Immunological aspects of adult T-cell leukemia/lymphoma (ATLL), a possible neoplasm of regulatory T-cells

Adult T-cell leukemia/lymphoma (ATLL) is a distinct disease caused by the first discovered human oncogenic retrovirus, human T-cell leukemia virus type-1 (HTLV-1). The peculiarity of this disease is not only in its causative agent HTLV-1 but also in the character of leukemia cells. ATLL cells express the mature helper/inducer T-cell antigens, CD2, CD3, CD4 and CD5 but usually lacking CD8. Despite CD4 expression, it has long been known that ATLL cells exhibit strong immunosuppressive activity in vitro. Notably, ATLL patients are in severely immunosuppressed conditions and this causes higher incidences of opportunistic infections than other types of leukemia and lymphoma. Since ATLL cells constitutively express CD25, this prompted investigators to study ATLL cells from the viewpoint of regulatory T cells (Treg cells). ATLL cells satisfy all the criteria of Treg cells, as they express Foxp3, the master gene of Treg lineage, the glucocorticoid-induced TNF receptor (GITR), and the cytotoxic T-lymphocyte associated molecul-4 (CTLA-4). Moreover, other profiles including chemokine receptor expression also support that ATLL is a neoplasm of Treg cell origin. Here we review the immunological aspects of ATLL cells and discuss this cell origin

Electronic structures of B-2p and C-2p of boron-doped diamond film by soft X-ray absorption and emission spectroscopy

X-ray absorption (XAS) and emission (XES) spectroscopy near B-K and C-K edges have been performed on metallic (~1at%B, B-diamond) and semiconducting (~0.1at%B and N, BN-diamond) doped-diamond films. Both B-K XAS and XES spectra shows metallic partial density of state (PDOS) with the Fermi energy of 185.3 eV, and there is no apparent boron-concentration dependence in contrast to the different electric property. In C-K XAS spectrum of B-diamond, the impurity state ascribed to boron is clearly observed near the Fermi level. The Fermi energy is found to be almost same with the top of the valence band of non-doped diamond, E_V, 283.9 eV. C-K XAS of BN-diamond shows both the B-induced shallow level and N-induced deep-and-broad levels as the in-gap states, in which the shallow level is in good agreement with the activation energy (E_a=0.37 eV) estimated from the temperature dependence of the conductivity, namely the change in C-2p PDOS of impurity-induced metallization is directly observed. The electric property of this diamond is mainly ascribed to the electronic structure of C-2p near the Fermi level. The observed XES spectra are compared with the DVX-alpha cluster calculation. The DVX-alpha result supports the strong hybridization between B-2p and C-2p observed in XAS and XES spectra, and suggests that the small amount of borons (<1at%) in diamond occupy the substitutional site rather than interstitial site.Comment: submitted to Phys. Rev. B, 5 pages and 5 figure

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

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

Water-soluble melatonins: Syntheses of melatonins carrying a glycosyl group at the 1-position

金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学部1-(β-D-Xylopyranosyl)- (2a), 1-(β-D-glucopyranosyl)- (2b), 1-(β-D-galactopyranosyl)- (2c), and 1-(α-D-arabinopyranosyl)melatonins (3b) are prepared as water-soluble melatonins starting from melatonin

Localized excitons in cubic Zn1-xCdxS lattice matched to GaAs

Excitonic properties have been studied in cubic Zn0.42Cd0.58S lattice matched to GaAs. At 2 K, the time-integrated photoluminescence spectrum was composed of single emission peaking at 2.863 eV and its LO-phonon replica. The linewidth of the main peak was 18.5 meV, which fairly well agreed with the theoretical value based on the disorder-induced broadening of exciton luminescence in alloys. In order to assess the emission mechanism, the transient luminescence decay was measured at various emission energies. At the high energy tail (2.883 eV), the luminescence showed exponential decay with a time constant of about 72 ps. On the other hand, the decay time increased with decreasing the detected emission energy. It was about 660 ps at the emission peak (2.863 eV). We interpret these features by means of the model of exciton localization

Elevated expression of CD30 in adult T-cell leukemia cell lines: possible role in constitutive NF-κB activation

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) is associated with the development of adult T-cell leukemia (ATL). HTLV-1 encoded Tax1 oncoprotein activates the transcription of genes involved in cell growth and anti-apoptosis through the NF-κB pathway, and is thought to play a critical role in the pathogenesis of ATL. While Tax1 expression is usually lost or minimal in ATL cells, these cells still show high constitutive NF-κB activity, indicating that genetic or epigenetic changes in ATL cells induce activation independent of Tax1. The aim of this study was to identify the molecules responsible for the constitutive activation of NF-κB in ATL cells using a retroviral functional cloning strategy. RESULTS: Using enhanced green fluorescent protein (EGFP) expression and blasticidin-resistance as selection markers, several retroviral cDNA clones exhibiting constitutive NF-κB activity in Rat-1 cells, including full-length CD30, were obtained from an ATL cell line. Exogenous stable expression of CD30 in Rat-1 cells constitutively activated NF-κB. Elevated expression of CD30 was identified in all ATL lines examined, and primary ATL cells from a small number of patients (8 out of 66 cases). CONCLUSION: Elevated CD30 expression is considered one of the causes of constitutive NF-κB activation in ATL cells, and may be involved in ATL development

Osteosynthesis for Geriatric Acetabular Fractures: An Epidemiological and Clinico-Radiological Study Related to Marginal or Roof Impaction

This retrospective study sought to elucidate the incidence rates of roof impaction (RI) and marginal impaction (MI) and radiological and clinical outcomes of open reduction and internal fixation (ORIF) for RI and MI in geriatric acetabular fractures. The cases of 68 patients aged ≥ 65 years (mean 71 years) treated with ORIF were analyzed. MI was present in 12 fractures (67%) and an RI of the weight-bearing surface was present in 24 (46%) of the potential fracture types. Regarding the reduction quality, 54% of the reductions were graded as anatomical, 37% as imperfect, and 9% as poor. In the clinical evaluations of the 45 patients who had > 1-year follow-up (follow-up rate: 66.2%), 18% were graded as excellent, 53% as good, 16% as fair, and 13% as poor. An anatomic reduction was strongly associated with good or excellent clinical and radiological outcomes. CT was superior to radiographs for detecting the residual displacement postoperatively. Postoperative deep infection occurred in four patients. Three patients (6.7%) underwent a total hip arthroplasty conversion due to secondary osteoarthritis of the hip. We recommend ORIF as the preferred surgical treatment option for displaced acetabular fractures in elderly patients

High Human T Cell Leukemia Virus Type-1(HTLV-1) Provirus Load in Patients with HTLV-1 Carriers Complicated with HTLV-1-unrelated disorders

<p>Abstract</p> <p>Background</p> <p>To address the clinical and virological significance of a high HTLV-1 proviral load (VL) in practical blood samples from asymptomatic and symptomatic carriers, we simultaneously examined VL and clonal expansion status using polymerase chain reaction (PCR) quantification (infected cell % of peripheral mononuclear cells) and Southern blotting hybridization (SBH) methods.</p> <p>Results</p> <p>The present study disclosed extremely high VL with highly dense smears with or without oligoclonal bands in SBH. A high VL of 10% or more was observed in 16 (43.2%) of a total of 33 samples (one of 13 asymptomatic carriers, 8 of 12 symptomatic carriers, and 7 of 8 patients with lymphoma-type ATL without circulating ATL cells). In particular, an extremely high VL of 50% or more was limited to symptomatic carriers whose band findings always contained at least dense smears derived from polyclonally expanded cells infected with HTLV-1. Sequential samples revealed that the VL value was synchronized with the presence or absence of dense smears, and declined at the same time as disappearing dense smears. Dense smears transiently emerged at the active stage of the underlying disease. After disappearance of the smears, several clonal bands became visible and were persistently retained, explaining the process by which the clonality of HTLV-1-infected cells is established. The cases with only oligoclonal bands tended to maintain a stable VL of around 20% for a long time. Two of such cases developed ATL 4 and 3.5 years later, suggesting that a high VL with oligoclonal bands may be a predisposing risk to ATL.</p> <p>Conclusion</p> <p>The main contributor to extremely high VL seems to be transient emergence of dense smears detected by the sensitivity level of SBH, corresponding to polyclonal expansion of HTLV-1-infected cells including abundant small clones. Major clones retained after disappearance of dense smears stably persist and acquire various malignant characteristics step by step.</p