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At least 559 records · Page 31Linked to original sources
PubMed2006

Antibody responses associated with the graft-versus-leukemia effect in adult T-cell leukemia.

Adult T-cell leukemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). The prognosis of ATL, especially the acute and lymphoma subtypes, is poor with conventional and high-dose chemotherapy. The effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ATL has been reported, suggesting the presence of a graft-versus-leukemia (GVL) effect against this malignancy. To identify the target antigens associated with tumor rejection, we used SEREX (serological identification of antigens by recombinant cDNA expression cloning) to screen ATL complementary DNA expression libraries with sera from an ATL patient who had a GVL response after allo-HSCT. Among the isolated clones, autocrine motility factor receptor (AMFR), which encodes a glycosylated transmembrane protein, was found to have selective reactivity with the sera obtained during tumor regression. Real-time reverse transcription polymerase chain reaction analysis for AMFR showed highest expression in the testis among normal tissues. Furthermore, aberrant AMFR expression was found in at least some ATL patients. Taken together, these findings suggest that AMFR may be one of the GVL antigens that provoke effective antitumor immunity against ATL in allogeneic settings.

Antibody Formation↗
PubMed1995

Adult T-cell leukemia.

Adult T-cell leukemia (ATL) was first reported in Japan, where it has a high incidence in the southwestern region. The retrovirus, human T-lymphotropic virus type I (HTLV-I), is the causative agent of ATL. In ATL-endemic areas, the rate of HTLV-I carriers is high. A definite diagnosis of ATL is based on the presence of HTLV-I proviral DNA in the tumor cell DNA. ATL cells originate from the CD4 subset of peripheral T cells. ATL shows diverse clinical features but can be divided into four subtypes:acute, chronic, smoldering, and lymphoma type. Chemotherapy is not effective; the acute and lymphoma types have a poor prognosis. Familial occurrence of ATL is common. HTLV-I infection is caused by transmission of live infected lymphocytes from mother to child, from man to woman, or by blood transfusion. Infection with HTLV-I can lead to other diseases, including HTLV-I-associated myelopathy/tropical spastic paraparesis and HTLV-I uveitis.

Adult↗
PubMed1996

[Inhibition of proliferation by retinoic acid on adult T cell leukemia cells].

We observed the effects of the retinoic acid (13-cis retinoic acid; 13-cis RA, and all-trans retinoic acid; ATRA) for the cell growth and the expression of CD 25 on peripheral blood mononuclear cells (PBMC) from 17 patients with adult T cell leukemia (ATL). Fourteen had acute type, 1 had chronic type, and 2 had smoldering type of ATL. We divided those patient into 3 groups (hyper-sensitive, sensitive and resistant group) by determined with reduction rate of [3H]-thymidine incorporation obtained before and after treatment with 13 -cis RA or ATRA respectively. Growth inhibition was not observed in normal PBMC by 13 -cis RA or ATRA. However, no down-regulation of CD 25 expression was observed on PBMC in all patients and normal individuals after treatment with 13-cis RA or ATRA. In the aspect of growth inhibition on PBMC in ATL patients, we tried to clarify the mechanism of the phenomenon. In agarose gel electrophoresis, extracted genomic DNA from retinoic acid treated PBMC in hyper-sensitive and sensitive ATL patients showed multimer DNA fragmentation pattern. On the other hand, genomic DNA from PBMC after treatment with retinoic acid in resistant ATL patients and normal individuals showed high molecular DNA pattern without fragmentation. Taken together, it is suggested that retinoic acid could induce growth inhibition of PBMC in some ATL patients resulting in DNA fragmentation, apoptosis. We deeply consider that retinoic acid may be an useful agent for ATL patients in clinical aspect.

Adult↗
PubMed2004

Impact of achilles tendon lengthening on functional limitations and perceived disability in people with a neuropathic plantar ulcer.

OBJECTIVE: An Achilles tendon-lengthening (ATL) procedure is effective at reducing ulcer recurrence in patients with diabetes, peripheral neuropathy, and a plantar ulcer, but its effects on functional limitations and perceived disability are unknown. The purpose of this study is to report the effects of an ATL and total contact casting (TCC) on the functional limitations and perceived disability of patients with neuropathic plantar ulcers. RESEARCH DESIGN AND METHODS: Twenty-eight subjects with a mean age of 55 +/- 10 years and a BMI of 33 +/- 6 kg/m(2) participated. All subjects had a history of diabetes, loss of protective sensation, limited ankle motion, and a recurrent forefoot ulcer. Subjects were randomized into two groups: an ATL group (n = 14), who received treatment of ATL, and TCC and a TCC group (n = 14), who received TCC only. Subjects completed a modified physical performance test (PPT) and the SF-36 Health Survey before treatment, after primary treatment and healing of the plantar forefoot ulcer, and 8 months after initial ulcer healing. RESULTS: There were no significant changes in functional limitations as measured by the PPT between groups or over time. The physical summary score of the SF-36 decreased slightly from before treatment to 8 months after initial ulcer healing in the ATL group (35 +/- 7 to 31 +/- 6), whereas the TCC group score increased during this time (34 +/- 8 to 39 +/- 11; P < 0.05). CONCLUSIONS: The ATL resulted in no measurable change in functional limitations, but patients receiving an ATL and TCC reported lower physical functioning at 8 months after initial ulcer healing than subjects receiving TCC alone and may require additional physical therapy to address this perceived disability.

Achilles Tendon↗
PubMed1993

Six Colombian patients with adult T-cell leukemia/lymphoma.

Six Colombian patients with adult T-cell leukemia/lymphoma (ATL) are presented. The clinical and hematological features, the familial clusters of human T lymphotropic virus type 1 (HTLV-I) carriers and the prognoses of the Colombian ATL patients were similar to those previously reported for Japanese ATL patients. The only difference was the mean age of onset, which was more than 20 years younger than in Japanese patients. Three patients with ATL were suffering from strongyloidiasis. In one patient it was suggested that ATL developed after horizontal transmission from his wife. In addition, there was a familial case of ATL and HAM/TSP. It seems that in some areas of Colombia, not only HTLV-I infection and HAM/TSP but also ATL are highly endemic.

Adolescent↗
PubMed1994

Down-regulation of CD3 antigen on adult T cell leukemia cells.

The immunological abnormality of T lymphocytes in patients with adult T cell leukemia (ATL) is characterized by the abnormal enhanced expression of the 55 kDa chain of the receptor for interleukin 2 (IL-2R/p55) (Tac), and down-regulation of CD3 antigen. Using serum and culture supernatants of leukemic cells from ATL patients (Group A) whose CD3 expression was down-regulated and those whose CD3 was not low (Group B), the possible mechanism of CD3 down-regulation on ATL cells was investigated. When PBMC from normal individuals were cultured with sera from ATL patients for 24 hrs, CD3 expression revealed by means of fluorescent intensity (MFI) was down-regulated by sera from ATL patients in Group A (MFI: Pt.1 = 51.6 +/- 4.5, Pt.2 = 48.0 +/- 6.9, Control = 96.5 +/- 6.6), not by sera from patients in Group B (MFI: Pt.3 = 105.5 +/- 7.9, Pt.4 = 102.5 +/- 8.3, Control = 96.5 +/- 6.6). When normal PBMC were cultured with supernatants of leukemic cells from ATL patients in Group A, the same CD3 down-regulating activity was also detected (MFI: Pt.1 = 78.0 +/- 10.2, Pt.2 = 70.6 +/- 8.7, Control = 94.0 +/- 6.6). By using gel-chromatography, the fractionated supernatants from ATL patients in Group A decreased CD3 expression of normal PBMC significantly (MFI: Pt.1 = 22.9 +/- 5.8, Pt.2 = 28.8 +/- 7.4, Control = 92.1 +/- 9.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1999

Epstein-Barr virus involvement in T-cell malignancy: significance in adult T-cell leukemia.

Epstein-Barr virus (EBV) was first reported as the causative virus of Burkitt's lymphoma in 1964. Since then, EBV has also been associated with infectious mononucleosis, AIDS and transplant-related B cell lymphomas, and nasopharyngeal cancer. The virus has further been linked with T cell lymphomas, Hodgkin disease, and NK leukemia or LGL leukemia, establishing a concept of a wide spectrum of EBV associated malignant disorders. EBV DNA encodes several proteins such as EBNA1-6, LMP 1, 2 and others. Recent studies have demonstrated that EBNA2, EBNA5, EBNA3A, EBNA 3C are essential for transformation, and that any gene product is not sufficient to transform cells by itself. Further there are different mechanisms of virus-associated transformation or carcinogenesis among EBV-associated malignant disorders. On the other hand, human T lymphotropic virus type I (HTLV-I) is known as a causative virus of adult T cell leukemia (ATL). However, precise molecular mechanisms of leukemogenesis in ATL still remains unclear. Some additional factors to HTLV-I infection are supposed to be involved in complete leukemogenesis. We demonstrated that HTLV-I infected T cells and primary ATL cells express EBV receptor/CD21 on the cell surface. Therefore, it is possible that EBV infection is one of the factors. We further investigated this possibility in 6 HTLV-I infected T cell lines and primary ATL cells from 18 patients with ATL. However, no EBV genome was detected in both T cell lines and primary ATL cells. EBV involved T-cell lymphoma has unique clinical manifestations as compared to non-EBV involved T-cell lymphoma. Therefore, it is still possible that a small group of ATL patients with unique clinical manifestations is associated with EBV.

Adult↗
PubMed2006

Attenuation of gastric mucosal inflammation induced by aspirin through activation of A2A adenosine receptor in rats.

AIM: To determine whether a specific adenosine A(2A) receptor agonist (ATL-146e) can ameliorate aspirin-induced gastric mucosal lesions in rats, and reduce neutrophil accumulation and production of pro-inflammatory cytokines. METHODS: Gastric lesions were produced by oral gavage of aspirin (200 mg/kg) and HCl (0.15 mol/L, 8.0 mL/kg). 4-{3-[6-Amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-cyclohexanecarboxylic acid methyl ester (ATL-146e, 2.5-5 mug/kg, IP) was injected 30 min before the administration of aspirin. Tissue myeloperoxidase (MPO) concentration in gastric mucosa was measured as an index of neutrophil infiltration. Gastric mucosal concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were determined by ELISA. Also, we examined the effect of ATL-146e on tissue prostaglandin E2 (PGE2) production and gastric secretion. RESULTS: Intragastric administration of aspirin induced multiple hemorrhagic erosions in rat gastric mucosa. The total length of gastric erosions (ulcer index) in control rats was 29.8+/-7.75 mm and was reduced to 3.8+/-1.42 mm after pretreatment with 5.0 g/kg ATL-146e (P<0.01). The gastric contents of MPO and pro-inflammatory cytokines were all increased after the administration of aspirin and reduced to nearly normal levels by ATL-146e. Gastric mucosal PGE2 concentration was not affected by intraperitoneal injection of ATL-146e. CONCLUSION: The specific adenosine A(2A) receptor agonist, ATL-146e, has potent anti-ulcer effects presumably mediated by its anti-inflammatory properties.

Animals↗
PubMed1999

Constitutive activation of NF-kappaB in primary adult T-cell leukemia cells.

Human T-cell leukemia virus type I (HTLV-I) is an etiologic agent of adult T-cell leukemia (ATL). The viral protein Tax induces the activation and nuclear translocalization of transcription factor NF-kappaB, which is proposed to play a crucial role in the transformation of T cells by HTLV-I. However, the HTLV-I genes including Tax are not expressed significantly in primary leukemic cells from ATL patients. In this study, we examined the basis for NF-kappaB activation in freshly isolated leukemic cells from ATL patients. We found that leukemic cells from ATL patients, like HTLV-I-infected T-cell lines, display constitutive NF-kappaB DNA binding activity and increased degradation of IkappaBalpha (an inhibitor of NF-kappaB). Whereas the NF-kappaB binding activity in Tax-expressing T-cell lines consisted mostly of p50/c-Rel, fresh ATL samples contained p50/p50 and p50/p65 heterodimers. One T-cell line derived from ATL leukemic cells, TL-Om1, displayed constitutive NF-kappaB activity, as well as enhanced degradation of IkappaBalpha, despite the lack of detectable Tax expression. Interestingly, the NF-kappaB in TL-Om1 consists of p50/p50 and p50/p65 like that in fresh primary leukemic cells. Our results suggest that activation of NF-kappaB occurs through a Tax-independent mechanism in leukemic cells of ATL patients, possibly due to differential NF-kappaB subunit activation.

DNA, Neoplasm↗
PubMedDate not supplied

HTLV-I serostatus of mothers of patients with adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis.

OBJECTIVES: It has been shown that > 90% of mothers of HTLV-I-infected children were themselves carriers of HTLV-I. This study was designed to determine the HTLV-I serostatus of mothers of patients with adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and to assess the association of age of exposure and disease outcome. STUDY DESIGN/METHODS: In a cross-sectional study of the HTLV-I serostatus of mothers of HTLV-I-seropositive patients with ATL and HAM/TSP, 36 living mothers of patients with ATL and 15 mothers of patients with TSP/HAM were traced and enrolled. RESULTS: Five of the 15 (33%) mothers of patients with HAM/TSP and 35 of the 36 (97.2%) mothers of patients with ATL were HTLV-I-seropositive. All patients were breast-fed and none received blood transfusions. CONCLUSION: This study confirms that infection with HTLV-I in early childhood can lead to ATL in later life, and that HAM/TSP can also result from early infection but more commonly results from infection acquired in adulthood. There are several reports of posttransfusion HAM/TSP, but ATL has not been reported following blood transfusion except in patients who were immunocompromised. Because the newborn infant is considered to be immunoincompetent, it seems that this is a necessary factor for the development of ATL after infection.

Adolescent↗
PubMed1999

A rapid method for determination of the relative copy number of HTLV-I proviral genome in HTLV-I carriers and adult T-cell leukemia patients by polymerase chain reaction.

Ten adult T-cell leukemia (ATL) patients and 11 asymptomatic human T-cell leukemia virus type I (HTLV-I) carriers were examined by polymerase chain reaction (PCR) assay with a reduced sensitivity to evaluate its utility in detecting the relative copy number of the HTLV-I genome in clinical samples. Differences in the intensities of the PCR products were observed between the acute type ATL patients and ATL patients in remission or carriers. Intense bands were found in all acute type ATL patients (6/6, 100%), while specific bands were seen in only 2 carriers (2/11, 18.2%). The bands found in one of the two patients in remission were weak. One patient, who had acute type ATL, had achieved a remission but later relapsed. Using this technique, we examined the differences in the intensities of the bands of the PCR products in a patient with acute type ATL who had achieved remission but later relapsed. Thus, this technique may be of clinical importance in diagnosing acute ATL and assessing the effect of therapy.

Adult↗
PubMed1992

Altered expression of protein kinase C in adult T-cell leukemia cells.

Protein kinase C (PKC) has been shown to be involved in the mitogenic response and in oncogenic cell transformation in many experimental models. We analyzed the expression of PKC in both highly purified leukemic T cells freshly isolated from adult T-cell leukemia (ATL) patients and control T lymphocytes obtained from healthy volunteers. PKC activity was decreased in the ATL cells as compared with the control T cells. Cytosolic PKC activity in the ATL cells was remarkably decreased, whereas particulate membrane PKC activity was similar to the control level. The percentage of PKC activity in the particulate fraction was 34% in the ATL cells and 19% in the control cells. Regarding the altered subcellular localization of PKC activity, phorbol ester-induced translocation of cytosolic PKC was inhibited in some ATL cases. Similarly to the decrease in PKC activity, there was a decrease in the expression of the major PKC isozymes II(beta) and III(alpha) in ATL cells. These results suggest impaired regulation of PKC expression in ATL as well as in many experimental cancers.

Adult↗
PubMed2004

Growth arrest and apoptosis in adult T cell leukemia cell lines following IL-2 deprivation.

Adult T-cell leukemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukemia virus type-I (HTLV-I). Since ATL cells often require IL-2 for their proliferation and survival, we examined the effect of IL-2 deprivation on the IL-2-dependent ATL cells established from ATL patients. After IL-2 withdrawal, these cells were arrested in the G1 phase and then underwent apoptosis. p27Kip1 was observed to act as a cell cycle inhibitor. A decrease in the amount of Bcl-xL was more distinct than that of Bcl-2, while Bax increased slightly during IL-2 withdrawal. The activation of caspase-3 and the loss of mitochondrial membrane potential were also observed. An overexpression of Bcl-xL protein in the KK1, one of the ATL cell lines, suppressed apoptosis by the 3rd day, however, apoptosis could not be prevented completely. Thereafter, a decrease in Bcl-xL and an activation of caspase-3 were observed even under the overexpression of Bcl-xL. The mitochondrial membrane potential and the intra-cellular levels of reactive oxygen species (ROS) also changed due to IL-2 deprivation. From these results, the IL-2 signals are considered to be essential for the survival of ATL cells, and the interruption of IL-2 signaling might thus be useful as a potentially new treatment for ATL.

Adult↗
PubMed1992

[Natural history of HTLV-I infection].

Adult T-cell leukemia (ATL), a disease entity first described by Takatsuki et al., is endemic in southwestern Japan, the Caribbean Islands, and in some parts of Africa. ATL patients are classified into four subtypes according to the clinical picture: acute, chronic, smoldering, and lymphoma type. The diagnosis of ATL is made from the characteristic clinical findings, the detection of serum antibodies to HTLV-I, and when necessary, the confirmation of monoclonal integration of HTLV-I proviral DNA in cellular DNA of ATL cells. Recently, diagnostic criteria for clinical subtypes of ATL were proposed by the Lymphoma Study Group in Japan: 1) smoldering type, normal lymphocyte level, no hypercalcemia, lactate dehydrogenase (LDH) value 1.5 times the upper limit of normal or lower, no lymphadenopathy, no involvement of liver, spleen, central nervous system (CNS), bone or gastrointestinal tract, and no ascites or pleural effusion: 2) chronic type, absolute lymphocytosis with T-lymphocytosis of greater than 3 x 10(9)/1, LDH value twice the upper limit of normal or lower, no hypercalcemia, no involvement of CNS, bone, or gastrointestinal tract, and no ascites or pleural effusion: 3) lymphoma type, no lymphocytosis, 1% or less abnormal lymphocytes, and histologically-proven lymphadenopathy: 4) acute type, remaining ATL patients who are not classified as any of the above types. Infection with HTLV-I is a direct cause of ATL. Furthermore, infection with this virus can indirectly cause many other diseases via the induction of immunodeficiency, such as chronic lung diseases, opportunistic lung infections, cancer of other organs, monoclonal gammopathy, chronic renal failure, strongyloidiasis, non-specific dermatomycosis, non-specific lymph node swelling, HTLV-I associated myelopathy (HAM/TSP), and HTLV-I uveitis.(ABSTRACT TRUNCATED AT 250 WORDS)

CD4-CD8 Ratio↗
PubMed1991

[A case of adult T-cell leukemia with a defective HTLV-I proviral DNA, in which the single T-cell clone appeared to have progressed from chronic phase to crisis].

A 39-year-old woman was first admitted to our hospital with increased white cell count on May, 1983. Physical examination showed only mild splenomegaly. Hematological examination revealed leukocytosis (14,600/microliters) with ATL cells (59%). Serum anti-HTLV-I antibody was positive. Examination of HTLV-I provirus in the abnormal T cells revealed the defective type. She was diagnosed as chronic type of ATL based on the clinical features. Cytogenetic study of the ATL cells revealed 47, xx, +4. For 12 months, she was followed without any therapy. WBC reduced to almost normal range and ATL cells decreased to 3 to 6% for 8 months. On May, 1985, she was readmitted to our hospital because of leukocytosis (32,200/microliters), and increased ATL cells (57%). She was diagnosed as crisis of ATL. Investigation of the proviral DNA and chromosome showed the same results as those of the chronic phase, indicating that ATL cells in both the chronic phase and the crisis phase originated from the same clone. She died after 3 months from massive diarrhea. Postmortem examination showed the extensive infiltration of leukemic cell in the small intestine.

Adult↗
PubMed1990

[Treatment of adult T-cell leukemia with intravenous administration of IFN-gamma-immunohistochemical studies of infiltrating cells in cutaneous lesions].

Three cases of adult T-cell leukemia (ATL) with cutaneous lesions of disseminated papules or nodules were treated with recombinant human interferon-gamma (IFN-gamma) by intravenous administration. Clinical stage of each case was different, i.e., 1) preleukemic state of ATL (pre-ATL), 2) chronic-type ATL, and 3) crisis-type ATL. We evaluated clinical efficacy of IFN-gamma, and performed immunohistochemical analysis of biopsy specimens derived from cutaneous lesions of the patients both before and during treatment. The case of pre-ATL achieved a complete remission of cutaneous lesions for 18 months. The other cases also obtained clinical responses with a shorter duration, but relapsed while they are still on IFN-gamma therapy. The cutaneous lesions reduced in size during the therapy associated with a decrease in the ratio of Leu3a + 3b (CD4)+ cells in all three cases. After the therapy, Leu7 (HNK-1)+ cells increased in all cases, and LeuM5 (CD11)+ cells did in two. These results suggested that IFN-gamma enhanced tumor immunity although its clinical effect was less clear. Only in the cutaneous lesions of pre-ATL case an increased number of LeuM5+ cells, probably monocyte-macrophage series in host defence, were seen before the therapy. And IFN-gamma was useful for this case after all.

Female↗
PubMed1990

Calcium dependency of the production of interleukin 1 and the expression of interleukin 1 receptors of human adult T-cell leukemia cells in vitro.

The effect of calcium on the production of interleukin 1 (IL 1) and the expression of IL 1 receptors (R) of adult T-cell leukemia (ATL) cells was studied in vitro. ATL cells freshly obtained from patients and ATL cell lines produced limited amounts of IL 1 by culturing in a low-calcium concentration of medium (less than 0.01 mM). However, the production of IL 1 was enhanced by the addition of calcium chloride to the medium in a concentration-dependent manner and reached the maximum at the higher calcium concentration (3-4 mM) than at the standard calcium concentration of medium (1.26 mM). The production of IL 1 from ATL cells was further enhanced by calcium ionophore. Furthermore, the expression of IL 1R on ATL cells was augmented in proportion to the extracellular calcium concentration and calcium ionophore. In accordance with the change of the extracellular calcium concentration, the intracellular calcium concentration of ATL cells detected by Fura 2 was changed. However, this calcium dependency was not observed in the human T-cell leukemia virus I-negative acute T-cell leukemia cells. These results suggest that calcium plays a critical role in the regulation of the production of IL 1 and the expression of IL 1R on ATL cells.

Adult↗
PubMed1990

[Serum deoxythymidine kinase in adult T-cell leukemia and its related disorders].

Using Prolifigen TK kit "Daiichi", the serum TK level were determined in patients with adult T-cell leukemia (ATL) and its related disorders. The mean level of serum TK at diagnosis was 279.9 U/l in acute type ATL, 27.8 U/l in chronic type ATL, 59.0 U/l in lymphoma type ATL, 3.1 U/l in pre-ATL and 2.4 U/l in HTLV-I carriers. In these patients, six other kinds of tumor markers such as lactic dehydrogenase, beta 2-microglobulin, immunosuppressive acidic protein, ferritin, tissue polypeptide antigen and carcinoembryonic antigen were also examined. Among the seven tumor markers, TK level showed the most significant difference among clinical subtypes of ATL. This indicates that the TK level is one of the promising parameters indicative of aggressiveness of ATL cells.

Adult↗