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Steven Jacobson - One of the best experts on this subject based on the ideXlab platform.
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human t lymphotropic virus type 1 htlv 1 and cellular immune response in htlv 1 associated myelopathy Tropical Spastic Paraparesis
Journal of NeuroVirology, 2020Co-Authors: Satoshi Nozuma, Ryuji Kubota, Steven JacobsonAbstract:Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T cell leukemia/lymphoma and HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HAM/TSP is an inflammatory disease of the spinal cord and clinically characterized by progressive Spastic Paraparesis, urinary incontinence, and mild sensory disturbance. The interaction between the host immune response and HTLV-1-infected cells regulates the development of HAM/TSP. HTLV-1 preferentially infects CD4+ T cells and is maintained by proliferation of the infected T cells. HTLV-1-infected cells rarely express viral antigens in vivo; however, they easily express the antigens after short-term culture. Therefore, such virus-expressing cells may lead to activation and expansion of antigen-specific T cell responses. Infected T cells with HTLV-1 and HTLV-1-specific CD8+ cytotoxic T lymphocytes invade the central nervous system and produce various proinflammatory cytokines and chemokines, leading to neuronal damage and degeneration. Therefore, cellular immune responses to HTLV-1 have been considered to play important roles in disease development of HAM/TSP. Recent studies have clarified the viral strategy for persistence in the host through genetic and epigenetic changes by HTLV-1 and host immune responses including T cell function and differentiation. Newly developed animal models could provide the opportunity to uncover the precise pathogenesis and development of clinically effective treatment. Several molecular target drugs are undergoing clinical trials with promising efficacy. In this review, we summarize recent advances in the immunopathogenesis of HAM/TSP and discuss the perspectives of the research on this disease.
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immunovirological markers in htlv 1 associated myelopathy Tropical Spastic Paraparesis ham tsp
Retrovirology, 2019Co-Authors: Yoshimi Enoseakahata, Steven JacobsonAbstract:Human T cell lymphotropic virus 1 (HTLV-1) is a human retrovirus and infects approximately 10–20 million people worldwide. While the majority of infected people are asymptomatic carriers of HTLV-1, only 4% of infected people develop HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HAM/TSP is a chronic, progressive, neurological disease which usually progresses slowly without remission, and is characterized by perivascular inflammatory infiltrates in chronic inflammatory lesions of the central nervous system (CNS), primarily affecting the spinal cord. A high HTLV-1 proviral load, high levels of antibodies against HTLV-1 antigens, and elevated concentration of proteins are detected in cerebrospinal fluid (CSF) of HAM/TSP patients. These chronically activated immune responses against HTLV-1 and infiltration of inflammatory cells including HTLV-1 infected cells into the CNS contribute to clinical disability and underlie the pathogenesis of HAM/TSP. Since the disease development of HAM/TSP mainly occurs in adults, with a mean age at onset of 40–50 years, it is important for HTLV-1-infected carriers and HAM/TSP patients to be monitored throughout the disease process. Recent advances in technologies and findings provide new insights to virological and immunological aspects in both the CNS as well as in peripheral blood. In this review, we focus on understanding the inflammatory milieu in the CNS and discuss the immunopathogenic process in HTLV-1-associated neurologic diseases.
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neuroimmunology of human t lymphotropic virus type 1 associated myelopathy Tropical Spastic Paraparesis
Frontiers in Microbiology, 2019Co-Authors: Satoshi Nozuma, Steven JacobsonAbstract:Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent of both adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HAM/TSP is clinically characterized by chronic progressive Spastic Paraparesis, urinary incontinence, and mild sensory disturbance. Given its well-characterized clinical presentation and pathophysiology, which is similar to the progressive forms of multiple sclerosis (MS), HAM/TSP is an ideal system to better understand other neuroimmunological disorders such as MS. Since the discovery of HAM/TSP, large numbers of clinical, virological, molecular, and immunological studies have been published. The host-virus interaction and host immune response play an important role for the development with HAM/TSP. HTLV-1-infected circulating T-cells invade the central nervous system (CNS) and cause an immunopathogenic response against virus and possibly components of the CNS. Neural damage and subsequent degeneration can cause severe disability in patients with HAM/TSP. Little progress has been made in the discovery of objective biomarkers for grading stages and predicting progression of disease and the development of molecular targeted therapy based on the underlying pathological mechanisms. We review the recent understanding of immunopathological mechanism of HAM/TSP and discuss the unmet need for research on this disease.
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Neuroimmunology of Human T-Lymphotropic Virus Type 1-Associated Myelopathy/Tropical Spastic Paraparesis
Frontiers Media S.A., 2019Co-Authors: Satoshi Nozuma, Steven JacobsonAbstract:Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent of both adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HAM/TSP is clinically characterized by chronic progressive Spastic Paraparesis, urinary incontinence, and mild sensory disturbance. Given its well-characterized clinical presentation and pathophysiology, which is similar to the progressive forms of multiple sclerosis (MS), HAM/TSP is an ideal system to better understand other neuroimmunological disorders such as MS. Since the discovery of HAM/TSP, large numbers of clinical, virological, molecular, and immunological studies have been published. The host-virus interaction and host immune response play an important role for the development with HAM/TSP. HTLV-1-infected circulating T-cells invade the central nervous system (CNS) and cause an immunopathogenic response against virus and possibly components of the CNS. Neural damage and subsequent degeneration can cause severe disability in patients with HAM/TSP. Little progress has been made in the discovery of objective biomarkers for grading stages and predicting progression of disease and the development of molecular targeted therapy based on the underlying pathological mechanisms. We review the recent understanding of immunopathological mechanism of HAM/TSP and discuss the unmet need for research on this disease
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common γ chain blocking peptide reduces in vitro immune activation markers in htlv 1 associated myelopathy Tropical Spastic Paraparesis
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Raya Massoud, Yoshimi Enoseakahata, Yutaka Tagaya, Nazli Azimi, Asjad Basheer, Steven JacobsonAbstract:Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a progressive inflammatory myelopathy occurring in a subset of HTLV-1-infected individuals. Despite advances in understanding its immunopathogenesis, an effective treatment remains to be found. IL-2 and IL-15, members of the gamma chain (γc) family of cytokines, are prominently deregulated in HAM/TSP and underlie many of the characteristic immune abnormalities, such as spontaneous lymphocyte proliferation (SP), increased STAT5 phosphorylation in the lymphocytes, and increased frequency and cytotoxicity of virus-specific cytotoxic CD8(+) T lymphocytes (CTLs). In this study, we describe a novel immunomodulatory strategy consisting of selective blockade of certain γc family cytokines, including IL-2 and IL-15, with a γc antagonistic peptide. In vitro, a PEGylated form of the peptide, named BNZ132-1-40, reduced multiple immune activation markers such as SP, STAT5 phosphorylation, spontaneous degranulation of CD8(+) T cells, and the frequency of transactivator protein (Tax)-specific CD8(+) CTLs, thought to be major players in the immunopathogenesis of the disease. This strategy is thus a promising therapeutic approach to HAM/TSP with the potential of being more effective than single monoclonal antibodies targeting either IL-2 or IL-15 receptors and safer than inhibitors of downstream signaling molecules such as JAK1 inhibitors. Finally, selective cytokine blockade with antagonistic peptides might be applicable to multiple other conditions in which cytokines are pathogenic.
Shuji Izumo - One of the best experts on this subject based on the ideXlab platform.
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Multiple spotty lesions of the spinal cord in a Chinese patient with human T-lymphotropic virus type 1-associated myelopathy/Tropical Spastic Paraparesis
Elsevier, 2018Co-Authors: Hongzhi Gao, Shuji Izumo, Ruowei Cai, Liping Liang, Hui Qin Xing, Ryuji KubotaAbstract:The case of a Chinese patient with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP), who showed typical neurological symptoms of the disease, is reported here. Since the presence of anti-HTLV-1 antibody was not investigated, this patient’s diagnosis of HAM/TSP was delayed for 4 years. Magnetic resonance imaging revealed multiple spotty lesions in the cervical spinal cord, probably reflecting pathological changes known as perivascular lymphocytic infiltrations of the spinal cord. As this is the first case report of a HAM/TSP patient in China, it is suggested that serological testing for HTLV-1 should be considered in patients with Spastic Paraparesis even in areas that are non-endemic for HTLV-1. Keywords: HTLV-1, HAM/TSP, China, MRI, Multiple spotty lesion
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htlv 1 associated myelopathy Tropical Spastic Paraparesis ham tsp a comparative study to identify factors that influence disease progression
Journal of the Neurological Sciences, 2016Co-Authors: Eiji Matsuura, Ryuji Kubota, Shuji Izumo, Satoshi Nozuma, Yuichi Tashiro, Hiroshi TakashimaAbstract:Abstract Objective HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) can progress slowly or rapidly even though a set of symptoms such as Spastic Paraparesis with pathological reflexes and sweating loss of the lower extremities are commonly observed in patients. Although most of the patients are thought to be infected to HTLV-1 from their mothers by breast feeding, symptoms of HAM/TSP typically manifest in patients later in life (50–60 years old in age) and also with a higher prevalence of women to men at a ratio of approximately 3:1. Probability of developing HAM/TSP and how fast an individual's disease may progress from the time of diagnosis could be multifactorial. Methods We reviewed the records of 150 patients with HAM/TSP admitted to Kagoshima University Hospital between 2002 and 2014. Laboratory data of cerebrospinal fluid and serum and the clinical measurements including age, age of disease onset, progression rate, duration of illness, initial symptoms, Osame's Motor Disability Score were evaluated. Rapid disease progression of the disease was defined by deterioration of motor disability by > 3 grades within 2 years. Results Of 150 HAM/TSP patients in our cohort, 114 cases (76%) were females. Patients presenting with rapid disease progression are approximately 15 years older at the age of onset than those with a protracted disease course, and have increased number of cell, and elevated levels of protein as well as anti-HTLV-1 antibody titer in the CSF, suggesting a more active inflammatory process. There is no significant difference in the average values of clinical and laboratory parameters between the sexes. Furthermore, there is no apparent correlation between rate of disease progression and gender. Conclusions Our results suggest that age and virus mediated inflammation are correlated with disease phenotypes while additional factors such as host or HTLV-1 genetics and gender may influence disease susceptibility.
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visualization of htlv 1 specific cytotoxic t lymphocytes in the spinal cords of patients with htlv 1 associated myelopathy Tropical Spastic Paraparesis
Journal of Neuropathology and Experimental Neurology, 2015Co-Authors: Eiji Matsuura, Ryuji Kubota, Hiroshi Takashima, Yuetsu Tanaka, Shuji IzumoAbstract:Activated human T-lymphotropic virus type-1 (HTLV-1)–specific CD8-positive cytotoxic T lymphocytes (CTLs) are markedly increased in the periphery of patients with HTLV-1–associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP), an HTLV-1–induced inflammatory disease of the CNS. Although virus-specific CTLs play a pivotal role to eliminate virus-infected cells, the potential role of HTLV-1–specific CTLs in the pathogenesis of HAM/TSP remains unclear. To address this issue, we evaluated the infiltration of HTLV-1–specific CTLs and the expression of HTLV-1 proteins in the spinal cords of 3 patients with HAM/TSP. Confocal laser scanning microscopy with our unique staining procedure made it possible to visualize HTLV-1–specific CTLs infiltrating the CNS of the HAM/TSP patients. The frequency of HTLV-1–specific CTLs was more than 20% of CD8-positive cells infiltrating the CNS. In addition, HTLV-1 proteins were detected in CD4-positive infiltrating T lymphocytes but not CNS resident cells. Although neurons were generally preserved, apoptotic oligodendrocytes were frequently in contact with CD8-positive cells; this likely resulted in demyelination. These findings suggest that the immune responses of the CTLs against HTLV-1–infected CD4-positive lymphocytes migrating into the CNS resulted in bystander neural damage.
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familial clusters of htlv 1 associated myelopathy Tropical Spastic Paraparesis
PLOS ONE, 2014Co-Authors: Satoshi Nozuma, Toshio Matsuzaki, Ryuji Kubota, Shuji Izumo, Eiji Matsuura, Osamu Watanabe, Hiroshi TakashimaAbstract:Objective HTLV-1 proviral loads (PVLs) and some genetic factors are reported to be associated with the development of HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). However, there are very few reports on HAM/TSP having family history. We aimed to define the clinical features and laboratory indications associated with HAM/TSP having family history. Methods Records of 784 HAM/TSP patients who were hospitalized in Kagoshima University Hospital and related hospitals from 1987 to 2012 were reviewed. Using an unmatched case-control design, 40 patients of HAM/TSP having family history (f-HAM/TSP) were compared with 124 patients suffering from sporadic HAM/TSP, who were admitted in series over the last 10 years for associated clinical features. Results Of the 784 patients, 40 (5.1%) were f-HAM/TSP cases. Compared with sporadic cases, the age of onset was earlier (41.3 vs. 51.6 years, p<0.001), motor disability grades were lower (4.0 vs. 4.9, p = 0.043) despite longer duration of illness (14.3 vs. 10.2 years, p = 0.026), time elapsed between onset and wheelchair use in daily life was longer (18.3 vs. 10.0 years, p = 0.025), cases with rapid disease progression were fewer (10.0% vs. 28.2%, p = 0.019), and protein levels in cerebrospinal fluid (CSF) were significantly lower in f-HAM/TSP cases (29.9 vs. 42.5 mg, p<0.001). There was no difference in HTLV-1 PVLs, anti-HTLV-1 antibody titers in serum and CSF, or cell number and neopterin levels in CSF. Furthermore, HTLV-1 PVLs were lower in cases with rapid disease progression than in those with slow progression in both f-HAM/TSP and sporadic cases. Conclusions We demonstrated that HAM/TSP aggregates in the family, with a younger age of onset and a slow rate of progression in f-HAM/TSP cases compared with sporadic cases. These data also suggested that factors other than HTLV-1 PVLs contribute to the disease course of HAM/TSP.
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cxcl10 and neopterin in csf are candidate prognostic biomarkers for htlv 1 associated myelopathy Tropical Spastic Paraparesis
Retrovirology, 2014Co-Authors: Yoshihisa Yamano, Ariella Colerreilly, Tomoo Sato, Steven Jacobson, Naoko Yagishita, Junji Yamauchi, Natsumi Araya, Atae Utsunomiya, Hitoshi Ando, Shuji IzumoAbstract:Human T-lymphotropic virus type 1 (HTLV-1) -associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a chronic neuroinflammatory disease. Since the disease course of HAM/TSP varies among patients, there is a dire need for biomarkers capable of predicting the rate of disease progression for earlier detection of high-risk patients. However, there have been no studies to date that have compared the prognostic values of multiple potential biomarkers for HAM/TSP. Peripheral blood and cerebrospinal fluid (CSF) samples from HAM/TSP patients and HTLV-1-infected control subjects were obtained and tested for several potential biomarkers, including chemokines and other cytokines, and 8 optimal candidates were selected based on receiver operating characteristic (ROC) analysis. Next, we evaluated the relationship between these candidates and the rate of disease progression in HAM/TSP patients, beginning with a Training Set of 30 patients and proceeding to a Test Set of 23 patients. We defined “deteriorating HAM/TSP” as distinctly worsening function (≥ 3 grades on Osame’s Motor Disability Score (OMDS)) over 4 y and “stable HAM/TSP” as unchanged or only slightly worsened function (1 grade on OMDS) over 4 y, and we compared the levels of the candidate biomarkers in patients divided into these 2 groups. The CSF levels of chemokine (C-X-C motif) ligand 10 (CXCL10), neopterin and the CSF cell count were well-correlated with disease progression, better even than HTLV-1 proviral load in PBMCs. Importantly, these results were cross-validated using the Test Set. Therefore, the CSF levels of CXCL10 and neopterin represent the most viable candidates for HAM/TSP prognostic biomarkers.
Abelardo Q.-c. Araújo - One of the best experts on this subject based on the ideXlab platform.
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polymorphisms in htlv 1 tax responsive elements in htlv 1 associated myelopathy Tropical Spastic Paraparesis patients are associated with reduced proviral load but not with disease progression
Journal of General Virology, 2021Co-Authors: Yago Cortes Pinheiro Gomes, Abelardo Q.-c. Araújo, Marcus Tulius T Silva, Ana Claudia Celestino Bezerra Leite, Marco A Lima, Isaac Lima Silva Filho, Ana Carolina Paulo Vicente, Otavio De Melo EspindolaAbstract:Human T-lymphotropic virus type 1 (HTLV-1) provirus expression is mainly directed by Tax-responsive elements (TRE) within the long terminal repeats (LTR). Mutations in TRE can reduce provirus expression and since a high proviral load (PVL) is a risk factor for the development of HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP), we evaluated polymorphisms in the 5' LTR and the association with PVL and disease progression. HTLV-1 LTR and tax sequences derived from asymptomatic carriers (AC) and HAM/TSP patients followed in a longitudinal study were analysed according to PVL and clinical severity. Individuals infected with HTLV-1 presenting the canonical TRE, considering strain ATK-1 as the consensus, displayed sustained higher PVL. By contrast, an LTR A125G mutation in TRE was associated with slightly reduced PVL only in HAM/TSP patients, although it did not influence the speed of disease progression. Moreover, this polymorphism was frequent in Latin American strains of the HTLV-1 Cosmopolitan Transcontinental subtype. Therefore, polymorphisms in the 5' TRE of HTLV-1 may represent one of the factors influencing PVL in HAM/TSP patients, especially in the Latin American population. Indeed, higher PVL in the peripheral blood has been associated with an increased inflammatory activity in the spinal cord and to a poorer prognosis in HAM/TSP. However, this event was not associated with TRE polymorphisms.
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lack of association between single nucleotide polymorphisms of pro and anti inflammatory cytokines and htlv 1 associated myelopathy Tropical Spastic Paraparesis development in patients from rio de janeiro brazil
BMC Infectious Diseases, 2018Co-Authors: Doris Schor, Abelardo Q.-c. Araújo, Luis Cristovao Porto, Eric Henrique Roma, Marcel De Souza Borges Quintana, Gustavo Milson Fabriciosilva, Maria Da Gloria Bonecinialmeida, Maria Jose AndradaserpaAbstract:HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a progressive neurological and inflammatory disease, associated with HTLV-1 infection. HAM/TSP neurological disease is a consequence of an inflammatory reaction, and adaptive immune responses, through the secretion of anti-inflammatory and pro-inflammatory cytokines, play an important role in the outcome of infection and disease progression. Studies addressing the association between cytokines functional single nucleotide polymorphisms and HAM/TSP development are scarce. The genetic polymorphisms of cytokine genes were evaluated in HAM/TSP patients (n = 68) and in asymptomatic HTLV-1 positive carriers (n = 83) from Rio de Janeiro, Brazil, in a case-control study. HTLV-1 infected patients were genotyped for SNPs in five cytokine genes: TNFA-308G/A, IL6-174G/C, IFNG + 874 T/A, TGFB at the codons + 10 T/C and + 25G/C, IL10-592C/A and -819C/T, and -1082A/G and proviral load (PVL) was quantified. Associations between genotypes, haplotypes, clinical outcome and pro viral load were evaluated. Lack of association between the cytokine polymorphisms and disease outcome was observed. The genotypes TNFA-308GG, IL6-174GG/GC, IL10-592AA and -819CC and TGFb1 high producers phenotypes were correlated with higher PVL in HAM/TSP patients versus asymptomatic carriers. We did not observe association between cytokine polymorphisms and risk for HAM/TSP development in Brazilian HTLV-1 infected individuals, regardless of differences in PVL between HAM/TSP versus asymptomatic carriers in specific cytokine polymorphisms.
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htlv 1 associated myelopathy Tropical Spastic Paraparesis
Nature Reviews Disease Primers, 2015Co-Authors: Charles R. M. Bangham, Abelardo Q.-c. Araújo, Yoshihisa Yamano, Graham P. TaylorAbstract:Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a progressive disease of the CNS that causes weakness or paralysis of the legs, lower back pain and urinary symptoms. HAM/TSP was first described in Jamaica in the nineteenth century, but the aetiology of the condition, infection with the retrovirus HTLV-1, was only identified in the 1980s. HAM/TSP causes chronic disability and, accordingly, imposes a substantial health burden in areas where HTLV-1 infection is endemic. Since the discovery of the cause of HAM/TSP, considerable advances have been made in the understanding of the virology, immunology, cell biology and pathology of HTLV-1 infection and its associated diseases. However, progress has been limited by the lack of accurate animal models of the disease. Moreover, the treatment of HAM/TSP remains highly unsatisfactory: antiretroviral drugs have little impact on the infection and, although potential disease-modifying therapies are widely used, their value is unproved. At present, clinical management is focused on symptomatic treatment and counselling. Here, we summarize current knowledge on the epidemiology, pathogenesis and treatment of HAM/TSP and identify areas in which further research is needed. For an illustrated summary of this Primer, visit: http://go.nature.com/tjZCFM.
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human t lymphotropic virus type 1 htlv 1 proviral load in asymptomatic carriers htlv 1 associated myelopathy Tropical Spastic Paraparesis and other neurological abnormalities associated with htlv 1 infection
Clinical Infectious Diseases, 2007Co-Authors: Marcus Tulius T Silva, Abelardo Q.-c. Araújo, Ramza C Harab, Ana Claudia Celestino Bezerra Leite, Doris Schor, Maria Jose AndradaserpaAbstract:Recent reports have demonstrated that human T lymphotropic virus type 1 (HTLV-1) is associated with other neurological abnormalities in addition to HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). It has been well established that high HTLV-1 proviral loads are associated with the development of HAM/TSP. We now demonstrate, for the first time, to our knowledge, that HTLV-1 proviral loads in patients with other neurological abnormalities are also significantly higher than in asymptomatic HTLV-1 carriers.
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disability and determinants of gait performance in Tropical Spastic Paraparesis htlv i associated myelopathy ham tsp
Spinal Cord, 2007Co-Authors: A C Franzoi, Abelardo Q.-c. AraújoAbstract:Cross-sectional. The aim of this survey is to describe the disability profile in a group of Tropical Spastic Paraparesis/HTLV-I-associated myelopathy patients, identifying the requirements for community ambulation. Terciary care unit, Rio de Janeiro, Brazil. Seventy-two patients were assessed (49 female and 23 male), referred by tertiary care centers, when a clinical protocol was applied. The sample had an average age of 40 years and an average of 137 months of duration of the disease. The most prevalent aspects of disability found were in gait and sphincter control areas. A total of 72% of the patients were community ambulators and 17% were restricted to wheel chair. Age, strength and low-back pain interfere in activities of daily living (P<0.05). A positive correlation was found between community ambulation and the knee extensors (r=0.80) and ankle plantar flexors (r=0.74). Strength, age, low-back pain, duration of disease, asymmetric onset of the symptoms and Spasticity interfered in the ability to walk (P<0.05). A rehabilitation program was proposed focusing on modifiable factors that affect disability level. It was possible to describe the profile of disability in this group of patients, identifying the requirements to the community ambulation. Not applicable.
Maria Jose Andradaserpa - One of the best experts on this subject based on the ideXlab platform.
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lack of association between single nucleotide polymorphisms of pro and anti inflammatory cytokines and htlv 1 associated myelopathy Tropical Spastic Paraparesis development in patients from rio de janeiro brazil
BMC Infectious Diseases, 2018Co-Authors: Doris Schor, Abelardo Q.-c. Araújo, Luis Cristovao Porto, Eric Henrique Roma, Marcel De Souza Borges Quintana, Gustavo Milson Fabriciosilva, Maria Da Gloria Bonecinialmeida, Maria Jose AndradaserpaAbstract:HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a progressive neurological and inflammatory disease, associated with HTLV-1 infection. HAM/TSP neurological disease is a consequence of an inflammatory reaction, and adaptive immune responses, through the secretion of anti-inflammatory and pro-inflammatory cytokines, play an important role in the outcome of infection and disease progression. Studies addressing the association between cytokines functional single nucleotide polymorphisms and HAM/TSP development are scarce. The genetic polymorphisms of cytokine genes were evaluated in HAM/TSP patients (n = 68) and in asymptomatic HTLV-1 positive carriers (n = 83) from Rio de Janeiro, Brazil, in a case-control study. HTLV-1 infected patients were genotyped for SNPs in five cytokine genes: TNFA-308G/A, IL6-174G/C, IFNG + 874 T/A, TGFB at the codons + 10 T/C and + 25G/C, IL10-592C/A and -819C/T, and -1082A/G and proviral load (PVL) was quantified. Associations between genotypes, haplotypes, clinical outcome and pro viral load were evaluated. Lack of association between the cytokine polymorphisms and disease outcome was observed. The genotypes TNFA-308GG, IL6-174GG/GC, IL10-592AA and -819CC and TGFb1 high producers phenotypes were correlated with higher PVL in HAM/TSP patients versus asymptomatic carriers. We did not observe association between cytokine polymorphisms and risk for HAM/TSP development in Brazilian HTLV-1 infected individuals, regardless of differences in PVL between HAM/TSP versus asymptomatic carriers in specific cytokine polymorphisms.
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human t lymphotropic virus type 1 htlv 1 proviral load in asymptomatic carriers htlv 1 associated myelopathy Tropical Spastic Paraparesis and other neurological abnormalities associated with htlv 1 infection
Clinical Infectious Diseases, 2007Co-Authors: Marcus Tulius T Silva, Abelardo Q.-c. Araújo, Ramza C Harab, Ana Claudia Celestino Bezerra Leite, Doris Schor, Maria Jose AndradaserpaAbstract:Recent reports have demonstrated that human T lymphotropic virus type 1 (HTLV-1) is associated with other neurological abnormalities in addition to HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). It has been well established that high HTLV-1 proviral loads are associated with the development of HAM/TSP. We now demonstrate, for the first time, to our knowledge, that HTLV-1 proviral loads in patients with other neurological abnormalities are also significantly higher than in asymptomatic HTLV-1 carriers.
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folliculitis decalvans and human t cell lymphotropic virus type i associated myelopathy Tropical Spastic Paraparesis
Clinical Infectious Diseases, 1995Co-Authors: Abelardo Q.-c. Araújo, Monica T. Rodrigues, Maria Jose Andradaserpa, Thomas A Paulofilho, Lygia A. F. PradoAbstract:Human T-cell lymphotropic virus type I (HTLV-I) can be associated with either adult T-cell leukemia or HTLV-I-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP), a chronic progressive immune-mediated myelopathy. Skin manifestations such as xerosis and erythema may be associated with HAM/TSP. Infective dermatitis due to Staphylococcus aureus or beta-hemolytic Streptococcus has recently been described as a marker for HTLV-I infection and as a probable risk factor for the development of adult T-cell leukemia and lymphoma in Jamaican children. We report a case of folliculitis decalvans, a rare chronic follicular inflammatory process of bacterial origin that is extremely resistant to treatment, in a patient with HAM/TSP. This case suggests the possibility that the disturbance of the immune system that was observed in patients with HAM/TSP can play a role in the persistence of this severe skin lesion. In addition, the findings of our case cast doubt on the hypothesis that the cause of infective dermatitis in persons infected with HTLV-I is immunosuppression due to congenital or perinatal infection of the immature immune system.
Kazunari Yamaguchi - One of the best experts on this subject based on the ideXlab platform.
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htlv 1 associated myelopathy Tropical Spastic Paraparesis ham tsp like disease and toxic epidermal necrolysis ten like disease in htlv 1 tax transgenic mice
Retrovirology, 2014Co-Authors: Takeo Ohsugi, Makoto Wakamiya, Saki Morikawa, Kumi Matsuura, Toshio Kumasaka, Kazunari YamaguchiAbstract:Human T-cell leukemia virus type 1 (HTLV-1) can cause an aggressive malignancy known as adult T-cell leukemia/lymphoma (ATLL), as well as inflammatory diseases such as HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). We created a transgenic mouse model of HTLV-1 infection by using the distal promoter of Lck to express tax in mature thymocytes and peripheral T lymphocytes. Major phenotypes of disease in this model were mature T cell leukemia/lymphoma similar to ATLL and an inflammatory arthropathy. While expanding the transgenic mouse colony, we also found 2.7% of transgenic mice developed a HAM/TSP-like disease and 2.4% of transgenic mice developed a toxic epidermal necrolysis (TEN)-like disease. The HAM/TSP-like disease with symmetrical Paraparesis of the hind limbs in transgenic mice was not inflammatory, unlike that found in HAM/TSP patients, but instead involved the invasion of histiocytic sarcoma cells into the lumbar spinal cord from the bone marrow where they had undergone extensive proliferation. Mice with the HAM/TSP-like disease showed abnormal expression of cytokines and chemokines, including TNF and IL-6. There are no reports of spontaneous symmetrical Paraparesis caused by histiocytic sarcoma in mice. TEN is characterized by a rash, bullae, and diffuse exfoliation of wide cutaneous surface areas, as seen in second-degree burns. Massive keratinocyte apoptosis is the hallmark of TEN. The TEN-like disease in transgenic mice occurred mainly in C57BL/6 background strain mice. These mice showed a skin detachment rate of greater than 30%. The pathology in transgenic mice with a TEN-like disease is currently under study and will be discussed.
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invasion of histiocytic sarcoma into the spinal cord of htlv 1 tax transgenic mice with htlv 1 associated myelopathy Tropical Spastic Paraparesis like disease
Oncology Research, 2012Co-Authors: Takeo Ohsugi, Makoto Wakamiya, Saki Morikawa, Kumi Matsuura, Jerald Mahesh Kumar, Toshio Kumasaka, Kazunari YamaguchiAbstract:Human T-cell leukemia virus type 1 (HTLV-1) can cause an aggressive malignancy known as adult T-cell leukemia/lymphoma (ATLL) as well as inflammatory diseases such as HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Transgenic (Tg) mice expressing HTLV-1 Tax also develop T-cell leukemia/lymphoma and an inflammatory arthropathy that resembles rheumatoid arthritis. We found that 8 of 297 Tax-Tg mice developed HAM/TSP-like disease with symmetrical Paraparesis of the hind limbs, but these symptoms were absent in non-Tg littermates and in other mice strains at our animal facilities. We could perform detailed evaluations for five of these mice. These evaluations showed that the disease was not inflammatory, unlike that in HAM/TSP patients, but instead involved the invasion of histiocytic sarcoma cells into the lumbar spinal cord from the bone marrow where they had undergone extensive proliferation.
