Southernmost carriers of HTLV-I/II in the world.

Science.gov (United States)

Cartier, L; Araya, F; Castillo, J L; Zaninovic, V; Hayami, M; Miura, T; Imai, J; Sonoda, S; Shiraki, H; Miyamoto, K

1993-01-01

To clarify the real distribution of HTLV-I and -II carriers among indigenous people in central and South America, blood samples collected from indigenous people in isolated regions of Southern Chile were examined. Among 199 inhabitants from Chiloe Island and Pitrufquen town, three cases (1.5%) showed positive anti-HTLV-I antibodies. Two out of the three (82-year-old male and 58-year-old female) reacted to HTLV-II-specific Gag and/or Env proteins but not to HTLV-I-specific ones. The latter case was confirmed as an HTLV-II carrier by polymerase chain reaction test.

HTLV-I and HTLV-II infections in hematologic disorder patients, cancer patients, and healthy individuals from Rio de Janeiro, Brazil.

Science.gov (United States)

Farias de Carvalho, S M; Pombo de Oliveira, M S; Thuler, L C; Rios, M; Coelho, R C; Rubim, L C; Silva, E M; Reis, A M; Catovsky, D

1997-07-01

To clarify the seroprevalence of human T-cell lymphotropic virus type I (HTLV-I) among hematologic and cancer patients in the State of Rio de Janeiro, Brazil, we investigated sera from 2430 individuals from the following groups: 152 patients with T-cell diseases, 250 with B-cell disorders, 67 with myeloid leukemia, 41 with Hodgkin's disease, 351 with a history of multiple blood transfusions, 235 patients with solid tumors of different types, and 109 family members of HTLV-I-infected patients. Antibodies to HTLV-I were screened by enzyme-linked immunosorbent assay or particle agglutination assays (or both). Repeatedly reactive samples were tested by Western blot and polymerase chain reaction assay to differentiate HTLV-I from HTLV-II. We found an increased seroprevalence rate of HTLV-I among those with lymphoid malignancies, mainly in T-cell diseases (28.9%), and these results were important in characterizing 44 cases of adult T-cell leukemia/lymphoma. We confirmed the presence of HTLV-I and HTLV-II infections in blood donors (0.4% and 0.1%, respectively), in patients exposed to multiple blood transfusions (10.2% and 0.8%, respectively), and in 30 (27.5%) of 109 family members of HTLV-I- or HTLV-II-infected patients. We also confirmed the high rate occurrence of adult T-cell leukemia/lymphoma among lymphoproliferative disorders in Rio de Janeiro, Brazil.

Evaluation of a new HTLV-I/II polymerase chain reaction

NARCIS (Netherlands)

Vrielink, H.; Zaaijer, H. L.; Cuypers, H. T.; van der Poel, C. L.; Woerdeman, M.; Lelie, P. N.; Winkel, C.; Reesink, H. W.

1997-01-01

AIM: Evaluation of a qualitative HTLV-I/II DNA polymerase chain reaction (PCR) test for the detection of HTLV-I/II DNA (Roche Diagnostic Systems, Branchburg, N.J., USA) in various panels. METHODS: The panels consisted of fresh EDTA blood samples from blood donors who were anti-HTLV-I/II ELISA

Nucleotide sequence analysis of HTLV-I isolated from cerebrospinal fluid of a patient with TSP/HAM: comparison to other HTLV-I isolates.

Science.gov (United States)

Mukhopadhyaya, R; Sadaie, M R

1993-02-01

Human T-cell leukemia virus type I (HTLV-I) has been associated with adult T-cell leukemia/lymphoma and the chronic neurologic disorder tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). To study the genetic structure of the virus associated with TSP/HAM, we have obtained and sequenced a partial genomic clone from an HTLV-I-positive cell line established from cerebrospinal fluid (CSF) of a Jamaican patient with TSP/HAM. This clone consisted of a 4.3-kb viral sequence containing the 5' long terminal repeat (LTR), gag, and N-terminal portion of the pol gene, with an overall 1.3% sequence variation resulting from mostly nucleotide substitutions, as compared to the prototype HTLV-I ATK-1. The gag and pol regions showed only 1.4% and 1.2% nucleotide variations, respectively. However, the U3 region of the LTR showed the highest sequence variation (3.6%), where several changes appear to be common among certain TSP/HAM isolates. Several of these changes reside within the 21-bp boundaries and the Tax-responsive element. It would be important to determine if the observed changes are sufficient to cause neurologic disorders similar to the murine leukemia virus system or simply reflect the divergent pool of HTLV-I from different geographic locations. At this time, we cannot rule out the possibility that the observed changes have either direct or indirect significance for the HTLV-I pathogenesis in TSP/HAM.

Serological Evidence of HTLV-I and HTLV-II Coinfections in HIV-1 Positive Patients in Belém, State of Pará, Brazil

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Vallinoto ACR

1998-01-01

Full Text Available The occurrence of HTLV-I/II and HIV-1 coinfections have been shown to be frequent, probably in consequence of their similar modes of transmission. This paper presents the prevalence of coinfection of HTLV among HIV-1 infected and AIDS patients in Belém, State of Pará, Brazil. A group of 149 patients attending the AIDS Reference Unit of the State Department of Health was tested for the presence of antibodies to HTLV-I/II using an enzyme immunoassay and the positive reactions were confirmed with a Western blot that discriminates between HTLV-I and HTLV-II infections. Four patients (2.7% were positive to HTLV-I, seven (4.7% to HTLV-II and one (0.7% showed an indeterminate pattern of reaction. The present results show for the first time in Belém not only the occurrence of HTLV-II/HIV-1 coinfections but also a higher prevalence of HTLV-II in relation to HTLV-I. Furthermore, it also enlarges the geographical limits of the endemic area for HTLV-II in the Amazon region of Brazil.

Hepatotoxicidade associada ao uso de esteroides anabolizantes

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Mónica Brinquinho

2017-06-01

Full Text Available O consumo de esteroides androgénicos anabolizantes tem vindo a aumentar no meio desportivo amador, sendo de fácil acesso apesar de se tratarem de substâncias proibidas. Estão descritos múltiplos efeitos laterais, sendo a hepatotoxicidade uma das mais reportadas. Apresentam-se dois casos clínicos representativos da lesão hepática associada ao consumo de esteroides anabolizantes. Ambos evidenciaram morbilidade significativa, embora nenhum deles tenha evoluído para falência hepática. Os autores pretendem chamar a atenção para o consumo destes fármacos, particularmente frequente em indivíduos jovens, praticantes de desporto amador.

Quantification of Human T-lymphotropic virus type I (HTLV-I) provirus load in a rural West African population: no enhancement of human immunodeficiency virus type 2 pathogenesis, but HTLV-I provirus load relates to mortality

DEFF Research Database (Denmark)

Ariyoshi, K; Berry, N; Cham, F

2003-01-01

Human T-lymphotropic virus type I (HTLV-I) provirus load was examined in a cohort of a population in Guinea-Bissau among whom human immunodeficiency virus (HIV) type 2 is endemic. Geometric mean of HIV-2 RNA load among HTLV-I-coinfected subjects was significantly lower than that in subjects...... infected with HIV-2 alone (212 vs. 724 copies/mL; P=.02). Adjusted for age, sex, and HIV status, the risk of death increased with HTLV-I provirus load; mortality hazard ratio was 1.59 for each log10 increase in HTLV-I provirus copies (P=.038). There is no enhancing effect of HTLV-I coinfection on HIV-2...... disease, but high HTLV-I provirus loads may contribute to mortality....

Doenças reumáticas auto-imunes em indivíduos infectados pelo HTLV-1 Autoimmune rheumatic diseases in HTLV-1 infected individuals

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Mônica Martinelli Nunes de Carvalho

2006-10-01

Full Text Available O HTLV-1 foi o primeiro retrovírus humano a ser associado às doenças malignas leucemia e linfoma de células T do adulto (LLTA. Ele está relacionado também a uma doença inflamatória crônica do sistema nervoso central (SNC conhecida como paraparesia espástica tropical/mielopatia associada ao HTLV-1 (PET/MAH. O HTLV-1 tem sido implicado na patogênese de várias doenças auto-imunes, tais como: diabetes, esclerose múltipla, dermatite infectiva, uveíte e artropatia. Ao longo dos anos, a infecção retroviral tem assumido um importante papel na patogênese das doenças reumáticas auto-imunes. Partículas semelhantes aos retrovírus têm sido identificadas em tecidos de pacientes com artrite reumatóide (AR, síndrome de Sjögren, lúpus eritematoso sistêmico (LES e polimiosite. A síndrome de Sjögren e a AR têm sido as doenças reumáticas mais encontradas nos pacientes infectados pelo HTLV-1, sendo a freqüência mais elevada nos pacientes com mielopatia. A alta prevalência de síndrome de Sjögren e de AR entre os indivíduos com mielopatia sugere que a carga viral e a resposta inflamatória exacerbada, que concorrem para o desenvolvimento da mielopatia, devem também influenciar no desenvolvimento das doenças reumáticas auto-imunes.The HTLV-1 was the first human retrovirus associated with adult T-cell leukemia/lymphoma (LLTA. The virus also causes a chronic inflammatory disease of the central nervous system named HTLV-1-associated myelopathy or tropical spastic paraparesis (HAM/TSP. HTLV-1 has been implicated in the pathogenesis of many autoimmune diseases, such as diabetes, multiple sclerosis, infective dermatitis, uveitis and arthropathy. It has long been suggested that retroviral infection may play a role in the pathogenesis of autoimmune rheumatic diseases. Particles resembling retroviruses have been reported in tissue from patients with rheumatoid arthritis (RA, Sjögren’s syndrome, systemic lupus erythematosus (SLE and

Modelling the role of Tax expression in HTLV-I persistence in vivo.

Science.gov (United States)

Li, Michael Y; Lim, Aaron G

2011-12-01

Human T-lymphotropic virus type I (HTLV-I) is a persistent human retrovirus characterized by life-long infection and risk of developing HAM/TSP, a progressive neurological and inflammatory disease, and adult T-cell leukemia (ATL). Chronically infected individuals often harbor high proviral loads despite maintaining a persistently activated immune response. Based on a new hypothesis for the persistence of HTLV-I infection, a three-dimensional compartmental model is constructed that describes the dynamic interactions among latently infected target cells, target-cell activation, and immune responses to HTLV-I, with an emphasis on understanding the role of Tax expression in the persistence of HTLV-I.

Reexamination of human T cell lymphotropic virus (HTLV-I/II) prevalence.

Science.gov (United States)

Zucker-Franklin, D; Pancake, B A; Marmor, M; Legler, P M

1997-06-10

In the United States, blood donors are being screened for infection with human T cell lymphotropic viruses I and II (HTLV-I/II) by serologic means, which detect antibodies to the structural proteins of these viruses. Because patients with mycosis fungoides (MF) usually do not have such antibodies even though their cells harbor HTLV-I Tax and/or pol proviral sequences, it was questioned whether the prevalence of HTLV infection among healthy blood donors may also be underestimated by current means of testing. To examine this possibility, a study on specimens of relatives of mycosis fungoides patients (MFR) was begun. In addition, to collect data more expeditiously, a cohort of former injection drug users (IDUs) was tested by routine serologic methods, as well as by PCR/Southern blot analysis for Tax, pol, and gag proviral sequences and Western blot analysis for antibodies to the Tax gene product. To date, 6/8 MFRs and 42/81 (51.8%) of HIV-negative IDUs proved to be positive for HTLV, whereas routine serology identified none of the MFR and only 18/81 (22.2%) of the IDUs. Among the latter test subjects, the incidence of HTLV-I also proved to be 10 times higher than expected. Therefore, it is likely that among healthy blood donors infection with HTLV-I/II is more prevalent than is currently assumed. Since Tax is the transforming sequence of HTLV-I/II, testing for Tax sequences and antibodies to its gene product may be desirable in blood transfusion and tissue donor facilities.

Cloning and transmembrane glycoprotein expression of the retrovirus HTLV-1 in mammals' cells

OpenAIRE

Penteado, Flora Cristina Lobo; Medeiros, Luciene; Orellana, Maristela Delgado; Palma, Patricia; Fontes, Aparecida Maria; Takayanagui, Osvaldo Massaiti; Covas, Dimas Tadeu

2006-01-01

O retrovírus linfotrópico de células T humanas tipo 1 é o agente etiológico da leucemia das células T do adulto e da paraparesia espástica tropical/mielopatia associada ao HTLV-1. O genoma proviral é composto por 9.032 pares de bases, contendo genes estruturais e regulatórios. A glicoproteína transmembrana gp 21 é codificada pelo gene estrutural env. O desenvolvimento de metodologias para a expressão heteróloga de proteínas, assim como a obtenção de uma linhagem celular que expresse a gp 21 r...

A new sensitive and quantitative HTLV-I-mediated cell fusion assay in T cells

International Nuclear Information System (INIS)

Pare, Marie-Eve; Gauthier, Sonia; Landry, Sebastien; Sun Jiangfeng; Legault, Eric; Leclerc, Denis; Tanaka, Yuetsu; Marriott, Susan J.; Tremblay, Michel J.; Barbeau, Benoit

2005-01-01

Similar to several other viruses, human T cell leukemia virus type I (HTLV-I) induces the formation of multinucleated giant cells (also known as syncytium) when amplified in tissue culture. These syncytia result from the fusion of infected cells with uninfected cells. Due to the intrinsic difficulty of infecting cells with cell-free HTLV-I virions, syncytium formation has become an important tool in the study of HTLV-I infection and transmission. Since most HTLV-I-based cell fusion assays rely on the use of non-T cells, the aim of this study was to optimize a new HTLV-I-induced cell fusion assay in which HTLV-I-infected T cell lines are co-cultured with T cells that have been transfected with an HTLV-I long terminal repeat (LTR) luciferase reporter construct. We demonstrate that co-culture of various HTLV-I-infected T cells with different transfected T cell lines resulted in induction of luciferase activity. Cell-to-cell contact and expression of the viral gp46 envelope protein was crucial for this induction while other cell surface proteins (including HSC70) did not have a significant effect. This quantitative assay was shown to be very sensitive. In this assay, the cell fusion-mediated activation of NF-κB and the HTLV-I LTR occurred through previously described Tax-dependent signaling pathways. This assay also showed that cell fusion could activate Tax-inducible cellular promoters. These results thus demonstrate that this new quantitative HTLV-I-dependent cell fusion assay is versatile, highly sensitive, and can provide an important tool to investigate cellular promoter activation and intrinsic signaling cascades that modulate cellular gene expression

Seroprevalencia de HTLV-I/II en hombres gays y trabajadoras sexuales de la Isla de Margarita, Venezuela HTLV-I/II seroprevalence among gay men and female sex workers from Margarita Island, Venezuela

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E. Castro de Batänjer

1998-08-01

Full Text Available Sabida la importante seroprevalencia en la Isla de Margarita para el HIV-1 nos propusimos conocer la seroprevalencia de HTLV-I/II en muestras de grupos epidemiologicamente importantes en su transmisión. El estudio se desarrolló con 141 trabajadoras sexuales y 40 hombres gays entre 1994 y 1997. Nuestros resultados permitieron establecer infección por HTLV-I en un hombre. Este es el primer reporte conocido sobre pesquisa epidemiológica de la infección por HTLV-I/II en la Isla de Margarita.In attention to the important HIV-1 seroprevalence observed in Margarita Island, we carried out this study to establish HTLV-I/II seroprevalence into target groups for sexual transmission. Therefore the survey was done with 141 female sex workers and 40 gay men between 1994 and 1997. We found HTLV-I infection in one man. This is the first known report to describe epidemiological features of HTLV-I/II infection in Margarita Island.

Prevalencia de infeccion por HTLV-I/II en donantes de sangre de la provincia de Santa Fe, Argentina Prevalence of HTLV-I/II infection among blood donors in Santa Fe Province, Argentina

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Roque O. Brun

2004-04-01

Full Text Available Subsecuentemente a que en 1997 el Programa Nacional de SIDA implementó un Programa deVigilancia Epidemiológica a escala nacional, se comenzaron a detectar anticuerpos anti-HTLV-I/II en donantes de sangre de la Provincia de Santa Fe. En base a ese hallazgo inicial, se consideró pertinente estimar la seroprevalencia de HTLV-I/II en donantes santafecinos en el curso de los 4 años siguientes. Así, desde 1997 hasta 2002, se estudiaron 9425 muestras provenientes de 17 de los 19 departamentos de la Provincia. Del total de muestras, 38 resultaron reactivas por técnicas de tamizaje, y de ellas 18 fueron confirmadas por western blot (WB. De esas muestras, 10 fueron HTLV-I/II seropositivas con una prevalencia final de 0.1% (10/9425, en tanto que 7 resultaron indeterminadas y 1 negativa. De las seropositivas, 2 (0.02 % eran HTLV, 3 (0.03 % HTLV-I, y 5 (0.05 % HTLV-II. Cabe destacar que por primera vez se constató la presencia de infección por HTLV-I/II en donantes de sangre de Santa Fe, y con una prevalencia mayor a las referidas para donantes de sangre de áreas no endémicas de Argentina. Estos datos fundamentan la necesidad de un screening sistemático para la infección por HTLV-I/II mediante normas regulatorias en bancos de sangre de esta provincia.Subsequent to the National Epidemiologic Surveillance Program developed in 1997 by the National AIDS Program, anti-HTLV-I/II antibodies among blood donors in Santa Fe Province started to be detected. On the basis of this initial finding, it was regarded of interest to evaluate the true HTLV-I/II seroprevalence in this population during a four-year survey. Thus, from 1997 up to 2002, 9425 samples were studied from 17 out of the 19 provincial departments. Out of the total sampling, 38 proved reactive by agglutination techniques, 18 of which were confirmed by western blot (WB. Out of the latter, 10 were HTLV-I/II seropositive with a final prevalence of 0.1% (10/9425, whereas 7 were indeterminate and 1

Population-based Seroprevalence of HTLV-I Infection in Golestan Province, South East of Caspian Sea, Iran.

Science.gov (United States)

Kalavi, Khodaberdi; Moradi, Abdolvahab; Tabarraei, Alijan

2013-03-01

Human T-cell lymphotropic virus type-1 is an oncornavirus that causes adult T cell leukemia (ATL) HTLV-I-associated myelopathy⁄tropical spastic paraparesis (HAM/TSP). Golestan province is located in North West of Khorasan province known as an endemic area for HTLV-I in Iran. This study aimed to evaluate seroprevalence of HTLV-I in Golestan province. In this cross-sectional descriptive study in 2007, blood samples were collected from 2034 healthy people residing in different parts of Golestan province. Sera were assessed for HTLV-I/II-specific antibodies by ELISA method and reactive samples were confirmed by Western blot. Demographic and serologic data were entered in SPSS version 11.5 and statistical analysis was performed. An overall HTLV-I/II prevalence of 0.7% was observed in 15 cases by ELISA. Six out of 15 were confirmed as HTLV-I by western blot. Regional variation in the prevalence of HTLV-I was observed; 0%, 0%, 0.1%, 1.9%, 0.3%, 0%, and 2.6% tested HTLV-I-positive from west to east of Golestan Province regions, respectively. Seropositivity increased with age. No association between HTLV-I infection and sex status was detected. Highest rate of HTLV-I seroprevalence was shown in east of this region located in neighborhood with Khorasan province, the only confirmed endemic area in Iran. It seems that eastern area of our province is endemic for HTLV-I. Further comprehensive detailed epidemiological and molecular studies are recommended.

Reexamination of human T cell lymphotropic virus (HTLV-I/II) prevalence

Science.gov (United States)

Zucker-Franklin, Dorothea; Pancake, Bette A.; Marmor, Michael; Legler, Patricia M.

1997-01-01

In the United States, blood donors are being screened for infection with human T cell lymphotropic viruses I and II (HTLV-I/II) by serologic means, which detect antibodies to the structural proteins of these viruses. Because patients with mycosis fungoides (MF) usually do not have such antibodies even though their cells harbor HTLV-I Tax and/or pol proviral sequences, it was questioned whether the prevalence of HTLV infection among healthy blood donors may also be underestimated by current means of testing. To examine this possibility, a study on specimens of relatives of mycosis fungoides patients (MFR) was begun. In addition, to collect data more expeditiously, a cohort of former injection drug users (IDUs) was tested by routine serologic methods, as well as by PCR/Southern blot analysis for Tax, pol, and gag proviral sequences and Western blot analysis for antibodies to the Tax gene product. To date, 6/8 MFRs and 42/81 (51.8%) of HIV-negative IDUs proved to be positive for HTLV, whereas routine serology identified none of the MFR and only 18/81 (22.2%) of the IDUs. Among the latter test subjects, the incidence of HTLV-I also proved to be 10 times higher than expected. Therefore, it is likely that among healthy blood donors infection with HTLV-I/II is more prevalent than is currently assumed. Since Tax is the transforming sequence of HTLV-I/II, testing for Tax sequences and antibodies to its gene product may be desirable in blood transfusion and tissue donor facilities. PMID:9177230

Identification of Human T-lymphotropic Virus Type I (HTLV-I Subtypes Using Restrited Fragment Length Polymorphism in a Cohort of Asymptomatic Carriers and Patients with HTLV-I-associated Myelopathy/tropical Spastic Paraparesis from São Paulo, Brazil

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Segurado Aluisio AC

2002-01-01

Full Text Available Although human T-lymphotropic virus type I (HTLV-I exhibits high genetic stability, as compared to other RNA viruses and particularly to human immunodeficiency virus (HIV, genotypic subtypes of this human retrovirus have been characterized in isolates from diverse geographical areas. These are currently believed not to be associated with different pathogenetic outcomes of infection. The present study aimed at characterizing genotypic subtypes of viral isolates from 70 HTLV-I-infected individuals from São Paulo, Brazil, including 42 asymptomatic carriers and 28 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, using restricted fragment length polymorphism (RFLP analysis of long terminal repeat (LTR HTLV-I proviral DNA sequences. Peripheral blood mononuclear cell lysates were amplified by nested polymerase chain reaction (PCR and amplicons submitted to enzymatic digestion using a panel of endonucleases. Among HTLV-I asymptomatic carriers, viral cosmopolitan subtypes A, B, C and E were identified in 73.8%, 7.1%, 7.1% and 12% of tested samples, respectively, whereas among HAM/TSP patients, cosmopolitan A (89.3%, cosmopolitan C (7.1% and cosmopolitan E (3.6% subtypes were detected. HTLV-I subtypes were not statistically significant associated with patients' clinical status. We also conclude that RFLP analysis is a suitable tool for descriptive studies on the molecular epidemiology of HTLV-I infections in our environment.

HTLV-I/II and blood donors: determinants associated with seropositivity in a low risk population

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Bernadette Catalan Soares

2003-08-01

Full Text Available OBJECTIVE: Blood donors in Brazil have been routinely screened for HTLV-I/II since 1993. A study was performed to estimate the prevalence of HTLV-I/II infection in a low risk population and to better understand determinants associated with seropositivity. METHODS: HTLV-I/II seropositive (n=135, indeterminate (n=167 and seronegative blood donors (n=116 were enrolled in an open prevalence prospective cohort study. A cross-sectional epidemiological study of positive, indeterminate and seronegative HTLV-I/II subjects was conducted to assess behavioral and environmental risk factors for seropositivity. HTLV-I/II serological status was confirmed using enzyme-linked immunosorbent assay (EIA and Western blot (WB. RESULTS: The three groups were not homogeneous. HTLV-I/II seropositivity was associated to past blood transfusion and years of schooling, a marker of socioeconomic status, and use of non-intravenous illegal drugs. CONCLUSIONS: The study results reinforce the importance of continuous monitoring and improvement of blood donor selection process.

Regulatory elements involved in tax-mediated transactivation of the HTLV-I LTR.

Science.gov (United States)

Seeler, J S; Muchardt, C; Podar, M; Gaynor, R B

1993-10-01

HTLV-I is the etiologic agent of adult T-cell leukemia. In this study, we investigated the regulatory elements and cellular transcription factors which function in modulating HTLV-I gene expression in response to the viral transactivator protein, tax. Transfection experiments into Jurkat cells of a variety of site-directed mutants in the HTLV-1 LTR indicated that each of the three motifs A, B, and C within the 21-bp repeats, the binding sites for the Ets family of proteins, and the TATA box all influenced the degree of tax-mediated activation. Tax is also able to activate gene expression of other viral and cellular promoters. Tax activation of the IL-2 receptor and the HIV-1 LTR is mediated through NF-kappa B motifs. Interestingly, sequences in the 21-bp repeat B and C motifs contain significant homology with NF-kappa B regulatory elements. We demonstrated that an NF-kappa B binding protein, PRDII-BF1, but not the rel protein, bound to the B and C motifs in the 21-bp repeat. PRDII-BF1 was also able to stimulate activation of HTLV-I gene expression by tax. The role of the Ets proteins on modulating tax activation was also studied. Ets 1 but not Ets 2 was capable of increasing the degree of tax activation of the HTLV-I LTR. These results suggest that tax activates gene expression by either direct or indirect interaction with several cellular transcription factors that bind to the HTLV-I LTR.

I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions

International Nuclear Information System (INIS)

Kusano, Shuichi; Yoshimitsu, Makoto; Hachiman, Miho; Ikeda, Masanori

2015-01-01

The I-mfa domain proteins HIC (also known as MDFIC) and I-mfa (also known as MDFI) are candidate tumor suppressor genes that are involved in cellular and viral transcriptional regulation. Here, we show that HIC and I-mfa directly interact with human T-cell leukemia virus type-1 (HTLV-1) Tax protein in vitro. In addition, HIC and I-mfa repress Tax-dependent transactivation of an HTLV-1 long terminal repeat (LTR) reporter construct in COS-1, Jurkat and high-Tax-producing HTLV-1-infected T cells. HIC also interacts with Tax through its I-mfa domain in vivo and represses Tax-dependent transactivation of HTLV-1 LTR and NF-κB reporter constructs in an interaction-dependent manner. Furthermore, we show that HIC decreases the nuclear distribution and stimulates the proteasomal degradation of Tax. These data reveal that HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability. - Highlights: • I-mfa domain proteins, HIC and I-mfa, specifically interact with HTLV-1 Tax. • HIC and I-mfa repress the Tax-dependent transactivation of HTLV-1 LTR. • HIC represses the Tax-dependent transactivation of NF-κΒ. • HIC decreases the nuclear distribution of Tax. • HIC stimulates the proteasomal degradation of Tax.

I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions

Energy Technology Data Exchange (ETDEWEB)

Kusano, Shuichi, E-mail: skusano@m2.kufm.kagoshima-u.ac.jp [Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Yoshimitsu, Makoto; Hachiman, Miho [Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Ikeda, Masanori [Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan)

2015-12-15

The I-mfa domain proteins HIC (also known as MDFIC) and I-mfa (also known as MDFI) are candidate tumor suppressor genes that are involved in cellular and viral transcriptional regulation. Here, we show that HIC and I-mfa directly interact with human T-cell leukemia virus type-1 (HTLV-1) Tax protein in vitro. In addition, HIC and I-mfa repress Tax-dependent transactivation of an HTLV-1 long terminal repeat (LTR) reporter construct in COS-1, Jurkat and high-Tax-producing HTLV-1-infected T cells. HIC also interacts with Tax through its I-mfa domain in vivo and represses Tax-dependent transactivation of HTLV-1 LTR and NF-κB reporter constructs in an interaction-dependent manner. Furthermore, we show that HIC decreases the nuclear distribution and stimulates the proteasomal degradation of Tax. These data reveal that HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability. - Highlights: • I-mfa domain proteins, HIC and I-mfa, specifically interact with HTLV-1 Tax. • HIC and I-mfa repress the Tax-dependent transactivation of HTLV-1 LTR. • HIC represses the Tax-dependent transactivation of NF-κΒ. • HIC decreases the nuclear distribution of Tax. • HIC stimulates the proteasomal degradation of Tax.

Quantification of Human T-lymphotropic virus type I (HTLV-I) provirus load in a rural West African population: no enhancement of human immunodeficiency virus type 2 pathogenesis, but HTLV-I provirus load relates to mortality

NARCIS (Netherlands)

Ariyoshi, Koya; Berry, Neil; Cham, Fatim; Jaffar, Shabbar; Schim van der Loeff, Maarten; Jobe, Ousman; N'Gom, Pa Tamba; Larsen, Olav; Andersson, Sören; Aaby, Peter; Whittle, Hilton

2003-01-01

Human T-lymphotropic virus type I (HTLV-I) provirus load was examined in a cohort of a population in Guinea-Bissau among whom human immunodeficiency virus (HIV) type 2 is endemic. Geometric mean of HIV-2 RNA load among HTLV-I-coinfected subjects was significantly lower than that in subjects infected

Human T-cell Lymphotropic Virus types I and II (HTLV-I/II in French Guiana: clinical and molecular epidemiology

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Kazanji Mirdad

2003-01-01

Full Text Available We review here the epidemiological studies performed by our group on human retrovirus HTLV-I and HTLV-II infections and the associated diseases in French Guiana since 1984. French Guiana is an overseas French administrative district located between Brazil and Surinam. Its population is characterized by a large variety of ethnic groups, including several populations of African origin and various populations of Amerindian origin. Several epidemiological studies of large samples of pregnant women and in remote villages showed that HTLV-I is highly endemic in this area but is restricted to groups of African origin, especially the Noir-Marrons. In this endemic population, the results of segregation analysis in a genetic epidemiological study were consistent with the presence of a dominant major gene predisposing to HTLV-I infection, especially in children. In contrast, HTLV-II infection appears to be rare in French Guiana, having been found in only a few individuals of Brazilian origin. From a molecular point of view, the HTLV-I strains present in the Noir-Marrons, Creoles and Amerindians appear to originate from Africa, as they belong to the large cosmopolitan molecular subtype A.

High incidence of antibodies to HTLV-I tax in blood relatives of adult T cell leukemia patients.

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Okayama, A; Chen, Y M; Tachibana, N; Shioiri, S; Lee, T H; Tsuda, K; Essex, M

1991-01-01

Adult T cell leukemia (ATL) is caused by the human T cell leukemia virus type I (HTLV-I). Although the mechanisms of the leukemogenic process are unknown, the tax gene may have a role in this process. Because clustering occurs with HTLV-I and ATL, members of ATL families were examined for antibodies to the tax protein and compared with matched HTLV-I-positive blood donors. To investigate the antibody response to this protein, a plasmid, pBHX-4, was constructed to express a recombinant tax protein (r-tax). For ATL patients and their HTLV-I antibody-positive blood relatives, the rate of seroreactivity with the r-tax protein was 67.3% (35/52), compared with 51.6% (97/188) for HTLV-I antibody-positive control blood donors (P less than .05). The difference between direct offspring of ATL patients and matched HTLV-I blood donors was even greater (84.2% [16/91] vs. 44.2% [42/95]; P less than .005). Thus, tax antibody positivity in direct offspring of ATL patients may reflect differences in time or route of HTLV-I infection. Alternatively, it might reflect genetic differences in host susceptibility or virus strain.

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

DEFF Research Database (Denmark)

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

1994-01-01

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

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

DEFF Research Database (Denmark)

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

1994-01-01

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

HTLV-I in the general population of Salvador, Brazil: a city with African ethnic and sociodemographic characteristics.

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Dourado, Inês; Alcantara, Luiz C J; Barreto, Maurício L; da Gloria Teixeira, Maria; Galvão-Castro, Bernardo

2003-12-15

The city of Salvador has the highest prevalence of HTLV-I among blood donors in Brazil. To study the prevalence of HTLV-I among the general population of Salvador, 30 "sentinel surveillance areas" were selected for the investigation of various infectious diseases, and 1385 individuals within these areas were surveyed according to a simple random sample procedure. ELISA was used to screen plasma samples for antibodies to HTLV-I, and the positive samples were tested by a confirmatory assay (Western blotting). The overall prevalence of HTLV-I was 1.76% (23/1385). Infection rates were 1.2% for males and 2.0% for females. Specific prevalence demonstrated an increasing linear trend with age. No one younger than 13 years of age was infected. Multivariate analysis estimated adjusted odds ratios for the association of HTLV-I with age of 9.7 (3.3; 30.4) for females and 12.3 (1.47; 103.1) for males. Less education and income might be associated with HTLV-I infection in females. Phylogenetic analysis of the long terminal repeat fragments showed that most of the samples belonged to the Latin American cluster of the Transcontinental subgroup (Cosmopolitan subtype). For the entire city of Salvador, it is estimated that approximately 40000 individuals are infected with HTLV-I. Our results suggest multiple post-Colombian introductions of African HTLV-Ia strains in Salvador.

A transgenic model of transactivation by the Tax protein of HTLV-I.

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Bieberich, C J; King, C M; Tinkle, B T; Jay, G

1993-09-01

The human T-lymphotropic virus type I (HTLV-I) Tax protein is a transcriptional regulatory protein that has been suggested to play a causal role in the development of several HTLV-I-associated diseases. Tax regulates expression of its own LTR and of certain cellular promoters perhaps by usurping the function of the host transcriptional machinery. We have established a transgenic mouse model system to define the spectrum of tissues in vivo that are capable of supporting Tax-mediated transcriptional transactivation. Transgenic mice carrying the HTLV-I LTR driving expression of the Escherichia coli beta-galactosidase (beta gal) gene were generated, and this LTR-beta gal gene was transcriptionally inactive in all tissues. When LTR-beta gal mice were mated to transgenic mice carrying the same LTR driving expression of the HTLV-I tax gene, mice that carried both transgenes showed restricted expression of the beta gal reporter gene in several tissues including muscle, bone, salivary glands, skin, and nerve. In addition, a dramatic increase in the number of beta gal-expressing cells was seen in response to wounding. These observations provide direct evidence for viral transactivation in vivo, delimit the tissues capable of supporting that transactivation, and provide a model system to study the mechanism of gene regulation by Tax.

Guia de manejo clínico do paciente com HTLV: aspectos neurológicos Guide of clinical management of HTLV patient: neurological aspects

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Carlos Maurício de Castro-Costa

2005-06-01

Full Text Available O Ministério da Saúde (Programa DST e Aids reuniu especialistas para elaborar um guia informativo de manejo do paciente com HTLV. Dentre os diferentes tópicos, foram contemplados os aspectos neurológicos associados à infecção pelo HTLV. Um caso suspeito de doença neurológica associada ao HTLV deve incluir alteração de força e reflexos, parestesias distais e disfunção autonômica. A investigação do caso suspeito deve ser baseada na síndrome exibida pelo paciente. Para o paciente com síndrome medular, deve-se solicitar ressonância magnética da medula ou mielografia, assim como, estudo do líquor. Para o paciente com síndrome neuropática ou miopática, deve-se solicitar eletroneuromiografia e dosagem de CPK, e para aquele com síndrome autonômica, pesquisa de hipotensão postural, ultrassonografia das vias urinárias e estudo urodinâmico. O tratamento pode ser sintomático (espasticidade, bexiga neurogênica, constipação intestinal e dor neuropática e específico a ser feito em centros especializados.The Brazilian Ministry of Health (STD and Aids Program invited specialists to make up an informative guide to deal with HTLV patients. Among the different topics, the neurological aspects associated to HTLV were contemplated. A suspected case should include changes in force and reflexes, distal paresthesiae and autonomic dysfunction. The investigation of such case should be based on the syndrome shown by the patient. For patients with spinal cord syndrome, magnetic resonance imaging or myelography as well as spinal fluid studies should be carried out. For patients with neuropathic or myopathic syndrome, electroneuromyography and CPK dosing should be done, and for those with autonomic syndrome, a search for postural hypotension, ultrasonography of urinary tract and urodynamic studies should be requested. The treatment may be symptomatic (spasticity, neurogenic bladder, intestinal constipation and neuropathic pain and specific

Evidence of preferential female prevalence of HTLV-I associated tropical spastic paraparesis in Bahia-Brazil

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O. A. Moreno-Carvalho

1992-06-01

Full Text Available In order to evaluate the prevalence of HTLV-I infection and its association with tropical spastic paraparesis (TSP in Bahia, a Northeastern State of Brazil, CSF and sera from TSP patients and CSF and/or sera from some selected groups of individuals were studied. The results seem to indicate a higher prevalence of HTLV-I infection in women than men with TSP and among individuals of HIV risk groups. Some alterations of routine analysis of CSF can suggest HTLV-I infection in TSP patients.

HTLV-I infection in the South West Indian Ocean islands, particularly in La Réunion and the Seychelles.

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Aubry, P; Bovet, P; Vitrac, D; Schooneman, F; Hollanda, J; Malvy, D; Gaüzère, B-A

2013-10-01

Data on HTLV-I are scarce in several Southwest Indian Ocean islands except for La Réunion and The Seychelles. The two cases of HTLV-I have been confirmed by Western-Blot in La Réunion, among blood donors. In Seychelles (87 400 inhabitants in 2012), where blood donors and some other cases are screened, HTLV-I was confirmed with a line immune assay in 43 persons and at least 10-20 patients are known to have tropical spastic paraparesia or adult T-cell lymphoma associated with HTLV-I. In the south-west Indian Ocean, a possibly important other issue may be co-infection of HTLV-1 with the Strongyloides stercoralis roundworm, which is endemic in all countries of the region and which can sometimes lead to severe symptomatic infestation.

The HTLV-I tax protein transcriptionally modulates OX40 antigen expression.

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Pankow, R; Dürkop, H; Latza, U; Krause, H; Kunzendorf, U; Pohl, T; Bulfone-Paus, S

2000-07-01

OX40 is a member of the TNF receptor family, expressed on activated T cells. It is the only costimulatory T cell molecule known to be specifically up-regulated in human T cell leukemia virus type-I (HTLV-I)-producing cells. In a T cell line, OX40 surface expression was shown to be induced by HTLV-I Tax alone. To understand molecular mechanisms of OX40 gene regulation and modulation by HTLV-I Tax, we have cloned the human OX40 gene and analyzed its 5'-flanking region. By reporter gene analysis with progressive 5' deletions from nucleotides -1259 to -64, we have defined a 157-bp DNA fragment as a minimal promoter for constitutive expression. In addition, we show that in the OX40+ cell line, Co, Tax is able to further increase OX40 surface expression. Up-regulation of OX40 promoter activity by Tax requires two upstream NF-kappaB sites, which are not active in the constitutive OX40 expression. Their deletion abrogates Tax responsiveness in reporter gene analysis. The site-directed mutagenesis of each NF-kappaB site demonstrates that cooperative NF-kappaB binding is a prerequisite for Tax-directed activity as neither site alone is sufficient for a full Tax responsiveness of the OX40 promoter. Upon Tax expression, both sites bind p65 and c-Rel. These data provide new insight into the direct regulation of OX40 by Tax and add to our understanding of the possible role of the OX40/OX40 ligand system in the proliferation of HTLV-I+ T cells.

Atypical presentation of syphilis in an HTLV-I infected patient

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Carnaúba Jr Dimas

2003-01-01

Full Text Available We report the case of a 44 year-old female, who presented a long-lasting, clinically atypical, secondary syphilis ("malignant syphilis" in the right foot, which started six months before medical evaluation. The patient had a serological diagnosis of HTLV-I infection and syphilis two years before the onset of the skin lesions, following a blood donation. As she believed she was allergic to penicillin, she initially received sulfamethoxazole + trimethoprim, without any improvement of the clinical picture. After failure of this first treatment regimen, she was given penicillin, which promoted complete healing of the lesion. We found evidence that infection by HTLV-I is capable of modifying the clinical course of secondary syphilis.

The introduction of anti-HTLV testing of blood donations and the risk of transfusion-transmitted HTLV, UK: 2002-2006.

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Davison, K L; Dow, B; Barbara, J A; Hewitt, P E; Eglin, R

2009-02-01

The objectives of the study were to describe the introduction of testing blood donations for antibodies to human T-cell lymphotropic virus (anti-HTLV) and to determine the risk of HTLV potentially infectious donations entering the UK blood supply. The rationale for testing was based on (i) evidence of transmission through transfusion in the UK, (ii) the serious nature of HTLV I-associated morbidity and (iii) evidence of infection in UK blood donors. From mid-2002, all blood donations made at UK blood centres were tested in pooled samples using Abbott-Murex HTLV I/II GE 80/81 enzyme immunoassay (EIA). Surveillance data were used to calculate the incidence and prevalence of anti-HTLV and derive estimates of risk. Between August 2002 and December 2006, 106 donations were confirmed positive for anti-HTLV (95 anti-HTLV I and 11 anti-HTLV II). Prevalence was 10-fold higher among donations from new donors than repeat (4.0 and 0.42 per 100 000 donations), and only one repeat donor had evidence of seroconversion. The risk of an HTLV I potentially infectious donation entering the UK blood supply was estimated at 0.11 per million donations (95% confidence interval 0.06 to 0.18). The current very low observed incidence and prevalence among blood donors reflect the very low estimated risk of an HTLV I-positive donation entering the UK blood supply. A change in either the epidemiology of HTLV in UK blood donors or the length of the window period of the test should prompt further review of the risk and a reassessment of anti-HTLV testing in the UK.

Identificação das competências de Liderança associadas ao comando dos Oficiais subalternos e capitães de Infantaria

OpenAIRE

Lopes, Luís

2015-01-01

O presente trabalho é subordinado ao tema “Identificação das competências de liderança associadas ao comando dos Oficiais Subalternos e Capitães de Infantaria.”, tem como objetivo identificar, analisar e interrelacionar os comportamentos de liderança percecionados pelos subordinados aos Oficiais Subalternos e Capitães de Infantaria nas suas tarefas diárias de comando e de que maneira os Oficiais conseguem obter dos seus homens desempenh...

Abundant tax protein expression in CD4+ T cells infected with human T-cell lymphotropic virus type I (HTLV-I) is prevented by cytotoxic T lymphocytes.

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Hanon, E; Hall, S; Taylor, G P; Saito, M; Davis, R; Tanaka, Y; Usuku, K; Osame, M; Weber, J N; Bangham, C R

2000-02-15

The role of the cellular immune response in human T-cell leukemia virus type I (HTLV-I) infection is not fully understood. A persistently activated cytotoxic T lymphocyte (CTL) response to HTLV-I is found in the majority of infected individuals. However, it remains unclear whether this CTL response is protective or causes tissue damage. In addition, several observations paradoxically suggest that HTLV-I is transcriptionally silent in most infected cells and, therefore, not detectable by virus-specific CTLs. With the use of a new flow cytometric procedure, we show here that a high proportion of naturally infected CD4+ peripheral blood mononuclear cells (PBMC) (between 10% and 80%) are capable of expressing Tax, the immunodominant target antigen recognized by virus-specific CTLs. Furthermore, we provide direct evidence that autologous CD8+ T cells rapidly kill CD4+ cells naturally infected with HTLV-I and expressing Tax in vitro by a perforin-dependent mechanism. Consistent with these observations, we observed a significant negative correlation between the frequency of Tax(11-19)-specific CD8+ T cells and the percentage of CD4+ T cells in peripheral blood of patients infected with HTLV-I. Those results are in accordance with the view that virus-specific CTLs participate in a highly efficient immune surveillance mechanism that persistently destroys Tax-expressing HTLV-I-infected CD4+ T cells in vivo. (Blood. 2000;95:1386-1392)

Seroprevalence of HTLV -I/II amongst Blood Donors in Osogbo ...

African Journals Online (AJOL)

Background: HTLV type I/II is a blood borne infection that can be transmitted via blood transfusion. Objective: To determine the seroprevalence of human T – lymphotropic virus among blood donors in Osogbo, Nigeria. Methods: Diagnosis of Human T. Lymphotropic virus antigen was carried out on 372 serum samples ...

Development and Evaluation of a Novel ELISA for Detection of Antibodies against HTLV-I Using Chimeric Peptides.

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Mosadeghi, Parvin; Heydari-Zarnagh, Hafez

2018-04-01

We aimed to develope a peptide-based indirect ELISA to detect antibodies against Human T-lymphotropic virus type I (HTLV-I). Two chimeric peptides (CP-1 and CP-2) were designed using linear immunodominant epitopes of gp-46-I, and gp21-I proteins, according to the sequence from Uniprot database. These peptides were studied initially in the ELISA using infected sera. The most promising peptideCP-1, was used to develop a peptide ELISA for detection of HTLV-I infected sera. The optimal conditions for CP-1ELISA were: the optimum coating buffer was 100mM NaHCO3, pH 9.6; coating peptide concentration was 10 µg/mL; the optimal blocking buffer was5% fetal bovine serum (FBS); the secondary antibody concentration was 1:2000; and serum dilution was 1:20. 20serum samples from HTLV-I infected patients were evaluated by ELISA developed. CP-1 showed high antigenicity while lacking any cross-reactivity with normal human sera. The results of evaluations indicated that in comparison with commercial ELISA, CP-1 ELISA showed good sensitivity and specificity. With further validation, CP-1as described in the present study could be introduced as novel reliable and cost-effective candidates for the high-specific screening of HTLV-I/-II infections in endemic regions.

T CD4+ cells count among patients co-infected with human immunodeficiency virus type 1 (HIV-1 and human T-cell leukemia virus type 1 (HTLV-1: high prevalence of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM Contagens de células T CD4+ na co-infecção HIV-1 e HTLV-1: alta prevalência da paraparesia espástica tropical/mielopatia associada ao HTLV-1

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Jorge Casseb

2007-08-01

Full Text Available INTRODUCTION: HIV positive patients co-infected with HTLV-1 may have an increase in their T CD4+ cell counts, thus rendering this parameter useless as an AIDS-defining event. OBJECTIVE: To study the effects induced by the co-infection of HIV-1 and HTLV-1 upon CD4+ cells. MATERIAL AND METHODS: Since 1997, our group has been following a cohort of HTLV-1-infected patients, in order to study the interaction of HTLV-1 with HIV and/or with hepatitis C virus (HCV, as well as HTLV-1-only infected asymptomatic carriers and those with tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM. One hundred and fifty HTLV-1-infected subjects have been referred to our clinic at the Institute of Infectious Diseases "Emílio Ribas", São Paulo. Twenty-seven of them were also infected with HIV-1 and HTLV-1-infection using two ELISAs and confirmed and typed by Western Blot (WB or polymerase chain reaction (PCR. All subjects were evaluated by two neurologists, blinded to the patient's HTLV status, and the TSP/HAM diagnostic was based on the World Health Organization (WHO classification. AIDS-defining events were in accordance with the Centers for Disease Control (CDC classification of 1988. The first T CD4+ cells count available before starting anti-retroviral therapy are shown compared to the HIV-1-infected subjects at the moment of AIDS defining event. RESULTS: A total of 27 HIV-1/HTLV-1 co-infected subjects were identified in this cohort; 15 already had AIDS and 12 remained free of AIDS. The median of T CD4+ cell counts was 189 (98-688 cells/mm³ and 89 (53-196 cells/mm³ for co-infected subjects who had an AIDS-defining event, and HIV-only infected individuals, respectively (p = 0.036. Eight of 27 co-infected subjects (30% were diagnosed as having a TSP/HAM simile diagnosis, and three of them had opportunistic infections but high T CD4+ cell counts at the time of their AIDS- defining event. DISCUSSION: Our results indicate that higher T CD4+ cells

The value of csf analysis for the differential diagnosis of HTLV-I associated myelopathy and multiple sclerosis Valor da análise do LCR para o diagnóstico diferencial de mielopatia associada ao HTLV-I e esclerose múltipla

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Marzia Puccioni-Sohler

1995-12-01

Full Text Available Cerebrospinal fluid (CSF and serum of 17 patients with HAM/TSP (HTLV-I associated myelopathy/ tropical spastic paraparesis, six with multiple sclerosis and six with idiopathic epilepsy (non inflammatory control from Brazil were analysed for the presence of intrathecal synthesis of virus-specific antibodies against measles, rubella, varicella zoster virus and herpes simplex virus by enzyme-linked immunosorbent assay (ELISA. All HAM/TSP and multiple sclerosis cases had an intrathecal immune response (oligoclonal IgG. In HAM/TSP, only 1/17 case showed a polyspecific intrathecal immune response against measles and rubella virus. In multiple sclerosis, specific antibodies against measles and rubella (MRZ response were observed in all patients but not in the control with idiopathic epilepsy. The diagnostic and theoretical relevance of mono- and polyspecific immune responses is discussed for these chronic neurological diseases.Amostras de líquido cefalorraquidiano (LCR e soro de 17 pacientes brasileiros com HAM/TSP, seis com esclerose múltipla e seis com epilepsia idiopática (controle não-inflamatório foram analisadas para a presença de anticorpos para os vírus do sarampo, rubéola, varicela zoster e herpes simples pelo método de ELISA. Todos os casos de HAM/TSP e esclerose múltipla tinham resposta imune intratecal (IgG oligoclonal. Somente 1/17 casos de HAM/TSP apresentavam resposta imune poliespecifica intratecal para sarampo e rubéola. Anticorpos específicos para sarampo e rubeola (resposta MRZ foram observados em todos os pacientes com esclerose múltipla, mas não nos controles com epilepsia idiopática. A relevância das respostas poliespecifica e monoespecifica é discutida para essas doenças neurológicas crônicas.

Interest of LQAS method in a survey of HTLV-I infection in Benin (West Africa).

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Houinato, Dismand; Preux, Pierre-Marie; Charriere, Bénédicte; Massit, Bruno; Avodé, Gilbert; Denis, François; Dumas, Michel; Boutros-Toni, Fernand; Salamon, Roger

2002-02-01

HTLV-I is heterogeneously distributed in Sub-Saharan Africa. Traditional survey methods as cluster sampling could provide information for a country or region of interest. However, they cannot identify small areas with higher prevalences of infection to help in the health policy planning. Identification of such areas could be done by a Lot Quality Assurance Sampling (LQAS) method, which is currently used in industry to identify a poor performance in assembly lines. The LQAS method was used in Atacora (Northern Benin) between March and May 1998 to identify areas with a HTLV-I seroprevalence higher than 4%. Sixty-five subjects were randomly selected in each of 36 communes (lots) of this department. Lots were classified as unacceptable when the sample contained at least one positive subject. The LQAS method identified 25 (69.4 %) communes with a prevalence higher than 4%. Using stratified sampling theory, the overall HTLV-I seroprevalence was 4.5% (95% CI: 3.6-5.4%). These data show the interest of LQAS method application under field conditions to detect clusters of infection.

HTLV-I carrier with unusual brain MR imaging findings

Energy Technology Data Exchange (ETDEWEB)

Yata, Shinsaku; Ogawa, Toshihide; Sugihara, Shuji; Matsusue, Eiji; Fujii, Shinya; Kinoshita, Toshibumi [Tottori University, Department of Pathophysiological and Therapeutic Science, Yonago (Japan); Faculty of Medicine, Tottori University, Yonago (Japan)

2004-09-01

We describe unusual brain MR imaging findings in a patient who is an HTLV-I carrier without myelopathy. T2-weighted MR images showed hyperintense signal abnormalities in the pyramidal tract, superior and middle cerebellar peduncles, and decussation of the superior cerebellar peduncles, in addition to subcortical white matter involvement. Diffusion-weighted images also showed hyperintense signal abnormalities in the same regions by T2 shine-through effect. (orig.)

Quantification of HTLV-I proviral load in experimentally infected rabbits

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Kindt Thomas J

2005-05-01

Full Text Available Abstract Background Levels of proviral load in HTLV-1 infected patients correlate with clinical outcome and are reasonably prognostic. Adaptation of proviral load measurement techniques is examined here for use in an experimental rabbit model of HTLV-1 infection. Initial efforts sought to correlate proviral load with route and dose of inoculation and with clinical outcome in this model. These methods contribute to our continuing goal of using the model to test treatments that alleviate virus infection. Results A real-time PCR assay was used to measure proviral load in blood and tissue samples from a series of rabbits infected using HTLV-1 inocula prepared as either cell-free virus particles, infected cells or blood, or by naked DNA injection. Proviral loads from asymptomatically infected rabbits showed levels corresponding to those reported for human patients with clinically silent HTLV-1 infections. Proviral load was comparably increased in 50% of experimentally infected rabbits that developed either spontaneous benign or malignant tumors while infected. Similarly elevated provirus was found in organs of rabbits with experimentally induced acute leukemia/lymphoma-like disease. Levels of provirus in organs taken at necropsy varied widely suggesting that reservoirs of infections exist in non-lymphoid organs not traditionally thought to be targets for HTLV-1. Conclusion Proviral load measurement is a valuable enhancement to the rabbit model for HTLV-1 infection providing a metric to monitor clinical status of the infected animals as well as a means for the testing of treatment to combat infection. In some cases proviral load in blood did not reflect organ proviral levels, revealing a limitation of this method for monitoring health status of HTLV-1 infected individuals.

Virus-induced dysfunction of CD4+CD25+ T cells in patients with HTLV-I-associated neuroimmunological disease.

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Yamano, Yoshihisa; Takenouchi, Norihiro; Li, Hong-Chuan; Tomaru, Utano; Yao, Karen; Grant, Christian W; Maric, Dragan A; Jacobson, Steven

2005-05-01

CD4(+)CD25(+) Tregs are important in the maintenance of immunological self tolerance and in the prevention of autoimmune diseases. As the CD4(+)CD25(+) T cell population in patients with human T cell lymphotropic virus type I-associated (HTLV-I-associated) myelopathy/tropical spastic paraparesis (HAM/TSP) has been shown to be a major reservoir for this virus, it was of interest to determine whether the frequency and function of CD4(+)CD25(+) Tregs in HAM/TSP patients might be affected. In these cells, both mRNA and protein expression of the forkhead transcription factor Foxp3, a specific marker of Tregs, were lower than those in CD4(+)CD25(+) T cells from healthy individuals. The virus-encoded transactivating HTLV-I tax gene was demonstrated to have a direct inhibitory effect on Foxp3 expression and function of CD4(+)CD25(+) T cells. This is the first report to our knowledge demonstrating the role of a specific viral gene product (HTLV-I Tax) on the expression of genes associated with Tregs (in particular, foxp3) resulting in inhibition of Treg function. These results suggest that direct human retroviral infection of CD4(+)CD25(+) T cells may be associated with the pathogenesis of HTLV-I-associated neurologic disease.

Establishment of HTLV-I-infected cell lines from peripheral blood mononuclear cells of Brazilian patients Estabelecimento de linhagens celulares infectadas por HTLV-I a partir de células mononucleares periféricas de pacientes brasileiros

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Carolina V. Pannuti

2004-08-01

Full Text Available To investigate epidemiological and pathogenetic features of HTLV-I infection, a cohort of carriers has been followed at the USP Teaching Hospital since 1991. This study describes the establishment of cell lines from peripheral blood mononuclear cells (PBMC of infected subjects. Ex vivo PBMC were cultured with those from a seronegative donor and morphologic evidence of cell transformation was obtained after 90 days with detection of multinucleated cells exhibiting cerebriform nuclei. Integration of HTLV-I proviral DNA and expression of viral antigens was demonstrated in culture by PCR and immunofluorescence. Cell lines were maintained for 240 days, gradually weaned from exogenous IL-2. Immunophenotyping of cell lines on flow cytometry yielded evidence of cell activation. Establishment of HTLV-I-infected cell lines from ex vivo PBMC is feasible and may be useful for studies on lymphocyte phenotypic changes and on mechanisms of HTLV-induced cell proliferation. Moreover they may be used with diagnostic purposes in immunofluorescence tests.Para investigar a epidemiologia e patogênese da infecção por HTLV-I seguimos coorte de portadores dessa retrovirose no HC-FMUSP desde 1991. Este estudo descreve o estabelecimento de linhagens celulares a partir de células mononucleares periféricas (CMP de indivíduos infectados. As CMP foram cultivadas com as de doador soronegativo, verificando-se após 90 dias evidência morfológica de transformação celular com detecção de células multinucleadas com núcleos cerebriformes. Demonstrou-se integração do DNA proviral e expressão in vitro de antígenos virais pela PCR e imunofluorescência. As linhagens celulares transformadas foram mantidas por 240 dias, com retirada gradual de IL-2 exógena. A imunofenotipagem por citometria de fluxo revelou ativação celular. O estabelecimento de linhagens celulares infectadas por HTLV-I a partir de CMP ex-vivo é exeqüível e pode ser útil na investigação de

Clonagem e expressão da glicoproteína transmembrana do vírus linfotrópico de células T humanas em sistema procarioto Cloning and expression of the transmembranic glycoprotein from human T cell lymphotropic virus in a prokaryotic system

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Elisa Maria de Sousa Russo-Carbolante

2007-06-01

Full Text Available O HTLV-1 é o vírus causador da leucemia/linfoma de célula T no adulto e de uma desordem neurológica conhecida por mielopatia associada ao HTLV ou paraparesia espástica tropical. Um dos modos de transmissão é pelo sangue contaminado e seus subprodutos e, devido ao risco de infecções associadas ao HTLV sua pesquisa na triagem de doadores de sangue foi introduzida no Brasil a partir de 1993. Os kits diagnósticos utilizados nos bancos de sangue nacionais são na sua maioria comprados de empresas estrangeiras. O Brasil não detém a tecnologia para produção deste material e há a necessidade de produção de sistemas de diagnóstico com tecnologia nacional. Neste trabalho, mostramos a expressão da gp21/HTLV-1 em Escherichia coli e sua reatividade frente a anticorpos monoclonais e de pacientes infectados. Expressar tais proteínas é o primeiro passo para obtenção de conjuntos diagnósticos com tecnologia brasileira.HTLV-1 is the virus that causes T cell lymphoma/leukemia in adults and a neurological disorder known as HTLV-associated myelopathy or tropical spastic paraparesis. One of the transmission means is through contaminated blood and its byproducts. Because of the risk of HTLV-associated infections, screening for HTLV was introduced for Brazilian blood donors in 1993. Most of the diagnostic kits used in the national blood banks are bought from foreign companies. Brazil does not have the technology to produce this material and there is a need to produce diagnostic systems with national technology. In this study, we show the expression of gp21/HTLV-1 in Escherichia coli and its reactivity towards monoclonal antibodies and the antibodies of infected patients. Expressing these proteins is the first step towards obtaining diagnostic kits with Brazilian biotechnology.

Detection of the HTLV-I gene on cytologic smear slides.

Science.gov (United States)

Kashima, Kenji; Nagahama, Junji; Sato, Keiji; Tanamachi, Hiroyuki; Gamachi, Ayako; Daa, Tsutomu; Nakayama, Iwao; Yokoyama, Shigeo

2002-01-01

To apply the polymerase chain reaction (PCR) for detection of the HTLV-I gene from cytologic smear slides. Samples were from seven cases of serum anti-ATL antibody (ATLA)-positive T-cell lymphoma and three from ATLA-negative T-cell lymphoma. Six of the seven ATLA-positive cases were confirmed to be ATLL by Southern blotting. From the seventh case a fresh sample for blotting could not obtained. DNA was extracted from the cytologic smear slides of all 10 cases; they had been stained with Papanicolaou or May-Giemsa stain, digested with proteinase K and precipitated with phenol and ethanol. The target sequence in the pX region of the HTLV-I gene was amplified by PCR. All seven ATLA-positive cases, including one that had not yet been confirmed by Southern blotting, showed a single band, as predicted, while the three ATLA-negative cases showed no band. If cytologic smear slides are available but a fresh sample is not, the PCR method should provide evidence that the virus is present since in our study sufficient DNA templates were successfully extracted from the stained cytologic smear slides for detection of the virus.

Dual infections with HIV-1, HIV-2 and HTLV-I are more common in older women than in men in Guinea-Bissau

DEFF Research Database (Denmark)

Holmgren, B; da Silva, Z; Larsen, Olav Ditlevsen

2003-01-01

OBJECTIVES: To investigate the association between the three human retroviruses, HIV-1, HIV-2 and HTLV-I. DESIGN: Community-based follow-up studies of retrovirus infections in two cohorts. METHODS: A total of 2057 individuals aged 35 years and over were eligible for inclusion. Participants were...... interviewed and had a blood sample drawn. Samples were analysed for HIV-1, HIV-2 and HTLV infections. Uni- and multivariate analyses that included behavioural and socio-economic factors were performed using logistic regression and Poisson regression models. RESULTS: A total of 1686 individuals participated...... with a blood sample in the HIV prevalence analyses and 1581 individuals participated in the HTLV-I prevalence analyses. The overall prevalence was 2.1% for HIV-1, 13.5% for HIV-2 and 7.1% for HTLV-I. Comparing the

Prevalence of HTLV-I antibody among two distinct ethnic groups inhabiting the Amazon region of Brazil Prevalência do anticorpo HTLV-I em dois grupos étnicos distintos habitando a região da Amazônia Brasileira

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C.M. Nakauchi

1992-08-01

Full Text Available HTLV-I seroprevalences of 3.63% (02/55, 12.19% (10/82 and 13.88% (10/72 were demonstrated among Tiryio, Mekranoiti and Xicrin Amazonian Indians, respectively, by the Western blotting enzyme assay (WBEI. By indirect immuno electron microscopy (IIEM, 2 Tiriyo, 9 Mekranoiti and 6 Xicrin Amerindians were reactive. Of 44 serum samples from Japanese immigrants, none reacted by any of the techniques before mentioned. One, 8 and 6 serum samples from Tiryio, Mekranoiti and Xicrin Indians, respectively, were both WBEI and IIEM positive. Our results strongly suggest that HTLV-I and/or an HTLV-I antigenic variant circulate (s among populations living in the Amazon region of Brazil.Soroprevalências para HTLV-I de 3,63% (02/55, 12,9% (10/82 e 13,88% (10/72 foram demonstradas entre os Tiryió, Mekranoiti e Xicrin, respectivamente - indígenas habitantes da Amazônia -, utilizando-se a técnica de "Western Blot" (WBEI. Por outro lado, a imunomicroscopia eletrônica indireta (IIME revelou como positivos 2 Tiryió, 9 Mekranoiti e 6 Xicrins. Das 44 amostras de soro oriundas de migrantes japoneses, nenhuma resultou positiva pelas duas técnicas antes mencionadas. Foram reativos por ambos os métodos, 1, 8 e 6 amostras dos índios Tiryió, Mekranoiti e Xicrin, respectivamente. Nossos resultados representam uma forte evidência de que o HTV-I e/ou variante(s antigenicamente similar(es circula(m entre populações que habitam a região amazônica do Brasil.

Dendritic cell maturation, but not type I interferon exposure, restricts infection by HTLV-1, and viral transmission to T-cells.

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Gergès Rizkallah

2017-04-01

Full Text Available Human T lymphotropic Virus type 1 (HTLV-1 is the etiological agent of Adult T cell Leukemia/Lymphoma (ATLL and HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP. Both CD4+ T-cells and dendritic cells (DCs infected with HTLV-1 are found in peripheral blood from HTLV-1 carriers. We previously demonstrated that monocyte-derived IL-4 DCs are more susceptible to HTLV-1 infection than autologous primary T-cells, suggesting that DC infection precedes T-cell infection. However, during blood transmission, breast-feeding or sexual transmission, HTLV-1 may encounter different DC subsets present in the blood, the intestinal or genital mucosa respectively. These different contacts may impact HTLV-1 ability to infect DCs and its subsequent transfer to T-cells. Using in vitro monocyte-derived IL-4 DCs, TGF-β DCs and IFN-α DCs that mimic DCs contacting HTLV-1 in vivo, we show here that despite their increased ability to capture HTLV-1 virions, IFN-α DCs restrict HTLV-1 productive infection. Surprisingly, we then demonstrate that it is not due to the antiviral activity of type-I interferon produced by IFN-α DCs, but that it is likely to be linked to a distinct trafficking route of HTLV-1 in IL-4 DCs vs. IFN-α DCs. Finally, we demonstrate that, in contrast to IL-4 DCs, IFN-α DCs are impaired in their capacity to transfer HTLV-1 to CD4 T-cells, both after viral capture and trans-infection and after their productive infection. In conclusion, the nature of the DCs encountered by HTLV-1 upon primo-infection and the viral trafficking route through the vesicular pathway of these cells determine the efficiency of viral transmission to T-cells, which may condition the fate of infection.

A Case Report of Positive HTLV-I Infection with Bilateral Facial Weakness and Myelitis

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M. Mazdeh

2005-04-01

Full Text Available Infection with human T cell lymphotropic virus type I (HTLV-I causes multiple neurologic disorder , due to the retroviruses.Spinal cord disease of this type is named TSP (tropical spastic paraparesis that were drawn to the attention of neurologists 45 years ago. The clinical picture is one of the slowly progressive paraparesis with increased tendon reflexes & Babinski signs ; disorder of sphincteric control is usually an early change. Paresthesia , reduced vibratory & position senses, & ataxia have been described. The diagnosis is confirmed by the detection the antibodies to the virus in serum . There are anecdotal reports of improvement with IV-administration of gammaglobulin. But HTLV1-infection has other clinical manifestations. This report presents a rare case with bilateral facial weakness as primary manifestation. This case is related to a 41 years old woman. The clinical picture was bilateral facial weekness and approximately after 2 months, she referred to hospital with myelitis. In primary exams and evaluation, the diagnose was HTLV-I infection. The diagnosis was confirmed by the detection of the antibodies against the virus in her serum. She dead after 2.5 months of the first sign due to disease severity and bulbar palsy. Possible transmission routes and the risk of encountering the disease outside endemic areas must be attended , and it is recommended to evaluate antibodies in the children of the patients.

Síndrome neuroléptica maligna: relato de caso com recorrência associada ao uso de olanzapina

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HANEL RICARDO A.

1998-01-01

Full Text Available A síndrome neuroléptica maligna (SNM consiste em reação idiossincrática a neurolépticos, provavelmente relacionada a bloqueio dos receptores dopaminérgicos nos gânglios da base, sendo por isso também conhecida como síndrome da deficiência aguda de dopamina.A SNM é caracterizada por hiperpirexia, alteração do nível de consciência, hipertonia, disfunção autonômica e insuficiência respiratória, podendo ainda ser encontrados rabdomiólise e leucocitose. O haloperidol é a droga mais frequentemente associada à síndrome. Relatamos o caso de um paciente de 30 anos que apresentou SNM em duas ocasiões diferentes, a primeira delas relacionada ao uso de haloperidol e clorpromazina e a segunda relacionada ao uso de olanzapina, fato este sem menção anterior na literatura indexada.

Combined Cytolytic Effects of a Vaccinia Virus Encoding a Single Chain Trimer of MHC-I with a Tax-Epitope and Tax-Specific CTLs on HTLV-I-Infected Cells in a Rat Model

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Takashi Ohashi

2014-01-01

Full Text Available Adult T cell leukemia (ATL is a malignant lymphoproliferative disease caused by human T cell leukemia virus type I (HTLV-I. To develop an effective therapy against the disease, we have examined the oncolytic ability of an attenuated vaccinia virus (VV, LC16m8Δ (m8Δ, and an HTLV-I Tax-specific cytotoxic T lymphocyte (CTL line, 4O1/C8, against an HTLV-I-infected rat T cell line, FPM1. Our results demonstrated that m8Δ was able to replicate in and lyse tumorigenic FPM1 cells but was incompetent to injure 4O1/C8 cells, suggesting the preferential cytolytic activity toward tumor cells. To further enhance the cytolysis of HTLV-I-infected cells, we modified m8Δ and obtained m8Δ/RT1AlSCTax180L, which can express a single chain trimer (SCT of rat major histocompatibility complex class I with a Tax-epitope. Combined treatment with m8Δ/RT1AlSCTax180L and 4O1/C8 increased the cytolysis of FPM1V.EFGFP/8R cells, a CTL-resistant subclone of FPM1, compared with that using 4O1/C8 and m8Δ presenting an unrelated peptide, suggesting that the activation of 4O1/C8 by m8Δ/RT1AlSCTax180L further enhanced the killing of the tumorigenic HTLV-I-infected cells. Our results indicate that combined therapy of oncolytic VVs with SCTs and HTLV-I-specific CTLs may be effective for eradication of HTLV-I-infected cells, which evade from CTL lysis and potentially develop ATL.

Increased mortality associated with HTLV-II infection in blood donors: a prospective cohort study

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Smith James W

2004-03-01

Full Text Available Abstract Background HTLV-I is associated with adult T-cell leukemia, and both HTLV-I and -II are associated with HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP. Several published reports suggest that HTLV-I may lead to decreased survival, but HTLV-II has not previously been associated with mortality. Results We examined deaths among 138 HTLV-I, 358 HTLV-II, and 759 uninfected controls enrolled in a prospective cohort study of U.S. blood donors followed biannually since 1992. Proportional hazards models yielded hazard ratios (HRs for the association between mortality and HTLV infection, controlling for sex, race/ethnicity, age, income, educational level, blood center, smoking, injection drug use history, alcohol intake, hepatitis C status and autologous donation. After a median follow-up of 8.6 years, there were 45 confirmed subject deaths. HTLV-I infection did not convey a statistically significant excess risk of mortality (unadjusted HR 1.9, 95%CI 0.8–4.4; adjusted HR 1.9, 95%CI 0.8–4.6. HTLV-II was associated with death in both the unadjusted model (HR 2.8, 95%CI 1.5–5.5 and in the adjusted model (HR 2.3, 95%CI 1.1–4.9. No single cause of death appeared responsible for the HTLV-II effect. Conclusions After adjusting for known and potential confounders, HTLV-II infection is associated with increased mortality among healthy blood donors. If replicated in other cohorts, this finding has implications for both HTLV pathogenesis and counseling of infected persons.

Prevalência de dor associada ao transporte de material escolar

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Windsor Ramos da Silva Júnior

2014-10-01

Full Text Available http://dx.doi.org/10.5007/1980-0037.2014v16n6p680 O objetivo do trabalho foi verificar a prevalência de dor associada ao transporte de material escolar por estudantes universitários. Realizou-se pesquisa transversal, quantitativa, descritiva-analítica, na qual foram avaliados 373 estudantes universitários da Universidade Estadual da Paraíba, entre fevereiro e setembro de 2012. As informações foram coletadas através de questionário sobre dados sociodemográficos, acadêmicos, transporte do material escolar e presença de dor, sendo ainda realizada a medição de dados antropométricos e pesagem de todos os volumes transportados pelo indivíduo. Os dados foram analisados de forma descritiva e inferencial através do software SPSSÒ 17.0. Utilizou-se modelo de Regressão Logística Hierárquica Binária, pelo método Backward LR, no qual o poder de influência das variáveis preditoras – divididas em blocos – foi testado na presença de dor musculoesquelética. Constatou-se uma prevalência de dor de 82,84%, com média geral de 5,21 pontos na Escala Visual Analógica (EVA para avaliação de dor. Nas mulheres, a influência exercida pela massa relativa dos volumes sobre a presença de dor foi 45,1% maior que entre os homens (OR = 0,689; IC95% = 0,503 – 0,942 para cada 1% de incremento. O tempo de carga, por sua vez, aumentou em 22,9% a probabilidade da presença de dor, a cada 15 minutos decorridos (OR = 1,229; IC95% = 1,090 – 1,386. Verificou-se alta prevalência de dor relacionada ao transporte de material escolar e a influência preditora de variáveis como peso relativo da carga transportada e tempo de transporte desse material, especialmente nos indivíduos do sexo feminino.

El HTLV-I y la PET/HAM un modelo de investigación en virología y biología molecular

OpenAIRE

Felipe García Vallejo; Martha C. Domínguez

2004-01-01

En la actualidad la infección por el virus linfotrópico humano tipo 1 (HTLV-1) ha sido confirmada epidemiológicamente en la Leucemia/Linfoma de las Células T del Adulto (ATLL) y en la Paraparesia Espástica Tropical/ Mielopatía Asociada al HTLV-I (PET/MAH) (1). El HTLV-I es endémico en varias áreas geográficas del mundo y representa un problema de salud pública global. En Colombia las áreas mas afectadas incluye...

Percepção da imagem corporal associada ao estado nutricional de crianças e adolescentes

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Maiara Battisti

2017-03-01

Full Text Available Objetivo: Analisar a relação entre a percepção dos pais quanto à imagem corporal de seus filhos e a autopercepção da imagem corporal das crianças e dos adolescentes em relação ao seu estado nutricional. Métodos: Estudo de caráter transversal, realizado entre março e abril de 2016 com 122 crianças e adolescentes, de 6 a 19 anos, e com os seus responsáveis. Com os escolares, foi aplicado um questionário contendo dados relativos ao gênero, peso, altura e à localização da área da escola (rural ou urbana, além da escala de silhuetas de Stunkard para avaliação da autopercepção da imagem corporal. Calcula-se o estado nutricional pelo índice de massa corporal (IMC classificando-o de acordo com os pontos de corte da Organização Mundial da Saúde (OMS 2007. Com os pais ou responsáveis, utilizou-se a escala de silhuetas de Stunkard e uma questão fechada sobre a preocupação com o estado nutricional da criança ou adolescente, além da identificação do gênero, idade e grau de parentesco (pais, avós, tios, irmão ou outro familiar. Dados analisados com teste de Fisher e p≤0,05 Resultados: Verificou-se que a percepção da imagem corporal dos pais esteve significativamente associada à autopercepção da imagem corporal de seus filhos (p≤0,001, bem como a autopercepção da imagem corporal dos escolares esteve associada ao seu estado nutricional (p≤0,001. Conclusão: Houve uma associação positiva entre a percepção dos pais em relação à imagem corporal de seus filhos e entre a autopercepção da imagem corporal das crianças e dos adolescentes com o seu estado nutricional.

HTLV-1/2 transfusional e hemovigilância: a contribuição dos estudos de look-back Transfusion-transmitted HTLV-1/2 and hemovigilance: the contribution of look-back studies

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Maria Sueli S. N. Lopes

2008-01-01

Full Text Available Os vírus linfotrópicos de células T humana tipo 1 (HTLV-1 e tipo 2 (HTLV-2 foram os primeiros retrovírus identificados em humanos, em 1980 e 1982, respectivamente. O HTLV-1 é associado à leucemia/linfoma de células T do adulto (ATL e mielopatia associada ao HTLV-1/ paraparesia espástica tropical (HAM/TSP. Tais vírus podem ser transmitidos por via vertical (mãe para criança principalmente pela amamentação; por via sexual e via parenteral (usuários de drogas e transfusão de sangue e componentes. Nas áreas endêmicas, as transmissões vertical e sexual têm sido as principais vias para a disseminação da infecção por HTLV-1. Porém, a hemotransfusão parece ter importante participação na introdução do HTLV em populações não endêmicas. A via mais eficaz de transmissão transfusional do HTLV-1 é através de componentes celulares do sangue contaminado. No passado, isso ocorria principalmente através da transfusão de sangue não testado para o HTLV-1/2. Eficiência de transmissão transfusional da ordem de 60% foi descrita nos primeiros trabalhos japoneses. Subseqüentemente, extremos de 13% a 80% foram descritos nos estudos retrospectivos realizados nos Estados Unidos. Tamanha variação na eficiência da transmissão transfusional foi influenciada pelos parâmetros: tipo do produto sangüíneo, tempo decorrido entre a coleta dos componentes celulares até seu uso transfusional e carga proviral do HTLV no doador. Estima-se que 4% a 8% dos receptores de unidades celulares infectados por HTLV-1 possam desenvolver HAM/TSP, sendo raros os casos descritos de ATL nestes receptores. "Look-back"é o termo usado em hemovigilância para um programa que notifica grupos de receptores de hemotransfusão, de seus riscos quanto à exposição a um agente infeccioso por ocasião de transfusão prévia. "Look-back targeted"é o programa para identificar receptores de unidades previamente doadas por doadores específicos e que subseq

HTLV-I associated myelopathy with multiple spotty areas in cerebral white matter and brain stem by MRI

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Hara, Yasuo; Takahashi, Mitsuo; Yoshikawa, Hiroo; Yorifuji, Shirou; Tarui, Seiichiro

1988-01-01

A 48-year-old woman was admitted with complaints of urinary incontinence and gait disturbance, both of which had progressed slowly without any sign of remission. Family history was not contributory. Neurologically, extreme spasticity was recoginized in the lower limbs. Babinski sign was positive bilaterally. Flower-like atypical lymphocytes were seen in blood. Positive anti-HTLV-I antibody was confirmed in serum and spinal fluid by western blot. She was diagnosed as having HTLV-I associated myelopathy (HAM). CT reveald calcification in bilateral globus pallidus, and MRI revealed multiple spotty areas in cerebral white matter and brain stem, but no spinal cord lesion was detectable. Electrophysiologically, brain stem auditory evoked potential (BAEP) suggested the presence of bilateral brain stem lesions. Neither median nor posterior tibial nerve somatosensory evoked potentials were evoked, a finding suggesting the existence of spinal cord lesion. In this case, the lesion was not confined to spinal cord, it was also observed in brain stem and cerebral white matter. Such distinct lesions in cerebral white matter and brain stem have not been reported in patients with HAM. It is suggested that HTLV-I is probably associated with cerebral white matter and brain stem.

HTLV-I en población de alto riesgo sexual de Pisco, Ica, Perú.

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Patricia GARRIDO

1997-07-01

Full Text Available Objetivo: Se estudiaron 141 personas con alto riesgo sexual en la ciudad de Pisco para detectar infección por HTLV-I. Material y Métodos: Se encuestaron y se tomaron muestras de sangre a 141 personas que involucró a trabajadoras sexuales (32, varones homosexuales (54, y varones bisexuales(55. Resultados: Tres de treintidós (10.4% trabajadoras sexuales fueron positivas; uno de cincuenticuatro (1.9% de varones homosexuales y ninguno de 55 bisexuales. Hubo una elevada frecuencia de parejas, así como el antecedente de enfermedades de transmisión sexual (ETS en estos grupos con comportamiento de riesgo. Conclusiones: El HTLV-I es una infección frecuente en grupos de alto riesgo sexual de Pisco-Perú. (Rev Med Hered 1997; 8:104-107.

Inhibition of Geranylgeranyl Transferase-I Decreases Cell Viability of HTLV-1-Transformed Cells

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Cynthia A. Pise-Masison

2011-10-01

Full Text Available Human T-cell leukemia virus type-1 (HTLV-1 is the etiological agent of adult T-cell leukemia (ATL, an aggressive and highly chemoresistant malignancy. Rho family GTPases regulate multiple signaling pathways in tumorigenesis: cytoskeletal organization, transcription, cell cycle progression, and cell proliferation. Geranylgeranylation of Rho family GTPases is essential for cell membrane localization and activation of these proteins. It is currently unknown whether HTLV-1-transformed cells are preferentially sensitive to geranylgeranylation inhibitors, such as GGTI-298. In this report, we demonstrate that GGTI-298 decreased cell viability and induced G2/M phase accumulation of HTLV-1-transformed cells, independent of p53 reactivation. HTLV-1-LTR transcriptional activity was inhibited and Tax protein levels decreased following treatment with GGTI-298. Furthermore, GGTI-298 decreased activation of NF-κB, a downstream target of Rho family GTPases. These studies suggest that protein geranylgeranylation contributes to dysregulation of cell survival pathways in HTLV-1-transformed cells.

Seroprevalence of HIV, HTLV-I/II and other perinatally-transmitted pathogens in Salvador, Bahia Soroprevalência do HIV, HTLV-I/II e outros patógenos de transmissão perinatal em Salvador, Bahia

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Jairo Ivo dos Santos

1995-08-01

Full Text Available Generation of epidemiological data on perinatally-transmitted infections is a fundamental tool for the formulation of health policies. In Brazil, this information is scarce, particularly in Northeast, the poorest region of the country. In order to gain some insights of the problem we studied the seroprevalence of some perinatally-transmitted infections in 1,024 low income pregnant women in Salvador, Bahia. The prevalences were as follow: HIV-1 (0.10%, HTLV-I/II (0.88%, T.cruzi (2.34%. T.pallidum (3.91%, rubella virus (77.44%. T.gondii IgM (2.87% and IgG (69.34%, HBs Ag (0.6% and anti-HBs (7.62%. Rubella virus and T.gondii IgG antibodies were present in more than two thirds of pregnant women but antibodies against other pathogens were present at much lower rates. We found that the prevalence of HTLV-I/II was nine times higher than that found for HIV-1. In some cases such as T.cruzi and hepatitis B infection there was a decrease in the prevalence over the years. On the other hand, there was an increase in the seroprevalence of T.gondii infection. Our data strongly recommend mandatory screening tests for HTLV-I/II, T.gondii (IgM, T.pallidum and rubella virus in prenatal routine for pregnant women in Salvador. Screening test for T.cruzi, hepatitis and HIV-1 is recommended whenever risk factors associated with these infections are suspected. However in areas with high prevalence for these infections, the mandatory screening test in prenatal care should be considered.A obtenção de dados epidemiológicos é de fundamental importância para o estabelecimento de políticas em Saúde Pública. No Brasil, essas informações são escassas, principalmente na região Nordeste. Para se obter alguns destes dados, avaliamos a soroprevalência de algumas infecções de transmissão perinatal, em cerca de 1024 gestantes de baixa renda, em Salvador, Bahia. Os resultados encontrados foram os seguintes: HIV-1 (0,10%, HTLV-I/II (0,88%, T.cruzi (2,34%, T.pallidum (3

Asociación entre infección por el virus linfotrópico humano de células T tipo I (HTLV-I y mortalidad en pacientes hospitalizados con tuberculosis

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Kristien Verdonck Bosteels

2004-10-01

Full Text Available El Perú es un país de alta prevalencia de tuberculosis (TBC y endémico para la infección por el virus linfotrópico humano de células T tipo I (HTLV-I. Objetivo: Determinar la asociación entre la infección por HTLV-I y la mortalidad de los pacientes hospitalizados por TBC. Material y métodos: Los pacientes que ingresaron consecutivamente con el diagnóstico de TBC a los servicios de hospitalización de los Departamentos de Medicina Interna y de Enfermedades Infecciosas, Tropicales y Dermatológicas del Hospital Nacional Cayetano Heredia fueron entrevistados y sometidos a una prueba diagnóstica para la infección por HTLV-I. Se revisaron sus historias clínicas y los libros de altas para definir el resultado de la hospitalización. Las variables clínicas y epidemiológicas que estuvieron asociadas con mortalidad durante la hospitalización en el análisis univariado fueron incluidos en un modelo de regresión logística múltiple. Resultados: Se incluyeron 193 pacientes hospitalizados con TBC; 14 tuvieron infección por HTLV-I (7.3%. En el análisis multivariado, la infección por HTLV-I (OR ajustado 9.4; IC 2.2 - 40.6, TBC meníngea (OR ajustado 3.8; IC 1.3 - 11.5 y la condición de infección por VIH desconocido (OR ajustado 0.2; IC 0.04 - 0.6 se encontraron asociadas con la mortalidad durante la hospitalización. Conclusión: Este estudio demuestra que la infección por HTLV-I es frecuente entre los pacientes hospitalizados con TBC y que existe una relación independiente entre esta infección y la mortalidad durante la hospitalización.(Rev Med Hered 2004;15:197-202.

Telomere Length, Proviral Load and Neurologic Impairment in HTLV-1 and HTLV-2-Infected Subjects

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Benjamin Usadi

2016-08-01

Full Text Available Short or damaged telomeres have been implicated in degenerative conditions. We hypothesized that analysis of telomere length (TL in human T-cell lymphotropic virus (HTLV infection and HTLV-associated neuropathy might provide clues to the etiology of HTLV-associated disease and viral dynamics. A subset of 45 human T-cell lymphotropic virus type 1 (HTLV-1, 45 human T-cell lymphotropic virus type 2 (HTLV-2, and 45 seronegative subjects was selected from the larger HTLV Outcomes Study (HOST cohort, matched on age, sex and race/ethnicity. Telomere-to-single-copy gene (T/S ratio (a measure of TL and HTLV-1 and HTLV-2 proviral loads were measured in peripheral blood mononuclear cells (PBMCs using quantitative PCR (qPCR. Vibration sensation measured by tuning fork during neurologic examinations performed as part of the HOST study allowed for an assessment of peripheral neuropathy. TL was compared between groups using t-tests, linear and logistic regression. Mean T/S ratio was 1.02 ± 0.16 in HTLV-1, 1.03 ± 0.17 in HTLV-2 and 0.99 ± 0.18 in HTLV seronegative subjects (p = 0.322. TL was not associated with HTLV-1 or -2 proviral load. Shorter TL was significantly associated with impaired vibration sense in the HTLV-2 positive group only. Overall, we found no evidence that telomere length was affected by chronic HTLV-1 and HTLV-2 infection. That TL was only associated with peripheral neuropathy in the HTLV-2-positive group is intriguing, but should be interpreted cautiously. Studies with larger sample size and telomere length measurement in lymphocyte subsets may clarify the relationship between TL and HTLV-infection.

Epidemiological analysis of HTLV-1 and HTLV-2 infection among different population in Central China.

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Yunyun Ma

Full Text Available BACKGROUND: HTLV-1 and HTLV-2 are retroviruses linked etiologically to various human diseases, and both of them can be transmitted by vertical route, sexual intercourse, blood transfusion and intravenous drug use. Recently, some HTLV-infected cases have been reported and this virus is mainly present in the Southeast coastal areas in China, but has not been studied for the people in Central China. OBJECTIVES: To know the epidemiologic patterns among different population samples in Central China and further identify risk factor for HTLV-1 and HTLV-2 infection. METHODS: From January 2008 to December 2011, 5480 blood samples were screened for HTLV-1/2 antibodies by using enzyme immunoassay, followed by Western Blot. RESULTS: The prevalence of HTLV-1 and HTLV-2 was found with infection rates 0.13% and 0.05% among all population samples for HTLV-1 and HTLV-2, respectively. The highest percentages of infection, 0.39% and 0.20%, were found in the high risk group, while only 0.06% and 0.03% in the blood donor group. There was only one case of HTLV-1 infection (0.11% among patients with malignant hematological diseases. Of seven HTLV-1 positive cases, six were co-infected with HBV, two with HCV and one with HIV. Among three HTLV-2 positive individuals all were co-infected with HBV, one with HCV. CONCLUSIONS: HTLV-1 and HTLV-2 have been detected in the Central China at low prevalence, with the higher infection rate among high risk group. It was also found that co-infection of HTLV-1/2 with HIV and HBV occurred, presumably due to their similar transmission routes. HTLV-1/2 antibody screen among certain population would be important to prevent the spread of the viruses.

HIV-1, HTLV-I and the interleukin-2 receptor: insights into transcriptional control.

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Böhnlein, E; Lowenthal, J W; Wano, Y; Franza, B R; Ballard, D W; Greene, W C

1989-01-01

In this study, we present direct evidence for the binding of the inducible cellular protein, HIVEN86A, to a 12-bp element present in the IL-2R alpha promoter. This element shares significant sequence similarity with the NF-kappa B binding sites present in the HIV-1 and kappa immunoglobulin enhancers. Transient transfection studies indicate that this kappa B element is both necessary and sufficient to confer tax or mitogen inducibility to a heterologous promoter. As summarized schematically in Fig. 5, the findings suggest that the HIVEN86A protein may play a central role in the activation of cellular genes required for T-cell growth, specifically the IL-2R alpha gene. In addition, the induced HIVEN86A protein also binds to a similar sequence present in the HIV-1 LTR leading to enhanced viral gene expression and ultimately T-cell death. Thus, mitogen activation of the HIV-1 LTR appears to involve the same inducible transcription factor(s) that normally regulates IL-2R alpha gene expression and T-cell growth. These findings further underscore the importance of the state of T-cell activation in the regulation of HIV-1 replication. Our results also demonstrate that HIVEN86A is induced by the tax protein of HTLV-I. Thus, in HTLV-I infected cells, normally the tight control of the transient expression of the IL-2R alpha gene is lost. The constitutive high-level display of IL-2 receptors may play a role in leukemic transformation mediated by HTLV-I (ATL). Apparently by the same mechanism, the tax protein also activates the HIV-1 LTR through the induction of HIVEN86A.(ABSTRACT TRUNCATED AT 250 WORDS)

Spread of human T-cell leukemia virus (HTLV-I) in the Dutch homosexual community

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Goudsmit, J.; de Wolf, F.; van de Wiel, B.; Smit, L.; Bakker, M.; Albrecht-van Lent, N.; Coutinho, R. A.

1987-01-01

Sequential sera of 697 homosexual men, participating in a prospective study (1984-1986) of the risk to acquire human immunodeficiency virus (HIV) or AIDS, were tested for antibodies to human T-cell leukaemia virus (HTLV-I) by particle agglutination and immunoblotting. No intravenous drug users were

Hipometilação do LINE-1 está Associada ao Risco de Doença Cardíaca Coronariana na População Chinesa

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Li Wei

2014-06-01

Full Text Available Fundamentos: O nível de metilação global do ADN de leucócitos no sangue tem sido associado ao risco de doença arterial coronariana (DAC, com resultados inconsistentes em diferentes populações. Faltam dados semelhantes da população chinesa, onde diferentes fatores genéticos, de estilo de vida e ambientais podem afetar a metilação do ADN e sua relação com o risco de DCC. Objetivos: Analisar se a metilação global está associada ao risco de doença coronariana na população chinesa. Métodos: Foram incluídos um total de 334 casos de DCC e 788 controles saudáveis. A metilação global do ADN de leucócitos de sangue foi estimada por meio da análise das repetições do LINE-1 usando pirosequenciamento de bissulfito. Resultados: Em uma análise inicial restrita aos controles o nível do LINE-1 diminui significativamente com a idade avançada, colesterol total elevado, e diagnóstico de diabetes. Na análise de caso-controle, a redução da metilação do LINE-1 foi associada ao aumento do risco de DCC, tendo a análise por quartil revelado uma odds ratio (IC 95% de 0,9 (0,6-1,4, 1,9 (1,3-2,9 e 2,3 (1,6 3.5 para o terceiro, segundo e primeiro (o mais baixo quartil (P da tendência < 0,001, respectivamente, em comparação com o quarto (o mais alto quartil. A metilação inferior (< mediana do LINE-1 esteve associada a 2,2 vezes (IC 95% = 1,7-3,0 o aumento de risco de doença coronariana. As estimativas de risco de DCC menores relacionadas com o LINE-1 tenderam a ser mais fortes entre os indivíduos com maior tercil de homocisteína (P interação = 0,042 e naqueles com diagnóstico de hipertensão arterial (P interação = 0,012. Conclusão: A hipometilação do LINE-1 está associada ao risco de doença coronariana na população chinesa. Fatores de risco de DCC potenciais tais como a idade avançada, colesterol total elevado, e diagnóstico de diabetes podem ter impacto na metilação global do ADN, exercendo, portanto, o seu

Frequency of the CCRD32 allele in Brazilians: a study in colorectal cancer and in HTLV-I infection

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Pereira Rinaldo W.

2000-01-01

Full Text Available The identification of a 32-bp deletion in the cc-chemokine receptor-5 gene (CCR5delta32 allele that renders homozygous individuals highly resistant to HIV infection has prompted worldwide investigations of the frequency of the CCR5delta32 allele in regional populations. It is important to ascertain if CCR5delta32 is a factor to be considered in the overall epidemiology of HIV in individual populations. With this in mind we determined the CCR5delta32 allele frequency in a large sample (907 individuals of the southeastern Brazilian urban population, stratified as follows: 322 healthy unrelated individuals, 354 unselected colorectal cancer patients, and 229 blood donors. The three groups displayed essentially identical allelic frequencies of CCR5delta32 and pairwise comparisons did not show significant differences. Thus, our results can be pooled to provide a reliable estimate of the CCR5delta32 allele frequency in the southeastern Brazil of 0.053 ± 0.005. The blood donors comprised 50 HTLV-I serologically negative individuals, 115 non-symptomatic individuals HTLV-I positive by ELISA but with indeterminate Western blot results, 49 healthy blood donors HTLV-I positive both at ELISA and Western blot and 15 patients with clinical spinal cord disease (HAM. A suggestive trend was observed, with the CCR5delta32 frequencies decreasing progressively in these four categories. However, when we applied Fischer's exact test no significant differences emerged. We believe that further studies in larger cohorts should be performed to ascertain whether the CCR5delta32 allele influences the chance of becoming infected or developing clinical symptoms of HTLV-I infection.

Prevalence of human T cell leukemia virus-I (HTLV-I antibody among populations living in the Amazon region of Brazil (preliminary report

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C. M. Nakauchi

1990-03-01

Full Text Available Forty-tree (31.4% out of 137 serum samples obtained from two Indian communities living in the Amazon region were found to be positive for HTLV-I antibody, as tested by enzyme-linked immunosorbent assay (Elisa. Eighty-two sera were collected from Mekranoiti Indians, yielding 39% of positivity, whereas 11 (20.0% or the 55 Tiriyo serum samples had antibody to HTLV-I. In addition, positive results occurred in 10 (23.2% out of 43 sera obtained from patients living in the Belem area, who were suffering from cancer affecting different organs. Five (16.7% out of 30 Elisa positive specimens were also shown to be positive by either Western blot analysis (WB or indirect immunogold electron microscopy (IIG-EM.

Descriptive study of HTLV infection in a population of pregnant women from the state of Pará, Northern Brazil Estudo descritivo da infecção pelo HTLV em uma população de gestantes do Estado do Pará, norte do Brasil

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Carina Guilhon Sequeira

2012-08-01

á, Norte do Brasil. MÉTODOS: 13,382 gestantes foram submetidas à triagem para HTLV durante o pré-natal, e aquelas com sorologia alterada para anti-HTLV foram submetidas ao teste de Western Blot (WB, para confirmar e discriminar portadoras do HTLV-1 e do HTLV-2. RESULTADOS: A soroprevalência do HTLV na população de gestantes foi de 0,3%, sendo o HTLV-1 identificado em 95,3% das pacientes. O perfil demográfico das portadoras do HTLV foi de: mulheres com idade entre 20-40 anos (78,4%; residentes na região metropolitana de Belém (67,6% e com nível educacional igual ao ensino médio (56,8%. Outras variáveis relacionadas à infecção foram: início das relações sexuais compreendido entre 12-18 anos (64,9%, e ter sido aleitada mais de 6 meses (51,4%. A maior parte das mulheres estudadas teve ao menos duas gestações anteriores (35,1%; e nenhum aborto (70,3%. Co-infecções (sífilis e HIV foram descritas em 10,8% (4/37 das gestantes. A soroprevalência da infecção pelo HTLV em gestantes atendidas em Unidades Básicas de Saúde do Estado do Pará, Norte do Brasil foi de 0,3% semelhante à descrita em outros estudos brasileiros. As variáveis relacionadas com a infecção são indicadores importantes na identificação de gestantes com maior tendência a soropositividade pelo HTLV, sendo uma estratégia de controle e prevenção, evitando a transmissão vertical.

Human T-Lymphotropic virus (HTLV type I in vivo integration in oral keratinocytes

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Martha C Domínguez

2011-03-01

Full Text Available Although the infection of HTLV-1 to cell components of the mouth have been previously reported, there was not until this report, a detailed study to show the characteristics of such infection. From 14 Tropical Spastic Paraparesis/ HTLV-1-Associated Myelopathy (HAM/TSP patients and 11 asymptomatic carrier individuals (AC coming from HTLV-1 endemic areas of southwest Pacific of Colombia, infected oral mucosa cells were primary cultured during five days. These cell cultures were immunophenotyped by dual color fluorescence cell assortment using different lymphocyte CD markers and also were immunohistochemically processed using a polyclonal anti-keratin antibody. Five days old primary cultures were characterized as oral keratinocytes, whose phenotype was CD3- /CD4-/CD8-/CD19-/CD14-/CD45-/A575-keratin+. From DNA extracted of primary cultures LTR, pol, env and tax HTLV-1 proviral DNA regions were differentially amplified by PCR showing proviral integration. Using poly A+ RNA obtained of these primary cultures, we amplify by RT-PCR cDNA of tax and pol in 57.14% (8/14 HAM/TSP patients and 27.28% (3/11 AC. Tax and pol poly A+ RNA were expressed only in those sIgA positive subjects. Our results showed that proviral integration and viral gene expression in oral keratinocytes are associated with a HTLV-1 specific local mucosal immune response only in those HTLV-1 infected individuals with detectable levels of sIgA in their oral fluids. Altogether the results gave strong evidence that oral mucosa infection would be parte of the systemic spreading of HTLV-1 infection.

MICOBIOTA ASSOCIADA À MADEIRA SERRADA DE Eucalyptus grandis HILL EX MAIDEN DURANTE A SECAGEM AO AR LIVRE

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Paulo Fernando Trugilho

2006-02-01

Full Text Available O objetivo principal deste trabalho foi o de acompanhar a secagem ao ar livre da madeira serrada de Eucalyptus grandis conduzida na região de Lavras, MG e identificar a micobiota associada à madeira em diversas fases da secagem. As tábuas foram cortadas de oito toras de 3,0 m de comprimento, oriundas de três árvores, com 27 anos de idade, plantadas em área experimental da UFLA. Dos resultados, pôde-se concluir que a secagem da madeira de Eucalyptus grandis ao ar livre, iniciada em janeiro, consumiu 158 dias até atingir umidade próxima a 12,5%. A curva de secagem foi representada por uma equação logarítmica com coeficiente de determinação (R2 igual a 98,3%. Os fungos causadores de bolores superficiais e de manchas tiveram maior ocorrência no início da secagem. As mais altas freqüências de fungos, verificadas no início da secagem, foram observadas para Penicillium spp. e Pestalotiopsis sp. O fungo Lentinus lepideus ocorreu com maior freqüência no final da secagem.

Lesões pulmonares associadas ao parasitismo por Sebekia oxycephala (Pentastomida em jacarés-açu (Melanosuchus niger Spix, 1825 oriundos de vida livre na Amazônia brasileira

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Adriana Maciel de C. Cardoso

2014-10-01

Full Text Available O presente estudo objetivou descrever as lesões pulmonares macro e microscópicas associadas ao parasitismo por Sebekia oxycephala em 100 espécimes de jacarés-açu (Melanosuchusniger, abatidos na Reserva de Desenvolvimento Sustentável Mamirauá, situada no Estado do Amazonas, Brasil. Durante a avaliação macroscópica, exemplares dos parasitos encontrados no tecido pulmonar foram coletados individualmente em AFA (Álcool etílico - Formalina - Ácido acético glacial e formol a 5% para avaliação parasitológica e classificação taxonômica. Amostras de tecido pulmonar de todos os animais, independentemente da ocorrência de lesões macroscópicas, foram fixadas em formol 10% e incluídas em parafina. Secções histológicas coradas por Hematoxilina-Eosina destas amostras foram avaliadas por meio de microscopia óptica. Macroscopicamente, 4 dos 100 animais (4% apresentaram espécimes de pentastomídeos no parênquima pulmonar. Os parasitos foram classificados taxonomicamente como pertencentes à espécie Sebekia oxycephala. Nenhuma alteração macroscópicas foi observada, porém, microscopicamente, lesões pulmonares foram encontradas em 37% dos casos, sendo que, lesões inflamatórias associadas ao parasitismo corresponderam a 75,6% dos mesmos (28/37. Nestes, segmentos degenerados e ovos de S. oxycephala encontravam-se envolvidos por cápsula de tecido conjuntivo fibroso e infiltrado inflamatório predominantemente composto por células gigantes do tipo corpo estranho. Três espécimes apresentaram espessamento de septos alveolares e sete exemplares continham infiltrado inflamatório granulocítico multifocal no parênquima pulmonar. As lesões associadas ao parasitismo, de modo geral, apresentaram intensidade discreta e parecem não representar uma causa importante de doença pulmonar entre a população estudada. Esta é a primeira descrição de lesões pulmonares em M. niger associadas ao parasitismo por S. oxycephala na Amaz

Fine tuning of the temporal expression of HTLV-1 and HTLV-2

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Ilaria eCavallari

2013-09-01

Full Text Available Human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2 are deltaretroviruses that share a common overall genetic organization, splicing pattern, and ability to infect and immortalize T-cells in vitro. However, HTLV-1 and HTLV-2 exhibit a clearly distinct pathogenic potential in infected patients. To find clues to the possible viral determinants of the biology of these viruses, recent studies investigated the timing of expression and the intracellular compartmentalization of viral transcripts in ex-vivo samples from infected patients.Results of these studies revealed a common overall pattern of expression of HTLV-1 and -2 with a two-phase kinetics of expression and a nuclear accumulation of minus-strand transcripts. Studies in cells transfected with HTLV-1 molecular clones demonstrated the strict Rex-dependency of this "two-phase" kinetics. These studies also highlighted interesting differences in the relative abundance of transcripts encoding the Tax and Rex regulatory proteins, and that of the accessory proteins controlling Rex expression and function, thus suggesting a potential basis for the different pathobiology of the two viruses.

Characteristic expression of HTLV-1 basic zipper factor (HBZ transcripts in HTLV-1 provirus-positive cells

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Yamada Yasuaki

2008-04-01

Full Text Available Abstract Background HTLV-1 causes adult T-cell leukemia (ATL. Although there have been many studies on the oncogenesis of the viral protein Tax, the precise oncogenic mechanism remains to be elucidated. Recently, a new viral factor, HTLV-1 basic Zip factor (HBZ, encoded from the minus strand mRNA was discovered and the current models of Tax-centered ATL cell pathogenesis are in conflict with this discovery. HBZs consisting of non-spliced and spliced isoforms (HBZ-SI are thought to be implicated in viral replication and T-cell proliferation but there is little evidence on the HBZ expression profile on a large scale. Results To investigate the role of HBZ-SI in HTLV-1 provirus-positive cells, the HBZ-SI and Tax mRNA loads in samples with a mixture of infected and non-infected cells were measured and then adjusted by dividing by the HTLV-I proviral load. We show here that the HBZ-SI mRNA level is 4-fold higher than non-spliced HBZ and is expressed by almost all cells harboring HTLV-1 provirus with variable intensity. The proviral-adjusted HBZ-SI and Tax quantification revealed a characteristic imbalanced expression feature of high HBZ and low Tax expression levels in primary ATL cells or high HBZ and very high Tax levels in HTLV-1-related cell lines (cell lines compared with a standard expression profile of low HBZ and low Tax in infected cells. Interestingly, according to the mutual Tax and HBZ expression status, HTLV-1-related cell lines were subcategorized into two groups, an ATL cell type with high HBZ and low Tax levels and another type with high Tax and either high or low HBZ, which was closely related to its cell origin. Conclusion This is the first comprehensive study to evaluate the mutual expression profile of HBZ and Tax in provirus-positive cells, revealing that there are quantitative and relative characteristic features among infected cells, primary ATL cells, and cell lines.

Role of IL-21 in HTLV-1 infections with emphasis on HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).

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Rajaei, Taraneh; Farajifard, Hamid; Rafatpanah, Houshang; Bustani, Reza; Valizadeh, Narges; Rajaei, Bahareh; Rezaee, Seyed Abdolrahim

2017-06-01

Interleukin-21 (IL-21) enhances the survival and cytotoxic properties of cytotoxic T cells (CTLs) and exhibits essential roles in controlling chronic viral infections. HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive inflammatory disease of the nervous system. The main determinant of disease progression is efficiency of the CTL response to Human T lymphotropic virus types I (HTLV-1). In this study, the expression of host IL-21 and HTLV-I Tax and proviral load (PVL) was evaluated to understand the role and mechanism of IL-21 in HTLV-1 infections and the subsequent development of HAM/TSP. A cross-sectional study was carried out on 20 HAM/TSP patients, 20 asymptomatic HTLV-1 carriers (ACs) and 20 healthy controls (HCs) to evaluate the expression of IL-21 and Tax and PVL in non-activated and phorbol myristate acetate (PMA)-ionomycin-activated peripheral blood mononuclear cells (PBMCs). The mean mRNA expression of IL-21 in the non-activated and activated PBMCs was higher (by 5-13 times) in the HAM/TSP patients than in ACs and HCs (p Tax and PVL was observed in the HAM/TSP subjects than ACs (p Tax gene expression was positively correlated with PVL (R = 0.595, p = 0.000) and IL-21 gene expression (R = 0.395, p = 0.021) in the HTLV-1-infected subjects. In conclusion, the increase in IL-21 mRNA expression may reflect the attempt of infected T cells to induce an appropriate antiviral response, and the decrease in IL-21 protein expression may reflect the inhibition of IL-21 mRNA translation by viral factors in favour of virus evasion and dissemination.

HTLV-1 cosmopolitan and HTLV-2 subtype b among pregnant women of non-endemic areas of Argentina.

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Berini, Carolina A; Delfino, Cecilia; Torres, Oscar; García, Gabriela; Espejo, Rogelio; Pianciola, Luis; Juarez, Mirna; Arribere, Graciela; Nadal, Mónica; Eirin, Maria E; Biglione, Mirna M

2013-06-01

The objective of this study was to estimate the prevalence of human T cell lymphotropic virus (HTLV)-1/2, HIV-1, hepatitis B virus (HBV), Trypanosoma cruzi, Treponema pallidum and Toxoplasma gondii infections and to identify the subtypes/subgroups of HTLV-1/2 among pregnant women (PW) from non-endemic provinces of Argentina. Methods A total of 2403 samples were screened for HTLV-1/2 and confirmed by western blot and PCR. The long terminal repeat (LTR) of HTLV-1 and HTLV-2 were amplified. Phylogenetic analysis was performed by Neighbour Joining by using molecular evolutionary genetics analysis (MEGA) 4.0. Among a total of 2403 PW studied, 6 (0.25%) tested positive for HTLV-1/2 (3 HTLV-1 (0.12%) and 3 HTLV-2 (0.12%)). The total prevalence when distributed by province was 0.3% (3/804) for Buenos Aires (BA), 0.4% (1/241) for BA surroundings, 0.1% (1/707) for Neuquen and 1.0% (1/95) for Ushuaia. In San Juan, no PW were HTLV-1/2 positive. The prevalence was similar when compared with rates among blood donors of the same areas and years. The phylogenetic analysis classified one sequence as HTLV-1 aA and one as HTLV-2b. The prevalence of HIV-1, HBV, T cruzi, T pallidum and T gondii was 0.6%, 0.2%, 1.4%, 1.2% and 20.9%, respectively. One case of HTLV-1/HIV-1 and one of HTLV-2/HIV-1 co-infection were detected. HTLV-1/2, which have been associated with different diseases, are circulating among PW of Argentina, even in non-endemic areas. Therefore, testing should be recommended in women who have risk factors for these infections given that the majority of HTLV-1/2 mother to child transmission can be prevented by the avoidance of breast feeding.

Clonagem e expressão da glicoproteína transmembrana do retrovírus HTLV-1 em células de mamíferos Cloning and transmembrane glycoprotein expression of the retrovirus HTLV-1 in mammals' cells

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Flora Cristina Lobo Penteado

2006-04-01

Full Text Available O retrovírus linfotrópico de células T humanas tipo 1 é o agente etiológico da leucemia das células T do adulto e da paraparesia espástica tropical/mielopatia associada ao HTLV-1. O genoma proviral é composto por 9.032 pares de bases, contendo genes estruturais e regulatórios. A glicoproteína transmembrana gp 21 é codificada pelo gene estrutural env. O desenvolvimento de metodologias para a expressão heteróloga de proteínas, assim como a obtenção de uma linhagem celular que expresse a gp 21 recombinante constitutivamente são os principais objetivos do trabalho. O fragmento codificante da gp 21 foi amplificado por Nested-PCR e clonado no vetor pCR2.1-TOPO. Posteriormente, foi realizada a subclonagem no vetor de expressão pcDNA3.1+. A transfecção da linhagem celular de mamíferos HEK 293 foi realizada de maneira transitória e permanente. A produção da gp 21 recombinante foi confirmada por citometria de fluxo e a linhagem celular produtora será utilizada em ensaios de imunogenicidade.The retrovirus HTLV-1 is the etiological agent of the adult T-cell leukemia and HTLV-1 associated myelopathy/tropical spastic paraparesis. The proviral genome has 9,032 base pairs, showing regulatory and structural genes. The env gene encodes for the transmembrane glycoprotein gp 21. The development of methodologies for heterologous protein expression, as well as the acquisition of a cellular line that constituently expresses the recombinant, were the main goals of this work. The DNA fragment that encodes for gp 21 was amplified by nested-PCR and cloned into a pCR2.1-TOPO vector. After which, a sub-cloning was realized using the expressing vector pcDNA3.1+. The transfection of mammalian cells HEK 293 was performed transitorily and permanently. Production of the recombinant gp 21 was confirmed by flux cytometry experiments and the cell line producing protein will be used in immunogenicity assays.

Detection of HTLV-IIa in blood donors in an urban area of the Amazon Region of Brazil (Belém, PA

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Ishak R.

1998-01-01

Full Text Available The human lymphotropic viruses type I (HTLV-I and type II (HTLV-II are members of a group of mammalian retroviruses with similar biological properties, and blood transfusion is an important route of transmission. HTLV-I is endemic in a number of different geographical areas and is associated with several clinical disorders. HTLV-II is endemic in several Indian groups of the Americas and intravenous drug abusers in North and South America, Europe and Southeast Asia. During the year of 1995, all blood donors tested positive to HTLV-I/II in the State Blood Bank (HEMOPA, were directed to a physician and to the Virus Laboratory at the Universidade Federal do Pará for counselling and laboratory diagnosis confirmation. Thirty-five sera were tested by an enzyme immune assay, and a Western blot that discriminates HTLV-I and HTLV-II infection. Two HTLV-II positive samples were submitted to PCR analysis of pX and env genomic region, and confirmed to be of subtype IIa. This is the first detection in Belém of the presence of HTLV-IIa infection among blood donors. This result emphasizes that HTLV-II is also present in urban areas of the Amazon region of Brazil and highlights the need to include screening tests that are capable to detect antibodies for both types of HTLV.

HTLV-1 HBZ Viral Protein: A Key Player in HTLV-1 Mediated Diseases

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Marco Baratella

2017-12-01

Full Text Available Human T cell leukemia virus type 1 (HTLV-1 is an oncogenic human retrovirus that has infected 10–15 million people worldwide. After a long latency, 3–5% of infected individuals will develop either a severe malignancy of CD4+ T cells, known as Adult T-cell Leukemia (ATL or a chronic and progressive inflammatory disease of the nervous system designated Tropical Spastic Paraparesis/HTLV-1-Associated Myelopathy (HAM/TSP. The precise mechanism behind HTLV-1 pathogenesis still remains elusive. Two viral regulatory proteins, Tax-1 and HTLV-1 bZIP factor (HBZ are thought to play a critical role in HTLV-1-associated diseases. Tax-1 is mainly involved in the onset of neoplastic transformation and in elicitation of the host’s inflammatory responses; its expression may be lost during cell clonal proliferation and oncogenesis. Conversely, HBZ remains constantly expressed in all patients with ATL, playing a role in the proliferation and maintenance of leukemic cells. Recent studies have shown that the subcellular distribution of HBZ protein differs in the two pathologies: it is nuclear with a speckled-like pattern in leukemic cells and is cytoplasmic in cells from HAM/TSP patients. Thus, HBZ expression and distribution could be critical in the progression of HTLV-1 infection versus the leukemic state or the inflammatory disease. Here, we reviewed recent findings on the role of HBZ in HTLV-1 related diseases, highlighting the new perspectives open by the possibility of studying the physiologic expression of endogenous protein in primary infected cells.

HTLV-1 HBZ Viral Protein: A Key Player in HTLV-1 Mediated Diseases.

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Baratella, Marco; Forlani, Greta; Accolla, Roberto S

2017-01-01

Human T cell leukemia virus type 1 (HTLV-1) is an oncogenic human retrovirus that has infected 10-15 million people worldwide. After a long latency, 3-5% of infected individuals will develop either a severe malignancy of CD4+ T cells, known as Adult T-cell Leukemia (ATL) or a chronic and progressive inflammatory disease of the nervous system designated Tropical Spastic Paraparesis/HTLV-1-Associated Myelopathy (HAM/TSP). The precise mechanism behind HTLV-1 pathogenesis still remains elusive. Two viral regulatory proteins, Tax-1 and HTLV-1 bZIP factor (HBZ) are thought to play a critical role in HTLV-1-associated diseases. Tax-1 is mainly involved in the onset of neoplastic transformation and in elicitation of the host's inflammatory responses; its expression may be lost during cell clonal proliferation and oncogenesis. Conversely, HBZ remains constantly expressed in all patients with ATL, playing a role in the proliferation and maintenance of leukemic cells. Recent studies have shown that the subcellular distribution of HBZ protein differs in the two pathologies: it is nuclear with a speckled-like pattern in leukemic cells and is cytoplasmic in cells from HAM/TSP patients. Thus, HBZ expression and distribution could be critical in the progression of HTLV-1 infection versus the leukemic state or the inflammatory disease. Here, we reviewed recent findings on the role of HBZ in HTLV-1 related diseases, highlighting the new perspectives open by the possibility of studying the physiologic expression of endogenous protein in primary infected cells.

Association of HTLV-I with Arnold Chiari syndrome and syringomyelia

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Graça Maria de Castro Viana

Full Text Available HTLV-I is associated with a broad spectrum of manifestations, including tropical spastic paraparesis and adult T-cell leukemia/lymphoma. Arnold Chiari syndrome is a condition characterized by herniation of the cerebellar tonsils through the foramen magnum. This condition should be suspected in all patients with headache and impaired motor coordination. Syringomyelia is a developmental anomaly that leads to the formation of an intramedullary cavity. Its clinical presentation is classically characterized by syringomyelic dissociation of sensation, with suspended distribution in the proximal portion of the trunk and upper limbs and preservation in other regions. We report here a case of association of the three diseases, which is rare in clinical practice, illustrating the difficulty in the diagnosis and therapeutic management of these conditions.

Involvement of HTLV-I Tax and CREB in aneuploidy: a bioinformatics approach

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Pumfery Anne

2006-07-01

Full Text Available Abstract Background Adult T-cell leukemia (ATL is a complex and multifaceted disease associated with human T-cell leukemia virus type 1 (HTLV-I infection. Tax, the viral oncoprotein, is considered a major contributor to cell cycle deregulation in HTLV-I transformed cells by either directly disrupting cellular factors (protein-protein interactions or altering their transcription profile. Tax transactivates these cellular promoters by interacting with transcription factors such as CREB/ATF, NF-κB, and SRF. Therefore by examining which factors upregulate a particular set of promoters we may begin to understand how Tax orchestrates leukemia development. Results We observed that CTLL cells stably expressing wild-type Tax (CTLL/WT exhibited aneuploidy as compared to a Tax clone deficient for CREB transactivation (CTLL/703. To better understand the contribution of Tax transactivation through the CREB/ATF pathway to the aneuploid phenotype, we performed microarray analysis comparing CTLL/WT to CTLL/703 cells. Promoter analysis of altered genes revealed that a subset of these genes contain CREB/ATF consensus sequences. While these genes had diverse functions, smaller subsets of genes were found to be involved in G2/M phase regulation, in particular kinetochore assembly. Furthermore, we confirmed the presence of CREB, Tax and RNA Polymerase II at the p97Vcp and Sgt1 promoters in vivo through chromatin immunoprecipitation in CTLL/WT cells. Conclusion These results indicate that the development of aneuploidy in Tax-expressing cells may occur in response to an alteration in the transcription profile, in addition to direct protein interactions.

Seroprevalence of HIV, HBV, HCV, and HTLV among Pregnant Women in Southwestern Nigeria.

Science.gov (United States)

Opaleye, Oluyinka Oladele; Igboama, Magdalene C; Ojo, Johnson Adeyemi; Odewale, Gbolabo

2016-01-01

Sexually transmitted infections (STIs) are major public health challenge especially in developing countries. This study was designed to determine the prevalence of Hepatitis B virus (HBV), Hepatitis C Virus (HCV), Human immunodeficiency virus (HIV), and Human T-cell lymphotropic Virus type I (HTLV-I) among pregnant women attending antenatal clinic, in Ladoke Akintola University Teaching Hospital, Osogbo, and South-Western Nigeria. One hundred and eighty two randomly selected pregnant women were screened for HBsAg, anti-HCV, anti-HIV and HTLV-1 IgM antibodies using commercially available ELISA kit. Of the 182 blood samples of pregnant women screened whose age ranged from 15-49 years, 13 (7.1%), 5 (2.7%), 9 (4.9%), and 44 (24.2%) were positive for HBsAg, anti-HCV, anti-HIV, and HTLV-1 IgM antibodies, respectively. The co-infection rate of 0.5% was obtained for HBV/HCV, HBV/HIV, HIV/HTLV-1, and HCV/HTLV-1 while 1.1% and 0% was recorded for HBV/HTLV-1 and HCV/HIV co-infections, respectively. Expected risk factors such as history of surgery, circumcision, tattooing and incision showed no significant association with any of the viral STIs (P > 0.05). This study shows that there is the need for a comprehensive screening of all pregnant women for HBsAg, anti-HCV, anti-HIV and HTLV-1 to prevent mother to child transmission of these viral infections and its attending consequences.

Human T-cell leukemia virus types I and II exhibit different DNase I protection patterns

International Nuclear Information System (INIS)

Altman, R.; Harrich, D.; Garcia, J.A.; Gaynor, R.B.

1988-01-01

Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are human retroviruses which normally infect T-lymphoid cells. HTLV-I infection is associated with adult T-cell leukemia-lymphoma, and HTLV-II is associated with an indolent form of hairy-cell leukemia. To identify potential transcriptional regulatory elements of these two related human retroviruses, the authors performed DNase I footprinting of both the HTLV-I and HTLV-II long terminal repeats (LTRs) by using extracts prepared from uninfected T cells, HTLV-I and HTLV-II transformed T cells, and HeLa cells. Five regions of the HTLV-I LTR and three regions of the HTLV-II LTR showed protection by DNase I footprinting. All three of the 21-base-pair repeats previously shown to be important in HTLV transcriptional regulation were protected in the HTLV-I LTR, whereas only one of these repeats was protected in the HTLV-II LTR. Several regions exhibited altered protection in extracts prepared from lymphoid cells as compared with HeLa cells, but there were minimal differences in the protection patterns between HTLV-infected and uninfected lymphoid extracts. A number of HTLV-I and HTLV-II LTR fragments which contained regions showing protection in DNase I footprinting were able to function as inducible enhancer elements in transient CAT gene expression assays in the presence of the HTLV-II tat protein. The alterations in the pattern of the cellular proteins which bind to the HTLV-I and HTLV-II LTRs may in part be responsible for differences in the transcriptional regulation of these two related viruses

Urodynamic features of the voiding dysfunction in HTLV-1 infected individuals

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Neviton M. Castro

2007-04-01

Full Text Available OBJECTIVE:To describe urodynamic abnormalities in HTLV-1 infected individuals presenting urinary symptoms and verify if these findings and quality of life (QOL evaluation correlate with overall neurological impairment. MATERIALS AND METHODS: From January/2001 to May/2004, 324 HTLV-1 seropositive subjects were evaluated to determine the occurrence of urinary symptoms. Urodynamic testing was performed in those who complained of frequency, urgency, or incontinence. They went through a complete clinical, neurological, and urological examination to investigate symptoms and signs of myelopathy. Neurological disability was assessed by Expanded Disability Status Scale (EDSS. RESULTS: From the 324 patients evaluated, 78 underwent the urodynamic testing. Fifty-seven individuals were females (73.1% and age ranged from 23 to 76 years (mean = 48.7 years; SD ± 11.6. Urodynamic testing was abnormal in 63 patients (80.8%. The major abnormality was detrusor overactivity (DO, observed in 33 individuals (33/63; 52.4%, followed by detrusor-external sphincter dyssynergia (DESD, diagnosed in 15 subjects (15/63; 25.4%. HAM/TSP patients had significantly more DESD than the HTLV-I carriers (p = 0.005; OR = 5.5; CI: 1.6 to 19.4. QOL was severely compromised in HAM/TSP patients. CONCLUSIONS: Prominent urodynamic abnormalities were identified in individuals genuinely considered as HTLV-I carriers, suggesting an early compromise of the urinary tract; whereas HAM/TSP patients presented urodynamic findings, which posed a potential risk to the upper urinary tract (dyssynergia. Urodynamic evaluation should be performed in all HTLV-I-infected individuals with voiding complaints.

[HTLV and "donating" milk].

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Rigourd, V; Meyer, V; Kieffer, F; Aubry, S; Magny, J-F

2011-08-01

In France, the screening for human T-cell leukemia/ lymphoma virus type 1 and 2 (HTLV-1 and HTLV-2) during the donation of human milk has been carried out from 1992 with the application of the circular DGS 24 November 1992. The screening for antibodies against these viruses is regulated and done systematically during every donation of milk. Breast feeding being the main mode of transmission of the HTLV-1, the last ministerial decree of 25 August 2010 has made the screening test compulsory for the anonymous donation and for the personalized donation (of a mother for her own child) from all women including those affected by the infection. The milk delivered by milk banks is pasteurized (62.5 °C for 30 minutes) before freezing at -18 °C, which inactivates the pathogens. This double means of prevention of the transmission of the HTLV-1 paradoxically seems disproportionate in the absence of any precautionary measure in the case of direct breast-feeding and the use of mother's raw milk. Indeed, in most neonatal intensive care units in maternity hospitals, unpasteurized milk is administered to the neonates without any systematic preliminary testing of the serological HTLV-1 status of the mother. An increased sensitization of the community of the obstetricians, midwives and neonatologists by the Association of the Milk Banks of France (ADLF) and the Société de pathologie exotique could address the issue of screening for HTLV-1 in "donated" milk and breast-feeding.

Frequency of mental disturbances in HTLV-1 patients in the state of Bahia, Brazil.

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Carvalho, André Gordilho Joaquim de; Galvão-Phileto, Ana Verena; Lima, Nana Santos; Jesus, Rogério Santos de; Galvão-Castro, Bernardo; Lima, Manuela Garcia

2009-02-01

Viral infections and chronic diseases have been associated with psychiatric disorders. Among these, increased depression has been reported in HTLV-1 patients. However, no studies on the prevalence of other mental disturbances have been carried out in these patients. Salvador is the city with the highest rate of infection with HTLV-1 in Brazil and it is estimated that approximately 40,000 inhabitants are infected. In our cross sectional study, we examined the frequency of mental disturbances in 50 HTLV-1 seropositive patients followed at the Centro Integrativo e Multidisciplinar de HTLV e Hepatites Virais (CHTLV) of the Escola Bahiana de Medicina e Saude Pública (EBMSP) in Salvador from January to November 2007. We used a questionnaire to collect clinical-epidemiologic data and the Mini International Neuropsychiatric Interview Brazilian Version 5.0.0 (M.I.N.I.) to evaluate the psychiatric disorders. The Statistical Package for Social Sciences (SPSS) was used for the analyses. Twenty-one (42%) HTLV-1 patients had a psychiatric co-morbidity; 17(34%) had mood disorders, 11 (22%) were anxious and one (2%) was an alcoholic. We found a high frequency of mental disturbances among HTLV-1 infected individuals, suggesting a possible association of this infection with psychiatric diseases.

The frequency of CD127low expressing CD4+CD25high T regulatory cells is inversely correlated with human T lymphotrophic virus type-1 (HTLV-1 proviral load in HTLV-1-infection and HTLV-1-associated myelopathy/tropical spastic paraparesis

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Chieia Marco

2008-07-01

Full Text Available Abstract Background CD4+CD25high regulatory T (TReg cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of TReg cell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of TReg cells in HTLV-1 asymptomatic carriers and in HTLV-1-associated neurological disease (HAM/TSP patients, and to correlate with measures of T cell activation. Results We were able to confirm that HTLV-I drives activation, spontaneous IFNγ production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4+ TReg cells (CD4+CD25high T cells in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4+ TReg cells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127low TReg cells in healthy control subjects. Finally, the proportion of CD127low TReg cells correlated inversely with HTLV-1 proviral load. Conclusion Taken together, the results suggest that TReg cells may be subverted in HAM/TSP patients, which could explain the marked cellular activation, spontaneous cytokine production, and proliferation of CD4+ T cells, in particular those expressing the CD25highCD127low phenotype. TReg cells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases.

[Duodenal Linphoma asociated to Strongyloides stercoralis infection. Two types of HTLV-1 infection].

Science.gov (United States)

Guevara Miranda, Julissa; Guzmán Rojas, Patricia; Espinoza-Ríos, Jorge; Mejía Cordero, Fernando

2017-01-01

Infection by the Human T- Lymphotropic virus I (HTLV-1) causes Adult T cell Leukemia-lymphoma (ATLL), being the duodenal involvement rare. Commonly, patients co-infected with HTLV-1 and Strongyloides stercoralis are seen due to the lack of TH2 response found on these patients. We describe a 48-year- old woman, from the jungle of Peru, with a family history of HTLV-1 infection, who presented with a History of chronic diarrhea and weight loss. HTLV-1 infection with ATLL and strongyloidiasis were diagnosed. Ivermectin treatment and chemotherapy were initiated, being stabilized, and discharged. We report this case because of the unusual coexistence in the duodenum of ATLL and strongyloidiasis.

Temporal development of cross-neutralization between HTLV-III B and HTLV-III RF in experimentally infected chimpanzees

NARCIS (Netherlands)

Goudsmit, J.; Thiriart, C.; Smit, L.; Bruck, C.; Gibbs, C. J.

1988-01-01

Sera from chimpanzees inoculated respectively with HTLV-III B, LAV, HTLV-III RF and brain tissue from an AIDS patient were analysed for neutralizing activity by two methods: a cell fusion inhibition test (CFI) using HTLV-III B infected cells as inoculum and CD4+ cells as target and a replication

BUSCA PELA "MUSCULARIDADE" E VARIÁVEIS ASSOCIADAS EM ADULTOS JOVENS

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Pedro Henrique Berbert de Carvalho

2016-04-01

Full Text Available Introdução: A busca pela "muscularidade" parece estar associada a diversas variáveis que impactam a saúde e a qualidade de vida dos sujeitos. No entanto, há uma carência de estudos sobre o construto, um baixo número de instrumentos de medida específicos para sua avaliação, além de reduzida avaliação de indivíduos do sexo masculino. Objetivo: Avaliar a busca pela "muscularidade" e associá-la a sintomas depressivos, autoestima, comportamentos de risco de transtornos alimentares e ao grau de comprometimento psicológico com o exercício físico. Métodos: Realizou-se um estudo transversal com 246 jovens adultos do sexo masculino. Foram utilizados instrumentos de autorrelato para avaliar a busca pela "muscularidade" (Drive for Muscularity Scale, autoestima (Rosenberg Self-Esteem Scale, sintomas depressivos (Beck Depression Inventory, comportamentos de risco de transtornos alimentares (Eating Attitudes Test-26 e o grau de comprometimento psicológico com o exercício físico (Commitment Exercise Scale. Foi utilizado o teste de associação de Pearson para verificar relação entre as variáveis do estudo e Análise de Regressão Linear Múltipla (forward para verificação do quanto as variáveis do estudo influenciam na busca pela "muscularidade". Resultados: A busca pela "muscularidade" esteve associada à autoestima (rpearson = 0,13; p < 0,05, aos comportamentos de risco de transtornos alimentares (rpearson = 0,20; p < 0,05 e ao grau de comprometimento psicológico ao exercício (rpearson = 0,62; p < 0,05. O grau de comprometimento psicológico com o exercício explicou 38,4% da variância total da busca pela "muscularidade", 12,3% da insatisfação com a "muscularidade" e 51,0% dos comportamentos orientados para a "muscularidade". Conclusão: A busca pela "muscularidade" está associada à baixa autoestima, aos comportamentos de risco de transtornos alimentares e, em especial, ao grau de comprometimento psicológico com o exerc

Dificuldades no diagnóstico da pneumonia associada ao ventilador

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Maria Augusta Machado

2003-11-01

Full Text Available RESUMO: A pneumonia associada ao ventilador é uma doença que apresenta elevada morbilidade e mortalidade. Por isso é importante um diagnóstico correcto, de modo a orientar a antibioterapia da forma mais adequada. No entanto, o seu diagnóstico é difícil, pois o quadro clínico e radiológico são inespecíficos, e critérios de diagnóstico estandardizados, que permitem a sua confirmação, são muito invasivos ou pouco frequentes. O desenvolvimento de técnicas de colheita com protecção das amostras e de culturas quantitativas tem tentado contornar o problema da contaminação das amostras obtidas por métodos de rotina e permitir a distinção entre colonização e infecção. A autora faz uma revisão sobre os diferentes métodos de diagnóstico desta entidade clínica.REV PORT PNEUMOL 2003; IX (6: 503-514 ABSTRACT: Ventilator associated pneumonia is associated with high morbidity and mortality. It is important a correct diagnosis in way to guide the antibiotic therapy in the most appropriate way. However, its diagnosis is difficult, because clinical and radiologic features are not specific and approaches to standard diagnosis, that allow its confirmation, are very invasive or not very frequent. Protected techniques and quantitative cultures have been trying to outline the problem of the contamination of the samples obtained by routine methods and to allow the distinction between colonization and infection. The author makes a revision on the different methods of diagnosis of this clinical entity.REV PORT PNEUMOL 2003; IX (6: 503-514 Palavras-chave: Pneumonia, ventilação mecânica, diagnóstico, Key-words: Pneumonia, mechanical ventilation, diagnosis

HTLV-1, Immune Response and Autoimmunity

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Juarez A S Quaresma

2015-12-01

Full Text Available Human T-lymphotropic virus type-1 (HTLV-1 infection is associated with adult T-cell leukemia/lymphoma (ATL. Tropical spastic paraparesis/HTLV-1-associated myelopathy (PET/HAM is involved in the development of autoimmune diseases including Rheumatoid Arthritis (RA, Systemic Lupus Erythematosus (SLE, and Sjögren’s Syndrome (SS. The development of HTLV-1-driven autoimmunity is hypothesized to rely on molecular mimicry, because virus-like particles can trigger an inflammatory response. However, HTLV-1 modifies the behavior of CD4+ T cells on infection and alters their cytokine production. A previous study showed that in patients infected with HTLV-1, the activity of regulatory CD4+ T cells and their consequent expression of inflammatory and anti-inflammatory cytokines are altered. In this review, we discuss the mechanisms underlying changes in cytokine release leading to the loss of tolerance and development of autoimmunity.

HTLV-1 infection is associated with a history of active tuberculosis among family members of HTLV-1-infected patients in Peru.

Science.gov (United States)

Verdonck, K; González, E; Schrooten, W; Vanham, G; Gotuzzo, E

2008-08-01

The purpose of this study was to assess the association between human T-lymphotropic virus 1 (HTLV-1) and a lifetime history of active tuberculosis (TB) among relatives of HTLV-1-infected patients. We reviewed clinical charts of all relatives of HTLV-1-infected index cases who attended our institute in Lima from 1990-2004. The data of 1233 relatives was analysed; 394 (32.0%) were HTLV-1 positive. Eighty-one subjects (6.6%) had a history of active TB, including 45/394 (11.4%) HTLV-1-positive and 36/839 (4.3%) HTLV-1-negative relatives (Phistory: HTLV-1 infection (adjusted OR 2.5, 95% CI 1.6-3.9), age (adjusted OR 1.3, 95% CI 1.1-1.5 per 10-year age increase) and relation to the index case (adjusted OR 2.6, 95% CI 1.3-5.1, for siblings vs. spouses of index cases). In conclusion, HTLV-1 infection may increase the susceptibility to active TB. In populations where both infections are frequent, such an association could affect the dynamics of TB.

Standardisation of Western blotting to detect HTLV-1 antibodies synthesised in the central nervous system of HAM/TSP patients

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Luiz Claudio Pereira Ribeiro

2013-09-01

Full Text Available Intrathecal synthesis of human T-lymphotropic virus type 1 (HTLV-1 antibodies (Abs represents conclusive evidence of a specific immune response in the central nervous system of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP patients. Western blotting (WB for HTLV Abs in serum is a confirmatory test for HTLV-1 infection. The aim of this study was to standardise the Western blot to demonstrate the intrathecal pattern of Abs against HTLV-1 proteins in HAM/TSP patients. Paired cerebrospinal fluid (CSF and serum samples were selected from 20 patients with definite HAM/TSP, 19 HTLV-1 seronegative patients and two HTLV-1 patients without definite HAM/TSP. The presence of reactive bands of greater intensity in the CSF compared to serum (or bands in only the CSF indicated the intrathecal synthesis of anti-HTLV-1 Abs. All definite HAM/TSP patients presented with an intrathecal synthesis of anti-HTLV-1 Abs; these Abs were not detected in the control patients. The most frequent intrathecal targets of anti-HTLV-1 Abs were GD21, rgp46-I and p24 and, to a lesser extent, p19, p26, p28, p32, p36, p53 gp21 and gp46. The intrathecal immune response against env (GD21 and rgp46-I and gag (p24 proteins represents the most important humoral pattern in HAM/TSP. This response may be used as a diagnostic marker, considering the frequent association of intrathecal anti-HTLV-1 Ab synthesis with HAM/TSP and the pathogenesis of this neurological disease.

Expressao genica associada ao estresse oxidativo no coracao de camundongo apos isquemia intestinal

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Frederico Somaio Neto

2014-03-01

Full Text Available FUNDAMENTO: O fenômeno da isquemia e reperfusão intestinal é um evento frequente na clínica e está associado a repercussões deletérias em órgãos a distância, em especial ao coração. OBJETIVO: Investigar a expressão gênica do estresse oxidativo e defesa antioxidante no coração de camundongos isogênicos, submetidos a isquemia e reperfusão intestinal (IR. MÉTODOS: Doze camundongos (C57BL/6 foram distribuídos em dois grupos: Grupo IR (GIR com 60 min de oclusão da artéria mesentérica superior, seguidos de 60 min de reperfusão. Grupo Controle (GC submetidos a anestesia e a laparotomia sem o procedimento de IR observados por 120 min. As amostras de intestino e coração foram processadas pelo método (RT-qPCR / Reverse transcriptase - quantitative Polymerase Chain Reaction para determinar a expressão gênica de 84 genes relacionados ao estresse oxidativo ("t" de Student, p < 0,05. RESULTADOS: Observou-se no tecido intestinal (GIR uma expressão significantemente aumentada em 65 (74,71% genes em relação ao tecido normal (GC, e 37 (44,04% genes estiveram hiperexpressos (maior que três vezes o limiar permitido pelo algoritmo. No tocante aos efeitos da I/R intestinal a distância no tecido cardíaco verificou-se a expressão significantemente aumentada de 28 genes (33,33%, mas somente oito genes (9,52% se hiperexpressaram três vezes acima do limiar. Quatro (7,14% desses oito genes se expressaram simultaneamente nos tecidos intestinal e cardíaco. No GIR notaram-se cardiomiócitos com núcleos de menor tamanho, picnóticos, ricos em heterocromatina e raros nucléolos, indicando sofrimento cardíaco. CONCLUSÃO: A I/R intestinal promoveu a hiperexpressão estatisticamente significante de oito genes associados ao estresse oxidativo a distância no tecido miocárdico.

HTLV-I en población de alto riesgo sexual de Pisco, Ica, Perú.

OpenAIRE

GARRIDO, Patricia; ANICAMA, Rolando; GOTUZZO, Eduardo; CHAUCA, Gloria; WATTS, Douglas

2013-01-01

Objetivo: Se estudiaron 141 personas con alto riesgo sexual en la ciudad de Pisco para detectar infección por HTLV-I. Material y Métodos: Se encuestaron y se tomaron muestras de sangre a 141 personas que involucró a trabajadoras sexuales (32), varones homosexuales (54), y varones bisexuales(55). Resultados: Tres de treintidós (10.4%) trabajadoras sexuales fueron positivas; uno de cincuenticuatro (1.9%) de varones homosexuales y ninguno de 55 bisexuales. Hubo una elevada frecuencia de parejas,...

Epidemiological characteristics and HIV-related oral lesions observed in patients from a Southern Brazilian city = Características epidemiológicas e das lesões bucais associadas ao HIV observadas em pacientes de uma cidade sul-brasileira

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Petruzzi, Maria Noel Marzano Rodrigues

2012-01-01

Conclusão: A elevada prevalência de doenças oportunistas e a rápida progressão para AIDS suscitam maior atenção para o diagnóstico precoce e acesso ao tratamento. Os profissionais devem ser alertados sobre a ocorrência de lesões bucais associadas ao HIV, pois podem sugerir a presença de infecção pelo vírus ou indicar uma pior condição de saúde do paciente

El HTLV-I y la PET/HAM un modelo de investigación en virología y biología molecular

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Felipe García Vallejo

2004-03-01

Full Text Available

En la actualidad la infección por el virus linfotrópico humano tipo 1 (HTLV-1 ha sido confirmada epidemiológicamente en la Leucemia/Linfoma de las Células T del Adulto (ATLL y en la Paraparesia Espástica Tropical/ Mielopatía Asociada al HTLV-I (PET/MAH (1. El HTLV-I es endémico en varias áreas geográficas del mundo y representa un problema de salud pública global. En Colombia las áreas mas afectadas incluyen diferentes poblaciones de la costa pacífica y del sur occidente. En el laboratorio de Biología Molecular y Patogénesis de la Facultad de Salud de la Universidad de del Valle, nos hemos planteado las siguientes preguntas para las cuales hemos realizado una serie de estudios moleculares:

• Cual fue el origen y cómo se dispersó el virus en Sur América y especialmente en Colombia.

• Cuales son los principales mecanismos moleculares involucrados en la progresión de la PET/MAH.

• Como es la integración de los provirus durante la progresión de la PET/MAH y cuales serían nuevos blancos moleculares virales y principios activos para el diseño de una nueva estrategia antirretroviral.

En la primera, nuestros datos filogenéticos sobre las regiones genómicas virales 3´LTR, Env y Tax obtenidos, permitieron determinar que el subtipo mas prevalente en Colombia es el cosmopolita, en el que los genotipos moleculares africanos son los más abundantes en la costa pacífica; en general nuestros resultados mostraron que la actual diversidad genética del HTLV-I en Colombia es compleja y es el resultado de varios eventos de introducción temporalmente separados (2-4.

Spontaneous neutrophil activation in HTLV-1 infected patients

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Jaqueline B. Guerreiro

Full Text Available Human T cell lymphotropic Virus type-1 (HTLV-1 induces lymphocyte activation and proliferation, but little is known about the innate immune response due to HTLV-1 infection. We evaluated the percentage of neutrophils that metabolize Nitroblue tetrazolium (NBT to formazan in HTLV-1 infected subjects and the association between neutrophil activation and IFN-gamma and TNF-alpha levels. Blood was collected from 35 HTLV-1 carriers, from 8 patients with HAM/TSP (HTLV-1- associated myelopathy; 22 healthy individuals were evaluated for spontaneous and lipopolysaccharide (LPS-stimulated neutrophil activity (reduction of NBT to formazan. The production of IFN-gamma and TNF-alpha by unstimulated mononuclear cells was determined by ELISA. Spontaneous NBT levels, as well as spontaneous IFN-gamma and TNF-alpha production, were significantly higher (p<0.001 in HTLV-1 infected subjects than in healthy individuals. A trend towards a positive correlation was noted, with increasing percentage of NBT positive neutrophils and levels of IFN-gamma. The high IFN-gamma producing HTLV-1 patient group had significantly greater NBT than healthy controls, 43±24% and 17±4.8% respectively (p< 0.001, while no significant difference was observed between healthy controls and the low IFN-gamma-producing HTLV-1 patient group (30±20%. Spontaneous neutrophil activation is another marker of immune perturbation resulting from HTLV-1 infection. In vivo activation of neutrophils observed in HTLV-1 infected subjects is likely to be the same process that causes spontaneous IFN-gamma production, or it may partially result from direct IFN-gamma stimulation.

ORIGIN AND PREVALENCE OF HUMAN T-LYMPHOTROPIC VIRUS TYPE 1 (HTLV-1 AND TYPE 2 (HTLV-2 AMONG INDIGENOUS POPULATIONS IN THE AMERICAS

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Arthur Paiva

2015-02-01

Full Text Available Human T-lymphotropic virus type 1 (HTLV-1 is found in indigenous peoples of the Pacific Islands and the Americas, whereas type 2 (HTLV-2 is widely distributed among the indigenous peoples of the Americas, where it appears to be more prevalent than HTLV-1, and in some tribes of Central Africa. HTLV-2 is considered ancestral in the Americas and is transmitted to the general population and injection drug users from the indigenous population. In the Americas, HTLV-1 has more than one origin, being brought by immigrants in the Paleolithic period through the Bering Strait, through slave trade during the colonial period, and through Japanese immigration from the early 20th century, whereas HTLV-2 was only brought by immigrants through the Bering Strait. The endemicity of HTLV-2 among the indigenous people of Brazil makes the Brazilian Amazon the largest endemic area in the world for its occurrence. A review of HTLV-1 in all Brazilian tribes supports the African origin of HTLV-1 in Brazil. The risk of hyperendemicity in these epidemiologically closed populations and transmission to other populations reinforces the importance of public health interventions for HTLV control, including the recognition of the infection among reportable diseases and events.

Novel interactions between the HTLV antisense proteins HBZ and APH-2 and the NFAR protein family: Implications for the HTLV lifecycles

Energy Technology Data Exchange (ETDEWEB)

Murphy, Jane; Hall, William W. [Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 (Ireland); Ratner, Lee [Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, Saint Louis, Missouri, United States of America (United States); Sheehy, Noreen [Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4 (Ireland)

2016-07-15

The human T-cell leukaemia virus type 1 and type 2 (HTLV-1/HTLV-2) antisense proteins HBZ and APH-2 play key roles in the HTLV lifecycles and persistence in the host. Nuclear Factors Associated with double-stranded RNA (NFAR) proteins NF90/110 function in the lifecycles of several viruses and participate in host innate immunity against infection and oncogenesis. Using GST pulldown and co-immunoprecipitation assays we demonstrate specific novel interactions between HBZ/APH-2 and NF90/110 and characterised the protein domains involved. Moreover we show that NF90/110 significantly enhance Tax mediated LTR activation, an effect that was abolished by HBZ but enhanced by APH-2. Additionally we found that HBZ and APH-2 modulate the promoter activity of survivin and are capable of antagonising NF110-mediated survivin activation. Thus interactions between HTLV antisense proteins and the NFAR protein family have an overall positive impact on HTLV infection. Hence NFARs may represent potential therapeutic targets in HTLV infected cells. - Highlights: • This study demonstrates for the first time interactions between NF90/110 and the HTLV antisense proteins HBZ and APH-2. • We show that NF90/110 significantly enhance LTR activation by the HTLV Tax protein, an effect that is abolished by HBZ but enhanced by APH-2. • The study shows that even though the HTLV antisense proteins activate survivin expression they antagonize the ability of NF90/110 to do so. • Overall we found that NF90/110 positively regulate HTLV infection and as such might represent a therapeutic target in infected cells.

Novel interactions between the HTLV antisense proteins HBZ and APH-2 and the NFAR protein family: Implications for the HTLV lifecycles

International Nuclear Information System (INIS)

Murphy, Jane; Hall, William W.; Ratner, Lee; Sheehy, Noreen

2016-01-01

The human T-cell leukaemia virus type 1 and type 2 (HTLV-1/HTLV-2) antisense proteins HBZ and APH-2 play key roles in the HTLV lifecycles and persistence in the host. Nuclear Factors Associated with double-stranded RNA (NFAR) proteins NF90/110 function in the lifecycles of several viruses and participate in host innate immunity against infection and oncogenesis. Using GST pulldown and co-immunoprecipitation assays we demonstrate specific novel interactions between HBZ/APH-2 and NF90/110 and characterised the protein domains involved. Moreover we show that NF90/110 significantly enhance Tax mediated LTR activation, an effect that was abolished by HBZ but enhanced by APH-2. Additionally we found that HBZ and APH-2 modulate the promoter activity of survivin and are capable of antagonising NF110-mediated survivin activation. Thus interactions between HTLV antisense proteins and the NFAR protein family have an overall positive impact on HTLV infection. Hence NFARs may represent potential therapeutic targets in HTLV infected cells. - Highlights: • This study demonstrates for the first time interactions between NF90/110 and the HTLV antisense proteins HBZ and APH-2. • We show that NF90/110 significantly enhance LTR activation by the HTLV Tax protein, an effect that is abolished by HBZ but enhanced by APH-2. • The study shows that even though the HTLV antisense proteins activate survivin expression they antagonize the ability of NF90/110 to do so. • Overall we found that NF90/110 positively regulate HTLV infection and as such might represent a therapeutic target in infected cells.

Human T-Lymphotropic Virus Type 1 (HTLV-1 and Regulatory T Cells in HTLV-1-Associated Neuroinflammatory Disease

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Yoshihisa Yamano

2011-08-01

Full Text Available Human T-lymphotropic virus type 1 (HTLV-1 is a retrovirus that is the causative agent of adult T cell leukemia/lymphoma (ATL and associated with multiorgan inflammatory disorders, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP and uveitis. HTLV-1-infected T cells have been hypothesized to contribute to the development of these disorders, although the precise mechanisms are not well understood. HTLV-1 primarily infects CD4+ T helper (Th cells that play a central role in adaptive immune responses. Based on their functions, patterns of cytokine secretion, and expression of specific transcription factors and chemokine receptors, Th cells that are differentiated from naïve CD4+ T cells are classified into four major lineages: Th1, Th2, Th17, and T regulatory (Treg cells. The CD4+CD25+CCR4+ T cell population, which consists primarily of suppressive T cell subsets, such as the Treg and Th2 subsets in healthy individuals, is the predominant viral reservoir of HTLV-1 in both ATL and HAM/TSP patients. Interestingly, CD4+CD25+CCR4+ T cells become Th1-like cells in HAM/TSP patients, as evidenced by their overproduction of IFN-γ, suggesting that HTLV-1 may intracellularly induce T cell plasticity from Treg to IFN-γ+ T cells. This review examines the recent research into the association between HTLV-1 and Treg cells that has greatly enhanced understanding of the pathogenic mechanisms underlying immune dysregulation in HTLV-1-associated neuroinflammatory disease.

Highlights on distinctive structural and functional properties of HTLV Tax proteins

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Romanelli, Maria Grazia; Diani, Erica; Bergamo, Elisa; Casoli, Claudio; Ciminale, Vincenzo; Bex, Françoise; Bertazzoni, Umberto

2013-01-01

Human T cell leukemia viruses (HTLVs) are complex human retroviruses of the Deltaretrovirus genus. Four types have been identified thus far, with HTLV-1 and HTLV-2 much more prevalent than HTLV-3 or HTLV-4. HTLV-1 and HTLV-2 possess strictly related genomic structures, but differ significantly in pathogenicity, as HTLV-1 is the causative agent of adult T cell leukemia and of HTLV-associated myelopathy/tropical spastic paraparesis, whereas HTLV-2 is not associated with neoplasia. HTLVs code for a protein named Tax that is responsible for enhancing viral expression and drives cell transformation. Much effort has been invested to dissect the impact of Tax on signal transduction pathways and to identify functional differences between the HTLV Tax proteins that may explain the distinct oncogenic potential of HTLV-1 and HTLV-2. This review summarizes our current knowledge of Tax-1 and Tax-2 with emphasis on their structure, role in activation of the NF-κB (nuclear factor kappa-B) pathway, and interactions with host factors. PMID:24058363

Proprioceptive neuromuscular facilitation in HTLV-I-associated myelopathy/tropical spastic paraparesis

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Vera Lúcia Santos de Britto

2014-01-01

Full Text Available Introduction: Human T cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP can impact the independence and motricity of patients. The aims of this study were to estimate the effects of physiotherapy on the functionality of patients with HAM/TSP during the stable phase of the disease using proprioceptive neuromuscular facilitation (PNF and to compare two methods of treatment delivery. Methods: Fourteen patients with human T cell lymphotropic virus type I (HTLV-I were randomly allocated into two groups. In group I (seven patients, PNF was applied by the therapist, facilitating the functional activities of rolling, sitting and standing, walking and climbing and descending stairs. In group II (seven patients, PNF was self-administered using an elastic tube, and the same activities were facilitated. Experiments were conducted for 1h twice per week for 12 weeks. Low-back pain, a modified Ashworth scale, the functional independence measure (FIM and the timed up and go test (TUG were assessed before and after the interventions. Results: In the within-group evaluation, low-back pain was significantly reduced in both groups, the FIM improved in group II, and the results of the TUG improved in group I. In the inter-group analysis, only the tone was lower in group II than in group I. Conclusions: Both PNF protocols were effective in treating patients with HAM/TSP.

Relato de Caso - Nefropatia de IgA associada ao ANCA com evolução favorável

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Flávia Lara Barcelos

2015-09-01

Full Text Available ResumoIntrodução:Os anticorpos anticitoplasma de neutrófilos (ANCA comumente estão relacionados a glomerulonefrites rapidamente progressivas (GnRP com padrão pauci-imune. Apesar disso, a literatura mostra uma incidência além da esperada de ANCA nas GnRP por imunocomplexos. A nefropatia por imunoglobulina A (NIgA crescêntica é uma das GnRP que pode se associar ao ANCA.Objetivo:Relatar caso de NigA com sinais clínicos de mau prognóstico associado ao ANCA com evolução favorável após imunossupressão.Método:Foi relatado caso de paciente com 38 anos com quadro de hipertensão arterial (HAS, insuficiência renal (CKD-EPI- 37 ml/min/1,73 m2, proteinúria subnefrótica e hematúria. Nos antecedentes pessoais, relatava epistaxes ocasionais, rinossinusite e episódio de artrite com remissão espontânea. Durante a investigação diagnóstica, foram detectados ANCA positivo 1/160 e anti-PR3, porém, com biópsia renal compatível com NIgA com 38% de crescentes na amostra. Foi realizado diagnóstico de NIgA associada ao ANCA, sendo indicado tratamento imunossupressor por seis meses com corticoterapia (pulsoterapia com metilprednisolona 1 g por 3 dias, seguido de prednisona 1 mg/kg/dia e ciclofosfamida (500 mg com aumento crescente da dose até 750 mg/m2. Paciente evolui com recuperação da função renal, além da redução da proteinúria e da titulação de ANCA.Conclusão:A importância da identificação dessa sobreposição está no comportamento agressivo dessa doença caracterizada pela presença de crescentes, atrofia tubular e disfunção renal que podem regredir com início precoce da imunossupressão.

Frequent HTLV-1 infection in the offspring of Peruvian women with HTLV-1-associated myelopathy/tropical spastic paraparesis or strongyloidiasis Infección frecuente por HTLV-1 en los hijos de mujeres peruanas con mielopatía/paraparesia espástica tropical asociada con el HTLV-1 o con estrongiloidiasis

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Eduardo Gotuzzo

2007-10-01

Full Text Available OBJECTIVES: To describe the frequency of HTLV-1 infection among offspring of mothers who had presented with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, strongyloidiasis, or asymptomatic HTLV-1 infection, and to identify factors associated with HTLV-1 infection. METHODS: In a descriptive study, records were reviewed of HTLV-1-positive women and their offspring who had been tested for HTLV infection at a public hospital in Lima, Peru, from 1989 to 2003. Sons and daughters of women who had presented with strongyloidiasis, HAM/TSP, or asymptomatic infection were eligible for this study. RESULTS: Three hundred seventy subjects were included: 279 were the offspring of 104 mothers presenting with HAM/TSP, 58 were the offspring of 22 mothers with strongyloidiasis, and 33 were the offspring of 26 asymptomatic mothers. Mean age of the offspring at the time of testing was 26 years (standard deviation 12. Nineteen percent of the offspring tested positive for HTLV-1: 6% (2/33 of those with asymptomatic mothers, 19% (52/279 among the offspring of mothers with HAM/TSP, and 31% (18/58 among the offspring of mothers presenting with strongyloidiasis On multiple logistic regression analysis, three factors were significantly associated with HTLV-1: (a duration of breast-feeding (odds ratio [OR] = 15.1; [4.2-54.1] for 12 to 24 months versus less than 6 months breast-feeding; (b clinical condition of the mother (OR = 8.3 [1.0-65.3] for HAM/TSP and OR = 11.5 [1.4-98.4] for strongyloidiasis in comparison with offspring of asymptomatic mothers; and (c transfusion history (OR = 5.5 [2.0-15.2]. CONCLUSIONS: In addition to known risk factors for HTLV-1 transmission (duration of breast-feeding and history of blood transfusion, maternal HAM/TSP and strongyloidiasis were associated with seropositivity among offspring of HTLV-1-infected mothers.OBJETIVOS: Describir la frecuencia de la infección por HTLV-1 en los hijos e hijas de madres diagnosticadas

Rinite crônica em portadores do HTLV-1: estudo histopatológico Chronic rhinitis in HTLV-1 carriers: a histopathologic study

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Fernando P. Gaspar Sobrinho

2012-04-01

Full Text Available A histopatologia nasal de portadores do HTLV-1 com rinite crônica é desconhecida. OBJETIVO: Descrever aspectos histopatológicos de portadores do HTLV-1 com rinite crônica. CASUÍSTICA E MÉTODOS: Amostras de mucosa nasal de 10 portadores do HTLV-1 com rinite crônica, sendo oito com rinite alérgica e dois com rinite não alérgica, foram estudadas por microscopia de luz. Amostras de 10 pacientes com rinite alérgica não infectados pelo HTLV-1 serviram como controle. RESULTADOS: Fibrose subepitelial foi maior nos pacientes com rinite alérgica infectados pelo HTLV-1 (p=0,01, enquanto o espessamento da membrana basal foi maior nos controles (p=0,03. Houve tendência a menor eosinofilia e edema entre os infectados pelo HTLV-1, sem significância estatística (p=0,2. Para o infiltrado linfocítico, não houve diferença entre os pacientes com rinite alérgica infectados e não infectados (p=1,0. Fibrose subepitelial com infiltrado linfocítico de intensidade leve a moderada foram os achados encontrados nos dois portadores do HTLV-1 com rinite não alérgica. CONCLUSÕES: O estudo sugere que a infecção pelo HTLV-1 pode modificar a histopatologia da rinite alérgica, sobretudo por maior fibrose, e pode estar relacionada a uma rinite crônica não alérgica com infiltrado linfocítico.The nasal histopathology of HTLV-1 carriers with chronic rhinitis is unknown. OBJECTIVE: To describe the histopathological features of HTLV-1 carriers with chronic rhinitis. MATERIALS AND METHODS: Biopsies of nasal mucosa of ten HTLV-1 carriers with chronic rhinitis (eight patients with allergic rhinitis and two patients with non-allergic rhinitis were studied using a light microscope. Samples from ten patients with allergic rhinitis not infected with HTLV-1 were used as controls. RESULTS: Subepithelial fibrosis was more pronounced in patients with allergic rhinitis infected with HTLV-1 (p=0.01, while the basement membrane thickness was greater in controls (p=0

Identification of clonally rearranged T-cell receptor beta chain genes in HTLV-I carriers as a potential instrument for early detection of neoplasia

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M.M. Sales

2005-05-01

Full Text Available We analyzed the genetic recombination pattern of the T-cell receptor beta-chain gene (TCR-beta in order to identify clonal expansion of T-lymphocytes in 17 human T-lymphotropic virus type I (HTLV-I-positive healthy carriers, 7 of them with abnormal features in the peripheral blood lymphocytes. Monoclonal or oligoclonal expansion of T-cells was detected in 5 of 7 HTLV-I-positive patients with abnormal lymphocytes and unconfirmed diagnosis by using PCR amplification of segments of TCR-beta gene, in a set of reactions that target 102 different variable (V segments, covering all members of the 24 V families available in the gene bank, including the more recently identified segments of the Vbeta-5 and Vbeta-8 family and the two diversity beta segments. Southern blots, the gold standard method to detect T-lymphocyte clonality, were negative for all of these 7 patients, what highlights the low sensitivity of this method that requires a large amount of very high quality DNA. To evaluate the performance of PCR in the detection of clonality we also analyzed 18 leukemia patients, all of whom tested positive. Clonal expansion was not detected in any of the negative controls or healthy carriers without abnormal lymphocytes. In conclusion, PCR amplification of segments of rearranged TCR-beta is reliable and highly suitable for the detection of small populations of clonal T-cells in asymptomatic HTLV-I carriers who present abnormal peripheral blood lymphocytes providing an additional instrument for following up these patients with potentially higher risk of leukemia.

[HTLV-1 in a Mapuche population].

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Inostroza, J; Díaz, P; Saunier, C

1990-12-01

The seroprevalence of HTLV-1 in 405 serum samples from South American Indians, Mapuches, from the IXth region of Chile was investigated using enzyme linked immunosorbent assay (ELISA). Six samples were positive and only 3 of them were also positive by western blot and radio immuno precipitation assay. This corresponds to a seroprevalence of 0.74% for HTLV-1 in healthy Mapuches, which differs from that observed in other populations throughout the world. Additional studies are necessary to evaluate the real magnitudes of HTLV-1 infection in Chile.

Intracellular Localization and Cellular Factors Interaction of HTLV-1 and HTLV-2 Tax Proteins: Similarities and Functional Differences

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Maria Grazia Romanelli

2011-05-01

Full Text Available Human T-lymphotropic viruses type 1 (HTLV-1 and type 2 (HTLV-2 present very similar genomic structures but HTLV-1 is more pathogenic than HTLV-2. Is this difference due to their transactivating Tax proteins, Tax-1 and Tax-2, which are responsible for viral and cellular gene activation? Do Tax-1 and Tax-2 differ in their cellular localization and in their interaction pattern with cellular factors? In this review, we summarize Tax-1 and Tax-2 structural and phenotypic properties, their interaction with factors involved in signal transduction and their localization-related behavior within the cell. Special attention will be given to the distinctions between Tax-1 and Tax-2 that likely play an important role in their transactivation activity.

Universal cytotoxic activity of a HTLV-1 Tax-specific T cell clone from an HLA-A*24:02⁺ patient with adult T-cell leukemia against a variety of HTLV-I-infected T-cells.

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Tanaka, Yukie; Yamazaki, Rie; Terasako-Saito, Kiriko; Nakasone, Hideki; Akahoshi, Yu; Nakano, Hirofumi; Ugai, Tomotaka; Wada, Hidenori; Yamasaki, Ryoko; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Kimura, Shun-ichi; Kikuchi, Misato; Kako, Shinichi; Kanda, Junya; Tanihara, Aki; Nishida, Junji; Kanda, Yoshinobu

2014-01-01

Adult T cell leukemia/lymphoma (ATL) is an aggressive mature T cell malignancy that is causally associated with human T cell lymphotropic virus type 1 (HTLV-1) infection. The HTLV-1 regulatory protein Tax aggressively accelerates the proliferation of host cells and is also an important target antigen for CD8(+) cytotoxic T cells (CTLs). We previously reported that several predominant HLA-A*24:02-restricted HTLV-1 Tax301-309-specific CTL clones commonly expressed a particular amino acid sequence motif (P-D-R) in complementarity-determining region 3 of T-cell receptor (TCR)-β chain among unrelated ATL patients who underwent allogeneic stem cell transplantation (allo-HSCT). Furthermore, a PDR-motif(+) CTL clone persistently existed in a long-term survivor as a central CTL clone with strong CTL activities after HSCT. Although a larger analysis of the relationship between PDR-motif(+) CTLs and the clinical course is required, the expression of PDR-motif(+) TCR on CD8(+) T cells may play a critical role in the management of anti-HTLV-1 activities for HLA-A24:02(+) ATL patients. Therefore, in this study, we prepared an HTLV-1 Tax301-309 peptide-specific CTL clone (HT-9) expressing PDR-motif(+) TCR isolated from a long-term survivor after HSCT, and evaluated its CTL activity against a variety of HTLV-1-infected T-cells from HLA-A*24:02(+) ATL patients. Before the assay of CTL function, we confirmed that HT-9 expressed less-differentiated effector-memory phenotypes (CD45RA(-)CCR7(-)CD27(+)CD28(+/-)CD57(+/-)) and T-cell exhaustion marker PD-1(+). In assays of CTL function, HT-9 recognized HTLV-1 Tax in an HLA-restricted fashion and demonstrated strong CTL activities against a variety of HTLV-1-infected T-cells from HLA-A*24:02(+) ATL patients regardless of whether the sources were autologous or allogeneic, but not normal cells. These data indicate that PDR-motif(+) TCR could be an important TCR candidate for TCR-gene immunotherapy for HLA-A24:02(+) ATL patients, provided

Aprendizagem organizacional e sustentabilidade ambiental: um estudo com as empresas associadas à REDEPETRO-RN

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José Marcione da Costa

2016-04-01

Full Text Available O objetivo desta pesquisa consistiu em verificar como as empresas associadas à REDEPETRO-RN estão desenvolvendo competências em sustentabilidade ambiental. A metodologia empregada neste trabalho foi do tipo quantitativo em relação ao processo, exploratório e descritivo quanto aos objetivos, básica no que concerne aos resultados e um estudo de campo quanto a sua modalidade. Os resultados apontaram que as empresas estão se esforçando para desenvolver competências relacionadas à sustentabilidade, tendo como grande influência no processo de desenvolvimento o porte e o número de colaboradores das empresas. A pesquisa ainda mostrou que as principais justificativas para o desenvolvimento de competências em sustentabilidade ambiental são aquelas que afetam em algum momento as questões financeiras das empresas. E, quanto às dificuldades, verificou-se que as questões relacionadas à falta de tempo e o nível de educação/escolaridade dos funcionários são os principais fatores negativos para a aprendizagem organizacional em sustentabilidade ambiental nas empresas associadas à REDEPETRO-RN.

The need to accessorize: Molecular roles of HTLV-1 p30 and HTLV-2 p28 accessory proteins in the viral life cycle

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Rajaneesh eAnupam

2013-09-01

Full Text Available Extensive studies of HTLV-1 and HTLV-2 over the last three decades have provided detailed knowledge on viral transformation, host-viral interactions and pathogenesis. HTLV-1 is the etiological agent of adult T cell leukemia (ATL and multiple neurodegenerative and inflammatory diseases while HTLV-2 disease association remains elusive, with few infected individuals displaying neurodegenerative diseases similar to HTLV-1. The HTLV group of oncoretroviruses has a genome that encodes structural and enzymatic proteins Gag, Pro and Env, regulatory proteins Tax and Rex, and several accessory proteins from the pX region. Of these proteins, HTLV-1 p30 and HTLV-2 p28 are encoded by the open reading frame (ORF II of the pX region. Like most other accessory proteins, p30 and p28 are dispensable for in vitro viral replication and transformation but are required for efficient viral replication and persistence in vivo. Both p30 and p28 regulate viral gene expression at the post-transcriptional level whereas p30 can also function at the transcriptional level. Recently, several reports have implicated p30 and p28 in multiple cellular processes, which provide novel insight into HTLV spread and survival and ultimately pathogenesis. In this review we summarize and compare what is known about p30 and p28, highlighting their roles in viral replication and viral pathogenesis.

Suppression of HTLV-1 transcription by SIRT1 deacetylase

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Tang, HMV; Jin, D; Gao, W; Chan, CP; Iha, H; Yuen, KS

2015-01-01

Infection with HTLV-1 causes adult T-cell leukemia and tropical spastic paraparesis in different subsets of infected people. Treatments for HTLV-1-associated diseases are unspecific and unsatisfactory. Prophylactic measures have not been developed. Although HTLV-1 pathogenesis involves multiple stages and factors, high proviral load has been singled out as a major risk factor which predicts disease. HTLV-1 encodes Tax transactivator that potently activates transcription from viral long termin...

Efeito da suplementação de creatina, associada ou não ao treinamento de força, sobre a peroxidação lipídica em mulheres idosas

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Christiano Robles Rodrigues ALVES

2014-03-01

Full Text Available O objetivo desse trabalho foi avaliar o efeito da suplementação de creatina associada ou não ao treinamento de força sobre a peroxidação lipídica em mulheres idosas. Foi conduzido um estudo clínico, randomizado, duplo-cego e controlado por placebo, no qual mulheres idosas foram randomizadas para compor quatro grupos: 1 suplementação com placebo (PL; n = 10; 2 suplementação com creatina (CR; n = 10; 3 suplementação com placebo associado ao treinamento de força (PL+TR; n = 6; e 4 suplementação com creatina associado ao treinamento de força (CR+TR; n = 8. Antes (PRE e após 24 semanas (POS de intervenção, foram coletadas amostras de sangue para posterior análise das concentrações plasmáticas de hidroperóxidos lipídicos por espectrofotometria. Nenhuma diferença estatística foi observada na concentração de hidroperóxidos lipídicos entre os grupos (PL: PRE = 48,7 ± 36,9; POS = 29,3 ± 18,8; delta = -13,0 ± 26,8; CR: PRE = 51,0 ± 46,0; POS = 54,2 ± 51,6; delta = -8,6 ± 30,2; PL+TR: PRE = 33,0 ± 11,2; POS = 47,3 ± 31,6; Δ = 14,3 ± 39,2; CR+TR: PRE = 18,5 ± 10,1; POS = 28,1 ± 17,9; delta = 9,7 ± 16,4 pmol.mg-1 de proteína total; p = 0,17. A suplementação de creatina associada ou não ao treinamento de força não afetou a peroxidação lipídica, um importante marcador de estresse oxidativo no plasma, em mulheres idosas.

Epidemiological Aspects and World Distribution of HTLV-1 Infection

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Antoine eGessain

2012-11-01

Full Text Available The human T-cell leukemia virus type 1 (HTLV-1, identified as the first human oncogenic retrovirus 30 years ago, is not an ubiquitous virus. HTLV-1 is present throughout the world, with clusters of high endemicity located often nearby areas where the virus is nearly absent. The main HTLV-1 highly endemic regions are the Southwestern part of Japan, sub-Saharan Africa and South America, the Caribbean area and foci in Middle East and Australo-Melanesia. The origin of this puzzling geographical or rather ethnic repartition is probably linked to a founder effect in some groups with the persistence of a high viral transmission rate. Despite different socio-economic and cultural environments, the HTLV-1 prevalence increases gradually with age, especially among women in all highly endemic areas. The three modes of HTLV-1 transmission are mother to child, sexual transmission and transmission with contaminated blood products. Twenty years ago, de Thé and Bomford estimated the total number of HTLV-1 carriers to be 10-20 millions people. At that time, large regions had not been investigated, few population-based studies were available and the assays used for HTLV-1 serology were not enough specific. Despite the fact that there is still a lot of data lacking in large areas of the world and that most of the HTLV-1 studies concern only blood donors, pregnant women or different selected patients or high-risk groups, we shall try based on the most recent data, to revisit the world distribution and the estimates of the number of HTLV-1 infected persons.Our best estimates range from 5-10 millions HTLV-1 infected individuals. However, these results were based on approximately 1.5 billion of individuals originating from known endemic areas with reliable available epidemiological data. Correct estimates in other highly populated regions such as China, India, the Maghreb and East Africa is currently not possible, thus, the current number of HTLV-1 carriers is very

Functional comparison of antisense proteins of HTLV-1 and HTLV-2 in viral pathogenesis

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Benoit eBarbeau

2013-08-01

Full Text Available The production of antisense transcripts from the 3’ long terminal repeat (LTR in human T-lymphotropic retroviruses has now been clearly demonstrated. After the identification of the antisense strand-encoded HTLV-1 bZIP (HBZ factor, we reported that HBZ could interact with CREB transcription factors and consequently turn off the important activating potential of the viral Tax protein on HTLV-1 5’ LTR promoter activity. We have recently accumulated new results demonstrating that antisense transcripts also exist in HTLV-2, -3 and -4. Furthermore, our data have confirmed the existence of encoded proteins from these antisense transcripts (termed antisense proteins of HTLVs or APHs. APHs are also involved in the down-regulation of Tax-dependent viral transcription. In this review, we will focus on the different molecular mechanisms used by HBZ and APH-2 to control viral expression. While HBZ interacts with CREB through its basic zipper domain, APH-2 binds to this cellular factor through a five amino acid motif localized in its carboxyl terminus. Moreover, unlike APH-2, HBZ possesses an N-terminal activation domain that also contributes to the inhibition of the viral transcription by interacting with the KIX domain of p300/CBP. On the other hand, HBZ was found to induce T-cell proliferation while APH-2 was unable to promote such proliferation. Interestingly, HTLV-2 has not been causally linked to human T-cell leukemia, while HTLV-1 is responsible for the development of the Adult T-cell Leukemia/Lymphoma (ATLL. We will further discuss the possible role played by antisense proteins in the establishment of pathologies induced by viral infection.

Animal Models Utilized in HTLV-1 Research

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Amanda R. Panfil

2013-01-01

Full Text Available Since the isolation and discovery of human T-cell leukemia virus type 1 (HTLV-1 over 30 years ago, researchers have utilized animal models to study HTLV-1 transmission, viral persistence, virus-elicited immune responses, and HTLV-1-associated disease development (ATL, HAM/TSP. Non-human primates, rabbits, rats, and mice have all been used to help understand HTLV-1 biology and disease progression. Non-human primates offer a model system that is phylogenetically similar to humans for examining viral persistence. Viral transmission, persistence, and immune responses have been widely studied using New Zealand White rabbits. The advent of molecular clones of HTLV-1 has offered the opportunity to assess the importance of various viral genes in rabbits, non-human primates, and mice. Additionally, over-expression of viral genes using transgenic mice has helped uncover the importance of Tax and Hbz in the induction of lymphoma and other lymphocyte-mediated diseases. HTLV-1 inoculation of certain strains of rats results in histopathological features and clinical symptoms similar to that of humans with HAM/TSP. Transplantation of certain types of ATL cell lines in immunocompromised mice results in lymphoma. Recently, “humanized” mice have been used to model ATL development for the first time. Not all HTLV-1 animal models develop disease and those that do vary in consistency depending on the type of monkey, strain of rat, or even type of ATL cell line used. However, the progress made using animal models cannot be understated as it has led to insights into the mechanisms regulating viral replication, viral persistence, disease development, and, most importantly, model systems to test disease treatments.

Causas básicas e associadas de morte por Aids, Estado de São Paulo, Brasil, 1998

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Santo Augusto Hasiak

2000-01-01

Full Text Available OBJETIVOS: Descrever o padrão da mortalidade devida a Aids segundo causas básica e associadas de morte no Estado de São Paulo, em 1998. MÉTODOS: Os dados sobre a mortalidade e a população residente no Estado de São Paulo, SP, para 1998, foram obtidos na Fundação Sistema Estadual de Análise de Dados (Seade. As causas de morte foram codificadas pelas disposições da Décima Revisão da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde. Os registros de Aids como causa básica e associada de morte foram recuperados e revistos. RESULTADOS: A Aids foi a causa básica em 4.619 mortes, correspondendo à décima causa (2,0% e ao coeficiente de mortalidade de 13,1 por 100.000 habitantes. As razões das mortes e os respectivos coeficientes entre homens e mulheres foram de 2,4 e 2,5. A Aids foi a segunda causa entre os homens de 20 a 34 anos de idade e entre as mulheres de 25 a 34. A idade média ao morrer entre as mulheres (34,1±12,2 anos foi estatisticamente menor que a dos homens (36,4±10,7 anos -- p<0,001. As principais causas associadas em mortes por Aids foram a insuficiência respiratória (36,1%, pneumonias (27,0%, tuberculose (19,6%, septicemias (18,6%, toxoplasmose (12,2%, pneumonia por P. carinii (8,3% e caquexia (7,9%. A Aids apresentou-se como causa associada em outras 84 mortes. As principais causas básicas destas mortes foram neoplasias malignas (28/84, afecções devidas ao uso do álcool (23/84 e diabetes mellitus (7/84. A idade média ao morrer por Aids como causa básica (35,7±11,2 anos foi estatisticamente menor que a idade média nas mortes em que Aids foi mencionada como causa associada (39,9±11,8 anos -- p<0,001. CONCLUSÕES: As causas múltiplas de morte resgatam parcialmente a história natural da Aids e oferecem subsídios para medidas preventivas adequadas e específicas.

Dynamics of human T-cell lymphotropic virus I (HTLV-I) infection of CD4+ T-cells.

Science.gov (United States)

Katri, Patricia; Ruan, Shigui

2004-11-01

Stilianakis and Seydel (Bull. Math. Biol., 1999) proposed an ODE model that describes the T-cell dynamics of human T-cell lymphotropic virus I (HTLV-I) infection and the development of adult T-cell leukemia (ATL). Their model consists of four components: uninfected healthy CD4+ T-cells, latently infected CD4+ T-cells, actively infected CD4+ T-cells, and ATL cells. Mathematical analysis that completely determines the global dynamics of this model has been done by Wang et al. (Math. Biosci., 2002). In this note, we first modify the parameters of the model to distinguish between contact and infectivity rates. Then we introduce a discrete time delay to the model to describe the time between emission of contagious particles by active CD4+ T-cells and infection of pure cells. Using the results in Culshaw and Ruan (Math. Biosci., 2000) in the analysis of time delay with respect to cell-free viral spread of HIV, we study the effect of time delay on the stability of the endemically infected equilibrium. Numerical simulations are presented to illustrate the results.

Influence of human t-cell lymphotropic virus type 1 (HTLV-1 Infection on laboratory parameters of patients with chronic hepatitis C virus Influência da infecção pelo vírus linfotrópico humano tipo 1 (HTLV-1 em parâmetros laboratoriais de pacientes com hepatite C crônica

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Daniela Fernandes Cardoso

2009-12-01

Full Text Available Hepatitis C virus (HCV and human T-cell lymphotropic virus type 1 (HTLV-1 share routes of transmission and some individuals have dual infection. Although some studies point to a worse prognosis of hepatitis C virus in patients co-infected with HTLV-1, the interaction between these two infections is poorly understood. This study evaluated the influence of HTLV-1 infection on laboratory parameters in chronic HCV patients. Twelve HTLV-1/HCV-coinfected patients were compared to 23 patients infected only with HCV, in regard to demographic data, risk factors for viral acquisition, HCV genotype, presence of cirrhosis, T CD4+ and CD8+ cell counts and liver function tests. There was no difference in regard to age, gender, alcohol consumption, smoking habits, HCV genotype or presence of cirrhosis between the groups. Intravenous drug use was the most common risk factor among individuals co-infected with HTLV-1. These patients showed higher TCD8+ counts (p = 0.0159 and significantly lower median values of AST and ALT (p = 0.0437 and 0.0159, respectively. In conclusion, we have shown that HCV/HTLV-1 co-infected patients differs in laboratorial parameters involving both liver and immunological patterns. The meaning of these interactions in the natural history of these infections is a matter that deserves further studies.O vírus da hepatite C (VHC e vírus linfotrópico humano tipo 1 (HTLV-1 compartilham formas de transmissão e algumas pessoas apresentam coinfecção. Embora alguns estudos apontem para um pior prognóstico da infecção pelo VHC em pacientes coinfectados com HTLV-1, a interação entre estas infecções é mal compreendida. Este estudo avaliou a influência da infecção pelo HTLV-1 em parâmetros laboratoriais de pacientes com VHC. 12 coinfectados VHC/HTLV-1 foram comparados com 23 pacientes monoinfectados com VHC, no que diz respeito aos dados demográficos, fatores de risco para aquisição viral, genótipo do VHC, presença de cirrose

PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival

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Amanda R. Panfil

2015-12-01

Full Text Available Human T-cell leukemia virus type-1 (HTLV-1 is a tumorigenic retrovirus responsible for development of adult T-cell leukemia/lymphoma (ATLL. This disease manifests after a long clinical latency period of up to 2–3 decades. Two viral gene products, Tax and HBZ, have transforming properties and play a role in the pathogenic process. Genetic and epigenetic cellular changes also occur in HTLV-1-infected cells, which contribute to transformation and disease development. However, the role of cellular factors in transformation is not completely understood. Herein, we examined the role of protein arginine methyltransferase 5 (PRMT5 on HTLV-1-mediated cellular transformation and viral gene expression. We found PRMT5 expression was upregulated during HTLV-1-mediated T-cell transformation, as well as in established lymphocytic leukemia/lymphoma cell lines and ATLL patient PBMCs. shRNA-mediated reduction in PRMT5 protein levels or its inhibition by a small molecule inhibitor (PRMT5i in HTLV-1-infected lymphocytes resulted in increased viral gene expression and decreased cellular proliferation. PRMT5i also had selective toxicity in HTLV-1-transformed T-cells. Finally, we demonstrated that PRMT5 and the HTLV-1 p30 protein had an additive inhibitory effect on HTLV-1 gene expression. Our study provides evidence for PRMT5 as a host cell factor important in HTLV-1-mediated T-cell transformation, and a potential target for ATLL treatment.

HTLV-1 bZIP factor induces inflammation through labile Foxp3 expression.

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Nanae Yamamoto-Taguchi

2013-09-01

Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 causes both a neoplastic disease and inflammatory diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. The HTLV-1 basic leucine zipper factor (HBZ gene is encoded in the minus strand of the proviral DNA and is constitutively expressed in infected cells and ATL cells. HBZ increases the number of regulatory T (Treg cells by inducing the Foxp3 gene transcription. Recent studies have revealed that some CD4⁺Foxp3⁺ T cells are not terminally differentiated but have a plasticity to convert to other T-cell subsets. Induced Treg (iTreg cells tend to lose Foxp3 expression, and may acquire an effector phenotype accompanied by the production of inflammatory cytokines, such as interferon-γ (IFN-γ. In this study, we analyzed a pathogenic mechanism of chronic inflammation related with HTLV-1 infection via focusing on HBZ and Foxp3. Infiltration of lymphocytes was observed in the skin, lung and intestine of HBZ-Tg mice. As mechanisms, adhesion and migration of HBZ-expressing CD4⁺ T cells were enhanced in these mice. Foxp3⁻CD4⁺ T cells produced higher amounts of IFN-γ compared to those from non-Tg mice. Expression of Helios was reduced in Treg cells from HBZ-Tg mice and HAM/TSP patients, indicating that iTreg cells are predominant. Consistent with this finding, the conserved non-coding sequence 2 region of the Foxp3 gene was hypermethylated in Treg cells of HBZ-Tg mice, which is a characteristic of iTreg cells. Furthermore, Treg cells in the spleen of HBZ-transgenic mice tended to lose Foxp3 expression and produced an excessive amount of IFN-γ, while Foxp3 expression was stable in natural Treg cells of the thymus. HBZ enhances the generation of iTreg cells, which likely convert to Foxp3⁻T cells producing IFN-γ. The HBZ-mediated proinflammatory phenotype of CD4⁺ T cells is implicated in the pathogenesis of HTLV-1-associated inflammation.

Short communication an interferon-γ ELISPOT assay with two cytotoxic T cell epitopes derived from HTLV-1 tax region 161-233 discriminates HTLV-1-associated myelopathy/tropical spastic paraparesis patients from asymptomatic HTLV-1 carriers in a Peruvian population.

Science.gov (United States)

Best, Ivan; López, Giovanni; Talledo, Michael; MacNamara, Aidan; Verdonck, Kristien; González, Elsa; Tipismana, Martín; Asquith, Becca; Gotuzzo, Eduardo; Vanham, Guido; Clark, Daniel

2011-11-01

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic and progressive disorder caused by the human T-lymphotropic virus type 1 (HTLV-1). In HTLV-1 infection, a strong cytotoxic T cell (CTL) response is mounted against the immunodominant protein Tax. Previous studies carried out by our group reported that increased IFN-γ enzyme-linked immunospot (ELISPOT) responses against the region spanning amino acids 161 to 233 of the Tax protein were associated with HAM/TSP and increased HTLV-1 proviral load (PVL). An exploratory study was conducted on 16 subjects with HAM/TSP, 13 asymptomatic carriers (AC), and 10 HTLV-1-seronegative controls (SC) to map the HAM/TSP-associated CTL epitopes within Tax region 161-233. The PVL of the infected subjects was determined and the specific CTL response was evaluated with a 6-h incubation IFN-γ ELISPOT assay using peripheral blood mononuclear cells (PBMCs) stimulated with 16 individual overlapping peptides covering the Tax region 161-233. Other proinflammatory and Th1/Th2 cytokines were also quantified in the supernatants by a flow cytometry multiplex assay. In addition, a set of human leukocyte antigen (HLA) class I alleles that bind with high affinity to the CTL epitopes of interest was determined using computational tools. Univariate analyses identified an association between ELISPOT responses to two new CTL epitopes, Tax 173-185 and Tax 181-193, and the presence of HAM/TSP as well as an increased PVL. The HLA-A*6801 allele, which is predicted to bind to the Tax 181-193 peptide, was overpresented in the HAM/TSP patients tested.

HBZ and its roles in HTLV-1 oncogenesis

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Tiejun eZhao

2012-07-01

Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 causes adult T-cell leukemia (ATL. The minus strand of HTLV-1 provirus encodes a bZIP protein donated as HTLV-1 bZIP factor (HBZ. Among the HTLV-1 regulatory and accessory genes, the tax and HBZ genes were thought to play critical roles in oncogenesis. However, HBZ is the only gene that remains intact and is consistently expressed in all ATL cases, while the tax gene is frequently inactivated by epigenetic modifications or deletion of the 5’LTR. HBZ gene promotes the proliferation of ATL cells through its mRNA form. Moreover, HBZ induces T-cell lymphoma and systemic inflammation in vivo. HBZ fulfills its functions mainly through regulating HTLV-1 5’LTR transcription and modulating a variety of cellular signaling pathways which are related with cell growth, immune response and T-cell differentiation. Taken together, the multiple functions of HBZ render its predominant function in leukemogenesis of ATL.

HTLV-1 tax specific CD8+ T cells express low levels of Tim-3 in HTLV-1 infection: implications for progression to neurological complications.

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Lishomwa C Ndhlovu

2011-04-01

Full Text Available The T cell immunoglobulin mucin 3 (Tim-3 receptor is highly expressed on HIV-1-specific T cells, rendering them partially "exhausted" and unable to contribute to the effective immune mediated control of viral replication. To elucidate novel mechanisms contributing to the HTLV-1 neurological complex and its classic neurological presentation called HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis, we investigated the expression of the Tim-3 receptor on CD8(+ T cells from a cohort of HTLV-1 seropositive asymptomatic and symptomatic patients. Patients diagnosed with HAM/TSP down-regulated Tim-3 expression on both CD8(+ and CD4(+ T cells compared to asymptomatic patients and HTLV-1 seronegative controls. HTLV-1 Tax-specific, HLA-A*02 restricted CD8(+ T cells among HAM/TSP individuals expressed markedly lower levels of Tim-3. We observed Tax expressing cells in both Tim-3(+ and Tim-3(- fractions. Taken together, these data indicate that there is a systematic downregulation of Tim-3 levels on T cells in HTLV-1 infection, sustaining a profoundly highly active population of potentially pathogenic T cells that may allow for the development of HTLV-1 complications.

Study of the peptide length and amino acid specific substitution in the antigenic activity of the chimeric synthetic peptides, containing the p19 core and gp46 envelope proteins of the HTLV-I virus.

Science.gov (United States)

Marin, Milenen Hernández; Rodríguez-Tanty, Chryslaine; Higginson-Clarke, David; Bocalandro, Yadaris Márquez; Peña, Lilliam Pozo

2005-10-28

Four chimeric synthetic peptides (Q5, Q6, Q7(multiply sign in circle), and Q8(multiply sign in circle)), incorporating immunodominant epitopes of the core p19 (105-124 a.a.) and envelope gp46 proteins (175-205 a.a.), of HTLV-I were obtained. Also, two gp46 monomeric peptides M4 and M5(multiply sign in circle) (Ser at position 192) were synthesized. The analysis of the influence of the peptide lengths and the proline to serine substitution on the chimeric and monomeric peptides' antigenicity, with regard to the chimeric peptides Q1, Q2, Q3(multiply sign in circle), and Q4(multiply sign in circle), reported previously, for HTLV-I was carried out. The peptides' antigenicity was evaluated in an ultramicroenzyme-linked immunosorbent assay (UMELISA) using sera of HTLV-I/II. The peptides' antigenicity was affected appreciably by the change of the peptide length and amino acid substitutions into the immunodominant sequence of gp46 peptide.

Seroprevalencia de HTLV-1/2 en donantes de sangre de la Provincia de Misiones Seroprevalence of HTLV-1/2 in blood donors from Misiones Province

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Richard Malan

2010-02-01

Full Text Available El Virus Linfotrópico T Humano tipo 1 (HTLV-1, primer oncorretrovirus humano descubierto, es el causante etiológico de la leucemia de células T del adulto (ATL y de la mielopatía asociada al HTLV-1 o paraparesia espástica tropical (HAM/TSP. Es endémico en distintas partes del mundo, inclusive en el noroeste argentino, donde ambas enfermedades fueron detectadas. El HTLV-2, no tiene un rol etiológico definido, si bien ha sido asociado con síndromes neurológicos similares a la HAM/TSP. Ambos virus son endémicos en comunidades originarias del continente americano, tribus de Africa y poblaciones en riesgo. Ambos retrovirus se transmiten por vía sexual, parenteral y de madre a hijo. El objetivo de este trabajo fue determinar la seroprevalencia de HTLV-1/2 en una población de donantes de sangre de la provincia de Misiones. Se analizaron 6912 donaciones de sangre recibidas en el Banco de Sangre Central de la Provincia de Misiones durante 2008. La detección de anticuerpos se realizó por ELISA y aglutinación de partículas, y las muestras reactivas fueron confirmadas por Western Blot. Del total de muestras, 5 resultaron seropositivas con una prevalencia final de 0.00072. De ellas, una era HTLV, tres HTLV-1 y una HTLV-2 positiva. Los donantes positivos provenían de Posadas, Eldorado y Oberá, sin antecedentes de riesgo. Este estudio demuestra la presencia de HTLV-1/2 en donantes de sangre de Misiones, con cifras similares a las notificadas en donantes de sangre de zonas no endémicas.Human T-cell Lymphotropic viruses type 1 (HTLV-1, the first human oncoretrovirus to be discovered, is the etiologic agent of Adult T-cell Leukemia (ATL and HTLV-1 Associated Mielopathy or Tropical Spastic Paraparesis (HAM/TSP. It is endemic worldwide, including the North of Argentina where both associated diseases have also been detected. No etiologic role has been described for HTLV-2, although it has been associated with HAM/TSP-like neurologic syndromes

Dual infections with HIV-1, HIV-2 and HTLV-I are more common in older women than in men in Guinea-Bissau

DEFF Research Database (Denmark)

Holmgren, B; da Silva, Z; Larsen, Olav Ditlevsen

2003-01-01

OBJECTIVES: To investigate the association between the three human retroviruses, HIV-1, HIV-2 and HTLV-I. DESIGN: Community-based follow-up studies of retrovirus infections in two cohorts. METHODS: A total of 2057 individuals aged 35 years and over were eligible for inclusion. Participants were...... interviewed and had a blood sample drawn. Samples were analysed for HIV-1, HIV-2 and HTLV infections. Uni- and multivariate analyses that included behavioural and socio-economic factors were performed using logistic regression and Poisson regression models. RESULTS: A total of 1686 individuals participated...... increased with age for all three retroviruses. Dual infections were more common in women than in men. Assuming independent distribution of the viruses, the observed prevalence of dual infections in women was significantly higher than expected, while the prevalence was not increased in men. The prevalence...

Microtubule proteins and their post-translational forms in the cerebrospinal fluid of patients with paraparesis associated with HTLV-I infection and in SH-SY5Y cells: An in vitro model of HTLV-I-induced disease

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HORACIO MALDONADO

2008-01-01

Full Text Available HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP is characterized by axonal degeneration of the corticospinal tracts. The specific requirements for transport of proteins and organelles to the distal part of the long axon are crucial in the corticospinal tracts. Microtubule dysfunction could be involved in this disease, configuring an axonal transport disease. We measured tubulin and its post-translational modified forms (acetylated and tyrosinated in CSF of patients and controls, as well as tau and its phosphorylated forms. There were no significant differences in the contents of tubulin and acetyl-tubulin between patients and controls; tyrosyl-tubulin was not detected. In HAM/TSP, tau levéis were significantly reduced, while the ratio of pT181/total tau was higher in patients than in controls, this being completely different from what is reported in other neurodegenerative diseases. Phosphorylation at T181 was also confirmed by Mass Spectrometry analysis. Western Blotting with monospecific polyclonal antibodies against pS199, pT205, pT231, pS262, pS356, pS396, pS404 and pS422 did not show differences in phosphorylation in these residues between patients and controls. Treating human SH-SY5Y neuroblastoma cells, a well-known in vitro neurite retraction model, with culture supernatant of MT-2 cells (HTLV-I infected cell line that secretes the viral Tax protein we observed neurite retraction and an increase in tau phosphorylation at T181. A disruption of normal phosphorylation of tau protein in T181 could result in its dysfunction, contributing to axonal damage.

Hiv/hbv, hiv/hcv and hiv/htlv-1 co infection among injecting drug user patients hospitalized at the infectious disease ward of a training hospital in iran

International Nuclear Information System (INIS)

Alavi, S.M.; Etemadi, A.

2007-01-01

To assess the prevalence and risk factors for HBV, HCV and HTLV-I co-infection in the Iranian HIV positive Injecting Drug Users (IDU) patients admitted in hospital. Analyses were based on 154 male IDU patients admitted in Infectious disease ward of Razi Hospital, Ahwaz, Iran, from April 2001 to March 2003. All of them had been tested for HIV infection (Elisa-antibody and Western blot), HBV surface antigen, HCV antibody and HTLV-1 antibody. One hundred and four patients (67.53%) were identified as HIV infected. Among HIV infected, HB surface antigen, HCV antibody and HTLV-I antibody were positive in 44.23% and 74.04% and 16.33% patients respectively. HCV/HBV/HIV and HCV/HBV/HIV/HTLV-1 co-infection were 20.20% and 8.65% respectively. Co-infection with HBV or HCV or HTLV-1 is common among hospitalized HIV-infected IDU patients in the region of study. HIV disease outcomes appear to be adversely affected by HBV/HCV/HTLV-I co-infection, so identification of these viral infections is recommended as routine tests for this population. (author)

Resposta ao estresse: II. Resiliência e vulnerabilidade

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Nicole Leite Galvão-Coelho

2015-06-01

Full Text Available ResumoA crescente exposição a estressores na vida cotidiana aumentou significativamente a investigação da resposta ao estresse nas duas últimas décadas. Embora associada a consequências negativas, pois muitas patologias físicas e mentais são desencadeadas por exposição crônica a estressores, esta resposta é indispensável para sobrevivencia do indivíduo e é extremamente adaptativa quando ativada de forma aguda. Na parte I desta revisão foram abordados os conceitos de homestase e alostase e os sistemas fisiológicos ativados durante a resposta ao estresse. Na parte II serão discutidos fatores que modulam a resposta ao estresse tais como sexo, temperamento, períodos críticos do desenvolvimento e a presença ou ausência de suporte social. A interação entre os fatores genéticos e ambientais gera os perfis da resposta psicofisiológica que caracterizam os fenótipos de susceptibilidade e resiliência frente aos estressores e sua relação com uma patologia mental cada vez mais presente na sociedade moderna, o transtorno de estresse pós-traumático.

Transcriptional and Epigenetic Regulatory Mechanisms Affecting HTLV-1 Provirus

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Paola Miyazato

2016-06-01

Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 is a retrovirus associated with human diseases, such as adult T-cell leukemia (ATL and HTLV-1-associated myelopathy/Tropic spastic paraparesis (HAM/TSP. As a retrovirus, its life cycle includes a step where HTLV-1 is integrated into the host genomic DNA and forms proviral DNA. In the chronic phase of the infection, HTLV‑1 is known to proliferate as a provirus via the mitotic division of the infected host cells. There are generally tens of thousands of infected clones within an infected individual. They exist not only in peripheral blood, but also in various lymphoid organs. Viral proteins encoded in HTLV-1 genome play a role in the proliferation and survival of the infected cells. As is the case with other chronic viral infections, HTLV-1 gene expression induces the activation of the host immunity against the virus. Thus, the transcription from HTLV-1 provirus needs to be controlled in order to evade the host immune surveillance. There should be a dynamic and complex regulation in vivo, where an equilibrium between viral antigen expression and host immune surveillance is achieved. The mechanisms regulating viral gene expression from the provirus are a key to understanding the persistent/latent infection with HTLV-1 and its pathogenesis. In this article, we would like to review our current understanding on this topic.

12th international conference on human retrovirology: HTLV and related retroviruses

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Lairmore Michael D

2005-10-01

Full Text Available Abstract The 12th International Conference on Human Retrovirology: HTLV and Related Retroviruses, was held at the Half Moon Hotel in Montego Bay, Jamaica, from June 22nd to June 25th 2005. The scientific conference, sponsored by the International Retrovirology Association, is held biennially at rotating international venues around the world. The meeting brings together basic scientists, epidemiologists and clinical researchers to discuss findings to prevent HTLV infection or develop new therapies against HTLV-mediated diseases. The Association fosters the education and training of young scientists to bring new approaches to the complex problems of HTLV research, such as translational research to bring findings from the laboratory into clinical trials that benefit HTLV-infected patients. The breadth and quality of research presentations and workshops at the 12th International Conference indicate that these goals are being accomplished. As HTLV research enters its third decade a new generation of scientists face many challenges. However, HTLV scientists and clinicians displayed exciting new approaches and discoveries during plenary talks and poster sessions. The conference encouraged research in HTLV infections and disease, fostered collaborations, and stimulated new partnerships between clinicians and scientists to encourage clinical trials and novel therapeutic interventions.

Uso da bandagem elástica associada ao tratamento fonoaudiológico no controle da sialorréia

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Wanessa Furtado Caneschi

2014-10-01

Full Text Available OBJETIVO:verificar a efetividade do uso da bandagem elástica associada ao tratamento fonoaudiológico no controle da sialorréia.MÉTODOS:estudo longitudinal realizado com onze crianças com quadro de sialorréia crônica e alteração neurológica. Foi verificada a percepção do fonoaudiólogo e do responsável acerca da gravidade e o número de toalhas/paninhos de boca utilizados ao dia. Empregou-se também a sialometria. Cada participante recebeu a aplicação da bandagem elástica Kinesio Tape na região da musculatura supra-hióidea por 30 dias. As crianças foram avaliadas sem a bandagem (T0, imediatamente após a retirada da bandagem (T1 e três meses após (T2. O tratamento fonoaudiológico foi realizado pelo o mesmo profissional em duas sessões semanais. Os dados foram analisados estatisticamente.RESULTADOS:no questionário verificou-se redução da queixa de engasgos com saliva em T1 (p=0,024.A média de uso diário de toalhas/paninhos era de quatro (10,2% em T0, duas (5,1% em T1 e quatro (10,2% em T2.De acordo com a sialometria, verificou-se redução da sialorréia de T0 para T1 (p=0,018 e ausência de diferença entre T0 e T2 (p=0,215 e aumento de T1 para T2 (p=0,05.De acordo com a percepção do fonoaudiólogo houve redução da sialorréia 30 dias após o uso da bandagem, entretanto não se observou melhora ao se comparar os resultados 30 dias após o uso e três meses sem a bandagem.CONCLUSÃO:a bandagem elástica se mostrou eficaz no controle da sialorréia durante seu período de uso, não sendo observada permanência dos resultados após interrupção da aplicação.

Regulation of HTLV-1 Gag budding by Vps4A, Vps4B, and AIP1/Alix

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Yokosawa Hideyoshi

2007-07-01

Full Text Available Abstract Background HTLV-1 Gag protein is a matrix protein that contains the PTAP and PPPY sequences as L-domain motifs and which can be released from mammalian cells in the form of virus-like particles (VLPs. The cellular factors Tsg101 and Nedd4.1 interact with PTAP and PPPY, respectively, within the HTLV-1 Gag polyprotein. Tsg101 forms a complex with Vps28 and Vps37 (ESCRT-I complex and plays an important role in the class E Vps pathway, which mediates protein sorting and invagination of vesicles into multivesicular bodies. Nedd4.1 is an E3 ubiquitin ligase that binds to the PPPY motif through its WW motif, but its function is still unknown. In the present study, to investigate the mechanism of HTLV-1 budding in detail, we analyzed HTLV-1 budding using dominant negative (DN forms of the class E proteins. Results Here, we report that DN forms of Vps4A, Vps4B, and AIP1 inhibit HTLV-1 budding. Conclusion These findings suggest that HTLV-1 budding utilizes the MVB pathway and that these class E proteins may be targets for prevention of mother-to-infant vertical transmission of the virus.

Large granular lymphocytosis in a patient infected with HTLV-II.

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Martin, M P; Biggar, R J; Hamlin-Green, G; Staal, S; Mann, D

1993-08-01

HTLV-II has been associated with a variety of lymphoproliferative disorders, including atypical hairy cell leukemia, chronic T cell leukemia, T prolymphocytic leukemia, and large granular lymphocytic leukemia. However, a direct or indirect role for HTLV-II in these disorders is not yet firmly established. We studied a patient diagnosed as having leukemia of the large granular lymphocyte (LGL) type who was HTLV-II seropositive, to determine if the expanded cell population was infected. Two populations of CD3-CD16+ LGL were identified; one was CD8+, the other CD8-. Populations of cells with these surface markers as well as normal CD3+CD4+ and CD3+CD8+ cells were separated by flow cytometric methods, DNA extracted, and gene regions of HTLV-II pol and tax amplified, using the polymerase chain reaction, and probed after Southern blotting. HTLV-II was detected in the CD3+CD8+ population, and not in the CD3-CD16+ large granular lymphocyte population. This finding indicates that the role of HTLV-II, if any, in LGL proliferation is indirect.

Adesão ao tratamento no transtorno bipolar

OpenAIRE

Santin,Aida; Ceresér,Keila; Rosa,Adriane

2005-01-01

O transtorno bipolar (TB) é uma doença crônica, recorrente, presente em 1,5% da população, estando associada a altas taxas de mortalidade e prejuízos socioeconômicos. O lítio, a carbamazepina e o ácido valpróico são os estabilizadores de humor mais usados. Em tratamentos prolongados, como é o caso do TB, a má-adesão dos pacientes é uma das maiores dificuldades. Verifica-se que fatores ligados ao paciente, aos medicamentos e aos médicos possam ser responsáveis pela baixa adesão. A psicoeducaçã...

Sensitivity and specificity of four assays to detect human T-lymphotropic virus type I or type I/II antibodies

NARCIS (Netherlands)

Vrielink, H.; Reesink, H. W.; Zaaijer, H. L.; van der Poel, C. L.; Cuypers, H. T.; Lelie, P. N.

1996-01-01

BACKGROUND: Assays that detect human T-lymphotropic virus type I and type II antibody (HTLV-I/II) are widely used in the routine screening of blood donors. STUDY DESIGN AND METHODS: Four commercially available anti-HTLV-I (Fujirebio and Organon Teknika) or -HTLV-I/II assays (Murex and Ortho) were

Efeito da teofilina associada ao beta2-agonista inalatório de curta ou longa duração, em pacientes com doença pulmonar obstrutiva crônica estável: revisão sistemática Effect of theophylline associated with short-acting or long-acting inhaled beta2-agonists in patients with stable chronic obstructive pulmonary disease: a systematic review

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Eliane Cristina Zacarias

2007-04-01

Full Text Available OBJETIVOS: Avaliar se o tratamento com teofilina associada ao beta2-agonista inalatório de curta ou longa duração é mais eficaz que o placebo e que o uso isolado de cada um dos fármacos, para os pacientes com doença pulmonar obstrutiva crônica estável. MÉTODOS: Realizou-se uma revisão sistemática com metanálise, sendo selecionados todos os ensaios clínicos aleatórios e duplo-cegos encontrados na literatura. RESULTADOS: Foram incluídos oito estudos. Teofilina associada ao beta2-agonista vs. placebo: houve melhora estatisticamente significante para o VEF1 (L, com média 0,27 (IC95% 0,11 a 0,43; e para a dispnéia, com média -0,78 (IC95% -1,26 a -0,29. Teofilina associada ao beta2-agonista vs. beta2-agonista isolado: nenhuma das metanálises realizadas detectou diferença entre os grupos. Teofilina associada ao beta2-agonista vs. teofilina isolada: houve melhora estatisticamente significante para a dispnéia, com média -0,19 (IC95% -0,34 a -0,04. CONCLUSÕES: Em pacientes com doença pulmonar obstrutiva crônica estável: 1 teofilina associada ao beta2-agonista é mais eficaz que o placebo, em relação ao VEF1 e dispnéia; 2a teofilina associada ao beta2-agonista é mais eficaz que a teofilina isolada, em relação à dispnéia; e 2b teofilina associada ao beta2-agonista não é mais eficaz que o beta2-agonista isolado, para quaisquer das variáveis estudadas.OBJECTIVES: To determine whether, in stable patients with chronic obstructive pulmonary disease, administration of theophylline in combination with short-acting or long-acting inhaled beta2-agonists is more efficacious than is a placebo or each of these drugs used in isolation. METHODS: A systematic review and meta-analysis were carried out. All randomized and double-blind clinical trials found in the literature were selected. RESULTS: A total of eight studies were included. In comparing the effect of theophylline combined with beta2-agonists to that of a placebo, we found a

Induction of polyclonal B cell activation and differentiation by the AIDS retrovirus (HTLV-III/LAV)

International Nuclear Information System (INIS)

Higgins, S.E.; Schnittman, S.M.; Lane, H.C.; Folks, T.; Koenig, S.; Fauci, A.S.

1986-01-01

The immune systems of individuals infected with HTLV-III/LAV are characterized by a profound defect in cellular immunity together with paradoxical polyclonal B cell activation. The present study examined the direct effects of HTLV-III/LAV on B lymphocytes. Peripheral blood B cells from healthy donors were incubated with a variety of HTLV-III/LAV isolates for 1 h and 3 H-thymidine incorporation was measured at multiple time points. Responses ranged from 9000-28,000 cpm and peaked on day 4. This B cell activation was not enhanced by the addition of interleukin-2 to culture, was not synergistic with Staphylococcus aureus Cowan I, was not modulated by the addition of T lymphocytes to culture, and was not associated with B cell transformation. Supernatant Ig could first be detected in virus-activated cultures at day 4, plateaued by day 8, and yielded a mean of 12,500 ng IgG+IgM/ml/50,000 B cells. Thus, HTLV-III/LAV is a potent T cell independent B cell mitogen capable of inducing B cell activation, proliferation, and differentiation comparable in magnitude to that of the most potent B cell activators. This biological property of HTLV-III/LAV may help explain the profound polyclonal B cell activation observed in patients with AIDS and may provide investigators with another probe for investigating the mechanisms of B cell activation

Prevalence and phylogenetic analysis of HTLV-1 in a segregated population in Iran.

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Rafatpanah, Houshang; Torkamani, Mahmood; Valizadeh, Narges; Vakili, Rosita; Meshkani, Baratali; Khademi, Hassan; Gerayli, Sina; Mozhgani, Sayed Hamid Reza; Rezaee, Seyed Abdolrahim

2016-07-01

Human T-lymphotropic virus type 1 (HTLV-1) infection is an important health issue that affects a variety of endemic areas. The Khorasan province, mainly its capital Mashhad in northeastern Iran, was reported to be as one of these endemic regions. Torbat-e Heydarieh, a large city Southwest border to Mashhad with a segregated population was investigated for the prevalence and associated risk factors of HTLV-1 infection in 400 randomly selected individuals. Blood samples were tested for the presence of HTLV-1 antibodies via the ELISA method and then were confirmed by an Immunoblot test. For the presence of HTLV-1 in lymphocytes of infected subjects, PCR was performed on LTR and TAX regions. DNA sequencing of LTR fragment was also carried out to determine the phylogenetic of HTLV-1, using the Maximum likelihood method. HTLV-1 sero-reactivity (sero-prevalence) among the study population was 2% (8/400), of which 1.25% had HTLV-1 provirus in lymphocytes (actual prevalence). HTLV-1 infection was significantly associated with the age, marital status, and history of blood transfusion (P cosmopolitan subtype A. HTLV-1 prevalence in Torbat-e Heydarieh (1.25%) is low comparing to those of both Mashhad (2-3%) and Neishabour (3.5-5%) in the province of Khorasan. Thus, traveling mobility and population mixing such as marriage, bureaucratic affairs, occupation, and economic activities could be the usual routs of HTLV-1 new wave of spreading in this segregated city. © 2015 Wiley Periodicals, Inc.

Soroprevalência e perfil imunofenotípico de células linfóides T em indivíduos soropositivos para o vírus linfotrópico de células T humanas Seroprevalence and immunophenotypic profile of T lymphocyte cells in human T lymphotropic virus seropositive individuals

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Geane F. de Sóuza

2003-03-01

Full Text Available O vírus linfotrópico de células T humana (HTLV é transmitido por transfusões, uso compartilhado de agulhas contaminadas, aleitamento e contato sexual. A prevalência varia de acordo com a região geográfica, grupo racial e população estudada. Cerca de 1% a 4% dos indivíduos infectados desenvolvem algum tipo de doença em decorrência da infecção. É reconhecida a associação entre o HTLV-I e leucemia de células T do adulto e paraparesia espástica tropical (PET. Embora a maioria dos portadores permaneça assintomática, existem evidências de comprometimento funcional da resposta imune celular. Os objetivos desse trabalho foram avaliar a prevalência de soropositividade para HTLV-I/II na população de doadores de sangue do HEMOCE e analisar o perfil imunofenotípico de células linfóides circulantes em 26 doadores soronegativos, 11 soropositivos para HTLV-I sintomáticos e 24 assintomáticos, comparando-os entre si. A prevalência da soropositividade para HTLV-I/II foi de 0,66%. No grupo de indivíduos contaminados pelo HTLV-I houve predomínio do sexo feminino e a maior média de idade. O grupo soropositivo apresentou menor valor de hemoglobina e o grupo sintomático evidenciou contagem de neutrófilos significativamente mais elevada. A contagem média de linfócitos não diferiu entre os grupos. A análise imunofenotípica mostrou que os valores médios de células CD3+, CD4+, CD8+ e relação CD4/CD8 não diferiram significativamente entre os grupos. Uma elevação de células CD8+ no grupo soropositivo foi observada embora não alcançasse significância estatística. A ativação de linfócitos CD8+ está envolvida na patogênese das doenças associadas ao HTLV-I. A definição do valor preditivo desse achado requer confirmação posterior.Human T lymphotropic virus (HTLV can be transmitted by transfusions of cellular blood products, shared use of contaminated syringes, breast feeding and sexual intercourse. The prevalence of

Roles of HTLV-1 basic Zip Factor (HBZ in Viral Chronicity and Leukemic Transformation. Potential New Therapeutic Approaches to Prevent and Treat HTLV-1-Related Diseases

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Jean-Michel Mesnard

2015-12-01

Full Text Available More than thirty years have passed since human T-cell leukemia virus type 1 (HTLV-1 was described as the first retrovirus to be the causative agent of a human cancer, adult T-cell leukemia (ATL, but the precise mechanism behind HTLV-1 pathogenesis still remains elusive. For more than two decades, the transforming ability of HTLV-1 has been exclusively associated to the viral transactivator Tax. Thirteen year ago, we first reported that the minus strand of HTLV-1 encoded for a basic Zip factor factor (HBZ, and since then several teams have underscored the importance of this antisense viral protein for the maintenance of a chronic infection and the proliferation of infected cells. More recently, we as well as others have demonstrated that HBZ has the potential to transform cells both in vitro and in vivo. In this review, we focus on the latest progress in our understanding of HBZ functions in chronicity and cellular transformation. We will discuss the involvement of this paradigm shift of HTLV-1 research on new therapeutic approaches to treat HTLV-1-related human diseases.

Evaluation of the use of real-time PCR for human T cell lymphotropic virus 1 and 2 as a confirmatory test in screening for blood donors Análise do uso da PCR em tempo real para HTLV-1 e 2 como teste confirmatório na triagem de doadores de sangue

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Rafaela Gomes Andrade

2010-04-01

Full Text Available INTRODUCTION: HTLV-1/2 screening among blood donors commonly utilizes an enzyme-linked immunosorbent assay (EIA, followed by a confirmatory method such as Western blot (WB if the EIA is positive. However, this algorithm yields a high rate of inconclusive results, and is expensive. METHODS: Two qualitative real-time PCR assays were developed to detect HTLV-1 and 2, and a total of 318 samples were tested (152 blood donors, 108 asymptomatic carriers, 26 HAM/TSP patients and 30 seronegative individuals. RESULTS: The sensitivity and specificity of PCR in comparison with WB results were 99.4% and 98.5%, respectively. PCR tests were more efficient for identifying the virus type, detecting HTLV-2 infection and defining inconclusive cases. CONCLUSIONS: Because real-time PCR is sensitive and practical and costs much less than WB, this technique can be used as a confirmatory test for HTLV in blood banks, as a replacement for WB.INTRODUÇÃO: A triagem para HTLV-1/2 em doadores de sangue geralmente utiliza imunoensaio enzimático, seguido de um método confirmatório como Western blot quando o EIA é positivo, mas este algoritmo mostra alta taxa de resultados inconclusivos, e elevado custo. MÉTODOS: Dois ensaios qualitativos de PCR em tempo real foram desenvolvidos para detectar HTLV-1 e 2 e um total de 318 amostras foram testadas por PCR (152 de doadores de sangue, 108 de portadores assintomáticos, 26 de pacientes HAM/TSP e 30 de indivíduos soronegativos. RESULTADOS: A sensibilidade e especificidade das PCR em relação aos resultados de WB foram de 99,4% e 98,5%, respectivamente. As PCR foram mais eficientes em identificar o tipo viral, a infecção pelo HTLV-2 e úteis para definir casos inconclusivos. CONCLUSÕES: Por serem sensíveis, práticas e de custo muito inferior ao do WB, as técnicas de PCR em tempo real podem ser usadas como teste confirmatório do HTLV em bancos de sangue, em substituição ao WB.

Prevalence ratio of HTLV-1 in nursing mothers from the state of Paraiba, Northeastern Brazil.

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Pimenta, Flávia C F; Kashima Haddad, Simone; de Medeiros Filho, João G; Costa, Maria José C; Diniz, Margareth F M; Fernandes, Melina P; de Araújo, Lenisio B; Pombo-de-Oliveira, Maria S

2008-08-01

The human T-cell lymphotropic virus type 1 (HTLV-1) was the first human retrovirus known as a direct causal agent of a malignant disease. The vertical route of HTLV transmission is the most frequent pathway of the virus contamination. This study was performed to determine the prevalence ratio of HTLV-1 infection among nursing women. From January 2004 to January 2005, blood samples from 1033 nursing mothers from Paraíba, Brazil were evaluated for HTLV antibodies by ELISA and HTLV-1 viral particles confirmed by polymerase chain reaction (PCR). HTLV antibodies were detected in 7 women. The overall seroprevalence ratio was 0.68% and HTLV-1 viral sequences were confirmed by PCR in 2 women. These preliminary data suggest that HTLV screening should be introduced as a mandatory test before breastfeeding and breast milk donation in Paraíba, Brazil. Additionally, counseling programs would help reduce the prevalence ratio of HTLV-1 infected individuals in this Brazilian region.

Making the invisible visible: searching for human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2 in Brazilian patients with viral hepatitis B and C

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Adele Caterino-de-Araujo

Full Text Available With this study, the authors hope to alert clinicians regarding the presence of human T-cell lymphotropic virus type 1 and 2 (HTLV-1/-2 infections in patients with viral hepatitis B and C in Brazil. HTLV-1/-2 were detected in 1.3% of hepatitis B virus (HBV- and 5.3% of hepatitis C virus (HCV-infected blood samples sent for laboratory viral load measurements. A partial association of human immunodeficiency virus (HIV-1 and HTLV-1/-2 infection was detected in patients with HCV (HIV+, 27.3%, whereas this association was almost 100% in HBV-infected patients (HIV+, all except one. The high prevalence of HTLV-1/-2 infection among patients with hepatitis C was of concern, as HTLV-1/-2 could change the natural course of subsequent liver disease. The authors suggest including HTLV-1/-2 serology in the battery of tests used when following patients with viral hepatitis in Brazil, regardless of the HIV status.

Making the invisible visible: searching for human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2) in Brazilian patients with viral hepatitis B and C.

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Caterino-de-Araujo, Adele; Alves, Fabiana Aparecida; Campos, Karoline Rodrigues; Lemos, Marcílio Figueiredo; Moreira, Regina Célia

2018-02-01

With this study, the authors hope to alert clinicians regarding the presence of human T-cell lymphotropic virus type 1 and 2 (HTLV-1/-2) infections in patients with viral hepatitis B and C in Brazil. HTLV-1/-2 were detected in 1.3% of hepatitis B virus (HBV)- and 5.3% of hepatitis C virus (HCV)-infected blood samples sent for laboratory viral load measurements. A partial association of human immunodeficiency virus (HIV)-1 and HTLV-1/-2 infection was detected in patients with HCV (HIV+, 27.3%), whereas this association was almost 100% in HBV-infected patients (HIV+, all except one). The high prevalence of HTLV-1/-2 infection among patients with hepatitis C was of concern, as HTLV-1/-2 could change the natural course of subsequent liver disease. The authors suggest including HTLV-1/-2 serology in the battery of tests used when following patients with viral hepatitis in Brazil, regardless of the HIV status.

Cytoplasmic Localization of HTLV-1 HBZ Protein: A Biomarker of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP).

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Baratella, Marco; Forlani, Greta; Raval, Goutham U; Tedeschi, Alessandra; Gout, Olivier; Gessain, Antoine; Tosi, Giovanna; Accolla, Roberto S

2017-01-01

HTLV-1 is the causative agent of a severe form of adult T cell leukemia/Lymphoma (ATL), and of a chronic progressive neuromyelopathy designated HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Two important HTLV-1-encoded proteins, Tax-1 and HBZ, play crucial roles in the generation and maintenance of the oncogenic process. Less information is instead available on the molecular and cellular mechanisms leading to HAM/TSP. More importantly, no single specific biomarker has been described that unambiguously define the status of HAM/TSP. Here we report for the first time the finding that HBZ, described until now as an exclusive nuclear protein both in chronically infected and in ATL cells, is instead exclusively localized in the cytoplasm of peripheral blood mononuclear cells (PBMC) from patients suffering of HAM/TSP. Interestingly, at the single cell level, HBZ and Tax-1 proteins are never found co-expressed in the same cell, suggesting the existence of mechanisms of expression uncoupling of these two important HTLV-1 viral products in HAM/TSP patients. Cells expressing cytoplasmic HBZ were almost exclusively found in the CD4+ T cell compartment that was not, at least in a representative HAM/TSP patient, expressing the CD25 marker. Less than 1 percent CD8+ T cells were fond positive for HBZ, while B cells and NK cells were found negative for HBZ in HAM/TSP patients. Our results identify the cytoplasmic localization of HBZ in HAM/TSP patient as a possible biomarker of this rather neglected tropical disease, and raise important hypotheses on the role of HBZ in the pathogenesis of the neuromyelopathy associated to HTLV-1 infection.

Cytoplasmic Localization of HTLV-1 HBZ Protein: A Biomarker of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP.

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Marco Baratella

2017-01-01

Full Text Available HTLV-1 is the causative agent of a severe form of adult T cell leukemia/Lymphoma (ATL, and of a chronic progressive neuromyelopathy designated HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP. Two important HTLV-1-encoded proteins, Tax-1 and HBZ, play crucial roles in the generation and maintenance of the oncogenic process. Less information is instead available on the molecular and cellular mechanisms leading to HAM/TSP. More importantly, no single specific biomarker has been described that unambiguously define the status of HAM/TSP. Here we report for the first time the finding that HBZ, described until now as an exclusive nuclear protein both in chronically infected and in ATL cells, is instead exclusively localized in the cytoplasm of peripheral blood mononuclear cells (PBMC from patients suffering of HAM/TSP. Interestingly, at the single cell level, HBZ and Tax-1 proteins are never found co-expressed in the same cell, suggesting the existence of mechanisms of expression uncoupling of these two important HTLV-1 viral products in HAM/TSP patients. Cells expressing cytoplasmic HBZ were almost exclusively found in the CD4+ T cell compartment that was not, at least in a representative HAM/TSP patient, expressing the CD25 marker. Less than 1 percent CD8+ T cells were fond positive for HBZ, while B cells and NK cells were found negative for HBZ in HAM/TSP patients. Our results identify the cytoplasmic localization of HBZ in HAM/TSP patient as a possible biomarker of this rather neglected tropical disease, and raise important hypotheses on the role of HBZ in the pathogenesis of the neuromyelopathy associated to HTLV-1 infection.

Avaliação da influência do infravermelho e da diatermia por microondas associados ao alongamento passivo no encurtamento dos músculos isquiotibiais - doi:10.5102/ucs.v5i1.416

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Aline Simões Alencastro

2008-11-01

Full Text Available A diatermia por microondas é uma modalidade de aquecimento profundo, e a radiação infravermelha aquece praticamente a epiderme. Em algumas práticas clínicas, para se obter um maior ganho da flexibilidade usam-se técnicas de alongamento associadas ao calor. Este estudo teve como objetivo verificar a influência e as diferenças na utilização dos recursos térmicos de calor profundo e superficial na flexibilidade da musculatura isquiotibial. Dezenove estudantes do Curso de Fisioterapia do Centro Universitário de Brasília foram distribuídos de forma aleatória em três grupos distintos: GC (alongamento muscular passivo, GCS (infravermelho associado ao alongamento passivo e GCP (diatermia por microondas associada ao alongamento. Os resultados foram obtidos através da analise do ângulo poplíteo antes e depois de cada intervenção, relacionando o recurso com o alongamento. Concluiu-se que a aplicação da termoterapia profunda ou superficial auxilia no alongamento da musculatura isquiotibial

Prevalence of HTLV-1/2 infections in Spain: A cross-sectional hospital-based survey.

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Treviño, Ana; García, Juan; de Mendoza, Carmen; Benito, Rafael; Aguilera, Antonio; Ortíz de Lejarazu, Raul; Ramos, José M; Trigo, Matilde; Eirós, Jose M; Rodríguez-Iglesias, Manuel; Torres, Alvaro; Calderón, Enrique; Hernandez, Araceli; Gomez, Cesar; Marcaida, Goizane; Soriano, Vincent

2010-08-01

The presence of antibodies to human T-lymphotropic virus (HTLV) types 1 and 2 was examined in 5742 sera belonging to consecutive adult outpatients attended during June 2008 at 13 different hospitals across Spain. Overall, 58.8% were female. Foreigners represented 8% of the study population. Seven individuals were seropositive for HTLV-2 (overall prevalence 0.12%). No cases of HTLV-1 infection were found. All HTLV-2(+) subjects were Spanish natives, of whom six were coinfected with HIV-1 and five with hepatitis C virus (HCV). Moreover, all but one of the HTLV-2(+) subjects had been intravenous drug users. In summary, this cross-sectional survey suggests that the rate of HTLV infection in Spain is low, and is mostly represented by HTLV-2. Infected individuals are generally Spanish natives with a prior history of intravenous drug use and are coinfected with HIV-1 and/or HCV.

The HBZ gene, a key player in HTLV-1 pathogenesis

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Green Patrick L

2009-08-01

Full Text Available Abstract Human T-cell leukemia virus type 1 (HTLV-1 causes adult T-cell leukemia/lymphoma (ATL and is also associated with a variety of lymphocyte-mediated diseases. The HTLV-1 basic leucine zipper (HBZ gene, found to be consistently expressed in ATL, has recently been the subject of intensive research efforts. In this review, we summarize recent findings about HBZ and discuss its roles and functions not only in the virus life cycle, but also in HTLV-1 disease pathogenesis.

Socio-demographic and epidemiological characteristics associated with human immunodeficiency virus type I (HIV-1 infection in HIV-1-explosed but uninfected individuals, and in HIV-1-infected patients from a southern brasilian population Características sociodemográficas e epidemiológicas associadas com a infecção pelo vírus da imunodeficiência humana tipo 1 (HIV-1 em indivíduos expostos ao HIV-1 mas não infectados e em pacientes infectados pelo HIV-1, provenientes da população da região Sul do Brasil

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Edna Maria Vissoci Reiche

2005-10-01

Full Text Available The ability to control human immunodeficiency virus type 1 (HIV-1 infection and progression of the disease is regulated by host and viral factors. This cross-sectional study describes the socio-demographic and epidemiological characteristics associated with HIV-1 infection in 1,061 subjects attended in Londrina and region, south of Brazil: 136 healthy individuals (Group 1, 147 HIV-1-exposed but uninfected individuals (Group 2, 161 HIV-1-infected asymptomatic patients (Group 3, and 617 patients with AIDS (Group 4. Data were obtained by a standardized questionnaire and serological tests. The age of the individuals ranged from 15.1 to 79.5 years, 54.0% and 56.1% of the Groups 3 and 4 patients, respectively, were men. The major features of groups 2, 3, and 4 were a predominance of education level up to secondary school (55.8%, 60.2% and 62.4%, respectively, sexual route of exposure (88.4%, 87.0% and 82.0%, respectively, heterosexual behavior (91.8%, 75.2% and 83.7%, respectively, and previous sexually transmitted diseases (20.4%, 32.5%, and 38.1%, respectively. The patients with AIDS showed the highest rates of seropositivity for syphilis (25.6%, of anti-HCV (22.3%, and anti-HTLV I/II obtained by two serological screening tests (6.2% and 6.8%, respectively. The results documenting the predominant characteristics for HIV-1 infection among residents of Londrina and region, could be useful for the improvement of current HIV-1 prevention, monitoring and therapeutic programs targeted at this population.Este estudo transversal descreve as principais características sociodemográficas e epidemiológicas associadas com a infecção pelo HIV-1 em 1.061 indivíduos atendidos em Londrina e região, Sul do Brasil: 136 indivíduos saudáveis (Grupo 1, 147 indivíduos expostos ao HIV-1 mas não infectados (Grupo 2, 161 pacientes infectados pelo HIV-1 assintomáticos (Grupo 3 e 617 pacientes com aids (Grupo 4. Os dados foram obtidos pela aplicação de um

Doença de Haff associada ao consumo de carne de Mylossoma duriventre (pacu-manteiga

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Oswaldo Tolesani Junior

2013-12-01

Full Text Available A rabdomiólise associada à doença de Haff é correlacionada com a ingestão de certos peixes e crustáceos de água doce, sendo causada por uma toxina não identificada. Relatamos o caso de um paciente que apresentou rabdomiólise cerca de 2 horas após ingerir o peixe de água doce Mylossoma duriventre (pacu-manteiga cerca de 3 anos após o relato de um surto de doença de Haff em Manaus.

Molecular insights on analogs of HIV PR inhibitors toward HTLV-1 PR through QM/MM interactions and molecular dynamics studies: comparative structure analysis of wild and mutant HTLV-1 PR.

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Selvaraj, Chandrabose; Singh, Poonam; Singh, Sanjeev Kumar

2014-12-01

Retroviruses HTLV-1 and HIV-1 are the primary causative agents of fatal adult T-cell leukemia and acquired immune deficiency syndrome (AIDS) disease. Both retroviruses are similar in characteristics mechanism, and it encodes for protease that mainly involved in the viral replication process. On the basis of the therapeutic success of HIV-1 PR inhibitors, the protease of HTLV-1 is mainly considered as a potential target for chemotherapy. At the same time, structural similarities in both enzymes that originate HIV PR inhibitors can also be an HTLV-1 PR inhibitor. But the expectations failed because of rejection of HIV PR inhibitors from the HTLV-1 PR binding pocket. In this present study, the reason for the HIV PR inhibitor rejection from the HTLV-1 binding site was identified through sequence analysis and molecular dynamics simulation method. Functional analysis of M37A mutation in HTLV PR clearly shows that the MET37 specificity and screening of potential inhibitors targeting MET37 is performed by using approved 90% similar HIV PR inhibitor compounds. From this approach, we report few compounds with a tendency to accept/donate electron specifically to an important site residue MET37 in HTLV-1 PR binding pocket. Copyright © 2014 John Wiley & Sons, Ltd.

A gravidade da cárie está associada à desnutrição proteico-calórica em pré-escolares?

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Cecilia Claudia Costa Ribeiro

2014-03-01

Full Text Available Avaliou-se se gravidade da cárie está associada à desnutrição proteico-calórica em pré-escolares. Foi realizado um estudo seccional aninhado a uma coorte retrospectiva de 625 crianças entre 24 -71 meses, em São Luís, Maranhão. Um modelo hierarquizado foi avaliado em cinco níveis: 1º Variáveis socioeconômicas (classe econômica, escolaridade materna, cor da pele; 2º Variáveis de acesso; 3º Baixo peso ao nascer e amamentação exclusiva; 4º Peso para altura aos 12 meses e 5º Gravidade da cárie e níveis de albumina (Alb. O desfecho foi desnutrição proteico-calórica (z escore altura para idade < -2. A prevalência do desfecho foi de 5,0 %, e da cárie foi de 32%. As variáveis do primeiro nível não foram associadas ao desfecho, porém a classe econômica foi mantida até o modelo final. As variáveis do segundo e do terceiro níveis não foram significativas. No quarto nível, peso para altura aos 12 meses não foi significativo, porém foi mantido até o modelo final. No último nível, os níveis de Alb não foram associados ao desfecho e a gravidade da doença cárie foi positivamente associada com desnutrição proteico-calórica em pré-escolares. A associação da gravidade da cárie com déficit antropométrico sinaliza que a saúde bucal deva ser parte importante nas políticas públicas de atenção à infância.

Immunological profile of HTLV-1-infected patients associated with infectious or autoimmune dermatological disorders.

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Jordana Grazziela Alves Coelho-dos-Reis

Full Text Available In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4(+HLA-DR(+, CD8(+ T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-α/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection.

Surface Transmission or Polarized Egress? Lessons Learned from HTLV Cell-to-Cell Transmission

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Jin, Jing; Sherer, Nathan; Mothes, Walther

2010-01-01

Commentary on Pais-Correia, A.M.; Sachse, M.; Guadagnini, S.; Robbiati, V.; Lasserre, R.; Gessain, A.; Gout, O.; Alcover, A.; Thoulouze, M.I. Biofilm-like extracellular viral assemblies mediate HTLV-1 cell-to-cell transmission at virological synapses. Nat. Med. 2010, 16, 83–89. PMID:21994650

Ubiquitination and sumoylation of the HTLV-2 Tax-2B protein regulate its NF-κB activity: a comparative study with the HTLV-1 Tax-1 protein

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2012-01-01

Background Retroviruses HTLV-1 and HTLV-2 have homologous genomic structures but differ significantly in pathogenicity. HTLV-1 is associated with Adult T cell Leukemia (ATL), whereas infection by HTLV-2 has no association with neoplasia. Transformation of T lymphocytes by HTLV-1 is linked to the capacity of its oncoprotein Tax-1 to alter cell survival and cell cycle control mechanisms. Among these functions, Tax-1-mediated activation of cellular gene expression via the NF-κB pathway depends on Tax-1 post-translational modifications by ubiquitination and sumoylation. The Tax-2 protein of HTLV-2B (Tax-2B) is also modified by ubiquitination and sumoylation and activates the NF-κB pathway to a level similar to that of Tax-1. The present study aims to understand whether ubiquitination and sumoylation modifications are involved in Tax-2B-mediated activation of the NF-κB pathway. Results The comparison of Tax-1 and Tax-2B lysine to arginine substitution mutants revealed conserved patterns and levels of ubiquitination with notable difference in the lysine usage for sumoylation. Neither Tax-1 nor Tax-2B ubiquitination and sumoylation deficient mutants could activate the NF-κB pathway and fusion of ubiquitin or SUMO-1 to the C-terminus of the ubiquitination and sumoylation deficient Tax-2B mutant strikingly restored transcriptional activity. In addition, ubiquitinated forms of Tax-2B colocalized with RelA and IKKγ in prominent cytoplasmic structures associated with the Golgi apparatus, whereas colocalization of Tax-2B with the RelA subunit of NF-κB and the transcriptional coactivator p300 in punctate nuclear structures was dependent on Tax-2B sumoylation, as previously observed for Tax-1. Conclusions Both Tax-1 and Tax-2 activate the NF-κB pathway via similar mechanisms involving ubiquitination and sumoylation. Therefore, the different transforming potential of HTLV-1 and HTLV-2 is unlikely to be related to different modes of activation of the canonical NF-κB pathway

Seroprevalence of HTLV1,2 Virus Among Injection Drug Addicts in Isfahan, 2007-2008

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Sh Farzaneh

2009-10-01

Full Text Available Introduction: Human T-cell lymphotropic virus (HTLV, is a member of the retroviridae family. Infection with this virus leads to adult T-cell leukemia (ATL and tropical spastic paraparesis (TSP. HTLV is endemic in Japan, parts of central Africa, Caribbean basin and Iran (Mashhad. Transmission routes of HTLV are believed to be from mother to child, especially during breastfeeding, sexual contact, and through blood transfusion or needle sharing. Considering the risk of HTLV infection among injection drug addicts, the authors evaluated the seroprevalence of HTLV1,2 infection among injection drug addicts in Isfahan Methods: This cross sectional study included a total of 150 injection drug users who were recruited at the drug abuse treatment clinic and the infectious diseases department of Alzahra university Hospital. Participants were interviewed using a structured questionnaire. Epidemiologic data were recorded and their blood samples were tested for HBs Ag and antibodies against HTLV1,2, human immunodeficiency virus (HIV and hepatitis C (HCV by Elisa method . Results were analyzed by SPSS software version 13. Results: Seroprevalence of HTLV1,2, HBV(HBs Ag, HCV and HIV was 2.7%, 1.3% 23.3% and 2.7%, respectively. Some of the subjects were co infected with two viruses. One patient was infected with both HCV Ab and HBs Ag , while another was positive for HIV Ab plus HBs Ag . Three were co infected with HCV and HIV. Among those with HTLV1,2, only one was HCV Ab positive. Only in one person with HTLV1,2 Ab had a positive history of blood transfusion. Conclusion: This study shows that this virus is present in injection drug users community of Isfahan and can be a potential source for transmission. But proposal of screening of HTLV1,2 among injection drug users in Isfahan requires further investigations.

Immunization against HTLV-I with chitosan and tri-methylchitosan nanoparticles loaded with recombinant env23 and env13 antigens of envelope protein gp46.

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Amirnasr, Maryam; Fallah Tafti, Tannan; Sankian, Mojtaba; Rezaei, Abdorrahim; Tafaghodi, Mohsen

2016-08-01

To prevent the spread of HTLV-I (Human T-lymphotropic virus type 1), a safe and effective vaccine is required. To increase immune responses against the peptide antigens can be potentiated with polymer-based nanoparticles, like chitosan (CHT) and trimethylchitosan (TMC), as delivery system/adjuvant. CHT and TMC nanoparticles loaded with recombinant proteins (env23 & env13) of gp46 were prepared by direct coating of antigens with positively charged polymers. The size of CHT and TMC nanoparticles (NPs) loaded with each antigen was about 400 nm. The physical stability of NPs was followed for 4 weeks. Both formulations showed to be stable for about 15 days. The immunogenicity of NPs loaded with antigens was studied after nasal and subcutaneous immunization in mice. Three immunizations (7.5 μg antigen) were performed with 2 weeks intervals. Two weeks after the last booster dose, sera IgG subtypes were measured. After subcutaneous administration, for both nanoparticulate antigens, serum IgG1 and IgGtotal levels were higher than antigen solution (P nanoparticles showed good immunoadjuvant potential. Env23 antigen was a better candidate for vaccination against HTLV-I, as it induced higher cellular immune responses, compared with env13. Copyright © 2016 Elsevier Ltd. All rights reserved.

Osteonecrose dos maxilares associada ao uso de bisfosfonatos: importante complicação do tratamento oncológico Bisphosphonate-associated jaws osteonecrosis: an important complication of oncology treatment

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Marco Antonio T. Martins

2009-02-01

Full Text Available Os bisfosfonatos são um grupo de medicamentos utilizados no tratamento de doenças malignas metastáticas e em outras doenças ósseas como osteoporose e doença de Paget. A despeito dos seus benefícios, uma importante complicação denominada de osteonecrose dos maxilares vem sendo observada nos pacientes usuários crônicos dos bisfosfonatos que se caracteriza clinicamente por exposições ósseas na região maxilofacial persistente, acompanhadas de osteomielite, geralmente sintomáticas e cujo tratamento é complexo. Este estudo tem por objetivo revisar a literatura sobre a osteonecrose associada ao uso dos bisfosfonatos, em especial, em oncologia, no período de 2003 a 2008. Serão apresentados e discutidos os fatores de risco, aspectos etiopatogênicos, clínicos, imagenológicos, terapêuticos e preventivos desta doença. Devido à dificuldade de tratamento da osteonecrose associada aos bisfosfonatos, o foco deve ser a prevenção, sendo o ideal a eliminação de quadros infecciosos orais antes da terapia com os bisfosfonatos ter sido iniciada e minimizar traumas em boca após o uso destes medicamentos.Bisphosphonates are drugs used in the treatment of malignant metastatic diseases and in other bone lesions such as osteoporosis and Paget´s disease. Besides their benefits, jaw osteonecrosis, an important side effect, has been observed in long-term users of these drugs. Jaw osteonecrosis is clinically characterized by prolonged maxillary and mandible bone exposure accompanied by osteomyelitis. These lesions are usually symptomatic and difficult to treat. This study has the objective of reviewing publications from 2003 to 2008 about bisphosphonate-associated jaw osteonecrosis, in particular in relation to oncology. Risk factors, and etiopathological, clinical, radiographic, therapeutic, and preventive aspects of this condition are presented and discussed. Due to the difficulty to treat this disease, the focus must be prevention, with the

Biophysical analysis of HTLV-1 particles reveals novel insights into particle morphology and Gag stochiometry

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Fogarty Keir H

2010-09-01

Full Text Available Abstract Background Human T-lymphotropic virus type 1 (HTLV-1 is an important human retrovirus that is a cause of adult T-cell leukemia/lymphoma. While an important human pathogen, the details regarding virus replication cycle, including the nature of HTLV-1 particles, remain largely unknown due to the difficulties in propagating the virus in tissue culture. In this study, we created a codon-optimized HTLV-1 Gag fused to an EYFP reporter as a model system to quantitatively analyze HTLV-1 particles released from producer cells. Results The codon-optimized Gag led to a dramatic and highly robust level of Gag expression as well as virus-like particle (VLP production. The robust level of particle production overcomes previous technical difficulties with authentic particles and allowed for detailed analysis of particle architecture using two novel methodologies. We quantitatively measured the diameter and morphology of HTLV-1 VLPs in their native, hydrated state using cryo-transmission electron microscopy (cryo-TEM. Furthermore, we were able to determine HTLV-1 Gag stoichiometry as well as particle size with the novel biophysical technique of fluorescence fluctuation spectroscopy (FFS. The average HTLV-1 particle diameter determined by cryo-TEM and FFS was 71 ± 20 nm and 75 ± 4 nm, respectively. These values are significantly smaller than previous estimates made of HTLV-1 particles by negative staining TEM. Furthermore, cryo-TEM reveals that the majority of HTLV-1 VLPs lacks an ordered structure of the Gag lattice, suggesting that the HTLV-1 Gag shell is very likely to be organized differently compared to that observed with HIV-1 Gag in immature particles. This conclusion is supported by our observation that the average copy number of HTLV-1 Gag per particle is estimated to be 510 based on FFS, which is significantly lower than that found for HIV-1 immature virions. Conclusions In summary, our studies represent the first quantitative biophysical

HTLV-3 infection and AIDS: risk of spread by heterosexual contact.

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Craske, J

1986-02-01

This article reviews current research evidence on the natural history, epidemiology, and clinical features of acquired immunodeficiency disease (AIDS) and presents guidelines for controlling the sexual transmission of human lymphotropic virus type III (HTLV-III) infection. The rapid spread of HTLV-III infection through homosexual communities in the US and Europe and its association with promiscuity initially obscured the fact that heterosexual transmission is also a significant risk factor for infection. Public health workers and epidemiologists are examining which sexual practices are most associated with the transmission of HTLV-III infection. Case-control studies in homosexuals have suggested that promiscuity, passive anal intercourse, and other sexual practices associated with rectal trauma and bleeding correlate with infection. Similar studies involving heterosexuals have not been conducted. However, the following guidelines have been proposed for couples where 1 partner has been found to be positive for HTLV-III antibodies: 1) sexual partners should be confined to established relationships; 2) anal intercourse should be avoided, even if the male uses a condom; 3) no oral contact with semen should occur; 4) if vaginal intercourse is practiced, the use of condom is essential; and 5) the only practices that are free from risk of infection are mutual masturbation and hand caresses. Since a high proportion of children of women with HTLV-III develop severe immunodeficiency, it is undesirable for women who are HTLV-III antibody positive to become pregnant. Furthermore, there is evidence that women who are HTLV-III antibody positive are more likely to develop AIDS if they become pregnant. A reliable method of permanent or reversible contraception is recommended for these women. Finally, men who are antibody positive should not donate sperm to a sperm bank.

Sequence variation of functional HTLV-II tax alleles among isolates from an endemic population: lack of evidence for oncogenic determinant in tax.

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Hjelle, B; Chaney, R

1992-02-01

Human T-cell leukemia-lymphoma virus type II (HTLV-II) has been isolated from patients with hairy cell leukemia (HCL). We previously described a population with longstanding endemic HTLV-II infection, and showed that there is no increased risk for HCL in the affected groups. We thus have direct evidence that the endemic form(s) of HTLV-II cause HCL infrequently, if at all. By comparison, there is reason to suspect that the viruses isolated from patients with HCL had an etiologic role in the disease in those patients. One way to reconcile these conflicting observations is to consider that isolates of HTLV-II might differ in oncogenic potential. To determine whether the structure of the putative oncogenic determinant of HTLV-II, tax2, might differ in the new isolates compared to the tax of the prototype HCL isolate, MO, four new functional tax cDNAs were cloned from new isolates. Sequence analysis showed only minor (0.9-2.0%) amino acid variation compared to the published sequence of MO tax2. Some codons were consistently different from published sequences of the MO virus, but in most cases, such variations were also found in each of two tax2 clones we isolated from the MO T-cell line. These variations rendered the new clones more similar to the tax1 of the pathogenic virus HTLV-I. Thus we find no evidence that pathologic determinants of HTLV-II can be assigned to the tax gene.

TRANSMISIÓN VERTICAL DE HTLV-1 EN EL PERÚ

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Villaverde, Jorge Alarcón; Romaní, Franco Romaní; Torres, Silvia Montano; Zunt, Joseph R.

2012-01-01

La infección por el virus linfotrópico humano de células T tipo 1 (HTLV-1) ha sido descrita en muchas áreas del mundo, como en los países del Caribe, Japón, África, Oceanía y en Sudamérica. En la presente revisión definimos la endemicidad del HTLV-1 en el país, planteando cuatro criterios epidemiológicos. Luego discutimos el tema central de la revisión: la transmisión vertical del HTLV-1, que en nuestro país sería uno de los principales mecanismos de transmisión. Dentro del desarrollo de este aspecto en particular, presentamos una estimación de la tasa de transmisión vertical y los factores de riesgo asociados con la transmisión vertical sobre la base de una revisión exhaustiva de estudios nacionales y extranjeros. Con esta revisión pretendemos dar una primera aproximación al estudio de la trasmisión vertical de HTLV-1, un aspecto poco estudiado en nuestro medio. PMID:21537777

HTLV-1 Tax protein recruitment into IKKε and TBK1 kinase complexes enhances IFN-I expression.

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Diani, Erica; Avesani, Francesca; Bergamo, Elisa; Cremonese, Giorgia; Bertazzoni, Umberto; Romanelli, Maria Grazia

2015-02-01

The Tax protein expressed by human T-cell leukemia virus type 1 (HTLV-1) plays a pivotal role in the deregulation of cellular pathways involved in the immune response, inflammation, cell survival, and cancer. Many of these effects derive from Tax multiple interactions with host factors, including the subunits of the IKK-complex that are required for NF-κB activation. IKKɛ and TBK1 are two IKK-related kinases that allow the phosphorylation of interferon regulatory factors that trigger IFN type I gene expression. We observed that IKKɛ and TBK1 recruit Tax into cellular immunocomplexes. We also found that TRAF3, which regulates cell receptor signaling effectors, forms complexes with Tax. Transactivation analyses revealed that expression of Tax, in presence of IKKɛ and TBK1, enhances IFN-β promoter activity, whereas the activation of NF-κB promoter is not modified. We propose that Tax may be recruited into the TBK1/IKKɛ complexes as a scaffolding-adaptor protein that enhances IFN-I gene expression. Copyright © 2014 Elsevier Inc. All rights reserved.

Genetic characterization and phylogeny of human T-cell lymphotropic virus type I from Chile.

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Ramirez, E; Cartier, L; Villota, C; Fernandez, J

2002-03-20

Infection with Human T-Cell Lymphotropic Virus type I (HTLV-I) have been associated with the development of the HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Phylogenetic analyses of HTLV-I isolates have revealed that HTLV-I can be classified into three major groups: the Cosmopolitan, Central African and Melanesian. In the present study, we analyzed the tax, 5' ltr, gag, pol, and env sequences of proviruses of PBMC from ten HAM/TSP patients to investigate the phylogenetic characterization of HTLV-I in Chilean patients. HTLV-I provirus in PBMC from ten Chilean patients with HAM/TSP were amplified by PCR using primers of tax, 5' ltr, gag, pol, and env genes. Amplified products of the five genes were purified and nucleotide sequence was determined by the dideoxy termination procedure. DNA sequences were aligned with the CLUSTAL W program. The results of this study showed that the tax, 5' ltr, gag, pol, and env gene of the Chilean HTLV-I strains had a nucleotide homology ranged from 98.1 to 100%, 95 to 97%, 98.9 to 100%, 94 to 98%, and 94.2 to 98.5% respect to ATK-1 clone, respectively. According to molecular phylogeny with 5' ltr gene, the Chilean HTLV-I strains were grouped with each other suggesting one cluster included in Transcontinental subgroup.

Clinical and immunological features of patients with atopy and concomitant HTLV-1 infection

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F.P. Gaspar-Sobrinho

2010-12-01

Full Text Available Human T-cell lymphotropic virus type 1 (HTLV-1 induces an exacerbated type 1 immune response characterized by high spontaneous IFN-γ and TNF-α production. Allergic rhinitis and asthma are associated with the type 2 immune response, with elevated secretion of IL-4 and IL-5. The aim of this study was to characterize the immune response in atopic HTLV-1 carriers. The cytokine profile of atopic HTLV-1 carriers (N = 10; all females was compared with that of non-atopic HTLV-1 carriers (N = 14; 9 females and 5 males. Mean patient age of atopic and non-atopic groups was 45 ± 8 and 38 ± 11 years, respectively. All atopic HTLV-1 carriers had rhinitis with or without asthma and a skin prick test positive for Dermatophagoides pteronyssinus antigen 1 (Derp-1. There was no difference in cytokine levels between the two groups in unstimulated peripheral blood mononuclear cell cultures. In cultures stimulated with Derp-1, IFN-γ levels tended to be higher (P = 0.06 and IL-5 levels were higher (P = 0.02 in atopic HTLV-1 patients than in non-atopic subjects. In contrast, IL-10 was lower (P = 0.004 in atopic than in non-atopic HTLV-1-infected subjects. This study shows that HTLV-1 infection with an exaggerated type 1 immune response does not prevent atopy. In this case, the exacerbated type 1 and type 2 immune responses were due to a lack of IL-10 production, a cytokine that plays an important role in down-modulating type 1 and type 2 immune responses and in preventing the development of chronic inflammatory diseases.

HTLV-1 specific CD8+ T cell function augmented by blockade of 2B4/CD48 interaction in HTLV-1 infection.

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Chibueze Chioma Ezinne

Full Text Available CD8+ T cell response is important in the response to viral infections; this response though is regulated by inhibitory receptors. Expression of inhibitory receptors has been positively correlated with CD8+ T cell exhaustion; the consequent effect of simultaneous blockade of these inhibitory receptors on CD8+ T cell response in viral infections have been studied, however, the role of individual blockade of receptor-ligand pair is unclear. 2B4/CD48 interaction is involved in CD8+T cell regulation, its signal transducer SAP (signaling lymphocyte activation molecule (SLAM-associated protein is required for stimulatory function of 2B4/CD244 on lymphocytes hence, we analyzed 2B4/CD244 (natural killer cell receptor and SAP (signaling lymphocyte activation molecule(SLAM-associated protein on total CD8+ and HTLV-1 specific CD8+T cells in HTLV-1 infection and the effect of blockade of interaction with ligand CD48 on HTLV-1 specific CD8+ T cell function. We observed a high expression of 2B4/CD244 on CD8+ T cells relative to uninfected and further upregulation on HTLV-1 specific CD8+ T cells. 2B4+ CD8+ T cells exhibited more of an effector and terminally differentiated memory phenotype. Blockade of 2B4/CD48 interaction resulted in improvement in function via perforin expression and degranulation as measured by CD107a surface mobilization on HTLV-1 specific CD8+ T cells. In the light of these findings, we thus propose an inhibitory role for 2B4/CD48 interaction on CD8+T cell function.

Erosividade das chuvas associada a períodos de retorno e probabilidade de ocorrência no estado do Rio de Janeiro

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Roriz Luciano Machado

2013-04-01

Full Text Available O conhecimento da erosividade das chuvas associada à probabilidade de ocorrência e ao período de retorno pode contribuir para o planejamento conservacionista de uma região, em médio e longo prazo. A fim de gerar informações para melhor utilizar modelos e controle da erosão, dados de chuvas de 30 séries pluviográficas e pluviométricas, abrangendo 25 municípios, entre 1933 e 2006, foram estudados quanto à adequação das séries e do cálculo da probabilidade de ocorrência teórica (P e período de retorno (T da erosividade das chuvas (EI30 e KE>25, para o Estado do Rio de Janeiro. Foi feita a espacialização do potencial erosivo associado aos períodos de retorno de 2, 5, 10, 20, 50 e 100 anos para todo o Estado. A erosividade anual média (EI30 ou fator R da USLE para qualquer localidade no Estado do Rio de Janeiro pode ser igualada ou superada pelo menos uma vez, em média, em um período de 1,8 a 2,1 anos, com faixa de 48,5 a 54,9 % de probabilidade de ocorrência teórica. As localidades que apresentam maior erosividade associada aos períodos de retorno estão situadas nas mesorregiões Metropolitanas e em partes das mesorregiões Sul e Centro Fluminense. Foi possível identificar de oito a 12 regiões homogêneas, quanto à distribuição espacial da erosividade associada aos períodos de retorno de dois para 100 anos no Estado. De modo geral, a maior variação da distribuição espacial da erosividade apresenta-se na faixa de período de retorno de dois a cinco anos.

HTLV-1 antibodies in serum and cerebrospinal fluid in tropical spastic paraparesis in Brazil

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A. Spina-França

1990-12-01

Full Text Available HTLV-l antibodies were investigated in serum and in CSF of 150 patients with neurologic disorders mainly myelopathies. The patients were considered into three groups according to the possible relationship of their disease to the presence of HTLV-l antibodies: no relationship risk (control group, occasional risk group, and possible risk group. In this latter are 56 patients with crural spastic paraparesis or paraplegia of unknown etiology (SP. HTLV-l antibodies were tested by the passive particle-agglutination method for anti-ATLA antibody detection. The search was negative in all patients of the control group, and positive (serum and/or CSF in 16.5% of the patients from the second group and in 55.4% of the SP patients group. Clinical patterns in SP cases with HTLV-l antibodies were those of tropical spastic paraparesis (TSP. CSF patterns considered (cytology, protein content and gamma-globulins rate were different between TSP group with HTLV-l antibodies in CSF and SP group with no HTLV-l antibodies detection either in serum or in CSF. The difference was significant. Results of this investigation confirm the high incidence of TSP in Brazil, and bring additional indication for searching HTLV-l antibodies in the CSF.

Comprehensive Antiretroviral Restriction Factor Profiling Reveals the Evolutionary Imprint of the ex Vivo and in Vivo IFN-β Response in HTLV-1-Associated Neuroinflammation.

Science.gov (United States)

Leal, Fabio E; Menezes, Soraya Maria; Costa, Emanuela A S; Brailey, Phillip M; Gama, Lucio; Segurado, Aluisio C; Kallas, Esper G; Nixon, Douglas F; Dierckx, Tim; Khouri, Ricardo; Vercauteren, Jurgen; Galvão-Castro, Bernardo; Saraiva Raposo, Rui Andre; Van Weyenbergh, Johan

2018-01-01

HTLV-1-Associated Myelopathy (HAM/TSP) is a progressive neuroinflammatory disorder for which no disease-modifying treatment exists. Modest clinical benefit from type I interferons (IFN-α/β) in HAM/TSP contrasts with its recently identified IFN-inducible gene signature. In addition, IFN-α treatment in vivo decreases proviral load and immune activation in HAM/TSP, whereas IFN-β therapy decreases tax mRNA and lymphoproliferation. We hypothesize this "IFN paradox" in HAM/TSP might be explained by both cell type- and gene-specific effects of type I IFN in HTLV-1-associated pathogenesis. Therefore, we analyzed ex vivo transcriptomes of CD4 + T cells, PBMCs and whole blood in healthy controls, HTLV-1-infected individuals, and HAM/TSP patients. First, we used a targeted approach, simultaneously quantifying HTLV-1 mRNA (HBZ, Tax), proviral load and 42 host genes with known antiretroviral (anti-HIV) activity in purified CD4 + T cells. This revealed two major clusters ("antiviral/protective" vs. "proviral/deleterious"), as evidenced by significant negative (TRIM5/TRIM22/BST2) vs. positive correlation (ISG15/PAF1/CDKN1A) with HTLV-1 viral markers and clinical status. Surprisingly, we found a significant inversion of antiretroviral activity of host restriction factors, as evidenced by opposite correlation to in vivo HIV-1 vs. HTLV-1 RNA levels. The anti-HTLV-1 effect of antiviral cluster genes was significantly correlated to their adaptive chimp/human evolution score, for both Tax mRNA and PVL. Six genes of the proposed antiviral cluster underwent lentivirus-driven purifying selection during primate evolution (TRIM5/TRIM22/BST2/APOBEC3F-G-H), underscoring the cross-retroviral evolutionary imprint. Secondly, we examined the genome-wide type I IFN response in HAM/TSP patients, following short-term ex vivo culture of PBMCs with either IFN-α or IFN-β. Microarray analysis evidenced 12 antiretroviral genes (including TRIM5α/TRIM22/BST2) were significantly up-regulated by IFN

Antibodies to the human T-cell lymphoma/leukemia virus type I in Dutch haemophiliacs

NARCIS (Netherlands)

Goudsmit, J.; Miedema, F.; Breederveld, C.; Terpstra, F.; Roos, M.; Schellekens, P.; Melief, C.

1986-01-01

95 Dutch haemophiliacs were tested for antibodies to membrane antigens on cells infected with human T-cell leukemia virus type I (HTLV-I-MA) by indirect immunofluorescence and to purified HTLV-I by enzyme-linked immunosorbent assay. Antibodies to HTLV-I-MA were present in 8 of 95 (8%) haemophiliacs,

Relative frequency of Human T-cell Lymphotropic Virus I/II in HIV/AIDS patients

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Mohsen Meidani

2014-01-01

Conclusion: In our survey, relative frequency of HTLV-I/II was 1.8% in HIV+ patients. This study reveals that relative frequency of HTLV-I/II in HIV positive patients is considerable but determining the need for screening of HTLV-I/II requires further investigation.

Evidence of a higher prevalence of HPV infection in HTLV-1-infected women: a cross-sectional study

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Sônia Sampaio Lôpo

2012-06-01

Full Text Available INTRODUCTION:HTLV-1 infection increases susceptibility to other infections. Few studies have addressed the co-infection between HPV and HTLV-1 and the immune response involved in this interaction. The aim of this study was to determine the prevalence of cervical HPV infection in HTLV-1-infected women and to establish the risk factors involved in this co-infection. METHODS: A cross-sectional study was carried out in Salvador, Brazil, between September 2005 and December 2008, involving 50 HTLV-1-infected women from the HTLV Reference Center and 40 uninfected patients from gynecological clinic, both at the Bahiana School of Medicine. HPV infection was assessed using hybrid capture. HTLV-1 proviral load was quantified using real-time polymerase chain reaction (PCR. RESULTS: The mean age of HTLV-1-infected women (38 ± 10 years was similar to that of the control group (36 ± 13 years. The prevalence of HPV infection was 44% in the HTLV-1-infected group and 22.5% in uninfected women (p = 0.03. HTLV-1-infected women had lower mean age at onset of sexual life (17 ± 3 years versus 19 ± 3 years; p = 0.03 and greater number of lifetime partners compared with the control group (4 ± 3 versus 2 ± 1; p < 0.01. In the group of HTLV-1-infected patients, there was neither difference in HTLV-1 proviral load between HPV-infected women and the uninfected. CONCLUSIONS: The prevalence of HPV infection was higher in HTLV-1-infected women. Further studies should be performed to evaluate the progression of this co-infection.

New Insights into HTLV-1 Particle Structure, Assembly, and Gag-Gag Interactions in Living Cells

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Jolene L. Johnson

2011-06-01

Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 has a reputation for being extremely difficult to study in cell culture. The challenges in propagating HTLV-1 has prevented a rigorous analysis of how these viruses replicate in cells, including the detailed steps involved in virus assembly. The details for how retrovirus particle assembly occurs are poorly understood, even for other more tractable retroviral systems. Recent studies on HTLV-1 using state-of-the-art cryo-electron microscopy and fluorescence-based biophysical approaches explored questions related to HTLV-1 particle size, Gag stoichiometry in virions, and Gag-Gag interactions in living cells. These results provided new and exciting insights into fundamental aspects of HTLV-1 particle assembly—which are distinct from those of other retroviruses, including HIV-1. The application of these and other novel biophysical approaches promise to provide exciting new insights into HTLV-1 replication.

Human parvovirus 4 prevalence among HTLV-1/2 infected individuals in Brazil.

Science.gov (United States)

Slavov, Svetoslav Nanev; Otaguiri, Katia Kaori; Smid, Jerusa; de Oliveira, Augusto Cesar Penalva; Casseb, Jorge; Martinez, Edson Zangiacomi; Covas, Dimas Tadeu; Eis-Hübinger, Anna Maria; Kashima, Simone

2017-04-01

Human parvovirus 4 (PARV4), a Tetraparvovirus, has been largely found in HIV, HBV, or HCV infected individuals. However, there is no data for the PARV4 occurrence in Human T-lymphotropic virus (HTLV-1/2) infected individuals, despite similar transmission routes. Here, PARV4 viremia was evaluated in 130 HTLV infected patients under care of a Brazilian HTLV outpatient clinic. PARV4 viremia was detected in 6.2% of the HTLV-1 infected patients. Most PARV4 positives showed no evidence for parenterally transmitted infections. It is suggested that in Brazil, transmission routes of PARV4 are more complex than in Europe and North America and resemble those in Africa. J. Med. Virol. 89:748-752, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Compartilhamento do conhecimento em incubadoras brasileiras associadas à ANPROTEC

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Ilse Maria Beuren

2007-06-01

Full Text Available Este artigo objetiva descrever o processo de compartilhamento do conhecimento em incubadoras brasileiras associadas à Associação Nacional de Entidades Promotoras de Empreendimentos de Tecnologias Avançadas (Anprotec. Para tanto, primeiramente, discorreu-se sobre a gestão do conhecimento, o compartilhamento do conhecimento nas organizações e a conceituação de incubadoras de empresas. Em seguida, procedeu-se ao estudo de levantamento ou survey, analisando o compartilhamento do conhecimento em 33 incubadoras brasileiras associadas à Anprotec, conforme relação disponível em seu site. Os dados foram coletados por meio de questionários enviados por correio eletrônico, com um retorno de 18%. Os resultados da pesquisa indicaram que há uma preocupação em gerar, difundir e, sobretudo, compartilhar informações e conhecimentos nas incubadoras estudadas. Quanto às formas de compartilhamento analisadas, verificou-se que as palestras, as reuniões, os encontros e as discussões são os eventos que apresentam maior grau de importância nas incubadoras. Por fim, observou-se que as incubadoras buscam pessoas especializadas para a realização de palestras ou seminários, bem como incentivam a participação dos empregados em encontros regionais e nacionais.

Bidirectional enhancing activities between human T cell leukemia-lymphoma virus type I and human cytomegalovirus in human term syncytiotrophoblast cells cultured in vitro.

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Tóth, F D; Aboagye-Mathiesen, G; Szabó, J; Liu, X; Mosborg-Petersen, P; Kiss, J; Hager, H; Zdravkovic, M; Andirkó, I; Aranyosi, J

1995-12-01

The syncytiotrophoblast layer of the human placenta has an important role in limiting transplacental viral spread from mother to fetus. Human cytomegalovirus (HCMV) is capable of establishing a latent infection in syncytiotrophoblast cells, with restriction of gene expression to immediate-early and early proteins. We analyzed the extent of replication of human T cell leukemia-lymphoma virus type I (HTLV-I) in human term syncytiotrophoblasts infected with HTLV-I alone or coinfected with HTLV-I and HCMV. Although syncytiotrophoblasts could be infected with cell-free HTLV-I, no viral protein expression was found in the singly infected cells. On the contrary, coinfection of the cells with HTLV-I and HCMV resulted in simultaneous replication of both viruses. Bidirectional enhancing activities between HTLV-I and HCMV were mediated primarily by the Tax and immediate-early proteins, respectively. The stimulatory effect of HTLV-I Tax on HCMV replication appeared to be mediated partly by tumor necrosis factor beta and transforming growth factor beta-1. We observed formation of pseudotypes with HTLV-I nucleocapsids within HCMV envelopes, whereas HCMV was not pseudotyped by HTLV-I envelopes in dually infected syncytiotrophoblast cells. Our data suggest that in vivo dual infection of syncytiotrophoblast cells with HTLV-I and HCMV may facilitate the transplacental transmission of both viruses.

Magnetic resonance imaging findings of HTLV-I-associated myelopathy

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Furukawa, Yoshitaka; Une, Humiho; Osame, Mitsuhiro

1989-02-01

Magnetic resonance imaging (MRI) of the brain was evaluated in 12 HAM (HTLV-I-associated myelopathy) patients (4 males and 8 females, mean age of 54 yrs) and compaired with 36 non-HAM controls (16 males and 20 females mean age of 52yrs). MRI of the brain was performed using a 0.5 Tesla superconducting unit. Imaging in all patients was done with the long spin echo (TR=2,000msec, TE=100msec) sequences, and 10mm contiguous axial slices of the entire brain were obtained in all cases. Except for two cases, MRI of the brain was abnormal in 10 (83%) HAM patients, while in controls, 18 (50%) cases were abnormal. The abnormalities were high intensity lesions through SE 2000/100 sequences (T/sub 2/ weighted image), and consisted of small isolated hemisphere lesions in 9 patients, periventricular changes in 9 patients, bilateral thalamic lesions in 2 patients and pontine lesions in 3 patients. We found that the factor of age was very important. In patients with ages below 59 yrs, 6 of 8 HAM patients (75%) had abnormalities, while in control cases, 6 of 23 (23%) had abnormalities in periventricular area. And in isolated hemisphere, 6 of 8 HAM patients (75%) had abnormalities, while in control cases, 3 of 23 (13%) had abnormalities. On the other hand, in patients with ages over 60 yrs, 3 of 4 (75%) HAM patients had abnormalities in periventricular area, while in controls, 10 of 13 cases (77%) had abnormalities, and in isolated hemisphere, 3 of 4 (75%) HAM patients had abnormalities, and in controls, 10 of 13 cases (77%) had abnormalities. Our data suggest that HAM patients with ages below 59 years will show a greater percentage of abnormalities than controls. (author).

Magnetic resonance imaging findings of HTLV-I-associated myelopathy

International Nuclear Information System (INIS)

Furukawa, Yoshitaka; Une, Humiho; Osame, Mitsuhiro

1989-01-01

Magnetic resonance imaging (MRI) of the brain was evaluated in 12 HAM (HTLV-I-associated myelopathy) patients (4 males and 8 females, mean age of 54 yrs) and compaired with 36 non-HAM controls (16 males and 20 females mean age of 52yrs). MRI of the brain was performed using a 0.5 Tesla superconducting unit. Imaging in all patients was done with the long spin echo (TR=2,000msec, TE=100msec) sequences, and 10mm contiguous axial slices of the entire brain were obtained in all cases. Except for two cases, MRI of the brain was abnormal in 10 (83%) HAM patients, while in controls, 18 (50%) cases were abnormal. The abnormalities were high intensity lesions through SE 2000/100 sequences (T 2 weighted image), and consisted of small isolated hemisphere lesions in 9 patients, periventricular changes in 9 patients, bilateral thalamic lesions in 2 patients and pontine lesions in 3 patients. We found that the factor of age was very important. In patients with ages below 59 yrs, 6 of 8 HAM patients (75%) had abnormalities, while in control cases, 6 of 23 (23%) had abnormalities in periventricular area. And in isolated hemisphere, 6 of 8 HAM patients (75%) had abnormalities, while in control cases, 3 of 23 (13%) had abnormalities. On the other hand, in patients with ages over 60 yrs, 3 of 4 (75%) HAM patients had abnormalities in periventricular area, while in controls, 10 of 13 cases (77%) had abnormalities, and in isolated hemisphere, 3 of 4 (75%) HAM patients had abnormalities, and in controls, 10 of 13 cases (77%) had abnormalities. Our data suggest that HAM patients with ages below 59 years will show a greater percentage of abnormalities than controls. (author)

Tropical spastic paraparesis and HTLV-1 associated myelopathy: clinical, epidemiological, virological and therapeutic aspects.

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Gessain, A; Mahieux, R

2012-03-01

In 1980, Human T cell leukemia/lymphoma virus type 1 (HTLV-1) was the first oncogenic human retrovirus to be discovered. HTLV-1 belongs to the Retroviridae family, the Orthoretrovirinae subfamily and to the deltaretrovirus genus. HTLV-1 preferentially infects CD4(+) lymphoid cells in vivo. Three molecules have been identified for binding and/or entry of HTLV-1: heparan sulfate proteoglycans, neuropilin-1, and glucose transporter 1. An efficient transfer of the virus from an infected cell to a target cell can occur through the formation of a viral synapse and/or by virofilm structure. As for all retroviruses, HTLV-1 genome possesses three major ORFs (gag, pol and env) encoding the structural and enzymatic proteins. HTLV-1 encodes also some regulatory and auxillary proteins including the tax protein with transforming activities and the HBZ protein which plays a role in the proliferation and maintenance of the leukemic cells. HTLV-1 is present throughout the world with clusters of high endemicity including mainly Southern Japan, the Caribbean region, areas in South America and in intertropical Africa. The worldwide HTLV-1 infected population is estimated to be around 10-20 million. HTLV-1 has three modes of transmission: (1): mother to child, mainly linked to prolonged breast-feeding; (2): sexual, mainly occurring from male to female and (3): contaminated blood products. HTLV-1 possesses a remarkable genetic stability. HTLV-1 is the etiological agent of mainly two severe diseases: a malignant T CD4(+) cell lymphoproliferation, of very poor prognosis, named Adult T cell Leukemia/Lymphoma (ATLL), and a chronic neuro-myelopathy named Tropical spastic paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM). The lifetime risk among HTLV-1 carriers is estimated to be around 0.25 to 3%. TSP/HAM mainly occurs in adults, with a mean age at onset of 40-50 years and it is more common in women than in men. Blood transfusion is a major risk factor for TSP/HAM development. Clinically

Human endogenous retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV-I-infected subjects using standard peptide screening methods.

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Jones, R Brad; Leal, Fabio E; Hasenkrug, Aaron M; Segurado, Aluisio C; Nixon, Douglas F; Ostrowski, Mario A; Kallas, Esper G

2013-01-10

An estimated 10-20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial. Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets. Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.

Endemic versus epidemic viral spreads display distinct patterns of HTLV-2b replication

International Nuclear Information System (INIS)

Gabet, Anne-Sophie; Moules, Vincent; Sibon, David; Nass, Catharie C.; Mortreux, Franck; Mauclere, Philippe; Gessain, Antoine; Murphy, Edward L.; Wattel, Eric

2006-01-01

As the replication pattern of leukemogenic PTLVs possesses a strong pathogenic impact, we investigated HTLV-2 replication in vivo in asymptomatic carriers belonging into 2 distinct populations infected by the same HTLV-2b subtype. They include epidemically infected American blood donors, in whom HTLV-2b has been present for only 30 years, and endemically infected Bakola Pygmies from Cameroon, characterized by a long viral endemicity (at least few generations). In blood donors, both the circulating proviral loads and the degree of infected cell proliferation were largely lower than those characterizing asymptomatic carriers infected with leukemogenic PTLVs (HTLV-1, STLV-1). This might contribute to explain the lack of known link between HTLV-2b infection and the development of malignancies in this population. In contrast, endemically infected individuals displayed high proviral loads resulting from the extensive proliferation of infected cells. The route and/or the duration of infection, viral genetic drift, host immune response, genetic background, co-infections or a combination thereof might have contributed to these differences between endemically and epidemically infected subjects. As the clonality pattern observed in endemically infected individuals is very reminiscent of that of leukemogenic PTLVs at the pre-leukemic stage, our results highlight the possible oncogenic effect of HTLV-2b infection in such population

HTLV-1 induced molecular mimicry in neurological disease.

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Lee, S M; Morcos, Y; Jang, H; Stuart, J M; Levin, M C

2005-01-01

As a model for molecular mimicry, we study patients infected with human T-lymphotropic virus type 1 (HTLV-1) who develop a neurological disease called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease with important biological similarities to multiple sclerosis (MS) (Khan et al. 2001; Levin et al. 1998, 2002a; Levin and Jacobson 1997). The study of HAM/TSP, a disease associated with a known environmental agent (HTLV-1), allows for the direct comparison of the infecting agent with host antigens. Neurological disease in HAM/TSP patients is associated with immune responses to HTLV-1-tax (a regulatory and immunodominant protein) and human histocompatibility leukocyte antigen (HLA) DRB1*0101 (Bangham 2000; Jacobson et al. 1990; Jeffery et al. 1999; Lal 1996). Recently, we showed that HAM/TSP patients make antibodies to heterogeneous nuclear ribonuclear protein A1 (hnRNP A1), a neuron-specific autoantigen (Levin et al. 2002a). Monoclonal antibodies to tax cross-reacted with hnRNP A1, indicating molecular mimicry between the two proteins. Infusion of cross-reactive antibodies with an ex vivo system completely inhibited neuronal firing indicative of their pathogenic nature (Kalume et al. 2004; Levin et al. 2002a). These data demonstrate a clear link between chronic viral infection and autoimmune disease of the central nervous system (CNS) in humans and, we believe, in turn will give insight into the pathogenesis of MS.

Association of Sicca Syndrome with Proviral Load and Proinflammatory Cytokines in HTLV-1 Infection

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Clara Mônica Lima

2016-01-01

Full Text Available The Sjögren syndrome has been diagnosed in patients with HTLV-1 associated myelopathy and dry mouth and dry eyes are documented in HTLV-1 carriers. However the diagnosis of Sjögren syndrome in these subjects has been contested. In this cross-sectional study, we evaluated the role of immunological factors and proviral load, in sicca syndrome associated with HTLV-1 in patients without myelopathy. Subjects were recruited in the HTLV-1 Clinic, from 2009 to 2011. The proviral load and cytokine levels (IFN-γ, TNF-α, IL-5, and IL-10 were obtained from a database containing the values presented by the subjects at admission in the clinic. Of the 272 participants, 59 (21.7% had sicca syndrome and in all of them anti-Sjögren syndrome related antigen A (SSA and antigen B (SSB were negatives. The production of TNF-α and IFN-γ was higher in the group with sicca syndrome (P<0.05 than in HTLV-1 infected subjects without sicca syndrome. Our data indicates that patients with sicca syndrome associated with HTLV-1 do not have Sjögren syndrome. However the increased production of TNF-α and IFN-γ in this group of patients may contribute to the pathogenesis of sicca syndrome associated with HTLV-1.

HTLV-1-infected thymic epithelial cells convey the virus to CD4+ T lymphocytes.

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Carvalho Barros, Luciana Rodrigues; Linhares-Lacerda, Leandra; Moreira-Ramos, Klaysa; Ribeiro-Alves, Marcelo; Machado Motta, Maria Cristina; Bou-Habib, Dumith Chequer; Savino, Wilson

2017-12-01

The human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of adult T cell leukemia/lymphoma (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD4 + T cells are the main target of HTLV-1, but other cell types are known to be infected, including immature lymphocytes. Developing T cells undergo differentiation in the thymus, through migration and interaction with the thymic microenvironment, in particular with thymic epithelial cells (TEC) the major component of this three dimensional meshwork of non-lymphoid cells. Herein, we show that TEC express the receptors for HTLV-1 and can be infected by this virus through cell-cell contact and by cell-free virus suspensions. The expression of anti-apoptosis, chemokine and adhesion molecules genes are altered in HTLV-1-infected TEC, although gene expression of antigen presentation molecules remained unchanged. Furthermore, HTLV-1-infected TEC transmitted the virus to a CD4 + T cell line and to CD4 + T cells from healthy donors, during in vitro cellular co-cultures. Altogether, our data point to the possibility that the human thymic epithelial cells play a role in the establishment and progression of HTLV-1 infection, functioning as a reservoir and transmitting the virus to maturing CD4 + T lymphocytes, which in turn will cause disease in the periphery. Copyright © 2017. Published by Elsevier GmbH.

Leukotrienes are upregulated and associated with human T-lymphotropic virus type 1 (HTLV-1-associated neuroinflammatory disease.

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Bruno Caetano Trindade

Full Text Available Leukotrienes (LTs are lipid mediators involved in several inflammatory disorders. We investigated the LT pathway in human T-lymphotropic virus type 1 (HTLV-1 infection by evaluating LT levels in HTLV-1-infected patients classified according to the clinical status as asymptomatic carriers (HACs and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP patients. Bioactive LTB(4 and CysLTs were both increased in the plasma and in the supernatant of peripheral blood mononuclear cell cultures of HTLV-1-infected when compared to non-infected. Interestingly, CysLT concentrations were increased in HAM/TSP patients. Also, the concentration of plasma LTB(4 and LTC(4 positively correlated with the HTLV-1 proviral load in HTLV-1-infected individuals. The gene expression levels of LT receptors were differentially modulated in CD4(+ and CD8(+ T cells of HTLV-1-infected patients. Analysis of the overall plasma signature of immune mediators demonstrated that LT and chemokine amounts were elevated during HTLV-1 infection. Importantly, in addition to CysLTs, IP-10 was also identified as a biomarker for HAM/TSP activity. These data suggest that LTs are likely to be associated with HTLV-1 infection and HAM/TSP development, suggesting their putative use for clinical monitoring.

Prevalência, fatores de risco e caracterização genética dos vírus linfotrópico de células T humana tipo 1 e 2 em pacientes infectados pelo vírus da imunodeficiência humana tipo 1 nas Cidades de Ribeirão Preto e São Paulo Prevalence, risk factors and genetic characterization of human T-cell lymphotropic virus types 1 and 2 in patients infected with human immunodeficiency virus type 1 in the cities of Ribeirão Preto and São Paulo

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Walter Kleine Neto

2009-06-01

Full Text Available O objetivo deste estudo foi definir a prevalência dos vírus linfotrópico de células T humana tipo 1 e 2 em pacientes positivos para o vírus da imunodeficiência humana tipo 1 no Estado de São Paulo, Brasil. Avaliamos 319 indivíduos atendidos em clínicas de Ribeirão Preto e Capital. Os pacientes foram entrevistados e testados sorologicamente. Foram seqüenciadas as regiões tax e long terminal repeat para diferenciação e determinação do subtipo. A soroprevalência geral foi de 7,5% (24/319 e esteve associada somente com uso de drogas injetáveis e ao vírus da hepatite tipo C (pThe aim of this study was to define the prevalence of human T cell lymphotropic virus types 1 and 2 in patients who were positive for human immunodeficiency virus type 1 in the State of São Paulo, Brazil. We evaluated 319 individuals infected with HIV type 1 who were attended at specialized clinics in two cities (Ribeirão Preto and São Paulo. The patients were interviewed and tested for antibodies against HTLV types 1 and 2 (Orthoâ HTLV-1/HTLV-2 Ab-Capture enzyme immunoassay. Direct DNA sequencing of polymerase chain reaction products from the tax region of HTLV type 2 and the long terminal repeat region of HTLV types 1 and 2 were performed to differentiate and determine the subtypes. The overall prevalence of anti-HTLV type 1 and 2 antibodies was 7.5% (24/319; 95% CI: 5.2-11.5. HTLV type 1 and 2 infection was associated with a history of injected drug use and with antibodies for hepatitis C virus (p 0.05. HTLV DNA was detected in 13 out of 24 samples, of which 12 were characterized as HTLV subtype 2c and one as HTLV subtype 1a. Among the 12 HTLV type 2 samples, seven were from injected drug users, thus indicating that this route is an important risk factor for HTLV type 2 transmission among our population infected with HIV type 1.

How to Control HTLV-1-Associated Diseases: Preventing de Novo Cellular Infection Using Antiviral Therapy

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Amandine Pasquier

2018-03-01

Full Text Available Five to ten million individuals are infected by Human T-cell Leukemia Virus type 1 (HTLV-1. HTLV-1 is transmitted through prolonged breast-feeding, by sexual contacts and by transmission of infected T lymphocytes through blood transfusion. One to ten percent of infected carriers will develop a severe HTLV-1-associated disease: Adult-T-cell leukemia/lymphoma (ATLL, or a neurological disorder named Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM. In vivo, HTLV-1 is mostly detected in CD4+ T-cells, and to a lesser extent in CD8+ T cells and dendritic cells. There is a strong correlation between HTLV-1 proviral load (PVL and clinical status of infected individuals. Thus, reducing PVL could be part of a strategy to prevent or treat HTLV-1-associated diseases among carriers. Treatment of ATLL patients using conventional chemotherapy has very limited benefit. Some chronic and acute ATLL patients are, however, efficiently treated with a combination of interferon α and zidovudine (IFN-α/AZT, to which arsenic trioxide is added in some cases. On the other hand, no efficient treatment for TSP/HAM patients has been described yet. It is therefore crucial to develop therapies that could either prevent the occurrence of HTLV-1-associated diseases or at least block the evolution of the disease in the early stages. In vivo, reverse transcriptase (RT activity is low in infected cells, which is correlated with a clonal mode of viral replication. This renders infected cells resistant to nucleoside RT inhibitors such as AZT. However, histone deacetylase inhibitors (HDACi associated to AZT efficiently induces viral expression and prevent de novo cellular infection. In asymptomatic STLV-1 infected non-human primates, HDACi/AZT combination allows a strong decrease in the PVL. Unfortunately, rebound in the PVL occurs when the treatment is stopped, highlighting the need for better antiviral compounds. Here, we review previously used strategies

Demandas de cuidado domiciliar da criança nascida exposta ao HIV na ótica da teoria ambientalista

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Ivana Cristina Vieira de Lima

Full Text Available Objetivou-se identificar as demandas de cuidado domiciliar da criança nascida exposta ao HIV, sob a perspectiva da teoria ambientalista. Trata-se de estudo qualitativo exploratório-descritivo realizado de janeiro a abril de 2011. Participaram dez mães infectadas pelo HIV, com crianças nascidas expostas ao vírus, em Fortaleza, Ceará. Constituíram-se como instrumentos de coleta de dados: câmera fotográfica descartável e digital e formulários para captação de informações em saúde associadas ao ambiente domiciliar. Os resultados foram contextualizados de acordo com a teoria e organizados em categorias: "vulnerabilidades associadas à estrutura física da moradia"; "ar intradomiciliar e peridomiciliar impuro"; "água utilizada para consumo"; "rede de esgoto e saneamento"; "iluminação e ventilação da residência". Conclui-se que o ambiente domiciliar oferece condições ambientais desfavoráveis para a criança. Urge a realização de intervenções focalizadas no ambiente domiciliar, para promover a saúde da criança nascida exposta ao HIV.

As tecnologias de processamento do leite associadas à problemática do seu consumo

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Santos, Cláudia Marisa de Sousa

2010-01-01

Dissertação de mest., Gerontologia Social, Escola Superior de Educação e Comunicação, Escola Superior de Saúde, Univ. do Algarve, 2010 O leite tem vários componentes que no seu conjunto fazem deste um alimento equilibrado e essencial para um estilo de vida saudável, embora o seu consumo possa estar associado a algumas patologias. No sentido de aprofundar esta questão, este trabalho teve como objectivo o estudo das problemáticas associadas ao consumo de leite, bem como as tecnol...

Identification and characterization of HTLV-1 HBZ post-translational modifications.

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Nathan Dissinger

Full Text Available Human T-cell leukemia virus type-1 (HTLV-1 is estimated to infect 15-25 million people worldwide, with several areas including southern Japan and the Caribbean basin being endemic. The virus is the etiological agent of debilitating and fatal diseases, for which there is currently no long-term cure. In the majority of cases of leukemia caused by HTLV-1, only a single viral gene, hbz, and its cognate protein, HBZ, are expressed and their importance is increasingly being recognized in the development of HTLV-1-associated disease. We hypothesized that HBZ, like other HTLV-1 proteins, has properties and functions regulated by post-translational modifications (PTMs that affect specific signaling pathways important for disease development. To date, PTM of HBZ has not been described. We used an affinity-tagged protein and mass spectrometry method to identify seven modifications of HBZ for the first time. We examined how these PTMs affected the ability of HBZ to modulate several pathways, as measured using luciferase reporter assays. Herein, we report that none of the identified PTMs affected HBZ stability or its regulation of tested pathways.

Pulmonary malakoplakia associated with immunodeficiency by HTLV-1 and HIV

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Manuela Madruga

2014-08-01

Full Text Available Malakoplakia is a rare chronic inflammatory disease often confused with neoplasia. In this paper we report two cases of pulmonary Malakoplakia, both with typical clinical diagnosis of tuberculosis and lung cancer. A patient with human T-lymphotropic virus type I (HTLV-1 and diagnosis of adult T-cell leukemia/lymphoma, and another patient with human immunodeficiency virus (HIV, which was treated for tuberculosis, but, after pulmonary lobectomy, was evidenced Rodococosis equi, progressed to death.

HTLV-1 Rex: the courier of viral messages, making use of the host vehicle

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Kazumi eNakano

2012-09-01

Full Text Available The human T-cell leukemia virus type 1 (HTLV-1 is a retrovirus causing an aggressive T-cell malignancy, adult T-cell leukemia (ATL. Although HTLV-1 has a compact RNA genome, it has evolved elaborate mechanisms to maximize its coding potential. The structural proteins Gag, Pro, and Pol are encoded in the unspliced form of viral mRNA, whereas the Env protein is encoded in singly spliced viral mRNA. Regulatory and accessory proteins, such as Tax, Rex, p30II, p12, and p13, are translated only from fully spliced mRNA. For effective viral replication, translation from all forms of HTLV-1 transcripts has to be achieved in concert, although unspliced mRNA are extremely unstable in mammalian cells. It has been well recognized that HTLV-1 Rex enhances the stability of unspliced and singly spliced HTLV-1 mRNA by promoting nuclear export and thereby, removing them from the splicing site. Rex specifically binds to the highly structured Rex responsive element (RxRE located at the 3′ end of all HTLV-1 mRNA. Rex then binds to the cellular nuclear exporter, CRM1, via its nuclear export signal domain and the Rex-viral transcript complex is selectively exported from the nucleus to the cytoplasm for effective translation of the viral proteins. Yet, the mechanisms by which Rex inhibits the cellular splicing machinery and utilizes the cellular pathways beneficial to viral survival in the host cell have not been fully explored. Furthermore, physiological impacts of Rex against homeostasis of the host cell via interactions with numerous cellular proteins have been largely left uninvestigated. In this review, we focus on the biological importance of HTLV-1 Rex in the HTLV-1 life cycle by following the historical path in the literature concerning this viral post-transcriptional regulator from its discovery to this day. In addition, for future studies, we discuss recently discovered aspects of HTLV-1 Rex as a post-transcriptional regulator and its use in host cellular

Comprehensive Antiretroviral Restriction Factor Profiling Reveals the Evolutionary Imprint of the ex Vivo and in Vivo IFN-β Response in HTLV-1-Associated Neuroinflammation

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Fabio E. Leal

2018-05-01

Full Text Available HTLV-1-Associated Myelopathy (HAM/TSP is a progressive neuroinflammatory disorder for which no disease-modifying treatment exists. Modest clinical benefit from type I interferons (IFN-α/β in HAM/TSP contrasts with its recently identified IFN-inducible gene signature. In addition, IFN-α treatment in vivo decreases proviral load and immune activation in HAM/TSP, whereas IFN-β therapy decreases tax mRNA and lymphoproliferation. We hypothesize this “IFN paradox” in HAM/TSP might be explained by both cell type- and gene-specific effects of type I IFN in HTLV-1-associated pathogenesis. Therefore, we analyzed ex vivo transcriptomes of CD4+ T cells, PBMCs and whole blood in healthy controls, HTLV-1-infected individuals, and HAM/TSP patients. First, we used a targeted approach, simultaneously quantifying HTLV-1 mRNA (HBZ, Tax, proviral load and 42 host genes with known antiretroviral (anti-HIV activity in purified CD4+ T cells. This revealed two major clusters (“antiviral/protective” vs. “proviral/deleterious”, as evidenced by significant negative (TRIM5/TRIM22/BST2 vs. positive correlation (ISG15/PAF1/CDKN1A with HTLV-1 viral markers and clinical status. Surprisingly, we found a significant inversion of antiretroviral activity of host restriction factors, as evidenced by opposite correlation to in vivo HIV-1 vs. HTLV-1 RNA levels. The anti-HTLV-1 effect of antiviral cluster genes was significantly correlated to their adaptive chimp/human evolution score, for both Tax mRNA and PVL. Six genes of the proposed antiviral cluster underwent lentivirus-driven purifying selection during primate evolution (TRIM5/TRIM22/BST2/APOBEC3F-G-H, underscoring the cross-retroviral evolutionary imprint. Secondly, we examined the genome-wide type I IFN response in HAM/TSP patients, following short-term ex vivo culture of PBMCs with either IFN-α or IFN-β. Microarray analysis evidenced 12 antiretroviral genes (including TRIM5α/TRIM22/BST2 were significantly

Biopsia por aspiración con aguja fina (BAAF) para el diagnóstico de linfoma no hodking cutáneo asociado a HTLV I-II. Presentación de caso.

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Núñez Carrión., Ericka Cecilia

2010-01-01

INTRODUCCIÓN: El HTLV-1 es el primer retrovirus oncógeno humano que fue aislado por vez primera. Más tarde se demostró que el virus del linfoma leucemia de células T humanas (HTLV-1) era el agente causal de la Leucemia/linfoma de células T del adulto (ATL). EL HTLV-1 es más común en Japón y en el Caribe que en los Estados Unidos. También se ha descrito posteriormente en varios países latinoamericanos incluyendo Perú. El HTLV-1 pertenece a la familia de los retrovirus humanos, con tropismo pos...

Genetic characterization of human T-cell lymphotropic virus type 1 in Mozambique: transcontinental lineages drive the HTLV-1 endemic.

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Ana Carolina P Vicente

2011-04-01

Full Text Available Human T-Cell Lymphotropic Virus Type 1 (HTLV-1 is the etiological agent of adult T-cell leukemia (ATL and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. It has been estimated that 10-20 million people are infected worldwide, but no successful treatment is available. Recently, the epidemiology of this virus was addressed in blood donors from Maputo, showing rates from 0.9 to 1.2%. However, the origin and impact of HTLV endemic in this population is unknown.To assess the HTLV-1 molecular epidemiology in Mozambique and to investigate their relationship with HTLV-1 lineages circulating worldwide.Blood donors and HIV patients were screened for HTLV antibodies by using enzyme immunoassay, followed by Western Blot. PCR and sequencing of HTLV-1 LTR region were applied and genetic HTLV-1 subtypes were assigned by the neighbor-joining method. The mean genetic distance of Mozambican HTLV-1 lineages among the genetic clusters were determined. Human mitochondrial (mt DNA analysis was performed and individuals classified in mtDNA haplogroups.LTR HTLV-1 analysis demonstrated that all isolates belong to the Transcontinental subgroup of the Cosmopolitan subtype. Mozambican HTLV-1 sequences had a high inter-strain genetic distance, reflecting in three major clusters. One cluster is associated with the South Africa sequences, one is related with Middle East and India strains and the third is a specific Mozambican cluster. Interestingly, 83.3% of HIV/HTLV-1 co-infection was observed in the Mozambican cluster. The human mtDNA haplotypes revealed that all belong to the African macrohaplogroup L with frequencies representatives of the country.The Mozambican HTLV-1 genetic diversity detected in this study reveals that although the strains belong to the most prevalent and worldwide distributed Transcontinental subgroup of the Cosmopolitan subtype, there is a high HTLV diversity that could be correlated with at least 3 different HTLV-1 introductions

Prevalence and genetic characterisation of HTLV-1 and 2 dual infections in patients with pulmonary tuberculosis in Central-West Brazil

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Aline Garcia Kozlowski

2014-02-01

Full Text Available Human T-cell lymphotropic virus (HTLV may impact the clinical course of tuberculosis (TB. Both infections are highly endemic in Brazil. The aim of this study was to assess the prevalence of HTLV-1/2 in TB patients in Central-West Brazil and to perform a genetic characterisation of the respective isolates. Of the 402 patients, six (1.49% were positive for anti-HTLV and five (1.24%; 95% confidence interval: 0.46-3.05 were infected with HTLV-1/2. Genetic characterisation demonstrated that the four HTLV-1 isolates belonged to the Transcontinental subgroup A of the Cosmopolitan subtype a and that the HTLV-2 isolate belonged to subtype a (HTLV-2a/c. The prevalence of HTLV infection observed in this study is higher than that observed in local blood donors and the HTLV-1 and 2 subtypes identified are consistent with those circulating in Brazil.

Infection with human T-lymphotropic virus types-1 and -2 (HTLV-1 and -2): Implications for blood transfusion safety.

Science.gov (United States)

Murphy, E L

2016-02-01

Many countries currently perform antibody screening for HTLV-1 infection in blood donors, and this intervention is likely cost-effective in preventing HTLV-1 related diseases in high prevalence countries. However, a number of high-income countries with low prevalence of HTLV-1 infection also perform universal HTLV-1 screening and debate has arisen regarding the cost-effectiveness of these strategies. Filter-based leukoreduction is likely to substantially reduce HTLV-1 transmission by removing infected lymphocytes, but actual laboratory data on its efficacy is currently lacking. Similarly, cost-effectiveness research on HTLV-1 prevention strategies is limited by poor data on prevalence, transmission efficacy and the cost of treating HTLV1 diseases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Toxoplasma gondii myelitis in a patient with adult T-cell leukemia-lymphoma Mielite por Toxoplasma gondii em um paciente com leucemia-linfoma de células T do adulto

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ELVES MACIEL

2000-12-01

Full Text Available Adult T cell leukemia-lymphoma (ATL caused by HTLV-I may be associated with severe immunosupression and several opportunistic infections. Toxoplasmic encephalitis is a common central nervous system opportunistic infection in severely immunosupressed patients, however spinal cord involvement by this parasite is rare. In this paper, we report a case of toxoplasmic myelitis in a patient with ATL.Leucemia de células T do adulto (ATL, causada pelo HTLV-I, pode estar associada com imunossupressão severa e muitas infecções oportunistas. Encefalite por toxoplasmose é uma infecção oportunista do sistema nervoso central em pacientes imunossuprimidos, no entanto o envolvimento da medula espinal por este parasita é raro. Neste artigo, apresentamos um caso de mielite em um paciente com ATL.

Failure to demonstrate human T cell lymphotropic virus type I in multiple sclerosis patients

DEFF Research Database (Denmark)

Fugger, L; Morling, N; Ryder, L P

1990-01-01

The polymerase chain reaction (PCR) technique was employed in searching for human T cell lymphotropic virus type I (HTLV-I) gag, env and pol sequences in samples of DNA prepared from two HTLV-I seropositive patients with tropical spastic paraparesis (TSP), the Swedish multiple sclerosis (MS......) patients who recently have been reported to be PCR-positive for HTLV-I gag and env sequences, and eight healthy individuals. Precautions were taken in order to reduce the risk of cross-contamination in the PCR. In the two TSP patients strong signals were obtained with gag, env and pol amplification primers...... data do not confirm the presence of HTLV-I sequences in MS patients....

PDZ binding motif of HTLV-1 Tax promotes virus-mediated T-cell proliferation in vitro and persistence in vivo.

Science.gov (United States)

Xie, Li; Yamamoto, Brenda; Haoudi, Abdelali; Semmes, O John; Green, Patrick L

2006-03-01

HTLV-1 cellular transformation and disease induction is dependent on expression of the viral Tax oncoprotein. PDZ is a modular protein interaction domain used in organizing signaling complexes in eukaryotic cells through recognition of a specific binding motif in partner proteins. Tax-1, but not Tax-2, contains a PDZ-binding domain motif (PBM) that promotes the interaction with several cellular PDZ proteins. Herein, we investigate the contribution of the Tax-1 PBM in HTLV-induced proliferation and immortalization of primary T cells in vitro and viral survival in an infectious rabbit animal model. We generated several HTLV-1 and HTLV-2 Tax viral mutants, including HTLV-1deltaPBM, HTLV-2+C22(+PBM), and HTLV-2+ C18(deltaPBM). All Tax mutants maintained the ability to significantly activate the CREB/ATF or NFkappaB signaling pathways. Microtiter proliferation assays revealed that the Tax-1 PBM significantly increases both HTLV-1- and HTLV-2-induced primary T-cell proliferation. In addition, Tax-1 PBM was responsible for the micronuclei induction activity of Tax-1 relative to that of Tax-2. Viral infection and persistence were severely attenuated in rabbits inoculated with HTLV-1deltaPBM. Our results provide the first direct evidence suggesting that PBM-mediated associations between Tax-1 and cellular proteins play a key role in HTLV-induced cell proliferation and genetic instability in vitro and facilitate viral persistence in vivo.

[Relevance of safety measures to avoid HTLV transmission by transfusion in 2014].

Science.gov (United States)

Laperche, S; Pillonel, J

2014-11-01

In high-income countries, the safety of blood transfusion related to viruses has reached a very high level, especially thanks to the implementation of multiple measures aimed at reducing the transfusion risk. The cost-effectiveness of these preventive measures is frequently discussed due to global financial resources, which are more and more limited. Hence, the revision of safety strategies is a key issue, especially when these strategies are redundant, as those implemented to avoid Human T-cell Lymphotropic Virus (HTLV) transmission, which are based on both antibodies screening and leucoreduction of blood products. The residual risk of the transmission of HTLV by transfusion has been recently estimated at 1 in 20 million donations (2010-2012) in France (excluding overseas territories). This estimation did not take into account the leucoreduction, which appears to be a very efficient preventive measure as the virus is strictly intra-cellular. To help decision-making, we have evaluated some parameters related to HTLV blood transmission. Firstly, the probability that an incident occurring during the leucoreduction process affects a HTLV-positive blood donation has been estimated at 1 in 178 million. Estimation of clinical consequences of HTLV-positive transfusions would affect 1 to 2 transfused-patients without leucoreduction, and one recipient every 192 years in case of 10% failures of the filtration method. Obviously, despite a risk, which appears to be controlled, HTLV screening will be disputed as soon as the efficiency of leucoreduction to totally prevent virus blood transmission will be proven and when pathogen inactivation methods are generalized to all blood cellular products. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Seroprevalence and molecular epidemiology of HTLV-1 isolates from HIV-1 co-infected women in Feira de Santana, Bahia, Brazil.

Science.gov (United States)

de Almeida Rego, Filipe Ferreira; Mota-Miranda, Aline; de Souza Santos, Edson; Galvão-Castro, Bernardo; Alcantara, Luiz Carlos

2010-12-01

HTLV-1/HIV-1 co-infection is associated with severe clinical manifestations, marked immunodeficiency, and opportunistic pathogenic infections, as well as risk behavior. Salvador, the capital of the State of Bahia, Brazil, has the highest HTLV-1 prevalence (1.74%) found in Brazil. Few studies exist which describe this co-infection found in Salvador and its surrounding areas, much less investigate how these viruses circulate or assess the relationship between them. To describe the epidemiological and molecular features of HTLV in HIV co-infected women. To investigate the prevalence of HTLV/HIV co-infection in surrounding areas, as well as the molecular epidemiology of HTLV, a cross sectional study was carried out involving 107 women infected with HIV-1 from the STD/HIV/AIDS Reference Center located in the neighboring City of Feira de Santana. Patient samples were submitted to ELISA, and HTLV infection was confirmed using Western Blot and Polymerase Chain Reaction (PCR). Phylogenetic analysis using Neighbor-Joining (NJ) and Maximum Likelihood (ML) was performed on HTLV LTR sequences in order to gain further insights about molecular epidemiology and the origins of this virus in Bahia. Four out of five reactive samples were confirmed to be infected with HTLV-1, and one with HTLV-2. The seroprevalence of HTLV among HIV-1 co-infected women was 4.7%. Phylogenetic analysis of the LTR region from four HTLV-1 sequences showed that all isolates were clustered into the main Latin American group within the Transcontinental subgroup of the Cosmopolitan subtype. The HTLV-2 sequence was classified as the HTLV-2c subtype. It was also observed that four HTLV/HIV-1 co-infected women exhibited risk behavior with two having parenteral exposure, while another two were sex workers. This article describes the characteristics of co-infected patients. This co-infection is known to be severe and further studies should be conducted to confirm the suggestion that HTLV-1 is spreading from

HIV/HTLV-1 co-infection

African Journals Online (AJOL)

result of a lymphoproliferative disorder. In the context of HIV co-infection, lympho- cytosis has been described during early sero- conversion associated with CMV, as well as in HIV/HTLV-1 co-infection where CD4+ lymphocytosis can be caused by both a reactive or clonal expansion. Consequently, patients with untreated ...

Interplay between the HTLV-2 Tax and APH-2 proteins in the regulation of the AP-1 pathway

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Marban Céline

2012-12-01

Full Text Available Abstract Background In contrast with human T-cell leukemia virus type 1 (HTLV-1 that causes ATL (adult T-cell leukemia, HTLV-2 has not been causally linked to malignant disease. The minus strand of the HTLV genomes encode the regulatory proteins HTLV-1 bZIP factor (HBZ for HTLV-1 and antisense protein of HTLV-2 (APH-2 for HTLV-2. Unlike the viral proteins Tax1 and Tax2, both HBZ and APH-2 are constitutively expressed in infected cells suggesting that they may play important roles in the pathogenesis of these viruses. To date, very little is known about the function of APH-2 except that it inhibits Tax2-mediated transcription of HTLV-2 genes. In the present study, we investigated the role of APH-2 in basal and Tax2B-mediated activation of the AP-1 pathway. Results We demonstrate that, unlike HBZ, APH-2 stimulates basal AP-1 transcription by interacting with c-Jun and JunB through its non-conventional bZIP domain. In addition, when Tax2 and APH-2 are co-expressed, they physically interact in vivo and in vitro and APH-2 acts as an inhibitor of Tax2-mediated activation of AP-1 transcription. Conclusions This report is the first to document that HTLV-2 can modulate the AP-1 pathway. Altogether our results reveal that, in contrast with HBZ, APH-2 regulates AP-1 activity in a Tax2-dependant manner. As the AP-1 pathway is involved in numerous cellular functions susceptible to affect the life cycle of the virus, these distinct biological properties between HBZ and APH-2 may contribute to the differential pathogenic potential of HTLV-1 and HTLV-2.

Seroepidemiology of human T-cell lymphotropic virus type-I in blood donors of Northeastern Iran, Sabzevar

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Mahtab Maghsudlu

2015-01-01

Full Text Available Background and Objectives: Human T-cell lymphotropic virus type-I (HTLV-I infection is considered as a public health challenge in endemic areas. The virus is associated with severe diseases, such as adult T-cell leukemia/lymphoma, and HTLV-I-associated myelopathy/tropical spastic paraparesis. One of the major routes of the HTLV-I transmission includes blood transfusion. Sabzevar is located in the endemic region of HTLV-I infection. The aim of the present study was to determine the seroprevalence of HTLV-I infection in the blood donors in Sabzevar. Materials and Methods: A total of 35,067 blood donors in Sabzevar from March 2009 to April 2012 who were screened with HTLV-I on the enzyme-linked immunosorbent assay screening test were included in this survey. Reactive samples that confirmed by western blot were considered to be seropositive cases. The required data were obtained from blood donors′ database of blood transfusion service. Results: The overall prevalence of HTLV-1 based on the positive result of western blot test was 0.14%. The seropositive donors aged 17-59 years with a mean age of 38.10 ± 11.82. The prevalence rates of HTLV-I infection in 3 years of study were 0.19%, 0.14%, and 0.09%, respectively. A significant relation between age, sex, educational level, and history of blood donation was observed with seropositivity of HTLV-I. Conclusion: The improvement of donor selection and laboratory screening caused a decline in the prevalence of infection in blood donors. Given the lower prevalence of infection in regular donors with lower age and higher educational level, more efforts should be done to attract blood donors from these populations.

Claritromicina associada com pirímetamina na toxoplasmose cerebral - relato de dois casos

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Marcos Olivicr Dalston

1995-12-01

Full Text Available Os autores relatam a resposta terapêutica da claritromicina associada com pirímetamina em dois casos de toxoplasmose cerebral ocorridos em pacientes com Síndrome de Imunodeficiência Adquirida (SIDA. Nos dois casos o diagnóstico foi presuntivo, baseando-se nas manifestações clínicas e na presença de lesões expansivas hipercaptantes detectadas na tomografia computadorizada (TC de crânio. Em ambos os casos, observou-se exantema com o uso da sulfadiazina e da clindamicina, razão pela qual tais medicamentos foram substituídos pela claritromicina (1,5 a 2g/dia associada à pirímetamina (25mg/dia. A resposta terapêutica foi favorável nos dois casos com melhora das manifestações neurológicas e dos achados neurorradiológicos. Os autores sugerem que a associação claritromicina com pirímetamina pode ser útil como opção terapêutica na toxoplasmose cerebral em pacientes com SIDA que apresentam intolerância ou outra contra-indicação ao emprego das sulfonamidas.

The burden of hospitalization due to overweight and obesity in Brazil Importância e custo das hospitalizações associadas ao sobrepeso e obesidade no Brasil

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Rosely Sichieri

2007-07-01

Full Text Available This article estimates the burden of hospitalization associated with overweight and obesity in Brazil. The analysis of all hospitalizations for men and women from 20 to 60 years of age was based on the National Healthcare Expenditure Database (SIH-SUS, covering more than 70% of all hospital admissions. Data were for the year 2001. Attributable fraction of hospitalizations associated with diseases related to obesity and overweight was based on the combined risks of United States and European cohorts. The population-attributable fraction for each disease studied was multiplied by values reimbursed to the hospitals and summed to obtain total direct costs. Overall costs of overweight and obesity represent 3.02% of total hospitalization costs for men and 5.83% for women, corresponding to 6.8 and 9.3% of all hospitalization (excluding pregnancy. Diseases associated with overweight and obesity had a significant impact on hospitalizations and economic costs in Brazil, and overall percentages were similar to those from developed countries. Since the nutritional transition is still under way in Brazil, overweight had a higher impact than obesity on disease prevalence and costs.Os custos de hospitalização associados ao sobrepeso/obesidade e às doenças associadas no Brasil foram estimados utilizando-se os dados das hospitalizações de homens e mulheres de 20 a 60 anos do Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH-SUS para o ano de 2001. O SUS cobre mais de 70% das hospitalizações. A fração atribuível a hospitalizações associadas com obesidade/sobrepeso ou doenças relacionadas foi estimada com base na combinação dos riscos relativos de coortes americanas e européias. O custo direto total do sobrepeso/obesidade foi estimado pela soma do risco atribuível à população para cada morbidade multiplicada pelo valor de reembolso de cada morbidade. O total de custos foi equivalente a 3,02% dos custos totais de

Development of molecular methods for detection and epidemiological investigation of HIV-1, HIV-2, and HTLV-I/II infections

NARCIS (Netherlands)

Meijer A; Borleffs JCC; Roosendaal G; van Loon AM; VIR; AZU; Van Creveld Kliniek Utrecht

1995-01-01

Het onderzoek dat hier wordt gepresenteerd werd gestart om de mogelijkheden van moleculaire methoden voor detectie en epidemiologisch onderzoek van HIV en HTLV infecties te onderzoeken. We presenteren de resultaten van een literatuurstudie en beschrijven de ontwikkeling en gedeeltelijke evaluatie

Análise proteômica de plasma de pacientes com infecção pulmonar associada à ventilação mecânica

OpenAIRE

Costa, Lucianna Auxi Teixeira Josino da

2016-01-01

Pneumonia associada à ventilação mecânica (PAV) tem altas prevalência e mortalidade. Fatores de risco somados aos os dados clínicos ajudam a sugeri-la, porém não a confirmam. O estudo microbiológico aumenta a acurácia diagnóstica e contribui no tratamento, porém nem sempre há crescimento bacteriano ou fúngico. Um perfil proteico plasmático auxiliaria no diagnóstico dos pacientes com infecção associada à ventilação mecânica. Cinquenta pacientes foram seguidos resultando em 14 com o diagnóstico...

HTLV-2B Tax oncoprotein is modified by ubiquitination and sumoylation and displays intracellular localization similar to its homologue HTLV-1 Tax

International Nuclear Information System (INIS)

Turci, Marco; Lodewick, Julie; Righi, Paola; Polania, Angela; Romanelli, Maria Grazia; Bex, Francoise; Bertazzoni, Umberto

2009-01-01

HTLV-1 is more pathogenic than HTLV-2B. The difference is generally attributed to the properties of their individual transactivating Tax proteins. By using internal Flag-6His tagged Tax-1 and Tax-2B, which display transcriptional activities comparable to the untagged proteins and can be recognized by a single anti-Flag antibody, we demonstrate that Tax-2B is modified by ubiquitination and sumoylation. In addition, Tax2B is distributed in punctuate nuclear structures that include the RelA subunit of NF-κB, as has been previously demonstrated for Tax-1

EPIDEMIOLOGY AND RISK FACTORS HTLV VIRUS INFECTION IN PREGNANT WOMEN

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Adriella Silva Oliveira

2014-05-01

Full Text Available This study aimed to perform an integrative review of the epidemiology and the main risk factors for infection with human T lymphotropic to cells (HTLV in pregnant women from the Brazilian scientific production. The articles were extracted from databases: Literature Latin American and Caribbean Health Sciences (LILACS, Medical Literature Analysis and Retrieval System Online (MEDLINE and Scientific Electronic Library Online (SCIELO, with nine selected articles published between the years 2000-2012. Upon review of the studies it was observed that Brazil has significant prevalence of HTLV in pregnant women, demonstrating the need for adequate attention to this indicator. Some risk factors indicated by the studies analyzed were: low education, criterion race/color (infected pregnant women were mostly black, brown or indigenous majority, vertical transmission, sexual transmission, multiple pregnancies and premature sexual activity. Therefore, it is Epidemiologia e fatores de risco da infecção do vírus HTLV em gestantes important serologic screening to prevent congenital infections, as well as the introduction of new studies on the infection in Brazil. Thus, it becomes evident the need for planning and implementation of prevention and control of HTLV in the prenatal for structuring measures that minimize the appearance of new infections in pregnant women and children due to vertical transmission, the main route of transmission.

HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo.

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Yorifumi Satou

2011-02-01

Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 is the causal agent of a neoplastic disease of CD4+ T cells, adult T-cell leukemia (ATL, and inflammatory diseases including HTLV-1 associated myelopathy/tropical spastic paraparesis, dermatitis, and inflammatory lung diseases. ATL cells, which constitutively express CD25, resemble CD25+CD4+ regulatory T cells (T(reg. Approximately 60% of ATL cases indeed harbor leukemic cells that express FoxP3, a key transcription factor for T(reg cells. HTLV-1 encodes an antisense transcript, HTLV-1 bZIP factor (HBZ, which is expressed in all ATL cases. In this study, we show that transgenic expression of HBZ in CD4+ T cells induced T-cell lymphomas and systemic inflammation in mice, resembling diseases observed in HTLV-1 infected individuals. In HBZ-transgenic mice, CD4+Foxp3+ T(reg cells and effector/memory CD4+ T cells increased in vivo. As a mechanism of increased T(reg cells, HBZ expression directly induced Foxp3 gene transcription in T cells. The increased CD4+Foxp3+ T(reg cells in HBZ transgenic mice were functionally impaired while their proliferation was enhanced. HBZ could physically interact with Foxp3 and NFAT, thereby impairing the suppressive function of T(reg cells. Thus, the expression of HBZ in CD4+ T cells is a key mechanism of HTLV-1-induced neoplastic and inflammatory diseases.

Prevalencia de anticuerpos contra HTLV-1 en una población negra de Colombia

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María C. Navas

1995-03-01

Full Text Available El virus linfotrópico humano 1 (HTLV-1 ha sido asociado con la leucemia de células T del adulto (ATL y la paraparesia espástica tropical (PET o mielopatía asociada con HTLV-1 (HAM. Aunque la prevalencia de anticuerpos contra el HTLV-1 ha sido descrita en diversos países, especialmente en Japón, poco se conoce acerca de este marcador de contacto viral en nuestra población. En este artículo describimos la ausencia de niveles de anticuerpos anti-HTLV-1 en el suero, medidos por la prueba de ELISA, en una población negra de la costa atlántica de Colombia. Nuestros hallazgos sugieren que: a este grupo descendiente de África no se ha expuesto al virus; b puede ser que algunos de los individuos incluidos en el estudio estén en período de incubación y, que debido a su juventud, no fue posible demostrar una respuesta humoral contra el virus; y, c como ha sido descrito en otros estudios, la prevalencia de anticuerpos anti-HTLV- 1 varía entre las diferentes regiones de Colombia.

Low prevalence of antibodies to human T-lymphotropic virus-I/II among blood donors in eastern Saudi Arabia.

Science.gov (United States)

Fawaz, Naglaa A; Tamim, Hala; Almawi, Wassim Y

2005-04-01

The seroprevalence of human T-lymphotropic virus (HTLV)-I/II was assessed in 13,443 consecutive blood donors in eastern Saudi Arabia between 1998 and 2001. Screening by enzyme-linked immunosorbent assay (ELISA) and confirmation by Western blot resulted in 8 (0.060%) positive cases, of which 5 (0.056%) belonged to Saudi and 3 (0.113%) to non-Saudi donors. The majority of the HTLV-positive donations (6/8) were for patients, and none had a history of known risk factor for HTLV-I/II transmission. Although the very low prevalence of HTLV-I/II among Saudi donors does not support routine screening, screening of donors from other nationalities may be initiated, especially those from HTLV-I/II endemic areas.

Transcriptional activation of immediate-early gene ETR101 by human T-cell leukaemia virus type I Tax

DEFF Research Database (Denmark)

Chen, Li; Ma, Shiliang; Li, Bo

2003-01-01

Human T-cell leukaemia virus type I (HTLV-I) Tax regulates viral and cellular gene expression through interactions with multiple cellular transcription pathways. This study describes the finding of immediate-early gene ETR101 expression in HTLV-I-infected cells and its regulation by Tax. ETR101...... was persistently expressed in HTLV-I-infected cells but not in HTLV-I uninfected cells. Expression of ETR101 was dependent upon Tax expression in the inducible Tax-expressing cell line JPX-9 and also in Jurkat cells transiently transfected with Tax-expressing vectors. Tax transactivated the ETR101 gene promoter......-DNA complex in HTLV-I-infected cell lines. EMSA with specific antibodies confirmed that the CREB transcription factor was responsible for formation of this specific protein-DNA complex. These results suggested that Tax directly transactivated ETR101 gene expression, mainly through a CRE sequence via the CREB...

Prevalence of human T-lymphotropic virus type I and type II antibody among blood donors in Eastern Saudi Arabia.

Science.gov (United States)

Ul-Hassan, Zahoor; Al-Bahrani, Ahmad T; Panhotra, Bodh R

2004-10-01

Human T-cell leukemia/lymphoma virus type I and type II (HTLV-I/II) infections can be transfusion associated, leading to tropical paraparesis, myelopathy and other neurological disorders. The aim of this study is to circumvent the risk of transmission through blood transfusion and to describe the prevalence of HTLV-I/II antibody among blood donors of Al-Hasa region and the cost effectiveness of screening blood donors. The study was conducted at the Department of Laboratory and Blood Bank, King Fahad Hospital, Al-Hofuf, Al-Hasa, Kingdom of Saudi Arabia during the period of 1997 to 2003. A total of 47426 blood donors were screened for HTLV-I/II antibody by enzyme-linked immunosorbent assay test, during the 7 years of study period. The positive samples were confirmed by western blot analysis. Overall, HTLV-I antibody positivity (confirmed by western blot) was 3/47426 (0.006%). Out of 3 donors positive for HTLV-I antibody during 1997 to 1998, 2 were expatriates (Indian) and one was native Saudi donor. Human T-cell leukemia/lymphoma virus type I antibody positivity among the native Saudi donors was 1/47426 (0.002%) (2/100000 blood donors). None of the donor were positive for HTLV-II antibody. During the last 5 consecutive years of the study period (1999-2003), none of the donor was positive for HTLV-I/II antibody. Al-Hasa region is non-endemic for HTLV-I/II virus infections. Screening of native Saudi blood donors for these viruses does not appear to be cost effective.

Establishment of a Pcr Technique for Determination of Htlv-1 Infection in Paraffin-Embedded Tissues

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M Rastin

2007-04-01

Full Text Available Introduction: HTLV-1 , the first known human retrovirus belongs to oncovirus subfamily of retroviruses. The major characteristic of HTLV-1 is its highly restricted geographic prevalence. Northern part of Khorasan is an endemic region of HTLV-1 infection. Epidemiological studies can help in designing preventive programs for HTLV-1 infection. The aim of this study was the establishment of a PCR technique for determination of HTLV-1 infection in paraffin-embedded tissues. Methods: In this experimental laboratory study for establishment of a technique, PCR was initially optimized using Beta-actin primers on various formalin fixed paraffin-embedded tissues from liver, spleen, skin and lymph nodes. The optimized concentration of Mgcl2 was 2mm, primer was 8 pmol. Optimized concentration of DNA was different according to the kind of tissue. HTLV-1 infection was determined by applying tax, pol, env and LTR primers on 50 paraffin-embedded lymph node tissues . The reporoducibility of this technique was shown for skin and lymph node tissues infected with HTLV-1. Resuls: In 50 lymph node tissues, one case with pathologic diagnosis of NHL was positive with all 5 sets of primers (tax, Pol, env and LTR primers and the other case was positive with only two sets of tax primers but was negative with pol, env and LTR primers. The prevalence of infection was 2% among lymph node specimens. (1 of 50 specimens and if the second case is considered, the prevalence would be 4%. Conclusion: Comparison of the results of this study with another study on blood specimens (seroprevalence2.3% was not statistically significant thus confirming the results of one another. (P=0.883

Escolhas Associadas ao Automóvel por Homens e por Mulheres: confluência ou divergência? Choices associated with automobiles for Men and Women: convergence or divergence? Opciones relacionadas con el Automóvil por Hombres y por Mujeres: ¿convergencia o divergencia?

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LICHT, René Henrique Götz

2009-03-01

Full Text Available RESUMOO aumento do poder de compra das mulheres tem levado empresas a adotarem estratégias de diferenciação de produtos e a produzirem produtos específicos para o público feminino. A indústria automobilística não está imune a este fenômeno, uma vez que as mulheres representam aproximadamente metade das vendas de automóvel no país. Considerando as diferenças de consumo e de comportamento entre mulheres e homens é colocada a seguinte questão: há diferenças entre escolhas associadas ao automóvel por homens e mulheres? Foram apresentados aos participantes itens presentes no dia-a-dia das pessoas, e que são por elas valorizados; e foi solicitado aos participantes que escolhessem e associassem estes itens ao automóvel. A análise dos resultados revelou haver mais semelhanças do que diferenças entre escolhas associadas ao automóvel por homens e escolhas associadas ao automóvel por mulheres. A semelhança entre as escolhas sugere que as representações, os significados e valores atribuídos ao automóvel por homens e por mulheres são similares e, desta forma, a estratégia de diferenciação de produtos não se aplica à indústria automobilística.ABSTRACTThe increase of the women purchase power has led some companies to adopt strategies of products differentiation as well as to produce specific products to the female public. The auto industry is not immune to this phenomenon, once the women represent, approximately, half of the automobile sales in the country. Considering the consumption and the behavior differences between women and men, it has set the following question: are there differences between the choices associated to the automobile by men and the choices associated to the automobile by women? It has been presented to the participants items found in the people’s day-by-day, which are valorized by them, and the participants have been asked to choose and associate these items to the automobile. The results analysis

Role of resident CNS cell populations in HTLV-1-associated neuroinflammatory disease.

Science.gov (United States)

Lepoutre, Veronique; Jain, Pooja; Quann, Kevin; Wigdahl, Brian; Khan, Zafar K

2009-01-01

Human T cell leukemia virus type 1 (HTLV-1), the first human retrovirus discovered, is the etiologic agent for a number of disorders; the two most common pathologies include adult T cell leukemia (ATL) and a progressive demyelinating neuroinflammatory disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The neurologic dysfunction associated with HAM/TSP is a result of viral intrusion into the central nervous system (CNS) and the generation of a hyperstimulated host response within the peripheral and central nervous system that includes expanded populations of CD4+ and CD8+ T cells and proinflammatory cytokines/chemokines in the cerebrospinal fluid (CSF). This robust, yet detrimental immune response likely contributes to the death of myelin producing oligodendrocytes and degeneration of neuronal axons. The mechanisms of neurological degeneration in HAM/TSP have yet to be fully delineated in vivo and may involve the immunogenic properties of the HTLV-1 transactivator protein Tax. This comprehensive review characterizes the available knowledge to date concerning the effects of HTLV-1 on CNS resident cell populations with emphasis on both viral and host factors contributing to the genesis of HAM/TSP.

Properties of HTLV-I transformed CD8+ T-cells in response to HIV-1 infection.

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Gulzar, N; Shroff, A; Buberoglu, B; Klonowska, D; Kim, J E; Copeland, K F T

2010-10-25

HIV-1 infection studies of primary CD8(+) T-cells are hampered by difficulty in obtaining a significant number of targets for infection and low levels of productive infection. Further, there exists a paucity of CD8-expressing T-cell lines to address questions pertaining to the study of CD8(+) T-cells in the context of HIV-1 infection. In this study, a set of CD8(+) T-cell clones were originated through HTLV-I transformation in vitro, and the properties of these cells were examined. The clones were susceptible to T-cell tropic strains of the virus and exhibited HIV-1 production 20-fold greater than primary CD4(+) T-cells. Productive infection resulted in a decrease in expression of CD8 and CXCR4 molecules on the surface of the CD8(+) T-cell clones and antibodies to these molecules abrogated viral binding and replication. These transformed cells provide an important tool in the study of CD8(+) T-cells and may provide important insights into the mechanism(s) behind HIV-1 induced CD8(+) T-cell dysfunction. Copyright © 2010 Elsevier Inc. All rights reserved.

BCL11B is frequently downregulated in HTLV-1-infected T-cells through Tax-mediated proteasomal degradation.

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Permatasari, Happy Kurnia; Nakahata, Shingo; Ichikawa, Tomonaga; Morishita, Kazuhiro

2017-08-26

Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia-lymphoma (ATLL). The HTLV-1-encoded protein Tax plays important roles in the proliferation of HTLV-1-infected T-cells by affecting cellular proteins. In this study, we showed that Tax transcriptionally and post-transcriptionally downregulates the expression of the tumor suppressor gene B-cell leukemia/lymphoma 11B (BCL11B), which encodes a lymphoid-related transcription factor. BCL11B expression was downregulated in HTLV-1-infected T-cell lines at the mRNA and protein levels, and forced expression of BCL11B suppressed the proliferation of these cells. The proteasomal inhibitor MG132 increased BCL11B expression in HTLV-1-infected cell lines, and colocalization of Tax with BCL11B was detected in the cytoplasm of HTLV-1-infected T-cells following MG132 treatment. shRNA knock-down of Tax expression also increased the expression of BCL11B in HTLV-1-infected cells. Moreover, we found that Tax physically binds to BCL11B protein and induces the polyubiquitination of BCL11B and proteasome-dependent degradation of BCL11B. Thus, inactivation of BCL11B by Tax protein may play an important role in the Tax-mediated leukemogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Human T-cell lymphotropic virus types I and II infections in a cohort of patients with neurological disorders in Belém, Pará, Brazil Infecção pelos vírus linfotrópicos humanos de células T tipos I e II entre pacientes com doença neurológica em Belém, Pará, Brasil

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Olinda Macêdo

2004-02-01

Full Text Available Serum- and/or- cerebrospinal fluid (CSF samples obtained from 190 patients suffering from chronic, progressive neurological disease were screened for the presence of human T-cell lymphotropic viruses type I (HTLV-I and type II (HTLV-II antibodies over a six-year period (1996 to 2001 in Belém, Pará, Brazil. Patients were of both sexes (male subjects, 52% with ages ranging from 2 to 79 years (mean, 35.9. Overall, 15 (7.9% subjects - of whom 12 (80% were female adults - reacted HTLV-I/II-seropositive when screened by enzyme-linked immunosorbent assay (ELISA. Serum samples from 14 of these patients were also analyzed using a recombinant Western blot (WB assay that yielded HTLV-I-, HTLV-II-, and HTLV-I/II- reactivities for 10 (71.4%, 3 (21.4% and 1 (7.2% of them, respectively. The yearly rates of HTLV-I/II antibodies ranged from 2.6% (2001 to 21.7% (2000, with progressively increasing seropositivities from 1998 to 2000. Altogether, walking difficulty (n = 5 subjects, spasticity (n = 4 and leg weakness (n = 3 accounted for 80% of symptoms recorded among the 15 patients whose sera had antibodies to HTLV-I/II as detected by ELISA. These findings provide evidence that both HTLV-I and HTLV-II play a role in the development of chronic myelopathy in Belém, Pará, Northern Brazil.Amostras de soro e/ou líquido céfalo-raquidiano (LCR foram obtidas de 190 pacientes com quadro de doença neurológica crônica e progressiva, com vistas à detecção de anticorpos para os vírus linfotrópicos humanos de células T dos tipos I (HTLV-I e II (HTLV-II, durante um período de seis anos (1996 a 2001 em Belém, Pará, Brasil. O grupo compreendia ambos os sexos (homens, 52%, com idades variando de 2 a 79 anos (média, 35,9 anos. Tomando-se os resultados como um todo, 15 (7,9% indivíduos, incluindo 12 (80% mulheres adultas, apresentaram anticorpos para HTLV-I/II a partir da triagem pelo procedimento imunoenzimático (ELISA. Soros de 14 desses pacientes também foram

Primeiro caso de febre maculosa brasileira branda associada à artrite

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Virgínia Lucia Nazario Bonoldi

2014-06-01

Full Text Available Descrevemos o primeiro caso brasileiro de Riquetsiose branda, agravada por monoartrite em joelho, em adulto jovem picado por carrapato na perna esquerda na região de Camburi, localizada no município de São Sebastião, sul da região costeira do estado de São Paulo, Mata Atlântica, Brasil. O paciente apresentou uma escara de inoculação no local da picada do carrapato, associada ao aumento ganglionar em virilha esquerda, febre, poliartralgia, cefaleia e erupção macular. Vinte dias após o episódio da picada de carrapato, o paciente apresentou monoartrite em joelho direito. O diagnóstico de Riquetsiose branda foi estabelecido pela análise imunológica sequencial em amostras de soro e líquido sinovial, tendo sido empregada a técnica de imunofluorescência (IF indireta para anticorpos reativos contra Rickettsia parkeri e Rickettsia rickettsii. A Riquetsiose branda é uma zoonose emergente, que deve ser investigada pelos médicos, incluindo reumatologistas, em pacientes que apresentem erupção macular, febre e, eventualmente, artrite, após visita ao sul da região costeira da Mata Atlântica no Brasil.

Molecular epidemiology of HIV, HBV, HCV, and HTLV-1/2 in drug abuser inmates in central Javan prisons, Indonesia.

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Prasetyo, Afiono Agung; Dirgahayu, Paramasari; Sari, Yulia; Hudiyono, Hudiyono; Kageyama, Seiji

2013-06-15

This study was conducted to determine the current molecular prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and human T lymphotropic virus-1/2 (HTLV-1/2) circulating among drug abuser inmates incarcerated in prisons located in Central Java, Indonesia. Socio-epidemiological data and blood specimens were collected from 375 drug abuser inmates in four prisons. The blood samples were analyzed with serological and molecular testing for HIV, HBV, HCV, HDV, and HTLV-1/2. The seroprevalence of HIV, HBsAg, HCV, HDV, and HTLV-1/2 in drug abuser inmates was 4.8% (18/375), 3.2% (12/375), 34.1% (128/375), 0% (0/375), and 3.7% (14/375), respectively. No co-infections of HIV and HBV were found. Co-infections of HIV/HCV, HIV/HTLV-1/2, HBV/HCV, HBV/HTLV-1/2, and HCV/HTLV-1/2 were prevalent at rates of 4% (15/375), 1.3% (5/375), 1.1% (4/375), 0.3% (1/375), and 2.1% (8/375), respectively. The HIV/HCV co-infection rate was significantly higher in injection drug users (IDUs) compared to non-IDUs. Triple co-infection of HIV/HCV/HTLV-1/2 was found only in three IDUs (0.8%). HIV CRF01_AE was found to be circulating in the inmates. HBV genotype B3 predominated, followed by C1. Subtypes adw and adr were found. HCV genotype 1a predominated among HCV-infected inmates, followed by 1c, 3k, 3a, 4a, and 1b. All HTLV-1 isolates shared 100% homology with HTLV-1 isolated in Japan, while all of the HTLV-2 isolates were subtype 2a. Drug abuser inmates in prisons may offer a unique community to bridge prevention and control of human blood-borne virus infection to the general community.

HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling.

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Huang, Qingsong; Niu, Zhiguo; Han, Jingxian; Liu, Xihong; Lv, Zhuangwei; Li, Huanhuan; Yuan, Lixiang; Li, Xiangping; Sun, Shuming; Wang, Hui; Huang, Xinxiang

2017-08-01

Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibition of NF-κB activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-κB induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-κB pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-κB activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-κB activation in HTLV-1-infected and Tax-expressing cells. Both NF-κB activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-κB activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target.

HTLV-1 and HIV-1 co-infection: A case report and review of the literature

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Carmen Isache

2016-01-01

HTLV and HIV share the same routes of transmission and the same tropism for T-lymphocytes. Co-infection occurs probably more frequently than we are aware, since testing for HTLV is not routinely performed in outpatient HIV clinics.

A case-control study of HTLV-infection among blood donors in Salvador, Bahia, Brazil - associated risk factors and trend towards declining prevalence Estudo da infecção do HTLV entre doadores de sangue de Salvador, Bahia, Brasil

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Augusto Mota

2006-06-01

Full Text Available Previous data suggest that Salvador, the capital of the State of Bahia, a northeastern state of Brazil, has the highest prevalence of HTLV infection in blood donors among Brazilian cities. The aim of this case-control study was to identify the determinants of risk for HTLV infection among blood donors in the city of Salvador. Between January 2000 and December 2003, 504 blood donors with positive screening tests for HTLV infection (unconfirmed prevalence of 0.48% were invited to participate in our study. A total of 154 had performed a Western Blot (WB test, 139 were of which found to be positive (false positive screening rate 9.9%. Using a standardized questionnaire, a single interviewer obtained information on demographic, socio-economical and educational characteristics, as well as sexual behavior from 91 out of the 139 positive by WB and from 194 HTLV-negative blood donors. Prevalence of HTLV infection was 0.48%. Multivariate analysis revealed women (OR 3.79 [1.61-8.88], p=0.002, low family income* (OR 3.37 [1.17-9.66], p=0.02, self-reported history of sexual transmitted diseases (OR 6.15 [2.04-18.51], p=0.001, 2 or more sexual partners during life (OR 9.29 [2.16-39.94], p=0.0020 and inconsistent use of condoms (OR 4.73 [1.98-11.26], p=0.0004 as risk factors for HTLV infection. In accordance with previous published data, our results point to an association between low socio-economical level, poor education and unsafe sexual behavior with HTLV infection. We observed a lower prevalence of HLTV infection when compared to previous data.Estudos anteriores sugerem que Salvador, capital da Bahia, um estado do Nordeste do Brasil, tem a maior prevalência de infecção por HTLV em doadores de sangue entre as cidades brasileiras. O objetivo deste estudo caso-controle foi identificar os determinantes de risco para a infecção por HTLV entre doadores de sangue em Salvador. Entre janeiro 2000 e dezembro 2003, 504 doadores de sangue positivos para a infec

Framework com as contribuições da convergência digital possibilitada pela utilização das tecnologias interativas da TV digital, associadas ao uso dos dispositivos móveis digitais, para a evolução do modelo brasileiro de governo eletrônico

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Ferreira, Marcus Vinicius Anátocles da Silva

2013-01-01

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro Tecnológico, Programa de Pós-Graduação em Engenharia e Gestão do Conhecimento, Florianópolis, 2013. Esta pesquisa tem como foco a concepção de um framework com as contribuições da convergência digital possibilitada pelas tecnologias interativas da TV Digital, associadas ao uso dos dispositivos móveis digitais, para a evolução do modelo de governo eletrônico no Brasil. A pesquisa utiliza como referência a validação do pressup...

Interaction of HTLV-1 Tax protein with the calreticulin: Implications for Tax nuclear export and secretion

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Alefantis, Timothy; Flaig, Katherine E.; Wigdahl, Brian; Jain, Pooja

2007-01-01

Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 transcriptional transactivator protein Tax plays an integral role in virus replication and disease progression. Traditionally, Tax is described as a nuclear protein where it performs its primary role as a transcriptional transactivator. However, recent studies have clearly shown that Tax can also be localized to t...

Manejo de capim pé-de-galinha em lavouras de soja transgênica resistente ao glifosato

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André da Rosa Ulguim

2013-01-01

Full Text Available O objetivo deste trabalho foi avaliar a resistência de capim pé-de-galinha (Eleusine indica ao glifosato, em lavouras de soja transgênica; avaliar o efeito de aplicações de glifosato em diferentes estádios de desenvolvimento; identificar práticas agronômicas associadas à seleção de biótipos resistentes; e avaliar a eficiência dos herbicidas cletodim, fluazifope-P-butílico, clomazona, glufosinato de amônio e glifosato nas plantas resistentes. Plantas escapes ao tratamento com glifosato foram coletadas em 24 propriedades, no Rio Grande do Sul. As plantas foram cultivadas em casa de vegetação, tendo-se avaliado a sua resistência ao glifosato. Os acessos resistentes foram selecionados e avaliados quanto ao efeito da aplicação do glifosato em diferentes estádios de crescimento e quanto à sensibilidade aos herbicidas. Foi aplicado um questionário aos produtores para identificação das práticas agronômicas associadas às falhas no controle. O controle de E. indica pelo glifosato é mais efetivo com a aplicação em estádios iniciais de desenvolvimento. Práticas agronômicas, como uso contínuo de baixas doses do herbicida, aplicação em estádios de desenvolvimento avançados das plantas daninhas (mais de um afilho e a ausência de rotação de culturas foram relacionadas às falhas de controle observadas. Os herbicidas cletodim, fluazifope-P-butílico e glufosinato de amônio são alternativas eficientes para o controle de E. indica.

Representações mentais da violência entre íntimos: estudo das ideologias associadas ao género

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Santos, Marina Sofia Dinis

2016-01-01

Dissertação de mestrado em Psicologia Clínica e da Saúde (Psicopatologia e Psicoterapias Dinâmicas), apresentada à Faculdade de Psicologia e Ciências da Educação da Universidade de Coimbra O presente estudo teve como principal objetivo perceber se as representações mentais sobre violência entre parceiros íntimos estão associadas a atitudes sexistas, patriarcais e à legitimação da violência entre íntimos. O estudo realizou-se numa amostra da população geral, constituída por 90 indivíduos do...

Evaluation of the role of TAX, HBZ, and HTLV-1 proviral load on the survival of ATLL patients.

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Akbarin, Mohammad Mehdi; Shirdel, Abbas; Bari, Alireza; Mohaddes, Seyedeh Tahereh; Rafatpanah, Houshang; Karimani, Ehsan Ghayour; Etminani, Kobra; Golabpour, Amin; Torshizi, Reza

2017-06-01

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with very poor prognosis and short survival, caused by the human T-lymphotropic virus type-1 (HTLV-1). The HTLV-1 biomarkers trans-activator x (TAX) and HTLV-1 basic leucine zipper factor (HBZ) are main oncogenes and life-threatening elements. This study aimed to assess the role of the TAX and HBZ genes and HTLV-1 proviral load (PVL) in the survival of patients with ATLL. Forty-three HTLV-1-infected individuals, including 18 asymptomatic carriers (AC) and 25 ATLL patients (ATLL), were evaluated between 2011 and 2015. The mRNA expression of TAX and HBZ and the HTLV-1 PVL were measured by quantitative PCR. Significant differences in the mean expression levels of TAX and HBZ were observed between the two study groups (ATLL and AC, P =0.014 and P =0.000, respectively). In addition, the ATLL group showed a significantly higher PVL than AC ( P =0.000). There was a significant negative relationship between PVL and survival among all study groups ( P =0.047). The HTLV-1 PVL and expression of TAX and HBZ were higher in the ATLL group than in the AC group. Moreover, a higher PVL was associated with shorter survival time among all ATLL subjects. Therefore, measurement of PVL, TAX , and HBZ may be beneficial for monitoring and predicting HTLV-1-infection outcomes, and PVL may be useful for prognosis assessment of ATLL patients. This research demonstrates the possible correlation between these virological markers and survival in ATLL patients.

HTLV-1 Alters T Cells for Viral Persistence and Transmission

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Azusa Tanaka

2018-03-01

Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 was the first retrovirus to be discovered as a causative agent of adult T-cell leukemia-lymphoma (ATL and chronic inflammatory diseases. Two viral factors, Tax and HTLV-1 bZIP factor (HBZ, are thought to be involved in the leukemogenesis of ATL. Tax expression is frequently lost due to DNA methylation in the promoter region, genetic changes to the tax gene, and deletion of the 5′ long terminal repeat (LTR in approximately half of all ATL cases. On the other hand, HBZ is expressed in all ATL cases. HBZ is known to function in both protein form and mRNA form, and both forms play an important role in the oncogenic process of HTLV-1. HBZ protein has a variety of functions, including the suppression of apoptosis, the promotion of proliferation, and the impairment of anti-viral activity, through the interaction with several host cellular proteins including p300/CBP, Foxp3, and Foxo3a. These functions dramatically modify the transcriptional profiling of host T cells. HBZ mRNA also promotes T cell proliferation and viability. HBZ changes infected T cells to CCR4+TIGIT+CD4+ effector/memory T cells. This unique immunophenotype enables T cells to migrate into various organs and tissues and to survive in vivo. In this review, we summarize how HBZ hijacks the transcriptional networks and immune systems of host T cells to contribute to HTLV-1 pathogenesis on the basis of recent new findings about HBZ and tax.

HTLV-1 modulates the frequency and phenotype of FoxP3+CD4+ T cells in virus-infected individuals

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Satou Yorifumi

2012-05-01

Full Text Available Abstract Background HTLV-1 utilizes CD4 T cells as the main host cell and maintains the proviral load via clonal proliferation of infected CD4+ T cells. Infection of CD4+ T cells by HTLV-1 is therefore thought to play a pivotal role in HTLV-1-related pathogenicity, including leukemia/lymphoma of CD4+ T cells and chronic inflammatory diseases. Recently, it has been reported that a proportion of HTLV-1 infected CD4+ T cells express FoxP3, a master molecule of regulatory T cells. However, crucial questions remain unanswered on the relationship between HTLV-1 infection and FoxP3 expression. Results To investigate the effect of HTLV-1 infection on CD4+ T-cell subsets, we used flow cytometry to analyze the T-cell phenotype and HTLV-1 infection in peripheral mononuclear cells (PBMCs of four groups of subjects, including 23 HTLV-1-infected asymptomatic carriers (AC, 10 patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP, 10 patients with adult T-cell leukemia (ATL, and 10 healthy donors. The frequency of FoxP3+ cells in CD4+ T cells in AC with high proviral load and patients with HAM/TSP or ATL was higher than that in uninfected individuals. The proviral load was positively correlated with the percentage of CD4+ T cells that were FoxP3+. The CD4+FoxP3+ T cells, themselves, were frequently infected with HTLV-1. We conclude that FoxP3+ T- cells are disproportionately infected with HTLV-1 during chronic infection. We next focused on PBMCs of HAM/TSP patients. The expression levels of the Treg associated molecules CTLA-4 and GITR were decreased in CD4+FoxP3+ T cells. Further we characterized FoxP3+CD4+ T-cell subsets by staining CD45RA and FoxP3, which revealed an increase in CD45RA−FoxP3low non-suppressive T-cells. These findings can reconcile the inflammatory phenotype of HAM/TSP with the observed increase in frequency of FoxP3+ cells. Finally, we analyzed ATL cells and observed not only a high frequency of FoxP3 expression

Detection of HTLV-III RNA in lungs of patients with AIDS and pulmonary involvement

International Nuclear Information System (INIS)

Chayt, K.J.; Harper, M.E.; Marselle, L.M.; Lewin, E.B.; Rose, R.M.; Oleske, J.M.; Epstein, L.G.; Wong-Staal, F.; Gallo, R.C.

1986-01-01

A majority of pediatric patients and rare adult patients with the acquired immunodeficiency syndrome (AIDS) develop a chronic respiratory disorder referred to as lymphocytic interstitial pneumonitis (LIP). Efforts to identify an infectious agent responsible for this process so far have failed. In this study, frozen sections of lungs from patients with AIDS and pulmonary disease were tested by in situ molecular hybridization for the presence of cells infected with human T-cell lymphotropic virus type III (HTLV-III) and expressing viral RNA. In the case of an infant with LIP, a relatively high frequency (0.1%) of cells in the lung were found to be positive for HTLV-III RNA. This number is the lower limit of total cells infected since the in situ hybridization technique as applied in this study depends on expression of HTLV-III genes, and previous evidence indicates that a proportion of cells infected with HTLV-III may not express viral RNA. Moreover, this degree of infection of the lung is likely limited to LIP, since in ten patients with AIDS and pulmonary diseases other than LIP, only 0% to 0.002% of cells in lung were positive for viral RNA expression. Thus, HTLV-III may play a direct causal role in the development of LIP in infected patients, implicating its involvement in yet another of the diverse clinical diseases associated with this virus

Influência da vitamina D associada ao interferon alfa-peguilado e ribavirina na resposta virológica sustentada na hepatite C crônica

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Luiza Vitelo ANDRIGHETTO; Jacqueline Shaurich dos SANTOS; Graziella NICOLETTI; Patricia Martins BOCK

2016-01-01

O objetivo deste trabalho foi avaliar a influência da vitamina D no tratamento de hepatite C com interferon-alfa peguilado e ribavirina. Foram utilizados artigos científicos relevantes publicados entre os anos de 2000 e 2015. Em diversos estudos foi observado que níveis mais elevados de vitamina D estavam associados à rápida resposta ao tratamento e à maior taxa de RVS, sugerindo que a deficiência de vitamina D pode estar ligada a uma falta de resposta ao tratamento antiviral. A i...

Human T-lymphotropic virus type I tax regulates the expression of the human lymphotoxin gene.

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Tschachler, E; Böhnlein, E; Felzmann, S; Reitz, M S

1993-01-01

Human T-lymphotropic virus type-I (HTLV-I)-infected T-cell lines constitutively produce high levels of lymphotoxin (LT). To analyze the mechanisms that lead to the expression of LT in HTLV-I-infected cell lines, we studied regulatory regions of the human LT promoter involved in the activation of the human LT gene. As determined by deletional analysis, sequences between +137 and -116 (relative to the transcription initiation site) are sufficient to direct expression of a reporter gene in the HTLV-I-infected cell line MT-2. Site-directed mutation of a of the single kappa B-like motif present in the LT promoter region (positions -99 to -89) completely abrogated LT promoter activity in MT-2 cells, suggesting that this site plays a critical role in the activation of the human LT gene. Transfection of LT constructs into HTLV-I-uninfected and -unstimulated Jurkat and U937 cell lines showed little to no activity of the LT promoter. Cotransfection of the same constructs with a tax expression plasmid into Jurkat cells led to detectable promoter activity, which could be significantly increased by stimulation of the cells with phorbol myristate acetate (PMA). Similarly, cotransfection of the LT promoter constructs and the tax expression plasmid into U937 cells led to significant promoter activity upon stimulation with PMA. These data suggest that HTLV-I tax is involved in the upregulation of LT gene expression in HTLV-I-infected cells.

Osteonecrose da mandíbula associada aos bifosfonatos em doentes com cancro do pulmão

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Inês Neves

2013-09-01

Full Text Available Resumo: A osteonecrose da mandíbula (ONM pode surgir como complicação do tratamento com bifosfonatos. Esta patologia tem sido descrita em doentes com cancro e o seu desenvolvimento associado a exposição prolongada a altas doses de bifosfonatos. Má higiene dentária, história de uso de próteses ou extração dentária, quimioterapia, corticosteroides e radioterapia da cabeça e pescoço são fatores de risco reportados. Nas fases iniciais pode ser assintomática, contudo, o doente posteriormente desenvolve dor significativa e exposição óssea progressiva. Os autores descrevem 3 casos de ONM em doentes com cancro do pulmão após exposição prolongada a bifosfonatos e na presença de fatores de risco conhecidos. A ONM pode atingir seriamente a qualidade de vida dos doentes com cancro. O diagnóstico precoce poderá reduzir ou mesmo evitar as consequências da lesão óssea progressiva. Abstract: Osteonecrosis of the jaw (ONJ can occur as a complication of bisphosphonate therapy. This condition has been described in cancer patients and its development has been associated with prolonged exposure to high doses of bisphosphonates. Bad dental hygiene, a history of prosthesis or dental extraction, chemotherapy, corticosteroids, and radiation therapy of the head and neck are risk factors reported. In the initial stages it may be asymptomatic, but the patient subsequently develops severe pain and progressive exposed bone. The authors describe three cases of ONJ in lung cancer patients after prolonged exposure to bisphosphonates and there were known risk factors. ONJ can seriously affect the quality of life of cancer patients. An early diagnosis may reduce or avoid the consequences of progressive bone lesion. Palavras-chave: Osteonecrose da mandíbula associada aos bifosfonatos, Cancro do pulmão, Fatores de risco, Tratamento, Keywords: Bisphosphonate-associated osteonecrosis of the

Infección por HTLV-1 y HIV en pacientes con herpes zoster en Perú

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Sandra Delgado

2011-07-01

Full Text Available Objetivos: Determinar la frecuencia de infección por el virus linfotrópico humano tipo 1 (HTLV-1 y VIH en pacientes con herpes zoster. Material y métodos: Estudio prospectivo observacional realizado entre agosto de 2005 y agosto de 2006. Se incluyeron pacientes adultos con diagnóstico de herpes zoster atendidos en los diferentes servicios del Hospital Nacional Cayetano Heredia. Un cuestionario de características clínicas y factores de riesgo asociados con infección por HTLV-1 y VIH fue completado previo a la toma de muestra. Se excluyeron los pacientes con resultados positivos previos para HTLV-1 y HIV. Resultados: Se incluyeron 44 pacientes, la edad promedio fue 48,1 ± 19,5; 24/44 (55% fueron mujeres. Infección solo por VIH se encontró en 4/44 (9% pacientes, todos menores de 35 años, mientras que infección solo por HTLV-1 se encontró en 2/44 (5% pacientes, todas mujeres mayores de 50 años. Un caso de infección dual fue encontrado en una mujer de 56 años. La tasa de infección por HTLV-1 fue 25% (3/12 en mujeres mayores de 50 años con compromiso de múltiples dermatomas. Conclusiones: En nuestro escenario, la infección por HTLV-1 es ligeramente mas frecuente en mujeres mayores de 50 años con herpes zoster. Por ello, el despistaje de HTLV-1 debe ser recomendado en este grupo etario, mientras que el despistaje de VIH es aún particularmente importante en pacientes jóvenes.(Rev Med Hered 2011;22:98-102.

Prevalence of HTLV-1/2 in pregnant women living in the metropolitan area of Rio de Janeiro.

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Denise Leite Maia Monteiro

2014-09-01

Full Text Available HTLV-1/2 infection can cause severe and disabling diseases in children and adults. The aim of the study was to estimate the prevalence of HTLV-1/2 infection in pregnant women living in the metropolitan area of Rio de Janeiro.1,204 pregnant women were tested upon hospital admission for delivery in two public hospitals in the cities of Rio de Janeiro and Mesquita, between November, 2012 and April, 2013. The samples were screened by chemiluminescent microparticle immunoassay (CMIA and reactive ones were confirmed by Western blot (WB. Epi-info software was used for building the database and performing the statistical analysis. Eight patients had confirmed HTLV-1/2 infection (7 HTLV-1, one HTLV-2, equivalent to a prevalence rate of 0.66%. Two further reactive screening tests had negative Western blot results and therefore were considered negative in the statistical analysis. All HTLV-1/2-positive patients were born in Rio de Janeiro, most were non-Caucasian (87.5%, in a stable relationship (62.5%, had at least ten years of formal education (62.5% and a monthly family income of up to US$600.00 (87.5%. There was only one case of coinfection with syphilis and none with HIV. The mean age of the infected women was 28.4 (SD = 6.3 years and of the seronegative ones was 24.8 (SD = 6.5 (p = 0.10. The median number of pregnancies were 3.0 and 1.0 (p = 0.06 and the median number of sexual partners were 3.5 and 3.0 (p = 0.33 in the seropositive and negative groups, respectively. There were no statistically significant differences between the groups.A significant prevalence of HTLV-1/2 was found in our population. The socio-epidemiological profile of carrier mothers was similar to the controls. Such findings expose the need for a public health policy of routine HTLV-1/2 screening in antenatal care, since counselling and preventive measures are the only strategies currently available to interrupt the chain of transmission and the future development of HTLV-1

HTLV Tax: a fascinating multifunctional co-regulator of viral and cellular pathways

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Robert eCurrer

2012-11-01

Full Text Available Human T cell lymphotropic virus type 1 (HTLV-1 has been identified as the causative agent of adult T cell leukemia (ATL and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. The virus infects between 15 and 20 million people worldwide of which approximately 2 to 5% develop ATL. The past 35 years of research have yielded significant insight into the pathogenesis of HTLV-1, including the molecular characterization of Tax, the viral transactivator and oncoprotein. In spite of these efforts, the mechanisms of oncogenesis of this pleiotropic protein remain to be fully elucidated. In this review, we illustrate the multiple oncogenic roles of Tax by summarizing a recent body of literature that refines our understanding of cellular transformation. A focused range of topics are discussed in this review including Tax-mediated regulation of the viral promoter and other cellular pathways, particularly the connection of the NF-κB pathway to both post-translational modifications of Tax and sub-cellular localization. Specifically, recent research on polyubiquitination of Tax as it relates to the activation of the IkappaB kinase (IKK complex is highlighted. Regulation of the cell cycle and DNA damage responses due to Tax are also discussed, including Tax interaction with minichromosome maintenance proteins and the role of Tax in chromatin remodeling. The recent identification of HTLV-3 has amplified the importance of the characterization of emerging viral pathogens. The challenge of the molecular determination of pathogenicity and malignant disease of this virus lies in the comparison of the viral transactivators of HTLV-1, -2, and -3 in terms of transformation and immortalization. Consequently, differences between the three proteins are currently being studied to determine what factors are required for the differences in tumorogenesis.

HTLV Tax: A Fascinating Multifunctional Co-Regulator of Viral and Cellular Pathways

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Currer, Robert; Van Duyne, Rachel; Jaworski, Elizabeth; Guendel, Irene; Sampey, Gavin; Das, Ravi; Narayanan, Aarthi; Kashanchi, Fatah

2012-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) has been identified as the causative agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The virus infects between 15 and 20 million people worldwide of which approximately 2–5% develop ATL. The past 35 years of research have yielded significant insight into the pathogenesis of HTLV-1, including the molecular characterization of Tax, the viral transactivator, and oncoprotein. In spite of these efforts, the mechanisms of oncogenesis of this pleiotropic protein remain to be fully elucidated. In this review, we illustrate the multiple oncogenic roles of Tax by summarizing a recent body of literature that refines our understanding of cellular transformation. A focused range of topics are discussed in this review including Tax-mediated regulation of the viral promoter and other cellular pathways, particularly the connection of the NF-κB pathway to both post-translational modifications (PTMs) of Tax and subcellular localization. Specifically, recent research on polyubiquitination of Tax as it relates to the activation of the IkappaB kinase (IKK) complex is highlighted. Regulation of the cell cycle and DNA damage responses due to Tax are also discussed, including Tax interaction with minichromosome maintenance proteins and the role of Tax in chromatin remodeling. The recent identification of HTLV-3 has amplified the importance of the characterization of emerging viral pathogens. The challenge of the molecular determination of pathogenicity and malignant disease of this virus lies in the comparison of the viral transactivators of HTLV-1, -2, and -3 in terms of transformation and immortalization. Consequently, differences between the three proteins are currently being studied to determine what factors are required for the differences in tumorogenesis. PMID:23226145

Human T-lymphotropic virus type-I infection, antibody titers and cause-specific mortality among atomic-bomb survivors

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Arisawa, Kokichi; Soda, Midori; Akahoshi, Masazumi [Radiation Effects Research Foundation, Nagasaki (Japan). Nagasaki Lab.; Matsuo, Tatsuki; Nakashima, Eiji; Tomonaga, Masao; Saito, Hiroshi

1998-08-01

There have been few longitudinal studies on the long-term health effects of human T-lymphotropic virus type-I (HTLV-I) infection. The authors performed a cohort study of HTLV-I infection and cause-specific mortality in 3,090 atomic-bomb survivors in Nagasaki, Japan, who were followed from 1985-1987 to 1995. The prevalence of HTLV-I seropositivity in men and women was 99/1,196 (8.3%) and 171/1,894 (9.0%), respectively. During a median follow-up of 8.9 years, 448 deaths occurred. There was one nonfatal case of adult T-cell leukemia/lymphoma (incidence rate=0.46 cases/1,000 person-years; 95% confidence interval (CI) 0.01-2.6). After adjustment for sex, age and other potential confounders, significantly increased risk among HTLV-I carriers was observed for deaths from all causes (rate ratio (RR)=1.41), all cancers (RR=1.64), liver cancer (RR=3.04), and heart diseases (RR=2.22). The association of anti-HTLV-I seropositivity with mortality from all non-neoplastic diseases (RR=1.40) and chronic liver diseases (RR=5.03) was of borderline significance. Possible confounding by blood transfusions and hepatitis C/B (HCV/HBV) viral infections could not be precluded in this study. However, even after liver cancer and chronic liver diseases were excluded, mortality rate was still increased among HTLV-I carriers (RR=1.32, 95% CI 0.99-1.78), especially among those with high antibody titers (RR=1.56, 95% CI 0.99-2.46, P for trend=0.04). These findings may support the idea that HTLV-I infection exerts adverse effects on mortality from causes other than adult T-cell leukemia/lymphoma. Further studies on confounding by HCV/HBV infections and the interaction between HCV/HBV and HTLV-I may be required to analyze the increased mortality from liver cancer and chronic liver diseases. (author)

Neurological aspects of HTLV-1 infection in Bahia: results from an 8-year cohort

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Davi Tanajura

2015-01-01

Full Text Available HTLV-1 is the causal agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, a disease observed in up to 5% of individuals infected with HTLV-1. However, infected individuals without the disease can present neurological complaints relating to sensory, motor or urinary manifestations. The aim of this study was to investigate the incidence of neurological manifestations among patients with HTLV-1. Method HTLV-1 patients in Salvador, Bahia, Brazil, were enrolled into a cohort study. Results Among 414 subjects, 76 had definite and 87 had possible or probable HAM/TSP at the baseline, whereas 251 subjects had no neurological signs or symptoms. Definite HAM/TSP developed in 5 patients (1.74%. The asymptomatic subjects were selected for analysis. The incidence rate expressed per 1,000 persons-year was calculated. It was 206 for hand numbness, 129 for nocturia and 126 for urinary urgency. In the neurological examination, leg hyperreflexia presented an average incidence rate of 76; leg paraparesis, 52; and Babinski sign, 36. Kaplan-Meyer curves categorized according to gender and proviral load showed that females and patients with proviral load of more than 100,000 copies per 106 peripheral blood mononuclear cells (PBMCs presented higher risk. Conclusion Development of neurological symptoms or signs occurred in up to 30% of asymptomatic subjects during 8 years of follow-up. Female gender and high proviral load were risk factors for neurological disease.

NF-κB signaling mechanisms in HTLV-1-induced adult T-cell leukemia/lymphoma.

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Harhaj, Edward William; Giam, Chou-Zen

2018-05-03

The human T-cell leukemia virus type 1 (HTLV-1) is a complex deltaretrovirus linked to adult T-cell leukemia/lymphoma (ATLL), a fatal CD4+ malignancy in 3-5% of infected individuals. The HTLV-1 Tax regulatory protein plays indispensable roles in regulating viral gene expression and activating cellular signaling pathways that drive the proliferation and clonal expansion of T cells bearing HTLV-1 proviral integrations. Tax is a potent activator of NF-κB, a key signaling pathway that is essential for the survival and proliferation of HTLV-1 infected T cells. However, constitutive NF-κB activation by Tax also triggers a senescence response, suggesting the possibility that only T cells capable of overcoming NF-κB-induced senescence can selectively undergo clonal expansion after HTLV-1 infection. Tax expression is often silenced in the majority of ATLL due to genetic alterations in the tax gene or DNA hypermethylation of the 5'-LTR. Despite the loss of Tax, NF-κB activation remains persistently activated in ATLL due to somatic mutations in genes in the T/B-cell receptor (T/BCR) and NF-κB signaling pathways. In this review, we focus on the key events driving Tax-dependent and independent mechanisms of NF-κB activation during the multi-step process leading to ATLL. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Avaliação do tempo para acesso ao tratamento do câncer de mama no Distrito Federal

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Barros, Ângela Ferreira [UNESP

2011-01-01

A alta taxa de mortalidade do câncer de mama em países em desenvolvimento é associada à falta de programas de detecção precoce, ao retardo no diagnóstico e tratamento, bem como às dificuldades para acesso aos serviços de saúde. O objetivo desse estudo foi identificar artigos que associaram o retardo no diagnóstico e tratamento com a evolução do câncer de mama, verificar os fatores associados ao atraso e apontar sugestões para minimizar o atraso no diagnóstico e tratamento do câncer de mama. F...

Hábitos alimentares e estado nutricional de doentes com problemas ligados ao álcool, antes e após consulta num Centro de Desintoxicação Alcoólica : trabalho de investigação : dietary habits and nutritional state of patients with alcohol-related problems, before and after a consultation in a Centre for Alcohol Detoxification

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Dias, Delphine Oliveira

2008-01-01

Resumo da tese:Objectivo: Caracterização de uma amostra de doentes com problemas ligados ao álcool, quanto ao estado nutricional e hábitos alimentares, antes e após uma consulta num centro de desintoxicação alcoólica. Métodos: A amostra era constituída por 69 indivíduos do sexo masculino e 14 do sexo feminino, que foram sujeitos a duas avaliações, uma associada ao consumo excessivo de álcool e outra, associada ao período de abstinência alcoólica. A avalição consistiu na recolha de dados antro...

Characteristics of co-infections by HCV and HBV among Brazilian patients infected by HIV-1 and/or HTLV-1

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Marcia Moreira

Full Text Available BACKGROUND: The human retroviruses HIV-1 and HTLV-1 share the routes of infection with hepatitis viruses B and C. Co-infection by these agents are a common event, but we have scarce knowledge on co-infection by two or more of these agents. OBJECTIVE: To evaluate the characteristics and risk factors for co-infections by HBV and HCV in patients infected by HIV-1 or/and HTLV-1, in Salvador, Brazil. METHODS: In a case-control study we evaluated patients followed in the AIDS and HTLV clinics of Federal University of Bahia Hospital. Clinical and epidemiological characteristics were reviewed, and patients were tested for the presence of serological markers of HBV and HCV infections. HCV-infected patients were tested by PCR to evaluate the presence of viremia. RESULTS: A total of 200 HIV-1, 213 HTLV-1-infected, and 38 HIV-HTLV-co-infected individuals were included. HIV-infected patients were more likely to have had more sexual partners in the lifetime than other patients' groups. HIV-HTLV-co-infected subjects were predominantly male. Patients infected by HTLV or co-infected had a significantly higher frequency of previous syphilis or gonorrhea, while HIV infection was mainly associated with HPV infection. Co-infection was significantly associated to intravenous drug use (IVDU. HBV and/or HCV markers were more frequently found among co-infected patients. HBV markers were more frequently detected among HIV-infected patients, while HCV was clearly associated with IVDU across all groups. AgHBs was strongly associated with co-infection by HIV-HTLV (OR = 22.03, 95% CI: 2.69-469.7, as well as confirmed HCV infection (p = 0.001. Concomitant HCV and HBV infection was also associated with retroviral co-infection. Patients infected by HTLV-1 had a lower chance of detectable HCV viremia (OR = 0.04, 95% CI: 0.002-0.85. CONCLUSIONS: Infection by HCV and/or HBV is frequent among patients presenting retroviral infection, but risk factors and prevalence for each

Descrição de um surto de lepidopterismo (dermatite associada ao contato com mariposas entre marinheiros, ocorrido em Salvador, Estado da Bahia Description of an outbreak of lepidopterism (dermatitis associated with contact with moths among sailors in Salvador, State of Bahia

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Shirlei Cristina Moreira

2007-10-01

Full Text Available A ocorrência uma dermatite pápulo-pruriginosa em toda a tripulação de um navio comercial filipino em Salvador, BA, foi associada ao contato com mariposas do gênero Hylesia. Esta enfermidade insólita é causada por cerdas corporais das mariposas (flechettes. O relato dos casos serve como alerta para possíveis situações semelhantes.An occurrence of pruritic papular dermatitis among the whole crew of a Filipino commercial ship in Salvador, State of Bahia, was associated with contact with Hylesia moths. This unusual type of dermatitis is caused by the bristles (flechettes on the moths' bodies. Reporting on such cases serves to warn about possible similar situations.

Freqüência das infecções pelo HIV-1, rubéola, sífilis, toxoplasmose, citomegalovírus, herpes simples, hepatite B, hepatite C, doença de Chagas e HTLV I/II em gestantes, do Estado de Mato Grosso do Sul Frequency of HIV-1, rubella, syphilis, toxoplasmosis, cytomegalovirus, simple herpes virus, hepatitis B, hepatitis C, Chagas’ disease and HTLV I/II infection in pregnant women of State of Mato Grosso do Sul

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Ernesto Antonio Figueiró-Filho

2007-04-01

Full Text Available Objetivou-se avaliar a freqüência das infecções por sífilis, rubéola, hepatite B, hepatite C, toxoplasmose, doença de Chagas, HTLV I/II, herpes simples, HIV-1 e citomegalovírus em gestantes e relacionar a faixa etária das pacientes com a freqüência das infecções. Estudo transversal de 32.512 gestantes submetidas à triagem pré-natal no período de novembro de 2002 a outubro de 2003. As freqüências encontradas foram de 0,2% para infecção pelo vírus HIV-1, 0,03% para rubéola, 0,8% para sífilis, 0,4% para toxoplasmose, 0,05% para infecção aguda pelo citomegalovírus, 0,02% pelo vírus herpes simples, 0,3% para hepatite B (HBsAg, 0,1% para hepatite C, 0,1% para HTLV I/II e 0,1% para doença de Chagas. Houve associação significativa entre faixa etária e infecções por rubéola, citomegalovírus, doença de Chagas e herpes vírus. As freqüências de rubéola, sífilis, toxoplasmose, doença de Chagas e citomegalovírus nas gestantes encontram-se abaixo dos valores descritos na literatura.It was aimed to estimate the frequency of syphilis, rubella, hepatitis B, hepatitis C, toxoplasmosis, Chagas’ disease, HTLV I/II, simple herpes virus, HIV-1 and cytomegalovirus in pregnant women and to evaluate the relationship between age and the frequency of the infections studied. A transversal study of 32,512 pregnant women submitted to pre-natal sreening in the period of November 2002 to October 2003. The frequency of the tried infections among the pregnant women were 0.2% of HIV-1, 0.03% of rubella, 0.8% of syphilis, 0.4% of toxoplasmosis, 0.05% of cytomegalovirus, 0.02% of simple herpes virus, 0.3% of HBsAg, 0.1% of hepatitis C, 0.1% of HTLV and 0.1% of Chagas’ disease. There was significative statistical association between age and prenatal infection of rubella, cytomegalovirus, Chagas’ disease and herpes virus. The rates of frequency of rubella, syphilis, toxoplasmosis, Chagas’ disease and cytomegalovirus in pregnant women

Finasteride-associated male infertility Infertilidade masculina associada ao uso de finasterida

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Sidney Glina

2004-01-01

Full Text Available Finasteride is a potent and specific inhibitor of the 5alpha-reductase enzyme in men. Clinical studies have shown that finasteride 1mg/day is effective for promoting hair growth in men with male pattern hair loss. However, there is a concern about the use of finasteride, especially in young fertile patients, because of its action on testosterone metabolism. This paper describes 3 cases of young patients who had very poor seminal quality during finasteride treatment (1 mg/day, and their seminal quality greatly improved after cessation of finasteride treatment. Two of them presented with a left varicocele and the other was obese. We hypothesize that finasteride may not dramatically change the spermatogenesis process in healthy men, but in patients with conditions related to infertility, an amplification of the negative influence of finasteride could occur. Future studies should be done to clarify the extent of the effect of finasteride in patients fertility problems.A finasterida é um potente e específico inibidor da enzima 5alfa-redutase em homens. Estudos clínicos demonstraram que finasterida 1mg/dia diminui a progressão da queda e aumenta o crescimento do cabelo em homens que sofrem de queda de cabelo hereditária. Por sua influência no metabolismo dos andrógenos existe uma preocupação a respeito do seu uso, principalmente em pacientes em idade fértil. Neste trabalho são descritos 3 casos de pacientes jovens, que apresentaram piora do espermograma durante o uso continuado de finasterida 1mg revertida após a suspensão do mesmo. Dois deles tinham varicocele unilateral e o terceiro era obeso. Aparentemente o tratamento com finasterida promoveu alteração significativa na qualidade seminal. Pode-se especular que talvez a finasterida por si só não traga alteração para a espermatogênese como reportado por Overstreet et al. (1999, mas que em pacientes de risco com possíveis causas de infertilidade associadas, possa ocorrer a

Interaction of HTLV-1 Tax protein with calreticulin: implications for Tax nuclear export and secretion.

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Alefantis, Timothy; Flaig, Katherine E; Wigdahl, Brian; Jain, Pooja

2007-05-01

Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 transcriptional transactivator protein Tax plays an integral role in virus replication and disease progression. Traditionally, Tax is described as a nuclear protein where it performs its primary role as a transcriptional transactivator. However, recent studies have clearly shown that Tax can also be localized to the cytoplasm where it has been shown to interact with a number of host transcription factors most notably NF-kappaB, constitutive expression of which is directly related to the T cell transforming properties of Tax in ATL patients. The presence of a functional nuclear export signal (NES) within Tax and the secretion of full-length Tax have also been demonstrated previously. Additionally, release of Tax from HTLV-1-infected cells and the presence of cell-free Tax was demonstrated in the CSF of HAM/TSP patients suggesting that the progression to HAM/TSP might be mediated by the ability of Tax to function as an extracellular cytokine. Therefore, in both ATL and HAM/TSP Tax nuclear export and nucleocytoplasmic shuttling may play a critical role, the mechanism of which remains unknown. In this study, we have demonstrated that the calcium binding protein calreticulin interacts with Tax by co-immunoprecipitation. This interaction was found to localize to a region at or near the nuclear membrane. In addition, differential expression of calreticulin was demonstrated in various cell types that correlated with their ability to retain cytoplasmic Tax, particularly in astrocytes. Finally, a comparison of a number of HTLV-1-infected T cell lines to non-infected T cells revealed higher expression of calreticulin in infected cells implicating a direct role for this protein in HTLV-1 infection.

HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma—A Tale of Two Proteins: Tax and HBZ

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Chou-Zen Giam

2016-06-01

Full Text Available HTLV-1 (Human T-cell lymphotropic virus type 1 is a complex human delta retrovirus that currently infects 10–20 million people worldwide. While HTLV-1 infection is generally asymptomatic, 3%–5% of infected individuals develop a highly malignant and intractable T-cell neoplasm known as adult T-cell leukemia/lymphoma (ATL decades after infection. How HTLV-1 infection progresses to ATL is not well understood. Two viral regulatory proteins, Tax and HTLV-1 basic zipper protein (HBZ, encoded by the sense and antisense viral transcripts, respectively, are thought to play indispensable roles in the oncogenic process of ATL. This review focuses on the roles of Tax and HBZ in viral replication, persistence, and oncogenesis. Special emphasis is directed towards recent literature on the mechanisms of action of these two proteins and the roles of Tax and HBZ in influencing the outcomes of HTLV-1 infection including senescence induction, viral latency and persistence, genome instability, cell proliferation, and ATL development. Attempts are made to integrate results from cell-based studies of HTLV-1 infection and studies of HTLV-1 proviral integration site preference, clonality, and clonal expansion based on high throughput DNA sequencing. Recent data showing that Tax hijacks key mediators of DNA double-strand break repair signaling—the ubiquitin E3 ligase, ring finger protein 8 (RNF8 and the ubiquitin E2 conjugating enzyme (UBC13—to activate the canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB and other signaling pathways will be discussed. A perspective on how the Tax-RNF8 signaling axis might impact genomic instability and how Tax may collaborate with HBZ to drive oncogenesis is provided.

Quantitative comparison of HTLV-1 and HIV-1 cell-to-cell infection with new replication dependent vectors.

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Dmitriy Mazurov

2010-02-01

Full Text Available We have developed an efficient method to quantify cell-to-cell infection with single-cycle, replication dependent reporter vectors. This system was used to examine the mechanisms of infection with HTLV-1 and HIV-1 vectors in lymphocyte cell lines. Effector cells transfected with reporter vector, packaging vector, and Env expression plasmid produced virus-like particles that transduced reporter gene activity into cocultured target cells with zero background. Reporter gene expression was detected exclusively in target cells and required an Env-expression plasmid and a viral packaging vector, which provided essential structural and enzymatic proteins for virus replication. Cell-cell fusion did not contribute to infection, as reporter protein was rarely detected in syncytia. Coculture of transfected Jurkat T cells and target Raji/CD4 B cells enhanced HIV-1 infection two fold and HTLV-1 infection ten thousand fold in comparison with cell-free infection of Raji/CD4 cells. Agents that interfere with actin and tubulin polymerization strongly inhibited HTLV-1 and modestly decreased HIV-1 cell-to-cell infection, an indication that cytoskeletal remodeling was more important for HTLV-1 transmission. Time course studies showed that HTLV-1 transmission occurred very rapidly after cell mixing, whereas slower kinetics of HIV-1 coculture infection implies a different mechanism of infectious transmission. HTLV-1 Tax was demonstrated to play an important role in altering cell-cell interactions that enhance virus infection and replication. Interestingly, superantigen-induced synapses between Jurkat cells and Raji/CD4 cells did not enhance infection for either HTLV-1 or HIV-1. In general, the dependence on cell-to-cell infection was determined by the virus, the effector and target cell types, and by the nature of the cell-cell interaction.

HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma—A Tale of Two Proteins: Tax and HBZ

Science.gov (United States)

Giam, Chou-Zen; Semmes, Oliver John

2016-01-01

HTLV-1 (Human T-cell lymphotropic virus type 1) is a complex human delta retrovirus that currently infects 10–20 million people worldwide. While HTLV-1 infection is generally asymptomatic, 3%–5% of infected individuals develop a highly malignant and intractable T-cell neoplasm known as adult T-cell leukemia/lymphoma (ATL) decades after infection. How HTLV-1 infection progresses to ATL is not well understood. Two viral regulatory proteins, Tax and HTLV-1 basic zipper protein (HBZ), encoded by the sense and antisense viral transcripts, respectively, are thought to play indispensable roles in the oncogenic process of ATL. This review focuses on the roles of Tax and HBZ in viral replication, persistence, and oncogenesis. Special emphasis is directed towards recent literature on the mechanisms of action of these two proteins and the roles of Tax and HBZ in influencing the outcomes of HTLV-1 infection including senescence induction, viral latency and persistence, genome instability, cell proliferation, and ATL development. Attempts are made to integrate results from cell-based studies of HTLV-1 infection and studies of HTLV-1 proviral integration site preference, clonality, and clonal expansion based on high throughput DNA sequencing. Recent data showing that Tax hijacks key mediators of DNA double-strand break repair signaling—the ubiquitin E3 ligase, ring finger protein 8 (RNF8) and the ubiquitin E2 conjugating enzyme (UBC13)—to activate the canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and other signaling pathways will be discussed. A perspective on how the Tax-RNF8 signaling axis might impact genomic instability and how Tax may collaborate with HBZ to drive oncogenesis is provided. PMID:27322308

Motor behavioral abnormalities and histopathological findings of Wistar rats inoculated with HTLV-1-infected MT2 cells

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C.C. Câmara

2010-07-01

Full Text Available The objective of the present study was to describe motor behavioral changes in association with histopathological and hematological findings in Wistar rats inoculated intravenously with human T-cell lymphotropic virus type 1 (HTLV-1-infected MT2 cells. Twenty-five 4-month-old male rats were inoculated with HTLV-1-infected MT2 cells and 13 control rats were inoculated with normal human lymphocytes. The behavior of the rats was observed before and 5, 10, 15, and 20 months after inoculation during a 30-min/rat testing time for 5 consecutive days. During each of 4 periods, a subset of rats was randomly chosen to be sacrificed in order to harvest the spinal cord for histopathological analysis and to obtain blood for serological and molecular studies. Behavioral analyses of the HTLV-1-inoculated rats showed a significant decrease of climbing, walking and freezing, and an increase of scratching, sniffing, biting, licking, and resting/sleeping. Two of the 25 HTLV-1-inoculated rats (8% developed spastic paraparesis as a major behavioral change. The histopathological changes were few and mild, but in some cases there was diffuse lymphocyte infiltration. The minor and major behavioral changes occurred after 10-20 months of evolution. The long-term observation of Wistar rats inoculated with HTLV-1-infected MT2 cells showed major (spastic paraparesis and minor motor abnormalities in association with the degree of HTLV-1-induced myelopathy.

HTLV-1 Tax plugs and freezes UPF1 helicase leading to nonsense-mediated mRNA decay inhibition.

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Fiorini, Francesca; Robin, Jean-Philippe; Kanaan, Joanne; Borowiak, Malgorzata; Croquette, Vincent; Le Hir, Hervé; Jalinot, Pierre; Mocquet, Vincent

2018-01-30

Up-Frameshift Suppressor 1 Homolog (UPF1) is a key factor for nonsense-mediated mRNA decay (NMD), a cellular process that can actively degrade mRNAs. Here, we study NMD inhibition during infection by human T-cell lymphotropic virus type I (HTLV-1) and characterise the influence of the retroviral Tax factor on UPF1 activity. Tax interacts with the central helicase core domain of UPF1 and might plug the RNA channel of UPF1, reducing its affinity for nucleic acids. Furthermore, using a single-molecule approach, we show that the sequential interaction of Tax with a RNA-bound UPF1 freezes UPF1: this latter is less sensitive to the presence of ATP and shows translocation defects, highlighting the importance of this feature for NMD. These mechanistic insights reveal how HTLV-1 hijacks the central component of NMD to ensure expression of its own genome.

Apelo ao consenso e impossibilidades da retórica: o caso do XI governo constitucional português

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Lopo, Teresa Teixeira

2016-01-01

Resumo Neste artigo analisa-se como se formulou o apelo ao consenso no discurso pedagógico oficial do XI governo constitucional português, considerando os valores orientadores do processo de decisão e as crenças associadas ao impacto da política educativa e os seus resultados, em termos dos consensos alcançados na relação com os partidos políticos com representação parlamentar. Verificou-se ter sido uma construção retórica feliz do discurso, a desencadear, para além da concordância naturalmen...

[SHTLV-I/II seroprevalence in blood donors of Hospital Pablo Tobón Uribe Blood Bank during the period 2014-2015].

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Muñoz, Manuela; Carvalho, Santiago; Donado, Jorge Hernando; Barco, Gloria Eugenia; Jaramillo, Sergio

2018-03-15

The human-T cell lymphotropic virus is a retrovirus with various types known so far. HTLV-I and HTLV-II are of clinically importance as they cause different diseases such as adult T-cell leukemia/lymphoma, tropical spastic paraparesis, and human T-lymphotropic virus type I-associated myelopathy (HAM). To estimate the prevalence of presumptive and confirmatory reactivity to HTLV-I/II in blood donors of Hospital Pablo Tobón Uribe Blood Bank between 2014 and 2015. The information was obtained from the Hospital Pablo Tobón Uribe Blood Bank database. We analyzed age, sex, place of origin, and place of residence of donors, and the reactivity using the screening test (ELISA) as well as the confirmatory test (immunoblot). The donor population studied included 6,275 men and 8,148 women, for a total of 14,423 donors recruited between March 1, 2014, and June 30, 2015. Of all tested donors, 25 were positive for HTLV-I/II by the screening test (ELISA). After performing the confirmatory test (immunoblot), only nine patients were positive for HTLV-I/II (36%), of whom eight were reactive to HTLV-I (32%) and one to HTLV-II (4%), for a global seroprevalence of 0.06% (CI 95%: 0.10-0.25). Our findings were consistent with those found in similar studies in non-endemic areas of the country and with those from studies at international level reported in the literature.

Epidemiology and risk factors HTLV virus infection in pregnant women.

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Adriella Silva Oliveira

2014-09-01

Full Text Available This study aimed to perform an integrative review of the epidemiology and the main risk factors for infection with human T lymphotropic to cells (HTLV in pregnant women from the Brazilian scientific production. The articles were extracted from databases: Literature Latin American and Caribbean Health Sciences (LILACS, Medical Literature Analysis and Retrieval System Online (MEDLINE and Scientific Electronic Library Online (SCIELO, with nine selected articles published between the years 2000-2012. Upon review of the studies it was observed that Brazil has significant prevalence of HTLV in pregnant women, demonstrating the need for adequate attention to this indicator. Some risk factors indicated by the studies analyzed were: low education, criterion race/color (infected pregnant women were mostly black, brown or indigenous majority, vertical transmission, sexual transmission, multiple pregnancies and premature sexual activity. Therefore, it is important serologic screening to prevent congenital infections, as well as the introduction of new studies on the infection in Brazil. Thus, it becomes evident the need for planning and implementation of prevention and control of HTLV in the prenatal for structuring measures that minimize the appearance of new infections in pregnant women and children due to vertical transmission, the main route of transmission.

Imaging spinal cord atrophy in progressive myelopathies: HTLV-I-associated neurological disease (HAM/TSP) and multiple sclerosis (MS).

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Azodi, Shila; Nair, Govind; Enose-Akahata, Yoshimi; Charlip, Emily; Vellucci, Ashley; Cortese, Irene; Dwyer, Jenifer; Billioux, B Jeanne; Thomas, Chevaz; Ohayon, Joan; Reich, Daniel S; Jacobson, Steven

2017-11-01

Previous work measures spinal cord thinning in chronic progressive myelopathies, including human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and multiple sclerosis (MS). Quantitative measurements of spinal cord atrophy are important in fully characterizing these and other spinal cord diseases. We aimed to investigate patterns of spinal cord atrophy and correlations with clinical markers. Spinal cord cross-sectional area was measured in individuals (24 healthy controls [HCs], 17 asymptomatic carriers of HTLV-1 (AC), 47 HAM/TSP, 74 relapsing-remitting MS [RRMS], 17 secondary progressive MS [SPMS], and 40 primary progressive MS [PPMS]) from C1 to T10. Clinical disability scores, viral markers, and immunological parameters were obtained for patients and correlated with representative spinal cord cross-sectional area regions at the C2 to C3, C4 to C5, and T4 to T9 levels. In 2 HAM/TSP patients, spinal cord cross-sectional area was measured over 3 years. All spinal cord regions are thinner in HAM/TSP (56 mm 2 [standard deviation, 10], 59 [10], 23 [5]) than in HC (76 [7], 83 [8], 38 [4]) and AC (71 [7], 78 [9], 36 [7]). SPMS (62 [9], 66 [9], 32 [6]) and PPMS (65 [11], 68 [10], 35 [7]) have thinner cervical cords than HC and RRMS (73 [9], 77 [10], 37 [6]). Clinical disability scores (Expanded Disability Status Scale [p = 0.009] and Instituto de Pesquisas de Cananeia [p = 0.03]) and CD8 + T-cell frequency (p = 0.04) correlate with T4 to T9 spinal cord cross-sectional area in HAM/TSP. Higher cerebrospinal fluid HTLV-1 proviral load (p = 0.01) was associated with thinner spinal cord cross-sectional area. Both HAM/TSP patients followed longitudinally showed thoracic thinning followed by cervical thinning. Group average spinal cord cross-sectional area in HAM/TSP and progressive MS show spinal cord atrophy. We further hypothesize in HAM/TSP that is possible that neuroglial loss from a thoracic inflammatory

HLA-DP antigens and HTLV-1 antibody status among Japanese with multiple sclerosis: evidence for an increased frequency of HLA-DPw4

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Ødum, Niels; Saida, T; Ohta, M

1989-01-01

, personal communication). Sera from all 34 patients and 38 controls (both from the HTLV-1 nonendemic, Kyoto region) were examined for the presence of HTLV-1 reacting antibodies by a highly sensitive radioimmuno assay (RIA) using two sources of HTLV-1 antigens, namely total crude protein preparations from...... disrupted HTLV-1 virions and affinity purified p24 HTLV-1 core proteins. The frequency of DPw4 was significantly increased to 35.3% in Japanese MS patients compared to 16.5% in controls (Relative Risk, RR = 2.8, p = 1.9 x 10(-2)). 41.6% of the MS patients gave clear typing responses with a PLT reagent which...... recognized a Dw2+ related specificity, which is higher than the frequency of Dw2 (6.8%) in Japanese. Fourteen of the 34 patient sera contrasting to none of the sera from 38 controls contained antibodies of IgG and/or IgM subclasses reacting with the HTLV-1 derived antigens. This difference is highly...

Anti-human T-lymphotropic virus type-I antibodies in atomic-bomb survivors

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Matsuo, Tatsuki; Nakashima, Eiji; Carter, R.L. [Radiation Effects Research Foundation, Nagasaki (Japan). Nagasaki Branch] [and others

1995-03-01

Adult T-cell leukemia (ATL), induced by human T-lymphotropic virus type-I (HTLV-I), is endemic in Nagasaki, Japan. To investigate the effects of atomic-bomb radiation on development of this specific type of leukemia, 6182 individuals in the Radiation Effects Research Foundation (RERF) Adult Health Study sample in Hiroshima and Nagasaki were examined for positive rate of HTLV-I antibody. Several lymphocyte parameters were also studied for 70 antibody-positive subjects in Nagasaki. The HTLV-I antibody-positive rate was higher in Nagasaki (6.36%) than in Hiroshima (0.79%) and significantly increased with increasing age, but no association was observed with radiation dose. Whether relationship existed between antibody titer levels and radiation dose among antibody-positive subjects was not clear. The frequency of abnormal lymphocytes tended to be higher in antibody-positive subjects than in antibody-negative subjects, and higher in females than in males regardless of radiation dose. The lymphocyte count was lower in antibody-positive subjects than in antibody-negative subjects and lower in female than in male subjects. No evidence was found to suggest that atomic-bomb radiation plays an important role in HTLV-I infection. (author).

Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms

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Mueller Nancy

2005-10-01

Full Text Available Abstract Background Human T-cell leukemia virus type I (HTLV-I causes adult T-cell leukemia (ATL after a long latent period. Among accessory genes encoded by HTLV-I, the tax gene is thought to play a central role in oncogenesis. However, Tax expression is disrupted by several mechanims including genetic changes of the tax gene, deletion/hypermethylation of 5'-LTR. To clarify the role of epigenetic changes, we analyzed DNA methylation and histone modification in the whole HTLV-I provirus genome. Results The gag, pol and env genes of HTLV-I provirus were more methylated than pX region, whereas methylation of 5'-LTR was variable and 3'-LTR was not methylated at all. In ATL cell lines, complete DNA methylation of 5'-LTR was associated with transcriptional silencing of viral genes. HTLV-I provirus was more methylated in primary ATL cells than in carrier state, indicating the association with disease progression. In seroconvertors, DNA methylation was already observed in internal sequences of provirus just after seroconversion. Taken together, it is speculated that DNA methylation first occurs in the gag, pol and env regions and then extends in the 5' and 3' directions in vivo, and when 5'-LTR becomes methylated, viral transcription is silenced. Analysis of histone modification in the HTLV-I provirus showed that the methylated provirus was associated with hypoacetylation. However, the tax gene transcript could not be detected in fresh ATL cells regardless of hyperacetylated histone H3 in 5'-LTR. The transcription rapidly recovered after in vitro culture in such ATL cells. Conclusion These results showed that epigenetic changes of provirus facilitated ATL cells to evade host immune system by suppressing viral gene transcription. In addition, this study shows the presence of another reversible mechanism that suppresses the tax gene transcription without DNA methylation and hypoacetylated histone.

Temporal regulation of HTLV-2 expression in infected cell lines and patients: evidence for distinct expression kinetics with nuclear accumulation of APH-2 mRNA

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Bender Cecilia

2012-09-01

Full Text Available Abstract Background Human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2 are delta retroviruses with similar genetic organization. Although both viruses immortalize T-cells in vitro, they exhibit distinct pathogenic potential in vivo. To search for possible differences in its expression strategy with respect to HTLV-1, we investigated the pattern of HTLV-2 expression in infected cell lines and peripheral blood mononuclear cells (PBMCs from infected patients using splice site-specific quantitative RT-PCR. Findings A novel alternative splice acceptor site for exon 2 was identified; its usage in env transcripts was found to be subtype-specific. Time-course analysis revealed a two-phase expression kinetics in an infected cell line and in PBMCs of two of the three patients examined; this pattern was reminiscent of HTLV-1. In addition, the minus-strand APH2 transcript was mainly detected in the nucleus, a feature that was similar to its HTLV-1 orthologue HBZ. In contrast to HTLV-1, expression of the mRNA encoding the main regulatory proteins Tax and Rex and that of the mRNAs encoding the p28 and truncated Rex inhibitors is skewed towards p28/truncated Rex inhibitors in HTLV-2. Conclusion Our data suggest a general converging pattern of expression of HTLV-2 and HTLV-1 and highlight peculiar differences in the expression of regulatory proteins that might influence the pathobiology of these viruses.

Deregulation of calcium fluxes in HTLV-I infected CD4-positive T-cells plays a major role in malignant transformation.

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Akl, Haidar; Badran, Bassam; El Zein, Nabil; Dobirta, Gratiela; Burny, Arsene; Martiat, Philippe

2009-01-01

The CD4+ T-cell malignancy induced by human T-cell leukemia virus type 1 (HTLV-I) infection and termed; Adult T-cell Leukemia lymphoma (ATLL), is caused by defects in the mechanisms underlying cell proliferation and cell death. In the CD4+ T-cells, calcium ions are central for both phenomena. ATLL is associated with a marked hypercalcemia in many patients. The consequence of a defect in the Ca2+ signaling pathway for lymphocyte activation is characterized by an impaired NFAT activation and transcription of cytokines, chemokines and many other NFAT target genes whose transcription is essential for productive immune defense. Fresh ATLL cells lack the TCR/CD3 and CD7 molecules on their surface. Whereas CD7 is a calcium transporter, reduction in calcium influx in response to T-cell activation was reported as a functional consequence of TCR/CD3 expression deficiency. Understanding these changes and identifying the molecular players involved might provide further insights on how to improve ATLL treatment.

Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome vs. HTLV-1+ leukemic cell lines

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Netchiporouk, Elena; Gantchev, Jennifer; Tsang, Matthew

2017-01-01

HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and present with classic erythematous pruritic patches and plaques that are typically seen in Mycosis Fungoides (MF) and Sézary Syndrome...... (SS), the most recognized variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV- 1 in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed CTCL vs. HTLV-1+ leukemic cells. We performed G-banding/spectral karyotyping, extensive gene expression analysis......, TP53 sequencing in the 11 patient-derived HTLV- 1+ (MJ and Hut102) vs. HTLV-1- (Myla, Mac2a, PB2B, HH, H9, Hut78, SZ4, Sez4 and SeAx) CTCL cell lines. We further tested drug sensitivities to commonly used CTCL therapies and studied the ability of these cells to produce subcutaneous xenograft tumors...

Regulatory T cell expansion in HTLV-1 and strongyloidiasis co-infection is associated with reduced IL-5 responses to Strongyloides stercoralis antigen.

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Martin Montes

2009-06-01

Full Text Available Human strongyloidiasis varies from a chronic but limited infection in normal hosts to hyperinfection in patients treated with corticosteroids or with HTLV-1 co-infection. Regulatory T cells dampen immune responses to infections. How human strongyloidiasis is controlled and how HTLV-1 infection affects this control are not clear. We hypothesize that HTLV-1 leads to dissemination of Strongyloides stercoralis infection by augmenting regulatory T cell numbers, which in turn down regulate the immune response to the parasite.To measure peripheral blood T regulatory cells and Strongyloides stercoralis larval antigen-specific cytokine responses in strongyloidiasis patients with or without HTLV-1 co-infection.Peripheral blood mononuclear cells (PBMCs were isolated from newly diagnosed strongyloidiasis patients with or without HTLV-1 co-infection. Regulatory T cells were characterized by flow cytometry using intracellular staining for CD4, CD25 and FoxP3. PBMCs were also cultured with and without Strongyloides larval antigens. Supernatants were analyzed for IL-5 production.Patients with HTLV-1 and Strongyloides co-infection had higher parasite burdens. Eosinophil counts were decreased in the HTLV-1 and Strongyloides co-infected subjects compared to strongyloidiasis-only patients (70.0 vs. 502.5 cells/mm(3, p = 0.09, Mann-Whitney test. The proportion of regulatory T cells was increased in HTLV-1 positive subjects co-infected with strongyloidiasis compared to patients with only strongyloidiasis or asymptomatic HTLV-1 carriers (median = 17.9% vs. 4.3% vs. 5.9 p<0.05, One-way ANOVA. Strongyloides antigen-specific IL-5 responses were reduced in strongyloidiasis/HTLV-1 co-infected patients (5.0 vs. 187.5 pg/ml, p = 0.03, Mann-Whitney test. Reduced IL-5 responses and eosinophil counts were inversely correlated to the number of CD4+CD25+FoxP3+ cells.Regulatory T cell counts are increased in patients with HTLV-1 and Strongyloides stercoralis co-infection and

HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role

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Fochi, Stefania; Mutascio, Simona; Bertazzoni, Umberto; Zipeto, Donato; Romanelli, Maria G.

2018-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4+/CD25+ T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed toward the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins. PMID:29515558

HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role.

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Fochi, Stefania; Mutascio, Simona; Bertazzoni, Umberto; Zipeto, Donato; Romanelli, Maria G

2018-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4 + /CD25 + T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed toward the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins.

Impact of depression on quality of life in people living with human T cell lymphotropic virus type 1 (HTLV-1) in Salvador, Brazil.

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Galvão-Castro, Ana Verena; Boa-Sorte, Ney; Kruschewsky, Ramon Almeida; Grassi, Maria Fernanda Rios; Galvão-Castro, Bernardo

2012-11-01

A previous study found the prevalence of depression in HTLV-1-infected patients to be approximately 30%, but few studies have attempted to correlate depression with quality of life (QOL) in these patients. The present study investigates the association between depression and QOL in people living with HTLV-1. A clinical-epidemiological questionnaire, the Mini International Neuropsychiatric Interview and the WHOQOL-Bref were applied to 88 HTLV-1-infected patients (32 with TSP/HAM) at the HTLV Center of the Bahiana School of Medicine and Public Health, Salvador, Brazil. The prevalence of depression among people living with HTLV-1 was 34.1%. Depression was significantly associated with a poor QOL in the physical, psychological, social relationship and environment domains, when controlling for other variables, such as gender, age, time of knowledge of serological diagnosis and presence of tropical spastic paraparesis/HTLV-1associated myelopathy (TSP/HAM). Moreover, patients with TSP/HAM experienced a reduction in their QOL in the physical, psychological and environment domains. Our results showed that depression negatively affects the quality of life of people living with HTLV-1, regardless of the presence of TSP/HAM. Since it is possible to improve a patient's QOL by treating depression, psychological evaluations are strongly recommended as a measure to integrate the treatment protocols of HTLV-1 intervention programs.

Quantitative PCR for HTLV-1 provirus in adult T-cell leukemia/lymphoma using paraffin tumor sections.

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Kato, Junki; Masaki, Ayako; Fujii, Keiichiro; Takino, Hisashi; Murase, Takayuki; Yonekura, Kentaro; Utsunomiya, Atae; Ishida, Takashi; Iida, Shinsuke; Inagaki, Hiroshi

2016-11-01

Detection of HTLV-1 provirus using paraffin tumor sections may assist the diagnosis of adult T-cell leukemia/lymphoma (ATLL). For the detection, non-quantitative PCR assay has been reported, but its usefulness and limitations remain unclear. To our knowledge, quantitative PCR assay using paraffin tumor sections has not been reported. Using paraffin sections from ATLLs and non-ATLL T-cell lymphomas, we first performed non-quantitative PCR for HTLV-1 provirus. Next, we determined tumor ratios and carried out quantitative PCR to obtain provirus copy numbers. The results were analyzed with a simple regression model and a novel criterion, cut-off using 95 % rejection limits. Our quantitative PCR assay showed an excellent association between tumor ratios and the copy numbers (r = 0.89, P paraffin tumor sections may be useful for the screening of ATLL cases, especially in HTLV-1 non-endemic areas where easy access to serological testing for HTLV-1 infection is limited. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Neuropatia paraneoplásica associada ao mastocitoma canino Paraneoplastic neuropathy associated with canine mast cell tumor

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Sabrina Marin Rodigheri

2008-06-01

Full Text Available As síndromes paraneoplásicas compreendem um grupo diverso de alterações clínicas associadas a neoplasias e ocorrem em sítios distantes do tumor primário ou de suas metástases. As neuropatias paraneoplásicas são distúrbios raros em cães, mas representam morbidade significativa e servem como importantes indicadores diagnósticos e prognósticos. O presente trabalho relata a ocorrência de dois casos de neuropatia paraneoplásica em cães com mastocitoma, considerando a apresentação clínica, o diagnóstico e as formas de tratamento utilizadas.Paraneoplastic syndromes comprise a diverse group of clinical anomalies associated with neoplasias and occur in a location distant from the primary tumor or of your metastasis. Paraneoplastic neuropathy are rare disturbs in dogs, but represent significant morbidity and are useful as diagnostic and prognostic indicators. This work report the occurrence of two cases of paraneoplastic neuropathy in dogs with mast cell tumor, considering the clinical signs, diagnosis and treatment used.

Regulation of IFN regulatory factor 4 expression in human T cell leukemia virus-I-transformed T cells.

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Sharma, Sonia; Grandvaux, Nathalie; Mamane, Yael; Genin, Pierre; Azimi, Nazli; Waldmann, Thomas; Hiscott, John

2002-09-15

IFN regulatory factor (IRF)-4 is a lymphoid/myeloid-restricted member of the IRF transcription factor family that plays an essential role in the homeostasis and function of mature lymphocytes. IRF-4 expression is tightly regulated in resting primary T cells and is transiently induced at the mRNA and protein levels after activation by Ag-mimetic stimuli such as TCR cross-linking or treatment with phorbol ester and calcium ionophore (PMA/ionomycin). However, IRF-4 is constitutively upregulated in human T cell leukemia virus type I (HTLV-I) infected T cells as a direct gene target for the HTLV-I Tax oncoprotein. In this study we demonstrate that chronic IRF-4 expression in HTLV-I-infected T lymphocytes is associated with a leukemic phenotype, and we examine the mechanisms by which continuous production of IRF-4 is achieved in HTLV-I-transformed T cells. IRF-4 expression in HTLV-1-infected cells is driven through activation of the NF-kappaB and NF-AT pathways, resulting in the binding of p50, p65, and c-Rel to the kappaB1 element and p50, c-Rel, and NF-ATp to the CD28RE element within the -617 to -209 region of the IRF-4 promoter. Furthermore, mutation of either the kappaB1 or CD28RE sites blocks Tax-mediated transactivation of the human IRF-4 promoter in T cells. These experiments constitute the first detailed analysis of human IRF-4 transcriptional regulation within the context of HTLV-I infection and transformation of CD4(+) T lymphocytes.

Stable human T-cell lymphotropic virus type 1 (HTLV-1) subtype a/subgroup a endemicity in Amerindians from Northwest Argentina: a health problem to be resolved.

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Eirin, Maria E; Berini, Carolina A; Jones, Leandro R; Dilernia, Dario A; Puca, Alberto A; Biglione, Mirna M

2010-12-01

Jujuy province, in Northwest Argentina, is known to be endemic for HTLV-1 infection. Moreover, foci of HTLV-1 associated pathologies have also been described in this region. To gain an insight into the current situation of HTLV-1/2 in this endemic area, a seroprevalence and phylogenetic study was performed among a Kolla community from Abra Pampa city and surroundings. Out of 112 individuals, 11 (9.8%) were confirmed as HTLV-1 positive and no HTLV-2 infection was detected. The phylogenetic analysis of the LTR region showed that all the HTLV-1 sequences belonged to the Cosmopolitan subtype a/transcontinental subgroup A, and were closely related to reference sequences from Peru, Argentina, and the South of Brazil (P = 0.82). Considering the cultural and historical features of this community and in spite of the mandatory detection of anti-HTLV-1/2 antibodies in blood banks since 2005, it would be important to implement new public health measures focused on decreasing HTLV-1 transmission in this endemic area.

TCF1 and LEF1 act as T-cell intrinsic HTLV-1 antagonists by targeting Tax.

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Ma, Guangyong; Yasunaga, Jun-ichirou; Akari, Hirofumi; Matsuoka, Masao

2015-02-17

Human T-cell leukemia virus type 1 (HTLV-1) is a delta-type retrovirus that induces malignant and inflammatory diseases during its long persistence in vivo. HTLV-1 can infect various kinds of cells; however, HTLV-1 provirus is predominantly found in peripheral CD4 T cells in vivo. Here we find that TCF1 and LEF1, two Wnt transcription factors that are specifically expressed in T cells, inhibit viral replication through antagonizing Tax functions. TCF1 and LEF1 can each interact with Tax and inhibit Tax-dependent viral expression and activation of NF-κB and AP-1. As a result, HTLV-1 replication is suppressed in the presence of either TCF1 or LEF1. On the other hand, T-cell activation suppresses the expression of both TCF1 and LEF1, and this suppression enables Tax to function as an activator. We analyzed the thymus of a simian T-cell leukemia virus type 1 (STLV-1) infected Japanese macaque, and found a negative correlation between proviral load and TCF1/LEF1 expression in various T-cell subsets, supporting the idea that TCF1 and LEF1 negatively regulate HTLV-1 replication and the proliferation of infected cells. Thus, this study identified TCF1 and LEF1 as Tax antagonistic factors in vivo, a fact which may critically influence the peripheral T-cell tropism of this virus.

Presentation of human T cell leukemia virus type 1 (HTLV-1) Tax protein by dendritic cells: the underlying mechanism of HTLV-1-associated neuroinflammatory disease.

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Manuel, Sharrón L; Schell, Todd D; Acheampong, Edward; Rahman, Saifur; Khan, Zafar K; Jain, Pooja

2009-11-01

HTLV-1 is the etiologic agent of a debilitating neurologic disorder, HAM/TSP. This disease features a robust immune response including the oligoclonal expansion of CD8+ CTLs specific for the viral oncoprotein Tax. The key pathogenic process resulting in the proliferation of CTLs and the presentation of Tax peptide remains uncharacterized. We have investigated the role of APCs, particularly DCs, in priming of the anti-Tax CTL response under in vitro and in vivo conditions. We investigated two routes (direct vs. indirect) of Tax presentation using live virus, infected primary CD4+/CD25+ T cells, and the CD4+ T cell line (C8166, a HTLV-1-mutated line that only expresses Tax). Our results indicated that DCs are capable of priming a pronounced Tax-specific CTL response in cell cultures consisting of naïve PBLs as well as in HLA-A*0201 transgenic mice (line HHD II). DCs were able to direct the presentation of Tax successfully through infected T cells, live virus, and cell-free Tax. These observations were comparable with those made with a known stimulant of DC maturation, a combination of CD40L and IFN-gamma. Our studies clearly establish a role for this important immune cell component in HTLV-1 immuno/neuropathogenesis and suggest that modulation of DC functions could be an important tool for therapeutic interventions.

Vasculopatia retiniana exsudativa tipo Coats associada a retinose pigmentar: ocorrência familiar Coats' type exudative vasculopathy associated with retinitis pigmentosa: familial occurrence

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Valdir Balarin Silva

2002-09-01

Full Text Available Os autores apresentam dois casos de vasculopatia retiniana tipo Coats associada a retinose pigmentar. Estes são os primeiros casos entre irmãos descritos no Brasil e nosso objetivo é anexar mais 2 casos, aos 47 descritos na literatura mundial.The authors presents two cases of Coats' type exsudative vasculopathy associated with retinitis pigmentosa. These are the first cases in siblings described in Brazil and our purpose is to add two more cases, to the 47 described in the world literature.

Immune activation induces immortalization of HTLV-1 LTR-Tax transgenic CD4+ T cells

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Swaims, Alison Y.; Khani, Francesca; Zhang, Yingyu; Roberts, Arthur I.; Devadas, Satish; Shi, Yufang; Rabson, Arnold B.

2010-01-01

Infection with the human T-cell leukemia virus-1 (HTLV-1) results in a variety of diseases including adult T-cell leukemia/lymphoma (ATL). Although the pathogenesis of these disorders is poorly understood, it involves complex interactions with the host immune system. Activation of infected T cells may play an important role in disease pathogenesis through induction of the oncogenic HTLV-1 Tax transactivator protein. To test this hypothesis, we employed transgenic mice in which Tax is regulate...

Low prevalence of human T-cell leukaemia virus-I and -II infection among drug users in Amsterdam, The Netherlands

NARCIS (Netherlands)

van den Hoek, J. A.; Al, E. J.; Huisman, J. G.; Goudsmit, J.; Coutinho, R. A.

1991-01-01

The prevalence of human T-cell leukaemia virus-I and -II infection was studied in a cohort of 346 intravenous and nonintravenous drug users in Amsterdam. Three participants (0.86%) had antibodies to HTLV-I by two commercially available HTLV-I enzyme immunoassays (EIA). Infection in these three

The cause of urinary symptoms among Human T Lymphotropic Virus Type I (HLTV-I infected patients: a cross sectional study

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Salgado Katia

2007-03-01

Full Text Available Abstract Background HTLV-I infected patients often complain of urinary symptomatology. Epidemiological studies have suggested that these individuals have a higher prevalence and incidence of urinary tract infection (UTI than seronegative controls. However, the diagnosis of UTI in these studies relied only on patient information and did not require confirmation by urine culture. The purpose of this study was to investigate the role of urinary tract infection (UTI as the cause of urinary symptoms in HTLV-I infected patients. Methods In this cross sectional study we interviewed, and cultured urine from, 157 HTLV-I seropositive individuals followed regularly at a specialized clinic. All patients were evaluated by a neurologist and classified according to the Expanded Disability Status Scale (EDSS. Urodynamic studies were performed at the discretion of the treating physician. Results Sixty-four patients complained of at least one active urinary symptom but UTI was confirmed by a positive urine culture in only 12 of these patients (19%; the majority of symptomatic patients (81% had negative urine cultures. To investigate the mechanism behind the urinary complaints in symptomatic individuals with negative urine cultures, we reviewed the results of urodynamic studies performed in 21 of these patients. Most of them (90.5% had abnormal findings. The predominant abnormalities were detrusor sphincter hyperreflexia and dyssynergia, findings consistent with HTLV-I-induced neurogenic bladder. On a multivariate logistic regression, an abnormal EDSS score was the strongest predictor of urinary symptomatology (OR 9.87, 95% CI 3.465 to 28.116, P Conclusion Urinary symptomatology suggestive of UTI is highly prevalent among HTLV-I seropositive individuals but true UTI is responsible for the minority of cases. We posit that the main cause of urinary symptoms in this population is neurogenic bladder. Our data imply that HLTV-I infected patients with urinary

Estrutura da vegetação de mangue associada ao gradiente de inundação no litoral norte do Espírito Santo, Brasil

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Vinícius Londe

2013-08-01

Full Text Available O manguezal é um ecossistema de grande complexidade que ocorre na interface entre os ambientes marinhos e terrestres, mas que apresenta baixa riqueza de espécies vegetais adaptadas às suas condições diferenciadas. Avaliar a estrutura e distribuição da vegetação no manguezal do rio Piraquê-Açu, ES, associando-as com parâmetros abióticos ao longo de um gradiente, foi o objetivo deste estudo. Em seis parcelas de 100 m² cada, foram registrados 306 indivíduos vivos e um morto, pertencentes às espécies Laguncularia racemosa, Rhizophora mangle, Avicennia schaueriana, Terminalia catappa e outras quatro indeterminadas, sendo L. racemosa de maior densidade, dominância, área basal e IVI. A altura média das árvores foi de 4,2 m (DP±1,9 e a CAP, de 12,4 cm (DP±9,5, estando a maioria dos indivíduos em classes de CAP até 10 cm. O manguezal encontrava-se em estado juvenil e pouco desenvolvido estruturalmente, e houve distinção na distribuição das espécies na área, com espécies associadas ocorrendo na parcela mais elevada e menos úmida. As variáveis abióticas diferiram entre as parcelas, contudo apenas a umidade do substrato apresentou relação significativa com a abundância de indivíduos e circunferência dos troncos.

Desenvolvimento cognitivo e de linguagem expressiva em um par de gêmeos dizigóticos: influência da síndrome de Down e da prematuridade associada ao muito baixo peso Expressive language and cognitive development in a dizygotic twin pair: influence of Down syndrome and prematurity combined with very low birth-weight

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Fabíola Custódio Flabiano

2009-01-01

Full Text Available O objetivo deste estudo foi descrever o desenvolvimento cognitivo e de linguagem expressiva de uma criança com síndrome de Down (SD e seu gemelar, ambos nascidos pré-termo muito baixo peso (PTMBP, observando a influência da SD e da prematuridade associada ao muito baixo peso no processo de desenvolvimento durante o período sensório-motor. Participaram deste estudo um par de gêmeos dizigóticos, ambos do sexo masculino, nascidos PTMBP, sendo que apenas um apresentava SD. A idade inicial dos sujeitos foi de sete meses e quatro dias de idade cronológica e quatro meses e 21 dias de idade corrigida, considerando que nasceram com 29 semanas de gestação, pesando menos de 1500g. Os sujeitos foram acompanhados durante 12 meses em sessões quinzenais de 45 minutos e os dados foram registrados mensalmente em vídeo. O Protocolo para Observação do Desenvolvimento Cognitivo e de Linguagem Expressiva (PODCLE foi utilizado para coleta e análise dos dados. Foram observadas diferenças significativas entre os gêmeos com relação ao desenvolvimento cognitivo e de linguagem expressiva. Apesar de apresentar melhor desempenho, o gemelar que não apresentava SD demonstrou um atraso importante, considerando-se as referências em relação ao desenvolvimento típico, evidenciando a influência da prematuridade associada ao muito baixo peso no desenvolvimento de linguagem e cognição. Os resultados obtidos para o outro gemelar sugerem que a SD levou ao aumento significativo deste atraso. A SD e a prematuridade associada ao muito baixo peso são condições que interferiram de forma negativa no desenvolvimento cognitivo e de linguagem expressiva apresentado pelo par de gêmeos estudado.The aim of this study was to describe expressive language and cognitive development in a child with Down syndrome (DS and his twin brother, both born preterm very low birth-weight (VLBW, observing the influence of Down syndrome and prematurity combined with very low birth

The pathogenesis of tropical spastic paraparesis/human T-cell leukemia type I-associated myelopathy

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Casseb J.

2000-01-01

Full Text Available Tropical spastic paraparesis/human T-cell leukemia type I-associated myelopathy (TSP/HAM is caused by a human T-cell leukemia virus type I (HTLV-I after a long incubation period. TSP/HAM is characterized by a chronic progressive paraparesis with sphincter disturbances, no/mild sensory loss, the absence of spinal cord compression and seropositivity for HTLV-I antibodies. The pathogenesis of this entity is not completely known and involves a multivariable phenomenon of immune system activation against the presence of HTLV-I antigens, leading to an inflammatory process and demyelination, mainly in the thoracic spinal cord. The current hypothesis about the pathogenesis of TSP/HAM is: 1 presence of HTLV-I antigens in the lumbar spinal cord, noted by an increased DNA HTLV-I load; 2 CTL either with their lytic functions or release/production of soluble factors, such as CC-chemokines, cytokines, and adhesion molecules; 3 the presence of Tax gene expression that activates T-cell proliferation or induces an inflammatory process in the spinal cord; 4 the presence of B cells with neutralizing antibody production, or complement activation by an immune complex phenomenon, and 5 lower IL-2 and IFN-gamma production and increased IL-10, indicating drive to a cytokine type 2 pattern in the TSP/HAM subjects and the existence of a genetic background such as some HLA haplotypes. All of these factors should be implicated in TSP/HAM and further studies are necessary to investigate their role in the development of TSP/HAM.

O diagnóstico clínico da pneumonia associada ao ventilador revisitado: validação comparativa usando biópsias pulmonares post-mottem imediatas

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Neus Fàbregas

2000-07-01

Full Text Available RESUMO: Efectuou-se um estudo prospectivo que englobou 25 doentes submetidos a ventilação mecânica e quevieram a falecer, com o objectivo de avaliar o valor diagnóstico dos criterios clínicos e o impacto dos testes microbiológicos na correcta determinação do diagnóstico de pneumonia associada ao ventilador (PAV. Forarn colhidas, logo após a morte, múltiplas amostras de biópsias de ambos os pulmões (16 amostras por doente, que foram submetidas a exame histológico e culturas quantitativas. O teste de referênda foi baseado na presença de pneumonia identificada histologicamente e, simultâneamente, numa cultura pulmonar positiva. A presença de infiltrados na radiografia de tórax e de dois de três critérios clínicos (leucocitose, secreções purulentas e febre- critérios de Johanson revelaram uma sensibilidade de 69% e uma especificidade de 75%. Os valores correspondentes, quando se utilizou o “clinical pulmonary infection score” (CPIS, foram de 77% e 42%. Os resultados das amostras colhidos quer por técnicas invasivas, quer por técnicas não invasivas apresentaram valores comparáveis. Com a combinação de todas as técnicas obteve-se uma sensibilidade de 85% e uma especificidade de 50%, não se alterando estes valores apesar da terapêutica prévia com antibióticos. Quando os resultados microbiológicos foram acrescentados aos critérios clínicos, a adequação dos diagnósticos com base nos resultados microbiológicos que corrigiram os resultados clínicos falsos positivos e falsos negativos (n=5, foram contrabalançãdos por uma proporção idêntica de diagnósticos inadequados (n=6. Conclusõe5: Os critérios clínicos revelaram valores diagnósticos razoáveis, não exibindo os critérios do CPIS valores superiores aos critérios clínicos convencionais. As técnicas não-invasivas e

Four regulatory elements in the human c-fos promoter mediate transactivation by HTLV-1 Tax protein.

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Alexandre, C; Verrier, B

1991-04-01

Expression of the human c-fos proto-oncogene is activated in trans by the Tax protein encoded by human T-cell leukemia virus type-1 (HTLV-1). Indeed, we show here that a HeLa clone stably transfected by Tax expresses Fos at a high level. We also show that multiple elements of the human c-fos promoter, i.e. the v-sis conditioned medium inducible element (SIE), the dyad symmetry element (DSE) necessary for growth factor induction, the octanucleotide direct repeat element (DR), and the cyclic AMP response element (CRE) centred at -60, can all mediate Tax transactivation. In the DSE, the 10bp central core that binds the serum response factor (SRF) is, by itself, sufficient to mediate Tax transactivation. Moreover, a CRE-binding protein is involved in Tax activation through the CRE-60 element. Since Fos is a transregulator of cellular genes, our results suggest that the oncoprotein plays a crucial role in T-cell transformation by HTLV-1 in conjunction with other Tax-inducible genes.

Occurrence of strongyloidiasis among patients with HTLV-1/2 seen at the outpatient clinic of the Núcleo de Medicina Tropical, Belém, State of Pará, Brazil.

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Furtado, Karen Cristini Yumi Ogawa; Costa, Carlos Araújo da; Ferreira, Louise de Souza Canto; Martins, Luisa Carício; Linhares, Alexandre da Costa; Ishikawa, Edna Aoba Yassui; Batista, Evander de Jesus Oliveira; Sousa, Maisa Silva de

2013-01-01

This study investigated the occurrence of Strongyloides stercoralis infestation and coinfection with HTLV-1/2 in Belém, Brazil. S. stercoralis was investigated in stool samples obtained from individuals infected with HTLV-1/2 and their uninfected relatives. The frequency of S. stercoralis was 9% (9/100), including six patients infected with HTLV-1 (14.3%), two patients infected with HTLV-2 (11.1%), and one uninfected relative. Two cases of hyperinfestation by S. stercoralis were characterized as HTLV-1. These results support the need for the routine investigation of S. stercoralis in patients with HTLV-1, in an attempt to prevent the development of severe forms of strongyloidiasis.

p53 functional impairment and high p21waf1/cip1 expression in human T-cell lymphotropic/leukemia virus type I-transformed T cells.

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Cereseto, A; Diella, F; Mulloy, J C; Cara, A; Michieli, P; Grassmann, R; Franchini, G; Klotman, M E

1996-09-01

Human T-cell lymphotropic/leukemia virus type I (HTLV-I) is associated with T-cell transformation both in vivo and in vitro. Although some of the mechanisms responsible for transformation remain unknown, increasing evidence supports a direct role of viral as well as dysregulated cellular proteins in transformation. We investigated the potential role of the tumor suppressor gene p53 and of the p53-regulated gene, p21waf1/cip1 (wild-type p53 activated fragment 1/cycling dependent kinases [cdks] interacting protein 1), in HTLV-I-infected T cells. We have found that the majority of HTLV-I-infected T cells have the wild-type p53 gene. However, its function in HTLV-I-transformed cells appears to be impaired, as shown by the lack of appropriate p53-mediated responses to ionizing radiation (IR). Interestingly, the expression of the p53 inducible gene, p21waf1/cip1, is elevated at the messenger ribonucleic acid and protein levels in all HTLV-I-infected T-cell lines examined as well as in Taxl-1, a human T-cell line stably expressing Tax. Additionally, Tax induces upregulation of a p21waf1/cip1 promoter-driven luciferase gene in p53 null cells, and increases p21waf1/cip1 expression in Jurkat T cells. These findings suggest that the Tax protein is at least partially responsible for the p53-independent expression of p21waf1/cip1 in HTLV-I-infected cells. Dysregulation of p53 and p21waf1/cip1 proteins regulating cell-cycle progression, may represent an important step in HTLV-I-induced T-cell transformation.

Human T Cell Leukemia Virus Type I Tax-Induced IκB-ζ Modulates Tax-Dependent and Tax-Independent Gene Expression in T Cells

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Ryuichiro Kimura

2013-09-01

Full Text Available Human T cell leukemia virus type I (HTLV-I is the etiologic agent of adult T cell leukemia (ATL and various inflammatory disorders including HTLV-I-associated myelopathy/tropical spastic paraparesis. HTLV-I oncoprotein Tax is known to cause permanent activation of many cellular transcription factors including nuclear factor-κB (NF-κB, cyclic adenosine 3′,5′-monophosphate response element-binding protein, and activator protein 1 (AP-1. Here, we show that NF-κB-binding cofactor inhibitor of NF-κB-ζ (IκB-ζ is constitutively expressed in HTLV-I-infected T cell lines and ATL cells, and Tax transactivates the IκB-ζ gene, mainly through NF-κB. Microarray analysis of IκB-ζ-expressing uninfected T cells demonstrated that IκB-ζ induced the expression of NF-κB. and interferon-regulatory genes such as B cell CLL/lymphoma 3 (Bcl3, guanylate-binding protein 1, and signal transducer and activator of transcription 1. The transcriptional activation domain, nuclear localization signal, and NF-κB-binding domain of IκB-ζ were required for Bcl3 induction, and IκB-ζ synergistically enhanced Tax-induced Bcl3 transactivation in an NF-κB-dependent manner. Interestingly, IκB-ζ inhibited Tax-induced NF-κB, AP-1 activation, and HTLV-I transcription. Furthermore, IκB-ζ interacted with Tax in vitro and this interaction was also observed in an HTLV-I-transformed T cell line. These results suggest that IκB-ζ modulates Tax-dependent and Tax-independent gene transcription in T cells. The function of IκB-ζ may be of significance in ATL genesis and pathogenesis of HTLV-I-associated diseases.

Hijacking of the O-GlcNAcZYME complex by the HTLV-1 Tax oncoprotein facilitates viral transcription.

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Groussaud, Damien; Khair, Mostafa; Tollenaere, Armelle I; Waast, Laetitia; Kuo, Mei-Shiue; Mangeney, Marianne; Martella, Christophe; Fardini, Yann; Coste, Solène; Souidi, Mouloud; Benit, Laurence; Pique, Claudine; Issad, Tarik

2017-07-01

The viral Tax oncoprotein plays a key role in both Human T-cell lymphotropic virus type 1 (HTLV-1)-replication and HTLV-1-associated pathologies, notably adult T-cell leukemia. Tax governs the transcription from the viral 5'LTR, enhancing thereby its own expression, via the recruitment of dimers of phosphorylated CREB to cAMP-response elements located within the U3 region (vCRE). In addition to phosphorylation, CREB is also the target of O-GlcNAcylation, another reversible post-translational modification involved in a wide range of diseases, including cancers. O-GlcNAcylation consists in the addition of O-linked-N-acetylglucosamine (O-GlcNAc) on Serine or Threonine residues, a process controlled by two enzymes: O-GlcNAc transferase (OGT), which transfers O-GlcNAc on proteins, and O-GlcNAcase (OGA), which removes it. In this study, we investigated the status of O-GlcNAcylation enzymes in HTLV-1-transformed T cells. We found that OGA mRNA and protein expression levels are increased in HTLV-1-transformed T cells as compared to control T cell lines while OGT expression is unchanged. However, higher OGA production coincides with a reduction in OGA specific activity, showing that HTLV-1-transformed T cells produce high level of a less active form of OGA. Introducing Tax into HEK-293T cells or Tax-negative HTLV-1-transformed TL-om1 T cells is sufficient to inhibit OGA activity and increase total O-GlcNAcylation, without any change in OGT activity. Furthermore, Tax interacts with the OGT/OGA complex and inhibits the activity of OGT-bound OGA. Pharmacological inhibition of OGA increases CREB O-GlcNAcylation as well as HTLV-1-LTR transactivation by Tax and CREB recruitment to the LTR. Moreover, overexpression of wild-type CREB but not a CREB protein mutated on a previously described O-GlcNAcylation site enhances Tax-mediated LTR transactivation. Finally, both OGT and OGA are recruited to the LTR. These findings reveal the interplay between Tax and the O-GlcNAcylation pathway

Tax gene expression and cell cycling but not cell death are selected during HTLV-1 infection in vivo

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Pinatel Christiane

2010-03-01

Full Text Available Abstract Background Adult T cell leukemia results from the malignant transformation of a CD4+ lymphoid clone carrying an integrated HTLV-1 provirus that has undergone several oncogenic events over a 30-60 year period of persistent clonal expansion. Both CD4+ and CD8+ lymphocytes are infected in vivo; their expansion relies on CD4+ cell cycling and on the prevention of CD8+ cell death. Cloned infected CD4+ but not CD8+ T cells from patients without malignancy also add up nuclear and mitotic defects typical of genetic instability related to theexpression of the virus-encoded oncogene tax. HTLV-1 expression is cancer-prone in vitro, but in vivo numerous selection forces act to maintain T cell homeostasis and are possibly involved in clonal selection. Results Here we demonstrate that the HTLV-1 associated CD4+ preleukemic phenotype and the specific patterns of CD4+ and CD8+ clonal expansion are in vivo selected processes. By comparing the effects of recent (1 month experimental infections performed in vitro and those observed in cloned T cells from patients infected for >6-26 years, we found that in chronically HTLV-1 infected individuals, HTLV-1 positive clones are selected for tax expression. In vivo, infected CD4+ cells are positively selected for cell cycling whereas infected CD8+ cells and uninfected CD4+ cells are negatively selected for the same processes. In contrast, the known HTLV-1-dependent prevention of CD8+ T cell death pertains to both in vivo and in vitro infected cells. Conclusions Therefore, virus-cell interactions alone are not sufficient to initiate early leukemogenesis in vivo.

Antidepressant treatment-emergent affective switch in bipolar disorder: a prospective case-control study of outcome Ciclagem afetiva associada a tratamento com antidepressivo no transtorno bipolar: estudo caso-controle prospectivo

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Renata Sayuri Tamada

2006-12-01

Full Text Available OBJECTIVE: Treatment-emergent affective switch has been associated to cycle acceleration and poorer outcome, but there are few studies addressing this issue. The aim of this study was to prospectively compare the outcome of patients presenting treatment-emergent affective switch with patients with spontaneous mania, regarding presence and polarity of a new episode and time to relapse. METHOD: Twenty-four patients with bipolar disorder according to the DSM-IV were followed for 12 months. Twelve patients had treatment-emergent affective switch and twelve had spontaneous mania. Patients were evaluated weekly with the Young Mania Rating Scale and the Hamilton Depression Scale until remission of the index episode, and monthly until completion of the 12-month follow-up. RESULTS: Eleven patients with treatment-emergent affective switch had a recurrence on follow-up, all of them with major depressive episodes. In the group with spontaneous mania, six patients had a recurrence: two had a depressive episode, and four had a manic episode (p = 0.069 for new episode, p = 0.006 for polarity of the episode. Patients with treatment-emergent affective switch relapsed in a shorter period than patients with spontaneous mania (p = 0.016. CONCLUSIONS: In this first prospective study, treatment-emergent affective switch patients were at greater risk of relapses, especially depressive episodes, and presented a shorter duration of remission when compared with patients with spontaneous mania.OBJETIVO: A ciclagem para mania associada ao antidepressivo tem sido relacionada à aceleração do ciclo e pior evolução, mas há poucos estudos na literatura sobre este assunto. O objetivo deste estudo foi comparar prospectivamente a evolução de pacientes com mania associada a antidepressivo com pacientes com mania espontânea, em relação a tempo para recaída e polaridade do novo episódio. MÉTODO: Vinte e quatro pacientes com transtorno bipolar, de acordo com os crit

The transcription elongation factor ELL2 is specifically upregulated in HTLV-1-infected T-cells and is dependent on the viral oncoprotein Tax

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Mann, Melanie C., E-mail: melanie.mann@viro.med.uni-erlangen.de; Strobel, Sarah, E-mail: sarah.strobel@viro.med.uni-erlangen.de; Fleckenstein, Bernhard, E-mail: bernhard.fleckenstein@viro.med.uni-erlangen.de; Kress, Andrea K., E-mail: andrea.kress@viro.med.uni-erlangen.de

2014-09-15

The oncoprotein Tax of human T-cell leukemia virus type 1 (HTLV-1) is a potent transactivator of viral and cellular transcription. Here, we identified ELL2 as the sole transcription elongation factor to be specifically upregulated in HTLV-1-/Tax-transformed T-cells. Tax contributes to regulation of ELL2, since transient transfection of Tax increases ELL2 mRNA, Tax transactivates the ELL2 promoter, and repression of Tax results in decrease of ELL2 in transformed T-lymphocytes. However, we also measured upregulation of ELL2 in HTLV-1-transformed cells exhibiting undetectable amounts of Tax, suggesting that ELL2 can still be maintained independent of continuous Tax expression. We further show that Tax and ELL2 synergistically activate the HTLV-1 promoter, indicating that ELL2 cooperates with Tax in viral transactivation. This is supported by our findings that Tax and ELL2 accumulate in nuclear fractions and that they co-precipitate upon co-expression in transiently-transfected cells. Thus, upregulation of ELL2 could contribute to HTLV-1 gene regulation. - Highlights: • ELL2, a transcription elongation factor, is upregulated in HTLV-1-positive T-cells. • Tax transactivates the ELL2 promoter. • Tax and ELL2 synergistically activate the HTLV-1 promoter. • Tax and ELL2 interact in vivo.

The transcription elongation factor ELL2 is specifically upregulated in HTLV-1-infected T-cells and is dependent on the viral oncoprotein Tax

International Nuclear Information System (INIS)

Mann, Melanie C.; Strobel, Sarah; Fleckenstein, Bernhard; Kress, Andrea K.

2014-01-01

The oncoprotein Tax of human T-cell leukemia virus type 1 (HTLV-1) is a potent transactivator of viral and cellular transcription. Here, we identified ELL2 as the sole transcription elongation factor to be specifically upregulated in HTLV-1-/Tax-transformed T-cells. Tax contributes to regulation of ELL2, since transient transfection of Tax increases ELL2 mRNA, Tax transactivates the ELL2 promoter, and repression of Tax results in decrease of ELL2 in transformed T-lymphocytes. However, we also measured upregulation of ELL2 in HTLV-1-transformed cells exhibiting undetectable amounts of Tax, suggesting that ELL2 can still be maintained independent of continuous Tax expression. We further show that Tax and ELL2 synergistically activate the HTLV-1 promoter, indicating that ELL2 cooperates with Tax in viral transactivation. This is supported by our findings that Tax and ELL2 accumulate in nuclear fractions and that they co-precipitate upon co-expression in transiently-transfected cells. Thus, upregulation of ELL2 could contribute to HTLV-1 gene regulation. - Highlights: • ELL2, a transcription elongation factor, is upregulated in HTLV-1-positive T-cells. • Tax transactivates the ELL2 promoter. • Tax and ELL2 synergistically activate the HTLV-1 promoter. • Tax and ELL2 interact in vivo

Human T Cell Leukemia Virus Type I Tax-Induced IκB-ζ Modulates Tax-Dependent and Tax-Independent Gene Expression in T Cells1

Science.gov (United States)

Kimura, Ryuichiro; Senba, Masachika; Cutler, Samuel J; Ralph, Stephen J; Xiao, Gutian; Mori, Naoki

2013-01-01

Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia (ATL) and various inflammatory disorders including HTLV-I-associated myelopathy/tropical spastic paraparesis. HTLV-I oncoprotein Tax is known to cause permanent activation of many cellular transcription factors including nuclear factor-κB (NF-κB), cyclic adenosine 3′,5′-monophosphate response element-binding protein, and activator protein 1 (AP-1). Here, we show that NF-κB-binding cofactor inhibitor of NF-κB-ζ (IκB-ζ) is constitutively expressed in HTLV-I-infected T cell lines and ATL cells, and Tax transactivates the IκB-ζ gene, mainly through NF-κB. Microarray analysis of IκB-ζ-expressing uninfected T cells demonstrated that IκB-ζ induced the expression of NF-κB. and interferon-regulatory genes such as B cell CLL/lymphoma 3 (Bcl3), guanylate-binding protein 1, and signal transducer and activator of transcription 1. The transcriptional activation domain, nuclear localization signal, and NF-κB-binding domain of IκB-ζ were required for Bcl3 induction, and IκB-ζ synergistically enhanced Tax-induced Bcl3 transactivation in an NF-κB-dependent manner. Interestingly, IκB-ζ inhibited Tax-induced NF-κB, AP-1 activation, and HTLV-I transcription. Furthermore, IκB-ζ interacted with Tax in vitro and this interaction was also observed in an HTLV-I-transformed T cell line. These results suggest that IκB-ζ modulates Tax-dependent and Tax-independent gene transcription in T cells. The function of IκB-ζ may be of significance in ATL genesis and pathogenesis of HTLV-I-associated diseases. PMID:24027435

The human T-lymphotropic virus type I tax gene can cooperate with the ras oncogene to induce neoplastic transformation of cells.

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Pozzatti, R; Vogel, J; Jay, G

1990-01-01

Epidemiologic studies have linked infection by the human T-lymphotropic virus type I (HTLV-I) with the development of adult T-cell leukemia. The low penetrance of the virus and the long latency for disease manifestation are factors that obscure the role of HTLV-I infection in oncogenesis. We have used an in vitro transformation assay system to determine directly whether the HTLV-I tax gene has transformation potential. Transfection of the tax gene alone into early-passage rat embryo fibroblasts did not induce morphological alterations. However, cotransfection of tax with the selectable marker plasmid pRSVneo gave rise to G418-resistant colonies that could be established as immortalized cell lines. Cotransfection of tax with the ras oncogene into rat embryo fibroblasts gave rise to foci of transformed cells that were highly tumorigenic in nude mice. These data represent a direct demonstration of the oncogenic potential of the tax gene in nonlymphoid cells and establish HTLV-I as a transforming virus.

Acurácia da radiografia de tórax associada a eletrocardiograma no diagnóstico de hipertrofia em hipertensos

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Sergio Marrone Ribeiro

2012-09-01

Full Text Available FUNDAMENTO: A radiografia de tórax e o eletrocardiograma (ECG tem sido criticados em razão de sua baixa sensibilidade no diagnóstico da Hipertrofia Ventricular Esquerda (HVE quando comparada ao ecocardiograma. Entretanto, esse exame não está disponível nos centros de atendimento primário para toda a população de hipertensos. OBJETIVO: Avaliar se a radiografia de tórax associada ao eletrocardiograma apresenta acurácia que justifique seu uso na detecção de HVE em hipertensos, bem como a utilidade do índice cardiotorácico e das radiografias oblíquas na avaliação das dimensões das câmaras cardíacas esquerdas. MÉTODOS: Estudo prospectivo realizado em 177 pacientes hipertensos consecutivos, através da radiografia do tórax, eletrocardiograma e ecocardiograma. Testes de acurácia foram utilizados para comparar esses métodos utilizando a ecocardiografia convencional como padrão de referência. RESULTADOS: O índice cardiotorácico mostrou sensibilidade de 17% para o diagnóstico de HVE, somente detectando alterações cardíacas mais acentuadas. As incidências póstero-anterior e perfil tiveram sensibilidade de 52%, aumentando para 54% quando a radiografia de tórax foi associada ao eletrocardiograma. As incidências oblíquas não melhoraram significativamente a acurácia da radiografia de tórax que, por sua vez, apresentou alta especificidade e boa sensibilidade para a detecção do aumento da aorta. Foi interessante notar que essa alteração estava presente em metade dos hipertensos com HVE. CONCLUSÃO: A associação da radiografia de tórax com eletrocardiograma é útil na avaliação inicial de hipertensos para o diagnóstico de hipertrofia ventricular esquerda, especialmente se a ecocardiografia não estiver disponível. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0

Human T-cell lymphotropic virus (HTLV)-associated encephalopathy: an under-recognised cause of acute encephalitis? Case series and literature review.

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Crawshaw, Ania A; Dhasmana, Divya; Jones, Brynmor; Gabriel, Carolyn M; Sturman, Steve; Davies, Nicholas W S; Taylor, Graham P

2018-04-01

Human T-cell lymphotropic virus (HTLV)-1-associated myelopathy (HAM) is well described. Clinical features are predominantly consistent with cord pathology, though imaging and autopsy studies also demonstrate brain inflammation. In general, this is subclinical; however, six cases have previously been reported of encephalopathy in HTLV-1-infected patients, without alternative identified aetiology. We describe three further cases of encephalitis in the UK HAM cohort (n = 142), whereas the annual incidence of acute encephalitis in the general population is 0.07-12.6 per 100,000. Clinical features included reduced consciousness, fever/hypothermia, headaches, seizures, and focal neurology. Investigation showed: raised CSF protein; pleocytosis; raised CSF:peripheral blood mononuclear cell HTLV-1 proviral load ratio; and MRI either normal or showing white matter changes in brain and cord. Four of the six previous case reports of encephalopathy in HTLV-infected patients also had HAM. Histopathology, reported in three, showed perivascular predominantly CD8+ lymphocytic infiltrates in the brain. One had cerebral demyelination, and all had cord demyelination. We have reviewed the existing six cases in the literature, together with our three new cases. In all seven with HAM, the spastic paraparesis deteriorated sub-acutely preceding encephalitis. Eight of the nine were female, and four of the seven treated with steroids improved. We propose that HTLV-associated encephalopathy may be part of the spectrum of HTLV-1-induced central nervous system disease.

From Immunodeficiency to Humanization: The Contribution of Mouse Models to Explore HTLV-1 Leukemogenesis

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Eléonore Pérès

2015-12-01

Full Text Available The first discovered human retrovirus, Human T-Lymphotropic Virus type 1 (HTLV-1, is responsible for an aggressive form of T cell leukemia/lymphoma. Mouse models recapitulating the leukemogenesis process have been helpful for understanding the mechanisms underlying the pathogenesis of this retroviral-induced disease. This review will focus on the recent advances in the generation of immunodeficient and human hemato-lymphoid system mice with a particular emphasis on the development of mouse models for HTLV-1-mediated pathogenesis, their present limitations and the challenges yet to be addressed.

As complexidades inerentes ao tema "mudanças climáticas": desafios e perspectivas para o ensino de física

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Reis, Danielle Aparecida dos; Silva, Luciano Fernandes; Figueiredo, Newton

2015-01-01

RESUMO: A articulação entre a física e a temática ambiental apresenta oportunidades para a construção de práticas educativas que privilegiam o tratamento das controvérsias e das complexidades associadas aos temas ambientais, como ocorre com o fenômeno das mudanças climáticas. Neste ensaio teórico destaca-se que a natureza complexa desse fenômeno climático favorece o surgimento das controvérsias, o que proporciona aos professores da Educação Básica possibilidades para o tratamento educativo di...

HTLV-1 bZIP Factor Impairs Anti-viral Immunity by Inducing Co-inhibitory Molecule, T Cell Immunoglobulin and ITIM Domain (TIGIT.

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Keiko Yasuma

2016-01-01

Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 infects CD4+ T cells and induces proliferation of infected cells in vivo, which leads to the onset of adult T-cell leukemia (ATL in some infected individuals. The HTLV-1 bZIP factor (HBZ gene, which is encoded in the minus strand of HTLV-1, plays critical roles in pathogenesis. In this study, RNA-seq and ChIP-seq analyses using HBZ transduced T cells revealed that HBZ upregulates the expression and promoter acetylation levels of a co-inhibitory molecule, T cell immunoglobulin and ITIM domain (TIGIT, in addition to those of regulatory T cells related genes, Foxp3 and Ccr4. TIGIT was expressed on CD4+ T cells from HBZ-transgenic (HBZ-Tg mice, and on ATL cells and HTLV-1 infected CD4+ T cells of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP in vivo. Expression of Blimp1 and IL-10 was upregulated in TIGIT+CD4+ cells of HBZ-Tg mice compared with TIGIT-CD4+ T cells, suggesting the correlation between TIGIT expression and IL-10 production. When CD4+ T cells from HBZ-Tg mice were stimulated with TIGIT's ligand, CD155, their production of the inhibitory cytokine IL-10 was enhanced. Furthermore, dendritic cells from HBZ-Tg mice produced high levels of IL-10 after stimulation. These data suggest that HBZ alters immune system to suppressive state via TIGIT and IL-10. Importantly, TIGIT suppressed T-cell responses to another HTLV-1 virus protein, Tax, in vitro. Blocking of TIGIT and PD-1 slightly increased anti-Tax T-cell activity in some HAM/TSP patients. These results suggest that HBZ-induced TIGIT on HTLV-1 infected cells impairs T-cell responses to viral antigens. This study shows that HBZ-induced TIGIT plays a pivotal role in attenuating host immune responses and shaping a microenvironment favorable to HTLV-1.

Interferon-γ Promotes Inflammation and Development of T-Cell Lymphoma in HTLV-1 bZIP Factor Transgenic Mice.

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Yu Mitagami

2015-08-01

Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 is an etiological agent of several inflammatory diseases and a T-cell malignancy, adult T-cell leukemia (ATL. HTLV-1 bZIP factor (HBZ is the only viral gene that is constitutively expressed in HTLV-1-infected cells, and it has multiple functions on T-cell signaling pathways. HBZ has important roles in HTLV-1-mediated pathogenesis, since HBZ transgenic (HBZ-Tg mice develop systemic inflammation and T-cell lymphomas, which are similar phenotypes to HTLV-1-associated diseases. We showed previously that in HBZ-Tg mice, HBZ causes unstable Foxp3 expression, leading to an increase in regulatory T cells (Tregs and the consequent induction of IFN-γ-producing cells, which in turn leads to the development of inflammation in the mice. In this study, we show that the severity of inflammation is correlated with the development of lymphomas in HBZ-Tg mice, suggesting that HBZ-mediated inflammation is closely linked to oncogenesis in CD4+ T cells. In addition, we found that IFN-γ-producing cells enhance HBZ-mediated inflammation, since knocking out IFN-γ significantly reduced the incidence of dermatitis as well as lymphoma. Recent studies show the critical roles of the intestinal microbiota in the development of Tregs in vivo. We found that even germ-free HBZ-Tg mice still had an increased number of Tregs and IFN-γ-producing cells, and developed dermatitis, indicating that an intrinsic activity of HBZ evokes aberrant T-cell differentiation and consequently causes inflammation. These results show that immunomodulation by HBZ is implicated in both inflammation and oncogenesis, and suggest a causal connection between HTLV-1-associated inflammation and ATL.

HTLV-1 Infection and Neuropathogenesis in the Context of Rag1-/-γc-/- (RAG1-Hu) and BLT Mice.

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Ginwala, Rashida; Caruso, Breanna; Khan, Zafar K; Pattekar, Ajinkya; Chew, Glen M; Corley, Michael J; Loonawat, Ronak; Jacobson, Steven; Sreedhar, Sreesha; Ndhlovu, Lishomwa C; Jain, Pooja

2017-09-01

To date, the lack of a suitable small animal model has hindered our understanding of Human T-cell lymphotropic virus (HTLV)-1 chronic infection and associated neuropathogenesis defined as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The host immune response plays a critical role in the outcome of HTLV-1 infection, which could be better tested in the context of humanized (hu) mice. Thus, we employ here the Balb/c-Rag1 -/- γc -/- or Rag1 as well as Bone marrow-Liver-Thymic (BLT) mouse models for engraftment of human CD34 + hematopoietic stem cells. Flow cytometry and histological analyses confirmed reconstitution of Rag1 and BLT mice with human immune cells. Following HTLV-1 infection, proviral load (PVL) was detected in the blood of Rag-1 and BLT hu-mice as early as 2 weeks post-infection (wpi) with sustained elevation in the subsequent weeks followed by Tax expression. Additionally, infection was compared between adult and neonatal Rag1 mice with both PVL and Tax expression considerably higher in the adult Rag1 mice as compared to the neonates. Establishment of peripheral infection led to lymphocytic infiltration with concomitant Tax expression and resulting myelin disruption within the central nervous system of infected mice. In addition, up-regulation in the expression of several immune checkpoint mediators such as programmed cell death-1 (PD-1), T-cell Ig and ITIM domain (TIGIT), and T cell Ig and mucin domain-3 protein (Tim-3) were observed on CD8 + T cells in various organs including the CNS of infected hu-mice. Collectively, these studies represent the first attempt to establish HTLV-1 neuropathogenesis in the context of Rag-1 and BLT hu-mice as potential novel tools for understanding HTLV-1 neuropathogenesis and testing of novel therapies such as immune checkpoint blockade in the amelioration of chronic HTLV-1 infection.

Human T-Cell Leukemia Virus Type I-Mediated Repression of PDZ-LIM Domain-Containing Protein 2 Involves DNA Methylation But Independent of the Viral Oncoprotein Tax

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Pengrong Yan

2009-10-01

Full Text Available Human T-cell leukemia virus type I (HTLV-I is the etiological agent of adult T-cell leukemia (ATL. Our recent studies have shown that one important mechanism of HTLV-I-Mediated tumorigenesis is through PDZ-LIM domain-containing protein 2 (PDLIM2 repression, although the involved mechanism remains unknown. Here, we further report that HTLV-I-Mediated PDLIM2 repression was a pathophysiological event and the PDLIM2 repression involved DNA methylation. Whereas DNA methyltransferases 1 and 3b but not 3a were upregulated in HTLV-I-transformed T cells, the hypomethylating agent 5-aza-2′-deoxycytidine (5-aza-dC restored PDLIM2 expression and induced death of these malignant cells. Notably, the PDLIM2 repression was independent of the viral regulatory protein Tax because neither short-term induction nor long-term stable expression of Tax could downregulate PDLIM2 expression. These studies provide important insights into PDLIM2 regulation, HTLV-I leukemogenicity, long latency, and cancer health disparities. Given the efficient antitumor activity with no obvious toxicity of 5-aza-dC, these studies also suggest potential therapeutic strategies for ATL.

HIV-1 subtypes and mutations associated to antiretroviral drug resistance in human isolates from Central Brazil Subtipos e mutações associadas à resistência aos anti-retrovirais em isolados de HIV-1 do Distrito Federal

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Daniela Marreco Cerqueira

2004-09-01

Full Text Available The detection of polymorphisms associated to HIV-1 drug-resistance and genetic subtypes is important for the control and treatment of HIV-1 disease. Drug pressure selects resistant variants that carry mutations in the viral reverse transcriptase (RT and protease (PR genes. For a contribution to the public health authorities in planning the availability of therapeutic treatment, we therefore described the genetic variability, the prevalence of mutations associated to drug resistance and the antiretroviral resistance profile in HIV-1 isolates from infected individuals in Central Brazil. Nineteen HIV-1 RNA samples from a Public Health Laboratory of the Federal District were reversely transcribed and cDNAs were amplified by nested PCR. One fragment of 297 bp coding the entire protease gene, and another of 647 bp, corresponding to the partial RT gene (codons 19-234, were obtained. Automated sequencing and BLAST analysis revealed the presence of 17 B and 2 F1 HIV-1 subtypes. The amino acid sequences were analyzed for the presence of resistance-associated mutations. A total of 6 PR mutations, 2 major and 4 accessory, and 8 RT mutations related to drug resistance were found. Our data suggest a high prevalence of HIV-1 B subtype in the studied population of Federal District as well as the presence of genetically-resistant strains in individuals failing treatment.A detecção de polimorfismos do HIV-1 que estejam associados à resistência às drogas anti-retrovirais e aos subtipos genéticos é importante para o controle e tratamento da infecção pelo HIV-1. A pressão exercida pela terapia anti-retroviral seleciona variantes resistentes com mutações nos genes virais da transcriptase reversa (RT e da protease (PR. Assim, visando contribuir com as autoridades de saúde pública na perspectiva de planejar a disponibilidade de um tratamento terapêutico, nós descrevemos a variabilidade genética e a prevalência de mutações associadas à resist

The Transcription Profile of Tax-3 Is More Similar to Tax-1 than Tax-2: Insights into HTLV-3 Potential Leukemogenic Properties

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Chevalier, Sébastien A.; Durand, Stéphanie; Dasgupta, Arindam; Radonovich, Michael; Cimarelli, Andrea; Brady, John N.

2012-01-01

Human T-cell Lymphotropic Viruses type 1 (HTLV-1) is the etiological agent of Adult T-cell Leukemia/Lymphoma. Although associated with lymphocytosis, HTLV-2 infection is not associated with any malignant hematological disease. Similarly, no infection-related symptom has been detected in HTLV-3-infected individuals studied so far. Differences in individual Tax transcriptional activity might account for these distinct physiopathological outcomes. Tax-1 and Tax-3 possess a PDZ binding motif in their sequence. Interestingly, this motif, which is critical for Tax-1 transforming activity, is absent from Tax-2. We used the DNA microarray technology to analyze and compare the global gene expression profiles of different T- and non T-cell types expressing Tax-1, Tax-2 or Tax-3 viral transactivators. In a T-cell line, this analysis allowed us to identify 48 genes whose expression is commonly affected by all Tax proteins and are hence characteristic of the HTLV infection, independently of the virus type. Importantly, we also identified a subset of genes (n = 70) which are specifically up-regulated by Tax-1 and Tax-3, while Tax-1 and Tax-2 shared only 1 gene and Tax-2 and Tax-3 shared 8 genes. These results demonstrate that Tax-3 and Tax-1 are closely related in terms of cellular gene deregulation. Analysis of the molecular interactions existing between those Tax-1/Tax-3 deregulated genes then allowed us to highlight biological networks of genes characteristic of HTLV-1 and HTLV-3 infection. The majority of those up-regulated genes are functionally linked in biological processes characteristic of HTLV-1-infected T-cells expressing Tax such as regulation of transcription and apoptosis, activation of the NF-κB cascade, T-cell mediated immunity and induction of cell proliferation and differentiation. In conclusion, our results demonstrate for the first time that, in T- and non T-cells types, Tax-3 is a functional analogue of Tax-1 in terms of transcriptional activation and

Modelación molecular y variación estructural de las integrasas de dos retrovirus humanos: HTLV-I y VIH-1

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Felipe García Vallejo

2009-01-01

Materiales y métodos: Tanto la integrasa del HTLV-I como la del VIH-1 son proteínas compuestas por 288 residuos de aminoácidos. Se encontró un parecido de estructuras terciarias entre los dominios catalíticos de las IN de VIH-1, ASV y RSV con la del HTLVI. A partir de 103 secuencias completas de la integrasa del VIH-1 se registraron, en 46 codones, un total de 53 sustituciones que se localizaron en diferentes posiciones de la proteína nativa; las más frecuentes fueron: N27G (32,1%, A265V (30,1%, L101I (31,1% y T123A (27,0%. Ninguna de las sustituciones más frecuentemente encontradas generó un cambio en el plegamiento nativo de la correspondiente región. Conclusión: La estructura tridimensional del dominio central catalítico de la integrasa condicionaría su actividad y su relación con moléculas potencialmente inhibidoras. Las sustituciones observadas fueron neutrales sin alterar la estructura nativa. Los resultados obtenidos confirman que la integrasa es un nuevo y promisorio blanco para el desarrollo de terapias antirretrovirales más efectivas en el siglo xxi.

Características clínicas e laboratoriais da meningite asséptica associada à vacina tríplice viral

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Lucena Rita

2002-01-01

Full Text Available Objetivos. Descrever os achados epidemiológicos, clínicos e liquóricos dos casos de meningite asséptica associada à vacina tríplice viral (sarampo, caxumba e rubéola, ocorridos no Estado da Bahia após campanha de vacinação em massa promovida pelo Ministério da Saúde do Brasil em agosto de 1997, e comparar esses casos aos de meningite asséptica não associada à vacina ocorridos no mesmo ano. Métodos. Entre março e outubro de 1997, foi realizado acompanhamento prospectivo de todos os indivíduos com idade de 1 a 12 anos admitidos no Hospital Couto Maia com diagnóstico clínico e laboratorial de meningite asséptica. A população do estudo foi dividida em dois grupos, representando indivíduos vacinados e não vacinados. Foram coletadas informações demográficas, clínicas e laboratoriais para ambos os grupos. Resultados. No mês de setembro, logo após a campanha de vacinação, 74 casos de meningite asséptica foram atendidos no Hospital Couto Maia, em comparação com a média mensal de 7,5 casos. Verificamos maior freqüência de rigidez de nuca e níveis mais altos de celularidade liquórica nas crianças cuja meningite foi associada à vacina. Por outro lado, houve maior número de casos com comprometimento encefálico no grupo de meningites não associadas à vacinação. Conclusões. Embora a meningite pós-vacinal tenha curso mais benigno, seu tratamento continua gerando custos com exames complementares e internações. As campanhas de vacinação em larga escala devem utilizar vacinas contendo cepas menos reatogênicas.

Regulation of human T-lymphotropic virus type I latency and reactivation by HBZ and Rex.

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Subha Philip

2014-04-01

Full Text Available Human T lymphotropic virus type I (HTLV-I infection is largely latent in infected persons. How HTLV-1 establishes latency and reactivates is unclear. Here we show that most HTLV-1-infected HeLa cells become senescent. By contrast, when NF-κB activity is blocked, senescence is averted, and infected cells continue to divide and chronically produce viral proteins. A small population of infected NF-κB-normal HeLa cells expresses low but detectable levels of Tax and Rex, albeit not Gag or Env. In these "latently" infected cells, HTLV-1 LTR trans-activation by Tax persists, but NF-κB trans-activation is attenuated due to inhibition by HBZ, the HTLV-1 antisense protein. Furthermore, Gag-Pol mRNA localizes primarily in the nuclei of these cells. Importantly, HBZ was found to inhibit Rex-mediated export of intron-containing mRNAs. Over-expression of Rex or shRNA-mediated silencing of HBZ led to viral reactivation. Importantly, strong NF-κB inhibition also reactivates HTLV-1. Hence, during HTLV-1 infection, when Tax/Rex expression is robust and dominant over HBZ, productive infection ensues with expression of structural proteins and NF-κB hyper-activation, which induces senescence. When Tax/Rex expression is muted and HBZ is dominant, latent infection is established with expression of regulatory (Tax/Rex/HBZ but not structural proteins. HBZ maintains viral latency by down-regulating Tax-induced NF-κB activation and senescence, and by inhibiting Rex-mediated expression of viral structural proteins.

Doença pulmonar intersticial associada a bronquiolite respiratória Respiratory bronchilitis-associated interstitial lung disease

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Sílvia CS. Rodrigues

2004-12-01

Full Text Available A doença pulmonar intersticial associada a bronquiolite respiratória faz parte do espectro anatomopatológico das lesões pulmonares infiltrativas difusas induzidas pela fumaça de cigarro. Raramente tem apresentação clínico-funcional exuberante. Descrevemos dois casos diagnosticados por biópsia pulmonar aberta, caracterizados por dispnéia de evolução insidiosa, baqueteamento digital, lesões císticas à tomografia computadorizada e hipoxemia ao exercício. Enfatizamos considerar, em indivíduos tabagistas, a doença pulmonar intersticial associada a bronquiolite respiratória no contexto das pneumopatias intersticiais císticas, juntamente com a linfangioleiomiomatose, o granuloma eosinofílico e a fibrose pulmonar idiopática.Respiratory bronchiolitis-associated interstitial lung disease is one of many within the spectrum of smoking-related diffuse infiltrative lung diseases. The clinical and functional characteristics are typically subtle. Herein, we describe two cases of diagnosed through open-lung biopsy, and characterized by insidious evolution of dyspnea, digital clubbing, cystic lesions on computed tomography scans, and hipoxemia upon exertion. We emphasize that, when smokers are evaluated, it is imprtant to consider a diagnosis of respiratory bronchiolitis-associated interstitial lung disease in the context of interstitial cystitis, as well as in that of lymphangioleiomyomatosis, eosinophilic granuloma and idiophatic pulmonary fibrosis.

Sarcopenia associada ao envelhecimento: aspectos etiológicos e opções terapêuticas Sarcopenia and aging: etiological aspects and therapeutic options

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Tatiana Alves de Araujo Silva

2006-12-01

Full Text Available A prevalência de incapacidade e dependência funcional é maior em idosos e está intimamente associada à redução da massa muscular, que ocorre, até mesmo, em indivíduos saudáveis. A sarcopenia parece decorrer da interação complexa de distúrbios da inervação, diminuição de hormônios, aumento de mediadores inflamatórios e alterações da ingestão protéico-calórica que ocorrem durante o envelhecimento. A perda de massa e força muscular é responsável pela redução de mobilidade e aumento da incapacidade funcional e dependência. Quando associada à fragilidade, esta perda gera custos econômicos e sociais. Neste artigo, pretende-se avaliar aspectos relacionados à gênese da sarcopenia, bem como analisar possíveis opções terapêuticas e de prevenção.The high prevalence of inability and functional dependence is an important problem in elderly people. It is closely related with aging decrease of lean muscle mass that occurs even in healthy subjects. Skeletal muscle mass deficiency, or sarcopenia, results from complex interactions between innervations disturbances, hormones deficiency, inflammatory cytokines and restriction in caloric-proteic ingestion. Loss of skeletal muscle mass and strength results in disability and functional dependency that are associated to frailty in many elderly people. These conditions represent enormous economic and social budget. In this article, we evaluate pathogenesis of sarcopenia and discuss potential therapies.

Malformações do sistema nervoso central e malformações associadas diagnosticadas pela ultrassonografia obstétrica

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Marcela Leonardo Barros

2012-12-01

Full Text Available OBJETIVO: Identificar a prevalência de malformações congênitas do sistema nervoso central (SNC e malformações associadas diagnosticadas pela ultrassonografia obstétrica. MATERIAIS E MÉTODOS: Estudo observacional, transversal, descritivo, em instituição de referência para gestações de alto risco. RESULTADOS: Malformações congênitas do SNC estiveram presentes sem outras malformações associadas em 65,78%, com a distribuição: hidrocefalia (37,5%, mielomeningocele (15%, encefalocele (12,5%, agenesia de corpo caloso (12,5%, anencefalia (12,5%, holoprosencefalia (7,5%, Dandy-Walker (7,5%, Arnold-Chiari (5,0%, hidranencefalia (5,0%, meningocele (5,0%, cisto aracnoideo (2,5%. Malformações congênitas de outros sistemas estiveram associadas às do SNC: craniofacial (73,9%, ortopédica (65,2%, cardiovascular (34,8%, geniturinária (30,4%, gastrintestinal (30,4%, respiratória (8,7%, sindrômica (8,7, oftalmológica (4,3%. A sensibilidade ultrassonográfica no estudo de malformações fetais do SNC foi 79,4%. A taxa de falso-negativos foi 20,5%. Dentre as limitações quantificáveis destaca-se o oligodrâmnio, presente em 25% dos falso-negativos. CONCLUSÃO: A ultrassonografia obstétrica possui boa sensibilidade no rastreio de malformações fetais do SNC, em especial com o aperfeiçoamento constante e domínio na utilização de métodos especializados, como o Doppler e a ultrassonografia volumétrica (3D/4D, contribuindo para firmar-se como modalidade de escolha nesta rotina. Complementar ao método, a ressonância magnética pode vir a fornecer subsídios para uma ainda melhor assistência perinatal.

Divergent strains of human T-lymphotropic virus type 1 (HTLV-1) within the Cosmopolitan subtype in Argentina.

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Eirin, Maria E; Dilernia, Dario A; Berini, Carolina A; Jones, Leandro R; Pando, Maria A; Biglione, Mirna M

2008-10-01

HTLV-1 Cosmopolitan subtype Transcontinental subgroup A has been described among aboriginal communities from the northwest endemic area of Argentina. Moreover, Transcontinental subgroup A and the Japanese subgroup B were reported among blood donors from the nonendemic central region of the country. We carried out the first HTLV-1 phylogenetic study in individuals residing in Buenos Aires capital city. Phylogenetic analysis performed on the LTR region showed that all 44 new strains clustered within the Cosmopolitan subtype, with 42 (95.4%) belonging to Transcontinental subgroup A. Of them, 20 (45.5%) strains grouped in the large Latin American cluster and 4 (9.1%) in the small Latin American cluster. The majority of them belonged to individuals of nonblack origin, grouped with Amerindian strains. Three (6.8%) were closely related to South African references and two monophyletic clusters including only HIV/HTLV-1 coinfected individuals were observed. Interestingly, two (4.5%) new sequences (divergent strains) branched off from all five known Cosmopolitan subgroups in a well-supported clade. In summary, these findings show that HTLV-1 Cosmopolitan subtype Transcontinental subgroup A is infecting residents of Buenos Aires, a nonendemic area of Argentina, and confirm the introduction of divergent strains in the country.

Basal encephalocele associated with morning glory syndrome: case report Encefalocele basal associada a síndrome "morning glory": relato de caso

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Ivanete Minotto

2007-12-01

Full Text Available The basal encephaloceles refer to rare entities and they correspond to herniation of brain tissue through defects of skull along the cribiform plate or the sphenoid bone. A rare morning glory syndrome, with characteristic retinal defect has been reported in association with basal encephaloceles. Hypophysis hormonal deficiencies may occur. We accounted for a pituitary dwarfism with delayed diagnosed transsphenoidal encephalocele associated with morning glory syndrome, showing the alterations found in retinography, computed tomography and magnetic resonance imaging.As encefaloceles basais são entidades raras e correspondem a herniações do tecido cerebral através de um defeito do crânio, ao longo da lâmina crivosa etmoidal ou do osso esfenoidal. A rara síndrome morning glory, com alterações de fundo de olho características pode apresentar-se associada à encefalocele basal. Deficiências hormonais hipofisárias podem ocorrer. Relatamos caso de nanismo hipofisário com encefalocele transesfenoidal de diagnóstico tardio associada à síndrome de morning glory, mostrando as alterações na retinografia, tomografia computadorizada e ressonância magnética.

Modelo para condução de decisões estratégicas associadas ao gerenciamento da inovação em produtos

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Angela de Moura Ferreira Danilevicz

2006-01-01

A inovação é uma das principais alternativas para manter a competitividade empresarial. Este trabalho apresenta um modelo para auxiliar nas decisões estratégicas associadas à inovação. Esse modelo é denominado DEIN – Decisões Estratégicas de INovação – e contempla tanto a inovação espontânea como a induzida. O modelo proposto foi construído a partir da análise do referencial teórico e entrevistas conduzidas junto a especialistas. Ele fornece uma estrutura para avaliar os diferentes elementos ...

The transcription elongation factor ELL2 is specifically upregulated in HTLV-1-infected T-cells and is dependent on the viral oncoprotein Tax.

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Mann, Melanie C; Strobel, Sarah; Fleckenstein, Bernhard; Kress, Andrea K

2014-09-01

The oncoprotein Tax of human T-cell leukemia virus type 1 (HTLV-1) is a potent transactivator of viral and cellular transcription. Here, we identified ELL2 as the sole transcription elongation factor to be specifically upregulated in HTLV-1-/Tax-transformed T-cells. Tax contributes to regulation of ELL2, since transient transfection of Tax increases ELL2 mRNA, Tax transactivates the ELL2 promoter, and repression of Tax results in decrease of ELL2 in transformed T-lymphocytes. However, we also measured upregulation of ELL2 in HTLV-1-transformed cells exhibiting undetectable amounts of Tax, suggesting that ELL2 can still be maintained independent of continuous Tax expression. We further show that Tax and ELL2 synergistically activate the HTLV-1 promoter, indicating that ELL2 cooperates with Tax in viral transactivation. This is supported by our findings that Tax and ELL2 accumulate in nuclear fractions and that they co-precipitate upon co-expression in transiently-transfected cells. Thus, upregulation of ELL2 could contribute to HTLV-1 gene regulation. Copyright © 2014 Elsevier Inc. All rights reserved.

Manifestações orais associada ao papilomavírus humano (hpv conceitos atuais: revisão bibliográfica Oral manifestations related to papillomavirus (hpv

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Therezita M.P.G. Castro

2004-08-01

Full Text Available O papilomavírus (HPV é um DNA vírus do grupo papovavírus, que é altamente transmissível sexualmente, sendo freqüente na região ano-genital e raro na mucosa oral. A sua implantação oral pode ser por auto-inoculação ou pelo contato oro-sexual. As manifestações orais associadas ao HPV são: papiloma, condiloma acuminado, verruga vulgar, hiperplasia epitelial focal, leucoplasias, líquen plano e carcinoma. O diagnóstico é dado pelo exame da lesão e confirmado pela biópsia, com a identificação do tipo de HPV pelas técnicas de biologia molecular (captura híbrida e PCR. O tratamento, dependendo da lesão, pode ser clínico e/ou cirúrgico, obtendo assim a cura clínica, pois o vírus permanece no epitélio da mucosa mesmo após o tratamento.The human papillomavirus (HPV is a DNA virus, of the papovavirus group, that is highly sexually transmittable. It is common in the anal and genital parts and rarely in the oral mucosa. The oral implantation can be by self-inoculation or by oral-sexual contact. The oral manifestations related to HPV are: papilloma, condyloma acuminatum, verruca vulgaris, focal epithelial hyperplasia, leukoplasia, lichen planus, and the squamous cell carcinoma. The diagnosis is performed by lesion exam and confirmed by biopsy, showing the HPV genotype by molecular biology techniques (hybrid capture and PCR. The treatment, depending on the lesion, can be clinical or surgical, allowing clinical cure, because the virus remains in the epithelium of the mucosa even after the treatment.

Involvement of TORC2, a CREB co-activator, in the in vivo-specific transcriptional control of HTLV-1

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Furuta Rika A

2009-08-01

Full Text Available Abstract Background Human T-cell leukemia virus type 1 (HTLV-1 causes adult T -cell leukemia (ATL but the expression of HTLV-1 is strongly suppressed in the peripheral blood of infected people. However, such suppression, which may explain the long latency in the development of ATL, is readily reversible, and viral expression resumes quickly with ex vivo culture of infected T -cells. To investigate the mechanism of in vivo -specific transcriptional suppression, we established a mouse model in which mice were intraperitoneally administered syngeneic EL4 T -lymphoma cells transduced with a recombinant retrovirus expressing a GFP-Tax fusion protein, Gax, under the control of the HTLV-1 enhancer (EL4-Gax. Results Gax gene transcription was silenced in vivo but quickly up-regulated in ex vivo culture. Analysis of integrated Gax reporter gene demonstrated that neither CpG methylation of the promoter DNA nor histone modification was associated with the reversible suppression. ChIP-analysis of LTR under suppression revealed reduced promoter binding of TFIIB and Pol-II, but no change in the binding of CREB or CBP/p300 to the viral enhancer sequence. However, the expression of TORC2, a co-activator of CREB, decreased substantially in the EL4-Gax cells in vivo, and this returned to normal levels in ex vivo culture. The reduced expression of TORC2 was associated with translocation from the nucleus to the cytoplasm. A knock-down experiment with siRNA confirmed that TORC2 was the major functional protein of the three TORC-family proteins (TORC1, 2, 3 in EL4-Gax cells. Conclusion These results suggest that the TORC2 may play an important role in the in vivo -specific transcriptional control of HTLV-1. This study provides a new model for the reversible mechanism that suppresses HTLV-1 expression in vivo without the DNA methylation or hypoacetylated histones that is observed in the primary cells of most HTLV-1 -infected carriers and a substantial number of ATL

Human T cell lymphotropic virus type I genomic expression and impact on intracellular signaling pathways during neurodegenerative disease and leukemia.

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Yao, J; Wigdahl, B

2000-01-01

HTLV-I has been identified as the etiologic agent of neoplasia within the human peripheral blood T lymphocyte population, and a progressive neurologic disorder based primarily within the central nervous system. We have examined the role of HTLV-I in these two distinctly different clinical syndromes by examining the life cycle of the virus, with emphasis on the regulation of viral gene expression within relevant target cell populations. In particular, we have examined the impact of specific viral gene products, particularly Tax, on cellular metabolic function. Tax is a highly promiscuous and pleiotropic viral oncoprotein, and is the most important factor contributing to the initial stages of viral-mediated transformation of T cells after HTLV-I infection. Tax, which weakly binds to Tax response element 1 (TRE-1) in the viral long terminal repeat (LTR), can dramatically trans-activate viral gene expression by interacting with cellular transcription factors, such as activated transcription factors and cyclic AMP response element binding proteins (ATF/CREB), CREB binding protein (CBP/p300), and factors involved with the basic transcription apparatus. At the same time, Tax alters cellular gene expression by directly or indirectly interacting with a variety of cellular transcription factors, cell cycle control elements, and cellular signal transduction molecules ultimately resulting in dysregulated cell proliferation. The mechanisms associated with HTLV-I infection, leading to tropical spastic paraparesis (TSP) are not as clearly resolved. Possible explanations of viral-induced neurologic disease range from central nervous system (CNS) damage caused by direct viral invasion of the CNS to bystander CNS damage caused by the immune response to HTLV-I infection. It is interesting to note that it is very rare for an HTLV-I infected individual to develop both adult T cell leukemia (ATL) and TSP in his/her life time, suggesting that the mechanisms governing development of these

INTERFERON BETA-1A TREATMENT IN HTLV-1-ASSOCIATED MYELOPATHY/TROPICAL SPASTIC PARAPARESIS: A CASE REPORT

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Graça Maria de Castro Viana

2014-09-01

Full Text Available Here a young patient (< 21 years of age with a history of infective dermatitis is described. The patient was diagnosed with myelopathy associated with HTLV-1/tropical spastic paraparesis and treated with interferon beta-1a. The disease was clinically established as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, and laboratory tests confirmed the presence of antibodies to HTLV-1 in the cerebrospinal fluid (CSF. Mumps, cytomegalovirus, Epstein-Barr virus, schistosomiasis, herpes virus 1 and 2, rubella, measles, varicella-zoster toxoplasmosis, hepatitis, HIV, and syphilis were excluded by serology. The patient was diagnosed with neurogenic bladder and presented with nocturia, urinary urgency, paresthesia of the lower left limb, a marked reduction of muscle strength in the lower limbs, and a slight reduction in upper limb strength. During the fourth week of treatment with interferon beta-1a, urinary urgency and paresthesia disappeared and clinical motor skills improved.

Niclosamide, an anti-helminthic molecule, downregulates the retroviral oncoprotein Tax and pro-survival Bcl-2 proteins in HTLV-1-transformed T lymphocytes

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Xiang, Di [Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033 (United States); Yuan, Yunsheng [Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033 (United States); Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai (China); Chen, Li [Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou (China); Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Liu, Xin; Belani, Chandra [Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033 (United States); Cheng, Hua, E-mail: hcheng@ihv.umaryland.edu [Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Department Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

2015-08-14

Adult T cell leukemia and lymphoma (ATL) is a highly aggressive form of hematological malignancy and is caused by chronic infection of human T cell leukemia virus type 1 (HTLV-1). The viral genome encodes an oncogenic protein, Tax, which plays a key role in transactivating viral gene transcription and in deregulating cellular oncogenic signaling to promote survival, proliferation and transformation of virally infected T cells. Hence, Tax is a desirable therapeutic target, particularly at early stage of HTLV-1-mediated oncogenesis. We here show that niclosamide, an anti-helminthic molecule, induced apoptosis of HTLV-1-transformed T cells. Niclosamide facilitated degradation of the Tax protein in proteasome. Consistent with niclosamide-mediated Tax degradation, this compound inhibited activities of MAPK/ERK1/2 and IκB kinases. In addition, niclosamide downregulated Stat3 and pro-survival Bcl-2 family members such as Mcl-1 and repressed the viral gene transcription of HTLV-1 through induction of Tax degradation. Since Tax, Stat3 and Mcl-1 are crucial molecules for promoting survival and growth of HTLV-1-transformed T cells, our findings demonstrate a novel mechanism of niclosamide in inducing Tax degradation and downregulating various cellular pro-survival molecules, thereby promoting apoptosis of HTLV-1-associated leukemia cells. - Highlights: • Niclosamide is a promising therapeutic candidate for adult T cell leukemia. • Niclosamide employs a novel mechanism through proteasomal degradation of Tax. • Niclosamide downregulates certain cellular pro-survival molecules.

Molecular cloning of human T-cell lymphotrophic virus type I-like proviral genome from the peripheral lymphocyte DNA of a patient with chronic neurologic disorders

International Nuclear Information System (INIS)

Reddy, E.P.; Mettus, R.V.; DeFreitas, E.; Wroblewska, Z.; Cisco, M.; Koprowski, H.

1988-01-01

Human T-cell lymphotropic virus type 1 (HTLV-I), the etiologic agent of human T-cell leukemia, has recently been shown to be associated with neurologic disorders such as tropical spastic paraparesis, HTLV-associated myelopathy, and possibly with multiple sclerosis. In this communication, the authors have examined one specific case of neurologic disorder that can be classified as multiple sclerosis or tropical spastic paraparesis. The patient suffering from chronic neurologic disorder was found to contain antibodies to HTLV-I envelope and gag proteins in his serum and cerebrospinal fluid. Lymphocytes from peripheral blood and cerebrospinal fluid of the patient were shown to express viral RNA sequences by in situ hybridization. Southern blot analysis of the patient lymphocyte DNA revealed the presence of HTLV-I-related sequences. Blot-hybridization analysis of the RNA from fresh peripheral lymphocytes stimulated with interleukin 2 revealed the presence of abundant amounts of genomic viral RNA with little or no subgenomic RNA. They have clones the proviral genome from the DNA of the peripheral lymphocytes and determined its restriction map. This analysis shows that this proviral genome is very similar if not identical to that of the prototype HTLV-I genome

Neurological manifestations in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis in the Amazon.

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Dias, G A S; Yoshikawa, G T; Koyama, R V L; Fujihara, S; Martins, L C S; Medeiros, R; Quaresma, J A S; Fuzii, H T

2016-02-01

A cross-sectional observational study was conducted. The aim was to analyze the clinical-functional profile of patients diagnosed with HTLV-1 (human T-lymphotropic virus type 1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in the Amazon region. Reference center for HTLV in the city of Belém, state of Pará, Brazil. Muscle strength, muscle tone, balance and the need for gait assistance among patients with HAM/TSP were evaluated. Among the 82 patients infected with HTLV-1, 27 (10 men and 17 women) were diagnosed with HAM/TSP. No statistically significant difference in muscle tone or strength was found between the lower limbs. Muscle weakness and spasticity were predominant in the proximal lower limbs. Patients with HAM/TSP are at a high risk of falls (P=0.03), and predominantly use either a cane or a crutch on one side as a gait-assistance device (P=0.02). Patients with HAM/TSP exhibit a similar clinical pattern of muscle weakness and spasticity, with a high risk of falls, requiring gait-assistance devices.

Roles of viral and cellular proteins in the expression of alternatively spliced HTLV-1 pX mRNAs

International Nuclear Information System (INIS)

Princler, Gerald L.; Julias, John G.; Hughes, Stephen H.; Derse, David

2003-01-01

The human T cell leukemia virus type 1 (HTLV-1) genome contains a cluster of at least five open reading frames (ORFs) near the 3' terminus within the pX region. The pX ORFs are encoded by mono- or bicistronic mRNAs that are generated by alternative splicing. The various pX mRNAs result from skipping of the internal exon (2-exon versus 3-exon isofoms) or from the utilization of alternative splice acceptor sites in the terminal exon. The Rex and Tax proteins, encoded by ORFs X-III and X-IV, have been studied intensively and are encoded by the most abundant of the alternative 3-exon mRNAs. The protein products of the other pX ORFs have not been detected in HTLV-1-infected cell lines and the levels of the corresponding mRNAs have not been accurately established. We have used real-time RT-PCR with splice-site specific primers to accurately measure the levels of individual pX mRNA species in chronically infected T cell lines. We have asked whether virus regulatory proteins or ectopic expression of cellular factors influence pX mRNA splicing in cells that were transfected with HTLV-1 provirus clones. In chronically infected cell lines, the pX-tax/rex mRNA was present at 500- to 2500-fold higher levels than the pX-tax-orfII mRNA and at approximately 1000-fold higher levels than pX-rex-orfI mRNA. Chronically infected cell lines that contain numerous defective proviruses expressed 2-exon forms of pX mRNAs at significantly higher levels compared to cell lines that contain a single full-length provirus. Cells transfected with provirus expression plasmids expressed similar relative amounts of 3-exon pX mRNAs but lower levels of 2-exon mRNA forms compared to cells containing a single, full-length provirus. The pX mRNA expression patterns were nearly identical in cells transfected with wild-type, Tax-minus, or Rex-minus proviruses. Cotransfection of cells with HTLV-1 provirus in combination with SF2/ASF expression plasmid resulted in a relative increase in pX-tax/rex m

Possible etiologies for tropical spastic paraparesis and human T lymphotropic virus I-associated myelopathy

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V. Zaninovic'

2004-01-01

Full Text Available The epidemiology of tropical spastic paraparesis/human T lymphotropic virus I (HTLV-I-associated myelopathy (TSP/HAM is frequently inconsistent and suggests environmental factors in the etiology of these syndromes. The neuropathology corresponds to a toxometabolic or autoimmune process and possibly not to a viral disease. Some logical hypotheses about the etiology and physiopathology of TSP and HAM are proposed. Glutamate-mediated excitotoxicity, central distal axonopathies, cassava, lathyrism and cycad toxicity may explain most cases of TSP. The damage caused to astrocytes and to the blood-brain barrier by HTLV-I plus xenobiotics may explain most cases of HAM. Analysis of the HTLV-I/xenobiotic ratio clarifies most of the paradoxical epidemiology of TSP and HAM. Modern neurotoxicology, neuroimmunology and molecular biology may explain the neuropathology of TSP and HAM. It is quite possible that there are other xenobiotics implicated in the etiology of some TSP/HAMs. The prevention of these syndromes appears to be possible today.

Peliculização de sementes de tomate associada ao paclobutrazol

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Aniela Pilar Campos de Melo

2014-06-01

Full Text Available O tratamento de sementes com paclobutrazol (PBZ deve ser aprimorado e tecnologias de recobrimento, como a peliculização, podem ser promissoras para aplicar uniformemente e fixar esse regulador no tegumento das sementes sem permitir um contato prejudicial ao embrião. Assim, determinaram-se os efeitos da peliculização de sementes com paclobutrazol no potencial fisiológico de sementes de tomate e as suas implicações no crescimento de mudas. Empregou-se o delineamento inteiramente casualizado, em esquema fatorial 2 x 4, sendo presença e ausência do polímero de revestimento Disco AG Red L-203® (0 e 150 mL kg-1 de semente e quatro concentrações de paclobutrazol - PBZ (0, 38,5, 76,9 e 115,4 mg L-1. A interação entre os fatores (peliculização x concentrações de paclobutrazol ocorreu somente para a variável condutividade elétrica. Independentemente da concentração, o paclobutrazol reduziu a germinação, emergência de plântulas, altura de parte aérea, área foliar e propiciou um aumento na detecção de clorofila. A peliculização não interfere na ação do paclobutrazol sobre as sementes. O paclobutrazol é eficiente no condicionamento da altura de mudas mas prejudica a germinação e o vigor de sementes.

Transactivation of the proenkephalin gene promoter by the Tax sub 1 protein of human T-cell lymphotropic virus type I

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Joshi, J.B. (National Heart, Lung, and Blood Inst., Bethesda, MD (United States)); Dave, H.P.G. (National Inst. of Health, Bethesda, MD (United States))

1992-02-01

Human T-cell lymphotropic virus type I (HTLV-I), an etiologic agent for adult T-cell leukemia, is strongly associated with certain neurological diseases. The HTLV-I genome encodes a protein, Tax{sub 1}, that transactivates viral gene transcription. CD4-positive T helper lymphocytes express the proenkephalin gene, and enkephalins have been implicated as neuroimmunomodulators. The authors have investigated the effect of Tax{sub 1} on the proenkephalin gene promoter in C6 rat glioma cells and demonstrated its transactivation. Analysis using 5{prime} deletion mutants of the promoter region showed that sequences upstream of base pair - 190 are necessary for maximal transactivation. Forskolin, a cAMP modulator, synergistically increased Tax{sub 1}-mediated transactivation of the proenkephalin promoter. Neither Tax{sub 1} transactivation alone nor Tax{sub 1}/cAMP synergism exclusively involved cAMP-responsive elements. Endogenous proenkephalin gene expression increased in Tax{sub 1}-expressing C6 cells. Since HTLV-I infects lymphocytes, which express proenkephalin mRNA, Tax{sub 1} transregulation of proenkephalin expression may provide bidirectional communication between the nervous and immune systems in HTLV-I-related diseases.

Cytokine profile and proviral load among Japanese immigrants and non-Japanese infected with HTLV-1 in a non-endemic area of Brazil.

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João Américo Domingos

Full Text Available The lifetime risk of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP development differs among ethnic groups. To better understand these differences, this prospective cohort study was conducted to investigate the cytokine profile and the HTLV-1 proviral load (PVL in Japanese and non-Japanese populations with HAM/TSP and asymptomatic carriers (ACs. The serum IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ levels were quantified using the Cytometric Bead Array in 40 HTLV-1-infected patients (11 HAM/TSP and 29 ACs and 18 healthy controls (HCs in Brazil. Among ACs, 15 were Japanese descendants and 14 were non-Japanese. Of 11 patients with HAM/TSP, only one was a Japanese descendant. The HTLV-1 PVL was quantified by real-time PCR. The HTLV-1 PVL was 2.7-fold higher in HAM/TSP patients than ACs. Regardless of the clinical outcome, the PVL was significantly higher in patients younger than 60 years than older patients. The HAM/TSP and ACs had higher IL-10 serum concentrations than that of HCs. The ACs also showed higher IL-6 serum levels than those of HCs. According to age, the IL-10 and IL-6 levels were higher in ACs non-Japanese patients older than 60 years. HAM/TSP patients showed a positive correlation between IL-6 and IL-17 and a negative correlation between the PVL and IL-17 and IFN-γ. In the all ACs, a significant positive correlation was observed between IL-2 and IL-17 and a negative correlation was detected between IL-10 and TNF-α. Only 6.25% of the Japanese patients were symptomatic carriers, compared with 41.67% of the non-Japanese patients. In conclusion, this study showed that high levels of HTLV-1 PVL was intrinsicaly associated with the development of HAM/TSP. A higher HTLV-1 PVL and IL10 levels found in non-Japanese ACs over 60 years old, which compared with the Japanese group depicts that the ethnic background may interfere in the host immune status. More researches also need to be undertaken regarding the host

Fatores associados à submissão ao teste rápido anti-HIV na assistência ao parto

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Maria Inês Couto de Oliveira

Full Text Available Resumo Os testes rápidos anti-HIV vêm sendo empregados nas maternidades com vistas à prevenção da transmissão vertical. O objetivo do estudo foi analisar os fatores associados à submissão ao teste rápido anti-HIV (desfecho. Estudo transversal, conduzido em 2009, em 15 hospitais do SUS do Rio de Janeiro/RJ, mediante entrevista a amostra representativa de 835 parturientes internadas e consulta a prontuários. Razões de prevalência ajustadas foram obtidas por regressão de Poisson, segundo modelo hierarquizado, permanecendo no modelo final as variáveis associadas ao desfecho (p ≤ 0,05. Segundo os prontuários (SP, 79,6% das mães foram submetidas ao teste rápido anti-HIV e, segundo as entrevistas (SE, 55,7%. No nível distal, a ausência de companheiro (SP, ter ≥ 6 moradores na residência (SP e a cor da pele não branca (SE se associaram a uma maior prevalência do desfecho. No nível intermediário, não dispor de sorologia negativa para o HIV do pré-natal (SP e SE se associou a uma maior prevalência do desfecho, bem como a realização de pré-natal na rede básica (SP e a não realização de pré-natal (SE. No nível proximal, o parto em hospital não certificado como amigo da criança se associou a uma maior prevalência do desfecho (SP e SE.

Globin haplotypes of human T-cell lymphotropic virus type I-infected individuals in Salvador, Bahia, Brazil, suggest a post-Columbian African origin of this virus.

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Alcantara, Luiz Carlos; Van Dooren, Sonia; Gonçalves, Marilda Souza; Kashima, Simone; Costa, Maria Cristina Ramos; Santos, Fred Luciano Neves; Bittencourt, Achilea Lisboa; Dourado, Inês; Filho, Antonio Andrade; Covas, Dimas Tadeu; Vandamme, Anne-Mieke; Galvão-Castro, Bernardo

2003-08-01

The city of Salvador, Bahia, Brazil, has sociodemographic characteristics similar to some African cities. Up to now, it has had the highest prevalence of human T-cell lymphotropic virus type I (HTLV-I) infection (1.74%) in the country. To investigate which strains of HTLV-I are circulating in Salvador, we studied isolates from 82 patients infected with HTLV-I: 19 from the general population, 21 from pregnant women, 16 from intravenous drug users, and 26 from patients and their family attending a neurologic clinic. Phylogenetic analysis from part of the LTR fragments showed that most of these isolates belonged to the Transcontinental subgroup of the Cosmopolitan subtype (HTLV-Ia). Only one sample from a pregnant woman was closely related to the Japanese subgroup, suggesting recent introduction of a Japanese HTLV-I lineage into Salvador. betaA-Globin haplotypes were examined in 34 infected individuals and found to be atypical, confirming the racial heterogeneity of this population. A total of 20 chromosomes were characterized as Central African Republic (CAR) haplotype (29.4%), 31 (45.6%) were characterized as Benin (BEN) haplotype, and 17 (25%) were characterized as Senegal (SEN) haplotype. Five patients' genotypes (14.7%) were CAR/CAR; 10 (29,4%), BEN/BEN; 9 (26.5%), CAR/BEN; 2 (5.9%), BEN/SEN; and 7 (20.6%), SEN/SEN. One patient's genotype (2.9%) was CAR/SEN. The betaA-globin haplotype distribution in Salvador is unusual compared with other Brazilian states. Our data support the hypothesis of multiple post-Columbian introductions of African HTLV-Ia strains in Salvador, Bahia, Brazil.

HTLV-1 Tax mediated downregulation of miRNAs associated with chromatin remodeling factors in T cells with stably integrated viral promoter.

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Saifur Rahman

Full Text Available RNA interference (RNAi is a natural cellular mechanism to silence gene expression and is predominantly mediated by microRNAs (miRNAs that target messenger RNA. Viruses can manipulate the cellular processes necessary for their replication by targeting the host RNAi machinery. This study explores the effect of human T-cell leukemia virus type 1 (HTLV-1 transactivating protein Tax on the RNAi pathway in the context of a chromosomally integrated viral long terminal repeat (LTR using a CD4(+ T-cell line, Jurkat. Transcription factor profiling of the HTLV-1 LTR stably integrated T-cell clone transfected with Tax demonstrates increased activation of substrates and factors associated with chromatin remodeling complexes. Using a miRNA microarray and bioinformatics experimental approach, Tax was also shown to downregulate the expression of miRNAs associated with the translational regulation of factors required for chromatin remodeling. These observations were validated with selected miRNAs and an HTLV-1 infected T cells line, MT-2. miR-149 and miR-873 were found to be capable of directly targeting p300 and p/CAF, chromatin remodeling factors known to play critical role in HTLV-1 pathogenesis. Overall, these results are first in line establishing HTLV-1/Tax-miRNA-chromatin concept and open new avenues toward understanding retroviral latency and/or replication in a given cell type.

Human T cell leukemia virus type I prevents cell surface expression of the T cell receptor through down-regulation of the CD3-gamma, -delta, -epsilon, and -zeta genes

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de Waal Malefyt, R.; Yssel, H.; Spits, H.; de Vries, J. E.; Sancho, J.; Terhorst, C.; Alarcon, B.

1990-01-01

Infection and transformation by human T cell leukemia virus type I (HTLV-I) up-regulates expression of several inducible genes including those coding for cytokines involved in the proliferation of normal and leukemic T cells. We demonstrate that HTLV-I can also shut off expression of the CD3-gamma,

Lidocaína com vasoconstrictor isolada e associada ao fentanil via peridural em cães Lidocaine with vasoconstrictor isolated and its combination with epidural fentanyl anesthesia in dogs

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Renata Navarro Cassu

2010-03-01

Full Text Available O objetivo deste estudo cego foi avaliar os efeitos cardiorrespiratórios e analgésicos de diferentes doses de fentanil associado à lidocaína com vasoconstrictor via peridural em cães. Foram avaliados 28 cães adultos, distribuídos em quatro tratamentos: 5mg kg-1 de lidocaína isolada (L e associada ao fentanil nas doses de 2,5, 5 e 7mg kg-1 (F2,5, F5 e F7, respectivamente. Quinze minutos antes da punção peridural, todos os animais foram tranquilizados por via intravenosa (IV com acepromazina (0,05mg kg-1, além de um bolus (IV de fentanil (2,5mg kg-1, administrado imediatamente antes da injeção peridural. Foram avaliados: frequência cardíaca (FC, eletrocardiograma (ECG, pressão arterial sistólica (PAS, frequência respiratória (f, gases sanguíneos, período de latência, duração e extensão do bloqueio sensitivo. Houve redução da FC após a anestesia peridural em relação ao basal em F2,5, F5 e F7. A FC foi superior no L em relação ao F5 e F7 aos 30 e 60 minutos após a anestesia peridural. O período de latência não variou entre os grupos, enquanto a duração do bloqueio foi superior no F5. Bloqueio sensitivo até a 6ª vértebra lombar foi observado em quatro animais no L. Bloqueio sensitivo até a 1ª vértebra lombar foi observado em cinco cães no F2,5 e F7 e em seis cães no F5. Conclui-se que a adição do fentanil à lidocaína determinou bloqueio sensitivo mais cranial em relação ao uso isolado desse anestésico local. Paralelamente, bloqueio anestésico mais duradouro foi determinado pela adição de 5mg kg-1 de fentanil à lidocaína em relação aos demais tratamentos.The objective of this blind study was to investigate the cardiopulmonary and analgesic effects of different doses of fentanyl combined with lidocaine by epidural route in dogs. Twenty-eight dogs were distributed in four treatments: 5mg kg-1 of lidocaine with vasoconstrictor alone (L and in combination with 2.5, 5 e 7mg kg-1 of fentanyl (F2

Human T-cell lymphotropic virus type 1 subtype C molecular variants among indigenous australians: new insights into the molecular epidemiology of HTLV-1 in Australo-Melanesia.

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Olivier Cassar

Full Text Available BACKGROUND: HTLV-1 infection is endemic among people of Melanesian descent in Papua New Guinea, the Solomon Islands and Vanuatu. Molecular studies reveal that these Melanesian strains belong to the highly divergent HTLV-1c subtype. In Australia, HTLV-1 is also endemic among the Indigenous people of central Australia; however, the molecular epidemiology of HTLV-1 infection in this population remains poorly documented. FINDINGS: Studying a series of 23 HTLV-1 strains from Indigenous residents of central Australia, we analyzed coding (gag, pol, env, tax and non-coding (LTR genomic proviral regions. Four complete HTLV-1 proviral sequences were also characterized. Phylogenetic analyses implemented with both Neighbor-Joining and Maximum Likelihood methods revealed that all proviral strains belong to the HTLV-1c subtype with a high genetic diversity, which varied with the geographic origin of the infected individuals. Two distinct Australians clades were found, the first including strains derived from most patients whose origins are in the North, and the second comprising a majority of those from the South of central Australia. Time divergence estimation suggests that the speciation of these two Australian clades probably occurred 9,120 years ago (38,000-4,500. CONCLUSIONS: The HTLV-1c subtype is endemic to central Australia where the Indigenous population is infected with diverse subtype c variants. At least two Australian clades exist, which cluster according to the geographic origin of the human hosts. These molecular variants are probably of very ancient origin. Further studies could provide new insights into the evolution and modes of dissemination of these retrovirus variants and the associated ancient migration events through which early human settlement of Australia and Melanesia was achieved.

The fragile x-associated tremor and ataxia syndrome (FXTAS A síndrome de tremor e ataxia associada ao X frágil (FXTAS

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Leonardo Pires Capelli

2010-10-01

Full Text Available FXTAS (Fragile X-associated tremor and ataxia syndrome is a late- onset neurodegenerative disorder affecting mainly men, over 50 years of age, who are carriers of the FMR1 gene premutation. The full mutation of this gene causes the fragile X syndrome (FXS, the most common cause of inherited mental retardation. Individuals affected by FXTAS generally present intention tremor and gait ataxia that might be associated to specific radiological and/or neuropathological signs. Other features commonly observed are parkinsonism, cognitive decline, peripheral neuropathy and autonomic dysfunction. Nearly a decade after its clinical characterization, FXTAS is poorly recognized in Brazil. Here we present a review of the current knowledge on the clinical, genetic and diagnostic aspects of the disease.A FXTAS (síndrome de tremor e ataxia associada ao X frágil é uma doença neurodegenerativa de início tardio que afeta principalmente homens acima dos 50 anos de idade, portadores de pré-mutação do gene FMR1. A mutação completa desse gene é responsável pela síndrome do cromossomo X frágil (SXF, a causa mais comum de deficiência mental herdada. Indivíduos afetados pela FXTAS geralmente apresentam tremor de intenção e ataxia de marcha que podem estar associados a sinais radiológicos ou neuropatológicos específicos. Outras características comumente observadas são parkinsonismo, declínio cognitivo, neuropatia periférica e disfunções autonômicas. Quase uma década após sua caracterização clínica, a FXTAS é mal conhecida por médicos no Brasil. Esta revisão apresenta o conhecimento atual sobre os aspectos clínicos, genéticos e diagnósticos da síndrome.

Compactação ruminal e obstrução intestinal em bovinos, associadas ao consumo de Agave sisalana Perrine (Agavaceae

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Eduardo M. Nascimento

Full Text Available Resumo: A compactação dos pré-estômagos é um transtorno digestivo resultante da ingestão de forragem de baixa qualidade, rico em lignina e com baixos níveis de energia e proteína digerível, associada ou não a restrição hídrica. O acúmulo de vegetais ricos em fibras indigeríveis pode levar também a formação de fitobezoares, causando transtornos digestivos e obstruções intestinais. Objetivou-se com este trabalho descrever os aspectos epidemiológicos e as alterações clínico-patológicas de um surto de alterações digestórias em bovinos alimentados com Agave sisalana. O rebanho acometido era formado por 22 animais adultos, criados de forma semiextensiva, que, devido a escassez de forragem, receberam no cocho, quase que exclusivamente, durante dois meses, o caule do A. sisalana cortado manualmente. Seis vacas apresentaram diminuição do apetite, distensão abdominal, redução dos períodos de ruminação e da produção de fezes. Um animal foi encaminhado ao Hospital Veterinário da Universidade Federal de Campina Grande. O diagnóstico presuntivo de compactação ruminal e obstrução intestinal foi dado pela epidemiologia, sinais clínicos e análise de fluido ruminal. Na necropsia observou-se rúmen, retículo e omaso repletos, com conteúdo fibroso e ressecado constituído por fibras de A. sisalana. No abomaso observou-se a presença de conteúdo pastoso e esverdeado a acastanhado. Em todos os pré-estômagos e no abomaso havia fitobezoares, que mediam entre 4 e 12 cm de diâmetro. No duodeno um fitobezoar obstruía parcialmente a luz do órgão, com a porção anterior repleta de conteúdo e a posterior vazia. Conclui-se que a alimentação com caules de A. sisalana por longos períodos causa compactação de pre-estômagos e formação de fitobezoares.

Epidemiological aspects of retrovirus (HTLV infection among Indian populations in the Amazon Region of Brazil

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Ricardo Ishak

Full Text Available HTLV was initially described in association with a form of leukemia in Japan and a neurological disease in the Caribbean. It was soon shown that HTLV-II was endemic among Amerindians and particularly among Brazilian Indians. The Amazon Region of Brazil is presently the largest endemic area for this virus and has allowed several studies concerning virus biology, the search for overt disease, epidemiological data including detailed demographic data on infected individuals, clear-cut geographic distribution, definition of modes of transmission and maintenance within small, epidemiologically-closed groups, and advances in laboratory diagnosis of the infection. A new molecular subtype named HTLV-IIc was further described on the basis of genome sequencing and phylogenetic analysis. This subtype is present in other areas of Brazil, indicating that the virus is additionally both a valuable marker for tracing past human migration routes in the Americas and a probable marker for social habits of the present human population. HIV, the other human retrovirus, is still not prevalent among indigenous communities in the Brazilian Amazon, but these groups are also easy targets for the virus.

Seroprevalencia del Virus Linfotrópico Humano de células T tipo 1 (HTLV-1 en pacientes con tiroiditis autoinmune.

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Ricardo Mori

2010-10-01

Full Text Available Objetivo: Describir la seroprevalencia de infección por HTLV-1 en pacientes con tiroiditis autoinmune. Material y Métodos: Estudio transversal realizado en pacientes con tiroiditis autoinmune que acudieron al consultorio de Endocrinología del Hospital Nacional Cayetano Heredia entre octubre del 2008 y enero del 2010. Se usó un cuestionario estructurado para obtener datos epidemiológicos y clínicos, paralelamente, se revisaron las historias clínicas para obtener datos de laboratorio. A los participantes se les tomó una muestra de sangre para el diagnóstico de HTLV-1 mediante prueba de ELISA y confirmación por Western Blot, previa firma de consentimiento informado. Resultados: Durante el período de estudio, se atendieron 285 pacientes con tiroiditis autoinmune. Se incluyeron 145 pacientes (50,9%; la edad media fue 48,1 ± 15 años y 135 (93,1% fueron de sexo femenino. Tres pacientes tuvieron infección por HTLV-1, con una prevalencia estimada de 2,1% (IC 95%: 0-4,4%. Los seropositivos fueron de sexo femenino y tuvieron el diagnóstico de Enfermedad de Graves hipertiroidea. La frecuencia de infección por HTLV-1 en este grupo fue de 5% (3/60; IC 95%: 0-11%. No se encontró diferencia significativa entre los pacientes HTLV-1 positivos y negativos en cuanto a características demográficas, clínicas y de laboratorio. Conclusión: La prevalencia de infección por HTLV-1 en los pacientes con tiroiditis autoinmune fue similar a la prevalencia estimada para la población peruana en general.(Rev Med Hered 2010;21:180-186.

Sensibilidade a cobre, estreptomicina e oxitetraciclina em Xanthomonas spp. associadas à mancha-bacteriana do tomate para processamento industrial

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Quezado-Duval Alice Maria

2003-01-01

Full Text Available Apesar de amplamente empregados em lavouras de tomate para processamento industrial no Brasil, fungicidas cúpricos e antibióticos registrados para uso agrícola nem sempre resultam em controle eficiente das bacterioses que afetam a cultura. O aparecimento de estirpes resistentes é uma das causas dessa baixa eficiência. Avaliou-se, in vitro, a sensibilidade a cobre, estreptomicina e oxitetraciclina de 389 isolados de Xanthomonas spp. associadas à mancha-bacteriana do tomateiro, sendo 92 de X. axonopodis pv. vesicatoria (60 do grupo "A"/raça T1 e 32 do "C"/raça T3, 93 de X. vesicatoria (grupo "B"/raça T2 e 204 de X. gardneri (grupo "D"/raça T2. Os isolados foram obtidos de plantas doentes em campos comerciais de tomate para processamento industrial nos estados de Goiás, Minas Gerais, Pernambuco e Bahia, nos anos de 1995 a 1998 e em 2000. Alíquotas de 5 ml de suspensões bacterianas foram depositadas em meio Nutriente-Ágar suplementado com sulfato de cobre, nas concentrações de 50 e 200 µg/ml; sulfato de estreptomicina, a 25 e 200 µg/ml e cloridrato de oxitetraciclina, a 25 µg/ml. Nenhum isolado foi resistente a oxitetraciclina, como também nenhum foi resistente ao cobre na concentração de 200 µg/ml do sulfato de cobre. No entanto, houve diferença entre isolados quanto à sensibilidade ao sulfato de cobre na concentração de 50 µg/ml e ao sulfato de estreptomicina nas duas concentrações empregadas. As freqüências de isolados de X. gardneri, X. axonopodis pv. vesicatoria (grupos "A" e "C" e X. vesicatoria resistentes à estreptomicina (25 µg/ml do produto usado foram, respectivamente, 98%, 38% e 2%, ao passo que, ao cobre, foram, respectivamente, 48%, 4% e 74%. Todos os isolados do grupo "C" foram sensíveis à estreptomicina e 97% sensíveis ao cobre.

HTLV-1 Tax protects against CD95-mediated apoptosis by induction of the cellular FLICE-inhibitory protein (c-FLIP).

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Krueger, Andreas; Fas, Stefanie C; Giaisi, Marco; Bleumink, Marc; Merling, Anette; Stumpf, Christine; Baumann, Sven; Holtkotte, Denise; Bosch, Valerie; Krammer, Peter H; Li-Weber, Min

2006-05-15

The HTLV-1 transactivator protein Tax is essential for malignant transformation of CD4 T cells, ultimately leading to adult T-cell leukemia/lymphoma (ATL). Malignant transformation may involve development of apoptosis resistance. In this study we investigated the molecular mechanisms by which HTLV-1 Tax confers resistance toward CD95-mediated apoptosis. We show that Tax-expressing T-cell lines derived from HTLV-1-infected patients express elevated levels of c-FLIP(L) and c-FLIP(S). The levels of c-FLIP correlated with resistance toward CD95-mediated apoptosis. Using an inducible system we demonstrated that both resistance toward CD95-mediated apoptosis and induction of c-FLIP are dependent on Tax. In addition, analysis of early cleavage of the BH3-only Bcl-2 family member Bid, a direct caspase-8 substrate, revealed that apoptosis is inhibited at a CD95 death receptor proximal level in Tax-expressing cells. Finally, using siRNA we directly showed that c-FLIP confers Tax-mediated resistance toward CD95-mediated apoptosis. In conclusion, our data suggest an important mechanism by which expression of HTLV-1 Tax may lead to immune escape of infected T cells and, thus, to persistent infection and transformation.

Radioimmunoassay and enzyme-linked immunoassay of antibodies to the core protein (P24) of human T-lymphotropic virus (HTLV III). [Acquired immunodeficiency syndrome (AIDS)

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Neurath, A R; Strick, N; Sproul, P

1985-05-01

Human T-cell lymphotropic viruses designated HTLV III or LAV are considered to represent the causative agents of the acquired immunodeficiency syndrome (AIDS). Therefore a simple direct RIA or ELISA method for antibodies to distinct epitopes of HTLV III/LAV structural components would be of great value. The authors describe RIA and ELISA assays which obviate the need for purified virus or virus proteins, do not utilize infected cells and thus do not diminish the source for continuous production of viral antigens and are specific for a major core protein of HTLV III/LAV.

O USO DA ELETROESTIMULAÇÃO MUSCULAR COM CORRENTE DE MÉDIA FREQUÊNCIA ASSOCIADA AO EXERCÍCIO RESISTIDO NO MÚSCULO GLÚTEO MÁXIMO: ESTUDO DE CASO

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Edilane Gonçalves MONÇÃO

2015-12-01

Full Text Available A partir do século XX as mulheres começaram a se preocupar mais com seu corpo, e procuram passar cada vez mais uma imagem de mulher feminina e atraente. A fisioterapia dermato – funcional é uma área dentro da fisioterapia que tem o objetivo de tratar das patologias estéticas, promovendo a essas mulheres um bem – estar e uma melhor qualidade de vida. A corrente russa associado a cinesioterapia, tem sido um recurso bastante utilizados para tratar a flacidez muscular e a hipotonia muscular, por produzir hipertrofia muscular e fortalecimento com resultados melhores e em pouco tempo. Este trabalho teve por objetivo analisar a efetividade da associação da corrente russa e do exercício resistido no musculo glúteo máximo. Caracterizado como sendo uma pesquisa experimental com uma voluntária com idade de 21 anos. A voluntária realizou 24 sessões por três vezes na semana em um período de dois meses, com duração média de quarenta minutos cada sessão. Foram analisadas a circunferência da região do quadril, e a qualidade da musculatura da região glútea, através do teste de pinçamento. Os resultados mostraram-se favoráveis ao uso da corrente russa associada a cinesioterapia na melhora da perimetria do quadril, causando um aumento de massa muscular e melhorando a flacidez muscular

Increased expression of OX40 is associated with progressive disease in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.

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Saito, Mineki; Tanaka, Reiko; Arishima, Shiho; Matsuzaki, Toshio; Ishihara, Satoshi; Tokashiki, Takashi; Ohya, Yusuke; Takashima, Hiroshi; Umehara, Fujio; Izumo, Shuji; Tanaka, Yuetsu

2013-05-07

OX40 is a member of the tumor necrosis factor receptor family that is expressed primarily on activated CD4+ T cells and promotes the development of effector and memory T cells. Although OX40 has been reported to be a target gene of human T-cell leukemia virus type-1 (HTLV-1) viral transactivator Tax and is overexpressed in vivo in adult T-cell leukemia (ATL) cells, an association between OX40 and HTLV-1-associated inflammatory disorders, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), has not yet been established. Moreover, because abrogation of OX40 signals ameliorates chronic inflammation in animal models of autoimmune disease, novel monoclonal antibodies against OX40 may offer a potential treatment for HTLV-1-associated diseases such as ATL and HAM/TSP. In this study, we showed that OX40 was specifically expressed in CD4+ T cells naturally infected with HTLV-1 that have the potential to produce pro-inflammatory cytokines along with Tax expression. We also showed that OX40 was overexpressed in spinal cord infiltrating mononuclear cells in a clinically progressive HAM/TSP patient with a short duration of illness. The levels of the soluble form of OX40 (sOX40) in the cerebrospinal fluid (CSF) from chronic progressive HAM/TSP patients or from patients with other inflammatory neurological diseases (OINDs) were not different. In contrast, sOX40 levels in the CSF of rapidly progressing HAM/TSP patients were higher than those in the CSF from patients with OINDs, and these patients showed higher sOX40 levels in the CSF than in the plasma. When our newly produced monoclonal antibody against OX40 was added to peripheral blood mononuclear cells in culture, HTLV-1-infected T cells were specifically removed by a mechanism that depends on antibody-dependent cellular cytotoxicity. Our study identified OX40 as a key molecule and biomarker for rapid progression of HAM/TSP. Furthermore, blocking OX40 may have potential in therapeutic intervention for

Imaging of human T-lymphotropic virus type I-associated chronic progressive myeloneuropathies

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Alcindor, F. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States)); Valderrama, R. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States)); Canavaggio, M. (Abbott Labs., North Chicago, IL (United States)); Lee, H. (Abbott Labs., North Chicago, IL (United States)); Katz, A. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States)); Montesinos, C. (Beth Israel Medical Center, Dept. of Neurology and Clinical Electrophysiology, New York, NY (United States)); Madrid, R.E. (New York State Office of Mental Retardation and Developmental Disabilities, Inst. for Basic Research in Developmental Disabilities, NY (United States)); Merino, R.R. (Beth Israel Medical Center, Dept. of Neurology and Clinical Electrophysiology, New York, NY (United States)); Pipia, P.A. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States))

1992-12-01

We studied magnetic resonance imaging (MRI) of the head and cervical spine and CT of the head in 46 patients (14 men, 32 women) with chronic progressive myeloneuropathy. The findings were correlated with human T-lymphotropic virus type I (HTLV-I) serology, race, country of origin, and age. We found a female predominance of 2:1. Most patients were aged between 30 and 50 years, and most were Caribbean immigrants and black. There were 9 men and 17 women with blood antibody titers to HTLV-I and 7 mem and 15 women with cerebrospinal fluid (CSF) titers. All patients with virus or antibodies in blood or CSF were Caribbean immigrants or black. T2-weighted cranial MRI showed scattered areas of high signal intensity in the cerebral white matter, usually in the periventricular and subcortical areas, but not in the posterior cranial fossa. Cranial CT revealed periventricular low density areas, ventricular enlargement, and atrophy MRI of the cervical spine showed atrophy of the cord. Myelography was normal in all 15 patients examined. No imaging differences were observed between the HTLV-I-positive and -negative patients. These findings, although consistent with demyelination, are not specific. (orig.)

Imaging of human T-lymphotropic virus type I-associated chronic progressive myeloneuropathies

International Nuclear Information System (INIS)

Alcindor, F.; Valderrama, R.; Canavaggio, M.; Lee, H.; Katz, A.; Montesinos, C.; Madrid, R.E.; Merino, R.R.; Pipia, P.A.

1992-01-01

We studied magnetic resonance imaging (MRI) of the head and cervical spine and CT of the head in 46 patients (14 men, 32 women) with chronic progressive myeloneuropathy. The findings were correlated with human T-lymphotropic virus type I (HTLV-I) serology, race, country of origin, and age. We found a female predominance of 2:1. Most patients were aged between 30 and 50 years, and most were Caribbean immigrants and black. There were 9 men and 17 women with blood antibody titers to HTLV-I and 7 mem and 15 women with cerebrospinal fluid (CSF) titers. All patients with virus or antibodies in blood or CSF were Caribbean immigrants or black. T2-weighted cranial MRI showed scattered areas of high signal intensity in the cerebral white matter, usually in the periventricular and subcortical areas, but not in the posterior cranial fossa. Cranial CT revealed periventricular low density areas, ventricular enlargement, and atrophy MRI of the cervical spine showed atrophy of the cord. Myelography was normal in all 15 patients examined. No imaging differences were observed between the HTLV-I-positive and -negative patients. These findings, although consistent with demyelination, are not specific. (orig.)

Resultados positivos do lavado broncoalveolar e das culturas quantitativas na suspeita da pneumonia tardia associada ao ventilador – estudo retrospectivo

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A.P. Vaz

2011-05-01

Full Text Available Resumo: Introdução: O lavado broncoalveolar (LBA com culturas quantitativas tem sido utilizado no sentido de permitir um aumento da especificidade diagnóstica da pneumonia associada ao ventilador (PAV, embora a técnica padrão para o diagnóstico definitivo desta entidade permaneça controversa. Objectivos: Avaliar a influência dos resultados positivos do LBA e das culturas quantitativas no diagnóstico microbiológico e no tratamento de doentes com suspeita de PAV tardia e antibioterapia prévia. Material e Métodos: Análise retrospectiva de doentes em unidade de cuidados intensivos (UCI polivalentes, com suspeita de PAV tardia e antibioterapia prévia, que apresentaram crescimento cultural nos LBA efectuados durante o período de um ano. Resultados: Dos 243 LBA realizados, obtiveram-se 71 (29,2% resultados positivos (60 doentes, 76,7% do sexo masculino, 54 ± 19 anos. O LBA foi realizado em mediana após 13 dias de ventilação invasiva, 11 dias de antibioterapia na UCI e no dia em que se instituiu um novo antibiótico perante a suspeita de PAV. Foi efectuada contagem de unidades formadoras de colónias (UFC/ml em 71,8% e simultaneamente obtido aspirado endotraqueal (AET para análise qualitativa em 85,9%. Verificou-se mudança terapêutica em 38,0%: correcção terapêutica (16,9%, descalação (12,7% e início de antibioterapia dirigida (8,4%. As alterações terapêuticas foram efectuadas na presença de >104 UFC em 84,2% e em concordância com o AET em 70,8%. Nos casos em que se verificou manutenção da antibioterapia (62,0% as culturas quantitativas teriam permitido descalação em 9,1%. A alteração na prescrição foi mais frequente na presença de >104 UFC (48,5%, do que nas situações em que as contagens de UFC foram inferiores ou a análise do LBA qualitativa (28,9%, p = 0,091. Não se verificaram diferen

HTLV-3/4 and simian foamy retroviruses in humans: discovery, epidemiology, cross-species transmission and molecular virology.

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Gessain, Antoine; Rua, Réjane; Betsem, Edouard; Turpin, Jocelyn; Mahieux, Renaud

2013-01-05

Non-human primates are considered to be likely sources of viruses that can infect humans and thus pose a significant threat to human population. This is well illustrated by some retroviruses, as the simian immunodeficiency viruses and the simian T lymphotropic viruses, which have the ability to cross-species, adapt to a new host and sometimes spread. This leads to a pandemic situation for HIV-1 or an endemic one for HTLV-1. Here, we present the available data on the discovery, epidemiology, cross-species transmission and molecular virology of the recently discovered HTLV-3 and HTLV-4 deltaretroviruses, as well as the simian foamy retroviruses present in different human populations at risk, especially in central African hunters. We discuss also the natural history in humans of these retroviruses of zoonotic origin (magnitude and geographical distribution, possible inter-human transmission). In Central Africa, the increase of the bushmeat trade during the last decades has opened new possibilities for retroviral emergence in humans, especially in immuno-compromised persons. Copyright © 2012 Elsevier Inc. All rights reserved.

CT Chest and pulmonary functional changes in patients with HTLV-associated myelopathy in the Eastern Brazilian Amazon.

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Luiz Fábio Magno Falcão

Full Text Available The aim of this study was to compare computed tomography (CT scans of chest and lung function among patients with Human T-Lymphotropic Virus Type 1 (HTLV with and without HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP. In this cross-sectional study performed between January 2013 and June 2016, we included 48 patients with HAM/TSP (19 women and 11 men and without HAM/TSP (12 women and 6 men. We compared CT findings and lung functions of these groups. Patients who had HAM/TSP had abnormal CT findings (P = 0.000, including more frequent bronchiectasis (P = 0.049, parenchymal bands (P = 0.007, interlobular septal thickening (P = 0.035, and pleural thickening (P = 0.009. In addition, neither patients with HAM/TSP (9/30; 30% nor the controls (0/18; 0% had obstructive or restrictive lung disease (P = 0.009. HTLV diagnosis should be considered in all patients with abnormal CT findings in whom no other cause is apparent. It is important to remember that lung disease increases the rates of morbidity and mortality in developing countries.

Robo-AO Kepler Asteroseismic Survey. I. Adaptive Optics Imaging of 99 Asteroseismic Kepler Dwarfs and Subgiants

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Schonhut-Stasik, Jessica S.; Baranec, Christoph; Huber, Daniel; Atkinson, Dani; Hagelberg, Janis; Marel, Nienke van der; Hodapp, Klaus W. [Institute for Astronomy, University of Hawai‘i at Mānoa, Hilo, HI 96720-2700 (United States); Ziegler, Carl; Law, Nicholas M. [Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3255 (United States); Gaidos, Eric [Department of Geology and Geophysics, University of Hawai‘i at Mānoa, Honolulu, HI 96822 (United States); Riddle, Reed, E-mail: jstasik@hawaii.edu [Division of Physics, Mathematics, and Astronomy, California Institute of Technology, Pasadena, CA 91125 (United States)

2017-10-01

We used the Robo-AO laser adaptive optics (AOs) system to image 99 main sequence and subgiant stars that have Kepler -detected asteroseismic signals. Robo-AO allows us to resolve blended secondary sources at separations as close as ∼0.″15 that may contribute to the measured Kepler light curves and affect asteroseismic analysis and interpretation. We report eight new secondary sources within 4.″0 of these Kepler asteroseismic stars. We used Subaru and Keck AOs to measure differential infrared photometry for these candidate companion systems. Two of the secondary sources are likely foreground objects, while the remaining six are background sources; however, we cannot exclude the possibility that three of the objects may be physically associated. We measured a range of i ′-band amplitude dilutions for the candidate companion systems from 0.43% to 15.4%. We find that the measured amplitude dilutions are insufficient to explain the previously identified excess scatter in the relationship between asteroseismic oscillation amplitude and the frequency of maximum power.

Tax Protein-induced Expression of Antiapoptotic Bfl-1 Protein Contributes to Survival of Human T-cell Leukemia Virus Type 1 (HTLV-1)-infected T-cells*♦

Science.gov (United States)

Macaire, Héloïse; Riquet, Aurélien; Moncollin, Vincent; Biémont-Trescol, Marie-Claude; Duc Dodon, Madeleine; Hermine, Olivier; Debaud, Anne-Laure; Mahieux, Renaud; Mesnard, Jean-Michel; Pierre, Marlène; Gazzolo, Louis; Bonnefoy, Nathalie; Valentin, Hélène

2012-01-01

Human T lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL). ATLL is a severe malignancy with no effective treatment. HTLV-1 regulatory proteins Tax and HTLV-1 basic leucine zipper factor (HBZ) play a major role in ATLL development, by interfering with cellular functions such as CD4+ T-cell survival. In this study, we observed that the expression of Bfl-1, an antiapoptotic protein of the Bcl-2 family, is restricted to HTLV-1-infected T-cell lines and to T-cells expressing both Tax and HBZ proteins. We showed that Tax-induced bfl-1 transcription through the canonical NF-κB pathway. Moreover, we demonstrated that Tax cooperated with c-Jun or JunD, but not JunB, transcription factors of the AP-1 family to stimulate bfl-1 gene activation. By contrast, HBZ inhibited c-Jun-induced bfl-1 gene activation, whereas it increased JunD-induced bfl-1 gene activation. We identified one NF-κB, targeted by RelA, c-Rel, RelB, p105/p50, and p100/p52, and two AP-1, targeted by both c-Jun and JunD, binding sites in the bfl-1 promoter of T-cells expressing both Tax and HBZ. Analyzing the potential role of antiapoptotic Bcl-2 proteins in HTLV-1-infected T-cell survival, we demonstrated that these cells are differentially sensitive to silencing of Bfl-1, Bcl-xL, and Bcl-2. Indeed, both Bfl-1 and Bcl-xL knockdowns decreased the survival of HTLV-1-infected T-cell lines, although no cell death was observed after Bcl-2 knockdown. Furthermore, we demonstrated that Bfl-1 knockdown sensitizes HTLV-1-infected T-cells to ABT-737 or etoposide treatment. Our results directly implicate Bfl-1 and Bcl-xL in HTLV-1-infected T-cell survival and suggest that both Bfl-1 and Bcl-xL represent potential therapeutic targets for ATLL treatment. PMID:22553204

Origin of HTLV-1 in hunters of nonhuman primates in Central Africa.

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Kazanji, Mirdad; Mouinga-Ondémé, Augustin; Lekana-Douki-Etenna, Sonia; Caron, Mélanie; Makuwa, Maria; Mahieux, Renaud; Gessain, Antoine

2015-02-01

Of 78 Gabonese individuals who had received bites from nonhuman primates (NHPs) while hunting, 7 were infected with human T lymphotropic virus (HTLV-1). Five had been bitten by gorillas and were infected with subtype B strains; however, a 12-year-old girl who was severely bitten by a Cercopithecus nictitans was infected with a subtype D strain that was closely related to the simian T lymphotropic virus (STLV-1) that infects this monkey species. Her mother was infected with a subtype B strain. These data confirm that hunters in Africa can be infected by HTLV-1 that is closely related to the strains circulating among local NHP game. Our findings strongly suggest that a severe bite represent a risk factor for STLV-1 acquisition. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Housing conditions as a social determinant of low birthweight and preterm low birthweight Condiciones de vivienda como determinante social de bajo peso al nacer y de prematuro de bajo peso al nacer Condições de moradia como determinante social de baixo peso ao nascer e prematuro de baixo peso

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Mario Vianna Vettore

2010-12-01

, historia obstétrica y cuidados prenatales. RESULTADOS: Condiciones de vivienda inadecuadas fueron independientemente asociadas con bajo peso al nacer (Inadecuadas - OR= 2,3 (1,1;4,6 y muy inadecuadas - OR=7,6 (2,1;27,6 y con prematuridad asociada al bajo peso al nacer (inadecuadas - OR=2,2 (1,1;4,3 y muy inadecuadas - OR=7,6 (2,4;23,9. Factores asociados con los resultados incluyeron cuidados prenatales inadecuados y prematuridad previa. Baja renta y bajo índice de masa corporal materno fueron asociados con bajo peso al nacer. CONCLUSIONES: Condiciones de vivienda inadecuadas fueron asociadas con bajo peso al nacer y prematuridad asociada al bajo peso al nacer.OBJETIVO: Avaliar a relação entre condições de moradia e baixo peso ao nascer e prematuridade associada ao baixo peso ao nascer nos filhos de mulheres de baixa renda. MÉTODOS: Foi realizado estudo caso-controle com mulheres no pós-parto residentes no município do Rio de Janeiro, RJ, em 2003-2005. Dois grupos de casos foram comparados com controles a termo e com peso normal (n = 393: baixo peso ao nascer (n = 96 e prematuridade associada ao baixo peso ao nascer (n = 68. As condições de moradia foram consideradas nos níveis: adequadas, inadequadas e muito inadequadas. As covariáveis investigadas foram características sociodemográficas, antropométricas, hábitos de risco, violência, ansiedade, satisfação com a gravidez, história obstétrica e cuidados pré-natais. RESULTADOS: Condições de moradia inadequadas foram independentemente associadas com baixo peso ao nascer (Inadequadas - OR = 2,3 (1,1;4,6 e muito inadequadas - OR = 7,6 (2,1;27,6 e com prematuridade associada ao baixo peso ao nascer (inadequadas - OR = 2,2 (1,1;4,3 e muito inadequadas - OR = 7,6 (2,4;23,9. Fatores associados com os desfechos incluíram cuidados pré-natais inadequados e prematuridade prévia. Baixa renda e baixo índice de massa corporal materno foram associados com baixo peso ao nascer. CONCLUSÕES: Condições de

The nuclear import of the human T lymphotropic virus type I (HTLV-1) tax protein is carrier- and energy-independent.

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Tsuji, Takahiro; Sheehy, Noreen; Gautier, Virginie W; Hayakawa, Hitoshi; Sawa, Hirofumi; Hall, William W

2007-05-04

HTLV-1 is the etiologic agent of the adult T cell leukemialymphoma (ATLL). The viral regulatory protein Tax plays a central role in leukemogenesis as a transcriptional transactivator of both viral and cellular gene expression, and this requires Tax activity in both the cytoplasm and the nucleus. In the present study, we have investigated the mechanisms involved in the nuclear localization of Tax. Employing a GFP fusion expression system and a range of Tax mutants, we could confirm that the N-terminal 60 amino acids, and specifically residues within the zinc finger motif in this region, are important for nuclear localization. Using an in vitro nuclear import assay, it could be demonstrated that the transportation of Tax to the nucleus required neither energy nor carrier proteins. Specific and direct binding between Tax and p62, a nucleoporin with which the importin beta family of proteins have been known to interact was also observed. The nuclear import activity of wild type Tax and its mutants and their binding affinity for p62 were also clearly correlated, suggesting that the entry of Tax into the nucleus involves a direct interaction with nucleoporins within the nuclear pore complex (NPC). The nuclear export of Tax was also shown to be carrier independent. It could be also demonstrated that Tax it self may have a carrier function and that the NF-kappaB subunit p65 could be imported into the nucleus by Tax. These studies suggest that Tax could alter the nucleocytoplasmic distribution of cellular proteins, and this could contribute to the deregulation of cellular processes observed in HTLV-1 infection.

Análise de custos entre a raquianestesia e a anestesia venosa com propofol associada ao bloqueio perianal local em operações anorretais Cost analysis between spinal and venous anesthesia with propofol associated with local perianal block in anorectal procedures

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Paulo Gustavo Kotze

2009-09-01

Full Text Available RACIONAL: Atualmente cerca de 90% das operações anorretais podem ser realizadas em regime ambulatorial. A técnica anestésica é fator fundamental na busca de menor tempo de internamento e redução de custos nestes procedimentos. Não há consenso na literatura sobre qual o melhor tipo de anestesia para essas operações. OBJETIVO: Comparar os custos da técnica de raquianestesia com bupivacaína 0,5% isobárica com a técnica de anestesia venosa com propofol associada ao bloqueio perianal local com lidocaína a 2% e bupivacaína 0,5% (anestesia combinada em pacientes submetidos a operações anorretais. MÉTODOS: Foram analisados dados de 99 pacientes submetidos à operações anorretais, divididos em dois grupos: grupo I (raquianestesia, composto por 50 pacientes e grupo II (anestesia combinada, composto por 49 pacientes. Foram estudados os procedimentos cirúrgicos, tempo de procedimento anestésico-cirúrgico, tempo de internamento e custos globais de cada paciente. RESULTADOS: Não houve diferença estatística significativa entre os grupos estudados em relação ao tipo de procedimento cirúrgico, sexo, idade e complicações. O tempo médio do procedimento anestésico-cirúrgico, no grupo I foi de 53,1 minutos e de 44,08 minutos no grupo II (P=0,034. O tempo médio de internamento foi de 19,68 horas no grupo I e de 7,08 horas no grupo II (PBACKGROUND: Approximately ninety percent of anorectal surgical procedures are performed in ambulatory basis. The choice of a proper anesthetic technique is important to achieve shorter hospital stay and low costs. There's no evidence in the literature that an ideal type of anesthesia for these procedures exists. AIM: To compare the costs of patients operated with spinal anesthesia (0,5% bupivacaine with combined anesthesia (propofol and local perineal block with 2% lidocaine and 0,5% bupivacaine in anorectal surgical procedures. METHODS: Data from 99 patients submitted to anorectal operations were

Alterações moleculares associadas à hemocromatose hereditária Molecular changes associated with hereditary hemochromatosis

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Paulo C. J. L. Santos

2009-01-01

Full Text Available A hemocromatose hereditária (HH é a mais comum doença autossômica em caucasianos e caracteriza-se pelo aumento da absorção intestinal de ferro, o qual resulta em acúmulo progressivo de ferro no organismo. A classificação da HH é realizada de acordo com a alteração genética encontrada, sendo os casos divididos em tipos 1, 2A, 2B, 3 e 4, quando a sobrecarga de ferro for associada aos genes HFE, HJV, HAMP, TFR2 e SLC40A1, respectivamente. Não existem estudos brasileiros que avaliaram a presença de mutações em genes relacionados à fisiopatologia da HH (genes HJV, HAMP, TFR2 e SLC40A1, além da pesquisa das três mutações no gene HFE (C282Y, H63D e S65C. Porém, está descrito, nos estudos realizados no Brasil, que alguns pacientes com sobrecarga de ferro primária não são portadores da HH tipo 1 (associada ao gene HFE. Portanto, é de suma importância a identificação das características genéticas dessa população, uma vez que outras mutações nos genes HJV, HAMP, TFR2 e SLC40A1 podem estar associadas à fisiopatologia da doença, podendo haver interações entre os genes alterados, de forma que possa auxiliar no entendimento da fisiopatologia da HH em pacientes brasileiros.Hereditary Hemochromatosis (HH is the most common autosomal disease in Caucasians. It is characterized by an increase in intestinal absorption of iron, which results in a progressive accumulation of iron in the body. The classification of HH is carried out according to the genetic alteration found; thus cases of HH are divided into Types 1, 2A, 2B, 3 and 4, when the iron overload is associated to the HFE, HJV, HAMP, TFR2 and SLC40A1 genes, respectively. There is research on the three HFE gene mutations (C282Y, H63D and S65C in the Brazilian population however there are no Brazilian studies that evaluate the presence of mutations in other genes related to the pathophysiology of HH (HJV, HAMP, TFR2 and SLC40A1 genes. Nevertheless, studies conducted in

Lack of evidence to support the association of a single IL28B genotype SNP rs12979860 with the HTLV-1 clinical outcomes and proviral load

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Sanabani Sabri Saeed

2012-12-01

Full Text Available Abstract Background The Interleukin 28B (IL28B rs12979860 polymorphisms was recently reported to be associated with the human T-cell leukemia virus type 1 (HTLV-1 proviral load (PvL and the development of the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. Methods In an attempt to examine this hypothesis, we assessed the association of the rs12979860 genotypes with HTLV-1 PvL levels and clinical status in 112 unrelated Brazilian subjects (81 HTLV-1 asymptomatic carriers, 24 individuals with HAM/TSP and 7 with Adult T cell Leukemia/Lymphoma (ATLL. Results All 112 samples were successfully genotyped and their PvLs compared. Neither the homozygote TT nor the heterozygote CT mutations nor the combination genotypes (TT/CT were associated with a greater PvL. We also observed no significant difference in allele distribution between asymptomatic carriers and patients with HTLV-1 associated HAM/TSP. Conclusions Our study failed to support the previously reported positive association between the IL28B rs12979860 polymorphisms and an increased risk of developing HAM/TSP in the Brazilian population.

Oral lesions associated with renal secondary hyperparathyroidism in an English bulldog/ Lesões orais associadas ao hiperparatireoidismo renal secundário em um Buldogue Inglês

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Antônio Carlos Faria dos Reis

2008-08-01

Full Text Available Renal secondary hyperparathyroidism is a complex clinical syndrome frequently described in dogs. However, in most cases, lesions are characterized by fibrous osteodystrophy of facial bones, affecting principally the mandible and the maxilla. There are few reports of renal secondary hyperparathyroidism associated with facial tumorous masses in the dog; similar findings in dogs have not been previously described in Brazil. This report describes the clinical, pathological, and radiological findings of this syndrome in a 14-month-old dog with oral tumorous-like lesions. The pathogenesis associated with this disease is also discussed.Hiperparatireoidismo renal secundário é uma síndrome clínica complexa freqüentemente descrita em cães. Entretanto, na maioria dos casos as lesões são caracterizadas por osteodistrofia fibrosa dos ossos faciais, afetando principalmente a mandíbula e a maxila. Existem poucos relatos do hiperparatireoidismo renal secundário associada a massas tumorais na face de cães; achados semelhantes em cães não foram anteriormente descritos no Brasil. Este relato descreve os achados clínicos, patológicos e radiológicos dessa síndrome em um cão de 14 meses de idade com lesões semelhantes a tumores na cavidade bucal. A patogenia associada a essa doença também é discutida.

Hepatotoxicity associated with microcystin/ Hepatotoxicidade associada à microcistina

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Ana Paula Frederico Rodrigues Loureiro Bracarense

2008-08-01

.Efluentes industriais e urbanos e a intensa exploração agrícola e de pescado têm levado à eutrofização de muitos mananciais de água, destinados ao consumo e às atividades recreacionais. A eutrofização das águas, freqüentemente, tem como conseqüência o desenvolvimento expressivo de cianobactérias. Estas florações induzem a sérios problemas, visto que a ocorrência de Microcystis aeruginosa, uma das cianobactérias mais difundidas, pode produzir microcistinas (MCs. O efeito citotóxico da MC tem sido descrito no fígado, pulmões, estômago e intestino. Mortes de seres humanos, de animais silvestres e domésticos têm sido associadas à exposição a MC. Esta pode ocorrer diretamente por ingestão, inalação, contato, inoculação intravenosa (hemodiálise ou indiretamente, pelo consumo de animais, dentre os quais os peixes e moluscos, que podem ingerir as cianobactérias e suas toxinas. A mais tóxica e também mais comum das MCs é a microcistina-LR (MC-LR, cujo órgão alvo é o fígado. A MC chega ao fígado especificamente por transporte dos ácidos biliares e, uma vez no citoplasma, inibe as proteínas fosfatases 1 e 2A, induzindo ao aumento da fosforilação protéica. Esta reação tem duas conseqüências: destruição do citoesqueleto, causando efeitos citotóxicos e descontrole da divisão celular, levando à promoção tumoral. A exposição aguda à MC induz severa hemorragia intra-hepática, necrose e apoptose, enquanto a exposição crônica pode causar neoplasia hepática ou intestinal. Também tem sido relatado que a hepatotoxicidade da MC está intimamente associada à formação intracelular de espécies reativas de oxigênio. A MC pode ser naturalmente degradada por bactérias ou pela radiação solar. Contudo, se não houver eficiente degradação, a MC poderá persistir na cadeia alimentar aquática. A contaminação de águas pela MC representa, portanto, perigo à saúde humana e de animais. Assim, esforços para evitar a eutrofização de

E-Learning associado ao turismo: caso de estudo numa unidade curricular de uma licenciatura do ensino superior

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Pedro M.G.L. Cascada

2014-07-01

Full Text Available O ensino à distância está cada vez mais presente nas instituições de ensino, em todos os níveis, através da utilização cada vez mais frequente das capacidades disponibilizadas pelas novas tecnologias de informação e comunicação. Neste âmbito, o e-Learning assume um papel cada vez mais importante para a disseminação do ensino à distância, sendo cada vez mais utilizado nos diversos níveis de ensino, com destaque para o ensino superior. Neste trabalho pretende-se caracterizar o ensino à distância, dando uma especial atenção ao e-Learning, às suas características, funcionalidades e formas de utilização que lhe estão associadas, bem como um enquadramento do momento atual de utilização do e-Learning. O caso de estudo foi aplicado a através de um questionário (online aplicado a estudantes de uma unidade curricular (UC do ensino superior português. Com os resultados obtidos no estudo obteve-se uma clara opinião por parte dos inquiridos sobre a importância das funcionalidades e pedagogias associadas ao e-Learning, e se devem ser mais utilizadas e desenvolvidas no futuro. Por outro lado, verificou-se que uma maior frequência de utilização deste tipo de ferramentas pode corresponder a um melhor desempenho dos estudantes.

USO DE PRÓPOLIS ASSOCIADA A OUTROS COMPONENTES NO TRATAMENTO DE FERIDAS ONCOLÓGICAS APÓS EXCISÃO

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José Sales Pereira Filho

2015-12-01

Full Text Available A própolis é utilizada terapeuticamente pelas suas propriedades anti-inflamatória, cicatrizante e anti-séptica, sendo tal uso regulamentado em se tratando de aplicação tópica. O objetivo deste estudo foi relatar o tempo médio de cicatrização de feridas oncológicas após excisão tratadas com a aplicação de uma formulação contendo própolis, mel, açúcar, manteiga e albumina em pó e disponibilizar ao meio científico uma alternativa eficaz nestes procedimentos. Foram avaliados os tempos de cicatrização de cinco pacientes com mais de 60 anos, de ambos os sexos, atendidos regularmente pelo médico responsável, Cirurgião Cutâneo, na Santa Casa de Misericórdia (Pavilhão São Miguel, Rio de Janeiro, RJ. Também foram relatadas suas experiências clínicas com a formulação há mais de 20 anos. O tempo de cicatrização médio foi equivalente a 39 dias e a região anatômica na qual foi observada maior prevalência de lesões associadas ao câncer de pele foi a cabeça. A formulação pode ser aplicada uma única vez ao dia, o que permite uma melhor adesão ao tratamento, tanto do paciente quanto de seus familiares.  Não foram observados efeitos colaterais que pudessem contraindicar o uso da formulação na totalidade dos casos e seu custo é baixo em comparação a outros métodos e produtos utilizados no tratamento.

Development of Graves' ophthalmopathy and uveitis after radioiodine therapy for Graves' disease in a patient with HTLA-I associated myelopathy (HAM)

International Nuclear Information System (INIS)

Ozawa, Yasunori; Migita, Masayoshi; Watanabe, Tomoji; Okuda, Itsuko; Takeshita, Akira; Takagi, Akio; Shishiba, Yoshimasa

1994-01-01

HTLV-I carriers or patients with HTLV-I associated myelopathy (HAM) are prone to immune-mediated inflammatory disorders. We present a 44-year-old female with HAM who developed Graves' disease. She developed severe Graves' ophthalmopathy shortly after 131 I therapy, concurrently with a remarkable increase in TSH-receptor antibody titer. Ophthalmopathy was aggravated in spite of prednisolone therapy and euthyroidism being maintained by thyroxine replacement. Uveitis also developed after 131 I therapy and iridocyclitis finally required trabeculotomy. This case suggests that HAM patients may have a higher risk of immune-mediated Graves' ophthalmopathy after 131 I therapy.(author)

Instrumento mensurador de adesao para hipertensos: contribuicao da Teoria da Resposta ao Item

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Malvina Thais Pacheco Rodrigues

2013-06-01

Full Text Available OBJETIVO: Analisar instrumento de medição da adesão ao tratamento da hipertensão por meio da "Teoria da Resposta ao Item". MÉTODOS: Estudo analítico com 406 hipertensos com complicações associadas, atendidos na atenção básica em Fortaleza, CE, 2011, pela "Teoria da Resposta ao Item". As etapas de execução foram: teste de dimensionalidade, calibração dos itens; tratamento dos dados e construção da escala, analisadas com base no modelo de resposta gradual. Estudo da dimensionalidade do instrumento foi feito pela análise da matriz de correlação policórica e análise fatorial de informação completa. Utilizou-se o software Multilog para calibração dos itens e estimação dos escores. RESULTADOS: Os itens referentes ao tratamento medicamentoso foram os mais diretamente relacionados à adesão, enquanto aqueles referentes ao tratamento não medicamentoso precisam ser reformulados, pois possuíram menor quantidade de informação psicométrica e baixa discriminação. A independência dos itens, o reduzido número de níveis da escala e as baixas variâncias explicadas no ajuste dos modelos mostraram as principais fragilidades do instrumento analisado. A "Teoria da Resposta ao Item" mostrou-se relevante para análise, pois avaliou o respondente quanto à adesão ao tratamento da hipertensão, ao nível de dificuldade dos itens e à sua capacidade de discriminação entre indivíduos com diferentes níveis de adesão, o que gerou maior quantidade de informação. CONCLUSÕES: O instrumento analisado é limitado para medir a adesão ao tratamento da hipertensão, mediante análise pela "Teoria da Resposta ao Item", e necessita de ajustes. A adequada formulação dos itens é importante para medir precisamente o traço latente desejado.

WRN-targeted therapy using inhibitors NSC 19630 and NSC 617145 induce apoptosis in HTLV-1-transformed adult T-cell leukemia cells

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R. Moles

2016-11-01

Full Text Available Abstract Background Human T-cell leukemia virus type 1 (HTLV-1 infection is associated with adult T-cell leukemia/lymphoma (ATLL, a lymphoproliferative malignancy with a dismal prognosis and limited therapeutic options. Recent evidence shows that HTLV-1-transformed cells present defects in both DNA replication and DNA repair, suggesting that these cells might be particularly sensitive to treatment with a small helicase inhibitor. Because the “Werner syndrome ATP-dependent helicase” encoded by the WRN gene plays important roles in both cellular proliferation and DNA repair, we hypothesized that inhibition of WRN activity could be used as a new strategy to target ATLL cells. Methods Our analysis demonstrates an apoptotic effect induced by the WRN helicase inhibitor in HTLV-1-transformed cells in vitro and ATL-derived cell lines. Inhibition of cellular proliferation and induction of apoptosis were demonstrated with cell cycle analysis, XTT proliferation assay, clonogenic assay, annexin V staining, and measurement of mitochondrial transmembrane potential. Results Targeted inhibition of the WRN helicase induced cell cycle arrest and apoptosis in HTLV-1-transformed leukemia cells. Treatment with NSC 19630 (WRN inhibitor induces S-phase cell cycle arrest, disruption of the mitochondrial membrane potential, and decreased expression of anti-apoptotic factor Bcl-2. These events were associated with activation of caspase-3-dependent apoptosis in ATL cells. We identified some ATL cells, ATL-55T and LMY1, less sensitive to NSC 19630 but sensitive to another WRN inhibitor, NSC 617145. Conclusions WRN is essential for survival of ATL cells. Our studies suggest that targeting the WRN helicase with small inhibitors is a novel promising strategy to target HTLV-1-transformed ATL cells.

Protein domains involved in both in vivo and in vitro interactions between human T-cell leukemia virus type I tax and CREB.

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Yin, M J; Paulssen, E J; Seeler, J S; Gaynor, R B

1995-06-01

Gene expression from the human T-cell leukemia virus type I (HTLV-I) long terminal repeat (LTR) is mediated by three cis-acting regulatory elements known as 21-bp repeats and the transactivator protein Tax. The 21-bp repeats can be subdivided into three motifs known as A, B, and C, each of which is important for maximal gene expression in response to Tax. The B motif contains nucleotide sequences known as a cyclic AMP response element (CRE) or tax-response element which binds members of the ATF/CREB family of transcription factors. Though mutations of this element in the HTLV-I LTR eliminate tax activation, Tax will not activate most other promoters containing these CRE sites. In this study, we investigated the mechanism by which Tax activates gene expression in conjunction with members of the ATF/CREB family. We found that Tax enhanced the binding of one member of the ATF/CREB family, CREB 1, to each of the three HTLV-I LTR 21-bp repeats but not another member designated CRE-BP1 or CREB2. Tax enhanced the binding of CREB1 to nonpalindromic CRE binding sites such as those found in the HTLV-I LTR, but Tax did not enhance the binding of CREB1 to palindromic CRE binding sites such as found in the somatostatin promoter. This finding may help explain the failure of Tax to activate promoters containing consensus CRE sites. These studies were extended by use of the mammalian two-hybrid system. Tax was demonstrated to interact directly with CREB1 but not with other bZIP proteins, including CREB2 and Jun. Site-directed mutagenesis of both Tax and CREB1 demonstrated that the amino terminus of Tax and both the basic and the leucine zipper regions of CREB1 were required for direct interactions between these proteins both in vivo and in vitro. This interaction occurred in vivo and thus did not require the presence of the HTLV-I 21-bp repeats, as previously suggested. These results define the domains required for interaction between Tax and CREB that are likely critical for the

Direct visualization of antigen-specific T cells: HTLV-1 Tax11-19- specific CD8(+) T cells are activated in peripheral blood and accumulate in cerebrospinal fluid from HAM/TSP patients.

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Greten, T F; Slansky, J E; Kubota, R; Soldan, S S; Jaffee, E M; Leist, T P; Pardoll, D M; Jacobson, S; Schneck, J P

1998-06-23

Human T lymphotropic virus type 1 (HTLV-1) -associated myelopathy/tropic spastic paraparesis is a demyelinating inflammatory neurologic disease associated with HTLV-1 infection. HTLV-1 Tax11-19-specific cytotoxic T cells have been isolated from HLA-A2-positive patients. We have used a peptide-loaded soluble HLA-A2-Ig complex to directly visualize HTLV-1 Tax11-19-specific T cells from peripheral blood and cerebrospinal fluid without in vitro stimulation. Five of six HTLV-1-associated myelopathy/tropic spastic paraparesis patients carried a significant number (up to 13.87%) of CD8(+) lymphocytes specific for the HTLV-1 Tax11-19 peptide in their peripheral blood, which were not found in healthy controls. Simultaneous comparison of peripheral blood and cerebrospinal fluid from one patient revealed 2.5-fold more Tax11-19-specific T cells in the cerebrospinal fluid (23.7% vs. 9.4% in peripheral blood lymphocyte). Tax11-19-specific T cells were seen consistently over a 9-yr time course in one patient as far as 19 yrs after the onset of clinical symptoms. Further analysis of HTLV-1 Tax11-19-specific CD8(+) T lymphocytes in HAM/TSP patients showed different expression patterns of activation markers, intracellular TNF-alpha and gamma-interferon depending on the severity of the disease. Thus, visualization of antigen-specific T cells demonstrates that HTLV-1 Tax11-19-specific CD8(+) T cells are activated, persist during the chronic phase of the disease, and accumulate in cerebrospinal fluid, showing their pivotal role in the pathogenesis of this neurologic disease.

Adesão às medidas preventivas de pneumonia associada à ventilação mecânica.

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Luany Caroline Adamovicz Bork

2015-01-01

Full Text Available Justificativa e Objetivos: Ressaltando a relevância da adoção de medidas preventivas de infecção para a realização de uma assistência livre de danos emergiu a necessidade de observar como a equipe de saúde aplica o bundle. Objetivou-se verificar a adesão de medidas preventivas de pneumonia pelos profissionais de saúde, da Unidade de Terapia Intensiva geral adulta de um hospital público, Ponta Grossa-PR. Métodos: Pesquisa transversal, de abordagem quantitativa, prospectiva e observacional, realizada no período de abril a julho de 2013. A amostra constituiu-se de 33 pacientes que estavam em ventilação mecânica, totalizando o registro de 1522 momentos de aplicações das medidas preventivas de pneumonia associada à ventilação mecânica (PAVM. Resultados: Dos 33 pacientes, 13 desenvolveram pneumonia, a média de idade foi de 59,72 anos e a prevalência foi do gênero feminino (44,44%. Verificou-se que os profissionais de saúde atenderam a cabeceira elevada dos leitos em média 69,80%, assim como aderiram à interrupção da sedação em média 66,66%, realizaram a higiene oral com clorexidina 94,61%, mantiveram o cuff do tubo orotraqueal (entre 20 e 25 mmH20 64,44%, adequaram o filtro de nebulizador para ficar dentro da validade 89,50% e em 93,4% das observações deixaram os circuitos livre de condensados. Analisou-se que o valor médio de dias passados em ventilação mecânica dos pacientes que adquiriram infecção foi de 15,85 (DP = 8,65 dias. Conclusão: Revela-se que quando a equipe aplica todas as medidas preventivas ao paciente sob ventilação mecânica há redução do risco de adquirir infecção no trato respiratório. DESCRITORES: Terapia intensiva; Pneumonia associada à ventilação mecânica; Infecção hospitalar; Equipe de assistência ao paciente.

HTLV-1 Tax-mediated TAK1 activation involves TAB2 adapter protein

International Nuclear Information System (INIS)

Yu Qingsheng; Minoda, Yasumasa; Yoshida, Ryoko; Yoshida, Hideyuki; Iha, Hidekatsu; Kobayashi, Takashi; Yoshimura, Akihiko; Takaesu, Giichi

2008-01-01

Human T cell leukemia virus type 1 (HTLV-1) Tax is an oncoprotein that plays a crucial role in the proliferation and transformation of HTLV-1-infected T lymphocytes. It has recently been reported that Tax activates a MAPKKK family, TAK1. However, the molecular mechanism of Tax-mediated TAK1 activation is not well understood. In this report, we investigated the role of TAK1-binding protein 2 (TAB2) in Tax-mediated TAK1 activation. We found that TAB2 physically interacts with Tax and augments Tax-induced NF-κB activity. Tax and TAB2 cooperatively activate TAK1 when they are coexpressed. Furthermore, TAK1 activation by Tax requires TAB2 binding as well as ubiquitination of Tax. We also found that the overexpression of TRAF2, 5, or 6 strongly induces Tax ubiquitination. These results suggest that TAB2 may be critically involved in Tax-mediated activation of TAK1 and that NF-κB-activating TRAF family proteins are potential cellular E3 ubiquitin ligases toward Tax

Claritromicina associada com pirímetamina na toxoplasmose cerebral - relato de dois casos

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Marcos Olivicr Dalston

1995-12-01

Full Text Available Os autores relatam a resposta terapêutica da claritromicina associada com pirímetamina em dois casos de toxoplasmose cerebral ocorridos em pacientes com Síndrome de Imunodeficiência Adquirida (SIDA. Nos dois casos o diagnóstico foi presuntivo, baseando-se nas manifestações clínicas e na presença de lesões expansivas hipercaptantes detectadas na tomografia computadorizada (TC de crânio. Em ambos os casos, observou-se exantema com o uso da sulfadiazina e da clindamicina, razão pela qual tais medicamentos foram substituídos pela claritromicina (1,5 a 2g/dia associada à pirímetamina (25mg/dia. A resposta terapêutica foi favorável nos dois casos com melhora das manifestações neurológicas e dos achados neurorradiológicos. Os autores sugerem que a associação claritromicina com pirímetamina pode ser útil como opção terapêutica na toxoplasmose cerebral em pacientes com SIDA que apresentam intolerância ou outra contra-indicação ao emprego das sulfonamidas.The authors report the use and tbe outcome of claritromycin associated with pyrimethamine in the treatment of toxoplasma encephalites in two patients with AIDS. Both patients had the diagnosis stablished on clinical grounds, positive sorology (IgG for toxoplasmosis and computed-tomographic (CT scan of the brain showing lesions consistent with T. gondii encephalitis. The two patients were initially treated with pyrimethamine and sulfadiazme, which was changed to clindamycin due to allergic reactions. These reactions (skin rash occurred with clindamycin as well and the patients were treated with claritromycin and pyrimethamine. The scheduled regimens were 1.5 to 2g of clarithromycin plus 25mg of pyrimethamine. The clinical response was very good in both cases with regression of neurologic signs and encephalitic abnormalities observed on CT scan. The authors suggest that clarithromycin associated with pyrimethamine may be an alternative treatment for toxoplasmosis in AIDS

Transformação genética de Sorghum bicolor (L. Moench) visando tolerância ao AL³

OpenAIRE

Brandão, Rosângela Luci

2014-01-01

A transformação genética tem sido frequentemente associada a programas de melhoramento genético. Esta técnica permite a introdução de gene(s) exógeno(s) no genoma das plantas, modificando características específicas. Pode ser uma importante ferramenta de auxílio aos programas de melhoramento convencional de sorgo. Entretanto, a maioria dos protocolos de transformação genética requer o estabelecimento prévio de sistemas de regeneração de plantas in vitro. Portanto, com a finalidade de produzir...

The MHC-II transactivator CIITA, a restriction factor against oncogenic HTLV-1 and HTLV-2 retroviruses: similarities and differences in the inhibition of Tax-1 and Tax-2 viral transactivators

Science.gov (United States)

Forlani, Greta; Abdallah, Rawan; Accolla, Roberto S.; Tosi, Giovanna

2013-01-01

The activation of CD4+ T helper cells is strictly dependent on the presentation of antigenic peptides by MHC class II (MHC-II) molecules. MHC-II expression is primarily regulated at the transcriptional level by the AIR-1 gene product CIITA (class II transactivator). Thus, CIITA plays a pivotal role in the triggering of the adaptive immune response against pathogens. Besides this well known function, we recently found that CIITA acts as an endogenous restriction factor against HTLV-1 (human T cell lymphotropic virus type 1) and HTLV-2 oncogenic retroviruses by targeting their viral transactivators Tax-1 and Tax-2, respectively. Here we review our findings on CIITA-mediated inhibition of viral replication and discuss similarities and differences in the molecular mechanisms by which CIITA specifically counteracts the function of Tax-1 and Tax-2 molecules. The dual function of CIITA as a key regulator of adaptive and intrinsic immunity represents a rather unique example of adaptation of host-derived factors against pathogen infections during evolution. PMID:23986750

Sudar vozila u vlasništvu istog leasing društva i problem treće osobe iz AO osiguranja

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Radionov, Nikoleta; Padovan, Adriana Vincenca

2012-01-01

U radu se razmatraju pravni odnosi koji nastaju u slučaju sudara dvaju (ili više) vozila u vlasništvu istog leasing društva (slučaj leasing – leasing). Prema uvriježenoj praksi na domaćem tržištu osiguranja, u takvim slučajevima dolazi do isključenja iz osiguranja šteta na vozilu temeljem osiguranja automobilske odgovornosti (AO), s obzirom na to da su vozila u vlasništvu istog leasing društva koje je i jedini osiguranik po policama AO oba (ili više) vozila sudionika nezgode. Primatelj leasin...

Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease

Science.gov (United States)

Ndhlovu, L C; Snyder-Cappione, J E; Carvalho, K I; Leal, F E; Loo, C P; bruno, F R; Jha, A R; Devita, D; Hasenkrug, A M; Barbosa, H M R; Segurado, A C; Nixon, D F; Murphy, E L; Kallas, E G

2009-01-01

Human T lymphotropic virus type 1 (HTLV-1) infects 10–20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4+ and fewer CD8+ cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4+ NK T subset are associated with HTLV-1 disease progression. PMID:19778295

Development of Graves' ophthalmopathy and uveitis after radioiodine therapy for Graves' disease in a patient with HTLA-I associated myelopathy (HAM)

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Ozawa, Yasunori; Migita, Masayoshi; Watanabe, Tomoji; Okuda, Itsuko; Takeshita, Akira; Takagi, Akio; Shishiba, Yoshimasa (Toranomon Hospital, Tokyo (Japan))

1994-09-01

HTLV-I carriers or patients with HTLV-I associated myelopathy (HAM) are prone to immune-mediated inflammatory disorders. We present a 44-year-old female with HAM who developed Graves' disease. She developed severe Graves' ophthalmopathy shortly after [sup 131]I therapy, concurrently with a remarkable increase in TSH-receptor antibody titer. Ophthalmopathy was aggravated in spite of prednisolone therapy and euthyroidism being maintained by thyroxine replacement. Uveitis also developed after [sup 131]I therapy and iridocyclitis finally required trabeculotomy. This case suggests that HAM patients may have a higher risk of immune-mediated Graves' ophthalmopathy after [sup 131]I therapy.(author).

Desarterialização transanal guiada por doppler associada ao reparo anorretal na doença hemorroidária: a técnica do THD Transanal desarterialization guided by Doppler associated to anorectal repair in hemorrhoids: THD technic

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Carlos Walter Sobrado-Junior

2012-12-01

Full Text Available INTRODUÇÃO: O tratamento cirúrgico para hemorroidas deve ter indicação individual e baseia-se no sintoma predominante (sangramento ou prolapso, na gravidade da doença e na presença ou ausência de componente externo (plicoma. Cabe ao cirurgião conhecer as mais variadas técnicas para que possa encontrar o tratamento mais adequado caso a caso. TÉCNICA: O procedimento THD consiste na ligadura alta seletiva e guiada por Doppler de até seis ramos arteriais submucosos que irrigam as hemorroidas, levando à sua desarterialização, associada à correção do prolapso (reparo anorretal ou lifting. Utiliza equipamento e kit especiais. CONCLUSÃO: A técnica do THD tem mostrado bons resultados iniciais. Por ser técnica cirúrgica em que se respeita a anatomia, ela age diretamente sobre a fisiopatologia da afecção e corrige suas principais consequências, ela parece bastante promissora. Sua aplicação inicial pode ser nos pacientes com doença hemorroidária de II grau, que tenham indicação de tratamento cirúrgico, e de III e IV graus, nestes últimos, podendo ser associada à ressecção de plicomas.INTRODUCTION: Surgical treatment for hemorrhoids should be indicated individually and is based on the predominant symptom (bleeding or prolapse, severity of disease and the presence or absence of external component (plicoma. Surgeons must choose among varied techniques the one suitable for each case. TECHNIC: The THD procedure consists of Doppler guided high ligation, selective to up six submucosal arterial branches that supply the hemorrhoids, leading to its desarterialization associated with prolapse repair (anorectal repair or lifting. It uses special equipment and kit. CONCLUSION: THD technique has shown good initial results. Because surgical technique respects the anatomy, it acts directly on the pathophysiology of the disease and corrects its principal consequences; it looks quite promising. Its initial application may be in patients

Lesão pulmonar aguda associada à transfusão Transfusion-related acute lung injury

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Antonio Fabron Junior

2007-04-01

Full Text Available Lesão pulmonar aguda associada à transfusão (transfusion-related acute lung injury, TRALI é uma complicação clínica grave relacionada à transfusão de hemocomponentes que contêm plasma. Recentemente, TRALI foi considerada a principal causa de morte associada à transfusão nos Estados Unidos e Reino Unido. É manifestada tipicamente por dispnéia, hipoxemia, hipotensão, febre e edema pulmonar não cardiogênico, que ocorre durante ou dentro de 6 h, após completada a transfusão. Embora o exato mecanismo não tenha sido totalmente elucidado, postula-se que TRALI esteja associada à infusão de anticorpos contra antígenos leucocitários (classes I ou II ou aloantígenos específicos de neutrófilos e a mediadores biologicamente ativos presentes em componentes celulares estocados. A maioria dos doadores implicados em casos da TRALI são mulheres multíparas. TRALI, além de ser pouco diagnosticada, pode ainda ser confundida com outras situações de insuficiência respiratória aguda. Um melhor conhecimento sobre TRALI pode ser crucial na prevenção e tratamento desta severa complicação transfusional.Transfusion-related acute lung injury (TRALI is a serious clinical syndrome associated with the transfusion of plasma-containing blood components. Recently, TRALI has come to be recognized as the leading cause of transfusion-related death in the United States and United Kingdom. This complication typically presents as shortness of breath, hypoxemia, hypotension, fever and noncardiogeneic pulmonary edema, all occurring during or within 6 h after transfusion. Although the mechanism of TRALI has not been fully elucidated, it has been associated with human leukocyte antigen antibodies (class I, class II or neutrophil alloantigens and with biologically active mediators in stored cellular blood components. Most of the donors implicated in cases of TRALI are multiparous women. Rarely diagnosed, TRALI can be confused with other causes of acute

Vaccine-associated paralytic Poliomyelitis: a case report of domiciliary transmission Poliomielite associada à vacina: descrição de caso por transmissão domiciliar

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José A. Paz

2000-06-01

Full Text Available Poliomyelitis associated with live strain vaccine is defined as the paralytic form of the acute anterior poliomyelitis related to the vaccine strain. Since these strains behave similarly to the wild-type virus, we can differentiate, epidemiologically, two types of vaccine-associated poliomyelitis: cases in which the patient was vaccinated and cases in which the patient had had contact with vaccinated individuals. We herein present the case of an unvaccinated child, with a clinical picture of an acute anterior poliomyelitis associated with the live strain vaccine, whose brother received the Sabin vaccine 20 days before the onset of the symptoms. Vaccine strain of the type 3 poliovirus was isolated in fecal culture and a presented mutation in nucleotide 472 (C®U in the 5' non-coding region, which is strongly related to the higher strain virulence.A poliomielite associada à vacina oral é definida como a forma paralítica da poliomielite anterior aguda decorrente da cepa vacinal. Uma vez que o comportamento da cepa vacinal é semelhante ao do vírus selvagem, epidemiologicamente podemos distinguir dois tipos de poliomielite associada à vacina, os casos em que o paciente foi vacinado e os casos em que o paciente teve contato com pessoas que receberam a vacina. Apresentamos o caso de um lactente não vacinado, que apresentou quadro de poliomielite anterior aguda associada à vacina oral, cujo irmão havia recebido a vacina Sabin 20 dias antes do início do quadro clínico. Na cultura de fezes do paciente foi isolado o poliovírus tipo 3, cepa vacinal, que apresentava mutação do nucleotídeo 472 (C®U na região 5' não codificadora, a qual está significativamente relacionada com a maior virulência da cepa.

Fatores anteriores ao ingresso como preditivos de evasão nos anos iniciais dos cursos superiores de tecnologia

OpenAIRE

Rafaela de Menezes Souza Brissac

2009-01-01

Resumo: A evasão de estudantes do ensino superior evidencia-se como fenômeno complexo, com conseqüências de ordem pessoal, institucional e social. Entre os estudos que buscam aprofundar o conhecimento sobre este fenômeno encontram-se os que se detém a pesquisar as causas e fatores associados à evasão de alunos neste nível de ensino. No que se refere às variáveis associadas à ocorrência da evasão, os estudos têm mostrado que é possível localizar fatores que são anteriores ao ingresso do estuda...

Human T-lymphotropic virus type 1 prevalence in northeastern Iran, Sabzevar: an epidemiologic-based study and phylogenetic analysis.

Science.gov (United States)

Azarpazhooh, Mahmoud Reza; Hasanpour, Kazem; Ghanbari, Mohsen; Rezaee, S A Rahim; Mashkani, Baratali; Hedayati-Moghaddam, Mohammad Reza; Valizadeh, Narges; Farid Hosseini, Reza; Foroghipoor, Mohsen; Soltanifar, Azadeh; Sahebari, Maryam; Azadmanesh, Keyhan; Hassanshahi, Gholahossein; Rafatpanah, Houshang

2012-09-01

Human T-lymphotropic virus type 1 (HTLV-I) is an important global health problem in the world mainly in the endemic areas of HTLV-I infection. It was previously reported that Mashhad, in northeastern Iran, is a new endemic region of HTLV-I. The aim of this study was to examine the prevalence and phylogenetic analysis of HTLV-I in Sabzevar, located in the southeast of Mashhad. In this cross-sectional study 1445 individuals were selected by multistage cluster sampling. Serum samples were screened for anti-HTLV-I antibody using enzyme-linked immunosorbent assay (ELISA); all of the ELISA-positive samples were confirmed by polymerase chain reaction (PCR). Long terminal repeat (LTR) sequencing was carried out to determine the type of HTLV-I in Sabzevar. In the primary screening by ELISA, 26/1445 (1.8%) of those sampled were reactive for HTLV-I antibody. Twenty-four out of 26 samples were confirmed HTLV-I infection by PCR (24/1445). The overall prevalence of HTLV-I infection in Sabzevar is 1.66%. The prevalence of the virus infection in men and women was 2.42% (11/455) and 1.31% (13/989), respectively. Seroprevalence was associated with age, increasing significantly among those older than 30 years (p=0.015), and a history of surgery (p=0.002), imprisonment (p=0.018), and hospitalization (p=0.005). Three out of 24 positive HTLV-I samples were selected for sequencing and phylogenetic analysis of LTR. The results showed that HTLV-I in Sabzevar belonged to the cosmopolitan subtype. The present study showed Sabzevar is a new endemic area for HTLV-I infection. Our study emphasizes that systemic HTLV-I screening of blood donors in Sabzevar and other cities in Khorasan province is important and should be taken into account.

HTLV in the Americas: challenges and perspectives El virus de la leucemia humana de células T (VLHT en las Américas: retos y perspectivas

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Anna Bárbara F. Carneiro-Proietti

2006-01-01

Full Text Available The first description of the human T-lymphotropic virus type 1 (HTLV-1 was made in 1980, followed closely by the discovery of HTLV-2, in 1982. Since then, the main characteristics of these viruses, commonly referred to as HTLV-1/2, have been thoroughly studied. Central and South America and the Caribbean are areas of high prevalence of HTLV-1 and HTVL-2 and have clusters of infected people. The major modes of transmission have been through sexual contact, blood, and mother to child via breast-feeding. HTLV-1 is associated with adult T-cell leukemia/lymphoma (ATL, HTLV-associated myelopathy/tropical spastic paraparesis (HAM/ TSP, and HTLV-associated uveitis as well as infectious dermatitis of children. More clarification is needed in the possible role of HTLV in rheumatologic, psychiatric, and infectious diseases. Since cures for ATL and HAM/TSP are lacking and no vaccine is available to prevent HTLV-1 and HTLV-2 transmission, these illnesses impose enormous social and financial costs on infected individuals, their families, and health care systems. For this reason, public health interventions aimed at counseling and educating high-risk individuals and populations are of vital importance. In the Americas this is especially important in the areas of high prevalence.La primera descripción del virus de la leucemia humana de células T tipo 1 (VLHT-1 se hizo en 1980, y al poco tiempo, en 1982, se descubrió el VLHT-2. Desde entonces las características principales de estos virus, a los que a menudo se les llama VLHT-1/2, se han estudiado exhaustivamente. Centroamérica, América del Sur y el Caribe son áreas con una alta prevalencia de VLHT-1 y VLHT-2 donde hay conglomerados de personas infectadas. Las principales vías de transmisión han sido el contacto sexual, la sangre y sus derivados, y la de madre a hijo por la leche materna. El VLHT-1 se asocia con la leucemia o el linfoma de células T maduras (LTM, la mielopatía o paraparesia tropical

Identification of a subset of perpheral T-cell lymphoma, not otherwise specified, characterized by FOXP3-positive regulatory T-cell phenotype, HTLV-1 negativity and poor outcome

DEFF Research Database (Denmark)

Pedersen, Martin Bjerregård; Hamilton-Dutoit, Stephen Jacques; Bendix, Knud

2014-01-01

Identification of a subset of perpheral T-cell lymphoma, not otherwise specified, characterized by FOXP3-positive regulatory T-cell phenotype, HTLV-1 negativity and poor outcome.......Identification of a subset of perpheral T-cell lymphoma, not otherwise specified, characterized by FOXP3-positive regulatory T-cell phenotype, HTLV-1 negativity and poor outcome....

Expansion in CD39+ CD4+ Immunoregulatory T Cells and Rarity of Th17 Cells in HTLV-1 Infected Patients Is Associated with Neurological Complications

Science.gov (United States)

Hasenkrug, Aaron M.; Bruno, Fernanda R.; Carvalho, Karina I.; Wynn-Williams, Harry; Neto, Walter K.; Sanabani, Sabri S.; Segurado, Aluisio C.; Nixon, Douglas F.; Kallas, Esper G.

2013-01-01

HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develops HAM/TSP. CD4+ T cells are the main target of infection and play a pivotal role in regulating immunity to HTLV and are hypothesized to participate in the pathogenesis of HAM/TSP. The CD39 ectonucleotidase receptor is expressed on CD4+ T cells and based on co-expression with CD25, marks T cells with distinct regulatory (CD39+CD25+) and effector (CD39+CD25−) function. Here, we investigated the expression of CD39 on CD4+ T cells from a cohort of HAM/TSP patients, HTLV-1 asymptomatic carriers (AC), and matched uninfected controls. The frequency of CD39+ CD4+ T cells was increased in HTLV-1 infected patients, regardless of clinical status. More importantly, the proportion of the immunostimulatory CD39+CD25− CD4+ T-cell subset was significantly elevated in HAM/TSP patients as compared to AC and phenotypically had lower levels of the immunoinhibitory receptor, PD-1. We saw no difference in the frequency of CD39+CD25+ regulatory (Treg) cells between AC and HAM/TSP patients. However, these cells transition from being anergic to displaying a polyfunctional cytokine response following HTLV-1 infection. CD39−CD25+ T cell subsets predominantly secreted the inflammatory cytokine IL-17. We found that HAM/TSP patients had significantly fewer numbers of IL-17 secreting CD4+ T cells compared to uninfected controls. Taken together, we show that the expression of CD39 is upregulated on CD4+ T cells HAM/TSP patients. This upregulation may play a role in the development of the proinflammatory milieu through pathways both distinct and separate among the different CD39 T cell subsets. CD39 upregulation may therefore serve as a surrogate diagnostic marker of progression and could potentially be a target for interventions to reduce the development of

Síndrome de Sweet associada à policitemia vera

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Moreira,Ângela Puccini; Souza,Flávia Feijó de; Gaspar,Neide Kalil; Quattrino,Ada Lobato; Vilar,Enoi Aparecida Guedes

2009-01-01

A síndrome de Sweet pode estar associada a malignidades hematológicas, principalmente, à leucemia mieloide aguda, porém existem poucos relatos demonstrando a associação com a policitemia vera. Relata-se o caso de doente do sexo masculino, de 65 anos, portador de policitemia vera,que evoluiu com aparecimento de síndrome de Sweet na sua forma paraneoplásica.

Anfíbios anuros de serrapilheira do parque Estadual do Rio Doce: resposta à disponibilidade de recursos e aos fatores climáticos

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Rievers, Camila Rabelo

2010-01-01

A herpetofauna associada à serrapilheira apresenta características complexas e particulares quanto ao uso de recursos e estratégias reprodutivas. Ainda há muitas lacunas sobre os padrões de distribuição, abundância, riqueza e diversidade da herpetofauna e os fatores que os influenciam. A presente dissertação teve como objetivo estudar a comunidade de anuros associados à serrapilheira do Parque Estadual do Rio Doce (PERD), e sua relação com a heterogeneidade do habitat, a disponibilidade de al...

Simultaneous RNA quantification of human and retroviral genomes reveals intact interferon signaling in HTLV-1-infected CD4+ T cell lines

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Moens Britta

2012-08-01

Full Text Available Abstract Background IFN-α contributes extensively to host immune response upon viral infection through antiviral, pro-apoptotic, antiproliferative and immunomodulatory activities. Although extensively documented in various types of human cancers and viral infections, controversy exists in the exact mechanism of action of IFN-α in human immunodeficiency virus type 1 (HIV-1 and human T-lymphotropic virus type 1 (HTLV-1 retroviral infections. Results IFN-α displayed strong anti-HIV-1 effects in HIV-1/HTLV-1 co-infected MT-4 cells in vitro, demonstrated by the dose-dependent inhibition of the HIV-1-induced cytopathic effect (IC50 = 83.5 IU/ml, p 50 = 1.2 IU/ml, p  Conclusions Taken together, our results indicate that both the absence of in vitro antiproliferative and pro-apoptotic activity as well as the modest post-transcriptional antiviral activity of IFN-α against HTLV-1, were not due to a cell-intrinsic defect in IFN-α signalisation, but rather represents a retrovirus-specific phenomenon, considering the strong HIV-1 inhibition in co-infected cells.

Serial transmission of human T-cell leukemia virus type I by blood transfusion in rabbits and its prevention by use of X-irradiated stored blood

Energy Technology Data Exchange (ETDEWEB)

Kotani, S.; Yoshimoto, S.; Yamato, K.; Fujishita, M.; Yamashita, M.; Ohtsuki, Y.; Taguchi, H.; Miyoshi, I.

1986-06-15

Human T-cell leukemia virus type I (HTLV-I) was serially transmitted for 5 passages from rabbit to rabbit by blood transfusion. The virus could be transmitted with 20 ml of whole blood or washed blood cell suspension (fresh or stored for 1-2 weeks at 4 degrees C) but not with cell-free plasma from seroconverted rabbits. Seroconversion occurred 2-4 weeks after blood transfusion and serum anti-HTLV-I titers ranged from 1:20 to 1:640 with the immunofluorescence assay. From transfusion recipients of the 1st to 4th passages, virus-producing cell lines were established by culturing lymphocytes in the presence of T-cell growth factor (TCGF). Three of the 4 cell lines became TCGF-independent after 2-12 months of continuous culture. Blood was transfused between rabbits of opposite sexes and the recipient origin of each cell line was determined by chromosome analysis. We also investigated the effect of X-irradiation (6,000 rad) on blood from seropositive rabbits. Seroconversion likewise occurred in rabbits transfused with blood that had been irradiated immediately before transfusion but not in rabbits transfused with blood that had been irradiated and stored for 1-2 weeks at 4 degrees C. Thus, our rabbit model shows that HTLV-I is serially transmissible by blood transfusion and that this can be prevented by irradiation of blood. The same procedure, therefore, may be useful for the prevention of transfusion-related transmission of HTLV-I in humans.

Economic burden of expected epidemiological changes in diseases related to tobacco, Mexico Impacto econômico das mudanças epidemiológicas esperadas nas doenças associadas ao tabaco, México

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Armando Arredondo

2007-08-01

Full Text Available OBJECTIVE: To determine health care costs and economic burden of epidemiological changes in diseases related to tobacco consumption. METHODS: A time-series analysis in Mexico (1994-2005 was carried out on seven health interventions: chronic obstructive pulmonary diseases, lung cancer with and without surgical intervention, asthma in smokers and non-smokers, full treatment course with nicotine gum, and full treatment course with nicotine patch. According with Box-Jenkins methodology, probabilistic models were developed to forecast the expected changes in the epidemiologic profile and the expected changes in health care services required for selected interventions. Health care costs were estimated following the instrumentation methods and validated with consensus technique. RESULTS: A comparison of the economic impact in 2006 vs. 2008 showed 20-90% increase in expected cases depending on the disease (pOBJETIVO: Avaliar os custos da atenção médica a doenças associadas ao tabagismo e o impacto econômico das mudanças epidemiológicas. MÉTODOS: Análise de série temporal no México (1994-2005 de sete intervenções médicas em relação a: doença pulmonar obstrutiva crônica, câncer de pulmão com e sem intervenção cirúrgica, asma bronquial em fumantes e não-fumantes, tratamento com adesivos para deixar de fumar, tratamento com goma de mascar. As mudanças epidemiológicas esperadas e as necessidades financeiras para atender a demanda de serviços foram avaliadas pelos modelos probabilísticos de Box-Jenkins. Os custos foram determinados de acordo com método de instrumentação e a técnica de consenso. RESULTADOS: A comparação do impacto das mudanças epidemiológicas previstas para 2006 e 2008 mostrou incremento de 20% a 90%, dependendo do tipo de intervenção. O incremento nos custos da atenção médica foi de 25% a 93%. Há indícios que a demanda de serviços de saúde para as intervenções investigadas continuarão aumentando

Sporadic on/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells.

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Mahgoub, Mohamed; Yasunaga, Jun-Ichirou; Iwami, Shingo; Nakaoka, Shinji; Koizumi, Yoshiki; Shimura, Kazuya; Matsuoka, Masao

2018-02-06

Viruses causing chronic infection artfully manipulate infected cells to enable viral persistence in vivo under the pressure of immunity. Human T-cell leukemia virus type 1 (HTLV-1) establishes persistent infection mainly in CD4+ T cells in vivo and induces leukemia in this subset. HTLV-1-encoded Tax is a critical transactivator of viral replication and a potent oncoprotein, but its significance in pathogenesis remains obscure due to its very low level of expression in vivo. Here, we show that Tax is expressed in a minor fraction of leukemic cells at any given time, and importantly, its expression spontaneously switches between on and off states. Live cell imaging revealed that the average duration of one episode of Tax expression is ∼19 hours. Knockdown of Tax rapidly induced apoptosis in most cells, indicating that Tax is critical for maintaining the population, even if its short-term expression is limited to a small subpopulation. Single-cell analysis and computational simulation suggest that transient Tax expression triggers antiapoptotic machinery, and this effect continues even after Tax expression is diminished; this activation of the antiapoptotic machinery is the critical event for maintaining the population. In addition, Tax is induced by various cytotoxic stresses and also promotes HTLV-1 replication. Thus, it seems that Tax protects infected cells from apoptosis and increases the chance of viral transmission at a critical moment. Keeping the expression of Tax minimal but inducible on demand is, therefore, a fundamental strategy of HTLV-1 to promote persistent infection and leukemogenesis. Copyright © 2018 the Author(s). Published by PNAS.

Perfil de extensão vocal em coristas após técnica de vibração de língua associada a escalas

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Amanda Thaís Lima

Full Text Available RESUMO: Objetivo: identificar o efeito imediato da técnica de vibração sonorizada de língua associada à variação tonal sobre o perfil de extensão vocal de coristas, analisando o tempo de prática de canto, naipe e tempo de execução do exercício. Métodos: estudo transversal quantitativo, com 13 cantores, sendo oito mulheres e cinco homens, com média de idade de 39±20,11 anos, pertencentes a diferentes naipes. O perfil de extensão vocal foi obtido a partir da análise pelo software Vocalgrama da CTS Informática. As amostras foram coletadas em três momentos: antes, após um minuto e após dois minutos de aplicação da técnica de vibração sonorizada de língua associada à variação tonal. Resultados: seis coristas (46,2% aumentaram o valor do perfil de extensão vocal, após dois minutos de execução da técnica. Os naipes sopranos e tenores apresentaram valores médios maiores do perfil de extensão vocal após dois minutos de exercício. Em relação ao tempo de prática de canto, não houve diferença entre os grupos no valor do perfil de extensão vocal em nenhum dos três momentos considerados. Conclusão: a técnica de vibração sonorizada de língua associada à variação tonal não interferiu no perfil de extensão vocal dos coristas estudados. Entretanto, o tempo de execução do exercício parece influenciar nos resultados.

Intrathecal synthesis of antibodies to HTLV-III in patients without AIDS or AIDS related complex

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Goudsmit, J.; Wolters, E. C.; Bakker, M.; Smit, L.; van der Noordaa, J.; Hische, E. A.; Tutuarima, J. A.; van der Helm, H. J.

1986-01-01

De novo synthesis in the central nervous system of IgG antibodies to human T cell lymphotropic virus type III (HTLV-III) (lymphadenopathy associated virus) was shown in seven of 10 seropositive men who had syphilis but not the acquired immune deficiency syndrome (AIDS) or AIDS related complex. None

FoxP3+ regulatory T cells are distinct from leukemia cells in HTLV-1-associated adult T-cell leukemia.

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Toulza, Frederic; Nosaka, Kisato; Takiguchi, Masafumi; Pagliuca, Tony; Mitsuya, Hiroaki; Tanaka, Yuetsu; Taylor, Graham P; Bangham, Charles R M

2009-11-15

Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL). It has been postulated that ATLL cells might act as regulatory T cells (T(regs)) which, in common with ATLL cells, express both CD25 and FoxP3, and so contribute to the severe immune suppression typical of ATLL. We report here that the frequency of CD25(+) cells varied independently of the frequency of FoxP3(+) cells in both a cross-sectional study and in a longitudinal study of 2 patients with chronic ATLL. Furthermore, the capacity of ATLL cells to suppress proliferation of heterologous CD4(+)CD25(-) cells correlated with the frequency of CD4(+) FoxP3(+) cells but was independent of CD25 expression. Finally, the frequency of CD4(+)FoxP3(+) cells was inversely correlated with the lytic activity of HTLV-1-specific CTLs in patients with ATLL. We conclude that ATLL is not a tumor of FoxP3(+) regulatory T cells, and that a population of FoxP3(+) cells distinct from ATLL cells has regulatory functions and may impair the cell-mediated immune response to HTLV-1 in patients with ATLL.

Adesão ao tratamento no transtorno bipolar Compliance to treatment in bipolar disorder

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Aida Santin

2005-01-01

Full Text Available O transtorno bipolar (TB é uma doença crônica, recorrente, presente em 1,5% da população, estando associada a altas taxas de mortalidade e prejuízos socioeconômicos. O lítio, a carbamazepina e o ácido valpróico são os estabilizadores de humor mais usados. Em tratamentos prolongados, como é o caso do TB, a má-adesão dos pacientes é uma das maiores dificuldades. Verifica-se que fatores ligados ao paciente, aos medicamentos e aos médicos possam ser responsáveis pela baixa adesão. A psicoeducação, a terapia cognitivo-comportamental e a terapia focada na família são estratégias propostas para o aumento da adesão.Bipolar disorder (BD is a chronic and recurrent illness that occurs in 1,5% of the population. This illness is associated with high rates of mortality and social/economic burden. Lithium, carbamazepine and valproic acid are the most used mood stabilizers. In long term treatments, as in BD, one of the main difficulties is the patient's adherence. It appears that factors associated to the patient, drug and the physician are responsible for the low adherence. The use of psycho-education, cognitive-behavioral therapy and focused family therapy have been put forward as a means to increase adherence.

Seropositividad al virus linfotrópico de células T humanas tipos I y II en donantes del Banco Municipal de Sangre de Caracas y factores de riesgo asociados

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Graciela León

2003-03-01

Full Text Available OBJETIVOS: Conocer la proporción de sangre descartada por seropositividad al virus linfotrópico de células T humanas (HTLV tipos I y II, la prevalencia de dicha infección y los probables factores de riesgo en donantes del Banco Municipal de Sangre de Caracas (BMSC. MÉTODOS: Se evaluaron serológicamente mediante ensayos de inmunoadsorción enzimática (ELISA 23 413 donantes atendidos entre julio del año 2000 y abril de 2001 en el BMSC. Las muestras repetidamente reactivas (RR se estudiaron por inmunoblot de Western (WB, como prueba suplementaria. Los donantes positivos o indeterminados por WB fueron citados a la consejería para realizar la confirmación mediante la amplificación de ácidos nucleicos por reacción en cadena de la polimerasa (PCR, recoger datos sobre sus antecedentes de riesgo y asesorarlos acerca de su estado. RESULTADOS. El 0,2% de las donaciones resultaron RR; de ellas 52,1% resultaron positivas en el WB (23 a HTLV I y 2 a HTLV II; 4,1% indeterminadas por WB; 29,2% negativas; y el 14,6% no pudo ser evaluado. Asistieron a la consejería 16 donantes (14 WB positivos a HTLV I, 1 a HTLV II y 1 indeterminado. Todos resultaron positivos en la RCP. No se encontraron diferencias significativas con el grupo control en cuanto a edad, sexo, tipo de donación, número de donaciones previas, antecedentes de transfusiones y comportamiento sexual. Se observaron diferencias significativas según los antecedentes de consumo de drogas no intravenosas (P < 0,05, y altamente significativas (P < 0,001 según los antecedentes de lactancia materna larga. Las madres estudiadas de seis de los donantes positivos que manifestaron haber tenido una larga lactancia materna resultaron positivas, al igual que el hijo mayor de la única pareja positiva de las 13 evaluadas. CONCLUSIONES. Se descartó el 0,2% de la sangre por resultar positiva al HTLV I/II. La prevalencia entre los donantes fue de 0,11%. En el 37,5% de los casos se pudo determinar la

Seropositividad al virus linfotrópico de células T humanas tipos I y II en donantes del Banco Municipal de Sangre de Caracas y factores de riesgo asociados

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León Graciela

2003-01-01

Full Text Available OBJETIVOS: Conocer la proporción de sangre descartada por seropositividad al virus linfotrópico de células T humanas (HTLV tipos I y II, la prevalencia de dicha infección y los probables factores de riesgo en donantes del Banco Municipal de Sangre de Caracas (BMSC. MÉTODOS: Se evaluaron serológicamente mediante ensayos de inmunoadsorción enzimática (ELISA 23 413 donantes atendidos entre julio del año 2000 y abril de 2001 en el BMSC. Las muestras repetidamente reactivas (RR se estudiaron por inmunoblot de Western (WB, como prueba suplementaria. Los donantes positivos o indeterminados por WB fueron citados a la consejería para realizar la confirmación mediante la amplificación de ácidos nucleicos por reacción en cadena de la polimerasa (PCR, recoger datos sobre sus antecedentes de riesgo y asesorarlos acerca de su estado. RESULTADOS. El 0,2% de las donaciones resultaron RR; de ellas 52,1% resultaron positivas en el WB (23 a HTLV I y 2 a HTLV II; 4,1% indeterminadas por WB; 29,2% negativas; y el 14,6% no pudo ser evaluado. Asistieron a la consejería 16 donantes (14 WB positivos a HTLV I, 1 a HTLV II y 1 indeterminado. Todos resultaron positivos en la RCP. No se encontraron diferencias significativas con el grupo control en cuanto a edad, sexo, tipo de donación, número de donaciones previas, antecedentes de transfusiones y comportamiento sexual. Se observaron diferencias significativas según los antecedentes de consumo de drogas no intravenosas (P < 0,05, y altamente significativas (P < 0,001 según los antecedentes de lactancia materna larga. Las madres estudiadas de seis de los donantes positivos que manifestaron haber tenido una larga lactancia materna resultaron positivas, al igual que el hijo mayor de la única pareja positiva de las 13 evaluadas. CONCLUSIONES. Se descartó el 0,2% de la sangre por resultar positiva al HTLV I/II. La prevalencia entre los donantes fue de 0,11%. En el 37,5% de los casos se pudo determinar la

In vitro activation of transcription by the human T-cell leukemia virus type I Tax protein.

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Matthews, M A; Markowitz, R B; Dynan, W S

1992-05-01

The human T-cell leukemia virus type I (HTLV-I) regulatory protein Tax activates transcription of the proviral long terminal repeats and a number of cellular promoters. We have developed an in vitro system to characterize the mechanism by which Tax interacts with the host cell transcription machinery. Tax was purified from cells infected with a baculovirus expression vector. Addition of these Tax preparations to nuclear extracts from uninfected human T lymphocytes activated transcription of the HTLV-I long terminal repeat approximately 10-fold. Transcription-stimulatory activity copurified with the immunoreactive 40-kDa Tax polypeptide on gel filtration chromatography, and, as expected, the effect of recombinant Tax was diminished in HTLV-I-infected T-lymphocyte extracts containing endogenous Tax. Tax-mediated transactivation in vivo has been previously shown to require 21-bp-repeat Tax-responsive elements (TxREs) in the promoter DNA. Stimulation of transcription in vitro was also strongly dependent on these sequences. To investigate the mechanism of Tax transactivation, cellular proteins that bind the 21-bp-repeat TxREs were prepared by DNA affinity chromatography. Recombinant Tax markedly increased the formation of a specific host protein-DNA complex detected in an electrophoretic mobility shift assay. These data suggest that Tax activates transcription through a direct interaction with cellular proteins that bind to the 21-bp-repeat TxREs.

Síndrome de Moebius associada a artrogripose: relato de caso e revisão da literatura

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Moreira Ana Tereza Ramos

2001-01-01

Full Text Available Os autores descrevem um caso de síndrome de Moebius associada a artogripose múltipla congênita, uma situação rara, sem relatos prévios na literatura latino-americana. A síndrome de Moebius é caracterizada por paralisia dos VII e VI pares cranianos, geralmente associada a outras anomalias ósseas e musculares, mais freqüentemente localizadas na parte distal das extremidades. A artrogripose múltipla congênita consiste de um grupo heterogêneo de alterações, sendo caracterizada por extrema rigidez e contratura das articulações, associada a hipoplasia ou ausência de desenvolvimento muscular e de tecidos moles. Pode ser parte de um complexo de anomalias congênitas multissistêmicas. Uma criança do sexo masculino, de cor branca, 3 anos, apresentava estrabismo convergente, oftalmoplegia, paralisia do VII par craniano e disgenesia da musculatura lingual, alterações compatíveis com a síndrome de Moebius. Associada às alterações oculares, foram encontradas alterações músculo-esqueléticas - mãos e antebraços em flexão e hipotrofia da cintura escapular - compatíveis com artrogripose. Foi realizado o tratamento cirúrgico do estrabismo com boa evolução pós-operatória. Sugerimos que, nos pacientes que apresentam síndrome de Moebius associada a alterações congênitas ósseas e musculares de extremidades, seja investigada a presença de artrogripose, pois acreditamos que tal síndrome não está sendo bem diagnosticada por ser pouco conhecida.

Ubiquitination of HTLV-I Tax in response to DNA damage regulates nuclear complex formation and nuclear export

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Marriott Susan J

2007-12-01

Full Text Available Abstract Background The HTLV-I oncoprotein, Tax, is a pleiotropic protein whose activity is partially regulated by its ability to interact with, and perturb the functions of, numerous cellular proteins. Tax is predominantly a nuclear protein that localizes to nuclear foci known as Tax Speckled Structures (TSS. We recently reported that the localization of Tax and its interactions with cellular proteins are altered in response to various forms of genotoxic and cellular stress. The level of cytoplasmic Tax increases in response to stress and this relocalization depends upon the interaction of Tax with CRM1. Cellular pathways and signals that regulate the subcellular localization of Tax remain to be determined. However, post-translational modifications including sumoylation and ubiquitination are known to influence the subcellular localization of Tax and its interactions with cellular proteins. The sumoylated form of Tax exists predominantly in the nucleus while ubiquitinated Tax exists predominantly in the cytoplasm. Therefore, we hypothesized that post-translational modifications of Tax that occur in response to DNA damage regulate the localization of Tax and its interactions with cellular proteins. Results We found a significant increase in mono-ubiquitination of Tax in response to UV irradiation. Mutation of specific lysine residues (K280 and K284 within Tax inhibited DNA damage-induced ubiquitination. In contrast to wild-type Tax, which undergoes transient nucleocytoplasmic shuttling in response to DNA damage, the K280 and K284 mutants were retained in nuclear foci following UV irradiation and remained co-localized with the cellular TSS protein, sc35. Conclusion This study demonstrates that the localization of Tax, and its interactions with cellular proteins, are dynamic following DNA damage and depend on the post-translational modification status of Tax. Specifically, DNA damage induces the ubiquitination of Tax at K280 and K284

Educação alimentar e nutricional associada a oficinas culinárias com alunos em uma escola pública

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Maria de Fátima Rezende

2015-12-01

Atividades em Educação Alimentar e Nutricional (EAN visam práticas alimentares saudáveis. Objetivo: desenvolver ações extensionistas em EAN a escolares. Método: trata-se de pesquisa participante em cinco encontros, pela abordagem de alimentos-tema, princípios de nutrição e de medidas higiênicas. Realizaram-se oficinas culinárias e diálogos sobre os conhecimentos adquiridos. As falas foram analisadas em categorias. Resultados: os escolares demonstraram interesse pela culinária, auxiliaram nas preparações e na higiene da cozinha. Sobre as aversões a alimentos, houve superação ao degustarem os pratos elaborados. Os conhecimentos sobre alimentação e nutrição foram valorizados. Conclui-se que o grupo se constituiu agregador e facilitador nas atividades em EAN associadas a oficinas culinárias, contribuindo à formação dos escolares.

Determinação de regiões de órbitas diretas estáveis ao redor da Lua

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de Melo, C. F.; Winter, O. C.; Vieira Neto, E.

2003-08-01

Neste Trabalho estamos investigando regiões do sistema Terra-Lua que contêm órbitas diretas estáveis ao redor da Lua visando a utilização destas órbitas em futuras missões de veículos espaciais como alternativas de trajetórias com baixo custo de manutenção. Adotando-se o problema restrito de três corpos, Terra-Lua-partícula, a localização e a extensão destas regiões de estabilidade foram investigadas numericamente considerando como estável toda órbita que permanece ao redor a Lua por, no mínimo, 1000 dias com energia de dois corpos da partícula em relação à Lua negativa. A estabilidade de tais regiões está associada a duas famílias de órbitas periódicas simples H1 e H2 e a órbitas quase-periódicas associadas a elas. Uma vez identificadas as regiões de estabilidade passamos a analisá-las introduzindo, paulatinamente, outras interações relevantes ao sistema como as perturbações do Sol (via problema restrito de quatro corpos), das marés, da pressão de radiação e do achatamento terrestre. Os resultados encontrados até o momento mostram que a perturbação do Sol é a única que reduz significativamente o tamanho das regiões de estabilidade. Também estamos investigando o comportamento de tais regiões quando características intrínsecas do sistema como as excentricidades das órbitas da Terra e da Lua e a inclinação da órbita Lua são consideradas. Com este estudo estamos reunindo informações que nos permitirão compreender a evolução das regiões de estabilidade no sistema Terra-Lua, bem como estabelecer parâmetros adequados para a utilização das trajetórias estáveis em futuras missões espaciais. Agradecimentos: Este projeto conta com o apoio do CNPq, da Capes e da Fapesp.

Effects of Physiotherapy in the Treatment of Neurogenic Bladder in Patients Infected with Human T-Lymphotropic Virus 1 (HTLV-1)

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Andrade, Rosana C.P.; Neto, José A.; Andrade, Luciana; Oliveira, Tatiane S. S.; Santos, Dislene N.; Oliveira, Cassius J.V.; Prado, Márcio J.; Carvalho, Edgar M.

2016-01-01

Objective To evaluate the efficacy of physiotherapy for urinary manifestations in patients with HTLV-1-associated lower urinary tract dysfunction. Methods Open clinical trial with 21 patients attending the physiotherapy clinic of the Hospital Universitário, Bahia, Brazil. Combinations of behavioral therapy, perineal exercises and intravaginal/intra-anal electrical stimulation were used. Results The mean age was 54±12 years and 67% were female. After treatment, there was an improvement in symptoms of urinary urgency, frequency, incontinence, nocturia and in the sensation of incomplete emptying (pPhysiotherapy was effective in cases of HTLV-1-associated neurogenic bladder, reducing symptoms, increasing perineal muscle strength, improving urodynamic parameters and quality of life. PMID:26724409

Adult T-cell leukemia/lymphoma associated with HTLV-1 infection in a Brazilian adolescent

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VALLE Antonio Carlos Francesconi do

2001-01-01

Full Text Available We present the case of a 15-year-old patient infected with HTLV-1 who developed a cutaneous T-cell lymphoma, confirmed by histopathological and immunohistochemical examination, as well as clinically and hematologically confirmed leukemia. The patient died 3 months after initial presentation of the disease. The rarity of the disease in this age group justifies the present report.

Surto de compactação primária de abomaso em bovinos leiteiros associado ao consumo de silagem de girassol

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Leonardo P. Mesquita

2012-06-01

Full Text Available Um surto de compactação primária de abomaso associada ao consumo de silagem de girassol ocorreu num rebanho bovino leiteiro do estado de Minas Gerais, do qual seis de 21 vacas secas em fase final de gestação e que recebiam silagem de girassol morreram. Os bovinos que adoeceram apresentaram distensão abdominal, fezes ressecadas e escassas e, nos bovinos que morreram, eram pastosas, escuras e fétidas; nesses havia também desidratação acentuada e palidez de mucosas. Três bovinos foram necropsiados e os achados patológicos eram constituídos principalmente por distensão acentuada do abomaso associada a grande quantidade de conteúdo alimentar ressecado coberto por coágulos de sangue. No abomaso havia úlceras, com perfuração da parede em um dos bovinos. A alimentação de bovinos de maior exigência nutricional com silagem de girassol de características indesejáveis como única fonte de volumoso foi o principal fator para a compactação de abomaso nos casos apresentados.

Acetylation of the c-MYC oncoprotein is required for cooperation with the HTLV-1 p30{sup II} accessory protein and the induction of oncogenic cellular transformation by p30{sup II}/c-MYC

Energy Technology Data Exchange (ETDEWEB)

Romeo, Megan M.; Ko, Bookyung; Kim, Janice; Brady, Rebecca; Heatley, Hayley C.; He, Jeffrey; Harrod, Carolyn K.; Barnett, Braden [Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX 75275-0376 (United States); Ratner, Lee [Departments of Medicine and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110 (United States); Lairmore, Michael D. [University of California-Davis, School of Veterinary Medicine, One Shields Avenue, Davis, CA 95618 (United States); Martinez, Ernest [Department of Biochemistry, University of California, Riverside, CA 92521 (United States); Lüscher, Bernhard [Institute of Biochemistry, Klinikum, RWTH Aachen University, Pauwelsstrasse 30, 52057 Aachen (Germany); Robson, Craig N. [Northern Institute for Cancer Research, Newcastle University, The Medical School, Newcastle upon Tyne, NE2 4HH (United Kingdom); Henriksson, Marie [Department of Microbiology, Cell and Tumor Biology, Karolinska Institutet, Stockholm (Sweden); Harrod, Robert, E-mail: rharrod@smu.edu [Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX 75275-0376 (United States)

2015-02-15

The human T-cell leukemia retrovirus type-1 (HTLV-1) p30{sup II} protein is a multifunctional latency-maintenance factor that negatively regulates viral gene expression and deregulates host signaling pathways involved in aberrant T-cell growth and proliferation. We have previously demonstrated that p30{sup II} interacts with the c-MYC oncoprotein and enhances c-MYC-dependent transcriptional and oncogenic functions. However, the molecular and biochemical events that mediate the cooperation between p30{sup II} and c-MYC remain to be completely understood. Herein we demonstrate that p30{sup II} induces lysine-acetylation of the c-MYC oncoprotein. Acetylation-defective c-MYC Lys→Arg substitution mutants are impaired for oncogenic transformation with p30{sup II} in c-myc{sup −/−} HO15.19 fibroblasts. Using dual-chromatin-immunoprecipitations (dual-ChIPs), we further demonstrate that p30{sup II} is present in c-MYC-containing nucleoprotein complexes in HTLV-1-transformed HuT-102 T-lymphocytes. Moreover, p30{sup II} inhibits apoptosis in proliferating cells expressing c-MYC under conditions of genotoxic stress. These findings suggest that c-MYC-acetylation is required for the cooperation between p30{sup II}/c-MYC which could promote proviral replication and contribute to HTLV-1-induced carcinogenesis. - Highlights: • Acetylation of c-MYC is required for oncogenic transformation by HTLV-1 p30{sup II}/c-MYC. • Acetylation-defective c-MYC mutants are impaired for foci-formation by p30{sup II}/c-MYC. • The HTLV-1 p30{sup II} protein induces lysine-acetylation of c-MYC. • p30{sup II} is present in c-MYC nucleoprotein complexes in HTLV-1-transformed T-cells. • HTLV-1 p30{sup II} inhibits apoptosis in c-MYC-expressing proliferating cells.

Ropivacaína isolada e associada ao fentanil ou ao tramadol administrados pela via peridural em cães Ropivacaine individually and in combination with fentanyl or tramadol, administered by peridural via in dogs

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Bruno Monteiro da Silva

2008-11-01

Full Text Available A anestesia peridural é amplamente difundida no meio veterinário, utilizando-se o anestésico local isolado ou associado aos opióides, capazes de promover aumento do efeito analgésico. O objetivo deste estudo foi avaliar a função cardiorrespiratória e analgésica da ropivacaína isolada ou associada ao fentanil ou tramadol. Para tanto, oito cães foram tranqüilizados com acepromazina, submetidos à anestesia peridural com um dos seguintes protocolos: GR (ropivacaína, GRF (ropivacaína + fentanil, GRT (ropivacaína + tramadol, em volume total de 0,25ml kg-1, e foram avaliados os parâmetros: freqüência cardíaca e respiratória, temperatura retal, pressão arterial sistólica, e gasometria do sangue arterial, os bloqueios sensitivo e motor, o grau de sedação e a ocorrência de possíveis efeitos indesejáveis. A diminuição da freqüência cardíaca nos grupos GRF e GRT foi mais intensa e ocorreu hipotermia significativa no GRF. Foi evidenciada sedação severa em GRF e GRT. O período de recuperação foi mais curto nos animais de GRT. O GRT foi o grupo que apresentou bloqueio mais cranial. Foram observadas bradicardia, hipotermia e síndrome de Shiff-Sherrington no período trans-anestésico em animais de todos os grupos. Nas 24 horas de período pós-anestésico, não foram evidenciados efeitos indesejáveis nos grupos. O GRF apresentou maior duração de anestesia e analgesia, enquanto que o GRT apresentou a menor duração de anestesia com analgesia intermediária e o GR apresentou duração intermediária, com menor analgesia. Não foram encontradas alterações respiratórias e hemogasométricas, porém, bradicardia, hipotermia e síndrome de Schiff-Sherrington, alterações trans-anestésicas comuns na anestesia peridural foram encontradas.Peridural anesthesia is broadly applied in the Veterinary field, using the isolated local anesthetic or in combination with opiates capable to increase the analgesic effect. This research

Two specific drugs, BMS-345541 and purvalanol A induce apoptosis of HTLV-1 infected cells through inhibition of the NF-kappaB and cell cycle pathways

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Wu Weilin

2008-06-01

Full Text Available Abstract Human T-cell leukemia virus type-1 (HTLV-1 induces adult T-cell leukemia/lymphoma (ATL/L, a fatal lymphoproliferative disorder, and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, a chronic progressive disease of the central nervous system after a long period of latent infection. Although the mechanism of transformation and leukemogenesis is not fully elucidated, there is evidence to suggest that the viral oncoprotein Tax plays a crucial role in these processes through the regulation of several pathways including NF-κB and the cell cycle pathways. The observation that NF-κB, which is strongly induced by Tax, is indispensable for the maintenance of the malignant phenotype of HTLV-1 by regulating the expression of various genes involved in cell cycle regulation and inhibition of apoptosis provides a possible molecular target for these infected cells. To develop potential new therapeutic strategies for HTLV-1 infected cells, in this present study, we initially screened a battery of NF-κB and CDK inhibitors (total of 35 compounds to examine their effects on the growth and survival of infected T-cell lines. Two drugs namely BMS-345541 and Purvalanol A exhibited higher levels of growth inhibition and apoptosis in infected cell as compared to uninfected cells. BMS-345541 inhibited IKKβ kinase activity from HTLV-1 infected cells with an IC50 (the 50% of inhibitory concentration value of 50 nM compared to 500 nM from control cells as measured by in vitro kinase assays. The effects of Purvalanol A were associated with suppression of CDK2/cyclin E complex activity as previously shown by us. Combination of both BMS-345541 and Purvalanol A showed a reduced level of HTLV-1 p19 Gag production in cell culture. The apparent apoptosis in these infected cells were associated with increased caspase-3 activity and PARP cleavage. The potent and selective apoptotic effects of these drugs suggest that both BMS-345541 and Purvalanol A

Two specific drugs, BMS-345541 and purvalanol A induce apoptosis of HTLV-1 infected cells through inhibition of the NF-kappaB and cell cycle pathways.

Science.gov (United States)

Agbottah, Emmanuel; Yeh, Wen-I; Berro, Reem; Klase, Zachary; Pedati, Caitlin; Kehn-Hall, Kyleen; Wu, Weilin; Kashanchi, Fatah

2008-06-10

Human T-cell leukemia virus type-1 (HTLV-1) induces adult T-cell leukemia/lymphoma (ATL/L), a fatal lymphoproliferative disorder, and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic progressive disease of the central nervous system after a long period of latent infection. Although the mechanism of transformation and leukemogenesis is not fully elucidated, there is evidence to suggest that the viral oncoprotein Tax plays a crucial role in these processes through the regulation of several pathways including NF-kappaB and the cell cycle pathways. The observation that NF-kappaB, which is strongly induced by Tax, is indispensable for the maintenance of the malignant phenotype of HTLV-1 by regulating the expression of various genes involved in cell cycle regulation and inhibition of apoptosis provides a possible molecular target for these infected cells. To develop potential new therapeutic strategies for HTLV-1 infected cells, in this present study, we initially screened a battery of NF-kappaB and CDK inhibitors (total of 35 compounds) to examine their effects on the growth and survival of infected T-cell lines. Two drugs namely BMS-345541 and Purvalanol A exhibited higher levels of growth inhibition and apoptosis in infected cell as compared to uninfected cells. BMS-345541 inhibited IKKbeta kinase activity from HTLV-1 infected cells with an IC50 (the 50% of inhibitory concentration) value of 50 nM compared to 500 nM from control cells as measured by in vitro kinase assays. The effects of Purvalanol A were associated with suppression of CDK2/cyclin E complex activity as previously shown by us. Combination of both BMS-345541 and Purvalanol A showed a reduced level of HTLV-1 p19 Gag production in cell culture. The apparent apoptosis in these infected cells were associated with increased caspase-3 activity and PARP cleavage. The potent and selective apoptotic effects of these drugs suggest that both BMS-345541 and Purvalanol A, which target

Organizaçao e funcionamento duma casa de abrigo de solidariedade social

Directory of Open Access Journals (Sweden)

Maria Jose Magalhaes

2011-12-01

Full Text Available A organização e o funcionamento de uma casa de abrigo de uma instituição humanista não feminista (chamada de "Solidariedade Social" constituiu o foco central desta pesquisa. Para isto, realizaram-se entrevistas semi-estruturadas às profissionais: à diretora da instituição, à diretora técnica e ao psicólogo. A análise apresenta uma visão de uma casa de abrigo normativa sobre o que deve ser uma mulher, incluindo as suas rotinas diárias, associada a uma organização rígida no que diz respeito a regras e horários. Mais ainda, perspectivando a mulher apenas como mãe e doméstica, esta perspectiva apresenta uma elevada tolerância à violência de gênero. A este respeito, este tipo de instituições corre sério risco de cair na perspectiva de "revitimizar" a vítima.

Kefir induces cell-cycle arrest and apoptosis in HTLV-1-negative malignant T-lymphocytes

Science.gov (United States)

Maalouf, Katia; Baydoun, Elias; Rizk, Sandra

2011-01-01

Background: Adult lymphoblastic leukemia (ALL) is a malignancy that occurs in white blood cells. The overall cure rate in children is 85%, whereas it is only 40% in adults. Kefir is an important probiotic that contains many bioactive ingredients, which give it unique health benefits. It has been shown to control several cellular types of cancer. Purpose: The present study investigates the effect of a cell-free fraction of kefir on CEM and Jurkat cells, which are human T-lymphotropic virus type I (HTLV-1)-negative malignant T-lymphocytes. Methods: Cells were incubated with different kefir concentrations. The cytotoxicity of the compound was evaluated by determining the percentage viability of cells. The effect of all the noncytotoxic concentrations of kefir on the proliferation of CEM and Jurkat cells was then assessed. The levels of transforming growth factor-alpha (TGF-α), transforming growth factor- beta1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and MMP-9 mRNA upon kefir treatment were then analyzed using reverse transcriptase polymerase chain reaction (RT-PCR). Finally, the growth inhibitory effects of kefir on cell-cycle progression/apoptosis were assessed by Cell Death Detection (ELISA) and flow cytometry. Results: The maximum cytotoxicity recorded after 48-hours treatment with 80 μg/μL kefir was only 42% and 39% in CEM and Jurkat cells, respectively. The percent reduction in proliferation was very significant, and was dose-, and time-dependent. In both cell lines, kefir exhibited its antiproliferative effect by downregulating TGF-α and upregulating TGF-β1 mRNA expression. Upon kefir treatment, a marked increase in cell-cycle distribution was noted in the preG1 phase of CEM and Jurkat cells, indicating the proapoptotic effect of kefir, which was further confirmed by Cell Death Detection ELISA. However, kefir did not affect the mRNA expression of metalloproteinases needed for the invasion of leukemic cell lines. Conclusion: In conclusion, kefir is

Kefir induces cell-cycle arrest and apoptosis in HTLV-1-negative malignant T-lymphocytes

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