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Marina Lobato Martins, Jacqueline Cronemberger Guimarães, João Gabriel Ribas, Luiz Cláudio Ferreira Romanelli, Anna Bárbara de Freitas Carneiro-Proietti
HTLV-1 proviral load (pvl) is an important risk marker for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but its value as prognostic marker is not well defined. Long-term prospective cohort studies are necessary to clarify this question. Here, we analyzed HTLV-1 pvl in the peripheral blood of 82 asymptomatic carriers (AC; 351 samples), 12 HAM/TSP patients (HAM; 46 samples), and six incident cases of HAM/TSP (iHAM), with serial samples collected before (n = 10) and after (n = 20) the disease onset...
September 27, 2016: Journal of Neurovirology
Jason Rosado, Sandra Morales, Giovanni Lopez, Daniel Clark, Kristien Verdonck, Eduardo Gotuzzo, Guy Van Camp, Michael Talledo
BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) is the etiologic agent of the HTLV-I-Associated Myelopathy-Tropical Spastic Paraparesis (HAM/TSP). Apoptosis is a mechanism of defense elicited by many triggers, including cross-linking of the FAS receptor expressed in viruses-infected cells, and the ligand FASL presented by T-cytotoxic cells. Since HAM/TSP has been associated with high levels of proviral load (PVL), we hypothesized that certain genotypes of single-nucleotide polymorphisms (SNPs) associated with a decreased protein expression of FAS and FASL could be risk factors for this disease...
September 7, 2016: Journal of Medical Virology
Fernanda Khouri Barreto, Ricardo Khouri, Filipe Ferreira de Almeida Rego, Luciane Amorim Santos, Maria Fernanda de Castro-Amarante, Izabela Bialuk, Cynthia A Pise-Masison, Bernardo Galvão-Castro, Antoine Gessain, Steven Jacobson, Genoveffa Franchini, Luiz Carlos Alcantara
The region known as pX in the 3' end of the human T-cell lymphotropic virus type 1 (HTLV-1) genome contains four overlapping open reading frames (ORF) that encode regulatory proteins. HTLV-1 ORF-I produces the protein p12 and its cleavage product p8. The functions of these proteins have been linked to immune evasion and viral infectivity and persistence. It is known that the HTLV-1 infection does not necessarily imply the development of pathological processes and here we evaluated whether natural mutations in HTLV-1 ORF-I can influence the proviral load and clinical manifestation of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)...
August 21, 2016: Infection, Genetics and Evolution
Yoshihisa Yamano, Ariella Coler-Reilly
The main feature of Human T-lymphotropic virus type I (HTLV-1) -associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis is a virus-induced hyperactive immune response that produces chronic inflammation in the central nervous system (CNS), but the mechanism by which HTLV-1 deregulates the immune response is unknown. We recently reported a high frequency of HTLV-1-infected CCR4(+) cells, including regulatory T cells. We showed that HTLV-1 induces a Th1-like state in these CCR4(+) cells via T-bet expression...
August 12, 2016: Journal of Neuroimmunology
Yoshimi Enose-Akahata, Breanna Caruso, Benjamin Haner, Emily Charlip, Govind Nair, Raya Massoud, Bridgette J Billioux, Joan Ohayon, William M Switzer, Steven Jacobson
BACKGROUND: Virus transmission from various wild and domestic animals contributes to an increased risk of emerging infectious diseases in human populations. HTLV-1 is a human retrovirus associated with acute T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 originated from ancient zoonotic transmission from nonhuman primates, although cases of zoonotic infections continue to occur. Similar to HTLV-1, the simian counterpart, STLV-1, causes chronic infection and leukemia and lymphoma in naturally infected monkeys, and combined are called primate T-lymphotropic viruses (PTLV-1)...
2016: Retrovirology
Michael C Levin, Sangmin Lee, Lidia A Gardner, Yoojin Shin, Joshua N Douglas, Hannah Salapa
Several years following its discovery in 1980, infection with human T-lymphotropic virus type 1 (HTLV-1) was shown to cause HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease biologically similar to progressive forms of multiple sclerosis (MS). In this manuscript, we review some of the clinical, pathological, and immunological similarities between HAM/TSP and MS with an emphasis on how autoantibodies to an RNA binding protein, heterogeneous nuclear ribonuclear protein A1 (hnRNP A1), might contribute to neurodegeneration in immune mediated diseases of the central nervous system...
July 17, 2016: Journal of Neuroimmunology
Daiani Cristina Cilião Alves, Rodrigo Haddad, Maurício Cristiano Rocha-Júnior, Virgínia Mara de Deus Wagatsuma, Gustavo Martelli-Palomino, Adriana Aparecida Marques, Osvaldo Massaiti Takayanagui, Dimas Tadeu Covas, Simone Kashima, Eduardo Antônio Donadi
Most HTLV-1-infected patients remain asymptomatic throughout life. The factors associated with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development have not been fully elucidated; immunological and genetic factors may be involved. It was previously reported the association of the 14-base pair INS/DEL HLA-G polymorphism on HTLV-1 infection susceptibility. Here, other polymorphic sites at the HLA-G 3´untranslate region (14-bp D/I, +3003C/T, +3010C/G, +3027A/C, +3035C/T, +3142C/G, +3187A/G and +3196C/G) were evaluated in 37 HTLV-1-infected individuals exhibiting HAM/TSP, 45 HTLV-1 asymptomatic carriers (HAC) and 153 uninfected individuals, followed-up at University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil...
July 22, 2016: Journal of General Virology
Reza Boostani, Ali Poorzahed, Zahra Ahmadi, Ali Mellat
INTRODUCTION: HTLV-I Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a progressive Myelopathy that mainly involves the corticospinal tract. Despite pronounced involvement of the lower limbs, patients also have abnormalities in their upper limbs. So, we studied somatosensory-evoked potentials (SSEPs) of the median nerve in HAM/TSP patients to determine the extent of the involvement of the pathway of the central nervous system, especially the cervical spinal cord. METHODS: In this cross sectional study, 48 patients with HAM/TSP who were referred to Qaem Hospital in Mashhad from October 2010 to October 2011 were evaluated for various indices, including SSEPs of the median nerve for N9, N11, N13, and N20 waveforms and also N11-13 and N13-20 Inter Peak Latency (IPL), severity of disease (based on Osama criteria), disease duration (less or more than 2 years), age, and gender...
May 2016: Electronic Physician
Paola Miyazato, Misaki Matsuo, Hiroo Katsuya, Yorifumi Satou
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...
2016: Viruses
Natsumi Araya, Tomoo Sato, Ariella Coler-Reilly, Naoko Yagishita, Yoshihisa Yamano
  A small percentage of those infected with human T-lymphotropic virus type 1 (HTLV-1) develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a debilitating neurodegenerative disease. This disease impacts essential bodily functions, and since currently available treatments are considered to be poorly effective, there is a dire need to develop a truly effective treatment to suppress disease progression. Recently, the authors and others have determined that HTLV-1 in HAM/TSP patients primarily infects T cells expressing the chemokine receptor CCR4...
2016: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
Maria Jose Montesdeoca Andrade, Edgar Patricio Correa Diaz, Maria Eugenia Buestán
Human T-cell lymphotropic virus type-1 (HTLV-1) is endemic in Japan, the Caribbean and in South American countries such as Ecuador. This virus is the cause of HTLV-1-associated myelopathy or tropical spastic paraparesis (HAM/TSP), a myelopathy characterised by chronic progressive paraparesis, spasticity and urinary symptoms. We report the case of a 40-year-old man who received a kidney transplant from a living donor and developed HAM/TSP, 24 months after transplant. The diagnosis was confirmed by detection of HTLV-1 in blood and cerebrospinal fluid by the ELISA and Western Blot tests...
June 6, 2016: BMJ Case Reports
Ariella L G Coler-Reilly, Naoko Yagishita, Hiroko Suzuki, Tomoo Sato, Natsumi Araya, Eisuke Inoue, Ayako Takata, Yoshihisa Yamano
BACKGROUND: At least one million people are infected with human T-lymphotropic virus type 1 (HTLV-1) in Japan, a small percentage of whom develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T-cell leukemia/lymphoma (ATLL). Patients with HAM/TSP suffer from progressively worsening myelopathic symptoms, such as motor disability and bladder dysfunction, and may become wheelchair-bound or even bedridden. METHODS: To learn more about this rare, debilitating disease, we established the national registration system "HAM-net" in March 2012...
2016: Orphanet Journal of Rare Diseases
Yasuo Shiohama, Tadasuke Naito, Toshio Matsuzaki, Reiko Tanaka, Takeaki Tomoyose, Hiroshi Takashima, Takuya Fukushima, Yuetsu Tanaka, Mineki Saito
BACKGROUND: Human T cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ), which is encoded by a minus strand mRNA, is thought to play important roles in the development of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, a comprehensive analysis of HBZ, including mRNA and protein expression, humoral immunoreactivity against HBZ, and HTLV-1 proviral load (PVL), in HTLV-1-infected individuals with different clinical status has not been reported previously...
2016: Retrovirology
Kevin G Buell, Aiysha Puri, Maria Antonietta Demontis, Charlotte L Short, Adine Adonis, Jana Haddow, Fabiola Martin, Divya Dhasmana, Graham P Taylor
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an immune mediated myelopathy caused by the human T-lymphotropic virus type 1 (HTLV-1). The efficacy of treatments used for patients with HAM/TSP is uncertain. The aim of this study is to document the efficacy of pulsed methylprednisolone in patients with HAM/TSP. Data from an open cohort of 26 patients with HAM/TSP was retrospectively analysed. 1g IV methylprednisolone was infused on three consecutive days. The outcomes were pain, gait, urinary frequency and nocturia, a range of inflammatory markers and HTLV-1 proviral load...
2016: PloS One
Lorena A Pinto, Cássio S Meira, Cristiane F Villarreal, Marcos A Vannier-Santos, Claudia V C de Souza, Ivone M Ribeiro, Therezinha C B Tomassini, Bernardo Galvão-Castro, Milena B P Soares, Maria F R Grassi
Human T-lymphotropic virus type 1 (HTLV-1) induces a strong activation of the immune system, especially in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Physalin F is a secosteroid with potent anti-inflammatory and immunomodulatory activities. The present study aimed to investigate the effects of physalin F on peripheral blood mononuclear cells (PBMC) of HAM/TSP subjects. A concentration-dependent inhibition of spontaneous proliferation of PBMC from HAM/TSP subjects was observed in the presence of physalin F, as evaluated by (3)H-thymidine uptake...
April 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Patience Uchenna Tweteise, Bernard Natukunda, Joel Bazira
Background. The human T-cell lymphotropic virus types 1 and 2 (HTLV 1/2) are retroviruses associated with different pathologies. HTLV-1 causes adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP); HTLV-2 is not clearly associated with a known clinical disease. Both viruses may be transmitted by whole blood transfusion, from mother to child predominantly through breastfeeding, and by sexual contact. Presently, none of the regional blood banks in Uganda perform routine pretransfusion screening for HTLV...
2016: Leukemia Research and Treatment
Beatriz Helena B Vasconcelos, Givago S Souza, Tatiana G C P Barroso, Luiz Carlos L Silveira, Rita Catarina M Sousa, Bianca Callegari, Marília B Xavier
BACKGROUND: The human T-Cell Lymphotropic Virus Type 1 (HTLV-1) is a retrovirus associated with neurological alterations; individuals with HTLV-1 infection may develop HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP). Frequent neurological complaints include foot numbness and leg weakness. In this study, we compared the distribution of the body weight on different areas of the foot in HTLV-1 patients with HAM/TSP, asymptomatic HTLV-1 patients, and healthy individuals...
2016: PloS One
James M Fox, Silva Hilburn, Maria-Antonietta Demontis, David W Brighty, Maria Fernanda Rios Grassi, Bernardo Galvão-Castro, Graham P Taylor, Fabiola Martin
Clonal expansion of human T-lymphotropic virus type-1 (HTLV-1) infected cells in vivo is well documented. Unlike human immunodeficiency virus type 1 (HIV-1), HTLV-1 plasma RNA is sparse. The contribution of the "mitotic" spread of HTLV-1 compared with infectious spread of the virus to HTLV-1 viral burden in established infection is uncertain. Since extrachromosomal long terminal repeat (LTR) DNA circles are indicators of viral replication in HIV-1 carriers with undetectable plasma HIV RNA, we hypothesised that HTLV-1 LTR circles could indicate reverse transcriptase (RT) usage and infectious activity...
March 2016: Viruses
Florent Percher, Patricia Jeannin, Sandra Martin-Latil, Antoine Gessain, Philippe V Afonso, Aurore Vidy-Roche, Pierre-Emmanuel Ceccaldi
Human T-cell Lymphotropic Virus type 1 (HTLV-1) is a human retrovirus that infects at least 5-10 million people worldwide, and is the etiological agent of a lymphoproliferative malignancy; Adult T-cell Leukemia/Lymphoma (ATLL); and a chronic neuromyelopathy, HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), as well as other inflammatory diseases such as infective dermatitis and uveitis. Besides sexual intercourse and intravenous transmission, HTLV-1 can also be transmitted from infected mother to child during prolonged breastfeeding...
February 2016: Viruses
Jessica L Martin, José O Maldonado, Joachim D Mueller, Wei Zhang, Louis M Mansky
Human T-cell leukemia virus type 1 (HTLV-1) was the first human retrovirus discovered. Studies on HTLV-1 have been instrumental for our understanding of the molecular pathology of virus-induced cancers. HTLV-1 is the etiological agent of an adult T-cell leukemia (ATL) and can lead to a variety of neurological pathologies, including HTLV-1-associated-myelopathy/tropical spastic paraparesis (HAM/TSP). The ability to treat the aggressive ATL subtypes remains inadequate. HTLV-1 replicates by (1) an infectious cycle involving virus budding and infection of new permissive target cells and (2) mitotic division of cells harboring an integrated provirus...
February 2016: Viruses
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