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At least 829 records · Page 46Linked to original sources
PubMed1999

Allogenic bone marrow transplantation as a treatment for adult T-cell leukemia.

We performed allogenic bone marrow transplantation (BMT) in two adult T-cell leukemia (ATL) patients with HLA-identical siblings as donors. One patient, with acute ATL, relapsed 3 months after BMT. The other, with chronic ATL, has become free of disease over 18 months after the BMT from his human T-cell lymphotropic virus type 1 (HTLV-1)-negative sibling, and we were unable to detect HTLV-1 in the patient's peripheral blood. Based on our results and those of others, although there have been limited numbers of patients, BMT may represent the only potentially curative treatment for ATL, and the presence of graft-vs.-host disease tends to be related to good results, which suggests the possibility that graft-vs.-leukemia effects may play an important role in allogenic BMT for ATL.

Adult↗
PubMed2000

Constitutive activation of LIL-Stat in adult T-cell leukemia cells.

The activation status of a recently identified STAT (signal transducers and activators of transcription) factor, LIL-Stat (lipopolysaccharide [LPS]/IL-1-inducible Stat) in adult T-cell leukemia (ATL) cells was investigated by electrophoretic mobility shift assays using nuclear extracts of leukemic cells from 7 patients with ATL and a GAS (gamma interferon activation site)-like element termed LILRE (LPS/IL-1-responsive element), which is found in the human prointerleukin 1beta (IL1B) gene. Spontaneous DNA binding of LIL-Stat was observed in all ATL cells examined. However, in normal human peripheral lymphocytes, DNA binding of LIL-Stat was detected only after stimulation with IL-1. These results demonstrated that LIL-Stat is constitutively activated in ATL cells. Furthermore, our transient transfection studies using LILRE chloramphenicol acetyltransferase (CAT) reporters argue that LIL-Stat in ATL cells functions as a transcriptional activator through binding to the LILRE in the IL1B gene. (Blood. 2000;95:2715-2718)

Acute Disease↗
PubMed2000

Real-time polymerase chain reaction for quantification of HTLV-1 proviral load: application for analyzing aberrant integration of the proviral DNA in adult T-cell leukemia.

We describe the establishment of a real-time polymerase chain reaction (PCR) assay for the quantitative estimation of human T-cell leukemia virus type 1 (HTLV-1) proviral load using a LightCycler Technology (Roche Diagnostics, Mannheim, Germany) instrument. Proviral DNA level represents a measure of the integrated viral genome in host cells, so we applied this technique to evaluate the tumor burden in adult T-cell leukemia (ATL) patients with aberrant integration patterns of HTLV-1 detected by standard Southern blot hybridization (SBH) analysis. In 14 of our 15 ATL cases with 2 or more bands detected by SBH analysis, the ATL cells were shown to harbor multiple copies of the provirus within 1 ATL cell. This result suggests the usefulness of real-time PCR quantification for the study of the relationship between ATL pathology and HTLV-1-induced pathogenesis.

DNA, Viral↗
PubMed2000

[Southern blot hybridization analysis for lymphoid neoplasms].

The recent remarkable progress of molecular biology gave us new tools for examination of the etiology and pathology of many diseases. Hence, the introduction of such techniques in our clinical laboratory area is becoming more important and indispensable year by year. In addition to morphological and phenotypical analysis, we are now establishing a molecular diagnosis system to support the clinical diagnosis of hematological malignancies. In the present study, we show our ongoing results focusing on adult T-cell leukemia(ATL). Southern blot analysis for detection of the monoclonal integration of HTLV-I proviral genome, a causative agent of ATL, was performed using digoxigenin-labeled probe. The sensitivity was equivalent to RI-labeled probe and was enough for clinical use. We are also doing Southern blot analysis for immunoglobulin heavy chain gene and T-cell receptor beta chain gene as custom service for the diagnosis of B-lymphoproliferative disorders and non-ATL T-lymphoproliferative disorders. We are reporting such results to the clinical site with our interpretation. Since the band size of the HTLV-I provirus obtained by Southern blot differed in each case and was sometimes smaller than the size of the complete virus, we further analyzed the structure of HTLV-I using long and accurate PCR(LA-PCR) and sequence-target-site PCR(STS-PCR). We found that the integrated HTLV-I provirus is divided into two subtypes, complete virus and defective virus. The incidence of defective virus was high in acute-type ATL compared with that in chronic- or lymphoma-type ATL. Although there are several difficulties in introducing such molecular analyses into the clinical laboratory area, we think that the need is increasing together with the progression of gene therapy and evidence-based medicine.

Blotting, Southern↗
PubMed2000

[A case of acute type adult T cell leukemia and human T-lymphotropic virus type I associated myelopathy who presented meningitis and polyradiculoneuropathy and improved with steroid treatment].

We reported a 35-year-old male patient with acute type adult T cell leukemia(ATL) and human T-lymphotropic virus type I associated myelopathy. He presented meningitis and polyradiculoneuropathy and improved with steroid treatment. He presented headache and sensory ataxia and these symptoms responded to steroid treatment. The usual clinical features of ATL were absent at onset. There existed ATL-like cells in the cerebrospinal fluid and HTLV-I proviral DNA in the blood. Therefore, we surmised that there was monoclonal hyperplasia of the infected cells. He presented ATL after 2 years remission. We pointed out that there was acute type of ATL in patients with meningitis and polyradiculoneuropathy, for which steroid treatment could be effective.

Adult↗
PubMed1999

[Clinical and experimental study of 9 cases of adult T cell leukemia].

OBJECTIVE: In order to clarify the clinical and laboratory features of adult T cell leukemia (ATL): morphology, immunology, cytogenetics, serology and molecular biology. METHODS: Indirect immunofluorescence assay and ELISA were used to detect serum HTLV-I antibody. The HTLV-I provirus sequence were amplified by PCR and confirmed by liquid hybridization. RESULTS AND CONCLUSION: Nine cases of ATL were diagnosed. The major clinical manifestation was lymph node enlargement found in all patients. Skin involvement and osteolysis were not frequent. The characteristic finding was leukemic cells with highly indented or lobulated flower-like nuclei in peripheral blood and bone marrow. ATL cells were CD2, CD3, CD4, CD25 positive and CD8 negative. No specific chromosome abnormality or HLA type was found. Seven of 8 patients examined had HTLV-I antibody. The HTLV-I provirus genome sequence integrated into host cell DNA was amplified by PCR and confirmed by liquid hybridization. All of these results showed that HTLV-I was also the etiological agent of ATL in China. One of the 9 cases of ATL was classified as lymphoma type, one as chronic-type, and the rest as acute type.

Adult↗
PubMed2002

Use of a human patient simulator for the advanced trauma life support course.

A highly anticipated and rewarding component of the Advanced Trauma Life Support (ATLS) program is the surgical skill station. Logistic, societal, and economic issues have resulted in development of human patient simulators (HPSs) as an alternative to the animal model. We studied initial student reaction to a simulator designed for this skill station. Fourteen participants in an ATLS Provider course completed the standard surgical skill stations and an experimental station using the Simulab Trauma Man HPS. After completion of the stations the students were asked to complete a 13-point satisfaction survey using a modified Likert scale (1 = strongly negative/dissatisfied, 5 = strongly positive/satisfied). Overall response was favorable. Students found the HPS to be superior to the animal model in teaching surgical airways [mean 3.64; standard deviation (SD) 0.93] and for management of pneumothorax (mean 3.86; SD 0.77). The students felt the HPS would be useful in ATLS and should be included as an option in training (mean 4.07; SD 0.92). Preliminary experience with an interactive HPS to teach the ATLS surgical skill station is well received by students when compared with standard methods. This strong acceptance supports inclusion of simulators in teaching ATLS skills.

Animals↗
PubMed1992

[Adult T-cell leukemia with Ki-1 expression].

A 64-year-old man was admitted to our hospital complaining of fever and edema in February, 1990. Lymph node biopsy revealed diffuse lymphoma pleomorphic type according to the LSG classification. On hematological examination, leukocyte count was 23,500/microliters, of which 36% abnormal lymphocytes expressing CD2, CD3, CD4 and CD25 as same as the lymph node cells. Anti-HTLV-I antibody in serum was positive. From these data, the diagnosis of adult T-cell leukemia (ATL) was made. ATL cells in the blood and lymph node expressed CD30 (Ki-1). CD30 positive ATL cells derived from the blood was increased after short-term culture. The induction of Ki-1 antigen in cell lines and short-term cultured cells from ATL patients was accompanied by the appearance of the HTLV-I related antigen. Then, we suggest that there was some relation between expression of the Ki-1 antigen and activation by HTLV-I in ATL cells.

Antigens, CD↗
PubMed1992

[Experimental study of laser ablation on lethal arrhythmias--features and effectiveness of epicardial mapping].

To find the exact location of the ventricular arrhythmogenic myocardium, we mapped activation times of local epicardial electrograms (ATLE: 16 bipolar electrodes, 2 x 2 cm2) aided by an on-line computer and guided laser ablation of lethal ventricular arrhythmias induced by aconitine. Thirty-six tests involved 12 dog hearts. Nd:YAG laser application converted ventricular tachycardias and fibrillation to sinus rhythm in all tests. Epicardial mapping results showed: Taking ECG lead II as reference, the differences among all ATLE were within 15ms, and there was no obvious conduct slow zone before drugging and after resuming sinus rhythm, even though 298 +/- 157 mm2 photocoagulation areas (n = 36) resulted from laser irradiation; During VT, the majority of ATLE were preexcited from 90 to 30 ms, and more than one breakthrough point existed, with one predominating; ATLE changed significantly after laser. The ectopic foci were located exactly by using ATLE for laser treatment.

Aconitine↗
PubMed1992

cDNA sequencing confirms HTLV-I expression in adult T-cell leukemia/lymphoma and different sequence variations in vivo and in vitro.

Human T-lymphotropic virus type I (HTLV-I) is the etiological agent of adult T-cell leukemia/lymphoma (ATL) and of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). In both diseases, expression of viral message can generally only be demonstrated by the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. We have previously reported on the the expression of at least four types of alternatively spliced pX mRNAs in vitro and in vivo (1). The sequence variation between HTLV-I pX cDNAs cloned from two different HTLV-I-infected cell lines and from uncultured primary peripheral blood mononuclear cells (PBMC) from two ATL patients was examined. None of the cDNA clones from one of the ATL samples was completely identical to any of the previously cloned cell line messages, establishing that the demonstration of HTLV-I mRNA in ATL is not the result of PCR contamination. Sequence analysis showed that differences between samples can be clustered according to their geographic origin. Cell line cDNAs showed a more marked sequence drift than ATL cDNAs, especially in the long terminal repeat (LTR), demonstrating association of intrastrain variability with culture in vitro. Intrastrain cDNA variability in vivo also suggests ongoing viral replication in infected individuals. A premature stop codon in the pX-II open reading frame (orf) was a common finding, suggesting that the complete putative pX-II protein is not essential for T-cell immortalization or HTLV-I replication.

Base Sequence↗
PubMed2007

Aspirin-triggered lipoxin A4 blocks reactive oxygen species generation in endothelial cells: a novel antioxidative mechanism.

Lipoxins and their aspirin-triggered carbon-15 epimers have emerged as mediators of key events in endogenous anti-inflammation and resolution. However, the implication of these novel lipid mediators on cardiovascular diseases such as hypertension, atherosclerosis, and heart failure has not been investigated. One of the major features shared by these pathological conditions is the increased production of reactive oxygen species (ROS) generated by vascular NAD(P)H oxidase activation. In this study, we have examined whether an aspirin-triggered lipoxin A (4) analog (ATL-1) modulates ROS generation in endothelial cells (EC). Pre-treatment of EC with ATL-1 (1 - 100 nM) completely blocked ROS production triggered by different agents, as assessed by dihydrorhodamine 123 and hydroethidine. Furthermore, ATL-1 inhibited the phosphorylation and translocation of the cytosplamic NAD(P)H oxidase subunit p47 (phox) to the cell membrane as well as NAD(P)H oxidase activity. Western blot and immunofluorescence microscopy analyses showed that ATL-1 (100 nM) impaired the redox-sensitive activation of the transcriptional factor NF- kappaB, a critical step in several events associated to vascular pathologies. These results demonstrate that ATL-1 suppresses NAD(P)H oxidase-mediated ROS generation in EC, strongly indicating that lipoxins may play a protective role against the development and progression of cardiovascular diseases.

Antioxidants↗
PubMed1991

Expression of terminal deoxynucleotidyltransferase gene in a case of adult T-cell leukemia.

A 37-year-old male from Kagoshima Prefecture was admitted with adult T-cell leukemia (ATL). Monoclonal integration of HTLV-1 proviral DNA was found, but the integration site was different from that of terminal deoxynucleotidyltransferase (TdT)-positive MT-1 cells (an ATL cell line). The ATL cells expressed enzymatically active TdT and exhibited 2100 b TdT mRNA, which corresponds to the thymus type of TdT mRNA. The same size of TdT mRNA was also detected in MT-1. Southern blot analyses revealed no differences in the gene structure of the promoter region of TdT genes between this ATL case and TdT-positive lymphoblastic leukemia cells. There is little possibility that cis-acting viral elements promote TdT gene expression by proviral integration. The activation of TdT gene in ATL may be mediated by other trans-acting factors.

Adult↗
PubMed1990

Rearrangements in the human T-cell-receptor alpha-chain locus in patients with adult T-cell leukemia carrying translocations involving chromosome 14q11.

We describe 5 cases of adult T-cell leukemia (ATL) carrying translocations at chromosome 14q11, where the genes for alpha- and delta-chains of the T-cell receptor (TCR alpha/delta) reside (Croce et al., 1985; Isobe et al., 1988). Since the TCR alpha/delta locus is the region where several types of chromosome translocations occur in T-cell tumors, rearrangements of the TCR alpha/delta locus in those ATL cases were studied as a first step to characterize these translocations at the molecular level. For this purpose we have generated an extensive series of probes to define the specificity and the diversity of rearrangement occurring at the widely spanned J alpha-C alpha locus and the complex D delta-J delta-C delta-V delta 2 locus. Using a set of probes, we have found the deletion of the TCR delta locus in all ATL cases, and at least 2 rearrangements in the J delta locus in each case of ATL. It is possible that translocations in the TCR alpha locus may be involved in ATL.

Chromosome Mapping↗
PubMed1990

Epidemiology and immunovirology of human T-cell leukemia/lymphoma virus type I-associated adult T-cell leukemia and chronic myelopathies as seen in France.

Seventeen patients with adult T-cell leukemia (ATL) and 21 with tropical spastic paraparesis/human T-cell leukemia/lymphoma virus type I (HTLV-I)-associated myelopathy (TSP/HAM) were observed during a 3-yr survey (1986-1988) in some hospitals in Paris, France. Most of them were black, originating from high-HTLV-I-endemic areas (West Indies or Africa), but two cases of TSP/HAM occurred in French Caucasians. In one case, the patient acquired the virus from a transfusion during a cardiac transplantation. Most of the ATL cases were diagnosed as acute leukemia or lymphoma, with a proliferation of CD2+, CD3+, CD4+, CD8-, DR+, and CD25+ lymphoid cells. Only three cases were diagnosed as a smoldering ATL. All of the TSP/HAM cases exhibited a spastic paraparesis with a chronic and slow evolution and high HTLV-I antibody titers in serum and cerebrospinal fluid, with a high HTLV-I antibody index and specific HTLV-I immunoglobulin = oligoclonal bands. In TSP/HAM, a high percentage of DR-expressing cells (15 to 40%) was found, with a slightly elevated CD4/CD8 ratio. This was associated with the presence of 1 to 10% abnormally shaped nuclei in lymphoid cells and a polyclonal integration of HTLV-I proviruses in these peripheral blood mononuclear cells. On the contrary, a clonal integration was always found in the ATL malignant cells (leukemic, lymph node, and cutaneous infiltrate). Long-term interleukin 2-dependent T-cell lines (CD2+, CD3+, CD4+, and WT31+) with activated T-cell markers (CD25+ and DR+) producing HTLV-I were established from ATL and TSP/HAM peripheral blood mononuclear cells.

Antigens, CD↗
PubMed1989

[Two color flow cytometry of lymphocytes from patients with adult T-cell leukemia].

Lymphocytes from eight patients with adult T-cell leukemia were analyzed by two color flow cytometry. Monoclonal antibodies (Leu 3 a, Leu 8, Leu 2 a and Leu 15) labelled with fluorescein isothiocyanate or phycoerythrin were used. The purpose was to identify the subsets of the lymphocytes as helper, suppressor/inducer, suppressor or cytotoxic by the surface marker of the cells. All eight patients had antibodies for ATLA. Proviral DNA in the lymphocytes was found in six patients. Summarising the results, OKT4-positive ATL cells were all of the helper T-cell subset, not the inducer subset. OKT8-positive ATL cells were also positive for OKT4 and were all of the cytotoxic T cell subset, not the suppressor subset. In two patients, some ATL cells had both OKT4 and OKT8 on the same cells, especially in the lymph nodes. In our study, ATL cells from eight cases of ATL had all of the helper T subset. These results suggest that the target cells of the human T cell leukemia/lymphoma virus type will be helper T cells.

Adult↗
PubMed1986

Absolute neutrophilia in adult T cell leukemia.

The numbers of neutrophils and platelets and the serum calcium (Ca) levels were examined in 12 patients with lymphoma-type adult T cell leukemia (ATL) and 35 patients with leukemic-type ATL. The same parameters were also studied in 17 patients with non-Hodgkin's lymphoma and 22 patients with acute lymphocytic leukemia as controls. The numbers of neutrophils and the serum Ca levels were significantly higher in leukemic-type ATL (P less than 0.01) and lymphoma-type ATL (P less than 0.05) than in the controls. However, no statistically significant correlation between the numbers of neutrophils and the levels of serum Ca in ATL was observed. Thus, these two abnormal clinical features might be caused by different humoral factors.

Adult↗
PubMed1987

Effect of 1 alpha,25-dihydroxyvitamin D3 on proliferation of activated T-cells and established human lymphotropic virus type I-positive T-cell lines.

The effects of 1 alpha, 25-dihydroxyvitamin D3 [1,25-(OH)2D3] on proliferation and de novo DNA synthesis were studied in the following established human leukemia cell lines: lymphoblastic T-cell lines HPB-ALL, CCRF-HSB-2, p12/lchikawa, and HPB-MLT; adult T-cell leukemia- (ATL) and human lymphotropic virus type I (HTLV-I)-infected T-cell lines HUT102, HUT-102B2, MT-1, MT-2, MJ, C2/MJ, KH-2, KH-2Lo, HPB-CTL-1, and ATN-C1; ATL-derived B-cell lines ATL-BK9 and ATL-BK10; lymphoblastic B-cell line Daudi; and myelocytic-monocytic lineage cell lines HL-60 and U937. 1,25(OH)2D3 inhibited proliferation and de novo DNA synthesis of phytohemagglutinin-P-activated T-cells and certain established HTLV-I-positive T-cells. However, it did not inhibit immature lymphoblastic T- and B-cells or ATL-derived B-cells. The degree of inhibition depended on the dose of 1,25(OH)2D3 and the heterogeneity of the established HTLV-I-positive T-cells. KH-2 and subclone KH-2Lo were markedly inhibited, and HPB-CTL-1 was moderately inhibited. Marked inhibition of DNA synthesis in KH-2Lo cells was observed in the proliferative phase of the cell cycle. No inhibition of KH-2Lo proliferation or expression of interleukin-2 and transferrin receptor was noted after removal of 1,25(OH)2D3 from the culture medium. 1,25(OH)2D3 inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced multinucleated cell formation of various HTLV-I-positive T-cell lines and TPA-induced HTLV-I p19 expression in KH-2Lo cells.

Antigens, Viral↗
PubMed1988

Production of bone-resorbing activity corresponding to interleukin-1 alpha by adult T-cell leukemia cells in humans.

The physicochemical properties and relationship of bone-resorbing activity and interleukin 1 (IL-1) produced by adult T-cell leukemia (ATL) cells and cell line were studied in vitro. The culture supernatant of ATL cell line, MT2, and peripheral blood lymphocytes freshly obtained from ATL patients had both IL-1 activity detected by the stimulation of murine thymocyte-proliferative responses and bone-resorbing activity detected by the stimulation of 45Ca release from prelabeled murine fetal bones. By Sephacryl S-200 column chromatography, both activities were eluted as a single peak at approximately Mr 15,000. By the chromatofocusing technique, the isoelectric point values of both activities were estimated as pH 4.8 and 5.2. Furthermore, both activities were absorbed with rabbit anti-IL-1 alpha antiserum, but not with anti-IL-1 beta antiserum. These results suggest that ATL cells and cell line produce bone-resorbing activity which corresponds to IL-1 alpha and that this IL-1 alpha is one of the most important causes of hypercalcemia in ATL patients.

Biological Assay↗