Li, Xiaofan; Zheng, Zhi-Ming

    2014-11-01

    Kaposi sarcoma-associated herpesvirus (KSHV) ORF57 is a multifunctional post-transcriptional regulator essential for viral gene expression during KSHV lytic infection. ORF57 requires interactions with various cellular proteins for its function. Here, we identified serine/arginine-rich splicing factor 3 (SRSF3, formerly known as SRp20) as a cellular cofactor involved in ORF57-mediated splicing of KSHV K8β RNA. In the absence of ORF57, SRSF3 binds to a suboptimal K8β intron and inhibits K8β splicing. Knockdown of SRSF3 promotes K8β splicing, mimicking the effect of ORF57. The N-terminal half of ORF57 binds to the RNA recognition motif of SRSF3, which prevents SRSF3 from associating with the K8β intron RNA and therefore attenuates the suppressive effect of SRSF3 on K8β splicing. ORF57 also promotes splicing of heterologous non-KSHV transcripts that are negatively regulated by SRSF3, indicating that the effect of ORF57 on SRSF3 activity is independent of RNA target. SPEN proteins, previously identified as ORF57-interacting partners, suppress ORF57 splicing activity by displacing ORF57 from SRSF3-RNA complexes. In summary, we have identified modulation of SRSF3 activity as the molecular mechanism by which ORF57 promotes RNA splicing.

  5. Kaposi's-sarcoma-associated-herpesvirus-activated dendritic cells promote HIV-1 trans-infection and suppress CD4{sup +} T cell proliferation

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    Liu, Wan; Qin, Yan; Bai, Lei [Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, the Chinese Academy of Sciences, Shanghai (China); Graduate School of the Chinese Academy of Sciences, Beijing (China); Lan, Ke [Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, the Chinese Academy of Sciences, Shanghai (China); Wang, Jian-Hua, E-mail: Jh_wang@sibs.ac.cn [Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, the Chinese Academy of Sciences, Shanghai (China)

    2013-06-05

    Infection of Kaposi's sarcoma-associated herpesvirus (KSHV) is commonly occurred in AIDS patients. KSHV and HIV-1 act cooperatively in regulating infection with each other and in human carcinogenesis. Dendritic cells (DCs), as the pivotal cells in host immunity, may be modulated by both viruses, for immunoevasion and dissemination, therefore, the interaction between DCs and each virus has been a prior focus for pathogenesis elucidation. Here, we assessed the potential effect of KSHV on DC–HIV-1 interaction. We found that KSHV stimulation could promote maturation of monocyte-derived DCs (MDDCs) and impaired the ability of MDDCs to drive proliferation of resting CD4{sup +} T cells, demonstrating the immunosuppression induced by KSHV. More importantly, KSHV-stimulated MDDCs could capture more HIV-1 and efficiently transferred these infectious viruses to Hut/CCR5 T cell line. Our results reveal the novel modulation of DC-mediated HIV-1 dissemination by KSHV, and highlight the importance of studying DC–HIV-1 interaction to elucidate HIV/AIDS pathogenesis. - Highlights: ► KSHV impaired the ability of MDDCs to drive proliferation of resting CD4{sup +} T cells. ► KSHV stimulation matured MDDCs and enhanced HIV-1 endocytosis. ► KSHV stimulated MDDCs increased ICAM-1 expression and tighten contact with T cells. ► KSHV-stimulated MDDCs promoted HIV-1 trans-infection of CD4{sup +} T cells.

  6. Kaposi sarcoma-associated herpesvirus and response to antiretroviral therapy: A prospective study of HIV-infected adults

    Science.gov (United States)

    Maskew, Mhairi; MacPhail, A Patrick; Whitby, Denise; Egger, Matthias; Fox, Matthew P.

    2013-01-01

    Background The possible impact of co-infection with Kaposi’s sarcoma associated herpes virus on the response to antiretroviral therapy (ART) is unknown. Prospective studies are rare, particularly in Africa. Methods We enrolled a prospective cohort of HIV-infected adults initiating ART in Johannesburg, South Africa. Subjects were defined as seropositive to KSHV if reactive to either KSHV lytic K8.1 or latent Orf73 antigen or both. Subjects were followed from ART initiation until 18-months on treatment. HIV viral load and CD4 counts were tested 6 monthly. Linear generalized estimating and log-binomial regression models were used to estimate the effect of KSHV infection on immunologic recovery and response as well as HIV viral load suppression within 18-months after ART initiation. Results 385 subjects initiating ART from November 2008-March 2009 were eligible including 184 (48%) KSHV+. The KSHV+ group was similar to the KSHV− in terms of age, gender, initiating CD4 count, body mass index, tuberculosis and haemoglobin levels. The KSHV+ group gained a similar number of cells at 6- (difference of 10 cells/mm3, 95% CI: −11–31), 12- (3 cells/mm3, 95% CI: −19–25) and 18-months (24 cells/mm3, 95% CI: −13–61) compared to the KSHV− group. Adjusted relative risk of failure to suppress viral load to <400 copies/mL (1.03; 95% CI: 0.90–1.17) were similar for KSHV+ and KSHV− by 6-months on treatment. Conclusions In a population with a high KSHV prevalence, HIV-positive adults co-infected with KSHV achieved similar immunologic and virologic responses to ART early after treatment initiation compared to those KSHV−. PMID:23614996

  7. Cyclooxygenase-2-prostaglandin E2-eicosanoid receptor inflammatory axis: a key player in Kaposi's sarcoma-associated herpes virus associated malignancies.

    Science.gov (United States)

    Paul, Arun George; Chandran, Bala; Sharma-Walia, Neelam

    2013-08-01

    The role of cyclooxygenase-2 (COX-2), its lipid metabolite prostaglandin E2 (PGE2), and Eicosanoid (EP) receptors (EP; 1-4) underlying the proinflammatory mechanistic aspects of Burkitt's lymphoma, nasopharyngeal carcinoma, cervical cancer, prostate cancer, colon cancer, and Kaposi's sarcoma (KS) is an active area of investigation. The tumorigenic potential of COX-2 and PGE2 through EP receptors forms the mechanistic context underlying the chemotherapeutic potential of nonsteroidal anti-inflammatory drugs (NSAIDs). Although role of the COX-2 is described in several viral associated malignancies, the biological significance of the COX-2/PGE2/EP receptor inflammatory axis is extensively studied only in Kaposi's sarcoma-associated herpes virus (KSHV/HHV-8) associated malignancies such as KS, a multifocal endothelial cell tumor and primary effusion lymphoma (PEL), a B cell-proliferative disorder. The purpose of this review is to summarize the salient findings delineating the molecular mechanisms downstream of COX-2 involving PGE2 secretion and its autocrine and paracrine interactions with EP receptors (EP1-4), COX-2/PGE2/EP receptor signaling regulating KSHV pathogenesis and latency. KSHV infection induces COX-2, PGE2 secretion, and EP receptor activation. The resulting signal cascades modulate the expression of KSHV latency genes (latency associated nuclear antigen-1 [LANA-1] and viral-Fas (TNFRSF6)-associated via death domain like interferon converting enzyme-like- inhibitory protein [vFLIP]). vFLIP was also shown to be crucial for the maintenance of COX-2 activation. The mutually interdependent interactions between viral proteins (LANA-1/vFLIP) and COX-2/PGE2/EP receptors was shown to play key roles in the biological mechanisms involved in KS and PEL pathogenesis such as blockage of apoptosis, cell cycle regulation, transformation, proliferation, angiogenesis, adhesion, invasion, and immune-suppression. Understanding the COX-2/PGE2/EP axis is very important to

  8. HITS-CLIP analysis uncovers a link between the Kaposi's sarcoma-associated herpesvirus ORF57 protein and host pre-mRNA metabolism.

    Directory of Open Access Journals (Sweden)

    Emi Sei

    2015-02-01

    Full Text Available The Kaposi's sarcoma associated herpesvirus (KSHV is an oncogenic virus that causes Kaposi's sarcoma, primary effusion lymphoma (PEL, and some forms of multicentric Castleman's disease. The KSHV ORF57 protein is a conserved posttranscriptional regulator of gene expression that is essential for virus replication. ORF57 is multifunctional, but most of its activities are directly linked to its ability to bind RNA. We globally identified virus and host RNAs bound by ORF57 during lytic reactivation in PEL cells using high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP. As expected, ORF57-bound RNA fragments mapped throughout the KSHV genome, including the known ORF57 ligand PAN RNA. In agreement with previously published ChIP results, we observed that ORF57 bound RNAs near the oriLyt regions of the genome. Examination of the host RNA fragments revealed that a subset of the ORF57-bound RNAs was derived from transcript 5' ends. The position of these 5'-bound fragments correlated closely with the 5'-most exon-intron junction of the pre-mRNA. We selected four candidates (BTG1, EGR1, ZFP36, and TNFSF9 and analyzed their pre-mRNA and mRNA levels during lytic phase. Analysis of both steady-state and newly made RNAs revealed that these candidate ORF57-bound pre-mRNAs persisted for longer periods of time throughout infection than control RNAs, consistent with a role for ORF57 in pre-mRNA metabolism. In addition, exogenous expression of ORF57 was sufficient to increase the pre-mRNA levels and, in one case, the mRNA levels of the putative ORF57 targets. These results demonstrate that ORF57 interacts with specific host pre-mRNAs during lytic reactivation and alters their processing, likely by stabilizing pre-mRNAs. These data suggest that ORF57 is involved in modulating host gene expression in addition to KSHV gene expression during lytic reactivation.

  9. In vivo evaluation of {sup 111}In-DTPA-N-TIMP-2 in Kaposi sarcoma associated with HIV infection

    Energy Technology Data Exchange (ETDEWEB)

    Kulasegaram, R.; Peters, B.S. [Academic Dept. of STD' S, Guys and St Thomas' Hospital, London (United Kingdom); Giersing, B.; Williamson, R.A. [Biosciences Dept., Kent Univ., Canterbury (United Kingdom); Page, C.J. [Dept. of Nuclear Medicine, Guys and St. Thomas' Hospital, London (United Kingdom); Blower, P.J. [Biosciences Dept., Kent Univ., Canterbury (United Kingdom); Dept. of Nuclear Medicine, Kent and Canterbury Hospital, Canterbury (United Kingdom); O' Doherty, M.J. [Dept. of Nuclear Medicine, Kent and Canterbury Hospital, Canterbury (United Kingdom); Dept. of Nuclear Medicine, Guys and St. Thomas' Hospital, London (United Kingdom)

    2001-06-01

    Matrix metalloproteinases are the major agents responsible for the degradation of extracellular matrix and are produced at high levels by transformed and tumour cells, where they participate in the metastatic process by allowing local invasion. They are also more active at sites of new normal growth and angiogenesis. In the early stages of Kaposi sarcoma (KS), in vitro studies have demonstrated that vascular invasion can be inhibited by inhibitors of matrix metalloproteinases. Imaging of visceral and cutaneous KS presents a problem and therefore the potential use of a labelled inhibitor of metalloproteinases, N-TIMP-2, with indium-111 was thought to present a possible imaging tool. The biokinetics, dosimetry and potential for imaging with {sup 111}In-DTPA-N-TIMP-2 were assessed in five patients with HIV infection and KS. Between 103.1 and 108.0 MBq of this agent was injected into each patient, and the dynamic uptake over the kidneys was assessed, whole body scans were performed and blood samples were obtained. The clearance from the blood was rapid, with a first component half-time of 16.6{+-}3.4 min and a second component half-time of 9.68{+-}2.68 h. Two out of five patients experienced minor shivering but one of these patients was generally unwell before the study. The last three patients had no such problems. The tracer distributed predominantly to the kidneys and did not localise in other tissues. No KS lesions were clearly identified. {sup 111}In-DTPA-N-TIMP-2 can be successfully prepared and administered to patients safely, with a biodistribution and dosimetry which would allow its use as an imaging tracer. It is unlikely to be of use for imaging KS, but may have a role in other tumours that produce matrix metalloproteinases. (orig.)

  10. Kaposi's sarcoma-associated herpesvirus-positive primary effusion lymphoma tumor formation in NOD/SCID mice is inhibited by neomycin and neamine blocking angiogenin's nuclear translocation.

    Science.gov (United States)

    Bottero, Virginie; Sadagopan, Sathish; Johnson, Karen E; Dutta, Sujoy; Veettil, Mohanan Valiya; Chandran, Bala

    2013-11-01

    Angiogenin (ANG) is a 14-kDa multifunctional proangiogenic secreted protein whose expression level correlates with the aggressiveness of several tumors. We observed increased ANG expression and secretion in endothelial cells during de novo infection with Kaposi's sarcoma-associated herpesvirus (KSHV), in cells expressing only latency-associated nuclear antigen 1 (LANA-1) protein, and in KSHV latently infected primary effusion lymphoma (PEL) BCBL-1 and BC-3 cells. Inhibition of phospholipase Cγ (PLCγ) mediated ANG's nuclear translocation by neomycin, an aminoglycoside antibiotic (not G418-neomicin), resulted in reduced KSHV latent gene expression, increased lytic gene expression, and increased cell death of KSHV(+) PEL and endothelial cells. ANG detection in significant levels in KS and PEL lesions highlights its importance in KSHV pathogenesis. To assess the in vivo antitumor activity of neomycin and neamine (a nontoxic derivative of neomycin), BCBL-1 cells were injected intraperitoneally into NOD/SCID mice. We observed significant extended survival of mice treated with neomycin or neamine. Markers of lymphoma establishment, such as increases in animal body weight, spleen size, tumor cell spleen infiltration, and ascites volume, were observed in nontreated animals and were significantly diminished by neomycin or neamine treatments. A significant decrease in LANA-1 expression, an increase in lytic gene expression, and an increase in cleaved caspase-3 were also observed in neomycin- or neamine-treated animal ascitic cells. These studies demonstrated that ANG played an essential role in KSHV latency maintenance and BCBL-1 cell survival in vivo, and targeting ANG function by neomycin/neamine to induce the apoptosis of cells latently infected with KSHV is an attractive therapeutic strategy against KSHV-associated malignancies.

  11. Kaposi's sarcoma-associated herpesvirus microRNA single-nucleotide polymorphisms identified in clinical samples can affect microRNA processing, level of expression, and silencing activity.

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    Han, Soo-Jin; Marshall, Vickie; Barsov, Eugene; Quiñones, Octavio; Ray, Alex; Labo, Nazzarena; Trivett, Matthew; Ott, David; Renne, Rolf; Whitby, Denise

    2013-11-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 12 pre-microRNAs that can produce 25 KSHV mature microRNAs. We previously reported single-nucleotide polymorphisms (SNPs) in KSHV-encoded pre-microRNA and mature microRNA sequences from clinical samples (V. Marshall et al., J. Infect. Dis., 195:645-659, 2007). To determine whether microRNA SNPs affect pre-microRNA processing and, ultimately, mature microRNA expression levels, we performed a detailed comparative analysis of (i) mature microRNA expression levels, (ii) in vitro Drosha/Dicer processing, and (iii) RNA-induced silencing complex-dependent targeting of wild-type (wt) and variant microRNA genes. Expression of pairs of wt and variant pre-microRNAs from retroviral vectors and measurement of KSHV mature microRNA expression by real-time reverse transcription-PCR (RT-PCR) revealed differential expression levels that correlated with the presence of specific sequence polymorphisms. Measurement of KSHV mature microRNA expression in a panel of primary effusion lymphoma cell lines by real-time RT-PCR recapitulated some observed expression differences but suggested a more complex relationship between sequence differences and expression of mature microRNA. Furthermore, in vitro maturation assays demonstrated significant SNP-associated changes in Drosha/DGCR8 and/or Dicer processing. These data demonstrate that SNPs within KSHV-encoded pre-microRNAs are associated with differential microRNA expression levels. Given the multiple reports on the involvement of microRNAs in cancer, the biological significance of these phenotypic and genotypic variants merits further studies in patients with KSHV-associated malignancies.

  12. miR-K12-7-5p encoded by Kaposi's sarcoma-associated herpesvirus stabilizes the latent state by targeting viral ORF50/RTA.

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    Xianzhi Lin

    Full Text Available Seventeen miRNAs encoded by Kaposi's sarcoma-associated herpesvirus (KSHV have been identified and their functions have begun to be characterized. Among these miRNAs, we report here that miR-K12-7 directly targets the replication and transcription activator (RTA encoded by open reading frame 50. We found that miR-K12-7 targeted the RTA 3' untranslated region (RTA3'UTR in a seed sequence-dependent manner. miR-K12-7-5p derived from miR-K12-7 mediates the inhibition of RTA expression, and the mutation of the seed match site totally abrogated the inhibitory effect of miR-K12-7 on RTA3'UTR. The inhibition of RTA expression by miR-K12-7 was further confirmed in the latently KSHV-infected 293/Bac36 cell line through transient transfection of miR-K12-7 expression plasmid or specific inhibitor of miR-K12-7-5p, respectively. The transient transfection of miR-K12-7 into 293/Bac36 cells reduced RTA expression and the expression of the downstream early genes regulated by RTA, and also the production of progeny virus was significantly reduced after treatment with chemical inducers. Our study revealed that another miRNA, miR-K12-7-5p, targets the viral immediate early gene RTA and that this miRNA contributes to the maintenance of viral latency.

  13. Piracy of prostaglandin E2/EP receptor-mediated signaling by Kaposi's sarcoma-associated herpes virus (HHV-8) for latency gene expression: strategy of a successful pathogen.

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    George Paul, Arun; Sharma-Walia, Neelam; Kerur, Nagaraj; White, Carl; Chandran, Bala

    2010-05-01

    Kaposi's sarcoma-associated herpes virus (KSHV) is implicated in the pathogenesis of KS, a chronic inflammation-associated malignancy. Cyclooxygenase-2 (COX-2) and its metabolite prostaglandin E2 (PGE2), two pivotal proinflammatory/oncogeneic molecules, are proposed to play roles in the expression of major KSHV latency-associated nuclear antigen-1 (LANA-1). Microsomal PGE2 synthase, PGE2, and its receptors (EP1, EP2, EP3, and EP4) were detected in KS lesions with the distinct staining of EP2/EP4 in KS lesions. In latently infected endothelial TIVE-LTC cells, EP receptor antagonists downregulated LANA-1 expression as well as Ca(2+), p-Src, p-PI3K, p-PKCzeta/lambda, and p-NF-kappaB, which are also some of the signal molecules proposed to be important in KS pathogenesis. Exogenous PGE2 and EP receptor agonists induced the LANA-1 promoter in 293 cells, and YY1, Sp1, Oct-1, Oct-6, C/EBP, and c-Jun transcription factors seem to be involved in this induction. PGE2/EP receptor-induced LANA-1 promoter activity was downregulated significantly by the inhibition of Ca(2+), p-Src, p-PI3K, p-PKCzeta/lambda, and p-NF-kappaB. These findings implicate the inflammatory PGE2/EP receptors and the associated signal molecules in herpes virus latency and uncover a novel paradigm that shows the evolution of KSHV genome plasticity to use inflammatory response for its survival advantage of maintaining latent gene expression. These data also suggest that potential use of anti-COX-2 and anti-EP receptor therapy may not only ameliorate the chronic inflammation associated with KS but could also lead to elimination of the KSHV latent infection and the associated KS lesions.

  14. Kaposi's Sarcoma Associated Herpesvirus Induces LYN Overexpression in Kaposis Sarcoma%Kaposi肉瘤相关疱疹病毒感染诱导LYN表达在其发病中的作用

    Institute of Scientific and Technical Information of China (English)

    张芳; 陈颖; 郭峰; 徐益明; 谭晓华; 杨磊; 李锋; 姬玉; 李冬妹

    2016-01-01

    Objective To analyze the function of Kaposi's Sarcoma associated herpesvirus (KSHV) infection in the expression of v-yes-1 Yamaguchi sarcoma viral related oncogene homolog (lyn) and reveal the mechanism in Kaposis Sarcoma (KS).Methods Primary human umbilical vein endothelial cells (HUVECs) were cultivated by enzyme infusion method and immunocytochemistry (ICC) was used to detect CD31 and CD34 to verify HUVECs.KSHV were extracted from BCBL-1 cells, then used to infect HUVECs.We observed the cell morphology variation using microscope and recorded imagines.PCR was used to amplificate KS330233 fragment to verify the infection.Western blot was used to detect the level of LYN, p-PI3K and p-AKT.Results HUVECs were cytomembrane staining for CD31 and cytoplasmic staining for CD34, which verified that the primary cultivated cells were HUVECs.After KSHV infected HUVECs, the cells showed long spindle morphology.The expression of LYN was increase and the expression of p-PI3K and p-AKT was also increased.Conclusion KSHV promoted overexpression of LYN in KSHV de novo infected HUVECs and increased the level of p-PI3K as well as p-AKT in PI3K/AKT signaling pathway.%目的 探讨Kaposi肉瘤相关疱疹病毒(kaposi's sarcoma associated herpesvirus,KSHV)感染对v-yes-1 Yamaguchi肉瘤病毒相关同源癌基因(v-yes-1 Yamaguchi sarcoma viral related oncogene homolog,LYN)表达的影响,及其在卡波氏肉瘤(kaposi's sarcoma,KS)发病机制中的作用.方法 采用酶灌注法原代培养脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs),运用免疫细胞化学检测CD34和CD31以验证HUVECs.从BCBL-1中提取KSHV病毒感染HUVECs,显微镜下观察细胞形态并拍照,PCR扩增KS330233证实感染成功.采用Western blot检测LYN表达及p-PI3K和p-AKT水平.结果 HUVECs中CD 31胞膜阳性和CD 34胞浆阳性,说明酶灌注法取得的细胞为HUVECs.KSHV感染HUVECs后细胞变为长梭形,LYN表达增高,同时p-PI3K

  15. Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas.

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    Irina Haecker

    Full Text Available KSHV is the etiological agent of Kaposi's sarcoma (KS, primary effusion lymphoma (PEL, and a subset of multicentricCastleman's disease (MCD. The fact that KSHV-encoded miRNAs are readily detectable in all KSHV-associated tumors suggests a potential role in viral pathogenesis and tumorigenesis. MiRNA-mediated regulation of gene expression is a complex network with each miRNA having many potential targets, and to date only few KSHV miRNA targets have been experimentally determined. A detailed understanding of KSHV miRNA functions requires high-through putribonomics to globally analyze putative miRNA targets in a cell type-specific manner. We performed Ago HITS-CLIP to identify viral and cellular miRNAs and their cognate targets in two latently KSHV-infected PEL cell lines. Ago HITS-CLIP recovered 1170 and 950 cellular KSHV miRNA targets from BCBL-1 and BC-3, respectively. Importantly, enriched clusters contained KSHV miRNA seed matches in the 3'UTRs of numerous well characterized targets, among them THBS1, BACH1, and C/EBPβ. KSHV miRNA targets were strongly enriched for genes involved in multiple pathways central for KSHV biology, such as apoptosis, cell cycle regulation, lymphocyte proliferation, and immune evasion, thus further supporting a role in KSHV pathogenesis and potentially tumorigenesis. A limited number of viral transcripts were also enriched by HITS-CLIP including vIL-6 expressed only in a subset of PEL cells during latency. Interestingly, Ago HITS-CLIP revealed extremely high levels of Ago-associated KSHV miRNAs especially in BC-3 cells where more than 70% of all miRNAs are of viral origin. This suggests that in addition to seed match-specific targeting of cellular genes, KSHV miRNAs may also function by hijacking RISCs, thereby contributing to a global de-repression of cellular gene expression due to the loss of regulation by human miRNAs. In summary, we provide an extensive list of cellular and viral miRNA targets representing an

  16. Differences in Kaposi sarcoma-associated herpesvirus-specific and herpesvirus-non-specific immune responses in classic Kaposi sarcoma cases and matched controls in Sicily.

    Science.gov (United States)

    Amodio, Emanuele; Goedert, James J; Barozzi, Patrizia; Riva, Giovanni; Firenze, Alberto; Bonura, Filippa; Viviano, Enza; Romano, Nino; Luppi, Mario

    2011-10-01

    Kaposi sarcoma (KS) might develop because of incompetent immune responses, both non-specifically and specifically against the KS-associated herpesvirus (KSHV). Peripheral blood mononuclear cells from 15 classic (non-AIDS) KS cases, 13 KSHV seropositives (without KS) and 15 KSHV-seronegative controls were tested for interferon-γ T-cell (enzyme-linked immunospot [Elispot]) responses to KSHV-latency-associated nuclear antigen (LANA), KSHV-K8.1 and CMV/Epstein-Barr virus (EBV) peptide pools. The forearm and thigh of each participant was also tested for delayed-type hypersensitivity (DTH) against common recall antigens. Groups were compared with Fisher exact test and multinomial logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). A KSHV Elispot response was detected in 10 (67%) classic KS cases, 11 (85%) KSHV seropositives (without KS) and two (13%) seronegative controls. All four cases with KSHV-LANA responses had current KS lesions, whereas five of six cases with KSHV-K8.1 responses had no lesions (P = 0.048). No case responded to both LANA and K8.1. Compared with the seronegative controls, the risk for classic KS was inversely related to DTH in the thigh (OR 0.71, 95% CI 0.55-0.94, P = 0.01), directly associated with DTH in the forearm (OR 1.35, 95% CI 1.02-1.80, P = 0.04) and tended to be increased fivefold per KSHV Elispot response (OR 5.13, 95% CI 0.86-30.77, P = 0.07). Compared with KSHV seropositives (without KS), the risk for classic KS was reduced fivefold (OR 0.20, CI 0.03-0.77, P = 0.04) per KSHV response. The CMV/EBV Elispot responses were irrelevant. Deficiency of both KSHV-specific and KSHV-non-specific immunity is associated with classic KS. This might clarify why Kaposi sarcoma responds to immune reconstitution.

  17. Primary B Lymphocytes Infected with Kaposi's Sarcoma-Associated Herpesvirus Can Be Expanded In Vitro and Are Recognized by LANA-Specific CD4+ T Cells

    Science.gov (United States)

    Nicol, Samantha M.; Sabbah, Shereen; Brulois, Kevin F.; Jung, Jae U.; Bell, Andrew I.

    2016-01-01

    ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) has tropism for B lymphocytes, in which it establishes latency, and can also cause lymphoproliferative disorders of these cells manifesting as primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). T cell immunity is vital for the control of KSHV infection and disease; however, few models of B lymphocyte infection exist to study immune recognition of such cells. Here, we developed a model of B lymphocyte infection with KSHV in which infected tonsillar B lymphocytes were expanded by providing mitogenic stimuli and then challenged with KSHV-specific CD4+ T cells. The infected cells expressed viral proteins found in PELs, namely, LANA and viral IRF3 (vIRF3), albeit at lower levels, with similar patterns of gene expression for the major latency, viral interleukin 6 (vIL-6), and vIRF3 transcripts. Despite low-level expression of open reading frame 50 (ORF50), transcripts for the immune evasion genes K3 and K5 were detected, with some downregulation of cell surface-expressed CD86 and ICAM. The vast majority of infected lymphocytes expressed IgM heavy chains with Igλ light chains, recapitulating the features seen in infected cells in MCD. We assessed the ability of the infected lymphocytes to be targeted by a panel of major histocompatibility complex (MHC) class II-matched CD4+ T cells and found that LANA-specific T cells restricted to different epitopes recognized these infected cells. Given that at least some KSHV latent antigens are thought to be poor targets for CD8+ T cells, we suggest that CD4+ T cells are potentially important effectors for the in vivo control of KSHV-infected B lymphocytes. IMPORTANCE KSHV establishes a latent reservoir within B lymphocytes, but few models exist to study KSHV-infected B cells other than the transformed PEL cell lines, which have likely accrued mutations during the transformation process. We developed a model of KSHV-infected primary B lymphocytes that

  18. Kaposi's sarcoma-associated herpesvirus K-Rta exhibits SUMO-targeting ubiquitin ligase (STUbL like activity and is essential for viral reactivation.

    Directory of Open Access Journals (Sweden)

    Yoshihiro Izumiya

    Full Text Available The small ubiquitin-like modifier (SUMO is a protein that regulates a wide variety of cellular processes by covalent attachment of SUMO moieties to a diverse array of target proteins. Sumoylation also plays an important role in the replication of many viruses. Previously, we showed that Kaposi's sarcoma-associated herpesvirus (KSHV encodes a SUMO-ligase, K-bZIP, which catalyzes sumoylation of host and viral proteins. We report here that this virus also encodes a gene that functions as a SUMO-targeting ubiquitin-ligase (STUbL which preferentially targets sumoylated proteins for degradation. K-Rta, the major transcriptional factor which turns on the entire lytic cycle, was recently found to have ubiquitin ligase activity toward a selected set of substrates. We show in this study that K-Rta contains multiple SIMs (SUMO interacting motif and binds SUMOs with higher affinity toward SUMO-multimers. Like RNF4, the prototypic cellular STUbL, K-Rta degrades SUMO-2/3 and SUMO-2/3 modified proteins, including promyelocytic leukemia (PML and K-bZIP. PML-NBs (nuclear bodies or ND-10 are storage warehouses for sumoylated proteins, which negatively regulate herpesvirus infection, as part of the intrinsic immune response. Herpesviruses have evolved different ways to degrade or disperse PML bodies, and KSHV utilizes K-Rta to inhibit PML-NBs formation. This process depends on K-Rta's ability to bind SUMO, as a K-Rta SIM mutant does not effectively degrade PML. Mutations in the K-Rta Ring finger-like domain or SIM significantly inhibited K-Rta transactivation activity in reporter assays and in the course of viral reactivation. Finally, KSHV with a mutation in the Ring finger-like domain or SIM of K-Rta replicates poorly in culture, indicating that reducing SUMO-conjugates in host cells is important for viral replication. To our knowledge, this is the first virus which encodes both a SUMO ligase and a SUMO-targeting ubiquitin ligase that together may generate

  19. A Structural Basis for BRD2/4-Mediated Host Chromatin Interaction and Oligomer Assembly of Kaposi Sarcoma-Associated Herpesvirus and Murine Gammaherpesvirus LANA Proteins

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    Krausze, Joern; Richter, Ulrike; Adler, Heiko; Fedorov, Roman; Pietrek, Marcel; Rückert, Jessica; Ritter, Christiane; Schulz, Thomas F.; Lührs, Thorsten

    2013-01-01

    Kaposi sarcoma-associated herpesvirus (KSHV) establishes a lifelong latent infection and causes several malignancies in humans. Murine herpesvirus 68 (MHV-68) is a related γ2-herpesvirus frequently used as a model to study the biology of γ-herpesviruses in vivo. The KSHV latency-associated nuclear antigen (kLANA) and the MHV68 mLANA (orf73) protein are required for latent viral replication and persistence. Latent episomal KSHV genomes and kLANA form nuclear microdomains, termed ‘LANA speckles’, which also contain cellular chromatin proteins, including BRD2 and BRD4, members of the BRD/BET family of chromatin modulators. We solved the X-ray crystal structure of the C-terminal DNA binding domains (CTD) of kLANA and MHV-68 mLANA. While these structures share the overall fold with the EBNA1 protein of Epstein-Barr virus, they differ substantially in their surface characteristics. Opposite to the DNA binding site, both kLANA and mLANA CTD contain a characteristic lysine-rich positively charged surface patch, which appears to be a unique feature of γ2-herpesviral LANA proteins. Importantly, kLANA and mLANA CTD dimers undergo higher order oligomerization. Using NMR spectroscopy we identified a specific binding site for the ET domains of BRD2/4 on kLANA. Functional studies employing multiple kLANA mutants indicate that the oligomerization of native kLANA CTD dimers, the characteristic basic patch and the ET binding site on the kLANA surface are required for the formation of kLANA ‘nuclear speckles’ and latent replication. Similarly, the basic patch on mLANA contributes to the establishment of MHV-68 latency in spleen cells in vivo. In summary, our data provide a structural basis for the formation of higher order LANA oligomers, which is required for nuclear speckle formation, latent replication and viral persistence. PMID:24146614

  20. Activation and Repression of Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycles by Short- and Medium-Chain Fatty Acids

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    Gorres, Kelly L.; Daigle, Derek; Mohanram, Sudharshan

    2014-01-01

    ABSTRACT The lytic cycles of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are induced in cell culture by sodium butyrate (NaB), a short-chain fatty acid (SCFA) histone deacetylase (HDAC) inhibitor. Valproic acid (VPA), another SCFA and an HDAC inhibitor, induces the lytic cycle of KSHV but blocks EBV lytic reactivation. To explore the hypothesis that structural differences between NaB and VPA account for their functional effects on the two related viruses, we investigated the capacity of 16 structurally related short- and medium-chain fatty acids to promote or prevent lytic cycle reactivation. SCFAs differentially affected EBV and KSHV reactivation. KSHV was reactivated by all SCFAs that are HDAC inhibitors, including phenylbutyrate. However, several fatty acid HDAC inhibitors, such as isobutyrate and phenylbutyrate, did not reactivate EBV. Reactivation of KSHV lytic transcripts could not be blocked completely by any fatty acid tested. In contrast, several medium-chain fatty acids inhibited lytic activation of EBV. Fatty acids that blocked EBV reactivation were more lipophilic than those that activated EBV. VPA blocked activation of the BZLF1 promoter by NaB but did not block the transcriptional function of ZEBRA. VPA also blocked activation of the DNA damage response that accompanies EBV lytic cycle activation. Properties of SCFAs in addition to their effects on chromatin are likely to explain activation or repression of EBV. We concluded that fatty acids stimulate the two related human gammaherpesviruses to enter the lytic cycle through different pathways. IMPORTANCE Lytic reactivation of EBV and KSHV is needed for persistence of these viruses and plays a role in carcinogenesis. Our direct comparison highlights the mechanistic differences in lytic reactivation between related human oncogenic gammaherpesviruses. Our findings have therapeutic implications, as fatty acids are found in the diet and produced by the human microbiota

  1. Kaposi's sarcoma associated herpesvirus tegument protein ORF75 is essential for viral lytic replication and plays a critical role in the antagonization of ND10-instituted intrinsic immunity.

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    Florian Full

    2014-01-01

    Full Text Available Nuclear domain 10 (ND10 components are restriction factors that inhibit herpesviral replication. Effector proteins of different herpesviruses can antagonize this restriction by a variety of strategies, including degradation or relocalization of ND10 proteins. We investigated the interplay of Kaposi's Sarcoma-Associated Herpesvirus (KSHV infection and cellular defense by nuclear domain 10 (ND10 components. Knock-down experiments in primary human cells show that KSHV-infection is restricted by the ND10 components PML and Sp100, but not by ATRX. After KSHV infection, ATRX is efficiently depleted and Daxx is dispersed from ND10, indicating that these two ND10 components can be antagonized by KSHV. We then identified the ORF75 tegument protein of KSHV as the viral factor that induces the disappearance of ATRX and relocalization of Daxx. ORF75 belongs to a viral protein family (viral FGARATs that has homologous proteins in all gamma-herpesviruses. Isolated expression of ORF75 in primary cells induces a relocalization of PML and dispersal of Sp100, indicating that this viral effector protein is able to influence multiple ND10 components. Moreover, by constructing a KSHV mutant harboring a stop codon at the beginning of ORF75, we could demonstrate that ORF75 is absolutely essential for viral replication and the initiation of viral immediate-early gene expression. Using recombinant viruses either carrying Flag- or YFP-tagged variants of ORF75, we could further corroborate the role of ORF75 in the antagonization of ND10-mediated intrinsic immunity, and show that it is independent of the PML antagonist vIRF3. Members of the viral FGARAT family target different ND10 components, suggesting that the ND10 targets of viral FGARAT proteins have diversified during evolution. We assume that overcoming ND10 intrinsic defense constitutes a critical event in the replication of all herpesviruses; on the other hand, restriction of herpesviral replication by ND10

  2. Screening for Kaposi sarcoma-associated genes by using Genechip technology%基因芯片表达谱筛选Kaposi肉瘤相关基因

    Institute of Scientific and Technical Information of China (English)

    王慧; 吕国栋; 王晓东; 惠艳; 刘辉; 林仁勇; 王星

    2011-01-01

    Objective To screen for Kaposi sarcoma (KS)-related genes. Methods Tissue samples were obtained from the lesion and normal skin of a patient with KS in Xinjiang Uygur Autonomous Region,and total RNA was extracted from these samples and reverse transcribed into cDNA. Real-time fluorescent quantitative reverse transcription PCR (RT-qPCR) was performed to determine the expression of K8.1, K2 and ORF50 in these samples. The cDNA was labeled with fluorescein and hybridized to a human 35K genome array containing 25 100 genes. Subsequently, the signal images were scanned by a laser scanner and acquired images were analyzed by software. Results RT-qPCR revealed the mRNA expression of K8.1, K2 and ORF50 in the KS tissues but not in the normal skin tissues, indicating that there was no crossed contamination in these specimens. Among the 25 100 genes, 1313 genes were identified to be differentially expressed between KS and normal skin tissues, including 756 up-regulated genes and 557 down-regulated genes. These differentially expressed genes, such as myeloid cell leukemia-1 gene (MCI-1), annexins (ANX) and serine proteinase inhibitor Kazal type 5 (SPINK5), were associated with apoptosis, angiogenesis, cell signaling, protein processing, cell cycle regulation, and so on. Conclusion The differentially expressed genes such as MCI-1 and SPINK5 may be associated with the development of KS.%目的 筛选Kaposi肉瘤相关基因.方法 新疆本地1例经典型Kaposi肉瘤患者,提取病灶组织及正常皮肤组织的总RNA,逆转录成cDNA,采用实时荧光定量PCR(RT-qPCR)的方法检测Kaposi肉瘤相关疱疹病毒(Kaposi sarcoma-associated herpersivims,KSHV)基因K8.1、K2、ORF50在组织中的表达来确定所取标本有无交叉污染.随后进行荧光标记制备探针,与含有25100条人类基因的35KcDNA基因表达谱芯片进行杂交,用扫描仪扫描芯片荧光信号图像,并用软件对扫描图像进行数字化处理和分析.结果 RT-qPCR检测

  3. 复制与转录激活子:治疗KSHV感染性疾病的新靶标%Replication and transcription activator: A new target for treatment of infectious diseases caused by Kaposi's sarcoma-associated herpesvirus

    Institute of Scientific and Technical Information of China (English)

    刘晓园; 刘晓辉

    2014-01-01

    卡波西肉瘤相关疱疹病毒(Kaposi's sarcoma-associated herpesvirus,KSHV)引起艾滋病相关恶性肿瘤卡波西肉瘤(Kaposi sarcoma,KS)、B淋巴细胞增生性疾病原发性积液淋巴瘤和多中心的淋巴结增生症.KSHV感染会经历潜伏和裂解性复制两个互相转换的阶段,而裂解阶段病毒的复制造成感染在组织中的散播,加速肿瘤恶化.由KSHV开放阅读框ORF50编码的复制与转录激活子(replication and transcription activator,RTA)是控制KSHV从潜伏向裂解复制转变的开关,并影响KS的病理进程,有望成为治疗KSHV感染性疾病的新靶标.

  4. Kaposi's Sarcoma-Associated Herpesvirus Rta Tetramers Make High-Affinity Interactions with Repetitive DNA Elements in the Mta Promoter To Stimulate DNA Binding of RBP-Jk/CSL ▿ †

    Science.gov (United States)

    Palmeri, Diana; Carroll, Kyla Driscoll; Gonzalez-Lopez, Olga; Lukac, David M.

    2011-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 [HHV-8]) is the etiologic agent of Kaposi's sarcoma (KS) and lymphoproliferative diseases. We previously demonstrated that the KSHV lytic switch protein Rta stimulates DNA binding of the cellular RBP-Jk/CSL protein, the nuclear component of the Notch pathway, on Rta target promoters. In the current study, we define the promoter requirements for formation of transcriptionally productive Rta/RBP-Jk/DNA complexes. We show that highly pure Rta footprints 7 copies of a previously undescribed repetitive element in the promoter of the essential KSHV Mta gene. We have termed this element the “CANT repeat.” CANT repeats are found on both strands of DNA and have a consensus sequence of ANTGTAACANT(A/T)(A/T)T. We demonstrate that Rta tetramers make high-affinity interactions (i.e., nM) with 64 bp of the Mta promoter but not single CANT units. The number of CANT repeats, their presence in palindromes, and their positions relative to the RBP-Jk binding site determine the optimal target for Rta stimulation of RBP-Jk DNA binding and formation of ternary Rta/RBP-Jk/DNA complexes. DNA binding and tetramerization mutants of Rta fail to stimulate RBP-Jk DNA binding. Our chromatin immunoprecipitation assays show that RBP-Jk DNA binding is broadly, but selectively, stimulated across the entire KSHV genome during reactivation. We propose a model in which tetramerization of Rta allows it to straddle RBP-Jk and contact repeat units on both sides of RBP-Jk. Our study integrates high-affinity Rta DNA binding with the requirement for a cellular transcription factor in Rta transactivation. PMID:21880753

  5. Activation of PI3K/AKT and ERK MAPK signal pathways is required for the induction of lytic cycle replication of Kaposi's Sarcoma-associated herpesvirus by herpes simplex virus type 1

    Directory of Open Access Journals (Sweden)

    Lv Zhigang

    2011-10-01

    Full Text Available Abstract Background Kaposi's sarcoma-associated herpesvirus (KSHV is causally linked to several acquired immunodeficiency syndrome-related malignancies, including Kaposi's sarcoma (KS, primary effusion lymphoma (PEL and a subset of multicentric Castleman's disease. Regulation of viral lytic replication is critical to the initiation and progression of KS. Recently, we reported that herpes simplex virus type 1 (HSV-1 was an important cofactor that activated lytic cycle replication of KSHV. Here, we further investigated the possible signal pathways involved in HSV-1-induced reactivation of KSHV. Results By transfecting a series of dominant negative mutants and protein expressing constructs and using pharmacologic inhibitors, we found that either Janus kinase 1 (JAK1/signal transducer and activator of transcription 3 (STAT3 or JAK1/STAT6 signaling failed to regulate HSV-1-induced KSHV replication. However, HSV-1 infection of BCBL-1 cells activated phosphatidylinositol 3-kinase (PI3K/protein kinase B (PKB, also called AKT pathway and inactivated phosphatase and tensin homologue deleted on chromosome ten (PTEN and glycogen synthase kinase-3β (GSK-3β. PTEN/PI3K/AKT/GSK-3β pathway was found to be involved in HSV-1-induced KSHV reactivation. Additionally, extracellular signal-regulated protein kinase (ERK mitogen-activated protein kinase (MAPK pathway also partially contributed to HSV-1-induced KSHV replication. Conclusions HSV-1 infection stimulated PI3K/AKT and ERK MAPK signaling pathways that in turn contributed to KSHV reactivation, which provided further insights into the molecular mechanism controlling KSHV lytic replication, particularly in the context of HSV-1 and KSHV co-infection.

  6. Kaposi sarcoma-associated herpes virus targets the lymphotactin receptor with both a broad spectrum antagonist vCCL2 and a highly selective and potent agonist vCCL3

    DEFF Research Database (Denmark)

    Lüttichau, Hans R; Johnsen, Anders H; Jurlander, Jesper;

    2007-01-01

    Large DNA viruses such as herpesvirus and poxvirus encode proteins that target and exploit the chemokine system of their host. These proteins have the potential to block or change the orchestrated recruitment of leukocytes to sites of viral infection. The genome of Kaposi sarcoma-associated herpes...... virus (KSHV) encodes three chemokine-like proteins named vCCL1, vCCL2, and vCCL3. In this study vCCL3 was probed in parallel with vCCL1 and vCCL2 against a panel of the 18 classified human chemokine receptors. In calcium mobilization assays vCCL1 acted as a selective CCR8 agonist, whereas vCCL2...... was found to act as a broad spectrum chemokine antagonist of human chemokine receptors, including the lymphotactin receptor. In contrast vCCL3 was found to be a highly selective agonist for the human lymphotactin receptor XCR1. The potency of vCCL3 was found to be 10-fold higher than the endogenous human...

  7. Kaposi's sarcoma-associated herpesvirus Lana-1 is a major activator of the serum response element and mitogen-activated protein kinase pathways via interactions with the Mediator complex.

    Science.gov (United States)

    Roupelieva, Maria; Griffiths, Samantha J; Kremmer, Elisabeth; Meisterernst, Michael; Viejo-Borbolla, Abel; Schulz, Thomas; Haas, Jürgen

    2010-05-01

    In cells infected with Kaposi's sarcoma-associated herpesvirus (KSHV), the activation of mitogen-activated protein kinase (MAPK) pathways plays a crucial role early after virus infection as well as during reactivation. In order to systematically identify viral proteins activating MAPK pathways in KSHV-infected cells, a clone collection of KSHV open reading frames (ORFs) was screened for induction of the serum response element (SRE), as SRE is induced by MAPKs. The strongest induction of the SRE was found with ORF73 (latency-associated nuclear antigen 1, or Lana-1), although weaker activation was also found with the kaposin B isoform, ORF54 (dUTPase) and ORF74 (G-protein-coupled receptor). The bipartite SRE is bound by a ternary complex consisting of serum response factor (SRF) and ternary complex factor. Lana-1 bound directly to SRF, but also to the MED25 (ARC92/ACID-1), MED15 (PCQAP) and MED23 (Sur-2) subunits of the Mediator complex, a multi-subunit transcriptional co-activator complex for RNA polymerase II. Lana-1-induced SRE activation was inhibited by the dominant-negative N-terminal domain of the MED25 mediator subunit, suggesting that this subunit mediates Lana-1-induced SRE activation. In summary, these data suggest a model in which Lana-1 acts as an adaptor between the transcription factor SRF and the basal transcriptional machinery.

  8. Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) replication and transcription factor activates the K9 (vIRF) gene through two distinct cis elements by a non-DNA-binding mechanism.

    Science.gov (United States)

    Ueda, Keiji; Ishikawa, Kayo; Nishimura, Ken; Sakakibara, Shuhei; Do, Eunju; Yamanishi, Koichi

    2002-12-01

    The replication and transcription activator (RTA) of Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, a homologue of Epstein-Barr virus BRLF1 or Rta, is a strong transactivator and inducer of lytic replication. RTA acting alone can induce lytic replication of KSHV in infected cell lines that originated from primary effusion lymphomas, leading to virus production. During the lytic replication process, RTA activates many kinds of genes, including polyadenylated nuclear RNA, K8, K9 (vIRF), ORF57, and so on. We focused here on the mechanism of how RTA upregulates the K9 (vIRF) promoter and identified two independent cis-acting elements in the K9 (vIRF) promoter that responded to RTA. These elements were finally confined to the sequence 5'-TCTGGGACAGTC-3' in responsive element (RE) I-2B and the sequence 5'-GTACTTAAAATA-3' in RE IIC-2, both of which did not share sequence homology. Multiple factors bound specifically with these elements, and their binding was correlated with the RTA-responsive activity. Electrophoretic mobility shift assay with nuclear extract from infected cells and the N-terminal part of RTA expressed in Escherichia coli, however, did not show that RTA interacted directly with these elements, in contrast to the RTA responsive elements in the PAN/K12 promoter region, the ORF57/K8 promoter region. Thus, it was likely that RTA could transactivate several kinds of unique cis elements without directly binding to the responsive elements, probably through cooperation with other DNA-binding factors.

  9. Kaposi's sarcoma-associated herpesvirus ORF57 functions as a viral splicing factor and promotes expression of intron-containing viral lytic genes in spliceosome-mediated RNA splicing.

    Science.gov (United States)

    Majerciak, Vladimir; Yamanegi, Koji; Allemand, Eric; Kruhlak, Michael; Krainer, Adrian R; Zheng, Zhi-Ming

    2008-03-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 facilitates the expression of both intronless viral ORF59 genes and intron-containing viral K8 and K8.1 genes (V. Majerciak, N. Pripuzova, J. P. McCoy, S. J. Gao, and Z. M. Zheng, J. Virol. 81:1062-1071, 2007). In this study, we showed that disruption of ORF57 in a KSHV genome led to increased accumulation of ORF50 and K8 pre-mRNAs and reduced expression of ORF50 and K-bZIP proteins but had no effect on latency-associated nuclear antigen (LANA). Cotransfection of ORF57 and K8beta cDNA, which retains a suboptimal intron of K8 pre-mRNA due to alternative splicing, promoted RNA splicing of K8beta and production of K8alpha (K-bZIP). Although Epstein-Barr virus EB2, a closely related homolog of ORF57, had a similar activity in the cotransfection assays, herpes simplex virus type 1 ICP27 was inactive. This enhancement of RNA splicing by ORF57 correlates with the intact N-terminal nuclear localization signal motifs of ORF57 and takes place in the absence of other viral proteins. In activated KSHV-infected B cells, KSHV ORF57 partially colocalizes with splicing factors in nuclear speckles and assembles into spliceosomal complexes in association with low-abundance viral ORF50 and K8 pre-mRNAs and essential splicing components. The association of ORF57 with snRNAs occurs by ORF57-Sm protein interaction. We also found that ORF57 binds K8beta pre-mRNAs in vitro in the presence of nuclear extracts. Collectively our data indicate that KSHV ORF57 functions as a novel splicing factor in the spliceosome-mediated splicing of viral RNA transcripts.

  10. Kaposi's Sarcoma-Associated Herpesvirus (KSHV Induces the Oncogenic miR-17-92 Cluster and Down-Regulates TGF-β Signaling.

    Directory of Open Access Journals (Sweden)

    Hong Seok Choi

    Full Text Available KSHV is a DNA tumor virus that causes Kaposi's sarcoma. Upon KSHV infection, only a limited number of latent genes are expressed. We know that KSHV infection regulates host gene expression, and hypothesized that latent genes also modulate the expression of host miRNAs. Aberrant miRNA expression contributes to the development of many types of cancer. Array-based miRNA profiling revealed that all six miRNAs of the oncogenic miR-17-92 cluster are up-regulated in KSHV infected endothelial cells. Among candidate KSHV latent genes, we found that vFLIP and vCyclin were shown to activate the miR-17-92 promoter, using luciferase assay and western blot analysis. The miR-17-92 cluster was previously shown to target TGF-β signaling. We demonstrate that vFLIP and vCyclin induce the expression of the miR-17-92 cluster to strongly inhibit the TGF-β signaling pathway by down-regulating SMAD2. Moreover, TGF-β activity and SMAD2 expression were fully restored when antagomirs (inhibitors of miR-17-92 cluster were transfected into cells expressing either vFLIP or vCyclin. In addition, we utilized viral genetics to produce vFLIP or vCyclin knock-out viruses, and studied the effects in infected TIVE cells. Infection with wildtype KSHV abolished expression of SMAD2 protein in these endothelial cells. While single-knockout mutants still showed a marked reduction in SMAD2 expression, TIVE cells infected by a double-knockout mutant virus were fully restored for SMAD2 expression, compared to non-infected TIVE cells. Expression of either vFLIP or vCycIin was sufficient to downregulate SMAD2. In summary, our data demonstrate that vFLIP and vCyclin induce the oncogenic miR-17-92 cluster in endothelial cells and thereby interfere with the TGF-β signaling pathway. Manipulation of the TGF-β pathway via host miRNAs represents a novel mechanism that may be important for KSHV tumorigenesis and angiogenesis, a hallmark of KS.

  11. Kaposi's Sarcoma-Associated Herpesvirus (KSHV) Induces the Oncogenic miR-17-92 Cluster and Down-Regulates TGF-β Signaling.

    Science.gov (United States)

    Choi, Hong Seok; Jain, Vaibhav; Krueger, Brian; Marshall, Vickie; Kim, Chang Hee; Shisler, Joanna L; Whitby, Denise; Renne, Rolf

    2015-01-01

    KSHV is a DNA tumor virus that causes Kaposi's sarcoma. Upon KSHV infection, only a limited number of latent genes are expressed. We know that KSHV infection regulates host gene expression, and hypothesized that latent genes also modulate the expression of host miRNAs. Aberrant miRNA expression contributes to the development of many types of cancer. Array-based miRNA profiling revealed that all six miRNAs of the oncogenic miR-17-92 cluster are up-regulated in KSHV infected endothelial cells. Among candidate KSHV latent genes, we found that vFLIP and vCyclin were shown to activate the miR-17-92 promoter, using luciferase assay and western blot analysis. The miR-17-92 cluster was previously shown to target TGF-β signaling. We demonstrate that vFLIP and vCyclin induce the expression of the miR-17-92 cluster to strongly inhibit the TGF-β signaling pathway by down-regulating SMAD2. Moreover, TGF-β activity and SMAD2 expression were fully restored when antagomirs (inhibitors) of miR-17-92 cluster were transfected into cells expressing either vFLIP or vCyclin. In addition, we utilized viral genetics to produce vFLIP or vCyclin knock-out viruses, and studied the effects in infected TIVE cells. Infection with wildtype KSHV abolished expression of SMAD2 protein in these endothelial cells. While single-knockout mutants still showed a marked reduction in SMAD2 expression, TIVE cells infected by a double-knockout mutant virus were fully restored for SMAD2 expression, compared to non-infected TIVE cells. Expression of either vFLIP or vCycIin was sufficient to downregulate SMAD2. In summary, our data demonstrate that vFLIP and vCyclin induce the oncogenic miR-17-92 cluster in endothelial cells and thereby interfere with the TGF-β signaling pathway. Manipulation of the TGF-β pathway via host miRNAs represents a novel mechanism that may be important for KSHV tumorigenesis and angiogenesis, a hallmark of KS.

  12. HIV-1 Tat promotes Kaposi's sarcoma-associated herpesvirus (KSHV vIL-6-induced angiogenesis and tumorigenesis by regulating PI3K/PTEN/AKT/GSK-3β signaling pathway.

    Directory of Open Access Journals (Sweden)

    Feng Zhou

    Full Text Available Kaposi's sarcoma (KS-associated herpesvirus (KSHV is etiologically associated with KS, the most common AIDS-related malignancy. KS is characterized by vast angiogenesis and hyperproliferative spindle cells. We have previously reported that HIV-1 Tat can trigger KSHV reactivation and accelerate Kaposin A-induced tumorigenesis. Here, we explored Tat promotion of KSHV vIL-6-induced angiogenesis and tumorigenesis. Tat promotes vIL-6-induced cell proliferation, cellular transformation, vascular tube formation and VEGF production in culture. Tat enhances vIL-6-induced angiogenesis and tumorigenesis of fibroblasts and human endothelial cells in a chicken chorioallantoic membrane (CAM model. In an allograft model, Tat promotes vIL-6-induced tumorigenesis and expression of CD31, CD34, SMA, VEGF, b-FGF, and cyclin D1. Mechanistic studies indicated Tat activates PI3K and AKT, and inactivates PTEN and GSK-3β in vIL-6 expressing cells. LY294002, a specific inhibitor of PI3K, effectively impaired Tat's promotion of vIL-6-induced tumorigenesis. Together, these results provide the first evidence that Tat might contribute to KS pathogenesis by synergizing with vIL-6, and identify PI3K/AKT pathway as a potential therapeutic target in AIDS-related KS patients.

  13. Chylothorax in a patient with metastatic Kaposi sarcoma: Differential diagnostic considerations

    OpenAIRE

    Ryan Alexander, DO; Magda Rizer, DO; William Burke, MD; Lawrence Ciment, MD

    2015-01-01

    Kaposi sarcoma (KS) is a low-grade mesenchymal tumor involving blood and lymphatic vessels. There are four types, based on clinical presentation: classic, endemic (Africana), iatrogenic (typically, involving renal allograft recipients), and AIDS-associated (epidemic). Kaposi's sarcoma-associated herpes virus infection has been linked along with other factors to the development of KS. The Kaposi's sarcoma-associated herpes virus interacts and encodes for numerous molecular proteins that play a...

  14. Expressions of Kaposi′ s sarcoma-associated herpesvirus type 8-associated microRNAs k12-1 and k12-12 in Kaposi′s sarcoma and their significance%Kaposi 肉瘤相关疱疹病毒8型相关微小RNA k12-1和 k12-12在 Kaposi 肉瘤组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    吴秀娟; 赵宗峰; 普雄明

    2015-01-01

    目的:检测 Kaposi 肉瘤肿瘤组织中 Kaposi 肉瘤相关疱疹病毒8型相关微小 RNA k12-1(kshv-miR-k12-1)和 k12-12(kshv-miR-k12-12)的表达,并探讨其与 Kaposi 肉瘤病理分期、HIV 感染、人疱疹病毒8型(HHV-8)感染、皮损面积之间的关系。方法选取液氮保存的 Kaposi 肉瘤肿瘤组织和瘤旁正常组织18对,采用 Trizol 法提取标本组织中的总 RNA 并反转录成 cDNA,采用 SYBR Green 实时荧光定量 PCR 法定量检测 kshv-miR-k12-1和 kshv-miR-k12-12,比较 Kaposi 肉瘤肿瘤组织及其瘤旁组织中 kshv-miR-k12-1和kshv-miR-k12-12表达的差异,并分析其与 Kaposi 肉瘤病理分期、HIV 和 HHV-8感染、皮损面积之间的关系。结果 kshv-miR-k12-1和 kshv-miR-k12-12在 Kaposi 肉瘤肿瘤组织中的2-ΔΔCt 值分别为(1.016±1.645)和(2.104±1.973),明显高于瘤旁正常组织,分别为0.029±0.019(t =2.542,P =0.016)和0.102±0.093(t =4.301, P =0.000)。不同 HIV 和 HHV-8感染状态、病理分期、皮损面积患者的 kshv-miR-k12-1和 kshv-miR-k12-12表达差异均无统计学意义(均 P >0.05)。结论 kshv-miR-k12-1和 kshv-miR-k12-12在 Kaposi 肉瘤肿瘤组织中呈明显高表达,但与 HIV 感染、HHV-8感染、病理分期及皮损面积无明显相关。%Objective To measure the expressions of Kaposi′s sarcoma-associated herpesvirus type 8 associated-microRNAs k12-1 (kshv-miR-k12-1)and k12-12 (kshv-miR-k12-12)in Kaposi′s sarcoma tissue, and to assess their relationship with pathological stage and lesion area of Kaposi′s sarcoma, HIV infection, and human herpesvirus type 8 (HPV-8)infection. Methods Totally, 18 paired tissue specimens stored in liquid nitrogen from Kaposi′ s sarcoma lesions and paralesional skin were collected. Total RNAs were extracted from these specimens by using Trizol reagent, and reversely transcribed into cDNA. SYBR Green real-time fluorescence-based quantitative PCR was performed

  15. NFκB pathway is down-regulated by 1α,25(OH)(2)-vitamin D(3) in endothelial cells transformed by Kaposi sarcoma-associated herpes virus G protein coupled receptor.

    Science.gov (United States)

    Gonzalez-Pardo, Verónica; D'Elia, Noelia; Verstuyf, Annemieke; Boland, Ricardo; Russo de Boland, Ana

    2012-09-01

    We have previously demonstrated that 1α,25 dihydroxy-vitamin D(3) (1α,25(OH)(2)D(3)) has antiproliferative effects on the growth of endothelial cells transformed by the viral G protein-coupled receptor associated to Kaposi sarcoma (vGPCR). In this work, we have investigated whether 1α,25(OH)(2)D(3) exerts its growth inhibitory effects by inhibiting the Nuclear Factor κ B (NFκB) pathway which is highly activated by vGPCR. Cell proliferation studies demonstrated that 1α,25(OH)(2)D(3), similarly to bortezomib, a proteosome inhibitor that suppresses the activation of NFκB, reduced the proliferation of endothelial cells transformed by vGPCR (SVEC-vGPCR). The activity of NFκB in these cells decreased by 70% upon 1α,25(OH)(2)D(3) treatment. Furthermore, time and dose response studies showed that the hormone significantly decreased NFκB and increased IκBα mRNA and protein levels in SVEC-vGPCR cells, whereas in SVEC only IκBα increased significantly. Moreover, NFκB translocation to the nucleus was inhibited and occurred by a mechanism independent of NFκB association with vitamin D(3) receptor (VDR). 1α,25(OH)(2)D(3)-induced increase in IκBα required de novo protein synthesis, and was independent of MAPK and PI3K/Akt pathways. Altogether, these results suggest that down-regulation of the NFκB pathway is part of the mechanism involved in the antiproliferative effects of 1α,25(OH)(2)D(3) on endothelial cells transformed by vGPCR. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Kaposi sarcoma: review and medical management update.

    Science.gov (United States)

    Fatahzadeh, Mahnaz

    2012-01-01

    Despite recent advances in our understanding of pathogenic mechanisms involved, the true nature of Kaposi sarcoma remains an enigma. Four clinical variants have been described for the disease, differing in natural history, site of predilection, and prognosis. All forms of Kaposi sarcoma may manifest in the oral cavity and Kaposi sarcoma-associated virus appears essential to development of all clinical variants. The spectrum of therapeutic strategies is broad and selection of appropriate intervention mandates a thorough understanding of disease spread and the patient's symptomatology, as well as risks and benefits of therapy. This article provides an overview of epidemiology, subtypes, clinical course, pathogenesis, and management strategies for Kaposi sarcoma.

  17. Expression of anti-HIV gene in Jurkat cell with Kaposi's sarcoma-associated herpes virus infection%卡波氏肉瘤相关病毒感染激活Jurkat细胞抗-HIV基因表达的研究

    Institute of Scientific and Technical Information of China (English)

    陈彬; 谭晓华; 王小波; 尹小菲; 杨磊

    2010-01-01

    目的:观察Jurkat细胞感染卡波氏肉瘤相关病毒(Kaposi's sarcoma-associated herpes virus,KSHV)后细胞内几条主要的抗HIV作用的基因(RANTES、APOBEC3G、APOBEC3F、MX1、MX2)表达情况.方法:首先用佛波酯(TPA)(20ng/ml)刺激BCBL-1细胞72小时,提取KSHV病毒滤液.然后把含KSHV滤液的RPMI-1640培养Jurkat细胞.24小时后,分别在感染后第3、5天收集细胞,提取细胞总RNA,通过实时定量PCR检测分析相关基因的表达情况.结果:通过对KSHV感染不同时期的细胞抗-HIV基因表达分析,结果显示:与未感染组相比,KSHV感染组的Jurkat细胞内的多条抗HIV-1基因表达上调.感染第3天,RANTES上调123倍,APOBEC3G上调3.12倍,A POBEC3F上调1.18倍,MIX1上调2.75倍.MIX2上调4.35倍,感染第5天RANTES上调11.91倍,MX1上调2.72倍,MIX2上调2.22倍.结论:KSHV感染在一定程度上激活Jurkat细胞抗HIV相关基因的表达.

  18. Kaposi`s sarcoma; Sarcome de Kaposi

    Energy Technology Data Exchange (ETDEWEB)

    Kirova, Y.M.; Belembaogo, E.; Frikha, H.; Yu, S.J.; Le Bourgeois, J.P. [Hopital Henri-Mondor, 94 - Creteil (France)

    1997-09-01

    Moriz Kaposi was the first who, in 1872, described five patients presenting with `sarcoma idiopathicum multiple hemorrhagicum`. In 1912 Sternberg termed this disease Kaposi`s sarcoma. Since then various forms of this rare disease have been observed. In 1914 Hallenberg described the first cases of African or endemic Kaposi`s sarcoma. In the 1960`s the first reports discussing Kaposi`s sarcoma following organ transplantation and immunosuppressive therapy were published. After 1981, the epidemic form associated with the acquired immunodeficiency syndrome (AIDS) was described. All these forms, their history, treatment methods and the role of radiation therapy in the management of this rare malignancy are discussed, and the literature is reviewed. (authors)

  19. Angiogenesis,Kaposi's Sarcoma and Kaposi's Sarcomaassociated Herpesvirus

    Institute of Scientific and Technical Information of China (English)

    Tao KANG; Feng-chun Ye; Shou-jiang gao; Lin-ding WANG

    2008-01-01

    Tumor angiogenesis is the uncontrolled growth of blood vessels in tumors,serving to supply nutrients and oxygen,and remove metabolic wastes.Kaposi's sarcoma (KS),a multifocal angioproliferative disorder characterized by spindle cell proliferation,neo-angiogenesis,inflammation,and edema,is associated with infection by Kaposi's sarcoma-associated herpesvirus (KSHV).Recent studies indicate that KSHV infection directly promotes angiogenesis and inflammation through an autocrine and paracrine mechanism by inducing pro-angiogenic and pro-inflammatory cytokines.Many of these cytokines are also expressed in KS lesions,implicating a direct role of KSI-IV in the pathogenesis of this malignancy.Several KSHV genes are involved in KSHV-induced angiogenesis.These studies have provided insights into the pathogenesis of KS,and identified potential therapeutic targets for this malignancy.

  20. What Is Kaposi Sarcoma?

    Science.gov (United States)

    ... Treatment? Kaposi Sarcoma About Kaposi Sarcoma What Is Kaposi Sarcoma? Cancer starts when cells in the body begin ... the lungs may cause trouble breathing. Types of Kaposi sarcoma The different types of KS are defined by ...

  1. mTOR inhibitors block Kaposi sarcoma growth by inhibiting essential autocrine growth factors and tumor angiogenesis.

    Science.gov (United States)

    Roy, Debasmita; Sin, Sang-Hoon; Lucas, Amy; Venkataramanan, Raman; Wang, Ling; Eason, Anthony; Chavakula, Veenadhari; Hilton, Isaac B; Tamburro, Kristen M; Damania, Blossom; Dittmer, Dirk P

    2013-04-01

    Kaposi sarcoma originates from endothelial cells and it is one of the most overt angiogenic tumors. In Sub-Saharan Africa, where HIV and the Kaposi sarcoma-associated herpesvirus (KSHV) are endemic, Kaposi sarcoma is the most common cancer overall, but model systems for disease study are insufficient. Here, we report the development of a novel mouse model of Kaposi sarcoma, where KSHV is retained stably and tumors are elicited rapidly. Tumor growth was sensitive to specific allosteric inhibitors (rapamycin, CCI-779, and RAD001) of the pivotal cell growth regulator mTOR. Inhibition of tumor growth was durable up to 130 days and reversible. mTOR blockade reduced VEGF secretion and formation of tumor vasculature. Together, the results show that mTOR inhibitors exert a direct anti-Kaposi sarcoma effect by inhibiting angiogenesis and paracrine effectors, suggesting their application as a new treatment modality for Kaposi sarcoma and other cancers of endothelial origin.

  2. Molecularly targeted therapy for Kaposi's sarcoma in a kidney transplant patient: case report, "what worked and what did not"

    Directory of Open Access Journals (Sweden)

    Correa-Rotter Ricardo

    2007-03-01

    Full Text Available Abstract Background Imatinib is a tyrosine-kinase inhibitor; for which there is limited information regarding its effects on AIDS Kaposi's sarcoma and none in patients with transplant-associated Kaposi's sarcoma. Sirolimus, an immunosuppressive drug used for kidney transplant, exhibits antiangiogenic activity related to impaired production of VEGF (vascular endothelial growth factor, clinical benefit has been reported in Kaposi's sarcoma associated with renal graft. Case Presentation Here we report a case of an 80 year old male, who developed Kaposi's Sarcoma nine months after receiving a living non-related donor kidney transplant at age 74. Three years after treatment with different chemotherapeutic agents for progressive cutaneous Kaposi's Sarcoma with no visceral involvement, he was prescribed Imatinib (200 mg/day for two weeks followed by 400 mg/day after four weeks of treatment he developed anasarca, further progression of KS and agranulocytosis. Imatinib was discontinued and there was significant clinical recovery. One year later his immunosuppressive therapy was changed to Sirolimus and regression of the Kaposi's sarcoma occurred. Conclusion The lack of benefit and severe toxicity associated with the use of Imatinib in this patient should alert clinicians of potentially adverse consequence of its use in patients with transplant associated Kaposi's sarcoma. On the other hand the positive response seen in this patient to Sirolimus even after a long evolution of Kaposi's sarcoma, multiple chemotherapy regimens and extensive cutaneous disease further suggest it therapeutical utility for transplant associated Kaposi's sarcoma.

  3. Do We Know What Causes Kaposi Sarcoma?

    Science.gov (United States)

    ... and Prevention Do We Know What Causes Kaposi Sarcoma? Kaposi sarcoma (KS) is caused by infection with a ... Sarcoma? Can Kaposi Sarcoma Be Prevented? More In Kaposi Sarcoma About Kaposi Sarcoma Causes, Risk Factors, and Prevention ...

  4. [Moritz Kaposi: further currency].

    Science.gov (United States)

    Rácz, I

    1987-03-01

    In connection with the frequent appearance of Kaposi's sarcoma in AIDS, the biography of Moritz Kohn/Kaposi, a dermatologist of Hungarian origin in Vienna, is presented. The merits and failures of his morphologically oriented concept are discussed. Today his activity is high estimed by dermatologists all over the world.

  5. What Are the Key Statistics about Kaposi Sarcoma?

    Science.gov (United States)

    ... Kaposi Sarcoma What Are the Key Statistics About Kaposi Sarcoma? Before the AIDS epidemic, Kaposi sarcoma (KS) was ... in Kaposi Sarcoma Research and Treatment? More In Kaposi Sarcoma About Kaposi Sarcoma Causes, Risk Factors, and Prevention ...

  6. What's New in Kaposi Sarcoma Research and Treatment?

    Science.gov (United States)

    ... Kaposi Sarcoma About Kaposi Sarcoma What’s New in Kaposi Sarcoma Research and Treatment? A great deal of research ... in Kaposi Sarcoma Research and Treatment? More In Kaposi Sarcoma About Kaposi Sarcoma Causes, Risk Factors, and Prevention ...

  7. Chylothorax in a patient with metastatic Kaposi sarcoma: Differential diagnostic considerations

    Directory of Open Access Journals (Sweden)

    Ryan Alexander, DO

    2015-01-01

    Full Text Available Kaposi sarcoma (KS is a low-grade mesenchymal tumor involving blood and lymphatic vessels. There are four types, based on clinical presentation: classic, endemic (Africana, iatrogenic (typically, involving renal allograft recipients, and AIDS-associated (epidemic. Kaposi's sarcoma-associated herpes virus infection has been linked along with other factors to the development of KS. The Kaposi's sarcoma-associated herpes virus interacts and encodes for numerous molecular proteins that play a role in the pathogenesis of KS, including latency-associated nuclear antigen, viral G protein-coupled receptor, viral FLICE inhibitory protein, and viral IL-6. KS primarily affects the skin and causes disseminated disease in a variety of organs. Involvement of visceral organs other than the lining of the alimentary tract is extremely rare. While the chylous pleural effusions of KS may resemble other pulmonary diseases (including lymphangioma, lymphangectasis, and lymphangioleiomyomatosis with chylous effusions at thoracic CT, differentiating features may allow for more prompt diagnosis and treatment. The presumptive diagnosis of AIDS-related pulmonary KS is often clinical. A tissue diagnosis is not required to establish the diagnosis of pulmonary KS. There are a variety of causes of chylothorax. The primary finding is a near-water-attenuating pleural effusion. The secondary findings of chylothorax can help differentiate the etiology.

  8. [Moritz Kaposi and his sarcoma].

    Science.gov (United States)

    van Kessel, Anne; Quint, Koen D

    2011-01-01

    Nowadays, Kaposi sarcoma is a multidisciplinary condition, not only observed by dermatologists. Since the HIV epidemic in the 80s and 90s of the last century, more insight into the aetiology of Kaposi sarcoma has been acquired. However, this sarcoma had already been described in 1872 by a Hungarian dermatologist named Moritz Kaposi (1832-1902). Kaposi described the entity as 'idiopathic multiple pigmented sarcoma of the skin'. This entity was an extraordinary diagnosis at that time, mostly observed in Jewish or Mediterranean men. In 1912, 10 years after the death of Moritz Kaposi, the entity name was changed to Kaposi sarcoma.

  9. Treatment Option Overview (Kaposi Sarcoma)

    Science.gov (United States)

    ... Treatment Childhood Vascular Tumors Treatment Research Kaposi Sarcoma Treatment (PDQ®)–Patient Version General Information About Kaposi Sarcoma ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  10. Pre-micro RNA signatures delineate stages of endothelial cell transformation in Kaposi sarcoma.

    Directory of Open Access Journals (Sweden)

    Andrea J O'Hara

    2009-04-01

    Full Text Available MicroRNAs (miRNA have emerged as key regulators of cell lineage differentiation and cancer. We used precursor miRNA profiling by a novel real-time QPCR method (i to define progressive stages of endothelial cell transformation cumulating in Kaposi sarcoma (KS and (ii to identify specific miRNAs that serve as biomarkers for tumor progression. We were able to compare primary patient biopsies to well-established culture and mouse tumor models. Loss of mir-221 and gain of mir-15 expression demarked the transition from merely immortalized to fully tumorigenic endothelial cells. Mir-140 and Kaposi sarcoma-associated herpesvirus viral miRNAs increased linearly with the degree of transformation. Mir-24 emerged as a biomarker specific for KS.

  11. Epidemic Kaposi Sarcoma

    Science.gov (United States)

    ... and its treatment, see the AIDSinfo website . Nonepidemic Gay-related Kaposi Sarcoma There is a type of ... better than another. Trials are based on past studies and what has been learned ... by their creator. In such cases, it is necessary to contact the writer, artist, ...

  12. Classic Kaposi Sarcoma

    Science.gov (United States)

    ... and its treatment, see the AIDSinfo website . Nonepidemic Gay-related Kaposi Sarcoma There is a type of ... better than another. Trials are based on past studies and what has been learned ... by their creator. In such cases, it is necessary to contact the writer, artist, ...

  13. Kaposis sarkom tolket som haematom

    DEFF Research Database (Denmark)

    Balle, Jesper R; Hasselager, Thomas

    2010-01-01

    Kaposi's sarcoma is a frequent skin cancer in HIV-positive patients, but is relatively uncommon in HIV-negative and non-immune compromised patients. We present a case of Kaposi's sarcoma of the face and scalp in a HIV-negative male with previous facial basal cell carcinoma....

  14. [Oral lesions in Kaposi sarcoma: clinical and radiotherapeutic considerations].

    Science.gov (United States)

    Barberis, M; Brenna Betti, N; Lauritano, D; Sangiani, L; Spadari, F; Villa, S

    1996-01-01

    The epidemic form of Kaposi's sarcoma is the most frequent tumor in sieropositive patients. Every part of the body including oral cavity is affected by these lesions. According to modern acknowledgement in treating oropharynge carcinoma, radiotherapy is used for management of oral Kaposi's sarcoma. This paper reports a study of 10 patients suffering from Kaposi's sarcoma correlated to AIDS (EKS) treated with radiotherapy and chemiotherapy, achieving good results, at the Istituto Nazionale per lo Studio e la Cura dei Tumori of Milan (Divisone di Radioterapia C) from 1988 to 1992. Treatment has been performed using linear accelerator (6 Mev) or Co 60 unity in order to reach the deepest layer of mucosa lesions. Radiotherapy schedule consisted of 150-200 cGy daily fractions given 5 times/week (w) for 4-5 w in split-course.

  15. What Should You Ask Your Doctor about Kaposi Sarcoma?

    Science.gov (United States)

    ... What Should You Ask Your Doctor About Kaposi Sarcoma? Kaposi Sarcoma Early Detection, Diagnosis, and Staging What Should You Ask Your Doctor About Kaposi Sarcoma? As you cope with Kaposi sarcoma (KS) and ...

  16. Drugs Approved for Kaposi Sarcoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Kaposi sarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  17. Plasmacytoid dendritic cells in skin lesions of classic Kaposi's sarcoma.

    Science.gov (United States)

    Karouni, Mirna; Kurban, Mazen; Abbas, Ossama

    2016-09-01

    Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), which allows them to provide anti-viral resistance and to link the innate and adaptive immunity by controlling the function of myeloid DCs, lymphocytes, and natural killer cells. pDCs are involved in the pathogenesis of several infectious [especially viral, such as Molluscum contagiosum (MC)], inflammatory/autoimmune, and neoplastic entities. Kaposi's sarcoma (KS) is a multifocal, systemic lympho-angioproliferative tumor associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Microscopy typically exhibits a chronic inflammatory lymphoplasmacytic infiltrate in addition to the vascular changes and spindle cell proliferation. Despite the extensive research done on the immune evasion strategies employed by KSHV, pDCs role in relation to KS has only rarely been investigated. Given this, we intend to investigate pDC occurrence and activity in the skin lesions of KS. Immunohistochemical staining for BDCA-2 (specific pDC marker) and MxA (surrogate marker for local type I IFN production) was performed on classic KS (n = 20) with the control group comprising inflamed MC (n = 20). As expected, BDCA-2+ pDCs were present in abundance with diffuse and intense MxA expression (indicative of local type I IFN production) in all inflamed MC cases (20 of 20, 100 %). Though present in all the KS cases, pDCs were significantly less abundant in KS than in inflamed MC cases, and MxA expression was patchy/weak in most KS cases. In summary, pDCs are part of the inflammatory host response in KS; however, they were generally low in number with decreased type I IFN production which is probably related to KSHV's ability to evade the immune system through the production of different viral proteins capable of suppressing IFN production as well as pDC function.

  18. Mycosis fungoides and Kaposi’s sarcoma association in an HIV-negative patient*

    Science.gov (United States)

    Bariani, Maria Carolina Prado Fleury; Fleury Júnior, Luiz Fernando Fróes; Ribeiro, Ana Maria Quinteiro; Carneiro, Siderley de Souza; Pereira, Tiago Arantes

    2016-01-01

    The association of mycosis fungoides and kaposi’s sarcoma in HIV-negative patients is a rare phenomenon. The presence of human herpesvirus 8 (HHV-8) – associated with all forms of Kaposi’s sarcoma – has also been recently identified in mycosis fungoides lesions. However, a causal association between HHV-8 and the onset of mycosis fungoides has not been established yet. The present case reports a patient who developed Kaposi’s sarcoma lesions after a two-year UVB phototherapy to treat a mycosis fungoides. Negative immunohistochemistry staining for Kaposi’s sarcoma-associated herpesvirus in the initial mycosis fungoides lesions strengthens the absence of a link between Kaposi’s sarcoma-associated herpesvirus and mycosis fungoides. Immunosuppression caused by the lymphoma and prolonged phototherapy were probably the contribut ing factors for the onset of Kaposi’s sarcoma.

  19. Skin Ultrasound in Kaposi Sarcoma.

    Science.gov (United States)

    Carrascosa, R; Alfageme, F; Roustán, G; Suarez, M D

    2016-05-01

    The use of ultrasound imaging has recently been increasing in numerous dermatologic diseases. This noninvasive technique provides additional details on the structure and vascularization of skin lesions. Kaposi sarcoma is a vascular tumor that typically arises in the skin and mucosas. It can spread to lymph nodes and internal organs. We performed B-mode and color Doppler ultrasound studies in 3 patients with a clinical diagnosis of Kaposi sarcoma confirmed by histological examination. We found differences in the ultrasound pattern between nodular and plaque lesions, in both B-mode and color Doppler. We believe that skin ultrasound imaging could be a useful technique for studying cutaneous Kaposi sarcoma, providing additional information on the structural and vascular characteristics of the lesion.

  20. Quantitative Determinations of Anti-Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) Antibody Levels in Men Who Have Sex with Men

    Science.gov (United States)

    Gogineni, Emile; Marshall, Vickie; Miley, Wendell; Bayat, Ahmad; Whitby, Denise; Kovacs, Joseph A.; Burbelo, Peter D.

    2013-01-01

    Infection with Kaposi’s Sarcoma-Associated Herpesvirus (KSHV/HHV-8) is common among men who have sex with men (MSM). Here quantitative anti-KSHV antibody levels were measured using Luciferase Immunoprecipitation Systems (LIPS) in a MSM cohort with and without HIV from the NIH Clinical Center. Antibodies were detected using a mixture of four KSHV antigens in the MSM cohort and in Kaposi Sarcoma (KS) patients. Along with HIV status, these results were compared with K8.1 and ORF73 ELISA, PCR virus detection, and additional LIPS testing. LIPS revealed that 25% (76/307) of the MSM cohort were KSHV seropositive, including 59 HIV+ and 17 HIV− subjects. The anti-KSHV antibody levels detected by LIPS were not statistically different between the KSHV+/HIV+ and KSHV+/HIV− subgroups, but were lower than the KS patients (P<0.0001). ELISA analysis of the MSM cohort detected a 35.5% frequency of KSHV infection and showed agreement with 81% of the samples evaluated by LIPS. Further LIPS testing with v-cyclin, a second ORF73 fragment and ORF38 reconciled some of the differences observed between LIPS and the ELISA immunoassays and the revised LIPS seroprevalence in the MSM cohort was increased to 31%. Additional quantitative antibody analysis demonstrated statistically lower KSHV antibody levels in MSM compared to KS patients, but no difference was found between KSHV infected with and without HIV coinfection. These findings also suggest that antibodies against v-cyclin and ORF38 are useful for identifying patients with asymptomatic KSHV infection. PMID:23541691

  1. Kinetics of Kaposi’s Sarcoma-Associated Herpesvirus Gene Expression

    OpenAIRE

    Sun, Ren; Lin, Su-Fang; Staskus, Katherine; Gradoville, Lyndle; Grogan, Elizabeth; Haase, Ashley; Miller, George

    1999-01-01

    Herpesvirus gene expression can be classified into four distinct kinetic stages: latent, immediate early, early, and late. Here we characterize the kinetic class of a group of 16 Kaposi’s sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 genes in a cultured primary effusion cell line and examine the expression of a subset of these genes in KS biopsies. Expression of two latent genes, LANA and vFLIP, was constitutive and was not induced by chemicals that induce the lytic cycle in prima...

  2. Recent advances in the study of Kaposi’s sarcoma-associated herpesvirus replication and pathogenesis

    Institute of Scientific and Technical Information of China (English)

    Denis; Avey; Brittany; Brewers; Fanxiu; Zhu

    2015-01-01

    It has now been over twenty years since a novel herpesviral genome was identified in Kaposi’s sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi’s sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.

  3. Treatment Options for Kaposi Sarcoma

    Science.gov (United States)

    ... and its treatment, see the AIDSinfo website . Nonepidemic Gay-related Kaposi Sarcoma There is a type of ... better than another. Trials are based on past studies and what has been learned ... by their creator. In such cases, it is necessary to contact the writer, artist, ...

  4. General Information about Kaposi Sarcoma

    Science.gov (United States)

    ... and its treatment, see the AIDSinfo website . Nonepidemic Gay-related Kaposi Sarcoma There is a type of ... better than another. Trials are based on past studies and what has been learned ... by their creator. In such cases, it is necessary to contact the writer, artist, ...

  5. The ubiquitin system and Kaposi’s sarcoma-associated herpesvirus

    Directory of Open Access Journals (Sweden)

    Akira eAshizawa

    2012-02-01

    Full Text Available Ubiquitination is a post-translational modification in which one or more ubiquitin molecules are covalently linked to lysine residues of target proteins. The ubiquitin system plays a key role in the regulation of protein degradation, including cell signaling, endocytosis, vesicle trafficking, apoptosis, and immune responses. Bacterial and viral pathogens exploit the cellular ubiquitin system by encoding their own proteins to serve their survival and replication in infected cells. Recent studies have revealed that Kaposi’s sarcoma-associated herpesvirus (KSHV manipulates the ubiquitin system of infected cells to facilitate cell proliferation, anti-apoptosis, and evasion from immunity. This review summarizes recent developments in our understanding of the molecular mechanisms used by KSHV to interact with the cellular ubiquitin machinery.

  6. Gastrointestinal Kaposi sarcoma with appendiceal involvement.

    Science.gov (United States)

    Egwuonwu, Steve; Gatto-Weis, Cara; Miranda, Roberto; Casas, Luis De Las

    2011-04-01

    Kaposi sarcoma is a vascular tumor manifesting as nodular lesions on skin, mucous membranes, or internal organs. This is a case of a 42-year-old human immunodeficiency virus- (HIV) positive bisexual male, not on highly active antiretroviral therapy (HAART) since diagnosis four years ago. He presented with a three-day history of abdominal pains, fever, vomiting, and a one-week history of melena stools. Endoscopy revealed Kaposi sarcoma in the stomach and duodenum. Postendoscopy, he developed acute abdomen. Exploratory laparotomy revealed extensive Kaposi sarcoma of the gastrointestinal tract with appendiceal involvement. The patient underwent appendectomy and had an uneventful recovery. A review of the literature discusses appendiceal Kaposi sarcoma with appendicitis, a rare but critical manifestation of gastrointestinal Kaposi sarcoma.

  7. Research progress on TLR4 expression in Kaposi's sarcoma with KSHV%TLR4在KSHV感染的卡波西肉瘤中表达的研究进展

    Institute of Scientific and Technical Information of China (English)

    李肖然(综述); 鲁晓擘(审校)

    2014-01-01

    Toll-like receptor 4 (TLR4) is one of the important members of Toll like receptors, which is a rec-ognition receptor of lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria. Activation of TLR4 induced a series of inflammatory mediators, including cytokines and chemokines, to produce a strong inflammatory re-action. TLR4 played an important role in anti-bacteria, inflammation, antiviral, and stress. TLR4 was also expressed in kaposi's sarcoma, which is infected by Kaposi's sarcoma associated herpesvirus (KSHV). This paper reviewed the most recent advancements of signal transduction mechanism of TLR4 in Kaposi's sarcoma.%TLR4(Toll-like receptor 4)是Toll样受体的一个重要的组成成员,是革兰氏阴性细胞壁成份脂多糖(LPS)的识别受体。活化TLR4将诱导产生一系列炎症介质,包括细胞因子、趋化因子等从而产生强有力的炎症反应,TLR4在抗细菌,抗病毒的炎症反应中,以及在应激状态下均发挥重要作用。TLR4在KSHV (Kaposi's sarcoma-associated herpesvirus,卡波西肉瘤相关疱疹病毒)感染的卡波西肉瘤中也有表达,本文就TLR4在KSHV感染的卡波西肉瘤中的信号转导机制及研究进展做一综述。

  8. Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study.

    Science.gov (United States)

    Polizzotto, Mark N; Uldrick, Thomas S; Wyvill, Kathleen M; Aleman, Karen; Peer, Cody J; Bevans, Margaret; Sereti, Irini; Maldarelli, Frank; Whitby, Denise; Marshall, Vickie; Goncalves, Priscila H; Khetani, Vikram; Figg, William D; Steinberg, Seth M; Zeldis, Jerome B; Yarchoan, Robert

    2016-12-01

    Purpose Kaposi's sarcoma (KS) is a multicentric tumor caused by Kaposi's sarcoma-associated herpesvirus. Unmet needs include therapies that are oral, anthracycline sparing, and deliverable in resource-limited settings. We evaluated pomalidomide, an oral immune modulatory agent, in patients with symptomatic KS. Methods The primary objectives were to assess tolerability, pharmacokinetics, and activity. Initial dosage level was 5 mg once per day for 21 days per 28-day cycle, with a de-escalated level of 3 mg if not tolerable, and aspirin 81 mg once per day thromboprophylaxis. HIV-infected patients required controlled viremia with either persistent KS despite 3 months of antiretroviral therapy (ART) or progressive KS despite 2 months of ART. Evaluations included tumor response and health-related quality of life (HRQL). Results Twenty-two patients were treated; 15 (68%) were HIV infected, 17 (77%) had advanced (T1) disease, and 19 (86%) previous KS therapy excluding ART. All were treated with 5 mg because no dose-limiting toxicities occurred. Over 156 cycles, the grade 3/4 adverse events possibly attributable to therapy were neutropenia (23 cycles, 10 patients), infection (1 cycle), and edema (1 cycle). Sixteen patients responded (73%; 95% CI, 50% to 89%): nine of 15 HIV-infected patients (60%; 95% CI, 32% to 84%) and all seven HIV-uninfected patients (100%; 95% CI, 59% to 100%). Median time to response was 4 weeks (range, 4 to 36 weeks). HRQL showed no impairment during therapy and improved satisfaction with appearance at end therapy ( P = .03). Significant increases in CD4(+) and CD8(+) cells were seen in patients with and without HIV, together with a transient increase in Kaposi's sarcoma-associated herpesvirus viral load at week 4 ( P = .05). Conclusion Pomalidomide is well tolerated and active in KS regardless of HIV status. Responses were rapid, with improved self-reported outcomes, and occurred in advanced and heavily pretreated disease. Correlative studies

  9. Kaposi's sarcoma herpesvirus microRNAs induce metabolic transformation of infected cells.

    Directory of Open Access Journals (Sweden)

    Ohad Yogev

    2014-09-01

    Full Text Available Altered cell metabolism is inherently connected with pathological conditions including cancer and viral infections. Kaposi's sarcoma-associated herpesvirus (KSHV is the etiological agent of Kaposi's sarcoma (KS. KS tumour cells display features of lymphatic endothelial differentiation and in their vast majority are latently infected with KSHV, while a small number are lytically infected, producing virions. Latently infected cells express only a subset of viral genes, mainly located within the latency-associated region, among them 12 microRNAs. Notably, the metabolic properties of KSHV-infected cells closely resemble the metabolic hallmarks of cancer cells. However, how and why KSHV alters host cell metabolism remains poorly understood. Here, we investigated the effect of KSHV infection on the metabolic profile of primary dermal microvascular lymphatic endothelial cells (LEC and the functional relevance of this effect. We found that the KSHV microRNAs within the oncogenic cluster collaborate to decrease mitochondria biogenesis and to induce aerobic glycolysis in infected cells. KSHV microRNAs expression decreases oxygen consumption, increase lactate secretion and glucose uptake, stabilize HIF1α and decreases mitochondria copy number. Importantly this metabolic shift is important for latency maintenance and provides a growth advantage. Mechanistically we show that KSHV alters host cell energy metabolism through microRNA-mediated down regulation of EGLN2 and HSPA9. Our data suggest that the KSHV microRNAs induce a metabolic transformation by concurrent regulation of two independent pathways; transcriptional reprograming via HIF1 activation and reduction of mitochondria biogenesis through down regulation of the mitochondrial import machinery. These findings implicate viral microRNAs in the regulation of the cellular metabolism and highlight new potential avenues to inhibit viral latency.

  10. c-myc in Kaposi's sarcoma: analyses by fluorescent in situ hybridization and immunohistochemistry.

    Science.gov (United States)

    Feller, K; Yang, S; Tung, N; Lee, J; Mahalingam, M

    2014-01-01

    The c-myc proto-oncogene plays a central role in the regulation of cellular transcription, differentiation, and apoptosis, and has been shown to be deregulated in many types of human cancer. Recent findings have demonstrated its amplification in select vascular neoplasms, such as secondary angiosarcomas, suggesting a role in angiogenesis as well. In vitro studies have shown that the c-Myc protein is an important regulatory molecule of spindle cell proliferation and migration in Kaposi's sarcoma (KS). In light of these findings, our primary aim was to ascertain whether c-myc, by promoting proliferation and angiogenesis, is an essential co-factor in the aetiopathogenesis of KS. We also attempted to determine a correlation between immunohistochemical expression of the c-Myc protein and c-myc gene copy amplification using fluorescent in situ hybridization (FISH). Samples analyzed included archival tissue of KS (n = 24). PCR for detection of Kaposi's sarcoma-associated herpesvirus DNA was performed on all samples of KS. For FISH analyses, a dual-labelled technique was employed and probes for the c-myc gene and chromosome 8 were used. The monoclonal anti-c-myc antibody, 9E10, was used for immunohistochemical analyses. While FISH analyses revealed no amplification of c-myc in any of the cases of KS, immunohistochemical analyses revealed positive staining for c-Myc in 13/24 cases (54%). Amplification of the c-myc gene was not witnessed in this preliminary study of 24 cases and thus cannot be correlated with the expression of the c-Myc protein. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

  11. Acroangiodermatitis (Pseudo-Kaposi sarcoma

    Directory of Open Access Journals (Sweden)

    Satyendra Kumar Singh

    2014-01-01

    Full Text Available Acroangiodermatitis or Pseudo-Kaposi sarcoma is a rare angioproliferative entity, related to chronic venous insufficiency or certain other vascular anomalies. It is often associated with chronic venous insufficiency, arteriovenous malformation of the legs, chronic renal failure treated with dialysis, paralyzed legs and amputation stumps. We hereby describe a case of 45 year old female presenting with pitting pedal edema, multiple ulcers over bilateral lower limbs with irregular margins with erythema and hyperpigmentation of the surrounding skin. Color Doppler study of bilateral lower limbs was normal. Histopathological examination from one of the lesions showed hyperplastic epidermis, proliferation of capillaries in dermis, hemosiderin deposits and lymphocytic infiltrate. These features thus confirmed the diagnosis of Acroangiodermatitis.

  12. Kaposi's Sarcoma Of The Lung: A Case Report.

    African Journals Online (AJOL)

    user

    Treatment for Kaposi's sarcoma include radiotherapy, chemotherapy and/or immunotherapy whereby ... Physical examination revealed an elderly man of ... Pulse rate was ... ultrasound was normal. .... effective treatment for pulmonary Kaposi's.

  13. Kinetics of Kaposi’s Sarcoma-Associated Herpesvirus Gene Expression

    Science.gov (United States)

    Sun, Ren; Lin, Su-Fang; Staskus, Katherine; Gradoville, Lyndle; Grogan, Elizabeth; Haase, Ashley; Miller, George

    1999-01-01

    Herpesvirus gene expression can be classified into four distinct kinetic stages: latent, immediate early, early, and late. Here we characterize the kinetic class of a group of 16 Kaposi’s sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 genes in a cultured primary effusion cell line and examine the expression of a subset of these genes in KS biopsies. Expression of two latent genes, LANA and vFLIP, was constitutive and was not induced by chemicals that induce the lytic cycle in primary effusion lymphoma (PEL) cell lines. An immediate-early gene, Rta (open reading frame 50 [ORF50]), was induced within 4 h of the addition of n-butyrate, and its 3.6-kb mRNA was resistant to inhibition by cycloheximide. Early genes, including K3 and K5 that are homologues of the “immediate-early” gene of bovine herpesvirus 4, K8 that is a positional homologue of Epstein-Barr virus BZLF1, vMIP II, vIL-6, and polyadenylated nuclear (PAN) RNA, appeared 8 to 13 h after chemical induction. A second group of early genes that were slightly delayed in their appearance included viral DHFR, thymidylate synthase, vMIP I, G protein-coupled receptor, K12, vBcl2, and a lytic transcript that overlapped LANA. The transcript of sVCA (ORF65), a late gene whose expression was abolished by Phosphonoacetic acid, an inhibitor of KSHV DNA replication, did not appear until 30 h after induction. Single-cell assays indicated that the induction of lytic cycle transcripts resulted from the recruitment of additional cells into the lytic cycle. In situ hybridization of KS biopsies showed that about 3% of spindle-shaped tumor cells expressed Rta, ORF K8, vIL-6, vMIP I, vBcl-2, PAN RNA, and sVCA. Our study shows that several KSHV-encoded homologues of cellular cytokines, chemokines, and antiapoptotic factors are expressed during the viral lytic cycle in PEL cell lines and in KS biopsies. The lytic cycle of KSHV, probably under the initial control of the KSHV/Rta gene, may directly contribute to tumor

  14. Kaposi's sarcoma following immune suppressive therapy for Wegener's granulomatosis.

    Science.gov (United States)

    Deschênes, Isabelle; Dion, Louise; Beauchesne, Claude; de Brum-Fernandes, Artur

    2003-03-01

    The association between Kaposi's sarcoma and infection with human herpesvirus 8 is now well recognized. Immunologic impairment is associated with 2 forms of Kaposi's sarcoma, epidemic [associated with human immunodeficiency virus (HIV) infection] and iatrogenic (associated with immunosuppressive treatment); both forms have become more common during the last decade. We describe an HIV negative 54-year-old man who developed Kaposi's sarcoma 2 months after the beginning of immuno-suppressive therapy for Wegener's granulomatosis (WG). With tapering of medication, complete remission of Kaposi's sarcoma was achieved in one year. To our knowledge, this is the second reported case of iatrogenic Kaposi's sarcoma in a patient with WG.

  15. Kaposi sarcoma following postmastectomy lymphedema.

    Science.gov (United States)

    Montero Pérez, Iria; Rodríguez-Pazos, Laura; Álvarez-Pérez, Adriana; Ferreirós, M Mercedes Pereiro; Aliste, Carlos; Suarez-Peñaranda, Jose Manuel; Toribio, Jaime

    2015-11-01

    Classical Kaposi sarcoma (KS) usually appears on lower extremities accompanied or preceded by local lymphedema. However, the development in areas of chronic lymphedema of the arms following mastectomy, mimicking a Stewart-Treves syndrome, has rarely been described. We report an 81-year-old woman who developed multiple, erythematous to purple tumors, located on areas of post mastectomy lymphedema. Histopathological examination evidenced several dermal nodules formed by spindle-shaped cells that delimitated slit-like vascular spaces with some red cell extravasation. Immunohistochemically, the human herpesvirus type 8 (HHV-8) latent nuclear antigen-1 was detected in the nuclei of most tumoral cells confirming the diagnosis of KS. Lymphedema could promote the development of certain tumors by altering immunocompetence. Although angiosarcoma (AS) is the most frequent neoplasia arising in the setting of chronic lymphedema, other tumors such as benign lymphangiomatous papules (BLAP) or KS can also develop in lymphedematous limbs. It is important to establish the difference between AS and KS because their prognosis and treatment are very different. Identification by immunohistochemistry of HHV-8 is useful for the distinction between KS and AS or BLAP.

  16. HIV-associated cutaneous Kaposi`s sarcoma - palliative local treatment by radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Saran, F.H. [Dept. of Radiotherapy and Oncology, Univ. Hospital, Frankfurt Univ. (Germany); Adamietz, I.A. [Dept. of Radiotherapy and Oncology, Univ. Hospital, Frankfurt Univ. (Germany); Thilmann, C. [Dept. of Radiotherapy and Oncology, Univ. Hospital, Frankfurt Univ. (Germany); Mose, S. [Dept. of Radiotherapy and Oncology, Univ. Hospital, Frankfurt Univ. (Germany); Boettcher, H.D. [Dept. of Radiotherapy and Oncology, Univ. Hospital, Frankfurt Univ. (Germany)

    1997-07-01

    The increasing number of HIV-infected patients makes palliative treatment of HIV-associated Kaposi`s sarcoma more common. We retrospectively evaluated a reduced fractionated radiotherapy with 20 Gy in respect to response rates and acute side-effects. From January 1992 to January 1995, 52 patients with HIV-associated Kaposi`s sarcoma were treated with 133 single portals. Six weeks after the end of radiotherapy 42 patients with 124 portals were evaluable with respect to response rates and side-effects. Of the treated portals 32% were judged as complete responses (CR), 55% as partial responses (PR) and 12% as no change (NC). Skin reactions RTOG, grade 1 were seen in 74% of the patients. Compared with literature data the reduced overall dose of 20 Gy in 10 fractions led to a reduction of CRs by approximately 50% while the overall response rate remained equal. The success of radiotherapy for the nodular component of Kaposi`s sarcoma can be improved, if a dose exceeding 20 Gy in 10 fractions is applied but at the cost of increasing side-effects in case that non-conventional fractionation schemes are used. (orig.).

  17. Treatment of classical Kaposi's sarcoma with gemcitabine

    NARCIS (Netherlands)

    Brambilla, L; Labianca, R; Ferrucci, SM; Taglioni, M; Boneschi, [No Value

    2001-01-01

    Background: Several drugs are active in aggressive classical Kaposi's sarcoma (CKS); chemotherapeutic agents with fewer side-effects, more rapid response and able to overcome resistance to previous treatment are advisable when treating patients in a second line. Gemcitabine, an analogue of deoxycyti

  18. Combination Therapy for Advanced Kaposi Sarcoma

    Science.gov (United States)

    In this clinical trial, adult patients with any form of advanced Kaposi sarcoma will be treated with liposomal doxorubicin and bevacizumab every 3 weeks for a maximum of six treatments.  Patients who respond to this therapy or have stable disease will rec

  19. Therapeutic strategies for epidemic Kaposi's sarcoma

    NARCIS (Netherlands)

    Aldenhoven, M.; Barlo, N. P.; Sanders, C. J. G.

    2006-01-01

    Kaposi's sarcoma (KS) remains the most commonly diagnosed malignancy in HIV-infected patients, and is one of the AIDS-defining diagnoses. Several different therapeutic options are available, but the optimal therapy is still unclear. The incidence of KS has sharply declined since highly active antire

  20. Immunosuppressive Therapy-Related Kaposi Sarcoma

    Science.gov (United States)

    ... and its treatment, see the AIDSinfo website . Nonepidemic Gay-related Kaposi Sarcoma There is a type of ... better than another. Trials are based on past studies and what has been learned ... by their creator. In such cases, it is necessary to contact the writer, artist, ...

  1. Kaposi's varicelliform eruption: A case series.

    Science.gov (United States)

    Ferrari, Bruno; Taliercio, Vanina; Luna, Paula; Abad, María Eugenia; Larralde, Margarita

    2015-01-01

    Kaposi's varicelliform eruption is a rare and potentially fatal viral infection caused mainly by reactivation of herpes simplex virus. It concomitantly occurs with pre-existing skin conditions, mostly atopic dermatitis, so it is predominately found in children. We present a case series that includes four adults, familial cases, and previously healthy patients. We also highlight clinical features, associations and therapeutic options.

  2. Antiproliferative effects of Bortezomib in endothelial cells transformed by viral G protein-coupled receptor associated to Kaposi's sarcoma.

    Science.gov (United States)

    Suares, A; Mori Sequeiros Garcia, M; Paz, C; González-Pardo, V

    2017-04-01

    The Kaposi's Sarcoma-associated Herpes virus G Protein-Coupled Receptor (vGPCR) is a key molecule in the pathogenesis of Kaposi Sarcoma. We have previously demonstrated that the proteasome inhibitor Bortezomib inhibits NF-κB pathway, which is required for tumor maintenance in endothelial cells that express vGPCR (vGPCR cells). In this work, we further investigated Bortezomib anti-proliferative mechanism of action. We demonstrated that Bortezomib decreases vGPCR cell number in a dose-dependent manner and induces cell morphology changes. Bortezomib decreases ERK1/2 phosphorylation whereas induces the accumulation of MKP-3 - a specific ERK1/2 MAP kinase phosphatase - in time and concentration dependent manner (1.5-32h; 0.25-1nM). The transcription factor FOXO1 is activated by dephosphorylation and regulates p21 expression. Here, we demonstrated that Bortezomib increases FOXO1 protein and decreases its phosphorylation in a concentration dependent manner (0.25-1nM). Bortezomib (0.5nM, 24h) also increase nuclear FOXO1 protein, in line with FOXO1 dephosphorylation induced by the drug. Consistent with FOXO1 dephosphorylation/activation, p21 mRNA expression is increased by Bortezomib in a MKP-3-dependent way. Bortezomib (0.5nM, 24h) also decreases VEGF, an ERK1/2 -dependent effect. It is concluded that in vGPCR cells, Bortezomib decreases ERK1/2 and FOXO1 phosphorylation through MKP-3 accumulation, leading ERK1/2 deactivation and FOXO1 activation respectively and, consequently, to cell proliferation inhibition, p21 induction and VEGF repression. Taken together, all these events contribute to the anti-tumoral effect of Bortezomib.

  3. Osseous Kaposi sarcoma in an HIV-positive patient

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, Loukas; Mylona, Sofia; Kalioras, Vasilios; Pomoni, Maria; Batakis, Nikolaos [Radiology Department, ' ' Korgialeneio-Benakeio' ' , Red Cross Hospital of Athens, 1 Athanasaki Street, 11526, Athens (Greece)

    2004-04-01

    A case of osseous Kaposi sarcoma in a 35-year-old man is described. The patient (HIV-positive for 8 years) suffered from cutaneous Kaposi sarcoma and presented with right-sided chest pain. He underwent a chest CT scan that revealed three osteolytic lesions involving rib and vertebra with large soft tissue masses, without cutaneous lesions at these sites. CT-guided core needle biopsy led to a histological diagnosis of Kaposi sarcoma. (orig.)

  4. A case of pulmonary Kaposi`s sarcoma in patient with renal transplantation : high resolution CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hye Seong; Kim, Hak Hee; Choi, Yeong Jin; Kim, Young Ok; Shinn, Kyung Sub [Catholic Univ., Seoul (Korea, Republic of). Coll. of Medicine

    1998-03-01

    Kaposi`s sarcoma accounts for more than 3% of neoplasms occurring in patients who have undergone a transplant. An epidemiologic study showed that in renal transplanted patients, the incidence of Kaposi`s sarcoma was 400 to 500 times higher than in controls of the same ethnic origin. We report a case of Kaposi`s sarcoma involving the lung and skin after immunosuppressive therapy in a patient with renal transplant. A plain chest radiograph showed diffusely increased interstital opacity with multiple, ill-defined small nodules in both lung fields. HRCT revealed multiple small nodules, predominantly in the peribronchovascular regions, and ill-defined areas of ground-glass opacity and consolidation in both lungs. (author). 10 refs., 1 fig.

  5. Dermoscopy of Kaposi's sarcoma: areas exhibiting the multicoloured 'rainbow pattern'.

    Science.gov (United States)

    Hu, S C-S; Ke, C-L K; Lee, C-H; Wu, C-S; Chen, G-S; Cheng, S-T

    2009-10-01

    Kaposi's sarcoma is a vascular tumour characterized by a proliferation of spindle cells and endothelial cells to form closely arranged slit-like vascular spaces. Currently, the definitive diagnosis of Kaposi's sarcoma relies on histology. The dermoscopic features of Kaposi's sarcoma are not clearly defined in the scientific literature. We seek to evaluate the dermoscopic features of Kaposi's sarcoma and compare them with other vascular tumours. One hundred forty-one lesions from seven patients with histologically proven Kaposi's sarcoma were evaluated using polarized light dermoscopy for the presence of various dermoscopic features. Twenty patients with other vascular tumours were also examined. Dermoscopic examination revealed bluish-reddish coloration (84% of lesions), multicoloured areas showing various colours of the rainbow spectrum (36%), scaly surface (29%), and small brown globules (15%). The 'rainbow pattern' was found in six out of seven patients with Kaposi's sarcoma and was not observed in other vascular tumours. In addition, there was an absence of dermoscopic features specific for other vascular and non-vascular skin tumours, such as well-defined lacunae or structured vascular pattern, in most of the Kaposi's sarcoma lesions. The most frequent dermoscopic patterns in Kaposi's sarcoma were found to be bluish-reddish coloration, the 'rainbow pattern', and scaly surface. The rainbow pattern is a dermoscopic feature which has not been previously described. We propose that dermoscopy, as an adjunct to clinical examination, may enhance accuracy in the preoperative diagnosis of Kaposi's sarcoma.

  6. Lymphangiectatic Kaposi's sarcoma in a patient with AIDS Sarcoma de Kaposi linfangiectásico em paciente com Aids

    Directory of Open Access Journals (Sweden)

    Mônica Santos

    2013-04-01

    Full Text Available Kaposi's sarcoma is a malignant disease that originates in the lymphatic endothelium. It has a broad spectrum of clinical manifestations. Its four distinct clinical forms are: classic, endemic, iatrogenic and epidemic Kaposi's sarcoma. In non-HIV-associated Kaposi's sarcoma, the disease is typically limited to the lower extremities, but in immunodeficient patients, it is a multifocal systemic disease. The clinical course of the disease differs among patients, ranging from a single or a few indolent lesions to an aggressive diffuse disease. Advanced Kaposi's sarcoma lesions, typically those on the lower extremities, are often associated with lymphedema. In this paper, we report a case of a patient with a rare form of AIDS-associated Kaposi sarcoma called lymphangiectatic Kaposis's sarcoma.O sarcoma de Kaposi é uma neoplasia originária do endotélio linfatico, que apresenta um amplo espectro de manifestações, com quatro formas clínicas: sarcoma de Kaposi clássico, endêmico, iatrogêncio e epidêmico ou associado ao HIV. Em pacientes imunocompetentes, a doença é tipicamente limitada às extremidades. Porém em pacientes imunideprimidos, o sarcoma de Kaposi é uma doença sistêmica multifocal. Apresenta cursos clínicos diferentes, desde simples lesões cutâneas isoladas até lesões agressivas e difusas, com ou sem envolvimento sistêmico. Lesões avançadas de sarcoma de Kaposi, principalmente as localizadas nas extremidades, podem apresentar linfedema. Neste trabalho, reportamos caso de paciente com forma rara de Sarcoma de Kaposi associado a Aids, chamada de sarcoma de Kaposi linfangiectásico.

  7. Lymphangioma-like Kaposi sarcoma: case report.

    Science.gov (United States)

    Posada García, Celia; García-Cruz, Aranzazu; García-Doval, Ignacio; De La Torre, Carlos; Cruces, Manuel José

    2009-09-15

    Kaposi sarcoma (KS) is a multifocal vascular disease with uncertain histogenesis. It is characterized by clinical and histologic polymorphism. The "lymphangioma-like" variant is very uncommon, accounting for less than 5% of all cases. We report the case of a 76-year-old woman, HIV negative, with a 4-year history of classic Kaposi sarcoma treated with cryotherapy who developed new bullous lesions on her lower extremities. Biopsy revealed histologic findings of lymphangioma-like KS (LLKS), together with areas of classic KS; HHV-8 staining was positive. Diagnosis of LLKS was made and the patient was proposed for radiotherapy. The lymphangioma-like Kaposi sarcoma is a rare morphologic expression of KS characterized by dilated and bizarrely shaped vascular channels lined by flattened endothelium permeating the dermis. "Bulla-like" lesions have been considered as a clinical hallmark of this variant. Its histologic appearance suggests a lymphatic origin of KS and it may resemble other vascular tumors. Findings of areas of typical KS and positive staining for HHV-8 may help to make a definitive diagnosis.

  8. Nuclear Localization and Cleavage of STAT6 Is Induced by Kaposi’s Sarcoma-Associated Herpesvirus for Viral Latency

    Science.gov (United States)

    Zhang, Liming; Li, Yuhong; Feng, Yanling; Xu, Jianqing; Wang, Bin; Yuan, Zhenghong; Robertson, Erle S.; Cai, Qiliang

    2017-01-01

    Emerging evidence implies that STAT6 plays an important role in both the adaptive and innate immune responses to virus infection. Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus agent associated with several human malignancies, including Kaposi’s sarcoma (KS) and primary effusion lymphomas (PELs). Previously, we demonstrated that KSHV blocks IL-4-induced STAT6 phosphorylation and retains a basal IL-13/STAT6 constitutive activation for cell survival and proliferation. However, the mechanism by which KSHV regulates STAT6 remains largely unknown. Here, we found that KSHV-encoded LANA interacts with STAT6 and promotes nuclear localization of STAT6 independent of the tyrosine 641-phosphorylation state. Moreover, nuclear localization of STAT6 is also dramatically increased in KS tissue. The latent antigen LANA induces serine protease-mediated cleavage of STAT6 in the nucleus, where the cleaved STAT6 lacking transactivation domain functions as a dominant-negative regulator to repress transcription of Replication and Transcription Activator (RTA) and in turn shut off viral lytic replication. Blockade of STAT6 by small interference RNA dramatically enhances expression of RTA, and in turn reduces KSHV-infected endothelial cell growth and colony formation. Taken together, these results suggest that nuclear localization and cleavage of STAT6 is important for modulating the viral latency and pathogenesis of KSHV. PMID:28099521

  9. Modulation of immune system by Kaposi’s sarcoma-associated herpesvirus:Lessons from viral evasion strategies

    Directory of Open Access Journals (Sweden)

    Hye-Ra eLee

    2012-03-01

    Full Text Available Kaposi’s sarcoma-associated herpesvirus (KSHV, a member of the herpesvirus family, has evolved to establish a long-term, latent infection of cells such that while they carry the viral genome gene expression is highly restricted. Latency is a state of cryptic viral infection associated with genomic persistence in their host and this hallmark of KSHV infection leads to several clinical-epidemiological diseases such as Kaposi’s sarcoma (KS, a plasmablastic variant of multicentric Castelman’s disease (MCD, and primary effusion lymphoma (PEL upon immune suppression of infected hosts. In order to sustain an efficient life-long persistency as well as their life cycle, KSHV dedicates a large portion of its genome to encode immunomodulatory proteins that antagonize its host’s immune system. In this review, we will describe our current knowledge of the immune evasion strategies employed by KSHV at distinct stages of its viral life cycle to control the host’s immune system.

  10. Histological variants of cutaneous Kaposi sarcoma

    Directory of Open Access Journals (Sweden)

    Pantanowitz Liron

    2008-07-01

    Full Text Available Abstract This review provides a comprehensive overview of the broad clinicopathologic spectrum of cutaneous Kaposi sarcoma (KS lesions. Variants discussed include: usual KS lesions associated with disease progression (i.e. patch, plaque and nodular stage; morphologic subtypes alluded to in the older literature such as anaplastic and telangiectatic KS, as well as several lymphedematous variants; and numerous recently described variants including hyperkeratotic, keloidal, micronodular, pyogenic granuloma-like, ecchymotic, and intravascular KS. Involuting lesions as a result of treatment related regression are also presented.

  11. Sarcoma de Kaposi asociado al VIH

    OpenAIRE

    Malagón Gutiérrez, Sandra Ximena; Chimenos Küstner, Eduardo

    1995-01-01

    La neoplasia más común asociada al VIH es el sarcoma de Kaposi (SK). Esta puede ser superficialmente mucocutánea o internamente visceral, apareciendo frecuentemente en la cavidad oral. Este tumor se ha relacionado con una proliferación atípica de estructuras vasculares, la cual haya sido inducida por un agente angiogénico estimulado a su vez por la infección retroviral. Este artículo es una revisión bibliográfica sobre esta lesión, la cual representa una patología importante para la profesión...

  12. Acroangiodermatite (pseudo-sarcoma de Kaposi

    Directory of Open Access Journals (Sweden)

    Azulay Rubem David

    2004-01-01

    Full Text Available Acroangiodermatite é enfermidade rara, caracterizada por lesões eritêmato-violáceas bem delimitadas que acometem pernas e pés com aspecto semelhante ao do sarcoma de Kaposi. É relatado o caso de paciente do sexo feminino, de 57 anos, com início súbito de lesões eritêmato-violáceas nas pernas sem outras alterações. O caso acrescenta aprendizado por sua dificuldade diagnóstica e reafirma a importância da imuno-histoquímica. Trata-se da publicação do primeiro caso brasileiro.

  13. Kaposi sarcoma incidence in Mozambique: national and regional estimates.

    Science.gov (United States)

    Meireles, Paula; Albuquerque, Gabriela; Vieira, Mariana; Foia, Severiano; Ferro, Josefo; Carrilho, Carla; Lunet, Nuno

    2015-11-01

    Kaposi sarcoma is expressed in four clinical variants, all associated with human herpes virus type 8 infection, namely, classic, endemic, immunosuppression-related and AIDS-related. The latter currently accounts for most of the burden of Kaposi sarcoma in sub-Saharan Africa, reflecting the frequency of HIV infection and its management. We aimed to estimate the incidence of Kaposi sarcoma in Mozambique and in its provinces. We estimated the number of incident cases of Kaposi sarcoma by adding up the expected number of endemic and AIDS-related cases. The former were estimated from the rates observed in Kyandondo, Uganda (1960-1971). The latter were computed from the number of AIDS-related deaths in each region, assuming that the ratio between the AIDS-related Kaposi sarcoma incident cases and the number of AIDS-related deaths observed in the city of Beira applies to all regions. A total of 3862 Kaposi sarcoma cases were estimated to have occurred in Mozambique in 2007, mostly AIDS-related, in the age group 25-49 years, and in provinces from South/Centre. The age-standardized incidence rates were 36.1/100 000 in men and 11.5/100 000 in women, with a more than three-fold variation across provinces. We estimated a high incidence of Kaposi sarcoma in Mozambique, along with large regional differences. These results can be used to improve disease management and to sustain political decisions on health policies.

  14. AIDS-related primary Kaposi sarcoma of the nasopharynx.

    Science.gov (United States)

    Çelenk, Fatih; Yilmaz, Metin; Asal, Korhan; Ekinci, Özgür; Tokgöz, Nil

    2011-06-01

    Primary nasopharyngeal Kaposi sarcoma is extremely rare, as only 1 case has been previously reported in the literature. We report a new case, which occurred in a 37-year-old man with a known history of acquired immune deficiency syndrome (AIDS). The patient presented with complaints of recurrent epistaxis and postnasal hemorrhage. Endoscopic examination detected a bluish, smooth, firm, nonpulsatile mass in the nasopharyngeal wall. Histopathologic findings on biopsy were consistent with Kaposi sarcoma. The tumor was successfully treated with radiotherapy. Kaposi sarcoma should be considered in the differential diagnosis of any AIDS patient who presents with recurrent unilateral nasal bleeding.

  15. Pseudo-Kaposi sarcoma (acroangiodermatitis): occurring after bullous erysipelas.

    Science.gov (United States)

    Kutlubay, Zekayi; Yardimci, Gürkan; Engin, Burhan; Demirkesen, Cuyan; Aydin, Övgü; Khatib, Rashid; Tuzun, Yalçın

    2015-05-18

    Pseudo-Kaposi sarcoma is a benign reactive vascular proliferative disorder, which can be seen at any age. It occurs when the chronic venous pressure changes result in vascular proliferation in the upper and mid dermis. This disease is divided into two subtypes: the most frequent subtype is the Mali type and seen in early ages. The Mali type is seen in chronic venous insufficiency and in those patients with arteriovenous shunts. The rare subtype is the Stewart-Bluefarb type. This disease must be distinguished from Kaposi sarcoma because of their clinical resemblance. Herein, we present a patient with pseudo-Kaposi sarcoma, which developed after bullous erysipelas.

  16. Human herpesvirus 8 open reading frame 26 and open reading frame 65 sequences from multiple myeloma patients: a shared pattern not found in Kaposi's sarcoma or primary effusion lymphoma.

    Science.gov (United States)

    Ma, H J; Sjak-Shie, N N; Vescio, R A; Kaminsky, M; Mikail, A; Pold, M; Parker, K; Beksac, M; Belson, D; Moss, T J; Wu, C H; Zhou, J; Zhang, L; Chen, G; Said, J W; Berenson, J R

    2000-11-01

    Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, has been implicated in the pathogenesis of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman's disease, and recently multiple myeloma (MM). DNA sequence analyses of HHV-8 suggest that multiple HHV-8 strains exist. We extracted DNA from 24 patients with MM and 3 patients with monoclonal gammopathy of undetermined significance and compared HHV-8 open reading frames (ORFs) 26 and 65 sequences with those derived from patients with KS, PEL, and two HHV-8-positive PEL cell lines KS-1 and BC-1. ORF26 sequence data suggest that MM patients are consistently carriers of HHV-8 strain subtype C3. All MM patients also consistently revealed either a single bp deletion or substitution at position 112197 in ORF65. This unique alteration is not present in patients with KS or PEL or in PEL cell lines. It occurs in the portion of ORF65 that is known to be responsible for a serological response to HHV-8.

  17. Pulmonary Kaposi sarcoma in six children

    Energy Technology Data Exchange (ETDEWEB)

    Theron, Salomine [University of Stellenbosch, Department of Radiology, Tygerberg Academic Hospital, Cape Town (South Africa); University of Stellenbosch, Department of Radiology, Tygerberg Hospital, Cape Town (South Africa); Andronikou, Savvas; Plessis, Jaco du; George, Reena; Mapukata, Ayanda; Grobbelaar, Marie; Hayes, Murray [University of Stellenbosch, Department of Radiology, Tygerberg Academic Hospital, Cape Town (South Africa); Goussard, Pierre [University of Stellenbosch, Department of Child Health, Tygerberg Academic Hospital, Cape Town (South Africa); Wieselthaler, Nicky [University of Cape Town, Department of Radiology, Red Cross Children' s Hospital, Cape Town (South Africa); Davidson, Alan [University of Cape Town, Department of Oncology, Red Cross Children' s Hospital, Cape Town (South Africa)

    2007-12-15

    Pulmonary involvement in Kaposi sarcoma is rare in children and can be difficult to distinguish from other pathology. To describe the radiological findings in paediatric pulmonary Kaposi sarcoma. Sequential chest radiographs of six children and CT scans of four of these children were evaluated retrospectively. Their ages ranged from 18 months to 10 years; four were male and two were female. All six children were HIV-positive. The observers were two radiologists. Chest radiographs revealed air-space (100%) and reticular (83%) opacification in the mid- and lower lung zones; pleural effusions were present in 83% of the children. All the children showed progressive air-space opacification on follow-up radiography. CT demonstrated bilateral air-space opacification in a perihilar distribution in all the children; reticular opacification was seen in 75%. All the children had mediastinal and axillary lymphadenopathy; 75% had bilateral hilar lymphadenopathy. In both adults and children, chest radiography demonstrates perihilar and lower zone involvement. Pleural effusions are more common on radiographs in children. Air-space disease and lymphadenopathy are much more common on CT in children than adults. (orig.)

  18. Oesophageal cancer and Kaposi's Sarcoma in Malawi: a ...

    African Journals Online (AJOL)

    Oesophageal cancer and Kaposi's Sarcoma in Malawi: a comparative analysis. ... Given that oesophageal cancer (OC) is common in Malawi and its outcome is so dismal, would it be pragmatic to promptly mitigate the effects of ... Article Metrics.

  19. Pulmonary Kaposi's sarcoma after heart transplantation: a case report

    Directory of Open Access Journals (Sweden)

    Kristiansen Glen

    2010-07-01

    Full Text Available Abstract Introduction Kaposi's sarcomas have been associated with different conditions of immunosuppression and are also known to be a typical complication of solid organ transplantations. Case presentation We report the case of a 65-year-old Turkish man with a history of heart transplantation 10 months ago who presented for clarification of his dyspnea. The patient had a known history of chronic obstructive pulmonary disease and a smoking history of 40 pack years. Radiologically, three progressively growing intra-pulmonary nodules were detected. The histology was diagnostic for a Kaposi's sarcoma. Visceral and especially primary intra-pulmonary Kaposi's sarcomas are very rare and have been described to have a rather unfavorable prognosis. Conclusions Even with a history suggestive for conventional lung cancer, Kaposi's sarcomas should be considered in patients after transplantation of solid organs. It should be noted that in a minority of cases this tumor exists in the absence of the typical cutaneous lesions.

  20. Clinical Manifestations of Kaposi Sarcoma Herpesvirus (KSHV Lytic Activation: Multicentric Castleman Disease (KSHV-MCD and the KSHV Inflammatory Cytokine Syndrome (KICS

    Directory of Open Access Journals (Sweden)

    Mark N. Polizzotto

    2012-03-01

    Full Text Available Soon after the discovery of Kaposi sarcoma associated herpesvirus (KSHV, it was appreciated that this virus was associated with most cases of multicentric Castleman disease (MCD arising in patients infected with human immunodeficiency virus (HIV. It has subsequently been recognized that KSHV-MCD is a distinct entity from other forms of MCD. Like MCD that is unrelated to KSHV, the clinical presentation of KSHV-MCD is dominated by systemic inflammatory symptoms including fevers, cachexia and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein. Pathologically KSHV-MCD is characterized by polyclonal, IgM-lambda restricted plasmacytoid cells in the intrafollicular areas of affected lymph nodes. A portion of these cells are infected with KSHV and a sizable subset of these cells express KSHV lytic genes including a viral homolog of interleukin-6 (vIL-6. Patients with KSHV-MCD generally have elevated KSHV viral loads in their peripheral blood. Production of vIL-6 and induction of human (h IL-6 both contribute to symptoms, perhaps in combination with overproduction of IL-10 and other cytokines. Until recently, the prognosis of patients with KSHV-MCD was poor. Recent therapeutic advances targeting KSHV-infected B cells with the anti-CD20 monoclonal antibody rituximab and utilizing KSHV enzymes to target KSHV-infected cells have substantially improved patient outcomes. Recently another KSHV-associated condition, the KSHV inflammatory cytokine syndrome (KICS has been described. Its clinical manifestations resemble those of KSHV-MCD but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV-MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, hIL-6 and IL-10 comparable to those seen in KSHV-MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms seen in some patients with severe Kaposi

  1. Primary Kaposi sarcoma of the subcutaneous tissue

    Directory of Open Access Journals (Sweden)

    Dezube Bruce J

    2008-09-01

    Full Text Available Abstract Background Involvement of the subcutis by Kaposi sarcoma (KS occurs primarily when cutaneous KS lesions evolve into deep penetrating nodular tumors. Primary KS of the subcutaneous tissue is an exceptional manifestation of this low-grade vascular neoplasm. Case presentation We present a unique case of acquired immune deficiency syndrome (AIDS-associated KS manifesting primarily in the subcutaneous tissue of the anterior thigh in a 43-year-old male, which occurred without overlying visible skin changes or concomitant KS disease elsewhere. Radiological imaging and tissue biopsy confirmed the diagnosis of KS. Conclusion This is the first documented case of primary subcutaneous KS occurring in the setting of AIDS. The differential diagnosis of an isolated subcutaneous lesion in an human immunodeficiency virus (HIV-infected individual is broad, and requires both imaging and a histopathological diagnosis to guide appropriate therapy.

  2. Thoracic manifestations of Kaposi`s sarcoma in AIDS: radiological findings; Manifestacoes toracicas do sarcoma de Kaposi na sindrome da imunodeficiencia adquirida: aspectos radiologicos

    Energy Technology Data Exchange (ETDEWEB)

    Marchiori, Edson [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Radiologia]|[Universidade Federal, Rio de Janeiro, RJ (Brazil); Baptista, Maria Ines Garcia; Cardenas, Gloria Pamela; Costa Praxedes, Marcia da [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Radiologia; Boechat, Lucia de Fatima; Quaresma, Patricia Souto Maior [Universidade Federal, Rio de Janeiro, RJ (Brazil). Hospital Universitario Clementino Fraga Filho. Servico de Radiodiagnostico

    1995-09-01

    The radiological findings of 189 cases of Kaposi`s sarcoma occurring in patients with AIDS were studied. There was also made pathological correlations in these patients. Interstitial reticular infiltrations were frequently detected on thoracic examination showing paracardiac confluent areas. There was also lymphadenopathy, gross nodules and pleural fluid accumulation. Although there was no detection of any pathognomonic aspect, the interstitial reticular infiltration finding together with the paracardiac confluent areas and associated with gross nodules, is highly indicative to thoracic involvement by the disease. (author). 32 refs., 5 figs., 2 tabs.

  3. The Kaposi Sarcoma Herpesvirus Latency-associated Nuclear Antigen DNA Binding Domain Dorsal Positive Electrostatic Patch Facilitates DNA Replication and Episome Persistence.

    Science.gov (United States)

    Li, Shijun; Tan, Min; Juillard, Franceline; Ponnusamy, Rajesh; Correia, Bruno; Simas, J Pedro; Carrondo, Maria A; McVey, Colin E; Kaye, Kenneth M

    2015-11-20

    Kaposi sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies. KSHV latency-associated nuclear antigen (LANA) mediates persistence of viral episomes in latently infected cells. LANA mediates KSHV DNA replication and segregates episomes to progeny nuclei. The structure of the LANA DNA binding domain was recently solved, revealing a positive electrostatic patch opposite the DNA binding surface, which is the site of BET protein binding. Here we investigate the functional role of the positive patch in LANA-mediated episome persistence. As expected, LANA mutants with alanine or glutamate substitutions in the central, peripheral, or lateral portions of the positive patch maintained the ability to bind DNA by EMSA. However, all of the substitution mutants were deficient for LANA DNA replication and episome maintenance. Mutation of the peripheral region generated the largest deficiencies. Despite these deficiencies, all positive patch mutants concentrated to dots along mitotic chromosomes in cells containing episomes, similar to LANA. The central and peripheral mutants, but not the lateral mutants, were reduced for BET protein interaction as assessed by co-immunoprecipitation. However, defects in BET protein binding were independent of episome maintenance function. Overall, the reductions in episome maintenance closely correlated with DNA replication deficiencies, suggesting that the replication defects account for the reduced episome persistence. Therefore, the electrostatic patch exerts a key role in LANA-mediated DNA replication and episome persistence and may act through a host cell partner(s) other than a BET protein or by inducing specific structures or complexes.

  4. Recent researches on the pathogenicity of Kaposi's sarcoma%Kaposi's肉瘤的病因探究

    Institute of Scientific and Technical Information of China (English)

    李磊; 朱淮民

    2013-01-01

    Kaposi's sarcoma is a kind of idiopathic malignant hemangioma.The infection has shown the close relationship between the clinical symptoms and its classification.The important factors that attribute to the pathogenesis are related to the genetic factors,the virus infection,cytokines,immune compromised conditions,etc.Recent epidemiology and pathology studies show that the human herpesivirus 8 (HHV8) infection is closely related with Kaposi's sarcoma.Apart from the main route of sexual transmission for HHV8 dispersal,there are some studies related to the blood-feeding arthropods that might play some role in the transmission of the disease.The definition,classification,etiology and pathogenesis of Kaposi's sarcoma were discussed in this paper.Recent research on "the promoter arthropod hypothesis" was also introduced.%Kaposi's肉瘤(Kaposi's sarcoma,KS)是一种特发性的恶性血管瘤,机体感染该病所表现出的临床症状与其分型密切相关.遗传因素、病毒感染、细胞因子、免疫低下等是致病的重要因素.近年来的研究表明,疱疹病毒8(human herpesivirus 8,HHV8)的发生与Kaposi's肉瘤的发生密切相关,除了性传播方式以外,吸血节肢动物可能在该疾病的传播方面有一定的作用.该文从Kaposi's肉瘤的定义及分型、病因及发病机制两个方面进行阐述,并介绍近年来吸血节肢动物在该病传播中的作用.

  5. Pulmonary involvement in Kaposi sarcoma: correlation between imaging and pathology.

    Science.gov (United States)

    Gasparetto, Taisa Davaus; Marchiori, Edson; Lourenço, Sílvia; Zanetti, Gláucia; Vianna, Alberto Domingues; Santos, Alair A S M D; Nobre, Luiz Felipe

    2009-07-14

    Kaposi sarcoma is a low-grade mesenchymal tumor involving blood and lymphatic vessels. There are four variants of this disease, each presenting a different clinical manifestation: classic or sporadic, African or endemic, organ transplant-related or iatrogenic, and AIDS-related or epidemic. Kaposi sarcoma is the most common tumor among patients with HIV infection, occurring predominantly in homosexual or bisexual men. The pulmonary involvement in Kaposi sarcoma occurs commonly in critically immunosupressed patients who commonly have had preceding mucocutaneous or digestive involvement.The etiology of Kaposi sarcoma is not precisely established; genetic, hormonal, and immune factors, as well as infectious agents, have all been implicated. There is evidence from epidemiologic, serologic, and molecular studies that Kaposi sarcoma is associated with human herpes virus type 8 infection. The disease starts as a reactive polyclonal angioproliferative response towards this virus, in which polyclonal cells change to form oligoclonal cell populations that expand and undergo malignant transformation.The diagnosis of pulmonary involvement in Kaposi sarcoma usually can be made by a combination of clinical, radiographic, and laboratory findings, together with the results of bronchoscopy and transbronchial biopsy. Chest high-resolution computed tomography scans commonly reveal peribronchovascular and interlobular septal thickening, bilateral and symmetric ill-defined nodules in a peribronchovascular distribution, fissural nodularity, mediastinal adenopathies, and pleural effusions. Correlation between the high-resolution computed tomography findings and the pathology revealed by histopathological analysis demonstrate that the areas of central peribronchovascular infiltration represent tumor growth involving the bronchovascular bundles, with nodules corresponding to proliferations of neoplastic cells into the pulmonary parenchyma. The interlobular septal thickening may represent

  6. Pulmonary involvement in Kaposi sarcoma: correlation between imaging and pathology

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    Vianna Alberto

    2009-07-01

    Full Text Available Abstract Kaposi sarcoma is a low-grade mesenchymal tumor involving blood and lymphatic vessels. There are four variants of this disease, each presenting a different clinical manifestation: classic or sporadic, African or endemic, organ transplant-related or iatrogenic, and AIDS-related or epidemic. Kaposi sarcoma is the most common tumor among patients with HIV infection, occurring predominantly in homosexual or bisexual men. The pulmonary involvement in Kaposi sarcoma occurs commonly in critically immunosupressed patients who commonly have had preceding mucocutaneous or digestive involvement. The etiology of Kaposi sarcoma is not precisely established; genetic, hormonal, and immune factors, as well as infectious agents, have all been implicated. There is evidence from epidemiologic, serologic, and molecular studies that Kaposi sarcoma is associated with human herpes virus type 8 infection. The disease starts as a reactive polyclonal angioproliferative response towards this virus, in which polyclonal cells change to form oligoclonal cell populations that expand and undergo malignant transformation. The diagnosis of pulmonary involvement in Kaposi sarcoma usually can be made by a combination of clinical, radiographic, and laboratory findings, together with the results of bronchoscopy and transbronchial biopsy. Chest high-resolution computed tomography scans commonly reveal peribronchovascular and interlobular septal thickening, bilateral and symmetric ill-defined nodules in a peribronchovascular distribution, fissural nodularity, mediastinal adenopathies, and pleural effusions. Correlation between the high-resolution computed tomography findings and the pathology revealed by histopathological analysis demonstrate that the areas of central peribronchovascular infiltration represent tumor growth involving the bronchovascular bundles, with nodules corresponding to proliferations of neoplastic cells into the pulmonary parenchyma. The interlobular

  7. Hidden Pictures of Kaposi's Sarcoma in Psoriatic Lesions: A Diagnostic Challenge

    Science.gov (United States)

    Yoo, Jisook; Jo, Mingyul; Kim, Min-Soo; Choi, Kwang-Hyun; Park, Hyang-Joon

    2016-01-01

    Kaposi's sarcoma is a multifocal proliferative vascular tumor involving the skin and other organ and psoriasis is a chronic cutaneous disease with papules and plaques with white scale. Development of Kaposi's sarcoma in psoriasis patients has been reported rarely. A 71-year-old man presented with multiple brownish to violaceous plaques on both feet and arms which were found 4 months ago. The biopsy confirmed Kaposi's sarcoma. The patient was diagnosed with psoriasis vulgaris 10 years ago and Kaposi's sarcoma lesions developed between psoriatic plaques. We herein report a rare case of simultaneous occurrence of Kaposi's sarcoma and psoriasis vulgaris which need quite different treatment. PMID:27904275

  8. Kaposi´s sarcoma, epidemic type. Case presentation

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    Gilberto Serrano Ocaña

    2009-05-01

    Full Text Available Before the AIDS epidemic, Kaposi's sarcoma was found mainly in elderly men of Mediterranean coast, eastern European background and Jewish ancestry (rarely in older women and is a slow growing skin tumor. In AIDS patients, the KS tends to develop more rapidly compromising the skin, lungs, gastrointestinal tract and other organs. In people with AIDS, Kaposi's sarcoma is caused by an interaction between HIV, a weakened immune system and human herpes virus 8. It affects approximately 20% of people with HIV that don’t take antiretroviral drugs. It is more common in homosexual’s patients, but may appear in any HIV positive individual, in Africa where heterosexual HIV transmission route is the most important can also be found in children and women. We are presenting a case of Kaposi sarcoma in a young female admitted at the Internal Medicine Department of Dora Nginza Hospital.

  9. Fine needle cytology of Kaposi's sarcoma in heterosexual male

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    Anjali R. Dhote

    2014-04-01

    Full Text Available Kaposi's sarcomas the most common malignancy associated with Human Herpesvirus-8 (HHV8 infection. Though name is sarcoma but it is low grade vascular neoplasm. It is the tumour which arises from endothelial lining of vessels as well as lymphatic channels. So it involved all sites such as skin, Gastro intestine, lungs along with lymph nodes. We are presenting one such case of 65 year immunocompromised Indian male presented with multiple non blanching reddish bluish nodules on all extremities, chest, back with submandibular and cervical lymphadenopathy. Fine needle aspiration cytology (FNAC was performed and diagnosis was given low grade spindle cell neoplasm consistent with Kaposi's sarcoma which was confirmed on histopathology as Kaposi's sarcoma. [Int J Res Med Sci 2014; 2(2.000: 789-791

  10. Sarcoma de Kaposi en conjuntiva bulbar

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    Ileana Agramonte Centelles

    Full Text Available Paciente masculino de 29 años de edad, raza blanca, soltero, profesor universitario, con antecedentes de padecer crisis de epilepsia tratado con fenitoína y actualmente controlado, menciona que desde hace aproximadamente 4 semanas comenzó con ojo rojo y molestias oculares del ojo derecho, por lo cual acudió a su área de salud donde fue tratado como cuadro de conjuntivitis. No mostró mejoría alguna, sino empeoramiento del cuadro clínico, y observó un enrojecimiento ocular intenso en el ángulo interno de dicho ojo que se fue extendiendo, acompañado de ligera fotofobia. Por la tórpida evolución del cuadro decidió acudir a nuestra institución por lo cual fue remitido a la Consulta de Oculoplastia. También refirió que desde hacía dos meses había presentado anorexia, dificultad al comer, así como pérdida de peso, por lo cual se decidió comenzar estudio y tratamiento. Se decidió realizar la resección de la masa tumoral en conjuntiva bulbar y se envió para estudio anatomopatológico. El resultado fue compatible con un sarcoma de Kaposi.

  11. Sarcoma de Kaposi en paciente con SIDA

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    Jesús Ramón León Polanco

    2015-01-01

    Full Text Available Se presenta el caso de un paciente masculino de 33 años de edad, con antecedentes de VIH-SIDA desde hace 10 años, que se mantiene en tratamiento con antirretrovirales. Durante todo este tiempo ha presentado varios episodios de infecciones respiratorias, incluyendo tuberculosis pulmonar 5 años atrás. Acude a consulta refiriendo edemas en miembros inferiores acompañado de lesiones en piel de color violáceo de un año de evolución, previamente interpretado como linfangitis rebelde al tratamiento y que se extendió a la cara interna de los muslos y a los miembros inferiores. Con pérdida de peso, no prurito en las lesiones, fiebre, lesiones en la mucosa oral. Se determinó hemoglobina 89 g/L, leucocitos 4,5 x 109 /L, se estudiaron las funciones hepática y renales resultando normales. Radiografías de tórax y ultrasonido abdominal normales. Se realizó estudio anatomopatológico de piel que informó Sarcoma de Kaposi. Se impuso tratamiento con quimioterapia

  12. Simultaneous lymph node involvement by Castleman disease and Kaposi sarcoma

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    Luciana Wernersbach Pinto

    2011-02-01

    Full Text Available Both multicentric Castleman disease and Kaposi sarcoma are more frequently observed in HIV infected patients. The coexistence of these Human herpesvirus 8 related lesions, in the same tissue, has been observed, but literature reports are scant. On the other hand, the expression of HHV-8-LANA-1 is easily demonstrable by immunohistochemistry. This has been shown to be a powerful tool for the diagnosis of these entities. The aim of this report is to communicate our experience with a case of multicentric Castleman disease occurring in the setting of HIV infection, which demonstrated microscopic Kaposi sarcoma in the same lymph node during the pathological work-up

  13. Diagnosis and treatment of HIV-related Kaposi's sarcoma

    NARCIS (Netherlands)

    Reyners, A.K.L.; Sprenger, H.G; Suurmeijer, A.J.H.; van der Graaf, W.T.A.

    2006-01-01

    A 42-year-old heterosexual man presented with bluish-purple spots on his skin and in his mouth cavity that had been present for a few months; a 48-year-old homosexual man had painful lymphadenopathy in the groins and left axilla. Both men appeared to have a Kaposi's sarcoma and to be HIV-positive. D

  14. Human immunodeficiency virus negative Kaposi sarcoma and lymphoproliferative disorders

    NARCIS (Netherlands)

    Fossati, S; Boneschi, [No Value; Ferrucci, S; Brambilla, L

    1999-01-01

    BACKGROUND. The concomitant occurrence of more than one primary neoplasm in the same individual has led researchers to seek possible common etiopathogenetic factors. Kaposi sarcoma (KS) is a multicentric neoplasm of vascular origin and perhaps viral etiology. Four forms of KS are known: classic or M

  15. Isolated Kaposi sarcoma of the finger pulp in an AIDS patient.

    Science.gov (United States)

    Aïm, F; Rosier, L; Dumontier, C

    2012-02-01

    A 63-year-old woman with long-standing AIDS and previous Kaposi sarcomas of the lower limb presented to our consultation complaining of a painful left ring finger with pulp enlargement. X-rays revealed an osteolytic lesion of the distal phalanx. We suspected an isolated osseous Kaposi sarcoma and at surgery we found a hemorrhagic lesion with bone extension into the phalanx. Bone involvement is rare in Kaposi sarcoma and even rarer in patients without a cutaneous location.

  16. Tonsillar Kaposi sarcoma in a patient with membranous glomerulonephritis on immunosuppressive therapy.

    Science.gov (United States)

    Al-Brahim, Nabeel; Zaki, Ashraf H; El-Merhi, Khaled; Ahmad, Mahmoud S

    2013-07-01

    Kaposi sarcoma is a malignant vascular neoplasm uncommonly seen in immunosuppressed patients. Herein we report an unusual case of tonsillar Kaposi sarcoma in a patient with membranous glomerulonephritis treated with prednisolone and cyclosporine. The patient presented after 10 months of starting the treatment with a tonsillar mass. Histological examination was typical of monomorphic spindle cell proliferation with slit-like vascular channels. The tumor cells expressed CD34, D2-40 and positive nuclear stain for HHV-8. Kaposi sarcoma is associated with immunosuppression and rarely occurs in the tonsil. Clinicians should be aware of this rare presentation of Kaposi sarcoma.

  17. Kaposi's sarcoma in an elderly man with Wegener's granulomatosis treated with cyclophosphamide and corticosteroids.

    Science.gov (United States)

    Erban, S B; Sokas, R K

    1988-05-01

    The association of Kaposi's sarcoma with malignant lymphoreticular diseases and immunosuppressive therapy is well documented. This report describes an elderly man who presented with fulminant Wegener's granulomatosis that responded to treatment with cyclophosphamide and corticosteroids. Rapidly progressing cutaneous Kaposi's sarcoma developed ten weeks after the start of immunosuppressive therapy yet regressed on discontinuation of the corticosteroid therapy, despite continuation of cyclophosphamide therapy. To our knowledge, this is the first reported case of Kaposi's sarcoma occurring in association with Wegener's granulomatosis. The literature on Kaposi's sarcoma in immunosuppressed patients is reviewed.

  18. Disseminated Kaposi sarcoma in a HIV negative patient.

    Science.gov (United States)

    Lin, Guoshu; Wang, Hongyan; Fan, Xing; Li, Hui; Wang, Zaixing; Lin, Da; Yang, Sen; Zhang, Xuejun

    2015-01-01

    Kaposi sarcoma (KS) is a neoplasm of the endothelial cells. It often manifests with multiple vascular nodules on the skin and other organs. It is a systemic, malignant and multifactor disease and has a variable course. We describe an elderly Chinese man who had a rapidly growing maroon nodule on his right foot, both arms and cheekbones. KS in HIV-negative patients has only been reported sporadically.

  19. CO2激光治疗Kaposis Sarcoma

    Institute of Scientific and Technical Information of China (English)

    李明仁; 王惠丰; 陈萍

    2001-01-01

    本文总结了用CO2激光治疗9例Kaposis Sarcoma(KS)的体会,KS随着艾滋病的出现而增多,其诊断、治疗有别于其他皮肤病灶.提出CO2激光治疗KS应注意的事项,探讨其诊断和治疗相关问题.

  20. Acute polyarticular synovitis as a rare presentation of Kaposi sarcoma

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    Larissa Larsen

    2014-01-01

    Full Text Available Patients with HIV are prone to a number of unusual infectious and malignant conditions, typically resulting from declining immune function. However, there are also a few of reports of HIV associated conditions potentially created by viral release of interleukin-6 (IL-6. Herein, we present a case of HIV IL-6-related systemic inflammatory syndrome, a Kaposi sarcoma (KS-associated syndrome in the absence of multicentric Castleman disease (MCD.

  1. [Historical Review of Kaposi sarcoma in pre-HAART era: evolution with different chemotherapy schedules and remission with ganciclovir use].

    Science.gov (United States)

    Volkow, Patricia; Jacquemin, Benedicte; Zinser, Juan W; Pérez-Padilla, Rogelio

    2016-10-01

    Ganciclovir has shown in vitro anti-human herpesvirus-8 activity, Kaposi sarcoma agent. We analyzed all Kaposi sarcoma patients from 1985 to 1996 pre-HAART era and identified Kaposi sarcoma/AIDS patients who achieved complete remission prior to HAART use.

  2. Histopathological analysis of vesicular and bullous lesions in Kaposi sarcoma

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    Kandemir Nilüfer

    2012-08-01

    Full Text Available Abstract Background In this study, the clinical and morphological features of vesiculobullous lesions observed in Kaposi sarcoma are analyzed, and the features of bullous Kaposi sarcoma cases are emphasized. Methods A total of 178 biopsy materials of 75 cases diagnosed as classic-type cutaneous Kaposi sarcoma were reviewed. Twenty-five cases showing vesiculobullous features were included in the study. Tumor, epidermis, dermis, and clinical data regarding these cases was evaluated. Results Vesicular changes were observed in 21 (12% out of 178 lesions of the 75 cases, while bullous changes were present in only 4 (2%. In all cases where vesicular and bullous changes were detected, tumor, epidermis, and dermis changes were similar. All cases were nodular stage KS lesions, whereas hyperkeratosis and serum exudation in the epidermis, marked edema in the dermis, and enlarged lymphatic vessels and chronic inflammatory response were observed. Conclusions Our findings suggest that changes in vascular resistance occurring during tumor progression are the most important factors comprising vesiculobullous morphology. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1646397188748474

  3. The prevalence of human herpesvirus 8 genotypes in Kaposi\\\\\\'s sarcoma in Iran by using molecular technique

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    Reza Shah Siah

    2013-10-01

    Full Text Available Background: In the Mediterranean region , Kaposi's sarcoma (KS has a high prevalence especially in patients with AIDS. Iran is located close to the Mediterranean region and the HIV prevalence is increasing in our country . In some stages, Kaposi's sarcoma is morphologically similar to other vascular tumors. Owing to the presence of human herpesvirus 8 (HHV-8 in all cases of Kaposi's sarcoma , detection of virus DNA by PCR method can help in the identification of non-diagnostic cases. Moreover, the prevalence of HHV-8 genotypes is different in various regions of the world and in different races. There are limited studies performed on the HHV-8 genotypes in Iranian population. Methods: Patients with Kaposi's sarcoma from 2001 to 2011 who refer to Tehran Razi Hospital were enrolled in this study. HHV-8 DNA was extracted from paraffin blocks and amplification of the virus genome was performed by PCR method . Finally, the target DNA fragment was used for sequencing and genotype determination. Results: PCR was performed on 53 cases. In 8 cases with suspicious morphology, PCR was negative and they were excluded from study. Of remaining 45 cases, 35 had positive PCR results, 7 had negative results and 3 had low PCR product. Samples from 28 cases that had positive PCR results, which were acceptable for genotyping, were chosen for sequencing. Twenty cases had genotype C, 7 cases had genotype A and one case was negative. The results are consistent with other studies in our geographical area. No correlation was found between the different microscopic stages and HHV-8 Genotypes. Conclusion: Since the HHV-8 is obtained in almost 100% of KS lesions and PCR s ensitivity in detection of the virus is close to 100 %, KS diagnosis can be confirmed in suspicious cases by detection of HHV-8 DNA on paraffin blocks. Moreover the prevalence of HHV-8 genotype was determined in Iran.

  4. Pulmonary involvement of Kaposi sarcoma in an AIDS patient: radiologic and pathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Ho; Goo, Jin Mo; Lee, Jun Woo; Chung, Myung Jin; Lee, Yu Jin; Im, Jung Gi [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2002-01-01

    Kaposi sarcoma is the most common malignancy in aquired immunodeficiency syndrome (AIDS), and when disseminated may involve any organ system. Pulmonary involvement of Kaposi sarcoma in AIDS patients has not been previously reported in Korea and we report one such case, confirmed pathologically at autopsy.

  5. Peginterferon alfa-2a for AIDS-associated Kaposi sarcoma: experience with 10 patients.

    Science.gov (United States)

    Rokx, Casper; van der Ende, Marchina E; Verbon, Annelies; Rijnders, Bart J A

    2013-11-01

    In this observational cohort study, 10 patients with extensive or treatment-refractory AIDS-associated Kaposi sarcoma were treated with peginterferon alfa-2a. Tumor responses were observed in 9 patients with a median progression-free survival of 645 days. Peginterferon alfa-2a could be an effective therapy for extensive or treatment-resistant Kaposi sarcoma.

  6. Imaging of Kaposi sarcoma in a transplanted liver: A rare case report

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    Saumya Gupta

    2015-06-01

    Full Text Available In post-transplant patients, de novo malignancies such as post-transplant lymphoproliferative disease (PTLD, lung carcinoma, renal cell carcinoma, cutaneous malignancies, and Kaposi sarcoma are now seen. The immunotherapy used to prevent graft failure indirectly increases their risk. We present a rare case of visceral Kaposi sarcoma in a patient with orthotopic liver transplant.

  7. Risk of Kaposi's sarcoma and of other cancers in Italian renal transplant patients

    Science.gov (United States)

    Serraino, D; Piselli, P; Angeletti, C; Minetti, E; Pozzetto, A; Civati, G; Bellelli, S; Farchi, F; Citterio, F; Rezza, G; Franceschi, S; Busnach, G

    2005-01-01

    A follow-up study of 1844 renal transplant patients in Italy showed a 113-fold increased risk for Kaposi's sarcoma. Kaposi's sarcoma risk was higher in persons born in southern than in northern Italy. Significant increases were also observed for cancers of the lip, liver, kidney and for non-Hodgkin's lymphoma. PMID:15668710

  8. Serologic association of human herpesvirus eight with posttransplant Kaposi's sarcoma in Saudi Arabia.

    Science.gov (United States)

    Qunibi, W; Al-Furayh, O; Almeshari, K; Lin, S F; Sun, R; Heston, L; Ross, D; Rigsby, M; Miller, G

    1998-02-27

    In Saudi Arabia, Kaposi's sarcoma occurs in 4.1% of renal transplant recipients and accounts for 70% of malignancies in this group. Human herpes virus 8 (HHV8) has been identified in the DNA of many of these patients. The association between HHV8 and Kaposi's sarcoma was investigated further in post-renal transplant Kaposi's sarcoma patients from a tertiary care hospital (King Faisal Specialist Hospital and Research Center) in Riyadh, Saudi Arabia (n = 14), and non-Kaposi's sarcoma controls with renal transplant (n = 18), chronic renal failure (n = 14), other cancers that did not affect renal function (n = 15), and healthy volunteers (n = 15). The median time from transplant to Kaposi's sarcoma was 13 months. A serum sample was assumed to have antibodies to HHV8 if antibody to either p40 or sVCA was detected. The prevalence of HHV8 seroreactivity was 13/14 (93%) in cases, 5/18 (28%) in renal transplants without Kaposi's sarcoma, and 11/62 (18%) in the aggregate control group. HHV8 seroreactivity was significantly more common (p 0.001) among transplant patients with Kaposi's sarcoma than those without this cancer (odds ratio, 33.80; 95% confidence interval, 2.96-904). These findings suggest an etiologic link between HHV8 and Kaposi's sarcoma presumably due to immunologic or cellular factors that influence host-virus interactions.

  9. [Kaposi sarcoma and HHV-8: a model of cutaneous cancer in immunosuppressed patients].

    Science.gov (United States)

    Dupin, Nicolas; Deleuze, Jean

    2014-03-01

    The virus HHV-8 will celebrate its twentieth birthday by the end of this year and its relationships with Kaposi sarcoma are not completely elucidated. HHV-8 is an enigmatic virus, with an inhomogeneous distribution, a salivary transmission while it is not an ubiquitous virus, at least in western countries. However, HHV-8 has a unique genetic equipment rending is role in Kaposi sarcoma more than plausible. While the virus is necessary, it appears that it is not sufficient as the development of Kaposi sarcoma is frequently associated with immunosuppression whatever the cause (iatrogenic, viral, age-related). Kaposi sarcoma should be more considered as an opportunistic tumour than a viral-induced cancer and the best treatment for Kaposi sarcoma is immune restoration at least when it is possible.

  10. Myasthenia gravis developing in an HIV-negative patient with Kaposi's sarcoma.

    Science.gov (United States)

    Mantero, Vittorio; Mascolo, Maria; Bandettini di Poggio, Monica; Caponnetto, Claudia; Pardini, Matteo

    2013-07-01

    Myasthenia gravis is a disorder of neuromuscular transmission caused by autoimmune mechanisms. We reported a possible association between seropositive myasthenia gravis and Kaposi's sarcoma in a HIV-negative subject and the observed interactions between the treatment regimen for these two conditions. A 62-year-old man came to our attention for ocular myasthenia gravis. He suffered from a classic form of Kaposi's sarcoma since about 1 year. When myasthenic symptoms worsened, the patient was started on prednisone and azathioprine. The patient had a significant worsening of Kaposi's sarcoma, so prednisone and azathioprine were reduced and he was treated with vinblastine, with improvement both in dermatologic than in neurological symptomatology. We propose some considerations: the potential correlation between Kaposi's sarcoma and myasthenia gravis through immunological mechanism; myasthenia gravis as a paraneoplastic manifestation of Kaposi's sarcoma, and the role of an antitumoral agent as a treatment for both the conditions.

  11. Usefulness of F-18 FDG PET/CT in a case of Kaposi sarcoma with an unexpected bone lesion.

    Science.gov (United States)

    Morooka, Miyako; Ito, Kimiteru; Kubota, Kazuo; Yanagisawa, Kunio; Teruya, Katsuji; Hasuo, Kahehiro; Shida, Yoshitaka; Minamimoto, Rhogo; Kikuchi, Yoshimi; Oka, Shinichi

    2011-03-01

    Bone lesions of Kaposi sarcoma are rare. A 56-year-old man who was HIV positive and was diagnosed with Kaposi sarcoma on the basis of the results of a biopsy of skin lesions, underwent F-18 FDG PET/CT scan for detecting Kaposi sarcoma lesions and other AIDS-related diseases. An abnormal uptake was observed in the lumbar spine. MRI showed a diffuse enhanced spine lesion, and Ga-67 and ²⁰¹Tl scanning were negative. As a result, the lesion was considered to be a Kaposi sarcoma, and the shrinkage of the lesion was noted after the therapy for Kaposi sarcoma.

  12. Ser-634 and Ser-636 of Kaposi’s sarcoma-associated herpesvirus RTA are involved in transactivation and are potential CDK9 phosphorylation sites

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    Wan-Hua eTsai

    2012-02-01

    Full Text Available The replication and transcription activator (RTA of Kaposi’s sarcoma-associated herpesvirus (KSHV, K-RTA, is a lytic switch protein that moderates the reactivation process of KSHV latency. By mass spectrometric analysis of affinity-purified K-RTA, we showed that Thr-513 or Thr-514 was the primary in vivo phosphorylation site. Thr-513 and Thr-514 are proximal to the nuclear localization signal (527KKRK530 and were previously hypothesized to be target sites of Ser/Thr kinase hKFC. However, substitutions of Thr with Ala at 513 and 514 had no effect on K-RTA subcellular localization or transactivation activity. By contrast, replacement of Ser with Ala at Ser-634 and Ser-636 located in a Ser/Pro-rich region of K-RTA, designated as S634A/S636A, produced a polypeptide with ∼10 kDa shorter in molecular weight and reduced transactivation in a luciferase reporter assay relative to the wild type. In contrast to prediction, the decrease in molecular weight was not due to lack of phosphorylation because the overall Ser and Thr phosphorylation state in K-RTA and S634A/S636A were similar, excluding that Ser-634 or Ser-636 motif served as docking sites for consecutive phosphorylation. Interestingly, S634A/S636A lost ~30% immuno-reactivity to MPM2, an antibody specific to pSer/pThr-Pro motif, indicating that 634SPSP637 motif was in vivo phosphorylated. By in vitro kinase assay, we showed that K-RTA is a substrate of CDK9, a Pro-directed Ser/Thr kinase central to transcriptional regulation. Importantly, the capability of K-RTA in associating with endogenous CDK9 was reduced in S634A/S636A, which suggested that Ser-634 and Ser-636 may be involved in CDK9 recruitment. In agreement, S634A/S636A mutant exhibited ~30% reduction in KSHV lytic cycle reactivation relative to that by the wild type K-RTA. Taken together, our data propose that Ser-634 and Ser-636 of K-RTA are phosphorylated by host transcriptional kinase CDK9 and such a process contributes to a full

  13. ESCRT-I Protein Tsg101 Plays a Role in the Post-macropinocytic Trafficking and Infection of Endothelial Cells by Kaposi’s Sarcoma-Associated Herpesvirus

    Science.gov (United States)

    Kumar, Binod; Dutta, Dipanjan; Iqbal, Jawed; Ansari, Mairaj Ahmed; Roy, Arunava; Chikoti, Leela; Pisano, Gina; Veettil, Mohanan Valiya; Chandran, Bala

    2016-01-01

    Kaposi’s sarcoma-associated herpesvirus (KSHV) binding to the endothelial cell surface heparan sulfate is followed by sequential interactions with α3β1, αVβ3 and αVβ5 integrins and Ephrin A2 receptor tyrosine kinase (EphA2R). These interactions activate host cell pre-existing FAK, Src, PI3-K and RhoGTPase signaling cascades, c-Cbl mediated ubiquitination of receptors, recruitment of CIB1, p130Cas and Crk adaptor molecules, and membrane bleb formation leading to lipid raft dependent macropinocytosis of KSHV into human microvascular dermal endothelial (HMVEC-d) cells. The Endosomal Sorting Complexes Required for Transport (ESCRT) proteins, ESCRT-0, -I, -II, and–III, play a central role in clathrin-mediated internalized ubiquitinated receptor endosomal trafficking and sorting. ESCRT proteins have also been shown to play roles in viral egress. We have recently shown that ESCRT-0 component Hrs protein associates with the plasma membrane during macropinocytosis and mediates KSHV entry via ROCK1 mediated phosphorylation of NHE1 and local membrane pH change. Here, we demonstrate that the ESCRT-I complex Tsg101 protein also participates in the macropinocytosis of KSHV and plays a role in KSHV trafficking. Knockdown of Tsg101 did not affect virus entry in HMVEC-d and human umbilical vein endothelial (HUVEC) cells but significantly inhibited the KSHV genome entry into the nucleus and consequently viral gene expression in these cells. Double and triple immunofluorescence, proximity ligation immunofluorescence and co-immuoprecipitation studies revealed the association of Tsg101 with the KSHV containing macropinosomes, and increased levels of Tsg101 association/interactions with EphA2R, c-Cbl, p130Cas and Crk signal molecules, as well as with upstream and downstream ESCRT components such as Hrs (ESCRT-0), EAP45 (ESCRT-II), CHMP6 (ESCRT-III) and CHMP5 (ESCRT-III) in the KSHV infected cells. Tsg101 was also associated with early (Rab5) and late endosomal (Rab7) stages of

  14. Kaposi sarcoma related to acquired immunodeficiency syndrome: hepatic findings on computed tomography and magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Daniel Nobrega da; Viana, Publio Cesar Cavalcante; Maciel, Rosangela Pereira; Rocha, Manoel de Souza; Gebrim, Eloisa Maria Mello Santiago [Universidade de Sao Paulo (USP), SP (Brazil). Hospital das Clinicas. Inst. de Radiologia]. E-mail: dnobrega@gmail.com

    2008-03-15

    Kaposi sarcoma is a neoplasm associated with immunosuppressive conditions, and involving blood and lymphatic vessels. It is the most frequent intrahepatic neoplasm in patients with acquired immunodeficiency syndrome. Computed tomography and magnetic resonance imaging demonstrate multiple small nodules, prominence and contrast-enhancement of periportal branches due to the presence of the neoplastic tissue. The authors report a case of a 47-year-old male patient with acquired immunodeficiency syndrome presenting disseminated Kaposi sarcoma. (author)

  15. Non-AIDS Kaposi's sarcoma in the head and neck area.

    Science.gov (United States)

    Patrikidou, Anna; Vahtsevanos, Kostas; Charalambidou, Martha; Valeri, Rosalia-Maria; Xirou, Persefoni; Antoniades, Kostas

    2009-02-01

    Kaposi's sarcoma is classified into 4 types: classic (sporadic), African (endemic), iatrogenic (transplant recipients), and epidemic (acquired immunodeficiency syndrome [AIDS]-associated). This article aims to feature a comprehensive review of non-AIDS Kaposi's sarcoma, including literature review and report of 3 cases. Case material was from our hospital's archive. Literature review was conducted via electronic and manual medical database searches. Biological aspects, diagnostic difficulties, investigation protocols, and management modalities are discussed.

  16. Multicentric Castleman's disease and Kaposi's sarcoma in a cyclosporin treated, HIV-1 negative patient: case report

    Directory of Open Access Journals (Sweden)

    van Oers MHJ

    2003-12-01

    Full Text Available Abstract Background Multicentric Castleman's disease (MCD is a rare disease, but is more frequent in AIDS patients. MCD has only been reported twice before in patients receiving immunosuppressive therapy after renal transplantation, and never in patients receiving immunosuppressive therapy without transplantation. About half of the cases of MCD are human herpesvirus 8 (HHV8 – related, in contrast to Kaposi's sarcoma, a more common complication arising after immunosuppression, where the virus is found in virtually all cases. Case presentation We report a HIV-1 negative, non-transplant patient who developed HHV8-associated multicentric Castleman's disease and Kaposi's sarcoma after 17 years of immunosuppressive treatment with cyclosporin A for a minimal change nephropathy. Chemotherapy with liposomal doxorubicin resolved both symptoms of multicentric Castleman's disease and Kaposi's sarcoma in this patient. A concomitant decline in the HHV8 viral load in serum/plasma, as determined by a quantitative real-time PCR assay, was observed. Conclusions Multicentric Castleman's disease can be a complication of cyclosporin A treatment. Both multicentric Castleman's disease and Kaposi's sarcoma in this patient were responsive to liposomal doxorubicin, the treatment of choice for Kaposi's sarcoma at the moment, again suggesting a common mechanism linking both disorders, at least for HHV8-positive multicentric Castleman's disease and Kaposi's sarcoma. HHV8 viral load measurements can be used to monitor effectiveness of therapy.

  17. Classic Kaposi's sarcoma treated with elastic stockings and outpatient follow-up of a 90-year-old patient.

    Science.gov (United States)

    Trevisan, Flavia; Cunha, Paulo Rowilson; Pinto, Clovis Antonio Lopes; Alves, Celia Antonia Xavier de Moraes

    2013-01-01

    Kaposi's sarcoma is a multifactorial angioproliferative disorder. The herpes virus 8 human contributes to its pathogenesis, but it is uncertain whether these lesions are only reactive hyperplasia to the virus or neoplasia. Four clinical types are described: classic, endemic, iatrogenic and HIV-associated. Classic Kaposi's sarcoma has no standard staging or treatment protocols. Some studies have shown the use of compression stockings in the treatment of lymphedema associated with Kaposi's sarcoma. We report the case of a 90 year-old patient with classic Kaposi's sarcoma treated with compression stockings who showed a satisfactory response.

  18. Classic Kaposi's sarcoma treated with elastic stockings and outpatient follow-up of a 90-year-old patient*

    Science.gov (United States)

    Trevisan, Flavia; Cunha, Paulo Rowilson; Pinto, Clovis Antonio Lopes; Alves, Celia Antonia Xavier de Moraes

    2013-01-01

    Kaposi's sarcoma is a multifactorial angioproliferative disorder. The herpes virus 8 human contributes to its pathogenesis, but it is uncertain whether these lesions are only reactive hyperplasia to the virus or neoplasia. Four clinical types are described: classic, endemic, iatrogenic and HIV-associated. Classic Kaposi's sarcoma has no standard staging or treatment protocols. Some studies have shown the use of compression stockings in the treatment of lymphedema associated with Kaposi's sarcoma. We report the case of a 90 year-old patient with classic Kaposi's sarcoma treated with compression stockings who showed a satisfactory response. PMID:24346919

  19. Morphologic and immunophenotypic evidence of in-situ Kaposi's sarcoma

    Directory of Open Access Journals (Sweden)

    Pantanowitz Liron

    2006-10-01

    Full Text Available Abstract Background The spectrum of Kaposi's sarcoma (KS has been expanded to include pre-KS lesions. Case Presentation We report, for the first time, a case providing direct histological evidence of the development of early (in-situ KS from mediastinal lymphatic vessels in the setting of chronic lymphedema in an HIV-positive patient. Spindle-shaped and endothelial cells in these early KS-appearing lesions were immunoreactive for HHV8, D2-40 and CD34. Conclusion Our findings suggest that HHV8-infected spindle-shaped cells associated with lymphangiogenesis that evolve into KS lesions, acquire from the outset an aberrant mixed vascular and lymphatic endothelial cell phenotype.

  20. 经典型Kaposi,s肉瘤放射治疗加生物治疗%Radiotherapy combined with biotherapy for Classic Kaposi,s sarcoma

    Institute of Scientific and Technical Information of China (English)

    许素玲; 吉军; 张瑾熔; 木尼热

    2003-01-01

    目的分析了8例Kaposi,s肉瘤(KS)的临床特点和放疗加生物治疗的疗效. 方法采用60钴或加速器χ线和电子线混合射线常规分割照射,总量36~61Gy.生物疗法包括LAK细胞和干扰素、免疫核糖核酸.结果除例1放疗后2个月死于糖尿病、例6失访外,其余均获长期生存.生存1年以上6/8,3年以上4/8,5年以上2/8.结论放射线治疗对KS有效,较晚期根治剂量以50Gy左右为宜,同时加生物治疗可能可以提高疗效.

  1. Value of conventionally fractionated radiotherapy for the local treatment of HIV associated Kaposi`s sarcoma; Wertigkeit konventionell fraktionierter Radiotherapie bei der lokalen Behandlung des HIV-assoziierten Kaposi-Sarkoms

    Energy Technology Data Exchange (ETDEWEB)

    Saran, F. [Abt. fuer Strahlentherapie und Onkologie, Zentrum der Radiologie, Frankfurt Univ. (Germany); Adamietz, I.A. [Abt. fuer Strahlentherapie und Onkologie, Zentrum der Radiologie, Frankfurt Univ. (Germany); Mose, S. [Abt. fuer Strahlentherapie und Onkologie, Zentrum der Radiologie, Frankfurt Univ. (Germany); Thilmann, C. [Abt. fuer Strahlentherapie und Onkologie, Zentrum der Radiologie, Frankfurt Univ. (Germany); Boettcher, H.D. [Abt. fuer Strahlentherapie und Onkologie, Zentrum der Radiologie, Frankfurt Univ. (Germany)

    1995-10-01

    From June 1991 to June 1993, 43 patients with 111 HIV-associated Kaposi`s sarcoma of the skin or oral cavity were treated. Lesions were irradiated with 5 to 12 MeV electrons or 60Co gamma-rays. The fractionation scheme was 5 times 2 Gy/week for skin and enoral lesions with a total reference dosage of up to 20 Gy. Side effects were assessed during therapy and the therapeutic result 6 weeks after end of treatment. Thirty-eight out of 111 lesions were judged as complete response (CR) (34%), 61/111 as partial response (PR) (55%) and 12/111 were judged as no change (NC) (11%). Overall response (CR + PR) was 89%. Two patients with lesions of oral cavity suffered from RTOG grade-IV mucositis after 10 and 14 Gy. In 71/106 skin lesions (67%), radiation induced RTOG grade-I reactions were observed. Conclusion: In patients with HIV associated Kaposi`s sarcoma effective palliation can be achieved by means of radiotherapy with an overall dose of 20 Gy in conventional fractionation. Yet, the fraction of patients with complete responses is with 34 to 47% lower compared with doses above 20 Gy (66 to 100%). With reference to the reported data our results point to a dose-response relationship for Kaposi`s sarcoma. Therefore higher total reference doses, e.g. 30 Gy with weekly 5 times 2 Gy or 24 Gy with 5 times 1.6 Gy for mucous lesions, respectively, are suggested as by this mean the complete response rate can be coubled. (orig./MG) [Deutsch] Von Juni 1991 bis Juni 1993 wurden 43 Patienten mit 111 HIV-assoziierten Kaposi-Sarkomen der Haut oder des Mund- und Rachenraums behandelt. Die Laesionen wurden mit 5- bis 12-MeV-Elektronen oder Co-60-Gammastrahlen bestrahlt. Das Fraktionierungsschema betrug 5mal 2 Gy/Woche bei kutanen und enoralen Laesionen bis zu einer Gesamtreferenzdosis von 20 Gy. Nebenwirkungen wurden waehrend und das Ergebnis sechs Wochen nach Abschluss der Radiotherapie beurteilt. In 38 von 111 Laesionen wurde eine komplette Remission (CR) erzielt (34%), in 61/111 eine

  2. Insights into pathogenic events of HIV-associated Kaposi sarcoma and immune reconstitution syndrome related Kaposi sarcoma

    Directory of Open Access Journals (Sweden)

    Lemmer Johan

    2008-01-01

    Full Text Available Abstract A decrease in the incidence of human immune deficiency virus-associated Kaposi sarcoma (HIV-KS and regression of some established HIV-KS lesions is evident after the introduction of highly active anti-retroviral treatment (HAART, and is attributed to generalized immune restoration, to the reconstitution of human herpesvirus (HHV-8 specific cellular immune responses, and to the decrease in HIV Tat protein and HHV-8 loads following HAART. However, a small subset of HIV-seropositive subjects with a low CD4+ T cell count at the time of introduction of HAART, may develop HIV-KS as immune reconstitution inflammatory syndrome (IRIS within 8 weeks thereafter.

  3. Sarcoma de Kaposi primário do pênis Primary Kaposi's sarcoma of the penis

    Directory of Open Access Journals (Sweden)

    Maira Mitsue Mukai

    2009-10-01

    Full Text Available Sarcoma de Kaposi é um tumor vascular que afeta a parede dos vasos linfáticos. Possui quatro formas: clássica, endêmica, iatrogênica e associada ao HIV. É uma doença sistêmica, maligna, multifatorial e de curso variável. A apresentação inicial no pênis é rara, e mais observada em pacientes HIV positivos. Em pacientes HIV negativos, os casos que ocorrem nesta região, apresentam-se com pápulas, nódulos, placas e lesões verruciformes, assintomáticas. Para o tratamento da forma clássica, dispõem-se de excisão cirúrgica, crioterapia, eletrocirurgia, laser e radioterapia. Neste trabalho, é relatado um caso raro de um paciente com a forma clássica, em região peniana tratado com sucesso com radioterapia.Kaposi's sarcoma is a vascular tumor involving the wall of lymphatic vessels. There are four types: classic, endemic, iatrogenic and HIV-associated. It is a systemic, malignant and multifactorial disease and has a variable course. The primary presentation on the penis is uncommon and is mainly observed in HIV-positive patients. In HIV-negative individuals, asymptomatic papules, nodules, plaques and verrucous lesions are found. The treatment for the classic form involves surgery, cryotherapy, electrosurgery, laser and radiation therapy. The authors present a rare case of a patient with the classic form on the penis, who was successfully treated by radiation therapy.

  4. Cavernous hemangioma-like kaposi sarcoma: histomorphologic features and differential diagnosis.

    Science.gov (United States)

    Onak Kandemir, Nilüfer; Barut, Figen; Doğan Gün, Banu; Solak Tekin, Nilgün; Hallaç Keser, Sevinç; Oğuz Özdamar, Sükrü

    2013-01-01

    Aim. Cavernous hemangioma-like Kaposi sarcoma is a rare morphologic type of Kaposi sarcoma. So far there are no cases in the literature defining the histological features of this morphologic spectrum in detail. In this study we presented two classical-type cutaneous Kaposi sarcoma cases with histologic findings resembling cavernous hemangioma in company with clinical and histopathological data. Cases. One hundred and eighty-five classical-type cutaneous Kaposi sarcoma lesions in 79 patients were assessed retrospectively in terms of histopathological features. Findings of two cases showing features of cavernous hemangioma-like Kaposi sarcoma whose clinical data could be accessed were presented in accompany with the literature data. Both cases were detected to have bluish-purple, protruded, irregularly bordered cutaneous lesions. Histopathological examination revealed a lesion formed by cavernous hemangioma-like vascular structures organized in a lobular pattern that became dilated and filled with blood. Typical histological findings of early-stage KS, consisting of mononuclear inflammation, extravasated erythrocytes, and a few immature vascular structures in superficial dermis, were observed. All cases were serologically HIV-1 negative. A positive reaction with HHV-8, CD31, CD34, and D2-40 monoclonal antibodies was identified at both cavernous hemangioma-like areas and in immature vascular structures. Results. Cavernous hemangioma-like Kaposi sarcoma is a rare Kaposi sarcoma variant presenting with diagnostic challenges, that may be confused with hemangioma. As characteristic morphological features may not be observed in every case, it is important for diagnostic purposes to show immunohistochemical HHV-8 positivity in this variant.

  5. Immune reconstitution inflammatory syndrome Kaposi sarcoma in the liver manifesting as acute obstructive hepatitis: another potential role for montelukast?

    Science.gov (United States)

    Read, P J; Lucas, S; Morris, S; Kulasegaram, R

    2013-02-01

    Immune reconstitution inflammatory syndrome has been described in Kaposi sarcoma, but does not usually manifest as acute hepatitis. We describe a case of rapid obstructive jaundice after initiation of antiretroviral therapy, in which the liver biopsy confirmed hepatic Kaposi sarcoma, and the clinical course was altered by the addition of montelukast.

  6. Complete histological regression of Kaposi's sarcoma following treatment with protease inhibitors despite persistence of HHV-8 in lesions

    DEFF Research Database (Denmark)

    Benfield, T L; Kirk, O; Elbrønd, B;

    1998-01-01

    There is no current curative treatment for HIV-related Kaposi's sarcoma. The identification of human herpesvirus-8 as a possible aetiological agent suggests potential efficacy of anti-viral agents. We report here on the complete histological remission of Kaposi's sarcoma following treatment...

  7. Iatrogenic colorectal Kaposi sarcoma complicating a refractory ulcerative colitis in a human immunodeficiency negative-virus patient.

    Science.gov (United States)

    Hamzaoui, Lamine; Kilani, Houda; Bouassida, Mahdi; Mahmoudi, Moufida; Chalbi, Emna; Siai, Karima; Ezzine, Heykel; Touinsi, Hassen; Azzouz, Mohamed M'saddak; Sassi, Sadok

    2013-01-01

    Kaposi sarcoma is a mesenchymal tumor associated to a human herpes virus-8. It often occurs in human immunodeficiency virus-positive subjects. Colorectal localization is rare. We report the case of a colorectal Kaposi sarcoma complicating a refractory ulcerative colitis treated with surgery after the failure of immunomodulator therapy in a human immunodeficiency virus-negative heterosexual man.

  8. Beral et al's 1990 paper on Kaposi's sarcoma among persons with AIDS: demonstrating the power of descriptive epidemiology.

    Science.gov (United States)

    Newton, Robert; Whitby, Denise

    2016-10-01

    Here we discuss the impact of Beral et al's 1990 paper "Kaposi's sarcoma among persons with AIDS: a sexually transmitted infection?" Not only did this paper galvanise research into the underlying infectious cause of Kaposi's sarcoma, it also demonstrated the power of observational epidemiology in pointing the way towards major discoveries.

  9. Bilateral tonsillar and esophageal Kaposi sarcoma in an HIV-negative patient.

    Science.gov (United States)

    Ozbudak, Irem Hicran; Guney, Kenan; Mutlu, Derya; Gelen, Tekinalp; Ozbilim, Gulay

    2011-07-01

    Tonsillar involvement in Kaposi sarcoma is extremely rare, as only a few such cases have been reported; all but 1 of these previously reported cases occurred in patients with human immunodeficiency virus (HIV) infection. We describe what to the best of our knowledge is the first reported case of concurrent bilateral tonsillar and esophageal Kaposi sarcoma in an HIV-negative patient. A 68-year-old man presented with sore throat and dysphagia. Clinical examination revealed the presence of bilateral and asymmetrical tonsillar masses, as well as generalized lymphadenopathy in the cervical chain. The masses were resected, and findings on histopathologic analysis were consistent with Kaposi sarcoma. In addition, human herpesvirus 8 was demonstrated on a tonsil specimen by polymerase chain reaction, and microinvasive squamous cell carcinoma was also detected. Later, another Kaposi sarcoma lesion was detected in the lower third of the esophagus. We recommend that clinicians not discount the possibility of oral classic Kaposi sarcoma in the workup of an immunocompetent patient with oral vascular lesions.

  10. Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Sonja Koopal

    2007-09-01

    Full Text Available Kaposi sarcoma is a tumor consisting of Kaposi sarcoma herpesvirus (KSHV-infected tumor cells that express endothelial cell (EC markers and viral genes like v-cyclin, vFLIP, and LANA. Despite a strong link between KSHV infection and certain neoplasms, de novo virus infection of human primary cells does not readily lead to cellular transformation. We have studied the consequences of expression of v-cyclin in primary and immortalized human dermal microvascular ECs. We show that v-cyclin, which is a homolog of cellular D-type cyclins, induces replicative stress in ECs, which leads to senescence and activation of the DNA damage response. We find that antiproliferative checkpoints are activated upon KSHV infection of ECs, and in early-stage but not late-stage lesions of clinical Kaposi sarcoma specimens. These are some of the first results suggesting that DNA damage checkpoint response also functions as an anticancer barrier in virally induced cancers.

  11. Kaposi Sarcoma of the Adrenal Gland Resembling Epithelioid Angiosarcoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Hassan Huwait

    2011-01-01

    Full Text Available Patients with human immunodeficiency virus infection are known to have increased risk of various neoplasms, including Kaposi sarcoma, which classically involves the skin and mucosal locations. The anaplastic variant of Kaposi sarcoma is rare and poorly documented in the literature. It is characterised clinically by a more aggressive behaviour and increased metastatic potential, and histologically by increased cellularity, mitotic rate, and rarely by epithelioid angiosarcoma-like morphology. We report herein a 64-year-old man with a long-standing history of human immunodeficiency virus infection who developed a right adrenal tumor with a high-grade anaplastic angiosarcoma-like morphology. Immunohistochemistry for human herpes virus-8 was strongly positive in the tumor cells. To the best of our knowledge, this is the first report of an anaplastic Kaposi sarcoma in the adrenal gland.

  12. Kaposi sarcoma of the ureter after liver transplant: case report and literature review.

    Science.gov (United States)

    Chen, Yu; Zhao, Liang; Qiu, Shao-peng; He, Xiao-shun

    2012-02-01

    Kaposi sarcoma after an organ transplant is rare and infrequently involves internal organs. There are 2 reported cases in the English literature of Kaposi sarcoma originating from the transplant ureter after kidney transplant. We report a case of Kaposi sarcoma that occurred in the native ureter of the liver transplant recipient. Initially, the patient refused any further investigation and management and 2 years subsequent, had to undergo a left radical nephroureterectomy owing to the loss of renal function and distending pain. He recovered very well and no recurrence was detected at 47 months' follow-up. To our knowledge, it is the first report in English. We review the literature on this topic and explore the therapeutic principles and histologic features of this sarcoma.

  13. Intestinal Kaposi's sarcoma may mimic gastrointestinal stromal tumor in HIV infection

    Institute of Scientific and Technical Information of China (English)

    A Zoufaly; S Schmiedel; AW Lohse; J van Lunzen

    2007-01-01

    Diffuse intestinal Kaposi's sarcoma shares macroscopic and histopathologic features with gastrointestinal stromal tumors. Correct diagnosis may pose a clinical challenge.We describe the case of a young HIV-1-infected African lady without advanced immunodeficiency, who presented with a diffuse spindle cell tumor of the gut. Initial diagnosis was of a gastrointestinal stromal tumor, based on endoscopy and histopathology. Further evaluation revealed evidence for human herpesvirus 8 (HHV8) and the diagnosis had to be changed to diffuse intestinal Kaposi's sarcoma. Antiretroviral triple therapy together with chemotherapy was commenced, and has led to the rapid remission of intestinal lesions. With a background of HIV infection, the presence of HHV8 as the causative agent of Kaposi's sarcoma should be determined, as distinct treatment is indicated.

  14. Sarcoma de kaposi endemico en un paciente VIH negativo

    Directory of Open Access Journals (Sweden)

    José Revilla-López

    Full Text Available El sarcoma de Kaposi (SK es un cáncer angioproliferativo inflamatorio multifocal asociado a herpes virus 8 (VHH-8. Se han descrito cuatro variantes clínico-epidemiológicas: clásico, endémico, iatrogénico y epidémico o asociado a VIH. Clínicamente puede ser indolente o agresivo, afecta principalmente áreas mucocutáneas con eventual compromiso visceral y de ganglios linfáticos. Se presenta frecuentemente y de forma más agresiva en la población VIH positiva. Presentamos un caso de un paciente varón de 27 años VIH negativo con lesión tumoral sangrante en el anillo de Waldeyer, múltiples adenopatías y lesiones exofíticas en pie que remiten con quimioterapia de emergencia basada en antraciclinas. El SK VIH negativo es una condición poco frecuente. Es importante tener en cuenta al Perú como región endémica para el VHH-8. La afectación oral del SK es una manifestación rara y de mal pronóstico, sin embargo, el factor VIH negativo podría conferirle un buen pronóstico

  15. Activating KIR/HLA complexes in classic Kaposi's Sarcoma

    Directory of Open Access Journals (Sweden)

    Guerini Franca R

    2012-04-01

    Full Text Available Abstract Background Classic Kaposi's Sarcoma (cKS is a rare vascular tumor associated with Human Herpesvirus 8 (KSHV infection, nevertheless not all KSHV-infected individuals have cKS. Objective We investigated whether particular KIR/HLA receptor/ligand genotypes would be preferentially present in KSHV-infected and uninfected individuals who have or have not developed cKS. Methods KIR/HLA genotypes were analyzed by molecular genotyping in 50 KSHV-infected individuals who did or did not have cKS and in 33 age-and sex-matched KSHV seronegative individuals. Results There was no association of individual KIR, HLA or receptor ligand combinations with KSHV infection. However, activating KIR and KIR/HLA genotypes were significantly more frequent in cKS cases, specifically KIR3DS1, KIR2DS1, and KIR2DS1 with its HLA-C2 ligand. Conclusion A nonspecific inflammatory response triggered by activation of NK cells upon KIR-HLA interaction could be associated with the pathogenesis of KS.

  16. Acute upper gastrointestinal bleeding secondary to Kaposi sarcoma as initial presentation of HIV infection.

    Science.gov (United States)

    Mansfield, Sara A; Stawicki, Stanislaw P A; Forbes, Rachel C; Papadimos, Thomas J; Lindsey, David E

    2013-12-01

    Despite our decades of experience with Kaposi Sarcoma its true nature remains elusive. This angioproliferative disease of the vascular endothelium has a propensity to involve visceral organs in the immunocompromised population. There are four variants of the disease and each has its own pathogenesis and evolution. While the common sources of upper gastrointestinal bleeding are familiar to surgeons and critical care physicians, here we present the exceedingly rare report of upper gastrointestinal bleeding attributable to this malady, explore its successful management, and review the various forms of Kaposi Sarcoma including the strategies in regard to their management.

  17. Concomitant Kaposi sarcoma and multicentric Castleman's disease in a heart transplant recipient.

    Science.gov (United States)

    Patel, Ami; Bishburg, Eliahu; Zucker, Mark; Tsang, Patricia; Nagarakanti, Sandhya; Sabnani, Indu

    2014-01-01

    Post-transplant human herpes virus -8 (HHV-8)/Kaposi sarcoma herpes virus (KSHV) infection is associated with neoplastic and non-neoplastic diseases. Kaposi sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphomas (PEL) are the most common HHV-8-associated neoplastic complications described in solid organ transplant (SOT) patients. Concurrent KS and MCD have been previously described after transplantation only twice - once after liver transplantation and once after renal transplantation. We describe a unique heart transplant patient who also developed concurrent KS and MCD. To our knowledge this is the first documented case of a heart transplant recipient presenting with these two HHV-8-mediated complications at the same time.

  18. Kaposi's肉瘤中转化生长因子Ⅱ型受体基因的表达及意义%Expression of TGF -βR Ⅱ in Kaposi's sarcoma and its significance

    Institute of Scientific and Technical Information of China (English)

    邹云敏; 张德志; 靳颖; 郭芳; 普雄明

    2012-01-01

    Objective:To investigate the expression and significance of type Ⅱ transforming growth factor beta receptor ( TGF - βR Ⅱ ) in Kaposis sarcoma. Methods: The expression of TGF - βR Ⅱ was detected in 30 cases of Kaposis sarcoma and 30 cases of hemangiomas by immunohistochemical method. Results: Among 30 cases of Kaposis sarcoma 14 cases were positive (46. 7% ) ,20 cases were positive (66. 7% ) among 30 cases of hemangiomas (P0. 05). Conclusion; TGF - βR Ⅱ expression in the dermis of tumor may be correlate with Kaposis sarcoma.%目的:探讨Kaposi's肉瘤中转化生长因子Ⅱ型受体基因(TGF-βRⅡ)的表达特点及其意义.方法:采用免疫组织化学技术检测30例Kaposi's肉瘤组织和30例皮肤良性血管瘤组织中TGF-βRⅡ的表达.结果:TGF-βRⅡ基因在Kaposi's肉瘤真皮瘤体中的表达阳性率为46.7% (14/30),在血管瘤真皮瘤体中表达阳性率为66.7% (20/30),(P<0.05).TGF-βRⅡ基因在Kaposi's肉瘤表皮中表达的阳性率为63.3%( 19/30),在血管瘤表皮中为53.3% (16/30),差异没有统计学意义(P>0.05).结论:TGF-βRⅡ基因在真皮瘤体中的表达与Kaposi's肉瘤的发生相关.

  19. The role of radiotherapy in the treatment of a conventional Kaposi sarcoma; Place de la radiotherapie dans le traitement du sarcome de Kaposi classique

    Energy Technology Data Exchange (ETDEWEB)

    El Omrani, A.; Khouchani, M.; El Morjani, T.; Mharech, A.; Tahri, A. [CHU Mohammed-VI, Marrakech (Morocco)

    2011-10-15

    The authors report a study which aimed at establishing the epidemio-clinical and evolution profile of patients irradiated for a localized Kaposi sarcoma. This retrospective study is based on 10 patients treated between 2005 and 2009. All patients have been irradiated. Even though this pathology is a matter of discussion for its viral or genetic origin, its radio-sensitivity results in local control and a longer survival. Short communication

  20. L'atteinte osseuse dans le sarcome de Kaposi classique et agressif: à propos d'un cas

    Science.gov (United States)

    Sbiyaa, Mouhcine; El Alaoui, Adil; El Bardai, Mohammed; Mezzani, Amine; Lahrach, Kamal; Marzouki, Amine; Boutayeb, Fawzi

    2016-01-01

    Le sarcome de Kaposi classique est une tumeur rare multifocale d'origine des cellules endothéliales vasculaires à caractère évolutif progressif et peu maligne. L'atteinte viscérale dans le sarcome de kaposi est parfois observée chez les patients VIH positif par contre la dissémination tumorale dans les ganglions lymphatiques viscérales dans le SK classique reste très rare. On rapporte un cas rare de sarcome de kaposi classique agressif de la main avec une évolution rapide et destructive. PMID:27347285

  1. Histological Subgroups in Classic Kaposi Sarcoma: A Preliminary Study

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    Nilüfer Onak Kandemir

    2010-06-01

    Full Text Available Background and Design: Kaposi sarcomas (KS are vascular tumors with a low malignant potential which include overlapping infectious, immunologic, and neoplastic processes. Recently, many histological subtypes have been defined. Material and Method: In the present study, 151 cutaneous classic KS lesions in 56 patients were retrospectively evaluated with regard to histological subtypes. Determination of the subtypes was based on the predominant histopathological component in the lesion. We examined changes in epidermis and dermis along with intratumoral inflammatory response characteristics in the lesions. By defining histopathological variants of the cases, differences regarding subtypes were investigated. Results: Cases that bear the ordinary characteristics of KS and those that can not be classified otherwise, comprised 82..8% of the study group. Twenty-six cases showed consistency with the subtypes outlined in the literature in terms of their histopathological properties. The most common histological subtype was the lymphangiectatic variant in 7.3% of the cases. Bullous (2.6%, lymphangioma like (2.6%, intravascular (2%, and pyogenic granuloma like (2% variants were less common. The most uncommon histological subtype was micronodular (0.6% type. Lymphangiectatic, bullous, intravascular, and pyogenic granuloma like variants were frequently observed in the nodular stage of KSs. Lympangioma like changes were seen to be present in the early KS lesions. Lymphangiectatic type was oftenly associated with bullous component, whereas pyogenic granuloma like type demonstrated superficial ulceration and intense inflammatory response. Lymphangioma like and intravascular types exhibited a characteristic appearance, while other variants were accompanied by components belonging to different subtypes. Conclusion: In KS, histopathological subtypes can develop as a result of different pathological processes. The next stage of the current study, which is one of the

  2. MAPPING OF NATURAL KAPOSI SARCOMA INHIBITOR USING NETWORK BIOLOGY APPROACH

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    Jayadeepa R. M.

    2012-03-01

    Full Text Available Identification of protein-ligand interaction networks on a proteome scale is crucial to address a wide range of biological problems such as correlating molecular functions to physiological processes and designing safe and efficient therapeutics. In this study we have developed a novel computational strategy to identify ligand binding profiles of proteins across gene families and applied it to predicting protein functions, elucidating molecular mechanisms of drug adverse effects, and repositioning safe pharmaceuticals to treat different diseases The resultant network is then extrapolated to proteomics level to sort out the genes only expressed in the specific cancer types. The network is statistically analyzed and represented by the graphical interpretation to encounter the hub nodes. The objective of developing a biological networking is for the evaluation and validation of cancer drugs and their targets. In the field of cancer biology, the drug and their targets holds a role of paramount importance. With the work conducted here it shows the study of relation between drug target networks. Kaposi’s sarcoma (KS is a systemic disease which can present with cutaneous lesions with or without internal involvement. Genes belonging to the group of proto-oncogenes and tumor suppressors are best targeted for cancer studies. Biological networks like gene regulatory networks, protein interaction network is usually created to simplify the studies. In the present study, 26 proteins as receptor were selected for the study; all the receptors were responsible for the cause of Kaposi’s sarcoma. Also, 121 natural anti-Kaposi Sarcoma compounds were selected from different sources the natural components were the best component for blocking of abnormal activity.

  3. Large Mass Arising From the Tongue as an Initially and Sole Manifestation of Kaposi Sarcoma

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    Amir Feily, Esmaeil Rafeie, Zahra Moosavi, Ahmad Khazanee, Nastaran Ranjbari, Kambiz Masoumi, Omid Ghasemzadeh, Mosleh Safarpoor

    2011-01-01

    Full Text Available We report a 30- year-old Iranian woman presenting with a red to yellowish, well demarcated, painless exophytic and lobulated mass originating from the right hand side of the tongue. An excisional biopsy was obtained and it was diagnosed histopathologically as Kaposi's sarcoma by detecting atypical spindle cells with rare mitoses delineating blood-filled vascular slits.

  4. Primary Kaposi's sarcoma in lymph nodes concurrent with chronic lymphatic leukemia.

    Science.gov (United States)

    Weshler, Z; Leviatan, A; Krasnokuki, D; Kopolovitch, J

    1979-02-01

    Both Kaposi's sarcoma and chronic lymphatic leukemia affect the lymph nodes, and not infrequently, the same patient. The authors describe the occurrence of both diseases in the same lymph node. The rarity of this finding suggests different histopathogenic origins of the two diseases.

  5. Targeting mTOR in HIV-Negative Classic Kaposi's Sarcoma

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    Ofer Merimsky

    2008-01-01

    Full Text Available A 66-year old female with HIV-negative classic Kaposi's sarcoma responded to mTOR targeting by rapamycin. The response was well documented by PET-CT. This case provides supporting evidence that the mTOR pathway may be important in the tumorigenesis of KS and that rapamycin may have activity in this disease.

  6. Molecular and immunohistochemical detection of Kaposi sarcoma herpesvirus/human herpesvirus-8.

    Science.gov (United States)

    Chadburn, Amy; Wilson, Janet; Wang, Y Lynn

    2013-01-01

    Kaposi sarcoma herpesvirus/human herpesvirus-8 (KSHV/HHV-8) is etiologically related to the development of several human diseases, including Kaposi sarcoma, primary effusion lymphoma (PEL)/extra-cavitary (EC) PEL, multicentric Castleman disease (MCD), and large B-cell lymphoma arising in KSHV/HHV-8-associated multicentric Castleman disease. Although serologic studies can identify persons infected with this virus, molecular genetics, specifically PCR (polymerase chain reaction) and immunohistochemical techniques, are rapid, sensitive, and specific, and are able to more closely link KSHV/HHV-8 to a given disease process. As these KSHV/HHV-8-related diseases cause significant morbidity and mortality in affected individuals, the identification of the virus within lesional tissue will allow for more targeted therapy.

  7. Cutaneous HIV-associated Kaposi sarcoma: a potential setting for management by clinical observation.

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    Beatrous, Surget V; Grisoli, Stratton B; Riahi, Ryan R; Cohen, Philip R

    2017-06-15

    Kaposi sarcoma (KS) is a malignancy of viral etiology whose course ranges from cutaneous limited lesions to fulminant disease with multi-organ involvement. Four clinical variants of the disease exist: classic, endemic, iatrogenic, and epidemic. Iatrogenic and epidemic variants of Kaposi sarcoma develop in the setting of immune suppression. Transplant recipients who develop iatrogenic KS typically demonstrate improvement of lesions following de-escalation of immunosuppressive therapy. Similarly, HIV-infected patients who begin highly active antiretroviral therapy (HAART) experience immune reconstitution, which can induce KS regression. We describe two patients with varying clinical outcomes of cutaneous-limited HIV-associated KS after immune reconstitution with HAART. We propose that immune reconstitution with HAART, followed by clinical and radiographic surveillance for disease progression, may be an appropriate initial management strategy for limited cutaneous HIV-associated KS. In patients with more extensive disease at presentation or failure of HAART alone, antineoplastic therapy should be instituted.

  8. Kaposi's sarcoma of the small intestine after renal transplantation : radiological and endoscopic findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun; Song, Ha Hun; Kang, Si Won; Shinn, Kyung Sub; Ahn, Byung Min [Taejon St. Mary' s Hospital, the Catholic Univ. of Korea, Taejon (Korea, Republic of)

    1997-03-01

    A case of Kaposi's sarcoma involving the small bowel two years after receiving a renal transplant is described. Immunosuppression had been achieved using cyclosporine A and prednisolone. Lesions extended from the duodenum to the ileum;radiologically, they were demonstrated on small bowel follow-through study and computed tomography as multiple small nodular intraluminal masses with or without central umbilication, and endoscopically, were seen as intramural mucosal elevations with a central crater-like ulceration.

  9. Descriptive epidemiology of Kaposi sarcoma in Europe. Report from the RARECARE project.

    Science.gov (United States)

    Stiller, C A; Trama, A; Brewster, D H; Verne, J; Bouchardy, C; Navarro, C; Chirlaque, M D; Marcos-Gragera, R; Visser, O; Serraino, D; Weiderpass, E; Dei Tos, A P; Ascoli, V

    2014-12-01

    Kaposi sarcoma (KS) is a virus-related malignancy which most frequently arises in skin, though visceral sites can also be involved. Infection with Kaposi sarcoma herpes virus (KSHV or HHV-8) is required for development of KS. Nowadays, most cases worldwide occur in persons who are immunosuppressed, usually because of HIV infection or as a result of therapy to combat rejection of a transplanted organ, but classic Kaposi sarcoma is predominantly a disease of the elderly without apparent immunosuppression. We analyzed 2667 KS incident cases diagnosed during 1995-2002 and registered by 75 population-based European cancer registries contributing to the RARECARE project. Total crude and age-standardized incidence rate was 0.3 per 100,000 per year with an estimated 1642 new cases per year in the EU27 countries. Age-standardized incidence rate was 0.8 per 100,000 in Southern Europe but below 0.3 per 100,000 in all other regions. The elevated rate in southern Europe was attributable to a combination of classic Kaposi sarcoma in some Mediterranean countries and the relatively high incidence of AIDS in several countries. Five-year relative survival for 2000-2002 by the period method was 75%. More than 10,000 persons were estimated to be alive in Europe at the beginning of 2008 with a past diagnosis of KS. The aetiological link with suppressed immunity means that many people alive following diagnosis of KS suffer comorbidity from a pre-existing condition. While KS is a rare cancer, it has a relatively good prognosis and so the number of people affected by it is quite large. Thus it provides a notable example of the importance of networking in diagnosis, therapy and research for rare cancers.

  10. (18)F-FDG PET/CT findings in a case with HIV (-) Kaposi sarcoma.

    Science.gov (United States)

    Ozdemir, E; Poyraz, N Y; Keskin, M; Kandemir, Z; Turkolmez, S

    2014-01-01

    Although mucocutaneous sites are the most frequently encountered sites of involvement, Kaposi Sarcoma (KS) may also occasionally involve the breast and the skeletal, endocrine, urinary and nervous systems.. Various imaging modalities may be used to delineate the extent of the disease by detecting unexpected sites of involvement. Herein, we report a case of classical type KS, in whom staging with (18)F-FDG PET/CT imaging disclosed widespread disease and unexpected findings of bone and salivary gland involvement.

  11. Classic type of Kaposi's sarcoma and human herpesvirus 8 infection in Xinjiang, China.

    Science.gov (United States)

    Dilnur, P; Katano, H; Wang, Z H; Osakabe, Y; Kudo, M; Sata, T; Ebihara, Y

    2001-11-01

    We report 17 cases of the classic type of Kaposi's sarcoma in Xinjiang, which is located in the north-western area of China surrounded by Mongolia in the east, Russia in the north and Kazakhstan in the west. Fifteen of the patients were of the Uygur people. All patients were male and did not have acquired immunodeficiency syndrome. Most of the lesions were found in the lower and/or upper extremities, with 16 patients showing multiple lesions. Immunohistochemical examination of the lesions revealed that human herpesvirus 8 (HHV-8)-encoded latency-associated nuclear antigen was expressed in the nuclei of spindle-shaped tumor cells. HHV-8 DNA was detected by polymerase chain reaction in all seven cases examined. Phylogenetic tree analysis revealed that DNA sequences of the HHV-8-encoded K1 gene in the seven Kaposi's sarcoma cases were classified as subtype C that was common in the Mediterranean, the Middle East and East Asian countries. In addition, using immunofluorescence we investigated the seroprevalence of HHV-8 in 73 Uygur patients with diseases other than Kaposi's sarcoma. Surprisingly, the serological study revealed that 34 of the patients (46.6%) were positive for antibodies against HHV-8, suggesting that HHV-8 infection is widespread in Xinjiang area. The occurrence of the classic type of Kaposi's sarcoma with a high seropositivity rate implies that Xinjiang is the most endemic area for HHV-8 infection in the world known to date. Considering that Xinjiang is located at the middle point of the Silk Road that used to extend from Rome to China, these data imply that the virus may have been in circulation in this area due to the migration of the people via the Silk Road.

  12. Detection of Human Herpes Virus 8 in Kaposi's sarcoma tissues at the University Teaching Hospital, Lusaka, Zambia.

    Science.gov (United States)

    Tembo, Rabecca; Kaile, Trevor; Kafita, Doris; Chisanga, Chrispin; Kalonda, Annie; Zulu, Ephraim; Samutela, Mulemba; Polepole, Pascal; Kwenda, Geoffrey

    2017-01-01

    Human herpes virus-8, a γ2-herpes virus, is the aetiological agent of Kaposi sarcoma. Recently, Kaposi's sarcoma cases have increased in Zambia. However, the diagnosis of this disease is based on morphological appearance of affected tissues using histological techniques, and the association with its causative agent, Human Herpes virus 8 is not sought. This means poor prognosis for affected patients since the causative agent is not targeted during diagnosis and KS lesions may be mistaken for other reactive and neoplastic vascular proliferations when only histological techniques are used. Therefore, this study was aimed at providing evidence of Human Herpes virus 8 infection in Kaposi's sarcoma tissues at the University Teaching Hospital in Lusaka, Zambia. One hundred and twenty suspected Kaposi's sarcoma archival formalin-fixed paraffin-wax embedded tissues stored from January 2013 to December 2014 in the Histopathology Laboratory at the University Teaching Hospital, Lusaka, Zambia were analysed using histology and Polymerase Chain Reaction targeting the ORF26 gene of Human Herpes virus 8. The predominant histological type of Kaposi's sarcoma detected was the Nodular type (60.7%) followed by the plaque type (22.6%) and patch type (16.7%). The nodular lesion was identified mostly in males (40.5%, 34/84) than females (20.2%, 17/84) (p=0.041). Human Herpes virus 8 DNA was detected in 53.6% (45/84) and mostly in the nodular KS lesions (60%, 27/84) (p=0.035). The findings in this study show that the Human Herpes virus-8 is detectable in Kaposi's sarcoma tissues, and, as previously reported in other settings, is closely associated with Kaposi's sarcoma. The study has provided important baseline data for use in the diagnosis of this disease and the identification of the virus in the tissues will aid in targeted therapy.

  13. Endoscopic Appearance of Oropharyngeal and Upper GI Kaposi's Sarcoma in an Immunocompromised Patient

    Science.gov (United States)

    Renno, Anas; Khan, Zubair; Alkully, Turki; Kamal, Sehrish; Nawras, Ali

    2017-01-01

    Introduction. Kaposi's sarcoma (KS) usually manifests as a cutaneous disease but GI manifestation is often rare. It is associated with human herpes virus-8 (HHV-8) and seen in immunocompromised patients. In the USA, use of highly active antiretroviral therapy (HAART) has drastically reduced incidence of KS in HIV patients. Case Presentation. A 65-year-old male with human immunodeficiency virus (HIV) was admitted to the intensive care unit (ICU) with cardiopulmonary arrest secondary to hyperkalemia of 7.5 meq/L. Following placement of orogastric and endotracheal tube (ETT), a significant amount of blood was noticed in the ETT. Hemoglobin trended down from 9.6 mg/dL to 6.7 mg/dL over five days. Stool guaiac was positive. Esophagogastroduodenoscopy (EGD) was performed and revealed multiple large hypervascularized violaceous submucosal nodular lesions with stigmata of bleeding seen on the soft palate and pharynx and within the cricopharyngeal area close to the vocal cords. Biopsy of the soft palate lesions showed proliferation of neoplastic spindle shaped cells arranged in bundles with slit-like capillary spaces containing erythrocytes consistent with Kaposi's sarcoma. Biopsy was positive for HHV-8. Colonoscopy was unremarkable. There were no cutaneous manifestations of the disease. Conclusion. GI involvement of Kaposi's sarcoma must be considered in immunocompromised patients and can be confirmed by endoscopic methods.

  14. Endolysosomal trafficking of viral G protein-coupled receptor functions in innate immunity and control of viral oncogenesis.

    Science.gov (United States)

    Dong, Xiaonan; Cheng, Adam; Zou, Zhongju; Yang, Yih-Sheng; Sumpter, Rhea M; Huang, Chou-Long; Bhagat, Govind; Virgin, Herbert W; Lira, Sergio A; Levine, Beth

    2016-03-15

    The ubiquitin-proteasome system degrades viral oncoproteins and other microbial virulence factors; however, the role of endolysosomal degradation pathways in these processes is unclear. Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma, and a constitutively active viral G protein-coupled receptor (vGPCR) contributes to the pathogenesis of KSHV-induced tumors. We report that a recently discovered autophagy-related protein, Beclin 2, interacts with KSHV GPCR, facilitates its endolysosomal degradation, and inhibits vGPCR-driven oncogenic signaling. Furthermore, monoallelic loss of Becn2 in mice accelerates the progression of vGPCR-induced lesions that resemble human Kaposi's sarcoma. Taken together, these findings indicate that Beclin 2 is a host antiviral molecule that protects against the pathogenic effects of KSHV GPCR by facilitating its endolysosomal degradation. More broadly, our data suggest a role for host endolysosomal trafficking pathways in regulating viral pathogenesis and oncogenic signaling.

  15. Future accelerators (?)

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    John Womersley

    2003-08-21

    I describe the future accelerator facilities that are currently foreseen for electroweak scale physics, neutrino physics, and nuclear structure. I will explore the physics justification for these machines, and suggest how the case for future accelerators can be made.

  16. Clinical Features, Presence of Human Herpesvirus-8 and Treatment Results in Classic Kaposi Sarcoma

    Directory of Open Access Journals (Sweden)

    Özlem Su

    2008-12-01

    Full Text Available Background and Design: Classic Kaposi sarcoma (KS occurs predominantly among the elderly, with Jews, Italians and Greeks. Classic KS has been seen relatively frequently in Turkey. Our aim was to evaluate the demographic, clinical features of Kaposi sarcoma and etiopathological role of human herpesvirus-8 (HHV-8. Treatment results of 18 classic Kaposi’s sarcoma were also concluded.Material and Method: Eighteen cases of classic Kaposi sarcoma diagnosed as clinically and histopathologically between January 2001 and August 2008 in our dermatology department were taken to this study. Demographic, clinical features and treatment results were reviewed retrospectively in all patients. HHV-8 was investigated in the lesional skin of 7 patients.Results: A male/female ratio of 2/1 was found. Mean age at diagnosis was 67.2 (37-94 years. Bilaterally lower extremities were involved in 15 patients (83.3%, the trunk was involved in 3 patients (16.6%. Plaques and nodules were the common type of lesions (66.6% and 55.5%. Nine patients had no symptoms (50%. Edema was the most common symptom (38.8%. A second primary malignancy was found in 2 patients (11.1%. HHV-8 was detected in 6 of the 7 patients(85.7%. Majority of the patients were treated with interferon alfa (subcutaneously and cryotherapy as a monotherapy or a combination therapy. Imiquimod was the second agent in combined treatment (27.7%. Conclusion: We suggest that interferon alfa and imiquimod can be used as first line therapy agents with their antiviral and immunmodulatuar features in the treatment of KKS. (Turkderm 2008; 42: 122-6

  17. Kaposi Sarcoma of Childhood: Inborn or Acquired Immunodeficiency to Oncogenic HHV-8.

    Science.gov (United States)

    Jackson, Carolyn C; Dickson, Mark A; Sadjadi, Mahan; Gessain, Antoine; Abel, Laurent; Jouanguy, Emmanuelle; Casanova, Jean-Laurent

    2016-03-01

    Kaposi sarcoma (KS) is an endothelial malignancy caused by human herpes virus-8 (HHV-8) infection. The epidemic and iatrogenic forms of childhood KS result from a profound and acquired T cell deficiency. Recent studies have shown that classic KS of childhood can result from rare single-gene inborn errors of immunity, with mutations in WAS, IFNGR1, STIM1, and TNFRSF4. The pathogenesis of the endemic form of childhood KS has remained elusive. We review childhood KS pathogenesis and its relationship to inherited and acquired immunodeficiency to oncogenic HHV-8.

  18. Kaposi sarcoma in a fingolimod-treated patient with multiple sclerosis.

    Science.gov (United States)

    Walker, Susan; Brew, Bruce

    2016-09-01

    Kaposi sarcoma (KS) is a vascular tumour of endothelial cell origin, associated with human herpes virus 8. It develops in one of four clinical settings, one of which is iatrogenic immunosuppression. We present the case of a 46year-old man with relapsing-remitting multiple sclerosis who developed KS in the context of fingolimod use. To our knowledge, this is the second reported case of KS in a fingolimod-treated individual. This case highlights potential risks associated with immunosuppression with this medicine and ongoing need for vigilance in assessing for such complications.

  19. A rare coexistence - Chronic lymphocytic leukemia and Kaposi sarcoma: Case report and review of the literature

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    Muhammet Bekir Hacioglu

    2015-01-01

    Full Text Available Chronic lymphocytic leukemia (CLL is the most common leukemia worldwide. Skin lesions associated with CLL mostly develop on the bases of infectious or a hemorrhagic origin with an estimated incidence of 25% of all the cases. Kaposi sarcoma (KS-associated with human herpes virus-8 infection is a spindle-cell, malignant, low-grade tumor originating from vascular and lymphatic endothelium. KS mostly presents with skin lesions as the initial presentation. The relation between these two pathologies has not yet been clarified up to date. Herein, we report a case of KS along with CLL to illustrate the possible relation between these two pathologies.

  20. Association of genetic variations in miR-146a rs2910164 and miR-149 rs11614913 with the development of classic Kaposi sarcoma.

    Science.gov (United States)

    Yang, H; Lu, Q L; Wu, X J; Ma, H Y; Qu, Y Y; Zhang, D Z; Pu, X M

    2016-11-03

    Classic Kaposi sarcoma is a type of vascular proliferative inflammatory disease. Previous studies have reported significant associations between microRNAs expression and the development of classic Kaposi sarcoma. Here, we conducted a case-control study to investigate the association between miR-146a and miR-149 genetic polymorphisms and risk of classic Kaposi sarcoma in a Chinese population. Both classic Kaposi sarcoma patients and healthy controls were recruited between December 2013 and October 2015. Genotyping of miR-146a and miR-149 was performed by polymerase chain reaction-coupled with restriction fragment length polymorphism. Results showed that the GG genotype of miR-146a was associated with increased risk to classic Kaposi sarcoma (OR = 6.00, 95%CI = 1.19-30.12), as compared with the CC genotype. In the recessive model, we found that the GG genotype carried a 4.55-fold increased risk to classic Kaposi sarcoma as compared with the CC + CG genotype (OR = 2.06, 95%CI = 1.04-20.29). In conclusion, our study demonstrated that miR-146a, but not miR-149 polymorphism, is associated with risk to classic Kaposi sarcoma in the Chinese population.

  1. Consensus of the Brazilian Society of Infectious Diseases and Brazilian Society of Clinical Oncology on the management and treatment of Kaposi's sarcoma

    Directory of Open Access Journals (Sweden)

    Érico Arruda

    2014-06-01

    Full Text Available Kaposi's sarcoma is a multifocal vascular lesion of low-grade potential that is most often present in mucocutaneous sites and usually also affects lymph nodes and visceral organs. The condition may manifest through purplish lesions, flat or raised with an irregular shape, gastrointestinal bleeding due to lesions located in the digestive system, and dyspnea and hemoptysis associated with pulmonary lesions. In the early 1980s, the appearance of several cases of Kaposi's sarcoma in homosexual men was the first alarm about a newly identified epidemic, acquired immunodeficiency syndrome. In 1994, it was finally demonstrated that the presence of a herpes virus associated with Kaposi's sarcoma called HHV-8 or Kaposi's sarcoma herpes virus and its genetic sequence was rapidly deciphered. The prevalence of this virus is very high (about 50% in some African populations, but stands between 2% and 8% for the entire world population. Kaposi's sarcoma only develops when the immune system is depressed, as in acquired immunodeficiency syndrome, which appears to be associated with a specific variant of the Kaposi's sarcoma herpes virus. There are no treatment guidelines for Kaposi's sarcoma established in Brazil, and thus the Brazilian Society of Clinical Oncology and the Brazilian Society of Infectious Diseases developed the treatment consensus presented here.

  2. Accelerating Value Creation with Accelerators

    DEFF Research Database (Denmark)

    Jonsson, Eythor Ivar

    2015-01-01

    accelerator programs. Microsoft runs accelerators in seven different countries. Accelerators have grown out of the infancy stage and are now an accepted approach to develop new ventures based on cutting-edge technology like the internet of things, mobile technology, big data and virtual reality. It is also...... with the traditional audit and legal universes and industries are examples of emerging potentials both from a research and business point of view to exploit and explore further. The accelerator approach may therefore be an Idea Watch to consider, no matter which industry you are in, because in essence accelerators...

  3. The CB1/CB2 receptor agonist WIN-55,212-2 reduces viability of human Kaposi's sarcoma cells in vitro.

    Science.gov (United States)

    Luca, Tonia; Di Benedetto, Giulia; Scuderi, Mariagrazia Rita; Palumbo, Marco; Clementi, Silvia; Bernardini, Renato; Cantarella, Giuseppina

    2009-08-15

    Kaposi's sarcoma is a highly vascularized mesenchymal neoplasm arising with multiple lesions of the skin. Endogenous cannabinoids have been shown to inhibit proliferation of a wide spectrum of tumor cells. We studied the effects of cannabinoids on human Kaposi's sarcoma cell proliferation in vitro. To do so, we first investigated the presence of the cannabinoid receptors CB(1) and CB(2) mRNAs in the human Kaposi's sarcoma cell line KS-IMM by RT-PCR and, subsequently, the effects of the mixed CB(1)/CB(2) agonist WIN-55,212-2 (WIN) on cell proliferation in vitro. WIN showed antimitogenic effects on Kaposi's sarcoma cells. Western blot analysis of Kaposi's sarcoma lysates suggested that WIN treatment induced activation of both caspase-3 and -6, as well as increased phosphorylation of the stress kinase p38 and JNK, along with transient phosphorylation of ERK(1/2). To better characterize the involvement of each single CB receptor in cannabinoid-induced cell death, we incubated Kaposi's sarcoma cells with different selective cannabinoid receptor agonists, respectively ACEA (CB(1)) and JWH-133 (CB(2)). None of the agonists was able to induce KS-IMM cell apoptosis. Moreover, we co-incubated Kaposi's sarcoma cells with WIN-55,212-2 and either the CB(1) receptor antagonist AM251, the CB(2) receptor antagonist AM630, or a combination of both substances. The CB(2) receptor antagonist AM630 was able to significantly increase survival of Kaposi's sarcoma cells treated with WIN. In view of the antiproliferative effects of cannabinoids on KS-IMM cells, one could envision the cannabinoid system as a potential target for pharmacological treatment of Kaposi's sarcoma.

  4. Accelerating Value Creation with Accelerators

    DEFF Research Database (Denmark)

    Jonsson, Eythor Ivar

    2015-01-01

    Accelerators can help to accelerate value creation. Accelerators are short-term programs that have the objective of creating innovative and fast growing ventures. They have gained attraction as larger corporations like Microsoft, Barclays bank and Nordea bank have initiated and sponsored accelera......Accelerators can help to accelerate value creation. Accelerators are short-term programs that have the objective of creating innovative and fast growing ventures. They have gained attraction as larger corporations like Microsoft, Barclays bank and Nordea bank have initiated and sponsored...... an approach to facilitate implementation and realization of business ideas and is a lucrative approach to transform research into ventures and to revitalize regions and industries in transition. Investors have noticed that the accelerator approach is a way to increase the possibility of success by funnelling...

  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...

  6. T4/T8 ratio and absolute T4 cell numbers in different clinical stages of Kaposi's sarcoma in AIDS.

    Science.gov (United States)

    Spornraft, P; Fröschl, M; Ring, J; Meurer, M; Goebel, F D; Ziegler-Heitbrock, H W; Riethmüller, G; Braun-Falco, O

    1988-07-01

    Thirty-seven men (36 homosexual or bisexual and one heterosexual) with epidemic Kaposi's sarcoma and underlying HIV infection were followed up over a period of up to 32 months. Fourteen patients (38%) died, with a median survival time of 7.2 months after the diagnosis of AIDS. Seventeen patients (46%) presented with one or more opportunistic infections, mostly Pneumocystis carinii pneumonia. Eighteen patients (49%) had lymphadenopathy syndrome according to the definition of the CDC. Using the Laubenstein-classification of Kaposi's sarcoma, all patients either remained stable or deteriorated, improvement was never observed. Absolute T4 lymphocyte counts and the T4/T8 ratio were not related to the disease stage. With the onset of B symptoms (systemic symptoms), however, the absolute T4 numbers and the T4/T8 ratio markedly decreased. Delayed type hypersensitivity also showed no relationship to the clinical stages of Kaposi's sarcoma. Thus, the clinical progression of Kaposi's sarcoma lesions seems to be largely independent of the immunological parameters investigated. However, the onset of B symptoms was observed to be related to changes in immune status.

  7. Human herpes virus-8 DNA in bronchoalveolar lavage samples from patients with AIDS-associated pulmonary Kaposi's sarcoma

    DEFF Research Database (Denmark)

    Benfield, T L; Dodt, K K; Lundgren, Jens Dilling

    1997-01-01

    Kaposi's sarcoma (KS) is the most frequent AIDS-associated neoplasm, and often disseminates to visceral organs, including the lungs. An ante-mortem diagnosis of pulmonary KS is difficult. Recently, DNA sequences resembling a new human herpes virus (HHV-8), have been identified in various forms...

  8. Langerhans cells in anaplastic Kaposi sarcoma with a paucivascular phenotype: a potential diagnostic pitfall.

    Science.gov (United States)

    Ramdial, Pratistadevi K; Sing, Yetish; Naicker, Shaun; Calonje, Eduardo; Sewram, Vikash; Singh, Bhugwan

    2011-04-01

    Anaplastic Kaposi sarcoma (AKS), a rare variant of Kaposi sarcoma, has a poorly recognized histomorphologic spectrum, including a paucivascular phenotype, that mimics a range of undifferentiated malignancies. This study, that highlights the hitherto undocumented phenomenon of S100-protein-positive Langerhans cells (SLCs) as a potential diagnostic pitfall in paucivascular AKS, involved review of nine such AKS that required diagnostic immunohistochemical (IHC) work-up. All biopsies had a predominant or exclusive spindle or epithelioid cell infiltrate. The first three tumors were diagnosed as malignant peripheral nerve sheath tumor (2) and metastatic melanoma (1), based on S100-protein immunopositivity. Biopsy of a co-existent pigmented sole lesion (patient 3) demonstrated nodular KS. Subsequent IHC investigation of these three tumors demonstrated an endothelial phenotype and HHV8 immunopositivity, confirming AKS. CD1a and langerin staining of the S100-protein-positive cells confirmed Langerhans cells as the cause of the diagnostic pitfall. Subsequently, six further paucivascular AKS with intratumoral SLCs were recognized on histomorphological and IHC appraisal. In conclusion, heightened awareness of the histomorphologic spectrum, appropriate IHC investigation, and informed appraisal thereof, are critical to the diagnosis of AKS with an undifferentiated phenotype, and the avoidance of IHC pitfalls, such as those caused by under-recognition and misinterpretation of bystander SLCs in AKS.

  9. Supraglottic Kaposi's Sarcoma in HIV-Negative Patients: Case Report and Literature Review

    Science.gov (United States)

    Server, Ela A.; Durna, Yusuf M.; Yigit, Ozgur; Bozkurt, Erol R.

    2016-01-01

    This paper presents a case report of an HIV-negative, supraglottic Kaposi's sarcoma patient. The 80-year-old male patient was admitted with complaints of hoarseness, difficulty in swallowing, and a stinging sensation in his throat for approximately six months. The endoscopic larynx examination revealed a lesion which had completely infiltrated the epiglottis, reached right aryepiglottic fold, was vegetating, pink and purple in color, multilobular, fragile, and shaped like a bunch of grapes, and partially blocked the bleeding airway passage. The case was discussed by the hospital's head-neck cancer committee and a surgery decision was made. A tracheotomy was performed under local anesthesia before the operation due to respiratory distress and endotracheal intubation difficulty. Direct laryngoscopy showed that the mass was limited in the supraglottic area, had invaded the entire left aryepiglottic fold and one-third of the front right aryepiglottic fold, and completely covered epiglottis. It should be remembered that although rare, Kaposi's sarcoma may be encountered in larynx malignancy cases. Disease-free survival may be achieved through local excision and postoperative radiotherapy. PMID:27375914

  10. Kaposi's sarcoma herpesvirus and HIV-1 seroprevalences in prostitutes in Djibouti.

    Science.gov (United States)

    Marcelin, Anne-Geneviève; Grandadam, Marc; Flandre, Philippe; Nicand, Elisabeth; Milliancourt, Catherine; Koeck, Jean-Louis; Philippon, Michel; Teyssou, Remy; Agut, Henri; Dupin, Nicolas; Calvez, Vincent

    2002-10-01

    Kaposi's sarcoma herpesvirus (KSHV) is linked causally to Kaposi's sarcoma. Epidemiological studies have shown that KSHV transmission can occur during sex among homosexual men, but heterosexual transmission seems to be very rare in KSHV low prevalence countries. A seroepidemiological study was conducted to determine whether KSHV is transmitted sexually between heterosexuals in an endemic country. Sera from 282 subjects of African origin living in Djibouti were tested for antibodies to KSHV and HIV-1. Among the 282 individuals, 43 were female prostitutes working in the streets (group 1), 123 were female prostitutes working in luxury bars (group 2), 41 were non-prostitute females (group 3), and 75 were non-prostitute males (group 4). KSHV seroprevalence was 26, 20, 17, and 36% in groups 1, 2, 3, and 4, respectively. The seroprevalence of KSHV is not different between street or bar prostitutes and non-prostitute females (OR = 1.67; P = 0.34 and OR = 1.18; P = 0.73). These results suggest that in this endemic country commercial sex work does not seem to be a risk factor for KSHV infection and provides evidence against heterosexual transmission of KSHV in the female population studied.

  11. Human herpesvirus 8 (HHV-8 and the etiopathogenesis of Kaposi's sarcoma Herpesvírus humano tipo 8 (HHV-8 e a etiopatogênese do sarcoma de Kaposi

    Directory of Open Access Journals (Sweden)

    Jair Carneiro Leão

    2002-08-01

    Full Text Available OBJECTIVE: To review the current literature on human herpesvirus 8 with particular attention to the aspects related to the etiopathogenesis of Kaposi's sarcoma. MATERIALS AND METHODS: The authors searched original research and review articles on specific aspects of human herpesvirus 8 infection, including virology, epidemiology, transmission, diagnosis, natural history, therapy, and Kaposi's sarcoma etiopathogenesis. The relevant material was evaluated and reviewed. RESULTS: Human herpesvirus 8 is a recently discovered DNA virus that is present throughout the world but with major geographic variation. In the Western world, the virus, transmitted mainly by means of sexual contact, is strongly associated with Kaposi's sarcoma and body cavity-based lymphoma and more controversially with multiple myeloma and other non-proliferative disorders. There is no specific effective treatment, but HIV protease inhibitors may play an indirect role in the clearance of human herpesvirus 8 DNA from peripheral blood mononuclear cells of HIV-infected patients. Human herpesvirus 8 DNA is present in saliva, but there are as yet no documented cases of nosocomial transmission to health care workers. The prevalence of human herpesvirus 8 among health care workers is probably similar to that in the general population. CONCLUSION: Human herpesvirus 8 appears to be, at least in Western Europe and United States, restricted to a population at risk of developing Kaposi's sarcoma. Human herpesvirus 8 certainly has the means to overcome cellular control and immune responses and thus predispose carriers to malignancy, particularly Kaposi's sarcoma. The wide diffusion of Human herpesvirus 8 in classic Kaposi's sarcoma areas appears to represent an important factor in the high incidence of the disease. However, additional co-factors are likely to play a role in the development of Kaposi's sarcoma.OBJETIVO: O objetivo do presente artigo foi revisar a literatura recente em rela

  12. RECIRCULATING ACCELERATION

    Energy Technology Data Exchange (ETDEWEB)

    BERG,J.S.; GARREN,A.A.; JOHNSTONE,C.

    2000-04-07

    This paper compares various types of recirculating accelerators, outlining the advantages and disadvantages of various approaches. The accelerators are characterized according to the types of arcs they use: whether there is a single arc for the entire recirculator or there are multiple arcs, and whether the arc(s) are isochronous or non-isochronous.

  13. LIBO accelerates

    CERN Multimedia

    2002-01-01

    The prototype module of LIBO, a linear accelerator project designed for cancer therapy, has passed its first proton-beam acceleration test. In parallel a new version - LIBO-30 - is being developed, which promises to open up even more interesting avenues.

  14. Accelerating Inspire

    CERN Document Server

    AUTHOR|(CDS)2266999

    2017-01-01

    CERN has been involved in the dissemination of scientific results since its early days and has continuously updated the distribution channels. Currently, Inspire hosts catalogues of articles, authors, institutions, conferences, jobs, experiments, journals and more. Successful orientation among this amount of data requires comprehensive linking between the content. Inspire has lacked a system for linking experiments and articles together based on which accelerator they were conducted at. The purpose of this project has been to create such a system. Records for 156 accelerators were created and all 2913 experiments on Inspire were given corresponding MARC tags. Records of 18404 accelerator physics related bibliographic entries were also tagged with corresponding accelerator tags. Finally, as a part of the endeavour to broaden CERN's presence on Wikipedia, existing Wikipedia articles of accelerators were updated with short descriptions and links to Inspire. In total, 86 Wikipedia articles were updated. This repo...

  15. Horizontal Accelerator

    Data.gov (United States)

    Federal Laboratory Consortium — The Horizontal Accelerator (HA) Facility is a versatile research tool available for use on projects requiring simulation of the crash environment. The HA Facility is...

  16. Future accelerators

    CERN Document Server

    Hübner, K

    1999-01-01

    An overview of the various schemes for electron-positron linear colliders is given and the status of the development of key components and the various test facilities is given. The present studies of muon-muon colliders and very large hadron colliders are summarized including the plans for component development and tests. Accelerator research and development to achieve highest gradients in linear accelerators is outlined. (44 refs).

  17. Incidentally Detected Kaposi Sarcoma of Adrenal Gland with Anaplastic Features in an HIV Negative Patient

    Directory of Open Access Journals (Sweden)

    Zeliha Esin Celik

    2016-01-01

    Full Text Available Kaposi sarcoma (KS, a vascular tumor caused by infection with human herpesvirus 8 (HHV8, is a systemic disease that can present with cutaneous lesions with or without visceral involvement. Very few cases of KS, most of which were associated with AIDS, have been reported in the adrenal gland. Anaplastic transformation of KS is a rare clinical presentation known as an aggressive disease with local recurrence and metastatic potential. We report here a 47-year-old HIV negative male presented with extra-adrenal symptoms and had an incidentally detected anaplastic adrenal KS exhibited aggressive clinical course. To the best of our knowledge, this is the first case of anaplastic primary adrenal KS without mucocutaneous involvement but subsequently developed other side adrenal metastases in an HIV negative patient.

  18. 特发性出血性肉瘤(Kaposi's Sarcoma)

    Institute of Scientific and Technical Information of China (English)

    王家璧

    2004-01-01

    特发性出血性肉瘤(Kaposi's sarcoma,KS)由病毒感染所致,多数检测到人类疱疹病毒8型(HHV8),我国多发生在维吾尔族,汉族及蒙族也有报告.临床上分4型:经典型、地方性非洲型、艾滋病相关型和同种异质移植型.本文报告6例经典型KS,皮损均为紫红色斑块和结节.2例采用干扰素治疗获得较好疗效.

  19. Hepatic Kaposi sarcoma: A case report and review of the literature

    Science.gov (United States)

    Van Leer-Greenberg, Brett; Kole, Abhisake; Chawla, Saurabh

    2017-01-01

    Kaposi sarcoma (KS) is an aggressive cancer caused by human herpesvirus-8, primarily seen in immunocompromised patients. As opposed to the well-described cutaneous manifestations and pulmonary complications of KS, hepatic KS is rarely reported before death as most patients with hepatic KS do not manifest symptoms or evidence of liver injury. In patients with acquired immune deficiency syndrome, hepatic involvement of KS is present in 12%-24% of the population on incidental imaging and in approximately 35% of patients with cutaneous KS if an autopsy was completed after their death. Patients with clinically significant hepatic injury due to hepatic KS usually have an aggressive course of disease with hepatic failure often progressing to multi-organ failure and death. Here we report an unusual presentation of acute liver injury due to hepatic KS and briefly review the published literature on hepatic KS. PMID:28217255

  20. A multiplex panel of plasma markers of immunity and inflammation in classical kaposi sarcoma.

    Science.gov (United States)

    Aka, Peter V; Kemp, Troy J; Rabkin, Charles S; Shiels, Meredith S; Polizzotto, Mark N; Lauria, Carmela; Vitale, Francesco; Pinto, Ligia A; Goedert, James J

    2015-01-15

    Kaposi sarcoma (KS) risk is affected by perturbed immunity. Herein, we compared plasma from 15 human immunodeficiency virus (HIV)-negative classic KS cases to plasma from 29 matched controls, using a multiplex panel of immunity markers. Of 70 markers, CXCL10 (IP-10), sIL-1RII, sIL-2RA, and CCL3 (MIP-1A) were strongly and significantly associated with KS, after adjustment for age and smoking status. These and previous observations are consistent with a tumor-promoting role for these cytokines, particularly CXCL10, but the small sample size and case-control design preclude firm conclusions on KS risk or pathogenesis. Larger, well-designed prospective studies are needed to better assess the association of these markers with KS.

  1. Kaposi sarcoma in a HIV uninfected man who has sex with men

    Directory of Open Access Journals (Sweden)

    Potthoff A

    2010-02-01

    Full Text Available Abstract Kaposi's sarcoma (KS is a rare angioproliferative tumor associated with human herpesvirus 8 (HHV-8 infection. Four clinical variants of KS have been described: classic, endemic, iatrogenic and HIV-associated. We describe a 53-year-old men who had sex with men with a rapidly growing nodule on his left foot. Histologically KS was confirmed. Our patient did not match the clinical subgroups as HIV infection or other immune disorders could be ruled out. KS in HIV-negative MSM has only been reported sporadically. It was shown that KS in these patients clinically resembles classic KS but occurs at a younger age, is limited to the skin, and is associated with a good prognosis.

  2. Kaposi sarcoma secondary to endogenous adrenocorticotropic hormone-dependent Cushing syndrome.

    Science.gov (United States)

    Mayor-Ibarguren, A; Roldán-Puchalt, M C; Sancho-Bueso, T; Pérez-López, C; Álvarez-Linera, J; Frutos, R; Álvarez-Escolá, C; Regojo-Zapata, R; Beato-Merino, M J; Herranz-Pinto, P; Lecumberri, B

    2016-06-01

    Kaposi sarcoma (KS) is an angioproliferative tumour that develops as a result of an infection by human herpesvirus 8, which is considered a necessary cause but not sufficient. Other factors - genetic, immunological and environmental - might play a role in the development of the disease. We report a case of KS secondary to endogenous Cushing syndrome (ECS) due to a pituitary adenoma, an association that has been reported only once. We also conducted a search through the Medline and PubMed databases for cases involving KS and ECS, finding only three additional cases that shared common clinical and prognostic features with ours. ECS might favour the development of KS due to immunosuppression. Dermatologists and other clinicians should be aware of this association, as it might be an underdiagnosed condition. It also has an important impact on the management of KS, and based on this review it relies on a good prognosis when ECS is well controlled.

  3. Incidentally Detected Kaposi Sarcoma of Adrenal Gland with Anaplastic Features in an HIV Negative Patient

    Science.gov (United States)

    Celik, Murat; Sen, Erdem; Cebeci, Hakan; Ata, Ozlem; Yavas, Cagdas

    2016-01-01

    Kaposi sarcoma (KS), a vascular tumor caused by infection with human herpesvirus 8 (HHV8), is a systemic disease that can present with cutaneous lesions with or without visceral involvement. Very few cases of KS, most of which were associated with AIDS, have been reported in the adrenal gland. Anaplastic transformation of KS is a rare clinical presentation known as an aggressive disease with local recurrence and metastatic potential. We report here a 47-year-old HIV negative male presented with extra-adrenal symptoms and had an incidentally detected anaplastic adrenal KS exhibited aggressive clinical course. To the best of our knowledge, this is the first case of anaplastic primary adrenal KS without mucocutaneous involvement but subsequently developed other side adrenal metastases in an HIV negative patient.

  4. A case of pityriasis rubra pilaris with associated focal acantholytic dyskeratosis complicated by Kaposi's varicelliform eruption.

    Science.gov (United States)

    Erdag, Gulsun; Lockman, Deborah; Tromberg, Jennifer; Cropley, Thomas; Patterson, James W

    2011-11-01

    The clinical and histopathological diagnosis of pityriasis rubra pilaris (PRP) can be difficult because clinical findings are often subtle in early stages, and microscopic findings can overlap with those of other skin diseases. Focal acantholytic dyskeratosis (FAD) can rarely be seen in PRP and can mimic Darier's disease, Grover's disease or other disorders characterized by these histopathologic features. Kaposi's varicelliform eruption is a widespread infection due to herpes simplex virus (HSV) types 1 and 2, coxsackievirus A16 or vaccinia virus, occurring in a preexisting dermatosis; only one case has been reported in PRP. We report a patient with PRP whose biopsies showed both herpes simplex infection and FAD. A complete understanding of the mechanism behind this eruption evolved gradually, aided in great measure by the histopathologic findings. Copyright © 2011 John Wiley & Sons A/S.

  5. Kaposi sarcoma and lymphadenopathy syndrome: limitations of abdominal CT in acquired immunodeficiency syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Moon, K.L. Jr.; Federle, M.P.; Abrams, D.I.; Volberding, P.; Lewis, B.J.

    1984-02-01

    Abdominal computed tomography (CT) was performed in 31 patients with Kaposi sarcoma (KS) related to acquired immunodeficiency syndrome (AIDS), three patients with classic KS, and 12 patients with the newly described lymphadenopathy syndrome (LNS). The frequency, distribution, and appearance of lymphadenopathy and splenomegaly were similar in the AIDS-related KS and LNS groups. Rectal and perirectal disease was identified in 86% of homosexual men studied; rectal KS could not be distinguished from proctitis on CT criteria alone. No CT abnormalities were seen in patients with classic KS. The CT demonstration of retroperitoneal, mesenteric, or pelvic adenopathy or of rectal or perirectal disease in patients with AIDS-related KS is not necessarily indicative of widespread involvement with the disease.

  6. Relationship between oral Kaposi 's sarcoma and HAART: contribution of two case reports.

    Science.gov (United States)

    Campo-Trapero, Julián; Del Romero-Guerrero, Jorge; Cano-Sánchez, Jorge; Rodríguez-Martín, Carmen; Martínez-González, José Ma; Bascones-Martínez, Antonio

    2008-11-01

    Two HIV infected patients not receiving Highly Active Antiretroviral Treatment (HAART) presented with epidemic Kaposi's sarcoma of the oral cavity. One patient initially refused HAART, but when the lesion became large enough to be noticeable he agreed to HAART associated with excision of the intraoral lesion by CO2 laser. The other patient developed KS and progressed to AIDS at two years after ceasing HAART due to adverse effects; he was referred to hospital for renewed administration of HAART. In both cases, the lesions observed in the oral cavity were the first clinical manifestation of AIDS. These reports underline the close relationship between the use of HAART and the control of KS lesions, highlighting the important role of the dentist in the identification and early diagnosis of these oral lesions.

  7. Liposomal doxorubicin (Doxil): an effective new treatment for Kaposi's sarcoma in AIDS.

    Science.gov (United States)

    James, N D; Coker, R J; Tomlinson, D; Harris, J R; Gompels, M; Pinching, A J; Stewart, J S

    1994-01-01

    The objective of this study was to assess the efficacy and toxicity of a novel Stealth liposomal encapsulated formulation of doxorubicin (Doxil). A Phase I/II dose escalation study was carried out in a specialist HIV oncology unit in a teaching hospital (predominantly in an outpatient department). Fifteen patients with HIV related, biopsy confirmed, cutaneous Kaposi's sarcoma, with or without visceral involvement of sufficient severity to require systemic chemotherapy, were treated. Most patients had poor prognosis disease as assessed by the Tumour/Immune status/Systemic symptoms (TIS) system and Karnofsky indices; six patients had previously received combination chemotherapy. Primary treatment consisted of a dose of Doxil 10 mg/m2, repeated after 2 weeks. If the Kaposi's sarcoma (KS) responded and the treatment was tolerated, the patient began maintenance therapy at the same dose every 2 weeks. If there was no clinical response, the dose was increased to 20 mg/m2 for the further two cycles, before proceeding to maintenance therapy. Treatment continued until other intercurrent disease, lack of further response, patient preference, or toxicity precluded further treatment. Tumour response was assessed 2 weeks after completion of at least two cycles of chemotherapy. Toxicity was assessed for each cycle. Doxil was well tolerated, and toxicity was manageable, the principal toxicity being haematological. A partial response rate of 11/15 (73%) was achieved, with disease stabilization in the remaining patients. We conclude that Doxil is an effective palliative treatment for epidemic KS in a patient group with a poor predicted outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. AIDS-associated Kaposi's sarcoma is linked to advanced disease and high mortality in a primary care HIV programme in South Africa

    Directory of Open Access Journals (Sweden)

    Chu Kathryn M

    2010-07-01

    Full Text Available Abstract Background AIDS-associated Kaposi's sarcoma is an important, life-threatening opportunistic infection among people living with HIV/AIDS in resource-limited settings. In western countries, the introduction of combination antiretroviral therapy (cART and new chemotherapeutic agents has resulted in decreased incidence and improved prognosis of AIDS-associated Kaposi's sarcoma. In African cohorts, however, mortality remains high. In this study, we describe disease characteristics and risk factors for mortality in a public sector HIV programme in South Africa. Methods We analysed data from an observational cohort study of HIV-infected adults with AIDS-associated Kaposi's sarcoma, enrolled between May 2001 and January 2007 in three primary care clinics. Paper records from primary care and tertiary hospital oncology clinics were reviewed to determine the site of Kaposi's sarcoma lesions, immune reconstitution inflammatory syndrome stage, and treatment. Baseline characteristics, cART use and survival outcomes were extracted from an electronic database maintained for routine monitoring and evaluation. Cox regression was used to model associations with mortality. Results Of 6292 patients, 215 (3.4% had AIDS-associated Kaposi's sarcoma. Lesions were most commonly oral (65% and on the lower extremities (56%. One quarter of patients did not receive cART. The mortality and lost-to-follow-up rates were, respectively, 25 (95% CI 19-32 and eight (95% CI 5-13 per 100 person years for patients who received cART, and 70 (95% CI 42-117 and 119 (80-176 per 100 person years for patients who did not receive cART. Advanced T stage (adjusted HR, AHR = 5.3, p Patients with AIDS-associated Kaposi's sarcoma presented with advanced disease and high rates of mortality and loss to follow up. Risk factors for mortality included advanced Kaposi's sarcoma disease and lack of chemotherapy use. Contributing factors to the high mortality for patients with AIDS

  9. Absolute dose measurement Gafchromic R EBT2 movies. Case Study of Kaposis sarcoma; Medida de dosis absoluta con peliculas Gafchromic EBT2. Caso practico de un sarcoma de Kaposi

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, L.; Moral, F. del; Meilan, E.; Azevedo Gomes, J. C. de; Tejeiro Garcia, A. G.; Andrade Alvarez, B.; Vazquez, J.; Nieto, I.; Medal, D.; Lopez Medina, A.; Francisco, S.; Salgado, M.; Munoz, V.

    2011-07-01

    Because of its high spatial resolution, low energy dependence and good response over a wide energy range, EBT2 Gafchromic films are widely used in many applications in radiotherapy for measuring relative dose. Despite being the most common use can be used to measure absolute dose. This text is an example of using films as EBT2 for in vivo absolute dose in a Kaposis sarcoma.

  10. 肝肾联合移植术后并发Kaposi's肉瘤(附1例报告)%Complicated Kaposi's Sarcoma After Associated Transplantation of Liver and Kidney(Report from 1 case)

    Institute of Scientific and Technical Information of China (English)

    陈统清; 黄英伟; 肖观清

    2004-01-01

    目的:探讨器官移植受者并发Kaposi's肉瘤的发生率、原因及诊治.方法:回顾分析1例肝肾联合移植术后合并Kaposi's肉瘤患者的临床诊治经过.结果:患者于术后17个月起病,首发症状为腹膜后淋巴结肿大,随后出现腹股沟淋巴结肿大及腹部红褐色斑丘疹,经病理活检确诊,CsA减量联合小剂量化疗,起病半年死亡.结论:Kaposi's肉瘤是器官移植受者的常见并发症,发病常与免疫抑制过度及HHV-8病毒感染有关,诊断依赖于组织病理学检查,予小剂量化疗及减少免疫抑制剂的用量,临床愈后差.

  11. Kaposi sarcoma in association with molluscum contagiosum: an uncommon diagnosis in a single biopsy and potential diagnostic pitfall.

    Science.gov (United States)

    Prasad Busarla, Satya Vara; Sayed, Shahin; Nazarian, Rosalynn M; Gimbel, Devon C; Moloo, Zahir; Sohani, Aliyah R

    2012-02-01

    Molluscum contagiosum is a cutaneous poxviral infection that is rarely associated with other skin diseases, such as cutaneous neoplasms. Such associations are likely to be coincidental, except in immunocompromised patients. Kaposi sarcoma, an angioproliferative neoplasm derived from lymphatic endothelium, is mediated by human herpes virus-8 infection and occurs with increased frequency in immunocompromised individuals. We report an unusual case of molluscum contagiosum with underlying cutaneous Kaposi sarcoma diagnosed in a single skin biopsy of a human immunodeficiency virus-positive patient. Our case highlights the importance of adequate sampling to avoid missing secondary diagnoses in histopathologic sections and alerts pathologists and dermatologists to the possibility of coinfection in high-risk patients by 2 virally-mediated skin conditions.

  12. Human immunodeficiency virus-associated giant conjunctival Kaposi's sarcoma: complete remission with antiretroviral therapy and systemic chemotherapy.

    Science.gov (United States)

    Eduardo-Sánchez, Y W; Fernández-Agrafojo, D

    2017-09-05

    A 35-year-old male patient with a large unilateral haemorrhagic conjunctival tumour lesion and another contralateral haemorrhagic conjunctival flat lesion associated with violaceous cutaneous macules on the extremities and angiomatous lesions in the upper gastrointestinal tract as initial clinical manifestation of HIV-related immunodeficiency. Cutaneous, gastric mucosal and conjunctival biopsy was consistent with Kaposi's sarcoma with complete remission after highly active antiretroviral therapy and systemic chemotherapy. HIV-related conjunctival Kaposi's sarcoma, even a large one, can have a good response to antiretroviral therapy and systemic chemotherapy without any additional topical eye treatment. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. 皮肤卡波西肉瘤1例%A case report of skin kaposi's sarcoma

    Institute of Scientific and Technical Information of China (English)

    张新民; 唐蜜; 梁青春; 曾利红

    2002-01-01

    @@ 卡波西肉瘤(Kaposi's sarcoma)国内罕见,随着人体免疫缺陷病毒感染和获得性免疫缺陷综合症的流行,及免疫抑制剂的应用,国内已有个别报道.我院于2001年12月3日收治1例,现报告如下.

  14. Palatal Actinomycosis and Kaposi Sarcoma in an HIV-Infected Subject with Disseminated Mycobacterium avium-intracellulare Infection

    Directory of Open Access Journals (Sweden)

    Yuria Ablanedo-Terrazas

    2012-01-01

    Full Text Available Actinomyces and Mycobacterium avium-intracellulare are facultative intracellular organisms, members of the bacterial order actinomycetales. Although Actinomyces can behave as copathogen when anatomic barriers are compromised, its coinfection with Mycobacterium avium-intracellulare has not previously been reported. We present the first reported case of palatal actinomycosis co-infection with disseminated MAC, in an HIV-infected subject with Kaposi sarcoma and diabetes. We discuss the pathogenesis of the complex condition of this subject.

  15. The role of Ephs, Ephrins, and growth factors in Kaposi sarcoma and implications of EphrinB2 blockade

    OpenAIRE

    Scehnet, Jeffrey S.; Ley, Eric J.; Krasnoperov, Valery; Liu, Ren; Manchanda, Parmeet K.; Sjoberg, Eric; Kostecke, Anna P.; Gupta, Sachin; Kumar, S. Ram; Gill, Parkash S.

    2009-01-01

    Kaposi sarcoma (KS) is associated with human herpesvirus (HHV)-8 and is dependent on the induction of vascular endothelial growth factors (VEGFs). VEGF regulates genes that provide arterial or venous identity to endothelial cells, such as the induction of EphrinB2, which phenotypically defines arterial endothelial cells and pericytes, and represses EphB4, which defines venous endothelial cells. We conducted a comprehensive analysis of the Eph receptor tyrosine kinases to determine which membe...

  16. A Murine Fibroblast Growth Factor (FGF) Receptor Expressed in CHO Cells is Activated by Basic FGF and Kaposi FGF

    Science.gov (United States)

    Mansukhani, Alka; Moscatelli, David; Talarico, Daniela; Levytska, Vera; Basilico, Claudio

    1990-06-01

    We have cloned a murine cDNA encoding a tyrosine kinase receptor with about 90% similarity to the chicken fibroblast growth factor (FGF) receptor and the human fms-like gene (FLG) tyrosine kinase. This mouse receptor lacks 88 amino acids in the extracellular portion, leaving only two immunoglobulin-like domains compared to three in the chicken FGF receptor. The cDNA was cloned into an expression vector and transfected into receptor-negative CHO cells. We show that cells expressing the receptor can bind both basic FGF and Kaposi FGF. Although the receptor binds basic FGF with a 15- to 20-fold higher affinity, Kaposi FGF is able to induce down-regulation of the receptor to the same extent as basic FGF. The receptor is phosphorylated upon stimulation with both FGFs, DNA synthesis is stimulated, and a proliferative response is produced in cells expressing the receptor, whereas cells expressing the cDNA in the antisense orientation show none of these responses to basic FGF or Kaposi FGF. Thus this receptor can functionally interact with two growth factors of the FGF family.

  17. Maladie de Kaposi à localisation broncho-pulmonaire révélant une infection VIH

    Science.gov (United States)

    Sebbar, Amal; Zaghba, Nahid; Benjelloun, Hanane; Bakhatar, Abdelaziz; Yassine, Najiba

    2015-01-01

    La maladie de Kaposi (MK) associée au VIH, forme dite épidémique, a été décrite la 1ère fois en 1981 par Hymmes. C'est l'affection maligne la plus fréquente au cours du SIDA. La MK est à l'origine de 10% des atteintes pleuropulmonaires au cours de l'infection par le VIH et 40% des pneumopathies en cas de MK cutanéomuqueuse. Les localisations pulmonaires occupent la deuxième place des atteintes viscérales après la forme digestive. Le diagnostic repose sur des arguments épidémiologiques, cliniques, radiologiques, biologiques, endoscopiques et histologiques. Nous rapportons un cas de MK broncho-pulmonaire compliquant une infection VIH chez un patient présentant une maladie de Kaposi cutanée de découverte fortuite au cours de l'atteinte pulmonaire. Le diagnostic a été retenu après avoir éliminé les maladies opportunistes à tropisme pulmonaire. Le Kaposi pulmonaire constitue l'atteinte la plus grave de la MK-sida et la survie après le diagnostic est courte malgré les thérapeutiques agressives. PMID:26958142

  18. Accelerated Unification

    OpenAIRE

    Arkani-Hamed, Nima; Cohen, Andrew; Georgi, Howard

    2001-01-01

    We construct four dimensional gauge theories in which the successful supersymmetric unification of gauge couplings is preserved but accelerated by N-fold replication of the MSSM gauge and Higgs structure. This results in a low unification scale of $10^{13/N}$ TeV.

  19. Particle Accelerators in China

    Science.gov (United States)

    Zhang, Chuang; Fang, Shouxian

    As the special machines that can accelerate charged particle beams to high energy by using electromagnetic fields, particle accelerators have been widely applied in scientific research and various areas of society. The development of particle accelerators in China started in the early 1950s. After a brief review of the history of accelerators, this article describes in the following sections: particle colliders, heavy-ion accelerators, high-intensity proton accelerators, accelerator-based light sources, pulsed power accelerators, small scale accelerators, accelerators for applications, accelerator technology development and advanced accelerator concepts. The prospects of particle accelerators in China are also presented.

  20. MUON ACCELERATION

    Energy Technology Data Exchange (ETDEWEB)

    BERG,S.J.

    2003-11-18

    One of the major motivations driving recent interest in FFAGs is their use for the cost-effective acceleration of muons. This paper summarizes the progress in this area that was achieved leading up to and at the FFAG workshop at KEK from July 7-12, 2003. Much of the relevant background and references are also given here, to give a context to the progress we have made.

  1. Laser acceleration

    Science.gov (United States)

    Tajima, T.; Nakajima, K.; Mourou, G.

    2017-02-01

    The fundamental idea of Laser Wakefield Acceleration (LWFA) is reviewed. An ultrafast intense laser pulse drives coherent wakefield with a relativistic amplitude robustly supported by the plasma. While the large amplitude of wakefields involves collective resonant oscillations of the eigenmode of the entire plasma electrons, the wake phase velocity ˜ c and ultrafastness of the laser pulse introduce the wake stability and rigidity. A large number of worldwide experiments show a rapid progress of this concept realization toward both the high-energy accelerator prospect and broad applications. The strong interest in this has been spurring and stimulating novel laser technologies, including the Chirped Pulse Amplification, the Thin Film Compression, the Coherent Amplification Network, and the Relativistic Mirror Compression. These in turn have created a conglomerate of novel science and technology with LWFA to form a new genre of high field science with many parameters of merit in this field increasing exponentially lately. This science has triggered a number of worldwide research centers and initiatives. Associated physics of ion acceleration, X-ray generation, and astrophysical processes of ultrahigh energy cosmic rays are reviewed. Applications such as X-ray free electron laser, cancer therapy, and radioisotope production etc. are considered. A new avenue of LWFA using nanomaterials is also emerging.

  2. Accelerators and the Accelerator Community

    Energy Technology Data Exchange (ETDEWEB)

    Malamud, Ernest; Sessler, Andrew

    2008-06-01

    In this paper, standing back--looking from afar--and adopting a historical perspective, the field of accelerator science is examined. How it grew, what are the forces that made it what it is, where it is now, and what it is likely to be in the future are the subjects explored. Clearly, a great deal of personal opinion is invoked in this process.

  3. accelerating cavity

    CERN Multimedia

    On the inside of the cavity there is a layer of niobium. Operating at 4.2 degrees above absolute zero, the niobium is superconducting and carries an accelerating field of 6 million volts per metre with negligible losses. Each cavity has a surface of 6 m2. The niobium layer is only 1.2 microns thick, ten times thinner than a hair. Such a large area had never been coated to such a high accuracy. A speck of dust could ruin the performance of the whole cavity so the work had to be done in an extremely clean environment.

  4. Impact accelerations

    Science.gov (United States)

    Vongierke, H. E.; Brinkley, J. W.

    1975-01-01

    The degree to which impact acceleration is an important factor in space flight environments depends primarily upon the technology of capsule landing deceleration and the weight permissible for the associated hardware: parachutes or deceleration rockets, inflatable air bags, or other impact attenuation systems. The problem most specific to space medicine is the potential change of impact tolerance due to reduced bone mass and muscle strength caused by prolonged weightlessness and physical inactivity. Impact hazards, tolerance limits, and human impact tolerance related to space missions are described.

  5. Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood.

    Science.gov (United States)

    Byun, Minji; Ma, Cindy S; Akçay, Arzu; Pedergnana, Vincent; Palendira, Umaimainthan; Myoung, Jinjong; Avery, Danielle T; Liu, Yifang; Abhyankar, Avinash; Lorenzo, Lazaro; Schmidt, Monika; Lim, Hye Kyung; Cassar, Olivier; Migaud, Melanie; Rozenberg, Flore; Canpolat, Nur; Aydogan, Gönül; Fleckenstein, Bernhard; Bustamante, Jacinta; Picard, Capucine; Gessain, Antoine; Jouanguy, Emmanuelle; Cesarman, Ethel; Olivier, Martin; Gros, Philippe; Abel, Laurent; Croft, Michael; Tangye, Stuart G; Casanova, Jean-Laurent

    2013-08-26

    Kaposi sarcoma (KS), a human herpes virus 8 (HHV-8; also called KSHV)-induced endothelial tumor, develops only in a small fraction of individuals infected with HHV-8. We hypothesized that inborn errors of immunity to HHV-8 might underlie the exceedingly rare development of classic KS in childhood. We report here autosomal recessive OX40 deficiency in an otherwise healthy adult with childhood-onset classic KS. OX40 is a co-stimulatory receptor expressed on activated T cells. Its ligand, OX40L, is expressed on various cell types, including endothelial cells. We found OX40L was abundantly expressed in KS lesions. The mutant OX40 protein was poorly expressed on the cell surface and failed to bind OX40L, resulting in complete functional OX40 deficiency. The patient had a low proportion of effector memory CD4(+) T cells in the peripheral blood, consistent with impaired CD4(+) T cell responses to recall antigens in vitro. The proportion of effector memory CD8(+) T cells was less diminished. The proportion of circulating memory B cells was low, but the antibody response in vivo was intact, including the response to a vaccine boost. Together, these findings suggest that human OX40 is necessary for robust CD4(+) T cell memory and confers apparently selective protective immunity against HHV-8 infection in endothelial cells.

  6. Effects of triterpene derivatives from Maytenus rigida on VEGF-induced Kaposi's sarcoma cell proliferation.

    Science.gov (United States)

    Martucciello, Stefania; Balestrieri, Maria Luisa; Felice, Francesca; Estevam, Charles dos Santos; Sant'Ana, Antonio Euzébio Goulart; Pizza, Cosimo; Piacente, Sonia

    2010-02-12

    Betulinic acid (BA) is a naturally occurring lupane-type triterpene which exhibits a variety of biological activities including potent cytotoxic properties. On the basis of the structural similarity to BA, two lupane derivatives namely lup-20(29)-ene-3beta,30-diol (1) and lup-20(29)-ene-3beta,28-diol (2), along with two friedelane derivatives, namely friedelan-3-one (3) and friedelan-3beta-ol (4), isolated from the Brazilian plant Maytenus rigida, have been evaluated for their anti-proliferative effect. Similarly to BA, compounds 1 and 3 at 1 microM concentration significantly inhibited the VEGF-induced Kaposi's sarcoma (KS) cell proliferation by 50%. In contrast, this effect was not found in control endothelial cells (EC). Moreover, compounds 1 and 3 showed a dose-dependent effect on the apoptotic cell death, as detected by FACS analysis and caspase-3 assay. Specifically, at 10 microM concentration, apoptosis was significantly induced (from 45% to 55% of hypodiploid cells vs control cells) and showed the same potency order observed for the anti-proliferative effect at 1 microM, i.e., compound 3>BA>compound 1. Taking into account the interest given rise by BA as anticancer agent, the comparable anti-proliferative activity shown by compounds 1 and 3 and BA, can give an impulse to further investigate lupane and friedelane derivatives as cytotoxic agents.

  7. Changing Incidence and Risk Factors for Kaposi Sarcoma by Time Since Starting Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Wyss, Natascha; Zwahlen, Marcel; Bohlius, Julia

    2016-01-01

    BACKGROUND:  Kaposi sarcoma (KS) remains a frequent cancer in human immunodeficiency virus (HIV)-positive patients starting combination antiretroviral therapy (cART). We examined incidence rates and risk factors for developing KS in different periods after starting cART in patients from European...... observational HIV cohorts. METHODS:  We included HIV-positive adults starting cART after 1 January 1996. We analyzed incidence rates and risk factors for developing KS up to 90 and 180 days and 1, 2, 5, and 8 years after cART start and fitted univariable and multivariable Cox regression models. RESULTS:  We...... included 109 461 patients from 21 prospective clinical cohorts in Europe with 916 incident KS cases. The incidence rate per 100 000 person-years was highest 6 months after starting cART, at 953 (95% confidence interval, 866-1048), declining to 82 (68-100) after 5-8 years. In multivariable analyses adjusted...

  8. Risk Factors for Seropositivity to Kaposi Sarcoma–Associated Herpesvirus Among Children in Uganda

    Science.gov (United States)

    Webb, Emily L.; Sebina, Ismail; Nalwoga, Angela; Muhangi, Lawrence; Miley, Wendell; Johnston, W. Thomas; Ndibazza, Juliet; Whitby, Denise; Newton, Robert; Elliott, Alison M.

    2013-01-01

    Background: Determinants of Kaposi sarcoma–associated herpesvirus (KSHV) seropositivity among children living in sub-Saharan African populations where infection is endemic are not well understood. Local environmental factors, including other infectious agents, may be key. Methods: Within the context of a well-characterized birth cohort, we examined associations between various factors and antibodies against KSHV, measured in stored plasma samples from 1823 mother–child pairs in Entebbe, Uganda. Results: Seroprevalence increased with increasing age of the child (P = 0.0003) and was higher among those with KSHV seropositive mothers than in those without (12% vs 9%; odds ratio: 1.4, 95% confidence interval: 1.1 to 2.0). It was also higher among children with HIV infection (29% vs 10%; odds ratio: 3.1, 95% confidence interval: 1.2 to 8.3) or malaria parasitemia (30% vs 10%; odds ratio: 4.1, 95% confidence interval: 2.4 to 7.0) than in children without. These associations were not explained by socioeconomic status. Conclusions: The finding that KSHV serostatus is associated with malaria parasitemia in children is novel. In a country endemic for KSHV, malaria may be a cofactor for KSHV infection or reactivation among children. PMID:23403859

  9. [Characteristics of Kaposi's sarcoma. A retrospective study in a reference hospital].

    Science.gov (United States)

    Avilés Izquierdo, J A; García-Andrade, C Recarte; Gómez-Cornejo, L Pastor; Lazaro Ochaíta, P; de Portugal Alvarez, J

    2003-04-01

    Kaposi's angiosarcoma (SK) is a vascular tumour that affects skin and other organs. Nowadays there is thought that immunosuppression is one of the factors related with its genesis. Show the information corresponding to the distribution of the SK, proportion of subtypes, evolution and therapeutic used. A 28 cases retrospective study. We obtained the personal background, habits, origin of the VIH when the SK was associated with AIDS, and treatment carry out. Type of SK and location, cutaneous presentation, complications and B symptoms. Treatment, response and adverse effects. Progression of the disease, average time of relapse and survival, and presence of the SK at death. 64% epidemic, 21% classic type and 14% associated with transplants. In 48% of the epidemic cases, the VIH assumed to homosexual habits and 18% to being ADVP. In all there was cutaneous affectation, 46% had affectation of mucouses, 11% adenopathies and 14% visceral extension. 71% received treatment: 40% chemotherapy, 35% radiotherapy and 18% cryotherapy. Progression: 11% became stable, in 50% there was local extension and systemic in 17%. The average survival was of 4.16 +/- 3 years. SK has a minor incidence in the homosexual population. The high proportion of classic and transplants associated affirm the role of immunosuppression as a predisposing factor. There were numerous local complications that were associated with B symptoms. The cryotherapy was used as the first option in the located forms and in the widespread ones was the chemotherapy.

  10. Kaposi's sarcoma with HHV8 infection and ANCA-associated vasculitis in a hemodialysis patient.

    Science.gov (United States)

    Fatma, Lilia Ben; Rais, Lamia; Mebazza, Amel; Azzouz, Haifa; Beji, Somaya; Krid, Madiha; Smaoui, Wided; Maiz, Hedi Ben; Zouaghi, Karim; Zitouna, Moncef; Osmane, Amel Ben; Moussa, Fatma Ben

    2013-11-01

    The association between Kaposi's sarcoma (KS) and human herpes virus eight (HHV-8) infection is rarely reported in hemodialysis (HD) patients. We report here the rare association of KS, HHV-8 and hepatitis C virus (HCV) infection as well as syphilis in a HD patient. We report the case of a 72-year-old woman who presented with microscopic polyangiitis with alveolar hemorrhage and pauci-immune necrosing and crescentic glomerulonephritis as well as renal failure requiring HD. Biological tests showed positive HCV and syphilis tests. The patient was treated by HD and intravenous pulse, followed by oral corticosteroids and six cyclophosphamide monthly pulses with remission of the alveolar hemorrhage, but without renal functional recovery as the patient remained HD dependent. Five months after the first treatment administration, she developed extensive purpuric lesions on her lower limbs, abdomen face and neck. A skin biopsy showed KS. The HHV-8 test was positive, with positive polymerase chain reaction-HHV8 in the serum and skin. After immunosuppression withdrawal, the KS skin lesions regressed rapidly without relapse after 12 months of follow-up, but alveolar hemorrhage relapsed after 16 months of follow-up. Our case showed that the immunosuppressed state related to multiple factors such as aging, vasculitis, HHV-8, HCV, syphilis, immunosuppressive therapy and HD may all have contributed to the development of KS in our patient.

  11. Gastrointestinal Bleeding and Diffuse Skin Thickening as Kaposi Sarcoma Clinical Presentation

    Science.gov (United States)

    Querido, Sara; Sousa, Henrique Silva; Pereira, Tiago Assis; Birne, Rita; Matias, Patrícia; Jorge, Cristina; Weigert, André; Adragão, Teresa; Bruges, Margarida; Machado, Domingos

    2015-01-01

    A 56-year-old African patient received a kidney from a deceased donor with 4 HLA mismatches in April 2013. He received immunosuppression with basiliximab, tacrolimus, mycophenolate mofetil, and prednisone. Immediate diuresis and a good allograft function were soon observed. Six months later, the serum creatinine level increased to 2.6 mg/dL. A renal allograft biopsy revealed interstitial fibrosis and tubular atrophy grade II. Toxicity of calcineurin inhibitor was assumed and, after a switch for everolimus, renal function improved. However, since March 2014, renal function progressively deteriorated. A second allograft biopsy showed no new lesions. Two months later, the patient was admitted due to anuria, haematochezia with anaemia, requiring 5 units of packed red blood cells, and diffuse skin thickening. Colonoscopy showed haemorrhagic patches in the colon and the rectum; histology diagnosis was Kaposi sarcoma (KS). A skin biopsy revealed cutaneous involvement of KS. Rapid clinical deterioration culminated in death in June 2014. This case is unusual as less than 20 cases of KS with gross gastrointestinal bleeding have been reported and only 6 cases had the referred bleeding originating in the lower gastrointestinal tract. So, KS should be considered in differential diagnosis of gastrointestinal bleeding in some kidney transplant patients. PMID:26783491

  12. Recreational drug use and risk of Kaposi's sarcoma in HIV- and HHV-8-coinfected homosexual men.

    Science.gov (United States)

    Chao, Chun; Jacobson, Lisa P; Jenkins, Frank J; Tashkin, Donald; Martínez-Maza, Otoniel; Roth, Michael D; Ng, Leslie; Margolick, Joseph B; Chmiel, Joan S; Zhang, Zuo-Feng; Detels, Roger

    2009-02-01

    Experimental data suggested that exposure to recreational drugs might adversely affect antitumor immunity, which led us to examine the hypothesis that use of marijuana, cocaine, poppers, and amphetamines might increase the risk of Kaposi's sarcoma (KS) in HIV- and HHV-8-coinfected homosexual men. We analyzed data prospectively collected from the Multicenter AIDS Cohort Study (MACS) between 1984 and 2002. Among the 1335 HIV- and HHV-8-coinfected white men, 401 KS cases were identified. Multivariable Cox regression models were used to estimate the effects of time-varying recreational drug use on KS risk adjusting for potential confounders. The effects of both recent use (6 months prior) of recreational drugs and lagged exposure (i.e., use from 3 and 5 years prior) were examined. We did not observe any clear association with KS for recent use of any of the four drugs. In the analyses using lagged exposures, KS risk was associated with use of poppers 3-5 years prior [hazard ratio (HR)(3 years prior) = 1.27, 95% CI (0.97-1.67), HR(5 years prior) = 1.46 (1.01-2.13)]. However, no clear dose-response relationship was observed. These findings do not support a biological association between use of these substances and KS development in HIV- and HHV-8-coinfected homosexual men.

  13. Kaposi's sarcoma herpesvirus microRNAs target caspase 3 and regulate apoptosis.

    Directory of Open Access Journals (Sweden)

    Guillaume Suffert

    2011-12-01

    Full Text Available Kaposi's sarcoma herpesvirus (KSHV encodes a cluster of twelve micro (miRNAs, which are abundantly expressed during both latent and lytic infection. Previous studies reported that KSHV is able to inhibit apoptosis during latent infection; we thus tested the involvement of viral miRNAs in this process. We found that both HEK293 epithelial cells and DG75 cells stably expressing KSHV miRNAs were protected from apoptosis. Potential cellular targets that were significantly down-regulated upon KSHV miRNAs expression were identified by microarray profiling. Among them, we validated by luciferase reporter assays, quantitative PCR and western blotting caspase 3 (Casp3, a critical factor for the control of apoptosis. Using site-directed mutagenesis, we found that three KSHV miRNAs, miR-K12-1, 3 and 4-3p, were responsible for the targeting of Casp3. Specific inhibition of these miRNAs in KSHV-infected cells resulted in increased expression levels of endogenous Casp3 and enhanced apoptosis. Altogether, our results suggest that KSHV miRNAs directly participate in the previously reported inhibition of apoptosis by the virus, and are thus likely to play a role in KSHV-induced oncogenesis.

  14. Radiation therapy of epidemic kaposi sarcoma: the Henri-Mondor hospital experience (643 patients); Radiotherapie du sarcome de kaposi epidemique: l`experience de l`hopital Henri-Mondor (643 patients)

    Energy Technology Data Exchange (ETDEWEB)

    Belembaogo, E.; Kirova, Y.; Frikha, H.; Yu, S.; Piedbois, P.; Le Bourgeois, J.P. [Hopital Henri-Mondor, 94 - Creteil (France). Dept. de cancerologie

    1998-01-01

    From June 1986 to December 1996, 643 patients presenting with acquired immunodeficiency syndrome (AIDS)-related epidemic Kaposi`s sarcoma were treated with irradiation at the Oncology Department of Henri Mondor University Hospital. Three-hundred eighty-seven patients (60 %) had previously received a treatment with interferon (259 patients, 40.2 %), vinblastine (225 patients, 34.5 %), doxorubicin (22 patients, 3.4 %), bleomycin (19 patients, 2.9 %), and/or antiviral treatment (216, 33.5 %). The radiotherapy was delivered by 4 MeV OR 8 MeV electron beam for extended cutaneous fields and 45-100 kV x-ray for localized fields. The delivered dose was 20 Gy in 2 weeks (2.5 Gy/fraction, 4 fractions/week) followed by 2 weeks rest and second series of 10 Gy in 1 week. For oral cavity lesions, we used a series of 15.2 Gy was delivered (1.9 Gy/fraction, 4 fractions/week), followed for three patients by a 3 week rest and by a similar second series of 15.2 Gy.Six-hundred and twenty-one patients were evaluable and the objective response rate was 92 %, with e complete regression of clinical and functional symptoms for all patients. The skin tolerance was good, with 7.3 % grade I reactions, 69.3 % of grade II reactions, and 23.4 % grade III reactions. There was a correlation between recurrence rate and the occurrence of opportunistic infections. This analysis shows the efficacy of dose radiotherapy for treatment of epidemic Kaposi sarcoma. (author)

  15. Aqueous immersion technique for the irradiation with photons Kaposi's sarcoma multiple foot and ankle; Tecnica de inmersion acuosa para la irradiacion con fotones del sarcoma de Kaposi multiple en pies y tobillos

    Energy Technology Data Exchange (ETDEWEB)

    Velazquez Miranda, S.; Munoz Carmona, D. M.; Ortyiz Seidel, M.; Gomez-Millan Barrachina, J.; Delgado Gil, M. M.; Ortega Rodriguez, M. J.; Dominguez Rodriguez, M.; Marquez Garcia Salazar, M.; Bayo Lozano, E.

    2011-07-01

    Classic Kaposi sarcoma presents as asymptomatic red-violaceus plaques, usually on the legs below the knees, ankles and soles preferentially. When the disease is spread on the skin preferential treatment is radiation therapy at low doses. Homogeneous irradiation of the various lesions could be very complex due to the irregular geometry of the feet, interdigital lesions on different planes. To overcome this problem, and in the case of disseminated disease and low doses, we propose the technique of dipping the tip in Cuba expanded polystyrene filled with saline with a methacrylate plate 2 cm in depth and irradiation with parallel opposed fields.

  16. Characterization of the complement inhibitory function of rhesus rhadinovirus complement control protein (RCP).

    Science.gov (United States)

    Okroj, Marcin; Mark, Linda; Stokowska, Anna; Wong, Scott W; Rose, Nicola; Blackbourn, David J; Villoutreix, Bruno O; Spiller, O Brad; Blom, Anna M

    2009-01-02

    Rhesus rhadinovirus (RRV) is currently the closest known, fully sequenced homolog of human Kaposi sarcoma-associated herpesvirus. Both these viruses encode complement inhibitors as follows: Kaposi sarcoma-associated herpesvirus-complement control protein (KCP) and RRV-complement control protein (RCP). Previously we characterized in detail the functional properties of KCP as a complement inhibitor. Here, we performed comparative analyses for two variants of RCP protein, encoded by RRV strains H26-95 and 17577. Both RCP variants and KCP inhibited human and rhesus complement when tested in hemolytic assays measuring all steps of activation via the classical and the alternative pathway. RCP variants from both RRV strains supported C3b and C4b degradation by factor I and decay acceleration of the classical C3 convertase, similar to KCP. Additionally, the 17577 RCP variant accelerated decay of the alternative C3 convertase, which was not seen for KCP. In contrast to KCP, RCP showed no affinity to heparin and is the first described complement inhibitor in which the binding site for C3b/C4b does not interact with heparin. Molecular modeling shows a structural disruption in the region of RCP that corresponds to the KCP-heparin-binding site. This makes RRV a superior model for future in vivo investigations of complement evasion, as RCP does not play a supportive role in viral attachment as KCP does.

  17. High prevalence of antibodies to human herpesvirus 8 in relatives of patients with classic Kaposi's sarcoma from Sardinia

    OpenAIRE

    Angeloni, Antonio; Heston, Lee; Uccini, Stefania; Sirianni, Maria Caterina; Cottoni, Francesca Maria Giovanna; Masala, Maria Vittoria; Cerimele, Decio; Lin, Su-Fang; Sun, Ren; Rigsby, Michael; Faggioni, Alberto; Miller, George

    1998-01-01

    A survey for antibodies to a recombinant small viral capsid antigen (sVCA) of human herpesvirus type 8 (HHV‐8) was conducted in Sardinia, one of the world's highest incidence areas for classic Kaposi's sarcoma (KS). Prevalence of antibodies to HHV‐8 sVCA was greatest in patients with KS (95%), followed by family members (39%) and a Sardinian control population age‐ and sex‐matched to the relatives (11%). Within families, prevalence of antibodies was about equal among spouses, children, and si...

  18. A rare coexistence--Chronic lymphocytic leukemia and Kaposi sarcoma: Case report and review of the literature.

    Science.gov (United States)

    Hacioglu, Muhammet Bekir; Sahin, Suleyman; Karatas, Fatih; Aytekin, Aydın

    2015-01-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia worldwide. Skin lesions associated with CLL mostly develop on the bases of infectious or a hemorrhagic origin with an estimated incidence of 25% of all the cases. Kaposi sarcoma (KS)-associated with human herpes virus-8 infection is a spindle-cell, malignant, low-grade tumor originating from vascular and lymphatic endothelium. KS mostly presents with skin lesions as the initial presentation. The relation between these two pathologies has not yet been clarified up to date. Herein, we report a case of KS along with CLL to illustrate the possible relation between these two pathologies.

  19. A prospective ascertainment of cancer incidence in sub-Saharan Africa: The case of Kaposi sarcoma.

    Science.gov (United States)

    Semeere, Aggrey; Wenger, Megan; Busakhala, Naftali; Buziba, Nathan; Bwana, Mwebesa; Muyindike, Winnie; Amerson, Erin; Maurer, Toby; McCalmont, Timothy; LeBoit, Philip; Musick, Beverly; Yiannoutsos, Constantin; Lukande, Robert; Castelnuovo, Barbara; Laker-Oketta, Miriam; Kambugu, Andrew; Glidden, David; Wools-Kaloustian, Kara; Martin, Jeffrey

    2016-05-01

    In resource-limited areas, such as sub-Saharan Africa, problems in accurate cancer case ascertainment and enumeration of the at-risk population make it difficult to estimate cancer incidence. We took advantage of a large well-enumerated healthcare system to estimate the incidence of Kaposi sarcoma (KS), a cancer which has become prominent in the HIV era and whose incidence may be changing with the rollout of antiretroviral therapy (ART). To achieve this, we evaluated HIV-infected adults receiving care between 2007 and 2012 at any of three medical centers in Kenya and Uganda that participate in the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium. Through IeDEA, clinicians received training in KS recognition and biopsy equipment. We found that the overall prevalence of KS among 102,945 HIV-infected adults upon clinic enrollment was 1.4%; it declined over time at the largest site. Among 140,552 patients followed for 319,632 person-years, the age-standardized incidence rate was 334/100,000 person-years (95% CI: 314-354/100,000 person-years). Incidence decreased over time and was lower in women, persons on ART, and those with higher CD4 counts. The incidence rate among patients on ART with a CD4 count >350 cells/mm(3) was 32/100,000 person-years (95% CI: 14-70/100,000 person-years). Despite reductions over time coincident with the expansion of ART, KS incidence among HIV-infected adults in East Africa equals or exceeds the most common cancers in resource-replete settings. In resource-limited settings, strategic efforts to improve cancer diagnosis in combination with already well-enumerated at-risk denominators can make healthcare systems attractive platforms for estimating cancer incidence.

  20. Nationwide registry-based analysis of cancer clustering detects strong familial occurrence of Kaposi sarcoma.

    Science.gov (United States)

    Kaasinen, Eevi; Aavikko, Mervi; Vahteristo, Pia; Patama, Toni; Li, Yilong; Saarinen, Silva; Kilpivaara, Outi; Pitkänen, Esa; Knekt, Paul; Laaksonen, Maarit; Artama, Miia; Lehtonen, Rainer; Aaltonen, Lauri A; Pukkala, Eero

    2013-01-01

    Many cancer predisposition syndromes are rare or have incomplete penetrance, and traditional epidemiological tools are not well suited for their detection. Here we have used an approach that employs the entire population based data in the Finnish Cancer Registry (FCR) for analyzing familial aggregation of all types of cancer, in order to find evidence for previously unrecognized cancer susceptibility conditions. We performed a systematic clustering of 878,593 patients in FCR based on family name at birth, municipality of birth, and tumor type, diagnosed between years 1952 and 2011. We also estimated the familial occurrence of the tumor types using cluster score that reflects the proportion of patients belonging to the most significant clusters compared to all patients in Finland. The clustering effort identified 25,910 birth name-municipality based clusters representing 183 different tumor types characterized by topography and morphology. We produced information about familial occurrence of hundreds of tumor types, and many of the tumor types with high cluster score represented known cancer syndromes. Unexpectedly, Kaposi sarcoma (KS) also produced a very high score (cluster score 1.91, p-value <0.0001). We verified from population records that many of the KS patients forming the clusters were indeed close relatives, and identified one family with five affected individuals in two generations and several families with two first degree relatives. Our approach is unique in enabling systematic examination of a national epidemiological database to derive evidence of aberrant familial aggregation of all tumor types, both common and rare. It allowed effortless identification of families displaying features of both known as well as potentially novel cancer predisposition conditions, including striking familial aggregation of KS. Further work with high-throughput methods should elucidate the molecular basis of the potentially novel predisposition conditions found in this

  1. Seroprevalence of Human herpesvirus 8 (HHV-8 and incidence of Kaposi's sarcoma in Iran

    Directory of Open Access Journals (Sweden)

    Nategh Rakhshandeh

    2011-04-01

    Full Text Available Abstract Seroepidemiological surveys show that the prevalence of human herpesvirus 8 (HHV-8 infection mostly varies in various geographical areas and reflects the local incidence of classic and endemic KS, being widespread in sub-Saharan Africa and Mediterranean countries and uncommon in the USA and Northern Europe. In the Middle East only few populations, such as Ashkenazi and Sephardic groups in Israel, have been adequately evaluated for HHV-8 seroprevalence. Among Iranian population a striking higher seroprevalence of HHV8 has been reported among haemodialysis (16.9%, renal transplant recipients (25% and HIV (45.7% patients compared to blood donors (2%. Kaposi's sarcoma (KS is the rarest cancer in Iran, with an annual age-standardized incidence varying from 0.10 to 0.17 per 100,000 in males and from 0.06 to 0.08 per 100,000 in females. KS, however, is one of the most important malignancies in Iranian renal transplanted patients affecting up to 2.4% of organ recipients. The epidemiology of HHV8 and KS in Iran needs further evaluation. While the high prevalence of HHV-8 antibodies in HIV positive and haemodialysis individuals may be attributed to high-risk sexual behavior and polytransfusions, respectively, unknown determinants may be responsible for high seroprevalence of HHV8 and high incidence of KS in solid organ recipients. A global survey on HHV8 seroprevalence in Iran is mandatory to define co-factors associated with HHV8 infection and KS risk in the general Iranian population and in specific patient groups.

  2. Phase II Study of Bevacizumab in Patients With HIV-Associated Kaposi's Sarcoma Receiving Antiretroviral Therapy

    Science.gov (United States)

    Uldrick, Thomas S.; Wyvill, Kathleen M.; Kumar, Pallavi; O'Mahony, Deirdre; Bernstein, Wendy; Aleman, Karen; Polizzotto, Mark N.; Steinberg, Seth M.; Pittaluga, Stefania; Marshall, Vickie; Whitby, Denise; Little, Richard F.; Yarchoan, Robert

    2012-01-01

    Purpose Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti–VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS. Patients and Methods Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months were administered bevacizumab 15 mg/kg intravenously on days 1 and 8 and then every 3 weeks. The primary objective was assessment of antitumor activity using modified AIDS Clinical Trial Group (ACTG) criteria for HIV-KS. HIV-uninfected patients were also eligible and observed separately. Results Seventeen HIV-infected patients were enrolled. Fourteen patients had been receiving effective HAART for at least 6 months (median, 1 year). Thirteen patients had advanced disease (ACTG T1), 13 patients had received prior chemotherapy for KS, and seven patients had CD4 count less than 200 cells/μL. Median number of cycles was 10 (range, 1 to 37 cycles); median follow-up was 8.3 months (range, 3 to 36 months). Of 16 assessable patients, best tumor responses observed were complete response (CR) in three patients (19%), partial response (PR) in two patients (12%), stable disease in nine patients (56%), and progressive disease in two patients (12%). Overall response rate (CR + PR) was 31% (95% CI, 11% to 58.7%). Four of five responders had received prior chemotherapy for KS. Over 202 cycles, grade 3 to 4 adverse events at least possibly attributed to therapy included hypertension (n = 7), neutropenia (n = 5), cellulitis (n = 3), and headache (n = 2). Conclusion Bevacizumab is tolerated in patients with HIV-KS and has activity in a subset of patients. PMID:22430271

  3. HHV-8 infection in patients with AIDS-related Kaposi's sarcoma in Brazil

    Directory of Open Access Journals (Sweden)

    Keller R.

    2001-01-01

    Full Text Available The aims of the present study were to determine the prevalence of human herpesvirus type 8 (HHV-8 in HIV-positive Brazilian patients with (HIV+/KS+ and without Kaposi's sarcoma (HIV+/KS- using PCR and immunofluorescence assays, to assess its association with KS disease, to evaluate the performance of these tests in detecting HHV-8 infection, and to investigate the association between anti-HHV-8 antibody titers, CD4 counts and staging of KS disease. Blood samples from 66 patients, 39 HIV+/KS+ and 27 HIV+/KS-, were analyzed for HHV-8 viremia in peripheral blood mononuclear cells by PCR and HHV-8 antigenemia for latent and lytic infection by immunofluorescence assay. Positive samples for latent nuclear HHV-8 antigen (LNA antibodies were titrated out from 1/100 to 1/409,600 dilution. Clinical information was collected from medical records and risk behavior was assessed through an interview. HHV-8 DNA sequences were detected by PCR in 74.3% of KS+ patients and in 3.7% of KS- patients. Serological assays were similar in detecting anti-LNA antibodies and anti-lytic antigens in sera from KS+ patients (79.5% and KS- patients (18.5%. HHV-8 was associated with KS whatever the method used, i.e., PCR (odds ratio (OR = 7.4, 95% confidence interval (CI = 2.16-25.61 or anti-LNA and anti-lytic antibodies (OR = 17.0, 95%CI = 4.91-59.14. Among KS+ patients, HHV-8 titration levels correlated positively with CD4 counts (rho 0.48, P = 0.02, but not with KS staging. HHV-8 is involved in the development of KS in different geographic areas worldwide, as it is in Brazil, where HHV-8 is more frequent among HIV+ patients. KS severity was associated with immunodeficiency, but no correlation was found between HHV-8 antibody titers and KS staging.

  4. Isolated penile Kaposi's sarcoma in a HIV-positive patient stable on treatment for three years.

    Science.gov (United States)

    Lebari, Dornubari; Gohil, Jesal; Patnaik, Lipsita; Wasef, Wafaa

    2014-07-01

    Kaposi's sarcoma (KS) is an AIDS-defining condition. Typically, KS affects the skin with or without visceral involvement. The extensive use of antiretroviral therapy (ART) has decreased the incidence of KS amongst the HIV-positive population. We report a case of a 40-year-old man with HIV-1 infection with CD4 count of 551 cells/mm(3)and an undetectable viral load who presented with two skin-coloured KS lesions on the prepuce of the penis. Diagnosis was confirmed by histopathology. He had been commenced on ART three years earlier with a nadir CD4 count of 255 cells/mm(3) He had achieved and maintained viral suppression since commencing ART. The patient was initially treated with cryotherapy and 5% imiquimod as the lesions were presumed to be warts. The lack of response to treatment prompted further investigation. We carried out a literature search of published cases of penile KS over the past 10 years. The majority of articles regarding penile KS were published in the pre-ART era and involved patients with AIDS. Over the past 10 years, published cases of penile KS have almost exclusively been in HIV-negative men. We found 10 published cases of penile KS in HIV-negative men and only one other published case of penile KS in a HIV-positive man, who had severe immune suppression with CD4 count below 200 cells/mm(3) This is the first case report to describe a HIV-positive patient stable on ART with a CD4 count above 200 cells/mm(3)and suppressed HIV-1 viral load, to develop two KS lesions on the penis. Clinicians have to remain suspicious of penile lesions and appreciate the crucial role a biopsy with histopathological analysis plays in confirming a diagnosis. In addition, this case illustrates that unusual presentations of KS can still occur in treated HIV-positive patients with sustained immune recovery.

  5. Nationwide registry-based analysis of cancer clustering detects strong familial occurrence of Kaposi sarcoma.

    Directory of Open Access Journals (Sweden)

    Eevi Kaasinen

    Full Text Available Many cancer predisposition syndromes are rare or have incomplete penetrance, and traditional epidemiological tools are not well suited for their detection. Here we have used an approach that employs the entire population based data in the Finnish Cancer Registry (FCR for analyzing familial aggregation of all types of cancer, in order to find evidence for previously unrecognized cancer susceptibility conditions. We performed a systematic clustering of 878,593 patients in FCR based on family name at birth, municipality of birth, and tumor type, diagnosed between years 1952 and 2011. We also estimated the familial occurrence of the tumor types using cluster score that reflects the proportion of patients belonging to the most significant clusters compared to all patients in Finland. The clustering effort identified 25,910 birth name-municipality based clusters representing 183 different tumor types characterized by topography and morphology. We produced information about familial occurrence of hundreds of tumor types, and many of the tumor types with high cluster score represented known cancer syndromes. Unexpectedly, Kaposi sarcoma (KS also produced a very high score (cluster score 1.91, p-value <0.0001. We verified from population records that many of the KS patients forming the clusters were indeed close relatives, and identified one family with five affected individuals in two generations and several families with two first degree relatives. Our approach is unique in enabling systematic examination of a national epidemiological database to derive evidence of aberrant familial aggregation of all tumor types, both common and rare. It allowed effortless identification of families displaying features of both known as well as potentially novel cancer predisposition conditions, including striking familial aggregation of KS. Further work with high-throughput methods should elucidate the molecular basis of the potentially novel predisposition conditions

  6. Kaposi's sarcoma: etiology and pathogenesis, inducing factors, causal associations, and treatments: facts and controversies.

    Science.gov (United States)

    Ruocco, Eleonora; Ruocco, Vincenzo; Tornesello, Maria Lina; Gambardella, Alessio; Wolf, Ronni; Buonaguro, Franco M

    2013-01-01

    Kaposi's sarcoma (KS), an angioproliferative disorder, has a viral etiology and a multifactorial pathogenesis hinged on an immune dysfunction. The disease is multifocal, with a course ranging from indolent, with only skin manifestations to fulminant, with extensive visceral involvement. In the current view, all forms of KS have a common etiology in human herpesvirus (HHV)-8 infection, and the differences among them are due to the involvement of various cofactors. In fact, HHV-8 infection can be considered a necessary but not sufficient condition for the development of KS, because further factors (genetic, immunologic, and environmental) are required. The role of cofactors can be attributed to their ability to interact with HHV-8, to affect the immune system, or to act as vasoactive agents. In this contribution, a survey of the current state of knowledge on many and various factors involved in KS pathogenesis is carried out, in particular by highlighting the facts and controversies about the role of some drugs (quinine analogues and angiotensin-converting enzyme inhibitors) in the onset of the disease. Based on these assessments, it is possible to hypothesize that the role of cofactors in KS pathogenesis can move toward an effect either favoring or inhibiting the onset of the disease, depending on the presence of other agents modulating the pathogenesis itself, such as genetic predisposition, environmental factors, drug intake, or lymph flow disorders. It is possible that the same agents may act as either stimulating or inhibiting cofactors according to the patient's genetic background and variable interactions. Treatment guidelines for each form of KS are outlined, because a unique standard therapy for all of them cannot be considered due to KS heterogeneity. In most cases, therapeutic options, both local and systemic, should be tailored to the patient's peculiar clinical conditions.

  7. Clinical presentation and outcome of epidemic Kaposi sarcoma in Ugandan children.

    Science.gov (United States)

    Gantt, Soren; Kakuru, Abel; Wald, Anna; Walusansa, Victoria; Corey, Lawrence; Casper, Corey; Orem, Jackson

    2010-05-01

    Kaposi sarcoma (KS) is one of the most common pediatric cancers in sub-Saharan Africa. Few data are available about the clinical presentation or response to treatment of children with epidemic (HIV-associated) KS. Medical records of all children with KS and HIV infection referred to the Uganda Cancer Institute in Kampala, Uganda from October 2004 to June 2007 were reviewed. Charts were abstracted for age, sex, location of KS lesions at presentation, biopsy results, CD4 T-cell count and percentage, and KS treatment and outcome. Seventy-three children with epidemic KS were identified, 37 males and 36 females. The median age was 10.1 years (range 2-18). KS presented with lymph node (LN) involvement in 60% of cases. The median absolute and percentage CD4 T-cells at presentation were 210 cells/microl and 7.4%, respectively. Those children with lymphadenopathic KS were younger (mean difference 3.7 years; P = 0.01) and had higher CD4 T-cell counts (mean difference 242 cells/microl; P = 0.03) than those without LN involvement. Of 32 patients for whom outcome data were available, a complete response to chemotherapy and/or antiretroviral therapy was documented in 20 (62.5%) patients. In comparison to cutaneous involvement, LN involvement of epidemic KS occurs at younger ages and at higher CD4 levels. This clinical presentation may reflect recent infection with human herpesvirus 8 followed by a rapid progression to malignancy. Favorable response to treatment was observed in the majority of cases, but prospective studies are needed to determine optimal management.

  8. Kaposi Sarcoma Risk in HIV-Infected Children and Adolescents on Combination Antiretroviral Therapy From Sub-Saharan Africa, Europe, and Asia

    DEFF Research Database (Denmark)

    Obel, Niels; Kirk, Ole

    2016-01-01

    BACKGROUND:  The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. METHODS:  We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS...

  9. Whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography images before and after chemotherapy for Kaposi sarcoma and highly active antiretrovirus therapy.

    Science.gov (United States)

    Morooka, Miyako; Ito, Kimiteru; Kubota, Kazuo; Minamimoto, Ryogo; Shida, Yoshitaka; Hasuo, Kanehiro; Ito, Tateki; Tasato, Daisuke; Honda, Haruhito; Teruya, Katsuji; Kikuchi, Yoshimi; Ohtomo, Kuni

    2010-12-01

    Kaposi sarcoma is an acquired immunodeficiency syndrome-related disease that mainly involves the skin, gastrointestinal gut, and lungs. Whole-body 18F-fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT) scanning is useful for simultaneous detection of multiple lesions of Kaposi sarcoma. We present a 67-year-old man with a history of infection with human immunodeficiency virus who presented with numerous cutaneous lesions. FDG-PET/CT images showed lesions in the skin, lung, and lymph nodes. The gastrointestinal lesions were detected using gastric fiberscopy (GF) and colon fiberscopy (CF). After Kaposi sarcoma therapy, the uptake in the lesions of the skin, lung, and lymph nodes decreased, but new lesions were detected in the pancreas and lumbar spine. He had pancreatitis and Candida spondilitis. Whole-body FDG-PET/CT is useful for detecting lesions and determining the extension to which the disease has spread, adding the gastrointestinal lesions by GF and CF. After therapy, FDG-PET/CT can be used to demonstrate which lesions remain active and to determine the overall response to treatment. In this case, we show how useful FDG-PET/CT is and how difficult it is to treat Kaposi sarcoma.

  10. Changing patterns of Kaposi's sarcoma in Danish acquired immunodeficiency syndrome patients with complete follow-up. The Danish Study Group for HIV Infection (DASHI)

    DEFF Research Database (Denmark)

    Lundgren, Jens Dilling; Melbye, M; Pedersen, C

    1995-01-01

    clinically and with consecutive CD4 cell count measurement from time of AIDS-defining illness to date of death or censoring date, whichever came first. The proportion of homo-/bisexual men (n = 520) with Kaposi's sarcoma (n = 100) at AIDS diagnosis declined from 31% before 1985 to 13% in 1990, whereas...

  11. Changing patterns of Kaposi's sarcoma in Danish acquired immunodeficiency syndrome patients with complete follow-up. The Danish Study Group for HIV Infection (DASHI)

    DEFF Research Database (Denmark)

    Lundgren, Jens Dilling; Melbye, M; Pedersen, C

    1995-01-01

    clinically and with consecutive CD4 cell count measurement from time of AIDS-defining illness to date of death or censoring date, whichever came first. The proportion of homo-/bisexual men (n = 520) with Kaposi's sarcoma (n = 100) at AIDS diagnosis declined from 31% before 1985 to 13% in 1990, whereas...

  12. Mesenchymal-to-endothelial transition in Kaposi sarcoma: a histogenetic hypothesis based on a case series and literature review.

    Directory of Open Access Journals (Sweden)

    Simona Gurzu

    Full Text Available OBJECTIVES: Although several studies have been conducted regarding Kaposi sarcoma (KS, its histogenesis still remains to be elucidated. The aim of our study was to analyze the immunophenotype of Kaposi sarcoma and to present a hypothesis about the histogenesis of this tumor, based on a case series and a review of relevant literature. METHODS: In 15 cases of KSs diagnosed during 2000-2011, the clinicopathological features were correlated with the immunoexpression of c-Kit, SMA, CD34, CD31, vascular endothelial growth factor (VEGF, COX-2, c-KIT, smooth muscle antigen (SMA, and stem cell surface marker CD105. RESULTS: Both CD105 and c-KIT rate of the spindle-shaped tumor cell positivity increased in parallel to the pathological stage. All cases displayed CD105 and weak c-KIT positivity in the endothelial cells. SMA, VEGF, and COX-2 were focally expressed in all cases. CD34 marked both endothelium and spindle-shaped tumor cells. No c-KIT expression was noticed in KS of the internal organs. CONCLUSIONS: KS seems to be a variant of myofibroblastic tumors that originates from the viral modified pluripotent mesenchymal cells of the connective tissue transformed in spindle-shaped KS cells, followed by a mesenchymal-endothelial transition and a myofibroblastic-like differentiation. This paper mailnly showed that KS cannot be considered a pure vascular tumor.

  13. Risk of classic Kaposi sarcoma with exposures to plants and soils in Sicily

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    Graubard Barry I

    2010-12-01

    Full Text Available Abstract Background Ecologic and in vitro studies suggest that exposures to plants or soil may influence risk of Kaposi sarcoma (KS. Methods In a population-based study of Sicily, we analyzed data on contact with 20 plants and residential exposure to 17 soils reported by 122 classic KS cases and 840 sex- and age-matched controls. With 88 KS-associated herpesvirus (KSHV seropositive controls as the referent group, novel correlates of KS risk were sought, along with factors distinguishing seronegatives, in multinomial logistic regression models that included matching variables and known KS cofactors - smoking, cortisone use, and diabetes history. All plants were summed for cumulative exposure. Factor and cluster analyses were used to obtain scores and groups, respectively. Individual plants and soils in three levels of exposure with Ptrend ≤ 0.15 were retained in a backward elimination regression model. Results Adjusted for known cofactors, KS was not related to cumulative exposures to 20 plants [per quartile adjusted odds ratio (ORadj 0.96, 95% confidence interval (CI 0.73 - 1.25, Ptrend = 0.87], nor was it related to any factor scores or cluster of plants (P = 0.11 to 0.81. In the elimination regression model, KS risk was associated with five plants (Ptrend = 0.02 to 0.10 and with residential exposure to six soils (Ptrend = 0.01 to 0.13, including three soils (eutric regosol, chromic/pellic vertisol used to cultivate durum wheat. None of the KS-associated plants and only one soil was also associated with KSHV serostatus. Diabetes was associated with KSHV seronegativity (ORadj 4.69, 95% CI 1.97 - 11.17, but the plant and soil associations had little effect on previous findings that KS risk was elevated for diabetics (ORadj 7.47, 95% CI 3.04 - 18.35 and lower for current and former smokers (ORadj 0.26 and 0.47, respectively, Ptrend = 0.05. Conclusions KS risk was associated with exposure to a few plants and soils, but these may merely be due to

  14. Disseminated bone lesions in AIDS-associated Kaposi sarcoma, a bad prognosis? About four cases

    Directory of Open Access Journals (Sweden)

    N Wassilew

    2012-11-01

    Full Text Available Kaposi sarcoma (KS can present with a wide range of clinical features ranging from minimal cutaneous disease to a rapidly progressing neoplasm. Bone lesions are most often discovered accidently in the context of radiological investigations done for the screening of KS-visceral involvement [1]. Little is known on clinical outcome and response to antiretroviral therapy (ART and/or chemotherapy of these lytic osseous lesions. We report four cases with bone involvement in the context of systemic KS and aim at describing the long-term clinical outcome in two of these patients. Cases of AIDS-associated KS with disseminated bone lesions were collected in the HIV Unit, University Hospital Geneva, Switzerland. Patients were compared on clinical, biological and radiological features and therapeutic responses. Between 2002 and 2012, four HIV1-infected patients with T1 stage of KS presented disseminated osseous lesions (Table 1. Mean age was 43 years (range 39 - 47 years, mean time of follow up until our analysis was 48.5 months (SD 53.8, and mean CD4 count at KS diagnosis was 190.5 c/mL (SD 202.8. All patients showed hypodense bone lesions predominating the axial skeleton (figure 1, but no radiological imaging was performed to search for peripheral bone lesions.No patient reported pain or experienced pathological fractures. In one patient a dual-energy X-ray absorptiometry (DXA showed a bone mineral density within normal range after 10 years of KS diagnosis with disseminated bone lesions. No radiological change was observed in that patient despite stable KS disease after 13 cycles of liposomal doxorubicin and ART (figure 1. We describe a well-documented long-term follow up of disseminated osseous AIDS-associated KS disease. In our four cases, lytic bone lesions were asymptomatic and were not associated with bone fragility. We even could confirm the KS nature of the lesions by bone biopsy in patient B (3 months after KS diagnosis, as the differential

  15. Rainbow pattern in Kaposi's sarcoma under polarized dermoscopy: a dermoscopic pathological study.

    Science.gov (United States)

    Cheng, S-T; Ke, C-L K; Lee, C-H; Wu, C-S; Chen, G-S; Hu, S C-S

    2009-04-01

    We found previously that the features of Kaposi's sarcoma (KS) under polarized dermoscopy are characterized by a bluish-reddish coloration, a scaly surface, small brown globules and, most distinctively, the multicoloured 'rainbow pattern'. To evaluate the significance of the rainbow pattern on dermoscopy as a diagnostic feature in KS, and to demonstrate that it is associated with the unique vascular structure of the tumour. More than 100 lesions from seven patients with histologically proven KS were examined with polarized light dermoscopy. Sixty-three patients with various other cutaneous vascular and nonvascular tumours were also examined. KS lesions exhibiting the rainbow pattern and KS lesions lacking the rainbow pattern on dermoscopy were excised, and dermoscopic features were compared with histopathological structures. The dermoscopic patterns of other vascular tumours were also compared with histological features. In addition, the changes in dermoscopic features and histological structures were assessed before and after surgical therapy in one patient with KS. On the basis of evaluations with polarized dermoscopy, the rainbow pattern was found to be a highly specific dermoscopic feature for KS. Histology of KS lesions showing the rainbow pattern under polarized light dermoscopy demonstrated a vascular lumen-rich pattern of closely arranged 'back-to-back' vascular structures, whereas histology of KS lesions without the rainbow pattern showed a vascular lumen-poor pattern with vascular lumina separated further apart by intervening stromal and cellular tissue. Other vascular tumours did not exhibit the rainbow pattern and were characterized histologically by variably sized vascular structures separated by substantial amounts of stromal and cellular tissue. In one patient with KS, disappearance of the rainbow pattern was associated with obliteration of the vascular structure following surgical ablation therapy. The rainbow pattern in KS is associated with the

  16. Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study

    Science.gov (United States)

    Polizzotto, Mark N.; Uldrick, Thomas S.; Wyvill, Kathleen M.; Aleman, Karen; Peer, Cody J.; Bevans, Margaret; Sereti, Irini; Maldarelli, Frank; Whitby, Denise; Marshall, Vickie; Goncalves, Priscila H.; Khetani, Vikram; Figg, William D.; Steinberg, Seth M.; Zeldis, Jerome B.

    2016-01-01

    Purpose Kaposi's sarcoma (KS) is a multicentric tumor caused by Kaposi's sarcoma–associated herpesvirus. Unmet needs include therapies that are oral, anthracycline sparing, and deliverable in resource-limited settings. We evaluated pomalidomide, an oral immune modulatory agent, in patients with symptomatic KS. Methods The primary objectives were to assess tolerability, pharmacokinetics, and activity. Initial dosage level was 5 mg once per day for 21 days per 28-day cycle, with a de-escalated level of 3 mg if not tolerable, and aspirin 81 mg once per day thromboprophylaxis. HIV-infected patients required controlled viremia with either persistent KS despite 3 months of antiretroviral therapy (ART) or progressive KS despite 2 months of ART. Evaluations included tumor response and health-related quality of life (HRQL). Results Twenty-two patients were treated; 15 (68%) were HIV infected, 17 (77%) had advanced (T1) disease, and 19 (86%) previous KS therapy excluding ART. All were treated with 5 mg because no dose-limiting toxicities occurred. Over 156 cycles, the grade 3/4 adverse events possibly attributable to therapy were neutropenia (23 cycles, 10 patients), infection (1 cycle), and edema (1 cycle). Sixteen patients responded (73%; 95% CI, 50% to 89%): nine of 15 HIV-infected patients (60%; 95% CI, 32% to 84%) and all seven HIV-uninfected patients (100%; 95% CI, 59% to 100%). Median time to response was 4 weeks (range, 4 to 36 weeks). HRQL showed no impairment during therapy and improved satisfaction with appearance at end therapy (P = .03). Significant increases in CD4+ and CD8+ cells were seen in patients with and without HIV, together with a transient increase in Kaposi's sarcoma–associated herpesvirus viral load at week 4 (P = .05). Conclusion Pomalidomide is well tolerated and active in KS regardless of HIV status. Responses were rapid, with improved self-reported outcomes, and occurred in advanced and heavily pretreated disease. Correlative studies support

  17. Solitary Kaposi's sarcoma in retromolar region of an HIV positive patient: case report Sarcoma de Kaposi em região retromolar de um paciente HIV positivo: relato de caso

    Directory of Open Access Journals (Sweden)

    Maiara de Moraes

    2012-02-01

    Full Text Available Kaposi's sarcoma is a malignant neoplasm of vascular origin. It occurs mainly among immune deficient individuals, thus it is the most common neoplasm among HIV- positive patients. Its pathogenesis is complex and has not been fully clarified. This case arouses particular interest due to its anatomic location in the retromolar region of a 39-year-old male HIV- positive patient, who presented low white blood cell count and was not undergoing antiretroviral therapy. The emergence of this lesion may be associated with highly active antiretroviral therapy (HAART discontinuation and leukopenia. Hence, the reestablishment of therapy allows a suitable therapeutic approach and contributes to prognosis and survival rates.Sarcoma de Kaposi é uma neoplasia maligna de origem vascular que ocorre principalmente em indivíduos com deficiência imunológica, sendo a neoplasia mais comum em pacientes HIV positivos. Sua patogênese é complexa e não está bem estabelecida. Este caso é de interesse pela localização anatômica em região retromolar de paciente soropositivo, que apresentou baixa contagem de células brancas do sangue e que não realizava terapia antirretroviral. O surgimento da lesão pode estar associado à interrupção da terapia antirretroviral altamente ativa (HAART e à baixa contagem leucocitária. Assim, o restabelecimento da terapia pode permitir a abordagem terapêutica e contribuir para o prognóstico e a sobrevida.

  18. Piezoelectric particle accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Kemp, Mark A.; Jongewaard, Erik N.; Haase, Andrew A.; Franzi, Matthew

    2017-08-29

    A particle accelerator is provided that includes a piezoelectric accelerator element, where the piezoelectric accelerator element includes a hollow cylindrical shape, and an input transducer, where the input transducer is disposed to provide an input signal to the piezoelectric accelerator element, where the input signal induces a mechanical excitation of the piezoelectric accelerator element, where the mechanical excitation is capable of generating a piezoelectric electric field proximal to an axis of the cylindrical shape, where the piezoelectric accelerator is configured to accelerate a charged particle longitudinally along the axis of the cylindrical shape according to the piezoelectric electric field.

  19. A challenging case of rapid progressive Kaposi sarcoma after renal transplantation: diagnostics by FDG PET/CT.

    Science.gov (United States)

    Reuter, Stefan; Vrachimis, Alexis; Huss, Sebastian; Wardelmann, Eva; Weckesser, Mathias; Pavenstädt, Hermann

    2014-09-01

    De-novo malignancy is a serious posttransplant complication. While the incidence of Kaposi sarcoma (KS) is low, the time for its diagnosis is early after renal transplantation. Typically, it can be identified because of the classical skin lesion. We herein report an unusual case of rapid progressive KS without skin lesions in a 52-year-old patient leading to death within 8 months after kidney transplantation. This striking case illustrates the usefulness of [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography for demonstrating the cause of unexplained deterioration of patient's condition. Early identification of KS is critical because early (modification of) therapy can substantially improve patient's prognosis.

  20. A Case of AIDS-related Kaposi's Sarcoma%艾滋病相关型Kaposi肉瘤1例

    Institute of Scientific and Technical Information of China (English)

    陈文颖; 李玉叶; 何黎; 杨欣平

    2011-01-01

    A 33-year-old male presented with purple nodules and plaques on his head, neck, chest, back and both upper extremities for 2 months. Laboratory examination revealed HIV antibody test was positive. The cell count of CD4 was 18/μL. Pathological examination confirmed the diagnosis of Kaposi's sarcoma.%患者男,33岁.头颈部、胸背、双上肢皮肤及口腔黏膜紫红色结节及斑块2月余.患者系男同性恋,有高危性接触史.实验室检查示HIV初筛及确认试验均为阳性,CD4细胞计数18个/μL,皮肤组织病理符合Kaposi肉瘤.

  1. Human herpes virus-8 DNA in bronchoalveolar lavage samples from patients with AIDS-associated pulmonary Kaposi's sarcoma

    DEFF Research Database (Denmark)

    Benfield, T L; Dodt, K K; Lundgren, Jens Dilling

    1997-01-01

    Kaposi's sarcoma (KS) is the most frequent AIDS-associated neoplasm, and often disseminates to visceral organs, including the lungs. An ante-mortem diagnosis of pulmonary KS is difficult. Recently, DNA sequences resembling a new human herpes virus (HHV-8), have been identified in various forms...... of KS. We hypothesized that these sequences are present in samples obtained by bronchoalveolar lavage (BAL) in patients with pulmonary KS. Utilizing a nested polymerase chain reaction (PCR), 7/12 BAL cell samples from HIV-infected patients with endobronchial KS were positive for HHV-8 DNA. In contrast......, only 2/39 samples from HIV-infected patients without evidence of KS were positive (p = 0.007). Detection of HHV-8 in BAL cells of patients with pulmonary KS was highly specific (95%), with a sensitivity of 58% and a positive predictive value of 78%. In conclusion, HHV-8 is associated with pulmonary KS...

  2. High prevalence of antibodies to human herpesvirus 8 in relatives of patients with classic Kaposi's sarcoma from Sardinia.

    Science.gov (United States)

    Angeloni, A; Heston, L; Uccini, S; Sirianni, M C; Cottoni, F; Masala, M V; Cerimele, D; Lin, S F; Sun, R; Rigsby, M; Faggioni, A; Miller, G

    1998-06-01

    A survey for antibodies to a recombinant small viral capsid antigen (sVCA) of human herpesvirus type 8 (HHV-8) was conducted in Sardinia, one of the world's highest incidence areas for classic Kaposi's sarcoma (KS). Prevalence of antibodies to HHV-8 sVCA was greatest in patients with KS (95%), followed by family members (39%) and a Sardinian control population age- and sex-matched to the relatives (11%). Within families, prevalence of antibodies was about equal among spouses, children, and siblings of KS patients, a finding that raises the possibilities of intrafamilial person-to-person or vertical transmission. Antibodies were detected 2-3 times more frequently in males than in females. The data show that prevalence of antibodies to HHV-8 sVCA correlates with the distribution of classic KS in a high- incidence area. Clustering of seroprevalence within some families suggests the presence of familial risk factors for active HHV-8 infection.

  3. Visceral Kaposi's Sarcoma Related to Human Herpesvirus-8 in Liver Transplant Recipient: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    H. Benhammane

    2012-01-01

    Full Text Available Background. Kaposi’s sarcoma (KS in transplant recipients is about 400 to 500 times rate in the general population. It is strongly associated to Human herpesvirus-8 (HHV-8 infection which has been found in 95% of KS lesions. The optimal approach to managing posttransplantation KS is to reduce or discontinue immunosuppressive therapy but this strategy carries a risk of the acute rejection of the graft. Recently, the use of an mTOR inhibitor has added new opportunities for KS treatment and prevention. Case Report. We report a case of 24 years-old Turkish woman with visceral HHV-8-associated Kaposi's sarcoma after orthotopic liver transplantation. Conclusion. Posttransplantation KS is considered an experimental model of virus induced tumor suggesting the usefulness of HHV-8 screening in transplant recipient and donor. Therapeutic approaches are complex and require a multidisciplinary team.

  4. Acceleration without Horizons

    CERN Document Server

    Doria, Alaric

    2015-01-01

    We derive the metric of an accelerating observer moving with non-constant proper acceleration in flat spacetime. With the exception of a limiting case representing a Rindler observer, there are no horizons. In our solution, observers can accelerate to any desired terminal speed $v_{\\infty} < c$. The motion of the accelerating observer is completely determined by the distance of closest approach and terminal velocity or, equivalently, by an acceleration parameter and terminal velocity.

  5. Sarcoma de Kaposi relacionado à síndrome da imunodeficiência adquirida: características do comprometimento hepático na tomografia computadorizada e na ressonância magnética Kaposi sarcoma related to acquired immunodeficiency syndrome: hepatic findings on computed tomography and magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Daniel Nobrega da Costa

    2008-04-01

    Full Text Available Sarcoma de Kaposi é uma neoplasia associada a condições de imunossupressão que acomete os vasos linfáticos e sanguíneos. É a neoplasia intra-hepática mais comum na síndrome da imunodeficiência adquirida. A tomografia computadorizada e a ressonância magnética revelam múltiplos pequenos nódulos, proeminência e realce dos planos periportais, devido à presença de tecido neoplásico. Os autores descrevem um caso de paciente masculino, de 47 anos de idade, com síndrome da imunodeficiência adquirida e sarcoma de Kaposi disseminado.Kaposi sarcoma is a neoplasm associated with immunosuppressive conditions, and involving blood and lymphatic vessels. It is the most frequent intrahepatic neoplasm in patients with acquired immunodeficiency syndrome. Computed tomography and magnetic resonance imaging demonstrate multiple small nodules, prominence and contrast-enhancement of periportal branches due to the presence of the neoplastic tissue. The authors report a case of a 47-year-old male patient with acquired immunodeficiency syndrome presenting disseminated Kaposi sarcoma.

  6. Accelerating flight: Edge with arbitrary acceleration

    CSIR Research Space (South Africa)

    Gledhill, Irvy MA

    2011-11-01

    Full Text Available ? temporal scales ? Euler ? convection ? Reynolds ? translational viscous ? Ekman ? rotational viscous ? Translational acceleration ? related to g ? Rotational accleration ? Rossby ? Coriolis ? Centrifugal ? Gravitational ? CSIR 2009...

  7. Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma.

    Science.gov (United States)

    Starita, Noemy; Di Monta, Gianluca; Cerasuolo, Andrea; Marone, Ugo; Anniciello, Anna Maria; Botti, Gerardo; Buonaguro, Luigi; Buonaguro, Franco M; Tornesello, Maria Lina

    2017-01-01

    Electrochemotherapy (ECT) has shown to be an effective treatment for cutaneous and subcutaneous Kaposi sarcoma (KS) lesions. However, no study has investigated the impact of ECT treatment on the kinetics of human herpesvirus type 8 (HHV8), which is considered the necessary causal agent of KS. We aimed to evaluate HHV8 viral load and expression levels in patients affected by classic KS who received one or more ECT treatments and have been followed semi annually for up to four years. A total of 27 classic KS patients were enrolled in this study. Tumour biopsies and blood samples were obtained before ECT treatment. Additional blood samples were collected at six month intervals for 12-48 months. HHV8 viral load and expression profiles of latent (ORF72 and ORF73) and lytic (K2, K8, K8.1, K10/K10.1, K10.5/K10.6 and ORF16) genes were assessed in all samples by real-time PCR. HHV8 ORF26 and K1 regions were amplified and subjected to direct nucleotide sequencing followed by phylogenetic analysis for variant identification. All KS biopsies and 46.4% of peripheral blood mononuclear cells (PBMCs) collected before ECT treatment were positive for HHV8 DNA. Viral load ranged from 0.02 to 2.3 copies per cell in KS lesions and 3.0 × 10(-7) to 6.9 × 10(-4) copies per cell in PBMCs. Overall, latent ORF72 and ORF73 as well as lytic K2, K8 and K10/K10.1 were expressed in all KS biopsies. ORF16 mRNA was detected in 71.4% and both K8.1 and K10.5/K10.6 mRNAs in 57.1% of KS samples. The ORF72, ORF73 and K2 transcripts were amplified in 37.5%, 25% and 25% of PBMCs collected before ECT, respectively. After the first ECT session, complete response was achieved in 20 out of 27 (74.1%) patients and HHV8 DNA was detected in four out of 27 (14.8%) PBMC samples at six month follow up. Phylogenetic analysis of ORF26 amplimers showed that most viral variants belonged to A/C (82.3%), and few to C2 (5.9%) or C3 (11.8%) subtype. The K1/VR1 variants fell into A (33.3%) and C (66.7%) HHV8 clade

  8. 2014 CERN Accelerator Schools: Plasma Wake Acceleration

    CERN Multimedia

    2014-01-01

    A specialised school on Plasma Wake Acceleration will be held at CERN, Switzerland from 23-29 November, 2014.   This course will be of interest to staff and students in accelerator laboratories, university departments and companies working in or having an interest in the field of new acceleration techniques. Following introductory lectures on plasma and laser physics, the course will cover the different components of a plasma wake accelerator and plasma beam systems. An overview of the experimental studies, diagnostic tools and state of the art wake acceleration facilities, both present and planned, will complement the theoretical part. Topical seminars and a visit of CERN will complete the programme. Further information can be found at: http://cas.web.cern.ch/cas/PlasmaWake2014/CERN-advert.html http://indico.cern.ch/event/285444/

  9. Pulmonary Kaposi Sarcoma: An Uncommon Cause of Respiratory Failure in the Era of Highly Active Antiretroviral Therapy—Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Stanley M. Nwabudike

    2016-01-01

    Full Text Available Kaposi Sarcoma (KS is the most common malignancy associated with Acquired Immune Deficiency Syndrome (AIDS and is caused by Human Herpesvirus 8 (HHV 8 or Kaposi Sarcoma Herpesvirus (KSHV. In about 90% of cases Kaposi Sarcoma is associated with cutaneous lesions; however visceral disease can occur in the absence of cutaneous involvement. In the era of Highly Active Antiretroviral Therapy (HAART, the incidence of KS has declined. Clinical features of pulmonary KS might be difficult to distinguish from pneumonia in the immunocompromised patients and could lead to diagnostic challenges. First-line treatment of KS is with HAART and the incidence has declined with its use. Systemic chemotherapy may play a role depending on the extent of the disease. We report the case of a young man who presented with pulmonary symptoms and was later found to have pulmonary KS. Interestingly this diagnosis was made in the absence of the classic skin lesions. His disease was complicated by progressive respiratory failure and he eventually died.

  10. Pulmonary Kaposi Sarcoma: An Uncommon Cause of Respiratory Failure in the Era of Highly Active Antiretroviral Therapy—Case Report and Review of the Literature

    Science.gov (United States)

    Hemmings, Stefan; Paul, Yonette; Habtegebriel, Yordanis; Polk, Octavius

    2016-01-01

    Kaposi Sarcoma (KS) is the most common malignancy associated with Acquired Immune Deficiency Syndrome (AIDS) and is caused by Human Herpesvirus 8 (HHV 8) or Kaposi Sarcoma Herpesvirus (KSHV). In about 90% of cases Kaposi Sarcoma is associated with cutaneous lesions; however visceral disease can occur in the absence of cutaneous involvement. In the era of Highly Active Antiretroviral Therapy (HAART), the incidence of KS has declined. Clinical features of pulmonary KS might be difficult to distinguish from pneumonia in the immunocompromised patients and could lead to diagnostic challenges. First-line treatment of KS is with HAART and the incidence has declined with its use. Systemic chemotherapy may play a role depending on the extent of the disease. We report the case of a young man who presented with pulmonary symptoms and was later found to have pulmonary KS. Interestingly this diagnosis was made in the absence of the classic skin lesions. His disease was complicated by progressive respiratory failure and he eventually died. PMID:27872774

  11. High Energy Particle Accelerators

    CERN Multimedia

    Audio Productions, Inc, New York

    1960-01-01

    Film about the different particle accelerators in the US. Nuclear research in the US has developed into a broad and well-balanced program.Tour of accelerator installations, accelerator development work now in progress and a number of typical experiments with high energy particles. Brookhaven, Cosmotron. Univ. Calif. Berkeley, Bevatron. Anti-proton experiment. Negative k meson experiment. Bubble chambers. A section on an electron accelerator. Projection of new accelerators. Princeton/Penn. build proton synchrotron. Argonne National Lab. Brookhaven, PS construction. Cambridge Electron Accelerator; Harvard/MIT. SLAC studying a linear accelerator. Other research at Madison, Wisconsin, Fixed Field Alternate Gradient Focusing. (FFAG) Oakridge, Tenn., cyclotron. Two-beam machine. Comments : Interesting overview of high energy particle accelerators installations in the US in these early years. .

  12. Improved plasma accelerator

    Science.gov (United States)

    Cheng, D. Y.

    1971-01-01

    Converging, coaxial accelerator electrode configuration operates in vacuum as plasma gun. Plasma forms by periodic injections of high pressure gas that is ionized by electrical discharges. Deflagration mode of discharge provides acceleration, and converging contours of plasma gun provide focusing.

  13. Accelerator Technology Division

    Science.gov (United States)

    1992-04-01

    In fiscal year (FY) 1991, the Accelerator Technology (AT) division continued fulfilling its mission to pursue accelerator science and technology and to develop new accelerator concepts for application to research, defense, energy, industry, and other areas of national interest. This report discusses the following programs: The Ground Test Accelerator Program; APLE Free-Electron Laser Program; Accelerator Transmutation of Waste; JAERI, OMEGA Project, and Intense Neutron Source for Materials Testing; Advanced Free-Electron Laser Initiative; Superconducting Super Collider; The High-Power Microwave Program; (Phi) Factory Collaboration; Neutral Particle Beam Power System Highlights; Accelerator Physics and Special Projects; Magnetic Optics and Beam Diagnostics; Accelerator Design and Engineering; Radio-Frequency Technology; Free-Electron Laser Technology; Accelerator Controls and Automation; Very High-Power Microwave Sources and Effects; and GTA Installation, Commissioning, and Operations.

  14. Accelerators, Colliders, and Snakes

    Science.gov (United States)

    Courant, Ernest D.

    2003-12-01

    The author traces his involvement in the evolution of particle accelerators over the past 50 years. He participated in building the first billion-volt accelerator, the Brookhaven Cosmotron, which led to the introduction of the "strong-focusing" method that has in turn led to the very large accelerators and colliders of the present day. The problems of acceleration of spin-polarized protons are also addressed, with discussions of depolarizing resonances and "Siberian snakes" as a technique for mitigating these resonances.

  15. The CERN Accelerator School

    CERN Multimedia

    2016-01-01

    Introduction to accelerator physics The CERN Accelerator School: Introduction to Accelerator Physics, which should have taken place in Istanbul, Turkey, later this year has now been relocated to Budapest, Hungary.  Further details regarding the new hotel and dates will be made available as soon as possible on a new Indico site at the end of May.

  16. Accelerators and Dinosaurs

    CERN Multimedia

    Turner, Michael Stanley

    2003-01-01

    Using naturally occuring particles on which to research might have made accelerators become extinct. But in fact, results from astrophysics have made accelerator physics even more important. Not only are accelerators used in hospitals but they are also being used to understand nature's inner workings by searching for Higgs bosons, CP violation, neutrino mass and dark matter (2 pages)

  17. Far field acceleration

    Energy Technology Data Exchange (ETDEWEB)

    Fernow, R.C.

    1995-07-01

    Far fields are propagating electromagnetic waves far from their source, boundary surfaces, and free charges. The general principles governing the acceleration of charged particles by far fields are reviewed. A survey of proposed field configurations is given. The two most important schemes, Inverse Cerenkov acceleration and Inverse free electron laser acceleration, are discussed in detail.

  18. Acceleration: It's Elementary

    Science.gov (United States)

    Willis, Mariam

    2012-01-01

    Acceleration is one tool for providing high-ability students the opportunity to learn something new every day. Some people talk about acceleration as taking a student out of step. In actuality, what one is doing is putting a student in step with the right curriculum. Whole-grade acceleration, also called grade-skipping, usually happens between…

  19. The Accelerator Reliability Forum

    CERN Document Server

    Lüdeke, Andreas; Giachino, R

    2014-01-01

    A high reliability is a very important goal for most particle accelerators. The biennial Accelerator Reliability Workshop covers topics related to the design and operation of particle accelerators with a high reliability. In order to optimize the over-all reliability of an accelerator one needs to gather information on the reliability of many different subsystems. While a biennial workshop can serve as a platform for the exchange of such information, the authors aimed to provide a further channel to allow for a more timely communication: the Particle Accelerator Reliability Forum [1]. This contribution will describe the forum and advertise it’s usage in the community.

  20. Is murine gammaherpesvirus-68 (MHV-68) a suitable immunotoxicological model for examining immunomodulatory drug-associated viral recrudescence?

    Science.gov (United States)

    Aligo, Jason; Walker, Mindi; Bugelski, Peter; Weinstock, Daniel

    2015-01-01

    Immunosuppressive agents are used for treatment of a variety of autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosis (SLE), and psoriasis, as well as for prevention of tissue rejection after organ transplantation. Recrudescence of herpesvirus infections, and increased risk of carcinogenesis from herpesvirus-associated tumors are related with immunosuppressive therapy in humans. Post-transplant lymphoproliferative disorder (PTLD), a condition characterized by development of Epstein Barr Virus (EBV)-associated B-lymphocyte lymphoma, and Kaposi's Sarcoma (KS), a dermal tumor associated with Kaposi Sarcoma-associated virus (KSHV), may develop in solid organ transplant patients. KS also occurs in immunosuppressed Acquired Immunodeficiency (AIDS) patients. Kaposi Sarcoma-associated virus (KSHV) is a herpes virus genetically related to EBV. Murine gammaherpes-virus-68 (MHV-68) is proposed as a mouse model of gammaherpesvirus infection and recrudescence and may potentially have relevance for herpesvirus-associated neoplasia. The pathogenesis of MHV-68 infection in mice mimics EBV/KSHV infection in humans with acute lytic viral replication followed by dissemination and establishment of persistent latency. MHV-68-infected mice may develop lymphoproliferative disease that is accelerated by disruption of the immune system. This manuscript first presents an overview of gammaherpesvirus pathogenesis and immunology as well as factors involved in viral recrudescence. A description of different types of immunodeficiency then follows, with particular focus on viral association with lymphomagenesis after immunosuppression. Finally, this review discusses different gammaherpesvirus animal models and describes a proposed MHV-68 model to further examine the interplay of immunomodulatory agents and gammaherpesvirus-associated neoplasia.

  1. Immunohistochemical detection of the latent nuclear antigen-1 of the human herpesvirus type 8 to differentiate cutaneous epidemic Kaposi sarcoma and its histological simulators Detecção imuno-histoquímica do antígeno nuclear latente-1 do herpesvirus tipo 8 para diferenciar o sarcoma de Kaposi epidêmico cutâneo de seus simuladores histológicos

    Directory of Open Access Journals (Sweden)

    Patricia Fonseca Pereira

    2013-04-01

    Full Text Available Kaposi's sarcoma is the most common neoplasia diagnosed in AIDS patients and the expression of the human herpesvirus-8 (HHV-8 latent nuclear antigen-1 has been useful for its histological diagnosis. The aim of this study is to confirm that immunohistochemistry is a valuable tool for differentiating KS from its simulators in skin biopsies of HIV patients. Immunohistochemical and histological analyses were performed in 49 Kaposi's sarcoma skin biopsies and 60 of its histological simulators. Positivity was present in the 49 Kaposi's sarcoma skin biopsies and no staining was observed in the 60 simulators analyzed, resulting in sensibility and specificity of 100%. HHV-8 immunohistochemical detection is an effective tool for diagnosing Kaposi's sarcoma, especially in early lesions in which neoplastic features are not evident. It also contributes to its histological differential diagnosis.O sarcoma de Kaposi é a neoplasia mais diagnosticada em pacientes com SIDA e a expressão do antígeno nuclear latente-1 do herpesvírus humano tipo-8 (HHV-8 tem se mostrado útil no seu diagnóstico histológico. O objetivo deste estudo é confirmar que o método imuno-histoquímico é uma ferramenta útil para diferenciar o sarcoma de Kaposi cutâneo de seus simuladores histológicos em pacientes HIV positivos. Análise histológica e imuno-histoquímica foram realizadas em 49 casos de sarcoma de Kaposi cutâneo e 60 casos de seus simuladores histológicos. Positividade à imuno-histoquímica para o antígeno nuclear latente 1 do HHV-8 foi observada nos 49 casos de sarcoma de Kaposi e nenhuma reação foi detectada nos 60 simuladores analisados, resultando em 100% de sensibilidade e especificidade. A detecção do HHV-8 por imuno-histoquímica é uma ferramenta útil para o diagnóstico de sarcoma de Kaposi, especialmente na lesão inicial cujo caráter neoplásico não é evidente, e contribui para seu diagnóstico diferencial histológico.

  2. Industrial Application of Accelerators

    CERN Document Server

    CERN. Geneva

    2017-01-01

    At CERN, we are very familiar with large, high energy particle accelerators. However, in the world outside CERN, there are more than 35000 accelerators which are used for applications ranging from treating cancer, through making better electronics to removing harmful micro-organisms from food and water. These are responsible for around $0.5T of commerce each year. Almost all are less than 20 MeV and most use accelerator types that are somewhat different from what is at CERN. These lectures will describe some of the most common applications, some of the newer applications in development and the accelerator technology used for them. It will also show examples of where technology developed for particle physics is now being studied for these applications. Rob Edgecock is a Professor of Accelerator Science, with a particular interest in the medical applications of accelerators. He works jointly for the STFC Rutherford Appleton Laboratory and the International Institute for Accelerator Applications at the Univer...

  3. Industrial Application of Accelerators

    CERN Document Server

    CERN. Geneva

    2017-01-01

    At CERN, we are very familiar with large, high energy particle accelerators. However, in the world outside CERN, there are more than 35000 accelerators which are used for applications ranging from treating cancer, through making better electronics to removing harmful micro-organisms from food and water. These are responsible for around $0.5T of commerce each year. Almost all are less than 20 MeV and most use accelerator types that are somewhat different from what is at CERN. These lectures will describe some of the most common applications, some of the newer applications in development and the accelerator technology used for them. It will also show examples of where technology developed for particle physics is now being studied for these applications. Rob Edgecock is a Professor of Accelerator Science, with a particular interest in the medical applications of accelerators. He works jointly for the STFC Rutherford Appleton Laboratory and the International Institute for Accelerator Applications at the Uni...

  4. Acceleration in astrophysics

    Energy Technology Data Exchange (ETDEWEB)

    Colgate, S.A.

    1993-12-31

    The origin of cosmic rays and applicable laboratory experiments are discussed. Some of the problems of shock acceleration for the production of cosmic rays are discussed in the context of astrophysical conditions. These are: The presumed unique explanation of the power law spectrum is shown instead to be a universal property of all lossy accelerators; the extraordinary isotropy of cosmic rays and the limited diffusion distances implied by supernova induced shock acceleration requires a more frequent and space-filling source than supernovae; the near perfect adiabaticity of strong hydromagnetic turbulence necessary for reflecting the accelerated particles each doubling in energy roughly 10{sup 5} to {sup 6} scatterings with negligible energy loss seems most unlikely; the evidence for acceleration due to quasi-parallel heliosphere shocks is weak. There is small evidence for the expected strong hydromagnetic turbulence, and instead, only a small number of particles accelerate after only a few shock traversals; the acceleration of electrons in the same collisionless shock that accelerates ions is difficult to reconcile with the theoretical picture of strong hydromagnetic turbulence that reflects the ions. The hydromagnetic turbulence will appear adiabatic to the electrons at their much higher Larmor frequency and so the electrons should not be scattered incoherently as they must be for acceleration. Therefore the electrons must be accelerated by a different mechanism. This is unsatisfactory, because wherever electrons are accelerated these sites, observed in radio emission, may accelerate ions more favorably. The acceleration is coherent provided the reconnection is coherent, in which case the total flux, as for example of collimated radio sources, predicts single charge accelerated energies much greater than observed.

  5. Particle-accelerator decommissioning

    Energy Technology Data Exchange (ETDEWEB)

    Opelka, J.H.; Mundis, R.L.; Marmer, G.J.; Peterson, J.M.; Siskind, B.; Kikta, M.J.

    1979-12-01

    Generic considerations involved in decommissioning particle accelerators are examined. There are presently several hundred accelerators operating in the United States that can produce material containing nonnegligible residual radioactivity. Residual radioactivity after final shutdown is generally short-lived induced activity and is localized in hot spots around the beam line. The decommissioning options addressed are mothballing, entombment, dismantlement with interim storage, and dismantlement with disposal. The recycle of components or entire accelerators following dismantlement is a definite possibility and has occurred in the past. Accelerator components can be recycled either immediately at accelerator shutdown or following a period of storage, depending on the nature of induced activation. Considerations of cost, radioactive waste, and radiological health are presented for four prototypic accelerators. Prototypes considered range from small accelerators having minimal amounts of radioactive mmaterial to a very large accelerator having massive components containing nonnegligible amounts of induced activation. Archival information on past decommissionings is presented, and recommendations concerning regulations and accelerator design that will aid in the decommissioning of an accelerator are given.

  6. Kaposi Sarcoma among HIV Infected Patients in Lagos University Teaching Hospital, Nigeria: A 14-Year Retrospective Clinicopathological Study

    Directory of Open Access Journals (Sweden)

    Olakanmi Akinde

    2016-01-01

    Full Text Available Background. Despite the increased incidence of Kaposi sarcoma (KS resulting from the Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS pandemic, there is still significant underreporting of KS in this environment. Objectives. This study was aimed at determining the incidence and clinicopathologic patterns of KS among HIV infected patients in Lagos University Teaching Hospital (LUTH, Nigeria, over a 14-year period: January 2000 to December 2013. Methodology. The materials for this study included patients’ hospital clinical files, duplicate copies of histopathologic reports, and tissue blocks and corresponding archival slides in the Anatomic and Molecular Pathology Department and the HIV/AIDS unit of the Department of Haematology. Results. Within the study period, 182 cases of KS were diagnosed, accounting for 1.2% of all patients managed for HIV/AIDS and 2.99% of solid malignant tumours. The male-to-female ratio and modal age group were 1 : 1.3 and 5th decade, respectively. Most cases (90% had purely mucocutaneous involvement with the lower limb being the commonest site (65.8%. The majority of lesions were plaques (65.8%. Vascular formation was the predominant histologic type seen (43.5%. Conclusion. KS in Lagos followed the same epidemiologic trend as other centers in Nigeria, with an increasing incidence in this era of HIV/AIDS.

  7. The Cancer-Associated Virus Landscape in HIV Patients with Oral Hairy Leukoplakia, Kaposi's Sarcoma, and Non-Hodgkin Lymphoma

    Directory of Open Access Journals (Sweden)

    Peter D. Burbelo

    2012-01-01

    Full Text Available Although HIV-positive patients are at higher risk for developing a variety of infection-related cancers, the prevalence of infections with the seven known cancer-associated viruses has not been studied. Luciferase immunoprecipitation systems were used to evaluate antiviral antibodies in four 23-person groups: healthy blood donors and HIV-infected patients with oral hairy leukoplakia (OLP, Kaposi's sarcoma (KS, or non-Hodgkin lymphoma (NHL. Antibody profiling revealed that all HIV-positive individuals were strongly seropositive for anti-gp41 and antireverse transcriptase antibodies. However, anti-p24 HIV antibody levels were highly variable and some OLP and KS patients demonstrated weak or negative responses. Profiling two EBV antigens revealed no statistical difference in antibody levels among the three HIV-infected groups. A high frequency of KSHV infection was detected in HIV patients including 100% of KS, 78% of OLP, and 57% of NHL patients. Most HIV-infected subjects (84% showed anti-HBV core antibodies, but only a few showed antibodies against HCV. MCV seropositivity was also common (94% in the HIV-infected individuals and KS patients showed statistically higher antibody levels compared to the OLP and NHL patients. Overall, 68% of the HIV-infected patients showed seropositivity with at least four cancer-associated viruses. Antibody profiles against these and other infectious agents could be useful for enhancing the clinical management of HIV patients.

  8. Kaposi Sarcoma among HIV Infected Patients in Lagos University Teaching Hospital, Nigeria: A 14-Year Retrospective Clinicopathological Study

    Science.gov (United States)

    Akinde, Olakanmi; Adeyemo, Titilope; Omoseebi, Oladipo; Ikeri, Nzechukwu; Okonkwo, Ikechukwu; Afolayan, Olatunji

    2016-01-01

    Background. Despite the increased incidence of Kaposi sarcoma (KS) resulting from the Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) pandemic, there is still significant underreporting of KS in this environment. Objectives. This study was aimed at determining the incidence and clinicopathologic patterns of KS among HIV infected patients in Lagos University Teaching Hospital (LUTH), Nigeria, over a 14-year period: January 2000 to December 2013. Methodology. The materials for this study included patients' hospital clinical files, duplicate copies of histopathologic reports, and tissue blocks and corresponding archival slides in the Anatomic and Molecular Pathology Department and the HIV/AIDS unit of the Department of Haematology. Results. Within the study period, 182 cases of KS were diagnosed, accounting for 1.2% of all patients managed for HIV/AIDS and 2.99% of solid malignant tumours. The male-to-female ratio and modal age group were 1 : 1.3 and 5th decade, respectively. Most cases (90%) had purely mucocutaneous involvement with the lower limb being the commonest site (65.8%). The majority of lesions were plaques (65.8%). Vascular formation was the predominant histologic type seen (43.5%). Conclusion. KS in Lagos followed the same epidemiologic trend as other centers in Nigeria, with an increasing incidence in this era of HIV/AIDS. PMID:27034839

  9. KS-Detect - Validation of Solar Thermal PCR for the Diagnosis of Kaposi's Sarcoma Using Pseudo-Biopsy Samples.

    Science.gov (United States)

    Snodgrass, Ryan; Gardner, Andrea; Jiang, Li; Fu, Cheng; Cesarman, Ethel; Erickson, David

    2016-01-01

    Resource-limited settings present unique engineering challenges for medical diagnostics. Diagnosis is often needed for those unable to reach central healthcare systems, making portability and independence from traditional energy infrastructure essential device parameters. In 2014, our group presented a microfluidic device that performed a solar-powered variant of the polymerase chain reaction, which we called solar thermal PCR. In this work, we expand on our previous effort by presenting an integrated, portable, solar thermal PCR system targeted towards the diagnosis of Kaposi's sarcoma. We call this system KS-Detect, and we now report the system's performance as a diagnostic tool using pseudo-biopsy samples made from varying concentrations of human lymphoma cell lines positive for the KS herpesvirus (KSHV). KS-Detect achieved 83% sensitivity and 70% specificity at high (≥ 10%) KSHV+ cell concentrations when diagnosing pseudo-biopsy samples by smartphone image. Using histology, we confirm that our prepared pseudo-biopsies contain similar KSHV+ cell concentrations as human biopsies positive for KS. Through our testing of samples derived from human cell lines, we validate KS-Detect as a viable, portable KS diagnostic tool, and we identify critical engineering considerations for future solar-thermal PCR devices.

  10. KS-Detect - Validation of Solar Thermal PCR for the Diagnosis of Kaposi's Sarcoma Using Pseudo-Biopsy Samples.

    Directory of Open Access Journals (Sweden)

    Ryan Snodgrass

    Full Text Available Resource-limited settings present unique engineering challenges for medical diagnostics. Diagnosis is often needed for those unable to reach central healthcare systems, making portability and independence from traditional energy infrastructure essential device parameters. In 2014, our group presented a microfluidic device that performed a solar-powered variant of the polymerase chain reaction, which we called solar thermal PCR. In this work, we expand on our previous effort by presenting an integrated, portable, solar thermal PCR system targeted towards the diagnosis of Kaposi's sarcoma. We call this system KS-Detect, and we now report the system's performance as a diagnostic tool using pseudo-biopsy samples made from varying concentrations of human lymphoma cell lines positive for the KS herpesvirus (KSHV. KS-Detect achieved 83% sensitivity and 70% specificity at high (≥ 10% KSHV+ cell concentrations when diagnosing pseudo-biopsy samples by smartphone image. Using histology, we confirm that our prepared pseudo-biopsies contain similar KSHV+ cell concentrations as human biopsies positive for KS. Through our testing of samples derived from human cell lines, we validate KS-Detect as a viable, portable KS diagnostic tool, and we identify critical engineering considerations for future solar-thermal PCR devices.

  11. Evaluation of non-invasive multispectral imaging as a tool for measuring the effect of systemic therapy in Kaposi sarcoma.

    Directory of Open Access Journals (Sweden)

    Jana M Kainerstorfer

    Full Text Available Diffuse multi-spectral imaging has been evaluated as a potential non-invasive marker of tumor response. Multi-spectral images of Kaposi sarcoma skin lesions were taken over the course of treatment, and blood volume and oxygenation concentration maps were obtained through principal component analysis (PCA of the data. These images were compared with clinical and pathological responses determined by conventional means. We demonstrate that cutaneous lesions have increased blood volume concentration and that changes in this parameter are a reliable indicator of treatment efficacy, differentiating responders and non-responders. Blood volume decreased by at least 20% in all lesions that responded by clinical criteria and increased in the two lesions that did not respond clinically. Responses as assessed by multi-spectral imaging also generally correlated with overall patient clinical response assessment, were often detectable earlier in the course of therapy, and are less subject to observer variability than conventional clinical assessment. Tissue oxygenation was more variable, with lesions often showing decreased oxygenation in the center surrounded by a zone of increased oxygenation. This technique could potentially be a clinically useful supplement to existing response assessment in KS, providing an early, quantitative, and non-invasive marker of treatment effect.

  12. False-Negative Results of Endoscopic Biopsy in the Diagnosis of Gastrointestinal Kaposi's Sarcoma in HIV-Infected Patients.

    Science.gov (United States)

    Nagata, Naoyoshi; Sekine, Katsunori; Igari, Toru; Hamada, Yohei; Yazaki, Hirohisa; Ohmagari, Norio; Akiyama, Junichi; Shimbo, Takuro; Teruya, Katsuji; Oka, Shinichi; Uemura, Naomi

    2012-01-01

    Kaposi's sarcoma (KS) is a rare endothelial neoplasm mainly involving the skin, but it is often associated with AIDS. Diagnosis of gastrointestinal (GI) tract KS, a common site of visceral involvement in AIDS, is important, but endoscopic biopsy carries a risk of false-negative results (FNRs) due to its submucosal appearance. This study sought to determine the rate and causes of FNR for endoscopic biopsy of GI-KS lesions. Endoscopic biopsy samples of 116 GI-KS lesions were reviewed retrospectively. All GI-KS lesions were confirmed to be resolved following KS therapy. FNRs were yielded for 41 of the lesions (35.3%). Among upper and lower GI sites, the esophagus was the only site significantly associated with FNRs (P FNRs (P FNRs were found in 35.3% of GI-KS lesions and were especially related to the site of the esophagus and endoscopic early stage (small size or patch appearance). An SMT with ulceration may be relatively easy to diagnose on endoscopic biopsy. Caution should be exercised when performing endoscopic biopsy of these lesions in AIDS patients and evaluating the histological features.

  13. Leaky Fermi accelerators

    CERN Document Server

    Shah, Kushal; Rom-Kedar, Vered; Turaev, Dmitry

    2015-01-01

    A Fermi accelerator is a billiard with oscillating walls. A leaky accelerator interacts with an environment of an ideal gas at equilibrium by exchange of particles through a small hole on its boundary. Such interaction may heat the gas: we estimate the net energy flow through the hole under the assumption that the particles inside the billiard do not collide with each other and remain in the accelerator for sufficiently long time. The heat production is found to depend strongly on the type of the Fermi accelerator. An ergodic accelerator, i.e. one which has a single ergodic component, produces a weaker energy flow than a multi-component accelerator. Specifically, in the ergodic case the energy gain is independent of the hole size, whereas in the multi-component case the energy flow may be significantly increased by shrinking the hole size.

  14. Accelerator reliability workshop

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, L.; Duru, Ph.; Koch, J.M.; Revol, J.L.; Van Vaerenbergh, P.; Volpe, A.M.; Clugnet, K.; Dely, A.; Goodhew, D

    2002-07-01

    About 80 experts attended this workshop, which brought together all accelerator communities: accelerator driven systems, X-ray sources, medical and industrial accelerators, spallation sources projects (American and European), nuclear physics, etc. With newly proposed accelerator applications such as nuclear waste transmutation, replacement of nuclear power plants and others. Reliability has now become a number one priority for accelerator designers. Every part of an accelerator facility from cryogenic systems to data storage via RF systems are concerned by reliability. This aspect is now taken into account in the design/budget phase, especially for projects whose goal is to reach no more than 10 interruptions per year. This document gathers the slides but not the proceedings of the workshop.

  15. Accelerator and radiation physics

    CERN Document Server

    Basu, Samita; Nandy, Maitreyee

    2013-01-01

    "Accelerator and radiation physics" encompasses radiation shielding design and strategies for hadron therapy accelerators, neutron facilities and laser based accelerators. A fascinating article describes detailed transport theory and its application to radiation transport. Detailed information on planning and design of a very high energy proton accelerator can be obtained from the article on radiological safety of J-PARC. Besides safety for proton accelerators, the book provides information on radiological safety issues for electron synchrotron and prevention and preparedness for radiological emergencies. Different methods for neutron dosimetry including LET based monitoring, time of flight spectrometry, track detectors are documented alongwith newly measured experimental data on radiation interaction with dyes, polymers, bones and other materials. Design of deuteron accelerator, shielding in beam line hutches in synchrotron and 14 MeV neutron generator, various radiation detection methods, their characteriza...

  16. Power Converters for Accelerators

    CERN Document Server

    Visintini, R

    2015-01-01

    Particle accelerators use a great variety of power converters for energizing their sub-systems; while the total number of power converters usually depends on the size of the accelerator or combination of accelerators (including the experimental setup), the characteristics of power converters depend on their loads and on the particle physics requirements: this paper aims to provide an overview of the magnet power converters in use in several facilities worldwide.

  17. Miniaturization Techniques for Accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Spencer, James E.

    2003-05-27

    The possibility of laser driven accelerators [1] suggests the need for new structures based on micromachining and integrated circuit technology because of the comparable scales. Thus, we are exploring fully integrated structures including sources, optics (for both light and particle) and acceleration in a common format--an accelerator-on-chip (AOC). Tests suggest a number of preferred materials and techniques but no technical or fundamental roadblocks at scales of order 1 {micro}m or larger.

  18. FFAGS for rapid acceleration

    Energy Technology Data Exchange (ETDEWEB)

    Carol J. Johnstone and Shane Koscielniak

    2002-09-30

    When large transverse and longitudinal emittances are to be transported through a circular machine, extremely rapid acceleration holds the advantage that the beam becomes immune to nonlinear resonances because there is insufficient time for amplitudes to build up. Uncooled muon beams exhibit large emittances and require fast acceleration to avoid decay losses and would benefit from this style of acceleration. The approach here employs a fixed-field alternating gradient or FFAG magnet structure and a fixed frequency acceleration system. Acceptance is enhanced by the use only of linear lattice elements, and fixed-frequency rf enables the use of cavities with large shunt resistance and quality factor.

  19. FFAGS FOR MUON ACCELERATION.

    Energy Technology Data Exchange (ETDEWEB)

    BERG,J.S.KAHN,S.PALMER,R.TRBOJEVIC,D.JOHNSTONE,C.KEIL,Y.OGITSU,T.OHMORI,C.SESSLER,A.KOSCIELNIAK,S.

    2003-06-26

    Due to their finite lifetime, muons must be accelerated very rapidly. It is challenging to make the magnets ramp fast enough to accelerate in a synchrotron, and accelerating in a linac is very expensive. One can use a recirculating accelerator (like CEBAF), but one needs a different arc for each turn, and this limits the number of turns one can use to accelerate, and therefore requires significant amounts of RF to achieve the desired energy gain. An alternative method for muon acceleration is using a fixed field alternating gradient (FFAG) accelerator. Such an accelerator has a very large energy acceptance (a factor of two or three), allowing one to use the same arc with a magnetic field that is constant over time. Thus, one can in principle make as many turns as one can tolerate due to muon decay, therefore reducing the RF cost without increasing the arc cost. This paper reviews the current status of research into the design of FFAGs for muon acceleration. Several current designs are described and compared. General design considerations are also discussed.

  20. High Gradient Accelerator Research

    Energy Technology Data Exchange (ETDEWEB)

    Temkin, Richard [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Dept. of Physics. Plasma Science and Fusion Center

    2016-07-12

    The goal of the MIT program of research on high gradient acceleration is the development of advanced acceleration concepts that lead to a practical and affordable next generation linear collider at the TeV energy level. Other applications, which are more near-term, include accelerators for materials processing; medicine; defense; mining; security; and inspection. The specific goals of the MIT program are: • Pioneering theoretical research on advanced structures for high gradient acceleration, including photonic structures and metamaterial structures; evaluation of the wakefields in these advanced structures • Experimental research to demonstrate the properties of advanced structures both in low-power microwave cold test and high-power, high-gradient test at megawatt power levels • Experimental research on microwave breakdown at high gradient including studies of breakdown phenomena induced by RF electric fields and RF magnetic fields; development of new diagnostics of the breakdown process • Theoretical research on the physics and engineering features of RF vacuum breakdown • Maintaining and improving the Haimson / MIT 17 GHz accelerator, the highest frequency operational accelerator in the world, a unique facility for accelerator research • Providing the Haimson / MIT 17 GHz accelerator facility as a facility for outside users • Active participation in the US DOE program of High Gradient Collaboration, including joint work with SLAC and with Los Alamos National Laboratory; participation of MIT students in research at the national laboratories • Training the next generation of Ph. D. students in the field of accelerator physics.

  1. Epidemiological surveillance of the HIV/AIDS complex through the analysis of trends in the incidence of Kaposi's sarcoma in Cali, Colombia

    Science.gov (United States)

    Saldarriaga-Cantillo, Alejandra; Londoño, Óscar; García, Luz Stella; Collazos, Paola

    2012-01-01

    Introduction: The Kaposi's sarcoma (KS) incidence has markedly changed in the general population since the onset of the AIDS epidemic in the eighties and after the introduction of the Highly Active Antiretroviral Therapy (HAART) in the nineties. Objective: To investigate incidence rate trends for Kaposi's sarcoma before and during the (HIV/AIDS) epidemic in Cali, Colombia. Methods: Exploratory ecological study that included all Kaposi's sarcoma cases identified by the Cali Cancer Registry from 1962-2007, and 12,887 cases of HIV/AIDS recorded in the Municipal Health Secretariat of Cali between 1986 and 2010. The joinpoint regression model was used to conduct the incidence rate analyses between the years 1962 and 2010. Results: A total of 349 KS cases were identified during the study period. Only 5.3% of the cases (n=20) were diagnosed in the pre-epidemic era (1963-1987), of these, 35% were women, and 90% of the tumors were located on the skin. In contrast, 94.7% of KS cases (n=329) were discovered after the emergence of HIV-AIDS. There was a significant decrease in the proportion of women (10.9%, p <0.001) and an increase in the frequency of tumors with an extra-cutaneous location (19.1%, p <0.01) compared to those cases diagnosed in the pre-epidemic era. Notification rates of HIV/AIDS have decreased since 2002 in both genders but KS incidence rates have decreased since 2004 in men only. Conclusion: The downward trend in the incidence of these diseases may be associated with factors that prevent the transmission of HIV infection or limit the spread of HIV in the community. Cancer registries represent a resource for timely, population-based surveil-lance of HIV-associated malignancies in Cali, Colombia. PMID:24893300

  2. Asia honours accelerator physicists

    CERN Multimedia

    2010-01-01

    "Steve Meyers of Cern and Jie Wei of Beijing's Tsinghua University are the first recipients of a new prize for particle physics. The pair were honoured for their contributions to numerous particle-accelerator projects - including Cern's Large Hadron Collider - by the Asian Committee for Future Accelerators (ACFA)..." (1 paragraph)

  3. COLLECTIVE-FIELD ACCELERATION

    Energy Technology Data Exchange (ETDEWEB)

    Sessler, Andrew M.

    1969-07-04

    Diverse methods proposed for the acceleration of particles by means of collective fields are reviewed. A survey is made of the various currently active experimental programs devoted to investigating collective acceleration, and the present status of the research is briefly noted.

  4. Accelerators Beyond The Tevatron?

    Energy Technology Data Exchange (ETDEWEB)

    Lach, Joseph; /Fermilab

    2010-07-01

    Following the successful operation of the Fermilab superconducting accelerator three new higher energy accelerators were planned. They were the UNK in the Soviet Union, the LHC in Europe, and the SSC in the United States. All were expected to start producing physics about 1995. They did not. Why?

  5. KEK digital accelerator

    Science.gov (United States)

    Iwashita, T.; Adachi, T.; Takayama, K.; Leo, K. W.; Arai, T.; Arakida, Y.; Hashimoto, M.; Kadokura, E.; Kawai, M.; Kawakubo, T.; Kubo, Tomio; Koyama, K.; Nakanishi, H.; Okazaki, K.; Okamura, K.; Someya, H.; Takagi, A.; Tokuchi, A.; Wake, M.

    2011-07-01

    The High Energy Accelerator Research Organization KEK digital accelerator (KEK-DA) is a renovation of the KEK 500 MeV booster proton synchrotron, which was shut down in 2006. The existing 40 MeV drift tube linac and rf cavities have been replaced by an electron cyclotron resonance (ECR) ion source embedded in a 200 kV high-voltage terminal and induction acceleration cells, respectively. A DA is, in principle, capable of accelerating any species of ion in all possible charge states. The KEK-DA is characterized by specific accelerator components such as a permanent magnet X-band ECR ion source, a low-energy transport line, an electrostatic injection kicker, an extraction septum magnet operated in air, combined-function main magnets, and an induction acceleration system. The induction acceleration method, integrating modern pulse power technology and state-of-art digital control, is crucial for the rapid-cycle KEK-DA. The key issues of beam dynamics associated with low-energy injection of heavy ions are beam loss caused by electron capture and stripping as results of the interaction with residual gas molecules and the closed orbit distortion resulting from relatively high remanent fields in the bending magnets. Attractive applications of this accelerator in materials and biological sciences are discussed.

  6. KEK digital accelerator

    Directory of Open Access Journals (Sweden)

    T. Iwashita

    2011-07-01

    Full Text Available The High Energy Accelerator Research Organization KEK digital accelerator (KEK-DA is a renovation of the KEK 500 MeV booster proton synchrotron, which was shut down in 2006. The existing 40 MeV drift tube linac and rf cavities have been replaced by an electron cyclotron resonance (ECR ion source embedded in a 200 kV high-voltage terminal and induction acceleration cells, respectively. A DA is, in principle, capable of accelerating any species of ion in all possible charge states. The KEK-DA is characterized by specific accelerator components such as a permanent magnet X-band ECR ion source, a low-energy transport line, an electrostatic injection kicker, an extraction septum magnet operated in air, combined-function main magnets, and an induction acceleration system. The induction acceleration method, integrating modern pulse power technology and state-of-art digital control, is crucial for the rapid-cycle KEK-DA. The key issues of beam dynamics associated with low-energy injection of heavy ions are beam loss caused by electron capture and stripping as results of the interaction with residual gas molecules and the closed orbit distortion resulting from relatively high remanent fields in the bending magnets. Attractive applications of this accelerator in materials and biological sciences are discussed.

  7. Nursing for one patient with classical Kaposi's sarcoma%1例经典型Kaposi肉瘤患者的护理

    Institute of Scientific and Technical Information of China (English)

    张昕婷

    2007-01-01

    @@ Kaposi肉瘤(Kaposi's sarcoma)是一种极其罕见的发生在皮肤、黏膜、淋巴结、内脏的恶性肿瘤,在临床上分为经典型、非洲地方型、免疫抑制/器官移植相关型和艾滋病相关型[3,4].我院2006年3-8月收治了1例经典型Kaposi肉瘤患者,现报道如下.

  8. Salivary production of IgA and IgG to human herpes virus 8 latent and lytic antigens by patients in whom Kaposi's sarcoma has regressed.

    Science.gov (United States)

    Mbopi-Keou, Francois-Xavier; Legoff, Jerome; Piketty, Christophe; Hocini, Hakim; Malkin, Jean-Elie; Inoue, Naoki; Scully, Crispian M; Porter, Stephen R; Teo, Chong-Gee; Belec, Laurent

    2004-01-23

    IgG and IgA antibodies with specificities to a latent and a lytic antigen of human herpes virus 8 (HHV-8) were detectable in the saliva and serum of eight patients whose Kaposi's sarcoma had regressed, seven of whom were HIV-1 infected. The measurement of antibody-specific activity and secretion rate, and the detection of secretory IgA all indicate anti-HHV-8 antibody activity in saliva. The specific humoral responses possibly influence mucosal replication of HHV-8, and in turn, that of HIV.

  9. Accelerators, Beams And Physical Review Special Topics - Accelerators And Beams

    Energy Technology Data Exchange (ETDEWEB)

    Siemann, R.H.; /SLAC

    2011-10-24

    Accelerator science and technology have evolved as accelerators became larger and important to a broad range of science. Physical Review Special Topics - Accelerators and Beams was established to serve the accelerator community as a timely, widely circulated, international journal covering the full breadth of accelerators and beams. The history of the journal and the innovations associated with it are reviewed.

  10. The Accelerated Kepler Problem

    CERN Document Server

    Namouni, Fathi

    2007-01-01

    The accelerated Kepler problem is obtained by adding a constant acceleration to the classical two-body Kepler problem. This setting models the dynamics of a jet-sustaining accretion disk and its content of forming planets as the disk loses linear momentum through the asymmetric jet-counterjet system it powers. The dynamics of the accelerated Kepler problem is analyzed using physical as well as parabolic coordinates. The latter naturally separate the problem's Hamiltonian into two unidimensional Hamiltonians. In particular, we identify the origin of the secular resonance in the accelerated Kepler problem and determine analytically the radius of stability boundary of initially circular orbits that are of particular interest to the problem of radial migration in binary systems as well as to the truncation of accretion disks through stellar jet acceleration.

  11. On Accelerated Black Holes

    CERN Document Server

    Letelier, P S; Letelier, Patricio S.; Oliveira, Samuel R.

    1998-01-01

    The C-metric is revisited and global interpretation of some associated spacetimes are studied in some detail. Specially those with two event horizons, one for the black hole and another for the acceleration. We found that the spacetime fo an accelerated Schwarzschild black hole is plagued by either conical singularities or lack of smoothness and compactness of the black hole horizon. By using standard black hole thermodynamics we show that accelerated black holes have higher Hawking temperature than Unruh temperature. We also show that the usual upper bound on the product of the mass and acceleration parameters (<1/sqrt(27)) is just a coordinate artifact. The main results are extended to accelerated Kerr black holes. We found that they are not changed by the black hole rotation.

  12. Particle acceleration by plasma

    CERN Document Server

    Ogata, A

    2002-01-01

    Plasma acceleration is carried out by using potential of plasma wave. It is classified by generation method of plasma wave such as the laser wake-field acceleration and the beat wave acceleration. Other method using electron beam is named the plasma wake-field acceleration (or beam wake-field acceleration). In this paper, electron acceleration by laser wake-field in gas plasma, ion source by laser radiation of solid target and nanoion beam generation by one component of plasma in trap are explained. It is an applicable method that ions, which run out from the solid target irradiated by laser, are used as ion source of accelerator. The experimental system using 800 nm laser, 50 mJ pulse energy and 50 fs pulse width was studied. The laser intensity is 4x10 sup 1 sup 6 Wcm sup - sup 2 at the focus. The target film of metal and organic substance film was used. When laser irradiated Al target, two particles generated, in front and backward. It is new fact that the neutral particle was obtained in front, because it...

  13. The miniature accelerator

    CERN Multimedia

    Antonella Del Rosso

    2015-01-01

    The image that most people have of CERN is of its enormous accelerators and their capacity to accelerate particles to extremely high energies. But thanks to some cutting-edge studies on beam dynamics and radiofrequency technology, along with innovative construction techniques, teams at CERN have now created the first module of a brand-new accelerator, which will be just 2 metres long. The potential uses of this miniature accelerator will include deployment in hospitals for the production of medical isotopes and the treatment of cancer. It’s a real David-and-Goliath story.   Serge Mathot, in charge of the construction of the "mini-RFQ", pictured with the first of the four modules that will make up the miniature accelerator. The miniature accelerator consists of a radiofrequency quadrupole (RFQ), a component found at the start of all proton accelerator chains around the world, from the smallest to the largest. The LHC is designed to produce very high-intensity beams ...

  14. Cosmic particle acceleration

    Energy Technology Data Exchange (ETDEWEB)

    Zimbardo, Gaetano; Perri, Silvia [Universita della Calabria, Dipartimento di Fisica, 87036 Rende (Italy)

    2014-07-01

    The most popular mechanism for the acceleration of cosmic rays, which is thought to operate in supernova remnant shocks as well as at heliospheric shocks, is the diffusive shock acceleration, which is a Fermi mechanism based on normal diffusion. On the other hand, in the last few years it has been shown that the transport of plasma particles in the presence of electric and magnetic turbulence can be superdiffusive rather than normal diffusive. The term 'superdiffusive' refers to the mean square displacement of particle positions growing superlinearly with time, as compared to the normal linear growth. In particular, superdiffusion is characterized by a non Gaussian statistical process called Levy random walk. We show how diffusive shock acceleration is modified by superdiffusion, and how this yields new predictions for the cosmic ray spectral index, for the acceleration time, and for the spatial profile of energetic particles. A comparison with observations of particle acceleration at heliospheric shocks and at supernova remnant shocks is done. We discuss how superdiffusive shock acceleration allows to explain the observations of hard ion spectra at the solar wind termination shock detected by Voyager 2, of hard radio spectra due to synchrotron emission of electrons accelerated at supernova remnant shocks, and how it can help to explain the observations of 'thin rims' in the X-ray synchrotron emission.

  15. Multicavity proton cyclotron accelerator

    Directory of Open Access Journals (Sweden)

    J. L. Hirshfield

    2002-08-01

    Full Text Available A mechanism for acceleration of protons is described, in which energy gain occurs near cyclotron resonance as protons drift through a sequence of rotating-mode TE_{111} cylindrical cavities in a strong nearly uniform axial magnetic field. Cavity resonance frequencies decrease in sequence from one another with a fixed frequency interval Δf between cavities, so that synchronism can be maintained between the rf fields and proton bunches injected at intervals of 1/Δf. An example is presented in which a 122 mA, 1 MeV proton beam is accelerated to 961 MeV using a cascade of eight cavities in an 8.1 T magnetic field, with the first cavity resonant at 120 MHz and with Δf=8 MHz. Average acceleration gradient exceeds 40 MV/m, average effective shunt impedance is 223 MΩ/m, but maximum surface field in the cavities does not exceed 7.2 MV/m. These features occur because protons make many orbital turns in each cavity and thus experience acceleration from each cavity field many times. Longitudinal and transverse stability appear to be intrinsic properties of the acceleration mechanism, and an example to illustrate this is presented. This acceleration concept could be developed into a proton accelerator for a high-power neutron spallation source, such as that required for transmutation of nuclear waste or driving a subcritical fission burner, provided a number of significant practical issues can be addressed.

  16. Optimization, in vitro cytotoxicity and penetration capability of deformable nanovesicles of paclitaxel for dermal chemotherapy in Kaposi sarcoma.

    Science.gov (United States)

    Pathak, Kamla; Sharma, Vijay; Sharma, Meenu

    2016-11-01

    Although much research has been published on ways to overcome the low oral bioavailability of paclitaxel, exploration of novel drug delivery systems that can target paclitaxel deep in to the dermal areas in AIDS-related Kaposi sarcoma (KS) have not yet been reported. Our aim was to develop deformable nanovesicles of paclitaxel capable of being used in dermal chemotherapy, especially deep into the dermal areas of AIDS related KS. Deformable nanovesicular formulations (TS1-TS15) composed of soya lecithin and span80 were prepared by the rotary evaporation sonication method within the constraints of our Box-Behnken design. The formulations were subjected to vesicle characterization and ex vivo permeation. The optimized vesicular suspension was formulated as a gel and assessed for in vitro cytotoxicity and penetration characteristics by confocal laser scanning microscopy (CLSM). TS9 with vesicle size characteristics of 185.76 ± 2.15 nm, zeta potential of -23.2 mV, deformability index = 138.02 and cumulative drug permeation of 89.80 ± 1.84% was identified as the optimized formulation. TEM revealed spherical vesicles with firm boundaries that were stable at 4 °C. TS9 was developed as carbopol 934P gel (TG) and compared with the control gel (CG) made with the pure drug (paclitaxel). TG showed significantly higher (p < 0.05) in vitro drug permeation and flux compared to the CG. In vitro cytotoxicity study on KSY-1 cell lines revealed higher IC50 (≤17) for TS against IC50 ≤19 for TG. CLSM confirmed the penetrating potential of transfersomes via TG to the dermal layers of skin, the proposed target site. Conclusively, deformable nonovesicles of paclitaxel appear as a feasible alternative to the conventional formulations of paclitaxel in the management of AIDS-related KS.

  17. Human Herpesvirus 8 (HHV8 sequentially shapes the NK cell repertoire during the course of asymptomatic infection and Kaposi sarcoma.

    Directory of Open Access Journals (Sweden)

    Stéphanie Dupuy

    2012-01-01

    Full Text Available The contribution of innate immunity to immunosurveillance of the oncogenic Human Herpes Virus 8 (HHV8 has not been studied in depth. We investigated NK cell phenotype and function in 70 HHV8-infected subjects, either asymptomatic carriers or having developed Kaposi's sarcoma (KS. Our results revealed substantial alterations of the NK cell receptor repertoire in healthy HHV8 carriers, with reduced expression of NKp30, NKp46 and CD161 receptors. In addition, down-modulation of the activating NKG2D receptor, associated with impaired NK-cell lytic capacity, was observed in patients with active KS. Resolution of KS after treatment was accompanied with restoration of NKG2D levels and NK cell activity. HHV8-latently infected endothelial cells overexpressed ligands of several NK cell receptors, including NKG2D ligands. The strong expression of NKG2D ligands by tumor cells was confirmed in situ by immunohistochemical staining of KS biopsies. However, no tumor-infiltrating NK cells were detected, suggesting a defect in NK cell homing or survival in the KS microenvironment. Among the known KS-derived immunoregulatory factors, we identified prostaglandin E2 (PGE2 as a critical element responsible for the down-modulation of NKG2D expression on resting NK cells. Moreover, PGE2 prevented up-regulation of the NKG2D and NKp30 receptors on IL-15-activated NK cells, and inhibited the IL-15-induced proliferation and survival of NK cells. Altogether, our observations are consistent with distinct immunoevasion mechanisms that allow HHV8 to escape NK cell responses stepwise, first at early stages of infection to facilitate the maintenance of viral latency, and later to promote tumor cell growth through suppression of NKG2D-mediated functions. Importantly, our results provide additional support to the use of PGE2 inhibitors as an attractive approach to treat aggressive KS, as they could restore activation and survival of tumoricidal NK cells.

  18. A Cases of AIDS Patient Related Kaposi' s Sarcoma%艾滋病相关型Kaposi肉瘤1例

    Institute of Scientific and Technical Information of China (English)

    付学敬; 徐彦春; 杜华; 许旭峰

    2012-01-01

    患者男,32岁.口腔上颚出现褐色增生物、面颈部及阴茎出现褐色斑块和结节4个月,周身乏力3个月.皮损组织病理示:真皮血管扩张,充血明显,部分呈出芽状生长,间质内可见小灶性梭型细胞.血清抗HIV抗体阳性;RPR(-);球蛋白52.2g/L;免疫全项:CD4:12细胞/μL; CD8:430细胞/μL; CD4/CD8:0.03;β微球蛋白6.4mg/L; A/G:0.7;WBC:1.4× 109/L,L:0.5×109/L.诊断:艾滋病相关型Kaposi肉瘤.%A 32-year-old male presented with brown lump on his Palate, and brown plaques , nodules on his face and penis about 4 months, and also felt lack power for 3 months. Histopathological examination showed that there were lots of vascular dilatation and congestion in the dermis, part of them presented budding shaped growth. There were small spindle cells gather together in the interstice. HIV (+); RPR(-); Globulins : 52.2 g/L; Immunonhistochemical examination showed: CD4: 12 cells /μL; CD8: 430 cells /μL; CD4/ CD8: 0.03; Beta microglobulin: 6.4mg/L; A/G 0.7; WBC 1.4×109/L; L 0.5×109/L. Diagnosis: AIDS related Kaposi's sarcoma.

  19. Regulatory T Cell Effect on CD8(+) T Cell Responses to Human Herpesvirus 8 Infection and Development of Kaposi's Sarcoma.

    Science.gov (United States)

    Lepone, Lauren M; Rappocciolo, Giovanna; Piazza, Paolo A; Campbell, Diana M; Jenkins, Frank J; Rinaldo, Charles R

    2017-03-02

    We assessed CD8(+) T cell reactivity to human herpesvirus 8 (HHV-8; Kaposi's sarcoma [KS]-associated herpesvirus) and the role of CD4(+)CD25(hi)FoxP3(+) regulatory T cells (Treg) in HHV-8- and HIV-coinfected participants of the Multicenter AIDS Cohort Study who did or did not develop KS. There were similarly low CD8(+) T cell interferon-γ responses to MHC class I-restricted epitopes of HHV-8 lytic and latent proteins over 5.7 years before KS in participants who developed KS compared to those who did not. T cell reactivity to HHV-8 antigens was low relative to responses to a combination of cytomegalovirus, Epstein-Barr virus and influenza A virus (CEF) peptide epitopes, and dominant HIV peptide epitopes. There was no change in %Treg in the HHV-8- and HIV-coinfected participants who did not develop KS, whereas there was a significant increase in %Treg in HHV-8- and HIV-coinfected participants who developed KS beginning 1.8 years before development of KS. Removal of Treg enhanced HHV-8-specific T cell responses in HHV-8- and HIV-coinfected participants who did or did not develop KS, with a similar pattern observed in response to CEF and HIV peptides. Thus, long-term, low levels of anti-HHV-8 CD8(+) T cell reactivity were present in both HHV-8- and HIV-coinfected men who did and did not develop KS. This was related to moderately enhanced Treg function.

  20. Human and viral interleukin-6 and other cytokines in Kaposi sarcoma herpesvirus-associated multicentric Castleman disease

    Science.gov (United States)

    Uldrick, Thomas S.; Wang, Victoria; Aleman, Karen; Wyvill, Kathleen M.; Marshall, Vickie; Pittaluga, Stefania; O’Mahony, Deirdre; Whitby, Denise; Tosato, Giovanna; Steinberg, Seth M.; Little, Richard F.

    2013-01-01

    Kaposi sarcoma herpesvirus (KSHV)-associated multicentric Castleman disease (MCD) is a polyclonal B-cell lymphoproliferative disorder. Human (h) IL-6 and a KSHV-encoded homolog, viral IL-6, have been hypothesized to contribute to its pathogenesis, but their relative contributions to disease activity is not well understood. We prospectively characterized KSHV viral load (VL), viral (v) and hIL-6, and other cytokines during KSHV-MCD flare and remission in 21 patients with 34 flares and 20 remissions. KSHV-VL, vIL-6, hIL-6, IL-10, and to a lesser extent TNF-α, and IL-1β were each elevated during initial flares compared with remission. Flares fell into 3 distinct IL-6 profiles: those associated with elevations of vIL6-only (2 flares, 6%), hIL-6 elevations only (17 flares, 50%), and elevations in both hIL-6 and vIL-6 (13 flares, 38%). Compared with hIL-6–only flares, flares with elevated hIL-6 plus vIL-6 exhibited higher C-reactive protein (CRP) (P = .0009); worse hyponatremia (P = .02); higher KSHV VL (P = .016), and higher IL-10 (P = .012). This analysis shows vIL-6 and hIL-6 can independently or together lead to KSHV-MCD flares, and suggests that vIL-6 and hIL-6 may jointly contribute to disease severity. These findings have implications for the development of novel KSHV-MCD therapies targeting IL-6 and its downstream signaling. This trial was registered at clinicaltrials.gov as #NCT099073. PMID:24174627

  1. Quantification of oral palatine Langerhans cells in HIV/AIDS associated oral Kaposi sarcoma with and without oral candidiasis.

    Science.gov (United States)

    Jivan, Vibha; Meer, Shabnum

    2016-01-01

    Langerhans cells (LCs) are effective antigen-presenting cells that function as "custodians" of mucosa, modifying the immune system to pathogen entry, and tolerance to self-antigen and commensal microbes. A reduction in number of LCs in human immunodeficiency virus (HIV)-positive individuals may predispose to local mucosal infections. To quantitatively determine the number of oral mucosal LCs in HIV/acquired immunodeficiency syndrome HIV/acquired immunodeficiency syndrome (AIDS) associated oral Kaposi sarcoma (KS) with/without oral candidiasis (OC) and to define in situ interrelationships between the cells, OC, and HIV infection. Thirty-two periodic acid-Schiff. (PAS) stained histologic sections of palatal HIV/AIDS associated KS with intact oral epithelium were examined for Candida and divided into two groups: . (1) KS coinfected with Candida and. (2) KS noninfected with Candida. Sections were immunohistochemically stained with CD1a. The standard length of surface epithelium was measured and number of positively stained LCs counted per unit length. Control cases included non-Candida infected palatal mucosa overlying pleomorphic adenoma. (PA) and oral mucosa infected with Candida in otherwise healthy individuals. LC number per unit length of surface epithelium was statistically significantly greatest in uninfected PA mucosa and lowest in KS coinfected with Candida (P = 0.0001). A statistically significant difference was also noted between uninfected PA mucosa and non-Candida infected KS (P = 0.0014), in KS coinfected with Candida and non-infected KS (P = 0.0035), between OC and PA (P = 0.0001), and OC and KS coinfected with Candida (P = 0.0247). LC numbers are significantly reduced in oral tissues of HIV/AIDS infected patients by Candida infection when compared to oral tissues without.

  2. Evaluation of the relationship between c-Kit expression and mean platelet volume in classic Kaposi's sarcoma*

    Science.gov (United States)

    Sehitoglu, Ibrahim; Bedir, Recep; Cure, Erkan; Cure, Medine Cumhur; Yuce, Suleyman; Dilek, Nursel

    2016-01-01

    Background c-Kit is a proto-oncogene that encodes tyrosine kinase receptor (CD117). Mean platelet volume (MPV) is a useful marker, providing information on platelet function and diameter. Objective To investigate c-Kit expression and intensity in patients with Kaposi's sarcoma (KS) and to investigate the relation between Ki-67 proliferation and MPV. Methods A total of 32 patients, diagnosed with classic cutaneous KS, were included in this study. We reevaluated the histopathological reports with the preparations, confirmed the diagnosis and then determined the patients' histopathological stages. c-Kit expression and Ki-67 proliferation were investigated immunohistochemically in KS cases, while MPV in all cases was checked. Results Although c-Kit expression was detected in 22 cases (68.8%), it was not expressed in 10 cases (31.2%). We detected 8 cases with + (25%), 6 with ++ (18.8%) and 8 with +++ (25%). Ki-67 expression was 5.0% (min-max 1.0-20.0). Relapse was observed in 5 cases (15.6%) out of 32. There was positive correlation between c-Kit expression and MPV (rs=0.598, p<0.001), and between c-Kit intensity and MPV (rs=0.588, p<0.001). Conclusion c-Kit is highly positive in KS. c-Kit positivity indicates a high risk of tumor growth, invasion and relapse. Furthermore, c-Kit expression stimulates megakaryocytes to release young and large thrombocytes into the periphery. Thus, high MPV, c-Kit expression and immunostaining intensity indicate high invasion and relapse in KS subjects. PMID:27579736

  3. Relative effects of phenolic constituents from Yucca schidigera Roezl. bark on Kaposi's sarcoma cell proliferation, migration, and PAF synthesis.

    Science.gov (United States)

    Balestrieri, Ciro; Felice, Francesca; Piacente, Sonia; Pizza, Cosimo; Montoro, Paola; Oleszek, Wieslaw; Visciano, Vincenzo; Balestrieri, Maria Luisa

    2006-05-14

    Yuccaols (A, B, C) are phenolic constituents isolated from Yucca schidigera bark characterized by unusual spirostructures made up of a C15 unit and a stilbenic portion closely related to resveratrol. These novel compounds are of particular interest for their antioxidant and anti-inflammatory properties. However, their effects on cell proliferation, migration, and platelet-activating factor (PAF) biosynthesis remain unknown. PAF, a potent mediator of inflammation, is known to promote angiogenesis and in vitro migration of endothelial cells and Kaposi's sarcoma (KS) cells. The objective of our study was to determine the effect of Yuccaols and resveratrol on the vascular endothelial growth factor (VEGF)-induced proliferation, migration, and PAF biosynthesis in KS cells. The results indicated that Yuccaols (25 microM) were more effective than resveratrol (25 microM) in inhibiting the VEGF-induced KS cell proliferation. Western blot analysis revealed that Yuccaols reduced the VEGF-induced phosphorylation of p38 and p42/44, thus indicating a possible interference with the mechanism underlying the VEGF-stimulated cell proliferation. Furthermore, Yuccaols completely inhibited the VEGF-stimulated PAF biosynthesis catalyzed by the acetyl-CoA:lyso-PAF acetyltransferase and enhanced its degradation through the PAF-dependent CoA-independent transacetylase (250% of control). In addition, Yuccaol C abrogated the PAF-induced cell motility whereas Yuccaol A and Yuccaol B reduced the cell migration from 7.6 microm/h to 6.1 microm/h and 5.6 microm/h, respectively. These results indicate that the anti-inflammatory properties attributed to Yucca schidigera can be ascribed to both resveratrol and Yuccaols and provide the first evidences of the anti-tumor and anti-invasive properties of these novel phenolic compounds.

  4. Application of Accelerators and Storage Rings: Accelerators in Medicine

    CERN Document Server

    Amaldi, U

    2013-01-01

    This document is part of Subvolume C 'Accelerators and Colliders' of Volume 21 'Elementary Particles' of Landolt-Börnstein - Group I 'Elementary Particles, Nuclei and Atoms'. It contains the the Section '11.3 Accelerators in Medicine' of the Chapter '11 Application of Accelerators and Storage Rings' with the content: 11.3 Accelerators in Medicine 11.3.1 Accelerators and Radiopharmaceuticals 11.3.2 Accelerators and Cancer Therapy

  5. Confronting Twin Paradox Acceleration

    Science.gov (United States)

    Murphy, Thomas W.

    2016-05-01

    The resolution to the classic twin paradox in special relativity rests on the asymmetry of acceleration. Yet most students are not exposed to a satisfactory analysis of what exactly happens during the acceleration phase that results in the nonaccelerated observer's more rapid aging. The simple treatment presented here offers both graphical and quantitative solutions to the problem, leading to the correct result that the acceleration-induced age gap is 2Lβ years when the one-way distance L is expressed in light-years and velocity β ≡v/c .

  6. The inflammatory kinase MAP4K4 promotes reactivation of Kaposi's sarcoma herpesvirus and enhances the invasiveness of infected endothelial cells.

    Directory of Open Access Journals (Sweden)

    Darya A Haas

    Full Text Available Kaposi's sarcoma (KS is a mesenchymal tumour, which is caused by Kaposi's sarcoma herpesvirus (KSHV and develops under inflammatory conditions. KSHV-infected endothelial spindle cells, the neoplastic cells in KS, show increased invasiveness, attributed to the elevated expression of metalloproteinases (MMPs and cyclooxygenase-2 (COX-2. The majority of these spindle cells harbour latent KSHV genomes, while a minority undergoes lytic reactivation with subsequent production of new virions and viral or cellular chemo- and cytokines, which may promote tumour invasion and dissemination. In order to better understand KSHV pathogenesis, we investigated cellular mechanisms underlying the lytic reactivation of KSHV. Using a combination of small molecule library screening and siRNA silencing we found a STE20 kinase family member, MAP4K4, to be involved in KSHV reactivation from latency and to contribute to the invasive phenotype of KSHV-infected endothelial cells by regulating COX-2, MMP-7, and MMP-13 expression. This kinase is also highly expressed in KS spindle cells in vivo. These findings suggest that MAP4K4, a known mediator of inflammation, is involved in KS aetiology by regulating KSHV lytic reactivation, expression of MMPs and COX-2, and, thereby modulating invasiveness of KSHV-infected endothelial cells.

  7. Sequence Analysis of Kaposi Sarcoma–Associated Herpesvirus (KSHV) MicroRNAs in Patients with Multicentric Castleman Disease and KSHV-Associated Inflammatory Cytokine Syndrome

    Science.gov (United States)

    Ray, Alex; Marshall, Vickie; Uldrick, Thomas; Leighty, Robert; Labo, Nazzarena; Wyvill, Kathy; Aleman, Karen; Polizzotto, Mark N.; Little, Richard F.; Yarchoan, Robert; Whitby, Denise

    2012-01-01

    Background Kaposi sarcoma–associated herpesvirus (KSHV) encodes 12 pre-microRNAs that yield 25 mature microRNAs. We previously reported phylogenetic analysis of the microRNA-coding region of KSHV from Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD) patients. We observed a high level of conservation for most sequences but also a divergent cluster of 5 KSHV sequences, including 2 from MCD patients. Methods KSHV microRNA sequences from 23 MCD patients and 7 patients with a newly described KSHV-associated inflammatory cytokine syndrome (KICS) were examined by amplification, cloning, and sequencing of a 646-bp fragment of K12/T0.7 encoding microRNA-K12-10 and microRNA-K12-12 and a 2.8-kbp fragment containing the remaining 10 pre-microRNAs. Results Phylogenetic analysis showed a distinct variant cluster consisting exclusively of MCD and KICS patients in all trees. Pearson χ2 analysis revealed that 40 single-nucleotide polymorphisms (SNPs) at various loci were significantly associated with MCD and KICS risk. Cluster analysis of these SNPs generated several combinations of 3 SNPs as putative indicators of MCD and KICS risk. Conclusions These findings show that MCD and KICS patients frequently have unusual KSHV microRNA sequences and suggest an association between the observed sequence variation and risk of MCD and KICS. PMID:22448005

  8. Vibration control in accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Montag, C.

    2011-01-01

    In the vast majority of accelerator applications, ground vibration amplitudes are well below tolerable magnet jitter amplitudes. In these cases, it is necessary and sufficient to design a rigid magnet support structure that does not amplify ground vibration. Since accelerator beam lines are typically installed at an elevation of 1-2m above ground level, special care has to be taken in order to avoid designing a support structure that acts like an inverted pendulum with a low resonance frequency, resulting in untolerable lateral vibration amplitudes of the accelerator components when excited by either ambient ground motion or vibration sources within the accelerator itself, such as cooling water pumps or helium flow in superconducting magnets. In cases where ground motion amplitudes already exceed the required jiter tolerances, for instance in future linear colliders, passive vibration damping or active stabilization may be considered.

  9. Compact particle accelerator

    Energy Technology Data Exchange (ETDEWEB)

    Elizondo-Decanini, Juan M.

    2017-08-29

    A compact particle accelerator having an input portion configured to receive power to produce particles for acceleration, where the input portion includes a switch, is provided. In a general embodiment, a vacuum tube receives particles produced from the input portion at a first end, and a plurality of wafer stacks are positioned serially along the vacuum tube. Each of the plurality of wafer stacks include a dielectric and metal-oxide pair, wherein each of the plurality of wafer stacks further accelerate the particles in the vacuum tube. A beam shaper coupled to a second end of the vacuum tube shapes the particles accelerated by the plurality of wafer stacks into a beam and an output portion outputs the beam.

  10. Rejuvenating CERN's Accelerators

    CERN Multimedia

    2004-01-01

    In the coming years and especially in 2005, CERN's accelerators are going to receive an extensive renovation programme to ensure they will perform reliably and effectively when the LHC comes into service.

  11. Joint International Accelerator School

    CERN Multimedia

    CERN Accelerator School

    2014-01-01

    The CERN and US Particle Accelerator Schools recently organised a Joint International Accelerator School on Beam Loss and Accelerator Protection, held at the Hyatt Regency Hotel, Newport Beach, California, USA from 5-14 November 2014. This Joint School was the 13th in a series of such schools, which started in 1985 and also involves the accelerator communities in Japan and Russia.   Photo courtesy of Alfonse Pham, Michigan State University.   The school attracted 58 participants representing 22 different nationalities, with around half from Europe and the other half from Asia and the Americas. The programme comprised 26 lectures, each of 90 minutes, and 13 hours of case study. The students were given homework each day and had an opportunity to sit a final exam, which counted towards university credit. Feedback from the participants was extremely positive, praising the expertise and enthusiasm of the lecturers, as well as the high standard and quality of their lectures. Initial dis...

  12. Dielectric assist accelerating structure

    Science.gov (United States)

    Satoh, D.; Yoshida, M.; Hayashizaki, N.

    2016-01-01

    A higher-order TM02 n mode accelerating structure is proposed based on a novel concept of dielectric loaded rf cavities. This accelerating structure consists of ultralow-loss dielectric cylinders and disks with irises which are periodically arranged in a metallic enclosure. Unlike conventional dielectric loaded accelerating structures, most of the rf power is stored in the vacuum space near the beam axis, leading to a significant reduction of the wall loss, much lower than that of conventional normal-conducting linac structures. This allows us to realize an extremely high quality factor and a very high shunt impedance at room temperature. A simulation of a 5 cell prototype design with an existing alumina ceramic indicates an unloaded quality factor of the accelerating mode over 120 000 and a shunt impedance exceeding 650 M Ω /m at room temperature.

  13. LHCb GPU Acceleration Project

    CERN Document Server

    AUTHOR|(SzGeCERN)744808; Campora Perez, Daniel Hugo; Neufeld, Niko; Vilasis Cardona, Xavier

    2016-01-01

    The LHCb detector is due to be upgraded for processing high-luminosity collisions, which will increase the load on its computation infrastructure from 100 GB/s to 4 TB/s, encouraging us to look for new ways of accelerating the Online reconstruction. The Coprocessor Manager is our new framework for integrating LHCb’s existing computation pipelines with massively parallel algorithms running on GPUs and other accelerators. This paper describes the system and analyzes its performance.

  14. Accelerating News Issue 2

    CERN Document Server

    Kahle, K; Wildner, E

    2012-01-01

    In this summer issue we look at how developments in collimator materials could have applications in aerospace and beyond, and how Polish researchers are harnessing accelerators for medical and industrial uses. We see how the LHC luminosity upgrade is linking with European industry and US researchers, and how the neutrino oscillation community is progressing. We find out the mid-term status of TIARA-PP and how it is mapping European accelerator education resources.

  15. Accelerating Cosmologies from Compactification

    CERN Document Server

    Townsend, P K; Townsend, Paul K.; Wohlfarth, Mattias N.R.

    2003-01-01

    A solution of the (4+n)-dimensional vacuum Einstein equations is found for which spacetime is compactified on a compact hyperbolic manifold of time-varying volume to a flat four-dimensional FLRW cosmology undergoing accelerated expansion in Einstein conformal frame. This shows that the `no-go' theorem forbidding acceleration in `standard' (time-independent) compactifications of string/M-theory does not apply to `cosmological' (time-dependent) hyperbolic compactifications.

  16. Biomedical accelerator mass spectrometry

    Science.gov (United States)

    Freeman, Stewart P. H. T.; Vogel, John S.

    1995-05-01

    Ultrasensitive SIMS with accelerator based spectrometers has recently begun to be applied to biomedical problems. Certain very long-lived radioisotopes of very low natural abundances can be used to trace metabolism at environmental dose levels ( [greater-or-equal, slanted] z mol in mg samples). 14C in particular can be employed to label a myriad of compounds. Competing technologies typically require super environmental doses that can perturb the system under investigation, followed by uncertain extrapolation to the low dose regime. 41Ca and 26Al are also used as elemental tracers. Given the sensitivity of the accelerator method, care must be taken to avoid contamination of the mass spectrometer and the apparatus employed in prior sample handling including chemical separation. This infant field comprises the efforts of a dozen accelerator laboratories. The Center for Accelerator Mass Spectrometry has been particularly active. In addition to collaborating with groups further afield, we are researching the kinematics and binding of genotoxins in-house, and we support innovative uses of our capability in the disciplines of chemistry, pharmacology, nutrition and physiology within the University of California. The field can be expected to grow further given the numerous potential applications and the efforts of several groups and companies to integrate more the accelerator technology into biomedical research programs; the development of miniaturized accelerator systems and ion sources capable of interfacing to conventional HPLC and GMC, etc. apparatus for complementary chemical analysis is anticipated for biomedical laboratories.

  17. Accelerators for America's Future

    Science.gov (United States)

    Bai, Mei

    2016-03-01

    Particle accelerator, a powerful tool to energize beams of charged particles to a desired speed and energy, has been the working horse for investigating the fundamental structure of matter and fundermental laws of nature. Most known examples are the 2-mile long Stanford Linear Accelerator at SLAC, the high energy proton and anti-proton collider Tevatron at FermiLab, and Large Hadron Collider that is currently under operation at CERN. During the less than a century development of accelerator science and technology that led to a dazzling list of discoveries, particle accelerators have also found various applications beyond particle and nuclear physics research, and become an indispensible part of the economy. Today, one can find a particle accelerator at almost every corner of our lives, ranging from the x-ray machine at the airport security to radiation diagnostic and therapy in hospitals. This presentation will give a brief introduction of the applications of this powerful tool in fundermental research as well as in industry. Challenges in accelerator science and technology will also be briefly presented

  18. Diffusive Shock Acceleration and Reconnection Acceleration Processes

    Science.gov (United States)

    Zank, G. P.; Hunana, P.; Mostafavi, P.; Le Roux, J. A.; Li, Gang; Webb, G. M.; Khabarova, O.; Cummings, A.; Stone, E.; Decker, R.

    2015-12-01

    Shock waves, as shown by simulations and observations, can generate high levels of downstream vortical turbulence, including magnetic islands. We consider a combination of diffusive shock acceleration (DSA) and downstream magnetic-island-reconnection-related processes as an energization mechanism for charged particles. Observations of electron and ion distributions downstream of interplanetary shocks and the heliospheric termination shock (HTS) are frequently inconsistent with the predictions of classical DSA. We utilize a recently developed transport theory for charged particles propagating diffusively in a turbulent region filled with contracting and reconnecting plasmoids and small-scale current sheets. Particle energization associated with the anti-reconnection electric field, a consequence of magnetic island merging, and magnetic island contraction, are considered. For the former only, we find that (i) the spectrum is a hard power law in particle speed, and (ii) the downstream solution is constant. For downstream plasmoid contraction only, (i) the accelerated spectrum is a hard power law in particle speed; (ii) the particle intensity for a given energy peaks downstream of the shock, and the distance to the peak location increases with increasing particle energy, and (iii) the particle intensity amplification for a particular particle energy, f(x,c/{c}0)/f(0,c/{c}0), is not 1, as predicted by DSA, but increases with increasing particle energy. The general solution combines both the reconnection-induced electric field and plasmoid contraction. The observed energetic particle intensity profile observed by Voyager 2 downstream of the HTS appears to support a particle acceleration mechanism that combines both DSA and magnetic-island-reconnection-related processes.

  19. Small type accelerator. Try for accelerator driven system

    CERN Document Server

    Mori, Y

    2003-01-01

    FFAG (Fixed-field alternating gradient) accelerator for accelerator driven subcritical reactor, which aims to change from long-lived radioactive waste to short-lived radioactivity, is introduced. It is ring accelerator. The performance needed is proton as accelerator particle, 10MW (total) beam power, about 1GeV beam energy, >30% power efficiency and continuous beam. The feature of FFAG accelerator is constant magnetic field. PoP (Proof-of-principle)-FFAG accelerator, radial type, was run at first in Japan in 2000. The excursion is about some ten cm. In principle, beam can be injected and extracted at any place of ring. The 'multi-fish' acceleration can accelerate beams to 100% duty by repeating acceleration. 150MeV-FFAG accelerator has been started since 2001. It tried to practical use, for example, treatment of cancer. (S.Y.)

  20. Dielectric laser accelerators

    Science.gov (United States)

    England, R. Joel; Noble, Robert J.; Bane, Karl; Dowell, David H.; Ng, Cho-Kuen; Spencer, James E.; Tantawi, Sami; Wu, Ziran; Byer, Robert L.; Peralta, Edgar; Soong, Ken; Chang, Chia-Ming; Montazeri, Behnam; Wolf, Stephen J.; Cowan, Benjamin; Dawson, Jay; Gai, Wei; Hommelhoff, Peter; Huang, Yen-Chieh; Jing, Chunguang; McGuinness, Christopher; Palmer, Robert B.; Naranjo, Brian; Rosenzweig, James; Travish, Gil; Mizrahi, Amit; Schachter, Levi; Sears, Christopher; Werner, Gregory R.; Yoder, Rodney B.

    2014-10-01

    The use of infrared lasers to power optical-scale lithographically fabricated particle accelerators is a developing area of research that has garnered increasing interest in recent years. The physics and technology of this approach is reviewed, which is referred to as dielectric laser acceleration (DLA). In the DLA scheme operating at typical laser pulse lengths of 0.1 to 1 ps, the laser damage fluences for robust dielectric materials correspond to peak surface electric fields in the GV /m regime. The corresponding accelerating field enhancement represents a potential reduction in active length of the accelerator between 1 and 2 orders of magnitude. Power sources for DLA-based accelerators (lasers) are less costly than microwave sources (klystrons) for equivalent average power levels due to wider availability and private sector investment. Because of the high laser-to-particle coupling efficiency, required pulse energies are consistent with tabletop microJoule class lasers. Combined with the very high (MHz) repetition rates these lasers can provide, the DLA approach appears promising for a variety of applications, including future high-energy physics colliders, compact light sources, and portable medical scanners and radiative therapy machines.

  1. Treatment response and mortality among patients starting antiretroviral therapy with and without Kaposi sarcoma: a cohort study.

    Directory of Open Access Journals (Sweden)

    Mhairi Maskew

    Full Text Available BACKGROUND: Improved survival among HIV-infected individuals on antiretroviral therapy (ART has focused attention on AIDS-related cancers including Kaposi sarcoma (KS. However, the effect of KS on response to ART is not well-described in Southern Africa. We assessed the effect of KS on survival and immunologic and virologic treatment responses at 6- and 12-months after initiation of ART. METHODS: We analyzed prospectively collected data from a cohort of HIV-infected adults initiating ART in South Africa. Differences in mortality between those with and without KS at ART initiation were estimated with Cox proportional hazard models. Log-binomial models were used to assess differences in CD4 count response and HIV virologic suppression within a year of initiating treatment. RESULTS: Between January 2001-January 2008, 13,847 HIV-infected adults initiated ART at the study clinics. Those with KS at ART initiation (n = 247, 2% were similar to those without KS (n = 13600,98% with respect to age (35 vs. 35yrs, presenting CD4 count (74 vs. 85cells/mm³ and proportion on TB treatment (37% vs. 30%. In models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis and year of ART initiation, KS patients were over three times more likely to have died at any time after ART initiation (hazard ratio[HR]: 3.62; 95% CI: 2.71-4.84 than those without KS. The increased risk was highest within the first year on ART (HR: 4.05; 95% CI: 2.95-5.55 and attenuated thereafter (HR: 2.30; 95% CI: 1.08-4.89. Those with KS also gained, on average, 29 fewer CD4 cells (95% CI: 7-52cells/mm³ and were less likely to increase their CD4 count by 50 cells from baseline (RR: 1.43; 95% CI: 0.99-2.06 within the first 6-months of treatment. CONCLUSIONS: HIV-infected adults presenting with KS have increased risk of mortality even after initiation of ART with the greatest risk in the first year. Among those who survive the first year on therapy, subjects with KS

  2. Evaluation of a Water-based Bolus Device for Radiotherapy to the Extremities in Kaposi's Sarcoma Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Seung Kwon; Kim, Yong Bae; Lee, Ik Jae [Yonsei University College of Medicine, Seoul (Korea, Republic of)] (and others)

    2008-09-15

    We designed a water-based bolus device for radiation therapy in Kaposi's sarcoma. This study evaluated the usefulness of this new device and compared it with the currently used rice-based bolus. Materials and Methods: We fashioned a polystyrene box and cut a hole in order to insert patient's extremities while the patient was in the supine position. We used a vacuum-vinyl based polymer to reduce water leakage. Next, we eliminated air using a vacuum pump and a vacuum valve to reduce the air gap between the water and extremities in the vacuum-vinyl box. We performed CT scans to evaluate the density difference of the fabricated water-based bolus device when the device in which the rice-based bolus was placed directly, the rice-based bolus with polymer-vinyl packed rice, and the water were all put in. We analyzed the density change with the air gap volume using a planning system. In addition, we measured the homogeneity and dose in the low-extremities phantom, attached to six TLD, and wrapped film exposed in parallel-opposite fields with the LINAC under the same conditions as the set-up of the CT-simulator. Results: The density value of the rice-based bolus with the rice put in directly was 14% lower than that of the water-based bolus. Moreover, the value of the other experiments in the rice-based bolus with the polymer-vinyl packed rice showed an 18% reduction in density. The analysis of the EDR2 film revealed that the water-based bolus shows a more homogeneous dose plan, which was superior by 4.0-4.4% to the rice-base bolus. The mean TLD readings of the rice-based bolus, with the rice put directly into the polystyrene box had a 3.4% higher density value. Moreover, the density value in the case of the rice-based bolus with polymer-vinyl packed rice had a 4.3% higher reading compared to the water-based bolus. Conclusion: Our custom-made water-based bolus device increases the accuracy of the set-up by confirming the treatment field. It also improves the

  3. Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric Castleman Disease (KSHV–MCD and the KSHV Inflammatory Cytokine Syndrome

    Directory of Open Access Journals (Sweden)

    Mark N. Polizzotto

    2012-03-01

    Full Text Available Soon after the discovery of Kaposi sarcoma (KS-associated herpesvirus (KSHV, it was appreciated that this virus was associated with most cases of multicentric Castleman disease (MCD arising in patients infected with human immunodeficiency virus. It has subsequently been recognized that KSHV–MCD is a distinct entity from other forms of MCD. Like MCD that is unrelated to KSHV, the clinical presentation of KSHV–MCD is dominated by systemic inflammatory symptoms including fevers, cachexia, and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein. Pathologically KSHV–MCD is characterized by polyclonal, IgM-lambda restricted plasmacytoid cells in the intrafollicular areas of affected lymph nodes. A portion of these cells are infected with KSHV and a sizable subset of these cells express KSHV lytic genes including a viral homolog of interleukin-6 (vIL-6. Patients with KSHV–MCD generally have elevated KSHV viral loads in their peripheral blood. Production of vIL-6 and induction of human (h IL-6 both contribute to symptoms, perhaps in combination with overproduction of IL-10 and other cytokines. Until recently, the prognosis of patients with KSHV–MCD was poor. Recent therapeutic advances targeting KSHV-infected B cells with the anti-CD20 monoclonal antibody rituximab and utilizing KSHV enzymes to target KSHV-infected cells have substantially improved patient outcomes. Recently another KSHV-associated condition, the KSHV inflammatory cytokine syndrome (KICS has been described. Its clinical manifestations resemble those of KSHV–MCD but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV–MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, homolog of human interleukin-6 and IL-10 comparable to those seen in KSHV–MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms

  4. Plasma-based accelerator structures

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Carl B. [Univ. of California, Berkeley, CA (United States)

    1999-12-01

    Plasma-based accelerators have the ability to sustain extremely large accelerating gradients, with possible high-energy physics applications. This dissertation further develops the theory of plasma-based accelerators by addressing three topics: the performance of a hollow plasma channel as an accelerating structure, the generation of ultrashort electron bunches, and the propagation of laser pulses is underdense plasmas.

  5. Uniform Acceleration in General Relativity

    CERN Document Server

    Friedman, Yaakov

    2016-01-01

    We extend de la Fuente and Romero's defining equation for uniform acceleration in a general curved spacetime from linear acceleration to the full Lorentz covariant uniform acceleration. In a flat spacetime background, we have explicit solutions. We use generalized Fermi-Walker transport to parallel transport the Frenet basis along the trajectory. In flat spacetime, we obtain velocity and acceleration transformations from a uniformly accelerated system to an inertial system. We obtain the time dilation between accelerated clocks. We apply our acceleration transformations to the motion of a charged particle in a constant electromagnetic field and recover the Lorentz-Abraham-Dirac equation.

  6. Cosmic Plasma Wakefield Acceleration

    Energy Technology Data Exchange (ETDEWEB)

    Chen, P

    2004-04-26

    Recently we proposed a new cosmic acceleration mechanism which was based on the wakefields excited by the Alfven shocks in a relativistically owing plasma. In this paper we include some omitted details, and show that there exists a threshold condition for transparency below which the accelerating particle is collision-free and suffers little energy loss in the plasma medium. The stochastic encounters of the random accelerating-decelerating phases results in a power-law energy spectrum: f({epsilon}) {proportional_to} 1/{epsilon}{sup 2}. As an example, we discuss the possible production of super-GZK ultra high energy cosmic rays (UHECR) in the atmosphere of gamma ray bursts. The estimated event rate in our model agrees with that from UHECR observations.

  7. Superconducting Accelerator Magnets

    CERN Document Server

    Mess, K H; Wolff, S

    1996-01-01

    The main topic of the book are the superconducting dipole and quadrupole magnets needed in high-energy accelerators and storage rings for protons, antiprotons or heavy ions. The basic principles of low-temperature superconductivity are outlined with special emphasis on the effects which are relevant for accelerator magnets. Properties and fabrication methods of practical superconductors are described. Analytical methods for field calculation and multipole expansion are presented for coils without and with iron yoke. The effect of yoke saturation and geometric distortions on field quality is studied. Persistent magnetization currents in the superconductor and eddy currents the copper part of the cable are analyzed in detail and their influence on field quality and magnet performance is investigated. Superconductor stability, quench origins and propagation and magnet protection are addressed. Some important concepts of accelerator physics are introduced which are needed to appreciate the demanding requirements ...

  8. Particle accelerator physics

    CERN Document Server

    Wiedemann, Helmut

    2007-01-01

    Particle Accelerator Physics is an in-depth and comprehensive introduction to the field of high-energy particle acceleration and beam dynamics. Part I gathers the basic tools, recalling the essentials of electrostatics and electrodynamics as well as of particle dynamics in electromagnetic fields. Part II is an extensive primer in beam dynamics, followed in Part III by the introduction and description of the main beam parameters. Part IV is devoted to the treatment of perturbations in beam dynamics. Part V discusses the details of charged particle accleration. Part VI and Part VII introduce the more advanced topics of coupled beam dynamics and the description of very intense beams. Part VIII is an exhaustive treatment of radiation from accelerated charges and introduces important sources of coherent radiation such as synchrotrons and free-electron lasers. Part IX collects the appendices gathering useful mathematical and physical formulae, parameters and units. Solutions to many end-of-chapter problems are give...

  9. Studies of accelerated compact toruses

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, C.W.; Eddleman, J.; Hammer, J.H.

    1983-01-04

    In an earlier publication we considered acceleration of plasma rings (Compact Torus). Several possible accelerator configurations were suggested and the possibility of focusing the accelerated rings was discussed. In this paper we consider one scheme, acceleration of a ring between coaxial electrodes by a B/sub theta/ field as in a coaxial rail-gun. If the electrodes are conical, a ring accelerated towards the apex of the cone undergoes self-similar compression (focusing) during acceleration. Because the allowable acceleration force, F/sub a/ = kappaU/sub m//R where (kappa < 1), increases as R/sup -2/, the accelerating distance for conical electrodes is considerably shortened over that required for coaxial electrodes. In either case, however, since the accelerating flux can expand as the ring moves, most of the accelerating field energy can be converted into kinetic energy of the ring leading to high efficiency.

  10. Microelectromechanical acceleration-sensing apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Robb M. (Albuquerque, NM); Shul, Randy J. (Albuquerque, NM); Polosky, Marc A. (Albuquerque, NM); Hoke, Darren A. (Albuquerque, NM); Vernon, George E. (Rio Rancho, NM)

    2006-12-12

    An acceleration-sensing apparatus is disclosed which includes a moveable shuttle (i.e. a suspended mass) and a latch for capturing and holding the shuttle when an acceleration event is sensed above a predetermined threshold level. The acceleration-sensing apparatus provides a switch closure upon sensing the acceleration event and remains latched in place thereafter. Examples of the acceleration-sensing apparatus are provided which are responsive to an acceleration component in a single direction (i.e. a single-sided device) or to two oppositely-directed acceleration components (i.e. a dual-sided device). A two-stage acceleration-sensing apparatus is also disclosed which can sense two acceleration events separated in time. The acceleration-sensing apparatus of the present invention has applications, for example, in an automotive airbag deployment system.

  11. Accelerating time to benefit

    DEFF Research Database (Denmark)

    Svejvig, Per; Geraldi, Joana; Grex, Sara

    Despite the ubiquitous pressure for speed, our approaches to accelerate projects remain constrained to the old-fashioned understanding of the project as a vehicle to deliver products and services, not value. This article explores an attempt to accelerate time to benefit. We describe and deconstruct...... of the time. Although all cases valued speed and speed to benefit, and implemented most practices proposed by the methodology, only three of the five projects were more successful in decreasing time to speed. Based on a multi-case study comparison between these five different projects and their respective...

  12. Accelerating News Issue 4

    CERN Document Server

    Szeberenyi, A; Wildner, E

    2012-01-01

    In this winter issue, we are very pleased to announce the approval of EuCARD-2 by the European Commission. We look at the conclusions of EUROnu in proposing future neutrino facilities at CERN, a new milestone reached by CLIC and progress on the SPARC upgrade using C-band technology. We also report on recent events: second Joint HiLumi LHC-LARP Annual Meeting and workshop on Superconducting technologies for the Next Generation of Accelerators aiming at closer collaboration with industry. The launch of the Accelerators for Society brochure is also highlighted.

  13. Shielding high energy accelerators

    CERN Document Server

    Stevenson, Graham Roger

    2001-01-01

    After introducing the subject of shielding high energy accelerators, point source, line-of-sight models, and in particular the Moyer model. are discussed. Their use in the shielding of proton and electron accelerators is demonstrated and their limitations noted. especially in relation to shielding in the forward direction provided by large, flat walls. The limitations of reducing problems to those using it cylindrical geometry description are stressed. Finally the use of different estimators for predicting dose is discussed. It is suggested that dose calculated from track-length estimators will generally give the most satisfactory estimate. (9 refs).

  14. Kaposi's Sarcoma: clinical and pathological aspects in patients seen at the Hospital Universitário Cassiano Antônio Moraes - Vitória - Espírito Santo - Brazil Sarcoma de Kaposi: achados clínico-patológicos nos pacientes atendidos no Hospital Universitário Cassiano Antônio Moraes - Vitória - Espírito Santo - Brazil

    Directory of Open Access Journals (Sweden)

    Ricardo Montibeler Tiussi

    2012-04-01

    Full Text Available BACKGROUND: Kaposi's sarcoma is a neoplasm of endothelial origin that is divided into four distinct types according to the clinical characteristics and the affected population: Classic (in elder men of Jewish or Mediterranean origin; Epidemic (in patients affected by AIDS; Endemic (in black African men and Iatrogenic (in patients under immunosuppressive regimens. Human herpesvirus 8 infection is essential but not sufficient for the sarcoma development. OBJECTIVE: To describe the epidemiological, clinical and histopathological aspects of patients with KS seen at the Dermatology Clinic -Cassiano Antônio Moraes University Hospital - Federal University of Espirito Santo, Vitória - ES. METHODS: A descriptive and retrospective study based on clinical charts of patients with KS seen at the Dermatology Clinic from 1986 to 2009. RESULTS: The majority of the 15 cases were male patients (93,3% and white (60%. Epidemic Kaposi's sarcoma occurred in 80%, and the Classic form in 20%, with no cases in the Endemic or Iatrogenic groups. All the histopatho logical exams of the cutaneous lesions were reviewed and a proliferation of fusiform cells, extravasated erythrocytes and vascular rifts among the largest vessels, assuming the "vessels in vessels" typical aspect, were seen. CONCLUSION: The number of cases of Kaposi's Sarcoma was linear throughout the years of the study, especially of the epidemic form, although the incidence and prevalence of AIDS increased in the state of Espírito Santo. Therefore, if we consider the relation between KS and AIDS, a decreasing line of Kaposi's sarcoma could be seen, especially after the introduction of HAART.FUNDAMENTOS: O Sarcoma de Kaposi é neoplasia de origem endotelial, dividida em quatro formas clínicas: clássica (homens idosos de origem judaica e mediterrânea, epidêmica (associada ao HIV, endêmica (negros africanos e iatrogênica (relacionada à imunossupressão. A infecção pelo herpes vírus humano tipo 8 (HHV

  15. Combined generating-accelerating buncher for compact linear accelerators

    Science.gov (United States)

    Savin, E. A.; Matsievskiy, S. V.; Sobenin, N. P.; Sokolov, I. D.; Zavadtsev, A. A.

    2016-09-01

    Described in the previous article [1] method of the power extraction from the modulated electron beam has been applied to the compact standing wave electron linear accelerator feeding system, which doesnt require any connection waveguides between the power source and the accelerator itself [2]. Generating and accelerating bunches meet in the hybrid accelerating cell operating at TM020 mode, thus the accelerating module is placed on the axis of the generating module, which consists from the pulsed high voltage electron sources and electrons dumps. This combination makes the accelerator very compact in size which is very valuable for the modern applications such as portable inspection sources. Simulations and geometry cold tests are presented.

  16. The CERN accelerator complex

    CERN Multimedia

    Christiane Lefèvre

    2008-01-01

    The LHC is the last ring (dark grey line) in a complex chain of particle accelerators. The smaller machines are used in a chain to help boost the particles to their final energies and provide beams to a whole set of smaller experiments, which also aim to uncover the mysteries of the Universe.

  17. The CERN Accelerator School

    CERN Multimedia

    2016-01-01

      Introduction to accelerator physics This course will take place in Istanbul, Turkey, from 18 to 30 September 2016. It is now open for registration, and further information can be found here: http://cas.web.cern.ch/cas/Turkey-2016/Turkey-advert.html

  18. The CERN Accelerator School

    CERN Multimedia

    2016-01-01

    Introduction to accelerator physics This course will take place in Budapest, Hungary, from 2 to 14 October 2016. It is now open for registration and further information can be found at: http://cas.web.cern.ch/cas/Hungary2016/Hungary-advert.html and http://indico.cern.ch/event/532397/.

  19. The CERN accelerator complex

    CERN Multimedia

    De Melis, Cinzia

    2016-01-01

    The LHC is the last ring (dark blue line) in a complex chain of particle accelerators. The smaller machines are used in a chain to help boost the particles to their final energies and provide beams to a whole set of smaller experiments, which also aim to uncover the mysteries of the Universe.

  20. Acceleration and Special Relativity

    CERN Document Server

    Yahalomi, E M

    2000-01-01

    The integration of acceleration over time before reaching the uniformvelocity turns out to be the source of all the special relativity effects. Itexplains physical phenomena like clocks comparisons. The equations forspace-time, mass and energy are presented. This phenomenon complements theexplanation for the twins paradox. A Universal reference frame is obtained.

  1. Prospects for Accelerator Technology

    Science.gov (United States)

    Todd, Alan

    2011-02-01

    Accelerator technology today is a greater than US$5 billion per annum business. Development of higher-performance technology with improved reliability that delivers reduced system size and life cycle cost is expected to significantly increase the total accelerator technology market and open up new application sales. Potential future directions are identified and pitfalls in new market penetration are considered. Both of the present big market segments, medical radiation therapy units and semiconductor ion implanters, are approaching the "maturity" phase of their product cycles, where incremental development rather than paradigm shifts is the norm, but they should continue to dominate commercial sales for some time. It is anticipated that large discovery-science accelerators will continue to provide a specialty market beset by the unpredictable cycles resulting from the scale of the projects themselves, coupled with external political and economic drivers. Although fraught with differing market entry difficulties, the security and environmental markets, together with new, as yet unrealized, industrial material processing applications, are expected to provide the bulk of future commercial accelerator technology growth.

  2. The CERN accelerator complex

    CERN Multimedia

    Haffner, Julie

    2013-01-01

    The LHC is the last ring (dark grey line) in a complex chain of particle accelerators. The smaller machines are used in a chain to help boost the particles to their final energies and provide beams to a whole set of smaller experiments, which also aim to uncover the mysteries of the Universe.

  3. SPS accelerating cavity

    CERN Multimedia

    1980-01-01

    One of the SPS acceleration cavities (200 MHz, travelling wave structure). On the ceiling one sees the coaxial transmission line which feeds the power from the amplifier, located in a surface building above, to the upstream end of the cavity. See 7603195 for more details, 7411032 for the travelling wave structure, and also 8104138, 8302397.

  4. The CERN accelerator complex

    CERN Multimedia

    Mobs, Esma Anais

    2016-01-01

    The LHC is the last ring (dark blue line) in a complex chain of particle accelerators. The smaller machines are used in a chain to help boost the particles to their final energies and provide beams to a whole set of smaller experiments, which also aim to uncover the mysteries of the Universe.

  5. Atmospheric and accelerator neutrinos

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Yoichiro [Kamioka Observatory, Institute for Cosmic Ray Research, University of Tokyo Higashi-Mozumi, Kamioka, Hida-City, Gifu 506-1205 (Japan)

    2006-05-15

    Results from the atmospheric neutrino measurements are presented. Evidence for the {nu}{sub {tau}} appearance in the atmospheric neutrino events was shown by statistical methods. The long baseline oscillation experiment using man-made neutrinos has confirmed the atmospheric neutrino oscillation. The future accelerator experiments are briefly discussed.

  6. SPS accelerating cavity

    CERN Multimedia

    CERN PhotoLab

    1981-01-01

    One of the SPS accelerating cavities (200 MHz, travelling wave structure). The power that is fed into the upstream end of the cavity is extracted at the downstream end and sent into a dump load. See 7603195 for more details, 7411032 for the travelling wave structure, and also 8011289, 8302397.

  7. Angular Accelerating White Light

    CSIR Research Space (South Africa)

    Dudley, Angela L

    2015-08-01

    Full Text Available Shaping XVI, 958104, San Diego, California, United States, 09 August 2015 Angular Accelerating White Light Angela Dudley*a,b, Christian Vetterc , Alexander Szameitc , and Andrew Forbesa,b a CSIR National Laser Centre, PO Box 395, Pretoria 0001...

  8. Neurodegeneration in accelerated aging.

    Science.gov (United States)

    Scheibye-Knudsen, Moren

    2016-11-01

    The growing proportion of elderly people represents an increasing economic burden, not least because of age-associated diseases that pose a significant cost to the health service. Finding possible interventions to age-associated disorders therefore have wide ranging implications. A number of genetically defined accelerated aging diseases have been characterized that can aid in our understanding of aging. Interestingly, all these diseases are associated with defects in the maintenance of our genome. A subset of these disorders, Cockayne syndrome, Xeroderma pigmentosum group A and ataxia-telangiectasia, show neurological involvement reminiscent of what is seen in primary human mitochondrial diseases. Mitochondria are the power plants of the cells converting energy stored in oxygen, sugar, fat, and protein into ATP, the energetic currency of our body. Emerging evidence has linked this organelle to aging and finding mitochondrial dysfunction in accelerated aging disorders thereby strengthens the mitochondrial theory of aging. This theory states that an accumulation of damage to the mitochondria may underlie the process of aging. Indeed, it appears that some accelerated aging disorders that show neurodegeneration also have mitochondrial dysfunction. The mitochondrial alterations may be secondary to defects in nuclear DNA repair. Indeed, nuclear DNA damage may lead to increased energy consumption, alterations in mitochondrial ATP production and defects in mitochondrial recycling, a term called mitophagy. These changes may be caused by activation of poly-ADP-ribose-polymerase 1 (PARP1), an enzyme that responds to DNA damage. Upon activation PARP1 utilizes key metabolites that attenuate pathways that are normally protective for the cell. Notably, pharmacological inhibition of PARP1 or reconstitution of the metabolites rescues the changes caused by PARP1 hyperactivation and in many cases reverse the phenotypes associated with accelerated aging. This implies that modulation

  9. Human Herpesvirus-8 Infection Associated with Kaposi Sarcoma, Multicentric Castleman's Disease, and Plasmablastic Microlymphoma in a Man with AIDS: A Case Report with Review of Pathophysiologic Processes

    Directory of Open Access Journals (Sweden)

    Christian Eaton

    2011-01-01

    Full Text Available Kaposi sarcoma (KS, multicentric Castleman's disease (MCD, and plasmablastic microlymphoma, are all linked to human herpesvirus-8 (HHV-8 infection and HIV-induced immunodeficiency. Herein, we describe the case of a Kenyan man diagnosed with HIV in 2000. He deferred highly active antiretroviral therapy (HAART and remained in good health until his CD4+ count declined in 2006. He was hospitalized with bacterial pneumonia in 2008, after which he agreed to take HAART but did so sporadically. In 2010, he was hospitalized with fever, lymphadenopathy, pancytopenia, and an elevated HHV-8 viral load. A lymph node biopsy showed findings consistent with KS, MCD, and plasmablastic microlymphoma. Eight months after starting liposomal doxorubicin, Rituximab, and a new HAART regimen, he has improved clinically, and his HIV and HHV-8 viral loads are suppressed. These three conditions, found in the same lymph node, underscore the inflammatory and malignant potential of HHV-8, particularly in the milieu of HIV-induced immunodeficiency.

  10. 艾滋病相关性直肠卡波西肉瘤1例%One case:AIDS-related Kaposi's sarcoma of the rectum

    Institute of Scientific and Technical Information of China (English)

    周树林; 赵月娟

    2011-01-01

    @@ 卡波西肉瘤(Kaposi's sarcoma)又称多发性特发性出血性肉瘤,是AIDS的常见并发症,1872年由Kaposi首次报告.AIDS相关性卡波西肉瘤国内外相关报道多见于皮肤、肺等部位,发生于直肠的卡波西肉瘤罕见报道.本文报道1例艾滋病相关性卡波西肉瘤原发于直肠,现结合临床病理特点对该病例CT征象进行分析探讨.

  11. THE ROLE OF GENETIC DETERMINANTS AND DISORDERS IN SYSTEMIC AND LOCAL IMMUNITY IN THE ETIOLOGY AND PATHOGENESIS OF HERPETIC ECZEMA (KAPOSI'S ECZEMA

    Directory of Open Access Journals (Sweden)

    A. S. Stadnikova

    2016-01-01

    Full Text Available This review presents an analysis of the literature data on the etiology and pathogenesis  of Herpetic Eczema (Kaposi's Eczema. Modern views on the complex genetic and phenotypic determinants of disease, reflecting the complex interactions between the skin and the immune system. Along with the general regularities characteristic of Herpetic Eczema in sufficient detail the reasons of infringements of functioning of the epidermal skin barrier, which contribute to an easier penetration of the Herpes Simplex  Virus in the skin and its binding  to cellular receptors in the implementation of the infectious process. The effect of systemic and local immunity, namely, changes in T-cell and interferon system in the development of the pathological process.

  12. Human herpesvirus 8 DNA load in leukocytes of human immunodeficiency virus-infected subjects: correlation with the presence of Kaposi's sarcoma and response to anticytomegalovirus therapy.

    Science.gov (United States)

    Boivin, G; Gaudreau, A; Toma, E; Lalonde, R; Routy, J P; Murray, G; Handfield, J; Bergeron, M G

    1999-02-01

    Specific human herpesvirus 8 (HHV-8) DNA sequences were found in leukocytes of 12 of 29 (41.4%) AIDS subjects with Kaposi's sarcoma (KS), whereas they were found in 4 of 43 (9.3%) AIDS subjects without KS (P = 0.003), although the peak HHV-8 DNA load in PCR-positive subjects with KS (mean, 425 copies per 0.2 microgram of DNA) did not significantly differ from the one found in PCR-positive patients without KS (mean, 218 copies). The use of intravenous ganciclovir or foscarnet therapy to treat cytomegalovirus disease did not affect the HHV-8 DNA load in seven patients for whom serial samples were analyzed.

  13. Nonlinear dynamics in particle accelerators

    CERN Document Server

    Dilão, Rui

    1996-01-01

    This book is an introductory course to accelerator physics at the level of graduate students. It has been written for a large audience which includes users of accelerator facilities, accelerator physicists and engineers, and undergraduates aiming to learn the basic principles of construction, operation and applications of accelerators.The new concepts of dynamical systems developed in the last twenty years give the theoretical setting to analyse the stability of particle beams in accelerator. In this book a common language to both accelerator physics and dynamical systems is integrated and dev

  14. Establishment of transplantable Kaposi's sarcoma animal models%移植性卡波西肉瘤动物模型的建立

    Institute of Scientific and Technical Information of China (English)

    袁虎; 吴秀娟; 梁俊琴; 普雄明

    2016-01-01

    目的:建立模拟卡波西肉瘤发展过程的移植性卡波西肉瘤的动物模型。方法将36只裸鼠随机分为A、B、C、D四个实验组,每组各9只。卡波西肉瘤细胞体外培养并计数,调节细胞悬液浓度为1³108/L、1³109/L、5³109/L、1³1010/L,各取0.2 ml分别接种于四组实验组裸鼠背部皮下。观察各组裸鼠肿瘤长出时间,肿瘤体积及颜色变化,待瘤体长到36 d时处死裸鼠,取下肿瘤组织进行组织病理学检查及免疫组化 CD31、CD34、AE1/AE3、S100、HHV-8。结果卡波西肉瘤细胞株皮下注射移植成瘤率为100%,肿瘤组织经免疫组化CD31、CD34染色阳性证实为血管来源肿瘤。4个实验组中裸鼠肿瘤均由斑点逐渐形成斑块、结节,各实验组小鼠瘤体体积随时间延长而逐渐增大,不同细胞浓度的实验组小鼠瘤体体积差异无统计学意义(P>0.05)。第36天不同细胞浓度的实验组小鼠瘤体重量差异无统计学意义(P>0.05)。结论成功建立了卡波西肉瘤细胞移植动物模型,且注射卡波西肉瘤细胞浓度越高,长出肿瘤的时间越短。%ObjectiveTo establish the transplantable Kaposi's sarcoma animal model to simulate the process of growth in Kaposi's sarcoma.Methods 36 nude mice were randomly divided into A group, B group, C group, D group with 9 mice in each group. The logarithmic growth phase Kaposi's sarcoma cells were calculated and regulated the cell concentration to 1×108/L, 1×109/L, 5×109/L, 1×1010/L. 0.2 ml different concentration of cells were implanted subcutaneous into the back of four groups respectively. The control group did not implant. The formation time, changes in volume and color of tumor were observed. All mice were sacrificed when the tumor grows on day 36 and removed the tumor to analyze the histopathology. Immunohistochemical staining was applied to test the number of CD31, CD34, AE1/AE3, S100, HHV-8.Results The Kaposi's sarcoma

  15. Mass spectrometry with accelerators.

    Science.gov (United States)

    Litherland, A E; Zhao, X-L; Kieser, W E

    2011-01-01

    As one in a series of articles on Canadian contributions to mass spectrometry, this review begins with an outline of the history of accelerator mass spectrometry (AMS), noting roles played by researchers at three Canadian AMS laboratories. After a description of the unique features of AMS, three examples, (14)C, (10)Be, and (129)I are given to illustrate the methods. The capabilities of mass spectrometry have been extended by the addition of atomic isobar selection, molecular isobar attenuation, further ion acceleration, followed by ion detection and ion identification at essentially zero dark current or ion flux. This has been accomplished by exploiting the techniques and accelerators of atomic and nuclear physics. In 1939, the first principles of AMS were established using a cyclotron. In 1977 the selection of isobars in the ion source was established when it was shown that the (14)N(-) ion was very unstable, or extremely difficult to create, making a tandem electrostatic accelerator highly suitable for assisting the mass spectrometric measurement of the rare long-lived radioactive isotope (14)C in the environment. This observation, together with the large attenuation of the molecular isobars (13)CH(-) and (12)CH 2(-) during tandem acceleration and the observed very low background contamination from the ion source, was found to facilitate the mass spectrometry of (14)C to at least a level of (14)C/C ~ 6 × 10(-16), the equivalent of a radiocarbon age of 60,000 years. Tandem Accelerator Mass Spectrometry, or AMS, has now made possible the accurate radiocarbon dating of milligram-sized carbon samples by ion counting as well as dating and tracing with many other long-lived radioactive isotopes such as (10)Be, (26)Al, (36)Cl, and (129)I. The difficulty of obtaining large anion currents with low electron affinities and the difficulties of isobar separation, especially for the heavier mass ions, has prompted the use of molecular anions and the search for alternative

  16. Acceleration of microparticle

    CERN Document Server

    Shibata, H

    2002-01-01

    A microparticle (dust) ion source has been installed at the high voltage terminal of the 3.75 MV single ended Van de Graaff electrostatic accelerator and a beam line for microparticle experiments has been build at High Fluence Irradiation Facility (HIT) of Research Center for Nuclear Science and Technology, the University of Tokyo. Microparticle acceleration has been successful in obtaining expected velocities of 1-20 km/s or more for micron or submicron sized particles. Development of in situ dust detectors and analyzers on board satellites and spacecraft in the expected mass and velocity range of micrometeoroids and investigation of hypervelocity impact phenomena by using time of flight mass spectrometry, impact flash or luminescence measurement and scanning electron or laser microscope observation for metals, ceramics, polymers and semiconductors bombarded by micron-sized particles were started three years ago. (author)

  17. Accelerated Parallel Texture Optimization

    Institute of Scientific and Technical Information of China (English)

    Hao-Da Huang; Xin Tong; Wen-Cheng Wang

    2007-01-01

    Texture optimization is a texture synthesis method that can efficiently reproduce various features of exemplar textures. However, its slow synthesis speed limits its usage in many interactive or real time applications. In this paper, we propose a parallel texture optimization algorithm to run on GPUs. In our algorithm, k-coherence search and principle component analysis (PCA) are used for hardware acceleration, and two acceleration techniques are further developed to speed up our GPU-based texture optimization. With a reasonable precomputation cost, the online synthesis speed of our algorithm is 4000+ times faster than that of the original texture optimization algorithm and thus our algorithm is capable of interactive applications. The advantages of the new scheme are demonstrated by applying it to interactive editing of flow-guided synthesis.

  18. accelerating cavity from LEP

    CERN Multimedia

    This is an accelerating cavity from LEP, with a layer of niobium on the inside. Operating at 4.2 degrees above absolute zero, the niobium is superconducting and carries an accelerating field of 6 million volts per metre with negligible losses. Each cavity has a surface of 6 m2. The niobium layer is only 1.2 microns thick, ten times thinner than a hair. Such a large area had never been coated to such a high accuracy. A speck of dust could ruin the performance of the whole cavity so the work had to be done in an extremely clean environment. These challenging requirements pushed European industry to new achievements. 256 of these cavities are now used in LEP to double the energy of the particle beams.

  19. Particle accelerator physics

    CERN Document Server

    Wiedemann, Helmut

    2015-01-01

    This book by Helmut Wiedemann is a well-established, classic text, providing an in-depth and comprehensive introduction to the field of high-energy particle acceleration and beam dynamics. The present 4th edition has been significantly revised, updated and expanded. The newly conceived Part I is an elementary introduction to the subject matter for undergraduate students. Part II gathers the basic tools in preparation of a more advanced treatment, summarizing the essentials of electrostatics and electrodynamics as well as of particle dynamics in electromagnetic fields. Part III is an extensive primer in beam dynamics, followed, in Part IV, by an introduction and description of the main beam parameters and including a new chapter on beam emittance and lattice design. Part V is devoted to the treatment of perturbations in beam dynamics. Part VI then discusses the details of charged particle acceleration. Parts VII and VIII introduce the more advanced topics of coupled beam dynamics and describe very intense bea...

  20. SUPERDIFFUSIVE SHOCK ACCELERATION

    Energy Technology Data Exchange (ETDEWEB)

    Perri, S.; Zimbardo, G. [Dipartimento di Fisica, Universita della Calabria, Ponte P. Bucci Cubo 31C, I-87036 Rende (Italy)

    2012-05-10

    The theory of diffusive shock acceleration is extended to the case of superdiffusive transport, i.e., when the mean square deviation grows proportionally to t{sup {alpha}}, with {alpha} > 1. Superdiffusion can be described by a statistical process called Levy random walk, in which the propagator is not a Gaussian but it exhibits power-law tails. By using the propagator appropriate for Levy random walk, it is found that the indices of energy spectra of particles are harder than those obtained where a normal diffusion is envisaged, with the spectral index decreasing with the increase of {alpha}. A new scaling for the acceleration time is also found, allowing substantially shorter times than in the case of normal diffusion. Within this framework we can explain a number of observations of flat spectra in various astrophysical and heliospheric contexts, for instance, for the Crab Nebula and the termination shock of the solar wind.

  1. Accelerating time to benefit

    DEFF Research Database (Denmark)

    Svejvig, Per; Geraldi, Joana; Grex, Sara

    Despite the ubiquitous pressure for speed, our approaches to accelerate projects remain constrained to the old-fashioned understanding of the project as a vehicle to deliver products and services, not value. This article explores an attempt to accelerate time to benefit. We describe and deconstruct...... the implementation of a large intervention undertaken in five project-based organizations in Denmark – the Project Half Double where the same project methodology has been applied in five projects, each of them in five distinct organizations in Denmark, as a bold attempt to realize double the benefit in half...... of the time. Although all cases valued speed and speed to benefit, and implemented most practices proposed by the methodology, only three of the five projects were more successful in decreasing time to speed. Based on a multi-case study comparison between these five different projects and their respective...

  2. Accelerating QDP++ using GPUs

    CERN Document Server

    Winter, Frank

    2011-01-01

    Graphic Processing Units (GPUs) are getting increasingly important as target architectures in scientific High Performance Computing (HPC). NVIDIA established CUDA as a parallel computing architecture controlling and making use of the compute power of GPUs. CUDA provides sufficient support for C++ language elements to enable the Expression Template (ET) technique in the device memory domain. QDP++ is a C++ vector class library suited for quantum field theory which provides vector data types and expressions and forms the basis of the lattice QCD software suite Chroma. In this work accelerating QDP++ expression evaluation to a GPU was successfully implemented leveraging the ET technique and using Just-In-Time (JIT) compilation. The Portable Expression Template Engine (PETE) and the C API for CUDA kernel arguments were used to build the bridge between host and device memory domains. This provides the possibility to accelerate Chroma routines to a GPU which are typically not subject to special optimisation. As an ...

  3. Accelerators for Cancer Therapy

    Science.gov (United States)

    Lennox, Arlene J.

    2000-05-30

    The vast majority of radiation treatments for cancerous tumors are given using electron linacs that provide both electrons and photons at several energies. Design and construction of these linacs are based on mature technology that is rapidly becoming more and more standardized and sophisticated. The use of hadrons such as neutrons, protons, alphas, or carbon, oxygen and neon ions is relatively new. Accelerators for hadron therapy are far from standardized, but the use of hadron therapy as an alternative to conventional radiation has led to significant improvements and refinements in conventional treatment techniques. This paper presents the rationale for radiation therapy, describes the accelerators used in conventional and hadron therapy, and outlines the issues that must still be resolved in the emerging field of hadron therapy.

  4. Hardware Accelerated Simulated Radiography

    Energy Technology Data Exchange (ETDEWEB)

    Laney, D; Callahan, S; Max, N; Silva, C; Langer, S; Frank, R

    2005-04-12

    We present the application of hardware accelerated volume rendering algorithms to the simulation of radiographs as an aid to scientists designing experiments, validating simulation codes, and understanding experimental data. The techniques presented take advantage of 32 bit floating point texture capabilities to obtain validated solutions to the radiative transport equation for X-rays. An unsorted hexahedron projection algorithm is presented for curvilinear hexahedra that produces simulated radiographs in the absorption-only regime. A sorted tetrahedral projection algorithm is presented that simulates radiographs of emissive materials. We apply the tetrahedral projection algorithm to the simulation of experimental diagnostics for inertial confinement fusion experiments on a laser at the University of Rochester. We show that the hardware accelerated solution is faster than the current technique used by scientists.

  5. NEW ACCELERATION METHODS

    Energy Technology Data Exchange (ETDEWEB)

    Sessler, A.M.

    1984-07-01

    But a glance at the Livingston chart, Fig. 1, of accelerator particle energy as a function of time shows that the energy has steadily, exponentially, increased. Equally significant is the fact that this increase is the envelope of diverse technologies. If one is to stay on, or even near, the Livingston curve in future years then new acceleration techniques need to be developed. What are the new acceleration methods? In these two lectures I would like to sketch some of these new ideas. I am well aware that they will probably not result in high energy accelerators within this or the next decade, but conversely, it is likely that these ideas will form the basis for the accelerators of the next century. Anyway, the ideas are stimulating and suffice to show that accelerator physicists are not just 'engineers', but genuine scientists deserving to be welcomed into the company of high energy physicists. I believe that outsiders will find this field surprisingly fertile and, certainly fun. To put it more personally, I very much enjoy working in this field and lecturing on it. There are a number of review articles which should be consulted for references to the original literature. In addition there are three books on the subject. Given this material, I feel free to not completely reference the material in the remainder of this article; consultation of the review articles and books will be adequate as an introduction to the literature for references abound (hundreds are given). At last, by way of introduction, I should like to quote from the end of Ref. 2 for I think the remarks made there are most germane. Remember that the talk was addressed to accelerator physicists: 'Finally, it is often said, I think by physicists who are not well-informed, that accelerator builders have used up their capital and now are bereft of ideas, and as a result, high energy physics will eventually--rather soon, in fact--come to a halt. After all, one can't build too many

  6. Future Accelerator Magnet Needs

    CERN Document Server

    Devred, Arnaud; Yamamoto, A

    2005-01-01

    Superconducting magnet technology is continually evolving in order to meet the demanding needs of new accelerators and to provide necessary upgrades for existing machines. A variety of designs are now under development, including high fields and gradients, rapid cycling and novel coil configurations. This paper presents a summary of R&D programs in the EU, Japan and the USA. A performance comparison between NbTi and Nb3Sn along with fabrication and cost issues are also discussed.

  7. Accelerated plate tectonics.

    Science.gov (United States)

    Anderson, D L

    1975-03-21

    The concept of a stressed elastic lithospheric plate riding on a viscous asthenosphere is used to calculate the recurrence interval of great earthquakes at convergent plate boundaries, the separation of decoupling and lithospheric earthquakes, and the migration pattern of large earthquakes along an arc. It is proposed that plate motions accelerate after great decoupling earthquakes and that most of the observed plate motions occur during short periods of time, separated by periods of relative quiescence.

  8. LEP copper accelerating cavities

    CERN Multimedia

    Laurent Guiraud

    1999-01-01

    These copper cavities were used to generate the radio frequency electric field that was used to accelerate electrons and positrons around the 27-km Large Electron-Positron (LEP) collider at CERN, which ran from 1989 to 2000. The copper cavities were gradually replaced from 1996 with new superconducting cavities allowing the collision energy to rise from 90 GeV to 200 GeV by mid-1999.

  9. French nuclear physics accelerator opens

    Science.gov (United States)

    Dumé, Belle

    2016-12-01

    A new €140m particle accelerator for nuclear physics located at the French Large Heavy Ion National Accelerator (GANIL) in Caen was inaugurated last month in a ceremony attended by French president François Hollande.

  10. Accelerator mass spectrometry.

    Science.gov (United States)

    Hellborg, Ragnar; Skog, Göran

    2008-01-01

    In this overview the technique of accelerator mass spectrometry (AMS) and its use are described. AMS is a highly sensitive method of counting atoms. It is used to detect very low concentrations of natural isotopic abundances (typically in the range between 10(-12) and 10(-16)) of both radionuclides and stable nuclides. The main advantages of AMS compared to conventional radiometric methods are the use of smaller samples (mg and even sub-mg size) and shorter measuring times (less than 1 hr). The equipment used for AMS is almost exclusively based on the electrostatic tandem accelerator, although some of the newest systems are based on a slightly different principle. Dedicated accelerators as well as older "nuclear physics machines" can be found in the 80 or so AMS laboratories in existence today. The most widely used isotope studied with AMS is 14C. Besides radiocarbon dating this isotope is used in climate studies, biomedicine applications and many other fields. More than 100,000 14C samples are measured per year. Other isotopes studied include 10Be, 26Al, 36Cl, 41Ca, 59Ni, 129I, U, and Pu. Although these measurements are important, the number of samples of these other isotopes measured each year is estimated to be less than 10% of the number of 14C samples.

  11. Accelerated Profile HMM Searches.

    Directory of Open Access Journals (Sweden)

    Sean R Eddy

    2011-10-01

    Full Text Available Profile hidden Markov models (profile HMMs and probabilistic inference methods have made important contributions to the theory of sequence database homology search. However, practical use of profile HMM methods has been hindered by the computational expense of existing software implementations. Here I describe an acceleration heuristic for profile HMMs, the "multiple segment Viterbi" (MSV algorithm. The MSV algorithm computes an optimal sum of multiple ungapped local alignment segments using a striped vector-parallel approach previously described for fast Smith/Waterman alignment. MSV scores follow the same statistical distribution as gapped optimal local alignment scores, allowing rapid evaluation of significance of an MSV score and thus facilitating its use as a heuristic filter. I also describe a 20-fold acceleration of the standard profile HMM Forward/Backward algorithms using a method I call "sparse rescaling". These methods are assembled in a pipeline in which high-scoring MSV hits are passed on for reanalysis with the full HMM Forward/Backward algorithm. This accelerated pipeline is implemented in the freely available HMMER3 software package. Performance benchmarks show that the use of the heuristic MSV filter sacrifices negligible sensitivity compared to unaccelerated profile HMM searches. HMMER3 is substantially more sensitive and 100- to 1000-fold faster than HMMER2. HMMER3 is now about as fast as BLAST for protein searches.

  12. Berkeley Proton Linear Accelerator

    Science.gov (United States)

    Alvarez, L. W.; Bradner, H.; Franck, J.; Gordon, H.; Gow, J. D.; Marshall, L. C.; Oppenheimer, F. F.; Panofsky, W. K. H.; Richman, C.; Woodyard, J. R.

    1953-10-13

    A linear accelerator, which increases the energy of protons from a 4 Mev Van de Graaff injector, to a final energy of 31.5 Mev, has been constructed. The accelerator consists of a cavity 40 feet long and 39 inches in diameter, excited at resonance in a longitudinal electric mode with a radio-frequency power of about 2.2 x 10{sup 6} watts peak at 202.5 mc. Acceleration is made possible by the introduction of 46 axial "drift tubes" into the cavity, which is designed such that the particles traverse the distance between the centers of successive tubes in one cycle of the r.f. power. The protons are longitudinally stable as in the synchrotron, and are stabilized transversely by the action of converging fields produced by focusing grids. The electrical cavity is constructed like an inverted airplane fuselage and is supported in a vacuum tank. Power is supplied by 9 high powered oscillators fed from a pulse generator of the artificial transmission line type.

  13. Optimizing accelerator technology

    CERN Multimedia

    Katarina Anthony

    2012-01-01

    A new EU-funded research and training network, oPAC, is bringing together 22 universities, research centres and industry partners to optimize particle accelerator technology. CERN is one of the network’s main partners and will host 5 early-stage researchers in the BE department.   A diamond detector that will be used for novel beam diagnostics applications in the oPAC project based at CIVIDEC. (Image courtesy of CIVIDEC.) As one of the largest Marie Curie Initial Training Networks ever funded by the EU – to the tune of €6 million – oPAC extends well beyond the particle physics community. “Accelerator physics has become integral to research in almost every scientific discipline – be it biology and life science, medicine, geology and material science, or fundamental physics,” explains Carsten P. Welsch, oPAC co-ordinator based at the University of Liverpool. “By optimizing the operation of accelerators, all of these...

  14. Particle Accelerator Focus Automation

    Directory of Open Access Journals (Sweden)

    Lopes José

    2017-08-01

    Full Text Available The Laboratório de Aceleradores e Tecnologias de Radiação (LATR at the Campus Tecnológico e Nuclear, of Instituto Superior Técnico (IST has a horizontal electrostatic particle accelerator based on the Van de Graaff machine which is used for research in the area of material characterization. This machine produces alfa (He+ and proton (H+ beams of some μA currents up to 2 MeV/q energies. Beam focusing is obtained using a cylindrical lens of the Einzel type, assembled near the high voltage terminal. This paper describes the developed system that automatically focuses the ion beam, using a personal computer running the LabVIEW software, a multifunction input/output board and signal conditioning circuits. The focusing procedure consists of a scanning method to find the lens bias voltage which maximizes the beam current measured on a beam stopper target, which is used as feedback for the scanning cycle. This system, as part of a wider start up and shut down automation system built for this particle accelerator, brings great advantages to the operation of the accelerator by turning it faster and easier to operate, requiring less human presence, and adding the possibility of total remote control in safe conditions.

  15. Particle Accelerator Focus Automation

    Science.gov (United States)

    Lopes, José; Rocha, Jorge; Redondo, Luís; Cruz, João

    2017-08-01

    The Laboratório de Aceleradores e Tecnologias de Radiação (LATR) at the Campus Tecnológico e Nuclear, of Instituto Superior Técnico (IST) has a horizontal electrostatic particle accelerator based on the Van de Graaff machine which is used for research in the area of material characterization. This machine produces alfa (He+) and proton (H+) beams of some μA currents up to 2 MeV/q energies. Beam focusing is obtained using a cylindrical lens of the Einzel type, assembled near the high voltage terminal. This paper describes the developed system that automatically focuses the ion beam, using a personal computer running the LabVIEW software, a multifunction input/output board and signal conditioning circuits. The focusing procedure consists of a scanning method to find the lens bias voltage which maximizes the beam current measured on a beam stopper target, which is used as feedback for the scanning cycle. This system, as part of a wider start up and shut down automation system built for this particle accelerator, brings great advantages to the operation of the accelerator by turning it faster and easier to operate, requiring less human presence, and adding the possibility of total remote control in safe conditions.

  16. Introduction to Microwave Linear [Accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Whittum, David H

    1999-01-04

    The elements of microwave linear accelerators are introduced starting with the principles of acceleration and accelerating structures. Considerations for microwave structure modeling and design are developed from an elementary point of view. Basic elements of microwave electronics are described for application to the accelerator circuit and instrumentation. Concepts of beam physics are explored together with examples of common beamline instruments. Charged particle optics and lattice diagnostics are introduced. Considerations for fixed-target and colliding-beam experimentation are summarized.

  17. Plasma accelerator experiments in Yugoslavia

    Science.gov (United States)

    Purić, J.; Astashynski, V. M.; Kuraica, M. M.; Dojčinovié, I. P.

    2002-12-01

    An overview is given of the results obtained in the Plasma Accelerator Experiments in Belgrade, using quasi-stationary high current plasma accelerators constructed within the framework of the Yugoslavia-Belarus Joint Project. So far, the following plasma accelerators have been realized: Magnetoplasma Compressor type (MPC); MPC Yu type; one stage Erosive Plasma Dynamic System (EPDS) and, in final stage of construction two stage Quasi-Stationary High Current Plasma Accelerator (QHPA).

  18. Accelerating in de Sitter spacetimes

    CERN Document Server

    Cotaescu, Ion I

    2014-01-01

    We propose a definition of uniform accelerated frames in de Sitter spacetimes exploiting the Nachtmann group theoretical method of introducing coordinates on these manifolds. Requiring the transformation between the static frame and the accelerated one to depend continuously on acceleration in order to recover the well-known Rindler approach in the flat limit, we obtain a result with a reasonable physical meaning.

  19. Prevention and Treatment of KSHV-associated Diseases with Antiviral Drugs

    Institute of Scientific and Technical Information of China (English)

    Ren-rong TIAN; Qing-jiao LIAO; Xulin CHEN

    2008-01-01

    s Kaposi's sarcoma-associated herpesvirus (KSHV) was first identified as the etiologic agent of Kaposi's sarcoma (KS) in 1994.KSHV infection is necessary,but not sufficient for the development of Kaposi sarcoma (KS),primary effusion lymphoma (PEL),and multicentric Castleman disease (MCD).Advances in the prevention and treatment of KSHV-associated Diseases have been achieved,even though current treatment options are ineffective,or toxic to many affected persons.The identification of new targets for potential future therapies and the randomized trial to evaluate the efficacy of new antivirals are required.

  20. Muon Acceleration - RLA and FFAG

    Energy Technology Data Exchange (ETDEWEB)

    Bogacz, Alex

    2011-10-01

    Various acceleration schemes for muons are presented. The overall goal of the acceleration systems: large acceptance acceleration to 25 GeV and 'beam shaping' can be accomplished by various fixed field accelerators at different stages. They involve three superconducting linacs: a single pass linear Pre-accelerator followed by a pair of multi-pass Recirculating Linear Accelerators (RLA) and finally a non-scaling FFAG ring. The present baseline acceleration scenario has been optimized to take maximum advantage of appropriate acceleration scheme at a given stage. The solenoid based Pre-accelerator offers very large acceptance and facilitates correction of energy gain across the bunch and significant longitudinal compression trough induced synchrotron motion. However, far off-crest acceleration reduces the effective acceleration gradient and adds complexity through the requirement of individual RF phase control for each cavity. The RLAs offer very efficient usage of high gradient superconducting RF and ability to adjust path-length after each linac pass through individual return arcs with uniformly periodic FODO optics suitable for chromatic compensation of emittance dilution with sextupoles. However, they require spreaders/recombiners switchyards at both linac ends and significant total length of the arcs. The non-scaling Fixed Field Alternating Gradient (FFAG) ring combines compactness with very large chromatic acceptance (twice the injection energy) and it allows for large number of passes through the RF (at least eight, possibly as high as 15).

  1. VLHC accelerator physics

    Energy Technology Data Exchange (ETDEWEB)

    Michael Blaskiewicz et al.

    2001-11-01

    A six-month design study for a future high energy hadron collider was initiated by the Fermilab director in October 2000. The request was to study a staged approach where a large circumference tunnel is built that initially would house a low field ({approx}2 T) collider with center-of-mass energy greater than 30 TeV and a peak (initial) luminosity of 10{sup 34} cm{sup -2}s{sup -1}. The tunnel was to be scoped, however, to support a future upgrade to a center-of-mass energy greater than 150 TeV with a peak luminosity of 2 x 10{sup 34} cm{sup -2} sec{sup -1} using high field ({approx} 10 T) superconducting magnet technology. In a collaboration with Brookhaven National Laboratory and Lawrence Berkeley National Laboratory, a report of the Design Study was produced by Fermilab in June 2001. 1 The Design Study focused on a Stage 1, 20 x 20 TeV collider using a 2-in-1 transmission line magnet and leads to a Stage 2, 87.5 x 87.5 TeV collider using 10 T Nb{sub 3}Sn magnet technology. The article that follows is a compilation of accelerator physics designs and computational results which contributed to the Design Study. Many of the parameters found in this report evolved during the study, and thus slight differences between this text and the Design Study report can be found. The present text, however, presents the major accelerator physics issues of the Very Large Hadron Collider as examined by the Design Study collaboration and provides a basis for discussion and further studies of VLHC accelerator parameters and design philosophies.

  2. APT accelerator. Topical report

    Energy Technology Data Exchange (ETDEWEB)

    Lawrence, G.; Rusthoi, D. [comp.] [ed.

    1995-03-01

    The Accelerator Production of Tritium (APT) project, sponsored by Department of Energy Defense Programs (DOE/DP), involves the preconceptual design of an accelerator system to produce tritium for the nation`s stockpile of nuclear weapons. Tritium is an isotope of hydrogen used in nuclear weapons, and must be replenished because of radioactive decay (its half-life is approximately 12 years). Because the annual production requirements for tritium has greatly decreased since the end of the Cold War, an alternative approach to reactors for tritium production, based on a linear accelerator, is now being seriously considered. The annual tritium requirement at the time this study was undertaken (1992-1993) was 3/8 that of the 1988 goal, usually stated as 3/8-Goal. Continued reduction in the number of weapons in the stockpile has led to a revised (lower) production requirement today (March, 1995). The production requirement needed to maintain the reduced stockpile, as stated in the recent Nuclear Posture Review (summer 1994) is approximately 3/16-Goal, half the previous level. The Nuclear Posture Review also requires that the production plant be designed to accomodate a production increase (surge) to 3/8-Goal capability within five years, to allow recovery from a possible extended outage of the tritium plant. A multi-laboratory team, collaborating with several industrial partners, has developed a preconceptual APT design for the 3/8-Goal, operating at 75% capacity. The team has presented APT as a promising alternative to the reactor concepts proposed for Complex-21. Given the requirements of a reduced weapons stockpile, APT offers both significant safety, environmental, and production-fexibility advantages in comparison with reactor systems, and the prospect of successful development in time to meet the US defense requirements of the 21st Century.

  3. Accelerated Innovation Pilot

    Science.gov (United States)

    Davis, Jeffrey

    2012-01-01

    Opportunities: I. Engage NASA team (examples) a) Research and technology calls . provide suggestions to AES, HRP, OCT. b) Use NASA@Work to solicit other ideas; (possibly before R+D calls). II. Stimulate collaboration (examples) a) NHHPC. b) Wharton Mack Center for Technological Innovation (Feb 2013). c) International ] DLR ] :envihab (July 2013). d) Accelerated research models . NSF, Myelin Repair Foundation. III. Engage public Prizes (open platform: InnoCentive, yet2.com, NTL; Rice Business Plan, etc.) IV. Use same methods to engage STEM.

  4. Accelerating abelian gauge dynamics

    CERN Document Server

    Adler, Stephen Louis

    1991-01-01

    In this paper, we suggest a new acceleration method for Abelian gauge theories based on linear transformations to variables which weight all length scales equally. We measure the autocorrelation time for the Polyakov loop and the plaquette at β=1.0 in the U(1) gauge theory in four dimensions, for the new method and for standard Metropolis updates. We find a dramatic improvement for the new method over the Metropolis method. Computing the critical exponent z for the new method remains an important open issue.

  5. 2014 CERN Accelerator Schools

    CERN Multimedia

    2014-01-01

    A specialised school on Power Converters will be held in Baden, Switzerland, from 7 to 14 May 2014. Please note that the deadline for applications is 7 FEBRUARY 2014. A course on Introduction to Accelerator Physics will be held in Prague, Czech Republic, from 31 August to 12 September 2014. Applications are now open for this school; the application deadline is 25 APRIL 2014. Further information on these schools and other CAS events can be found on the CAS website and on the Indico page. For further information please contact Barbara.strasser@cern.ch

  6. Hardware Accelerated Power Estimation

    CERN Document Server

    Coburn, Joel; Raghunathan, Anand

    2011-01-01

    In this paper, we present power emulation, a novel design paradigm that utilizes hardware acceleration for the purpose of fast power estimation. Power emulation is based on the observation that the functions necessary for power estimation (power model evaluation, aggregation, etc.) can be implemented as hardware circuits. Therefore, we can enhance any given design with "power estimation hardware", map it to a prototyping platform, and exercise it with any given test stimuli to obtain power consumption estimates. Our empirical studies with industrial designs reveal that power emulation can achieve significant speedups (10X to 500X) over state-of-the-art commercial register-transfer level (RTL) power estimation tools.

  7. Medical applications of accelerators

    CERN Document Server

    Rossi, Sandro

    1998-01-01

    At Present, about five thousands accelerators are devoted to biomedical applications. They are mainly used in radiotherapy, research and medical radioisotopes production. In this framework oncological hadron-therapy deserves particular attention since it represents a field in rapid evolution thanks to the joint efforts of laboratories with long experiences in particle physics. It is the case of CERN where the design of an optimised synchrotron for medical applications has been pursued. These lectures present these activities with particular attention to the new developments which are scientifically interesting and/or economically promising.

  8. ACCELERATING NANO-TECHNOLOGICAL

    DEFF Research Database (Denmark)

    Jensen, Jens Stissing; Koch, Christian

    2007-01-01

    By viewing the construction industry as a technological innovation system (TIS) this paper discusses possible initiatives to accelerate nanotechnological innovations. The point of departure is a recent report on the application of nano-technology in the Danish construction industry, which concludes...... of the system are furthermore poorly equipped at identifying potentials within high-tech areas. In order to exploit the potentials of nano-technology it is thus argued that an alternative TIS needs to be established. Initiatives should identify and support “incubation rooms” or marked niches in order...

  9. Methylation in the promoter region of HHV-8 ORF50 in Kaposis sarcoma%卡波西肉瘤中HHV-8 ORF50启动子基因甲基化的研究

    Institute of Scientific and Technical Information of China (English)

    吴曹英; 张德志; 邹云敏; 普雄明

    2013-01-01

    目的:探讨人类疱疹病毒8型(HHV-8)ORF50启动子区在经典型卡波西肉瘤(经典型KS)与艾滋相关型卡波西肉瘤(AIDS-KS)中甲基化状态的差异.方法:采用甲基化特异性PCR (MSP)检测经典型KS与AIDS-KS的甲基化状态,分析检测结果.结果:37例经典型KS中14例发生甲基化,甲基化阳性率为38%;18例AIDS-KS中5例发生甲基化,甲基化阳性率为28%.两者甲基化状态的差异无统计学意义(P>0.05).结论:经典型KS与AIDS-KS中HHV-8ORF50启动子的甲基化状态无明显的差异,HHV-8ORF50启动子的甲基化状态可能与HIV感染无关.%Objective:To study the difference between the classical Kaposi's sarcoma and AIDS related Kaposi's sarcoma(AIDS-KS) in the promoter region of human herpesvirus 8 (HHV-8).Methods:To use the methylation specific PCR (MSP) to detect the methylation status between the classical Kaposi's sarcoma and AIDS-KS.Results:14(38%) of 37 cases of classical Kaposi's sarcoma were methylated,while 5 (28%) of 18 cases AIDS-KS were methylated,(P > 0.05).Conclusion:There was no significant difference between the classical Kaposi's sarcoma and AIDS-KS of methylation status in the promoter region of HHV-8 ORF50,maybe the infection of HIV had nothing to do with the status of methylation in the promoter region of HHV-8 ORF50.

  10. Acceleration without Temperature

    CERN Document Server

    Doria, Alaric

    2015-01-01

    We show that while some non-uniformly accelerating observers (NUAOs) do indeed see a Bose-Einstein distribution of particles for the expectation value of the number operator in the Minkowski vacuum state, the density matrix is non-thermal and therefore a definition of temperature is not warranted. This is due to the fact that our NUAOs do not see event horizons in the spacetime. More specifically, the Minkowski vacuum state is perceived by our NUAOs as a single-mode squeezed state as opposed to the two-mode squeezed state characteristic of uniformly accelerating observers. Both single and two-mode squeezed states are pure quantum states; however, tracing over degrees of freedom in one of the modes of the two-mode squeezed state reduces the pure density matrix to a thermal density matrix. It is this property in the two-mode squeezed state that allows one to consistently define a temperature. In the single-mode case, an equivalent tracing is neither required nor available.

  11. Particle acceleration mechanisms

    CERN Document Server

    Petrosyan, V

    2008-01-01

    We review the possible mechanisms for production of non-thermal electrons which are responsible for non-thermal radiation in clusters of galaxies. Our primary focus is on non-thermal Bremsstrahlung and inverse Compton scattering, that produce hard X-ray emission. We briefly review acceleration mechanisms and point out that in most astrophysical situations, and in particular for the intracluster medium, shocks, turbulence and plasma waves play a crucial role. We consider two scenarios for production of non-thermal radiation. The first is hard X-ray emission due to non-thermal Bremsstrahlung by nonrelativistic particles. Non-thermal tails are produced by accelerating electrons from the background plasma with an initial Maxwellian distribution. However, these tails are accompanied by significant heating and they are present for a short time of <10^6 yr, which is also the time that the tail will be thermalised. Such non-thermal tails, even if possible, can only explain the hard X-ray but not the radio emission...

  12. Accelerator School Success

    CERN Multimedia

    2004-01-01

    Accelerator specialists don't grow on trees: training them is the job of the CERN Accelerator School (CAS). Group photo during visit to the Daresbury Laboratory. CAS and the CCLRC Daresbury Laboratory jointly organised a specialised school on Power Converters in Warrington, England from 12-18 May 2004. The last CAS Power Converter course was in 1990, so there was plenty of ground to cover. The challenging programme proposed a review of the state of the art and the latest developments in the field, including 30 hours of tuition. The school also included a visit to the CCLRC Daresbury laboratory, a one-day excursion to Liverpool and Chester and a themed (Welsh medieval) dinner at the school's closure. A record attendance of 91 students of more than 20 different nationalities included not only participants from Europe and North America but also from Armenia, Taiwan, India, Turkey, Iran and for the first time, fee-paying students from China and Australia. European industry showed a welcome and solid interest in...

  13. Acceleration in Linear and Circular Motion

    Science.gov (United States)

    Kellington, S. H.; Docherty, W.

    1975-01-01

    Describes the construction of a simple accelerometer and explains its use in demonstrating acceleration, deceleration, constant speed, measurement of acceleration, acceleration and the inclined plane and angular and radial acceleration. (GS)

  14. 2014 Joint International Accelerator School: Beam Loss and Accelerator Protection

    CERN Document Server

    JAS - Joint US-CERN-Japan-Russia Accelerator School

    2016-01-01

    Many particle accelerators operate with very high beam power and very high energy stored in particle beams as well as in magnet systems. In the future, the beam power in high intensity accelerators will further increase. The protection of the accelerator equipment from the consequences of uncontrolled release of the energy is essential. This was the motivation for organizing a first school on beam losses and accelerator protection (in general referred to as machine protection). During the school the methods and technologies to identify, mitigate, monitor and manage the technical risks associated with the operation of accelerators with high-power beams or subsystems with large stored energy were presented. At the completion of the school the participants should have been able to understand the physical phenomena that can damage machine subsystems or interrupt operations and to analyze an accelerator facility to produce a register of technical risks and the corresponding risk mitigation and management strategie...

  15. Relationship between open reading frame 26 subtypes in human herpesvirns-8 and Kaposi's sarcoma%人类疱疹病毒8型ORF26基因亚型与Kaposi肉瘤的相关性研究

    Institute of Scientific and Technical Information of China (English)

    吴秀娟; 普雄明; 吴卫东

    2008-01-01

    Objective To learn the subtypes of open reading frame 26 (ORF26) of human herpesvirus 8 (HHV-8) in patients with Kaposi's sarcoma, and to evaluate the relationship of ORF26 subtypes to clinical types and invasiveness of Kaposi's sarcoma. Methods Thirty-two paraffin-embeded tissue speci-mens of Kaposi's sarcoma were collected in the Department of Dermatology, People's Hospital of Xinjiang Uygur Autonomous Region, from 1996 to 2007. DNA was extracted from these specimens, nested-PCR was used to amplify HHV-8 DNA. PCR products were subjected to bi-directional sequencing after extraction from agarose gels. Phylogenetic analysis was carded out by using the software DNAStar, program Clustal W and PHYLIP package for the determination of ORF26 subtype. Fisher's exact test was performed to evaluate the relationship of ORF26 subtypes to clinical types and invasiveness of Kaposi's sarcoma. Results Of the 32 specimens, 30 were positive for HHV-8 DNA with a positivity rate of 93.75%, and 6 specimens of AIDS related Kaposi's sarcoma were all positive. ORF26 A subtype was detected in the HHV-8 DNA of 17 posi-tive specimens, and C subtype in that of other 13 specimens. Neither the incidence of mucosal lesions nor the distribution of clinical subtypes was of significant difference between patients with ORF26 A subtype and those with ORF26 C subtype (both P > 0.05). Conclusions A and C may be the predominate subtypes of ORF 26 in HHV-8 of patients with Kaposi's sarcoma, and the ORF26 subtype is unrelated to the presence of mucosal lesions in or the clinical types of patients with Kaposi's sarcoma.%目的 明确Kaposi肉瘤患者感染的人类疱疹病毒8型(HHV-8)ORF26基因亚型分类,初步探讨其与Kaposi肉瘤不同临床分型及侵袭性的相关性.方法 对32例Kaposi肉瘤石蜡包埋组织进行HHV-8 DNA抽提、扩增、双向测序,使用DNAStar软件、Clustal W软件和PHYLIP软件包对测序结果进行系统发生学分析,从而确定HHV-8 ORF26基因亚型,

  16. 人疱疹病毒8型ORF75基因亚型与Kaposi肉瘤的相关性研究%Study on the ORF75 subtypes of human herpesvirus-8 in patients with Kaposi's sarcoma

    Institute of Scientific and Technical Information of China (English)

    马春雷; 普雄明; 吴卫东; 张德志; 吴秀娟

    2009-01-01

    Objective To profile the subtypes of open reading frame 75(ORF75)of human herpesvirus 8(HHV-8)in patients with Kaposi's sarcoma,and to evaluate their relationship with clinical phenotypes and invasiveness of Kaposi's sarcoma.Methods Twenty-five paraffin-embeded tissue specimens of Kaposi's sarcoma were collected in the Department of Dermatology.People's Hospiml of Xinjiang Uygur Autonomous Region.DNA was extracted from these specimens.and nested-PCR was performed to amplify HHV-8 DNA followed bv bi-directional sequencing.Phylogenetic analysis was carried out by using the software DNASTAR,Clustal W program and PHYLIP package so as to identify the ORF75 subtyoe of HHV-8.Results HHV-8 DNA was detected in 21(84%)out of the 25 samples,and 7 cases of AIDS-associated Kaposi's sarcoma were all positive for HHV-8.Among the 21 patients carrying HHV-8 DNA,18 were positive for subtype A ORF75.3 for subtype C ORF75.The ORF75 subtypes had no significant correlation with the presence of mucosal lesions or clinical phenotypes of Kaposi's sarcoma.Conclusions The majority of patients with Kaposi's sarcoma in Xinjiang are infected with HHV-8 of ORF 75 subtype A and C.The ORF75 subtypes of HHV-8 have no correlation with the presence of mucosal lesions or clinical phenotypes of Kaposi's sarcoma.%目的 探讨人类疱疹病毒8型(HHV-8)ORF75基因亚型,与Kaposi肉瘤不同临床分型及侵袭性的相关性.方法 对25例新疆Kaposi肉瘤石蜡包埋组织进行HHV-8 DNA抽提、扩增及双向测序,使用Clustal W软件和PHYLIP软件包对测序结果进行发生学分析,从而确定HHV-8 ORF75基因哑型.结果 25例Kaposi肉瘤中,21例HHV-8阳性,阳性率为84%,其中7例AIDS相关型Kaposi肉瘤患者HHV-8均阳性.21例HHV-8阳性患者中,18例为HHV-8 ORF75 A亚型,3例为C亚型;不同亚型间Kaposi肉瘤患者有无黏膜损害及临床分型的分布差异均无统计学意义(P>0.05).结论 新疆Kaposi肉瘤患者感染HHV-8 ORF75

  17. Investigation on laser accelerators. Plasma beat wave accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Miura, Akihiko; Miyamoto, Yasuaki; Hagiwara, Masayoshi; Suzuki, Mitsutoshi; Sudo, Osamu [Power Reactor and Nuclear Fuel Development Corp., Tokai, Ibaraki (Japan). Tokai Works

    1998-04-01

    Laser accelerator technology has characteristics of high energy, compact, short pulse and high luminescence{center_dot}low emittance. This means potential many applications in wide ranges of fields as well as high energy and nuclear physics. High power short laser pulses are injected to a plasma in the typical example of laser accelerators. Large electric fields are induced in the plasma. Electrons in the plasma are accelerated with the ponderomotive force of the electric field. The principles of interaction on beat wave, wakefield accelerators, inverse free electron laser and inverse Cherenkov radiation are briefly introduced. The overview of plasma beat wave accelerator study is briefly described on the programs at Chalk River Laboratories(Canada), UCLA(USA), Osaka Univ. (Japan) and Ecole Polytechnique (France). Issues of the plasma beat wave accelerator are discussed from the viewpoint of application. Existing laser technologies of CO{sub 2}, YAG and YFL are available for the present day accelerator technology. An acceleration length of beat wave interaction is limited due to its phase condition. Ideas on multi-staged acceleration using the phasing plasma fiber are introduced. (Y. Tanaka)

  18. CERN Accelerator School: Registration open for Advanced Accelerator Physics course

    CERN Multimedia

    2015-01-01

    Registration is now open for the CERN Accelerator School’s Advanced Accelerator Physics course to be held in Warsaw, Poland from 27 September to 9 October 2015.   The course will be of interest to physicists and engineers who wish to extend their knowledge of accelerator physics. The programme offers core lectures on accelerator physics in the mornings and a practical course with hands-on tuition in the afternoons.  Further information can be found at: http://cas.web.cern.ch/cas/Poland2015/Warsaw-advert.html http://indico.cern.ch/event/361988/

  19. CERN Accelerator School: Registration open for Advanced Accelerator Physics course

    CERN Multimedia

    2015-01-01

    Registration is now open for the CERN Accelerator School’s Advanced Accelerator Physics course to be held in Warsaw, Poland from 27 September to 9 October 2015.   The course will be of interest to physicists and engineers who wish to extend their knowledge of Accelerator Physics. The programme offers core lectures on accelerator physics in the mornings and a practical course with hands-on tuition in the afternoons.  Further information can be found at: http://cas.web.cern.ch/cas/Poland2015/Warsaw-advert.html http://indico.cern.ch/event/361988/

  20. Prevalence and predictors of kaposi sarcoma herpes virus seropositivity: a cross-sectional analysis of HIV-infected adults initiating ART in Johannesburg, South Africa

    Directory of Open Access Journals (Sweden)

    Maskew Mhairi

    2011-11-01

    Full Text Available Abstract Background Kaposi sarcoma (KS is the most common AIDS-defining tumour in HIV-infected individuals in Africa. Kaposi sarcoma herpes virus (KSHV infection precedes development of KS. KSHV co-infection may be associated with worse outcomes in HIV disease and elevated KSHV viral load may be an early marker for advanced HIV disease among untreated patients. We examined the prevalence of KSHV among adults initiating antiretroviral therapy (ART and compared immunological, demographic and clinical factors between patients seropositive and seronegative for KSHV. Results We analyzed cross-sectional data collected from 404 HIV-infected treatment-naïve adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa between November 2008 and March 2009. Subjects were screened at ART initiation for antibodies to KSHV lytic K8.1 and latent Orf73 antigens. Seropositivity to KSHV was defined as positive to either lytic KSHV K8.1 or latent KSHV Orf73 antibodies. KSHV viremia was determined by quantitative PCR and CD3, 4 and 8 lymphocyte counts were determined with flow cytometry. Of the 404 participants, 193 (48% tested positive for KSHV at ART initiation; with 76 (39% reactive to lytic K8.1, 35 (18% to latent Orf73 and 82 (42% to both. One individual presented with clinical KS at ART initiation. The KSHV infected group was similar to those without KSHV in terms of age, race, gender, ethnicity, smoking and alcohol use. KSHV infected individuals presented with slightly higher median CD3 (817 vs. 726 cells/mm3 and CD4 (90 vs. 80 cells/mm3 counts than KSHV negative subjects. We found no associations between KSHV seropositivity and body mass index, tuberculosis status, WHO stage, HIV RNA levels, full blood count or liver function tests at initiation. Those with detectable KSHV viremia (n = 19, however, appeared to present with signs of more advanced HIV disease including anemia and WHO stage 3 or 4 defining conditions compared to those in whom