Cell life from the cell cycle to the signaling transduction and response to stimuli is finely tuned by protein post-translational modifications(PTMs).PTMs alter the conformation,the stability,the localization,and henc...Cell life from the cell cycle to the signaling transduction and response to stimuli is finely tuned by protein post-translational modifications(PTMs).PTMs alter the conformation,the stability,the localization,and hence the pattern of interactions of the targeted protein.Cell pathways involve the activation of enzymes,like kinases,ligases and transferases,that,once activated,act on many proteins simultaneously,altering the state of the cell and triggering the processes they are involved in.Viruses enter a balanced system and hijack the cell,exploiting the potential of PTMs either to activate viral encoded proteins or to alter cellular pathways,with the ultimate consequence to perpetuate through their replication.Human T-lymphotropic virus type 1(HTLV-1)is known to be highly oncogenic and associates with adult T-cell leukemia/lymphoma,HTLV-1-associated myelopathy/tropical spastic paraparesis and other inflammatory pathological conditions.HTLV-1 protein activity is controlled by PTMs and,in turn,viral activity is associated with the modulation of cellular pathways based on PTMs.More knowledge is acquired about the PTMs involved in the activation of its proteins,like Tax,Rex,p12,p13,p30,HTLV-I basic leucine zipper factorand Gag.However,more has to be understood at the biochemical level in order to counteract the associated fatal outcomes.This review will focus on known PTMs that directly modify HTLV-1 components and on enzymes whose activity is modulated by viral proteins.展开更多
This review analyses current data concerning co-infection with hepatitis C virus(HCV) and human T lymphotropic virus(HTLV)-1/2 in people who inject drugs(PWID), with a particular focus on disease burden and global imp...This review analyses current data concerning co-infection with hepatitis C virus(HCV) and human T lymphotropic virus(HTLV)-1/2 in people who inject drugs(PWID), with a particular focus on disease burden and global implications for virological outcome. In addition, the available treatment options for HTLV-1/2 are summarized and the on-going and likely future research challenges are discussed. The data in this review was obtained from 34 articles on HCV/HTLV-1/2 co-infection in PWID retrieved from the Pub Med literature database and published between 1997 and 2015. Despite unavailable estimates of the burden of HCV/HTLV-1/2 co-infection in general, the epidemiologic constellation of HTLV-1/2 shows high incidence in PWID with history of migration, incarceration, and other blood-borne infectious diseases such as HCV or human immunodeficiency virus. The most recent research data strongly suggest that HTLV-1 co-infection can influence HCV viral load, HCV sustained virological response to α-interferon treatment, and HCV-related liver disease progression. In short, outcome of HCV infection is worse in the context of HTLV-1 co-infection, yet more studies are needed to gain accurate estimations of the burden of HCV/HTLV-1/2 co-infections. Moreover, in the current era of new direct-acting antiviral treatments for HCV and proven HTLV-1/2 treatment options, prospective clinical and treatment studies should be carried out, with particular focus on the PWID patient population, with the aim of improving virological outcomes.展开更多
Human T-cell lymphotropic virus type 1(HTLV-1)-associated myelopathy/tropical spastic paraparesis(HAM/TSP) is a slowly progressive neurodegenerative disorder in which lesions of the central nervous system cause progre...Human T-cell lymphotropic virus type 1(HTLV-1)-associated myelopathy/tropical spastic paraparesis(HAM/TSP) is a slowly progressive neurodegenerative disorder in which lesions of the central nervous system cause progressive weakness, stiffness, and a lower limb spastic paraparesis. In some cases, polymyositis, inclusion bodymyositis, or amyotrophic lateral sclerosis-like syndromes are associated with HTLV-1. TSP was first described in Jamaica in 1888 and known as Jamaican peripheral neuritis before TSP was related to HTLV-1 virus, the first retrovirus being identified, and the disease is since named HAM/TSP. There is no established treatment program for HAM/TSP. Prevention is difficult in lowincome patients(i.e., HTLV-1 infected breast feeding mothers in rural areas, sex workers). Thus, there is a need for new therapeutic avenues. Therapeutic approaches must be based on a better understanding, not only of clinical and clinicopathological data, but also of the pathophysiology of the affection. Consequently, a better understanding of existing or newly developed animal models of HAM/TSP is a prerequisite step in the development of new treatments.展开更多
Enteropathy-associated T-cell lymphoma （EATL） is a rare peripheral T-cell lymphoma classified into 2 types, with or without celiac disease, based on histology. Type 2 EATL is less commonly associated with celiac dis...Enteropathy-associated T-cell lymphoma （EATL） is a rare peripheral T-cell lymphoma classified into 2 types, with or without celiac disease, based on histology. Type 2 EATL is less commonly associated with celiac disease, in which cells are characterized by being monomorphic and small- to medium-sized. Cells are characterized by CD8 and CD56 expression and c-MYC oncogene locus gain. We present an atypical case of type 2 EATL in the jejunum, with human T-lymphotropic virus-1 that was CD4- CDS＋ CD56- CD30- CD25- TIA-I＋ and granzyme B＋ on immunohistological staining. It also displayed translocation of chromosome 8p24 （c-MYC）, as de- termined by fluorescent/n situ hybridization. Mucosalspreading and intraepithelial invasion by lymphoma with villous atrophy were detected adjacent to the mucosal layer. The lymphoma may be derived from in- traepithelial CD8＋ T cells, similar to celiac disease.展开更多
AIM: To review the characteristics of hematological malignancies in tropical areas, and to focus on the specific difficulties regarding their management. METHODS: This is a retrospective narrative review of cases of p...AIM: To review the characteristics of hematological malignancies in tropical areas, and to focus on the specific difficulties regarding their management. METHODS: This is a retrospective narrative review of cases of patients with hematological malignancies. All medical files of patients with malignant disease whose treatment was coordinated by the HematoOncology service of the Cayenne Hospital in French Guiana between the 1st of January 2010 and the 31 st of December 2012 were reviewed. Clinical data were extracted from the medical files and included: Demographic data, comorbidities, serological status for human immunodeficiency virus, human T-lymphotropic virus 1(HTLV1), hepatitis B virus and hepatitis C virusinfections, cytology and pathology diagnoses, disease extension, treatment, organization of disease management, and follow-up. The subgroup of patients with hematological malignancies and virus-related malignancies were reviewed. Cases involving patients with Kaposi sarcoma, and information on solid tumor occurrence in virus-infected patients in the whole patient population were included. Since the data were rendered anonymous, no informed consent was obtained from the patients for this retrospective analysis. Data were compiled using EXCEL® software, and the data presentation is descriptive only. The references search was guided by the nature of the data and discussion. RESULTS: In total, the clinical files of 594 patients(pts) were reviewed. Hematological malignancies were observed in 87 patients, and Kaposi sarcoma in 2 patients. In total, 70 patients had a viral infection, and 34 of these also had hematological malignancies. The hematological diagnoses were: Multiple myeloma in 27 pts, lymphoma(L) in 43 pts, myeloproliferative disorders in 17 pts and Kaposi sarcoma in two patients. The spectrum of non-Hodgkin lymphomas(NHL) was: Burkitt L(1 pt), follicular L(5 pts), chronic lymphocytic leukemia(5 pts), high-grade NHL(9 pts), mucosa-associated lymphoid tissue NHL(4 pts), T-cell lymphoma(4 pts), Adul展开更多
Human T lymphotropic virus type 1 (HTLV-1) is endemic in the southern part of Japan. Infection of the virus can cause adult T cell leukemia/lymphoma (ATL), while most infected individuals remain in a carrier state for...Human T lymphotropic virus type 1 (HTLV-1) is endemic in the southern part of Japan. Infection of the virus can cause adult T cell leukemia/lymphoma (ATL), while most infected individuals remain in a carrier state for a long period of time. Although rare cases of carriers, like ATL patients, who developed opportunistic infections, have been reported, hematological changes of carriers who are prone to opportunistic infections have not been well defined. Here, we present a case of an HTLV-1 carrier who developed Mycobacterium intracellulare infection and Pneumocystis jirovecii pneumonia (PcP) simultaneously. Flow cytometric analysis of bone marrow cells revealed an aberrant compositional change similar to that in ATL patients. This suggests the presence of a pre-ATL state prior to the development of ATL, which is notable in terms of underlying cellular immunodeficiency.展开更多
Intravenously injected “99mTc-ciprofloxacin” is rapidly accumulated and washed from the septic focus. Lymphotropic injections provide targeted and long-lasting effect of antibiotics. After injection into the intersp...Intravenously injected “99mTc-ciprofloxacin” is rapidly accumulated and washed from the septic focus. Lymphotropic injections provide targeted and long-lasting effect of antibiotics. After injection into the interspinous ligament the drug slowly enters the inflammation area (by-passing the urinary organs and liver), where it is maximally accumulated only after 24 h, which allows to reduce the number of injections and the total dose of the antibiotic.展开更多
目的探讨成人T细胞白血病/淋巴瘤(adult T celll eukemia/lymphoma,ATLL)的临床表现、病理形态学特征、诊断及鉴别诊断。方法收集福建省肿瘤医院病理科2017年10月至2018年5月诊断的4例ATLL蜡块,采用HE染色、免疫组织化学及聚合酶链反应(...目的探讨成人T细胞白血病/淋巴瘤(adult T celll eukemia/lymphoma,ATLL)的临床表现、病理形态学特征、诊断及鉴别诊断。方法收集福建省肿瘤医院病理科2017年10月至2018年5月诊断的4例ATLL蜡块,采用HE染色、免疫组织化学及聚合酶链反应(PCR)和测序技术,观察组织学特征、免疫表型,检测人类T细胞白血病病毒(HTLV)1前病毒DNA,并结合文献进行复习。结果4例ATLL患者,男性2例,女性2例,年龄38~80岁,均为福建省籍居民。主要临床表现为淋巴结肿大、肝脾肿大、皮肤损害、高钙血症、淋巴细胞增多等。光镜下正常结构完全破坏,不典型淋巴样细胞弥漫浸润,背景中炎性细胞稀少。不典型淋巴细胞中等大至大,具有明显的多形性,核不规则、染色质粗块状,核仁明显,部分病例细胞形态间变,可见特征性分叶状核的"花细胞"。夹杂转化的母细胞,散在伴扭曲或脑回样核的巨细胞。免疫组织化学示肿瘤细胞弥漫一致表达CD2、CD3、CD5、CD4、CD25,不表达CD7、CD8及细胞毒分子。3例仅转化的大细胞表达CD30,1例弥漫表达CD30。4例均为EB病毒编码的小RNA阴性,HTLV-1前病毒阳性。结论ATLL是一种少见并具有独特的临床和病理学特征的T细胞肿瘤,应与非特殊型外周T细胞淋巴瘤、间变性淋巴瘤激酶阴性间变性大细胞淋巴瘤、皮肤蕈样霉菌病等鉴别。高钙血症、全身性疾病,特征性"花细胞",以及免疫表型CD3^+、CD4^+、CD25^+、CD7^-高度提示为ATLL。HTLV-1前病毒基因检测阳性才可确诊ATLL。展开更多
用间接免疫荧光法对福建部分沿海地区1703人进行了嗜人 T 细胞病毒Ⅰ型(HTLV-Ⅰ)抗体测定。HTLV-Ⅰ的抗体阳性率为2.3%,其中白血病患者的抗体阳性率(71%)显著高于其他疾病患者(2.7%)和健康献血员(0.6%)。表明了该地区 HTLV-Ⅰ感染率明...用间接免疫荧光法对福建部分沿海地区1703人进行了嗜人 T 细胞病毒Ⅰ型(HTLV-Ⅰ)抗体测定。HTLV-Ⅰ的抗体阳性率为2.3%,其中白血病患者的抗体阳性率(71%)显著高于其他疾病患者(2.7%)和健康献血员(0.6%)。表明了该地区 HTLV-Ⅰ感染率明显高于国内其他地区的报道。部分病毒携带者的体征和实验室指标有明显增加。展开更多
文摘Cell life from the cell cycle to the signaling transduction and response to stimuli is finely tuned by protein post-translational modifications(PTMs).PTMs alter the conformation,the stability,the localization,and hence the pattern of interactions of the targeted protein.Cell pathways involve the activation of enzymes,like kinases,ligases and transferases,that,once activated,act on many proteins simultaneously,altering the state of the cell and triggering the processes they are involved in.Viruses enter a balanced system and hijack the cell,exploiting the potential of PTMs either to activate viral encoded proteins or to alter cellular pathways,with the ultimate consequence to perpetuate through their replication.Human T-lymphotropic virus type 1(HTLV-1)is known to be highly oncogenic and associates with adult T-cell leukemia/lymphoma,HTLV-1-associated myelopathy/tropical spastic paraparesis and other inflammatory pathological conditions.HTLV-1 protein activity is controlled by PTMs and,in turn,viral activity is associated with the modulation of cellular pathways based on PTMs.More knowledge is acquired about the PTMs involved in the activation of its proteins,like Tax,Rex,p12,p13,p30,HTLV-I basic leucine zipper factorand Gag.However,more has to be understood at the biochemical level in order to counteract the associated fatal outcomes.This review will focus on known PTMs that directly modify HTLV-1 components and on enzymes whose activity is modulated by viral proteins.
文摘This review analyses current data concerning co-infection with hepatitis C virus(HCV) and human T lymphotropic virus(HTLV)-1/2 in people who inject drugs(PWID), with a particular focus on disease burden and global implications for virological outcome. In addition, the available treatment options for HTLV-1/2 are summarized and the on-going and likely future research challenges are discussed. The data in this review was obtained from 34 articles on HCV/HTLV-1/2 co-infection in PWID retrieved from the Pub Med literature database and published between 1997 and 2015. Despite unavailable estimates of the burden of HCV/HTLV-1/2 co-infection in general, the epidemiologic constellation of HTLV-1/2 shows high incidence in PWID with history of migration, incarceration, and other blood-borne infectious diseases such as HCV or human immunodeficiency virus. The most recent research data strongly suggest that HTLV-1 co-infection can influence HCV viral load, HCV sustained virological response to α-interferon treatment, and HCV-related liver disease progression. In short, outcome of HCV infection is worse in the context of HTLV-1 co-infection, yet more studies are needed to gain accurate estimations of the burden of HCV/HTLV-1/2 co-infections. Moreover, in the current era of new direct-acting antiviral treatments for HCV and proven HTLV-1/2 treatment options, prospective clinical and treatment studies should be carried out, with particular focus on the PWID patient population, with the aim of improving virological outcomes.
文摘Human T-cell lymphotropic virus type 1(HTLV-1)-associated myelopathy/tropical spastic paraparesis(HAM/TSP) is a slowly progressive neurodegenerative disorder in which lesions of the central nervous system cause progressive weakness, stiffness, and a lower limb spastic paraparesis. In some cases, polymyositis, inclusion bodymyositis, or amyotrophic lateral sclerosis-like syndromes are associated with HTLV-1. TSP was first described in Jamaica in 1888 and known as Jamaican peripheral neuritis before TSP was related to HTLV-1 virus, the first retrovirus being identified, and the disease is since named HAM/TSP. There is no established treatment program for HAM/TSP. Prevention is difficult in lowincome patients(i.e., HTLV-1 infected breast feeding mothers in rural areas, sex workers). Thus, there is a need for new therapeutic avenues. Therapeutic approaches must be based on a better understanding, not only of clinical and clinicopathological data, but also of the pathophysiology of the affection. Consequently, a better understanding of existing or newly developed animal models of HAM/TSP is a prerequisite step in the development of new treatments.
文摘Enteropathy-associated T-cell lymphoma （EATL） is a rare peripheral T-cell lymphoma classified into 2 types, with or without celiac disease, based on histology. Type 2 EATL is less commonly associated with celiac disease, in which cells are characterized by being monomorphic and small- to medium-sized. Cells are characterized by CD8 and CD56 expression and c-MYC oncogene locus gain. We present an atypical case of type 2 EATL in the jejunum, with human T-lymphotropic virus-1 that was CD4- CDS＋ CD56- CD30- CD25- TIA-I＋ and granzyme B＋ on immunohistological staining. It also displayed translocation of chromosome 8p24 （c-MYC）, as de- termined by fluorescent/n situ hybridization. Mucosalspreading and intraepithelial invasion by lymphoma with villous atrophy were detected adjacent to the mucosal layer. The lymphoma may be derived from in- traepithelial CD8＋ T cells, similar to celiac disease.
文摘AIM: To review the characteristics of hematological malignancies in tropical areas, and to focus on the specific difficulties regarding their management. METHODS: This is a retrospective narrative review of cases of patients with hematological malignancies. All medical files of patients with malignant disease whose treatment was coordinated by the HematoOncology service of the Cayenne Hospital in French Guiana between the 1st of January 2010 and the 31 st of December 2012 were reviewed. Clinical data were extracted from the medical files and included: Demographic data, comorbidities, serological status for human immunodeficiency virus, human T-lymphotropic virus 1(HTLV1), hepatitis B virus and hepatitis C virusinfections, cytology and pathology diagnoses, disease extension, treatment, organization of disease management, and follow-up. The subgroup of patients with hematological malignancies and virus-related malignancies were reviewed. Cases involving patients with Kaposi sarcoma, and information on solid tumor occurrence in virus-infected patients in the whole patient population were included. Since the data were rendered anonymous, no informed consent was obtained from the patients for this retrospective analysis. Data were compiled using EXCEL® software, and the data presentation is descriptive only. The references search was guided by the nature of the data and discussion. RESULTS: In total, the clinical files of 594 patients(pts) were reviewed. Hematological malignancies were observed in 87 patients, and Kaposi sarcoma in 2 patients. In total, 70 patients had a viral infection, and 34 of these also had hematological malignancies. The hematological diagnoses were: Multiple myeloma in 27 pts, lymphoma(L) in 43 pts, myeloproliferative disorders in 17 pts and Kaposi sarcoma in two patients. The spectrum of non-Hodgkin lymphomas(NHL) was: Burkitt L(1 pt), follicular L(5 pts), chronic lymphocytic leukemia(5 pts), high-grade NHL(9 pts), mucosa-associated lymphoid tissue NHL(4 pts), T-cell lymphoma(4 pts), Adul
文摘Human T lymphotropic virus type 1 (HTLV-1) is endemic in the southern part of Japan. Infection of the virus can cause adult T cell leukemia/lymphoma (ATL), while most infected individuals remain in a carrier state for a long period of time. Although rare cases of carriers, like ATL patients, who developed opportunistic infections, have been reported, hematological changes of carriers who are prone to opportunistic infections have not been well defined. Here, we present a case of an HTLV-1 carrier who developed Mycobacterium intracellulare infection and Pneumocystis jirovecii pneumonia (PcP) simultaneously. Flow cytometric analysis of bone marrow cells revealed an aberrant compositional change similar to that in ATL patients. This suggests the presence of a pre-ATL state prior to the development of ATL, which is notable in terms of underlying cellular immunodeficiency.
文摘Intravenously injected “99mTc-ciprofloxacin” is rapidly accumulated and washed from the septic focus. Lymphotropic injections provide targeted and long-lasting effect of antibiotics. After injection into the interspinous ligament the drug slowly enters the inflammation area (by-passing the urinary organs and liver), where it is maximally accumulated only after 24 h, which allows to reduce the number of injections and the total dose of the antibiotic.
文摘目的探讨成人T细胞白血病/淋巴瘤(adult T celll eukemia/lymphoma,ATLL)的临床表现、病理形态学特征、诊断及鉴别诊断。方法收集福建省肿瘤医院病理科2017年10月至2018年5月诊断的4例ATLL蜡块,采用HE染色、免疫组织化学及聚合酶链反应(PCR)和测序技术,观察组织学特征、免疫表型,检测人类T细胞白血病病毒(HTLV)1前病毒DNA,并结合文献进行复习。结果4例ATLL患者,男性2例,女性2例,年龄38~80岁,均为福建省籍居民。主要临床表现为淋巴结肿大、肝脾肿大、皮肤损害、高钙血症、淋巴细胞增多等。光镜下正常结构完全破坏,不典型淋巴样细胞弥漫浸润,背景中炎性细胞稀少。不典型淋巴细胞中等大至大,具有明显的多形性,核不规则、染色质粗块状,核仁明显,部分病例细胞形态间变,可见特征性分叶状核的"花细胞"。夹杂转化的母细胞,散在伴扭曲或脑回样核的巨细胞。免疫组织化学示肿瘤细胞弥漫一致表达CD2、CD3、CD5、CD4、CD25,不表达CD7、CD8及细胞毒分子。3例仅转化的大细胞表达CD30,1例弥漫表达CD30。4例均为EB病毒编码的小RNA阴性,HTLV-1前病毒阳性。结论ATLL是一种少见并具有独特的临床和病理学特征的T细胞肿瘤,应与非特殊型外周T细胞淋巴瘤、间变性淋巴瘤激酶阴性间变性大细胞淋巴瘤、皮肤蕈样霉菌病等鉴别。高钙血症、全身性疾病,特征性"花细胞",以及免疫表型CD3^+、CD4^+、CD25^+、CD7^-高度提示为ATLL。HTLV-1前病毒基因检测阳性才可确诊ATLL。
文摘用间接免疫荧光法对福建部分沿海地区1703人进行了嗜人 T 细胞病毒Ⅰ型(HTLV-Ⅰ)抗体测定。HTLV-Ⅰ的抗体阳性率为2.3%,其中白血病患者的抗体阳性率(71%)显著高于其他疾病患者(2.7%)和健康献血员(0.6%)。表明了该地区 HTLV-Ⅰ感染率明显高于国内其他地区的报道。部分病毒携带者的体征和实验室指标有明显增加。
