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Adult T‐cell leukemia (ATL) is a life‐threatening malignant neoplasm of CD4+ T cells resulted from human T‐cell leukemia virus type I (HTLV‐I). Tax1 protein of HTLV‐I can induce malignant proliferation of T‐cells by modulating the expression of growth factors such as platelet‐derived growth factor (PDGF). Here, we aimed to investigate the proviral load (PVL) of HTLV‐I in ATL and also to evaluate the mRNA expression of B chain of PDGF and PDGF‐β receptors in ATL patients and HTLV‐I‐infected healthy carriers. To this end, peripheral blood mononuclear cells (PBMCs) were isolated by using Ficoll‐Histophaque density centrifugation. The mean of HTLV‐I PVL in ATL patients (42,759 ± 15,737 copies/104 cells [95% CI, 9557‐75962]) was significantly (p =.01) higher than that in healthy carriers (650 ± 107 copies/104 cells [95% CI, 422‐879], respectively. The HTLV‐I PVL in ATL patients exhibited a significant correlation with PBMC count (R =.495, p =.001). The mRNA expression of Tax, B chain of PDGF, and PDGF‐β receptor genes was significantly higher in healthy carriers than in patients with ATL. In conclusion, the expression of the canonical PDGFβ and its receptor, and their correlation with Tax expression cannot be a suitable indicator and/or prognostic factor for progression of ATL in HTLV‐I carriers. [ABSTRACT FROM AUTHOR]

Objective(s): Human T cell leukaemia virus type 1 (HTLV-1) is associated with adult T cell leukaemia (ATL), a malignant lymphoproliferative disease that infects CD4 T cells. It is not clear why the majority of HTLV-1-infected individuals remain asymptomatic carries (ACs) and a minority develop ATL. Cellular immune response has a critical role in ATL and destroys malignant and HTLV-1-infected cells. Perforin and granzyme have important functional roles in apoptosis and destruction of infected cells. In the present study we examined the role of perforin and granzyme in ATL patients and ACs. Materials and Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from ATL patients and ACs by using Ficoll-hypaque density centrifugation. RNA was extracted and cDNA was synthesized. A real-time PCR TaqMan method was designed and optimized for evaluation of perforin, granzyme, tax, and HBZ gene expression. HTLV-1 proviral load (PVL) was quantified in patients with ATL and ACs. Results: The mRNA expression of tax and HBZ was significantly higher in ATL patients than ACs (P=0.011 and P=0.0001,respectively). The HTLV-1 PVL was higher in ATL patients compared to with AC group (P=0.015). There was a significant increase in perforin gene expression in ACs compared with ATL patients (P=0.002). Furthermore, the expression of granzyme was also higher in ACs compared with ATL patients, and significant differences were observed between the two groups (P=0.036). Conclusion: Low expression of perforin and granzyme in ATL patients seems to influence the efficiency of CTL function and destruction of HTLV-1-infected cells, which might contribute to the disease pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Adult T-cell leukemia/lymphoma (ATLL) is caused by human T-cell lymphotropic virus type-1 (HTLV-1). HTLV-1 oncogenes can induce malignancy through controlled gene expression of cell cycle checkpoints in the host cell. HTLV-I genes play a pivotal role in overriding cell cycle checkpoints and deregulate cellular division. In this study, we aimed to determine and compare the HTLV-1 proviral load and the gene expression levels of cyclin-dependent kinase-2 (CDK2), CDK4, p53, and retinoblastoma (Rb) in ATLL and carrier groups. Methods: A total of twenty-five ATLL patients (12 females and 13 males) and 21 asymptomatic carriers (10 females and 11 males) were included in this study. TaqMan real-time polymerase chain reaction assay was used for evaluation of proviral load and gene expression levels of CDK2, CDK4, p53, and Rb. Statistical analysis was used to compare proviral load and gene expression levels between two groups, using SPSS version 18. Results: The mean scores of the HTLV-1 proviral load in the ATLL patients and healthy carriers were 13067.20±6400.41 and 345.79±78.80 copies/104 cells, respectively (P=0.000). There was a significant correlation between the gene expression levels of CDK2 and CDK4 (P=0.01) in the ATLL group. Conclusions: Our findings demonstrated a significant difference between the ATLL patients and healthy carriers regarding the rate of proviral load and the gene expression levels of p53 and CDK4; accordingly, proviral load and expression levels of these genes may be useful in the assessment of disease progression and prediction of HTLV-1 infection outcomes. [ABSTRACT FROM AUTHOR]

Objective(s): Incidence of neurocognitive and psychological disorders may be related to serum homocystein (Hcy), cobalamin (vitamin B12) and folate levels in old people. The aim of this study was to assess the relation between Hcy, cobalamin, folate and neurocognitive and/or psychological disorders in the elderly. Materials and Methods: In this cross-sectional study, 280 subjects with = 65 years old, were evaluated. The subjects were selected from 12 regions of Mashhad, Iran, over March to October 2009. After blood sampling, data were collected by questionnaire, face to face interview and performing neurocognitive and psychological tests. The sera of 250 persons were analyzed for cobalamin and folate by RIA method. Amongst the aforementioned samples, 78 cases with cobalamin <300 pg/ml and folate <6.5 ng/ml were analyzed for Hcy by ELISA method. Results: Amongst the people, 126 (45%) were male and 154 (55%) were female. The prevalence of hyperhomocysteinemia (HHcy) was 59.5% and 37.1% in male and female respectively (P -value =0.049). Hcy inversely correlated to cobalamin (r=-0.282, P=0.014) and to folate (r=-0.203, P=0.014). Hcy, cobalamin and folate correlations to neurocognitive and psychological impairments were not statically significant. Conclusion: Hyper Hcy or low cobalamin and folate in the elderly, are prevalent but their relationships with neurocognitive and psychological impairments is controversial. If these relationships had been confirmed, performing a single serum Hcy or cobalamin test would have been enough to diagnose and prevent neurocognitive impairments and inversely, neurocognitive-psychological sign and symptoms could have meant probable tissue vitamin deficiencies. However methods of assessing neurocognitive and psychological markers with validity and reliability of clinical and laboratory tests for finding aforementioned relationships should be revised. [ABSTRACT FROM AUTHOR]

The study of tumor viruses paves the way for understanding the mechanisms of virus pathogenesis, including those involved in establishing infection and dissemination in the host tumor affecting immune-compromised patients. The processes ranging from viral infection to progressing malignancy are slow and usually insufficient for establishment of transformed cells that develop cancer in only a minority of infected subjects. Therefore, viral infection is usually not the only cause of cancer, and further environmental and host factors, may be implicated. HTLV-I, in particular, is considered as an oncovirus cause of lymphoproliferative disease such as adult T cell leukemia/lymphoma (ATL) and disturbs the immune responses which results in HTLV-I associated meylopathy/tropical spastic parapresis (HAM/TSP). HTLV-I infection causes ATL in a small proportion of infected subjects (2-5%) following a prolonged incubation period (15-30 years) despite a strong adaptive immune response against the virus. Overall, these conditions offer a prospect to study the molecular basis of tumorgenicity in mammalian cells. In this review, the oncogencity of HTLV-I is being considered as an oncovirus in context of ATL. [ABSTRACT FROM AUTHOR]

Objective(s): Systemic lupus erythematosus (SLE) is an autoimmune disease with unknown etiology. Some environmental factors can induce SLE in genetically susceptible individuals; for example, sun exposure and some viral infections may emerge the disease manifestations. Human T lymphotropic virus type 1 (HTLV-I) can dysregulate the human immune system, and the role of this virus in the pathogenesis of autoimmune diseases is under investigation. There are conflicting data about the role of HTLV-I in the pathogenesis of several autoimmune diseases such as SLE. In this study, we have focused on the correlation between HTLV-I infection and SLE in the northeast of Iran, an endemic area for the virus. Materials and Methods: One hundred and thirty women with SLE and 915 healthy controls were screened for HTLV-I by enzyme linked immunosorbent assay (ELISA). Western blot method was used for confirmation of the positive results done by ELISA in the patients and the control group. Results: Two (1.5%) of the patients and 23 (2.5%) of the healthy controls were HTLV-I seropositive. There was not a statistical difference between patients and controls in the number of HTLV-I seropositive samples (P=0.49). Conclusion: This cross-sectional case-control study did not find any association between HTLV-I and SLE. With regard to the previous studies, these controversies may stem from differences in ethnic background. Geographical and environmental factors should also be taken into account. [ABSTRACT FROM AUTHOR]

Objective(s): Human T Lymphocyte Virus Type one (HTLV-I) is a retrovirus that infects about 10-20 million people worldwide. Khorasan province in Iran is an endemic area. The majority of HTLV-I-infected individuals sustain healthy carriers but small proportion of infected population developed two progressive diseases: HAM/TSP and ATL. The proviral load could be a virological marker for disease monitoring, therefore in the present study HTLV-I proviral load has been evaluated in ATL and compared to HAM/TSP and healthy carriers. Materials and Methods: In this case series study, 47 HTLV-I infected individuals including 13 ATL, 23 HAM/TSP and 11 asymptomatic subjects were studied. Peripheral blood mononuclear cells (PBMCs) were investigated for presence of HTLV-I DNA provirus by PCR using LTR and Tax fragments. Then in infected subjects, HTLV-I proviral load was measured using real time PCR TaqMan method. Results: The average age of patients in ATL was 52±8, in HAM/TSP 45.52±15.17 and in carrier's 38.65±14.9 years which differences were not statistically significant. The analysis of data showed a significant difference in mean WBC among study groups (ATL vs HAM/ TSP and carriers P=0.0001). Moreover, mean HTLV-I proviral load was 11967.2 ± 5078, 409 ± 71.3 and 373.6 ± 143.3 in ATL, HAM/TSP and Healthy Carriers, respectively. The highest HTLV-I proviral load was measured in ATL group that had a significant correlation with WBC count (R=0.495, P=0.001). The proviral load variations between study groups was strongly significant (ATL vs carrier P=0.0001; ATL vs HAM/TSP P= 0.0001 and HAM/TSP vs carriers P< 0.05). Conclusion: The present study demonstrated that HTLV-I proviral load was higher in ATL group in comparison with HAM/TSP and healthy carriers. Therefore, HTLV-I proviral load is a prognostic factor for development of HTLV-I associated diseases and can be used as a monitoring marker for the efficiency of therapeutic regime. [ABSTRACT FROM AUTHOR]

Introduction: Despite widespread use of 67Gallium for lymphoma evaluation, timing of imaging after injection is a matter of controversy and to the extent of our knowledge no direct comparison has been made between early and delayed gallium images. We aimed to compare 24 and 48 hours post injection planar gallium imaging for evaluation of lymphoma recurrence. Methods: 255 patients suspicious of recurrent lymphoma were included in the study. Twenty four and 48 hours post injection (10 mCi) whole body Gallium imaging was performed. Semi-quantitative evaluation (background corrected) was carried out in positive whole body 67Gallium scans. Diagnosis of recurrence was made by combination of clinical or pathologic examination if possible. In 59 patients the final diagnosis was made by tissue biopsy. In case of uncertain diagnosis, follow up of the patients (mean duration of 13 months) was used. The diagnosis was finally made by the referring hematologist. Results: Whole body gallium scintigraphy was positive in 115 out of 150 patients with recurrence (sensitivity of 76%). Comparison of the 24 and 48 hour images did not show any new lesion in the 48 hour images. However, delayed 48 hours images were required for definite detection of the gallium avid lesions in the abdominal and pelvic areas in 40 patients. Semi-quantitative evaluation of the lesions showed higher lesion to background ratio for 48 compared to the 24 hour images (p<0.001). Conclusions: Considering higher lesion to background activity in the 48 hour images, delayed whole body 67Gallium imaging may be more desirable for diagnosis of recurrent lymphoma, however 24 hour images may be sufficient. Delayed imaging can be reserved for suspicious activities (such as in abdominal images). This strategy can save time and is more convenient for the imaging centers. [ABSTRACT FROM AUTHOR]

Introduction Genetic background has known to be associated with the outcome of human T cell lymphotropic virus (HTLV) type I infection. In The present study we investigate the association between GM-CSF gene polymorphisms with the outcome of HTLV-I infection. Materials and Methods We analyzed 3 single-nucleotide polymorphisms in the promter region of granulocyte macrophage colony stimulating factor (GM-CSF) at positions -677*A/C, -1440*A/G and -1916*T/C in 68 patients with HTLVI- associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 77 HTLV-I-seropositive asymptomatic carriers and 175 healthy controls from an area in Iran, Mashhad, where HTLV-I is endemic. Results No significant differences were observed in the distribution of GM-CSF polymorphisms between HAM/TSP patients, HTLV-I carriers and healthy controls (P> 0.05). The -677*A/C polymorphism fall within the transcriptional enhancer factor-2 (TEF-2) binding site, so an electrophoretic mobility shift assay (EMSA) was performed to determine the effects of polymorphisms on protein binding to the GM-CSF promoter. The result showed a significantly higher binding efficiency of nuclear protein to the A allele compared with the C allele. Conclusion Our study suggests that polymorphisms in the GM-CSF promoter is not associated with the outcome of HTLV-I infection, however, GM-CSF polymorphism at position -677 could indeed influence gene expression. [ABSTRACT FROM AUTHOR]

Objective(s): One of the special types of cutaneous leishmaniasis is the Chronic Lupoid Leishmaniasis (CLL), which abnormal immune responses have been implicated in its pathogenesis. On the other hand, HTLV-I infection has been known to exist in some infectious diseases. Human T cell lymphotropic virus type I (HTLV-I) and cutaneous leishmaniasis exists endemically in Mashhad. The objective of this study was to evaluate the frequency of HTLV-I in CLL patients. Materials and Methods: This cross sectional study involved 51 CLL patients admitted to cutaneous leishmaniasis clinics of Ghaem and Imam Reza hospitals in Mashhad, Iran. The blood samples were examined for serology tests by ELISA method. Results: The results of the tests for evaluating the existence of HTLV-I in 51 patients in this research were proved to be negative. Conclusion: According to this pilot study, the frequency of HTLV-I in CLL patients is not higher than normal population. [ABSTRACT FROM AUTHOR]

Background: A specific chromosomal abnormality, the Philadelphia chromosome (BCR-ABL fusion), is present in all patients with chronic myeloid leukemia (CML). The b2a2 and b3a2 fusion mRNAs encode p210 fusion protein p210 and e1a2 encode p190. The aim of this study was to evaluate the frequency of BCR-ABL fusion transcript variants in Northeast of Iranian CML patients and to compare the laboratory results of our patients., Methods: This study was conducted in 85 peripheral blood and bone marrow samples of CML patients. Ribonucleic acid (RNA) was extracted by a commercial kit, RT- PCR for identifying BCR-ABL fusions was carried out by using designed primers and the PCR products were electrophoresed in agarose gels. Finally, statistical analysis was performed for variant frequency identification and their comparison was performed., Results: All patients examined were positive for BCR/ABL rearrangement. Fusion of b3a2 was detected in 53 (62.35%) patients, b2a2 in 25 (29.41), e1a2 in 1 (1.17%) and coexpression of b3a2 and e1a2 in 6 (7.05%) patients. There were significant differences between the mean age in patients with b3a2 positive ( 44.07 years) and in b3a2 negative group (50.35 years) however, no significant differences were seen between sex and b2a2 (P=0.61), b3a2 (P=0.79) and e1a2 (P=0.20)., Conclusions: This study showed higher frequency b3a2 than b2a2 and e1a2 transcripts in CML patients in Northeast Iran and there was no association between e1a2 transcripts frequencies and monocytosis in peripheral blood., Competing Interests: There is no conflict of interest.

Background: Adult T-cell leukemia/lymphoma (ATLL) is caused by human T-cell lymphotropic virus type-1 (HTLV-1). HTLV-1 oncogenes can induce malignancy through controlled gene expression of cell cycle checkpoints in the host cell. HTLV-I genes play a pivotal role in overriding cell cycle checkpoints and deregulate cellular division. In this study, we aimed to determine and compare the HTLV-1 proviral load and the gene expression levels of cyclin-dependent kinase-2 (CDK2), CDK4, p53, and retinoblastoma (Rb) in ATLL and carrier groups., Methods: A total of twenty-five ATLL patients (12 females and 13 males) and 21 asymptomatic carriers (10 females and 11 males) were included in this study. TaqMan real-time polymerase chain reaction assay was used for evaluation of proviral load and gene expression levels of CDK2, CDK4, p53, and Rb. Statistical analysis was used to compare proviral load and gene expression levels between two groups, using SPSS version 18., Results: The mean scores of the HTLV-1 proviral load in the ATLL patients and healthy carriers were 13067.20±6400.41 and 345.79±78.80 copies/10 4 cells, respectively (P=0.000). There was a significant correlation between the gene expression levels of CDK2 and CDK4 (P=0.01) in the ATLL group., Conclusion: Our findings demonstrated a significant difference between the ATLL patients and healthy carriers regarding the rate of proviral load and the gene expression levels of p53 and CDK4; accordingly, proviral load and expression levels of these genes may be useful in the assessment of disease progression and prediction of HTLV-1 infection outcomes.

Background: Health care officials and legislators need accurate data on prevalence and numbers of individuals with bleeding disorders in order to plan and allot their budgets; the manufacturers of coagulation factors also need these data to estimate the amount of factors required to prevent scarcity of these products., Materials and Methods: We surveyed the prevalence of haemophilia A, haemophilia B, von Willebrand's disease and rare bleeding disorders in North-Eastern Iran. The survey was done in the period from September 2009 to March 2011. Information was collected from the medical records in three major hospitals and a haemophilia centre; the patients' updated data were obtained by telephone., Results: Overall in the current survey 552 patients with inherited coagulation disorders were identified and their medical records obtained. Of these, 429 (77.5%) had common bleeding disorders (haemophilia A, haemophilia B, von Willebrand's disease), 85 (15.6%) had rare bleeding disorders (deficiency of coagulation factors V, VII, X, XIII, I, XI, combined factor V and VIII deficiency) and 38 (6.9%) had platelet disorders.The commonest bleeding disorders were haemophilia A (n=287, 51.9%), haemophilia B (n=92, 16.6%), von Willebrand's disease (n=50, 9%), factor V deficiency (n=21, 3.8%), factor VII deficiency (n=19, 3.4%), factor X deficiency (n=2, 0.36%), combined factor V and VIII deficiency (n=28, 5.8%), factor XIII deficiency (n=11, 1.99%), factor XI deficiency (n=2, 0.4%), afibrinogenaemia (n=2, 0.36%) and platelet disorders (n=38, 6.9%)., Discussion: There is notable population of individuals with bleeding disorders in North-Eastern Iran.

Objective(s): One of the different types of skin leishmaniasis is the Chronic Lupoid Leishmaniasis (CLL), which is caused by abnormal immune response. On the other hand, HTLV-I has been known to exist in some infectious diseases. Human T cell lymphotropic virus type1 (HTLV-I) and cutanous leishmaniasis exists endemically in Mashhad. The objective of this study was to evaluate the prevalence of HTLV-I in CLL patients., Materials and Methods: This cross sectional study involved 51 CLL patients admitted to cutaneous leishmaniasis clinics of Ghaem and Imam Reza hospitals in Mashhad, Iran. The blood samples were examined for serology tests through ELISA method., Results: The results of the experiments for evaluating the existence of HTLV-I in 51 patients under study in this research were proved to be negative., Conclusion: According to this pilot study, the distribution of HTLV-I in CLL patients is not higher than normal population.

The underlying mechanisms leading to the development of human T-cell lymphotropic virus type I (HTLV-I) associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-I infected individuals are not fully understood. Host genetic factors appear to be involved as risk factors for developing HAM/TSP. We investigated the possible contribution of interleukin-10 (IL-10) as a risk factor to HAM/TSP by comparing frequencies of promoter region single nucleotide polymorphisms in HTLV-I infected Iranian patients who either remained asymptomatic or developed HAM/TSP and asymptomatic HTLV-I carriers. Healthy, uninfected individuals from the same region served as healthy controls. Significant differences were observed in the distribution of IL-10 promoter alleles and genotypes at position -819 and -592 between HAM/TSP patients and healthy controls (P=0.01), and between HTLV-I carriers and healthy controls (P=0.02). The frequency of the low IL-10 producer haplotype (-1082*A, -819*T, -592*A) was significantly associated with HTLV-I carriage or HAM/TSP compared with healthy controls (P=0.02 and 0.01, respectively). Our results suggest that IL-10 -819*T and -592*A alleles are significant risk factors for developing HTLLV-I infection but do not appear to convey additional risk for developing HAM/TSP.

Objective(s): Human T Lymphocyte Virus Type one (HTLV-I) is a retrovirus that infects about 10-20 million people worldwide. Khorasan province in Iran is an endemic area. The majority of HTLV-I-infected individuals sustain healthy carriers but small proportion of infected population developed two progressive diseases: HAM/TSP and ATL. The proviral load could be a virological marker for disease monitoring, therefore in the present study HTLV-I proviral load has been evaluated in ATL and compared to HAM/TSP and healthy carriers., Materials and Methods: In this case series study, 47 HTLV-I infected individuals including 13 ATL, 23 HAM/TSP and 11 asymptomatic subjects were studied. Peripheral blood mononuclear cells (PBMCs) were investigated for presence of HTLV-I DNA provirus by PCR using LTR and Tax fragments. Then in infected subjects, HTLV-I proviral load was measured using real time PCR TaqMan method., Results: The average age of patients in ATL was 52±8, in HAM/TSP 45.52±15.17 and in carrier's 38.65±14.9 years which differences were not statistically significant. The analysis of data showed a significant difference in mean WBC among study groups (ATL vs HAM/TSP and carriers P=0.0001). Moreover, mean HTLV-I proviral load was 11967.2 ± 5078, 409 ± 71.3 and 373.6 ± 143.3 in ATL, HAM/TSP and Healthy Carriers, respectively. The highest HTLV-I proviral load was measured in ATL group that had a significant correlation with WBC count (R=0.495, P=0.001). The proviral load variations between study groups was strongly significant (ATL vs carrier P=0.0001; ATL vs HAM/TSP P= 0.0001 and HAM/TSP vs carriers P< 0.05). Conclusion : The present study demonstrated that HTLV-I proviral load was higher in ATL group in comparison with HAM/TSP and healthy carriers. Therefore, HTLV-I proviral load is a prognostic factor for development of HTLV-I associated diseases and can be used as a monitoring marker for the efficiency of therapeutic regime.

Human T-cell lymphotropic virus type I (HTLV-I) associated adult T-cell leukemia/lymphoma (ATLL) is endemic in southern Japan, the Caribbean, intertropical Africa, and Brazil. Recently north east Iran, particularly the region of Mashhad, has been recognized as a new endemic region. ATLL is an aggressive T-cell lymphoproliferative disorder. Patients with ATLL have high plasma levels of VEGF that induce angiogenesis. Prognosis of ATLL remains poor because of immunosuppression and intrinsic resistance to chemotherapy. Important advances in the treatment of ATLL were reported with the combination of zidovudine (AZT) and interferon-alpha. We investigated the effect of AZT/IFN treatment on vascular endothelium growth factor (VEGF) plasma levels and HTLV-I proviral load in ATLL patients from the region of Mashhad. We confirmed that AZT/IFN treatment induces a high response rate and prolonged survival with minimal side effects. We also confirmed that VEGF plasma levels and HTLV-I proviral load are higher in ATLL patients than in asymptomatic carriers. We finally showed that AZT/IFN treatment reduced both HTLV-I proviral load and importantly VEGF plasma levels, suggesting a potential antiangiogenic effect of this therapy. These results provide further evidence for the efficacy and the mechanism of action of AZT/IFN therapy for ATLL in a developing country.

Spinal cord compression due to extramedullary hematopoiesis is a rare manifestation of thalassemia. We present a 28-year-old woman with beta-thalassemia intermedia and progressive paraparesis. She had a thoracic extradural extramedullary mass lesion on MRI. She improved after receiving multiple transfusions. Clinical awareness of this phenomenon with early treatment is essential for a successful outcome.