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At least 955 records · Page 53Linked to original sources
PubMed1994

A lymphokine, provisionally designated interleukin T and produced by a human adult T-cell leukemia line, stimulates T-cell proliferation and the induction of lymphokine-activated killer cells.

In early phases of human T-cell lymphotrophic virus I-induced adult T-cell leukemia (ATL), the malignant cell proliferation is associated with an autocrine process involving coordinate expression of interleukin (IL) 2 and its receptor. However, during late-phase ATL, leukemic cells no longer produce IL-2 yet continue to express high-affinity IL-2 receptors. During studies to define pathogenic mechanisms that underlie this IL-2-independent proliferation, we demonstrated that the ATL cell line HuT-102 secretes a lymphokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Conditioned medium from HuT-102, when added to the IL-2-dependent CTLL-2 line, yielded a stimulation index of 230. Since CTLL-2 was purported to be IL-2-specific, we performed a number of studies to exclude IL-2 production by HuT-102. Stimulation of CTLL-2 cells by HuT-102-conditioned medium was not meaningfully inhibited by addition of an antiserum to IL-2. Furthermore, uninduced HuT-102 cells did not express mRNA encoding IL-2 as assessed by Northern blot analysis. No biological activity on CTLL-2 cells was mediated by purified IL-1, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12, IL-13, or granulocyte/macrophage colony-stimulating factor, thus differentiating these factors from IL-T. Based on preliminary biochemical data, IL-T is a protein with a pI value of 4.5 and a molecular mass in SDS gels of 14 kDa. In addition to its action on CTLL-2 cells, 3200-fold-purified IL-T stimulated proliferation of the human cytokine-dependent T-cell line Kit-225. Furthermore, addition of IL-T enhanced cytotoxic activity of large granular lymphocytes (i.e., induced lymphokine-activated killer cells). Thus, IL-T is a lymphokine that plays a role in T-cell proliferation and induction of lymphokine-activated killer cells. Furthermore, IL-T may contribute to IL-2-independent proliferation of select ATL cells and lines.

Animals↗
PubMed2001

Biophysical modelling of proton radiation effects based on amorphous track models.

PURPOSE: To define a photon-equivalent dose in charged particle therapy one needs to know the RBE (Relative Biological Effectiveness) in the target region as well as in the surrounding tissue. RBE estimates are difficult since both the physical input parameters, i.e. LET distributions, and, even more so, the biological input parameters, i.e. cell nucleus size and local response, are not known in general. Track structure theory provides a basis for predicting dose-response curves for particle irradiation. There are (at least) two somewhat different algorithms: the Amorphous Track Partition model (ATP) and the Amorphous Track Local effect model (ATL). Both have been reported to give good agreement with observed radiobiological data. We were interested in a general comparison and in the predictive power of these models for protons. MATERIALS AND METHODS: We compared the principles of the two track structure approaches. The general dependencies of the model predictions on the input parameters are investigated. The model predictions for protons with respect to cell survival of V79 cells are compared with measurements. RESULTS: Although based on similar assumptions, the application of track structure theory in terms of the computational procedure is different for the two models. The ATP model provides a set of equations to predict inter- and intratrack radiation response whereas the ATL model is based on Monte Carlo simulations. One conceptual difference is the use of average doses in subtargets in the ATP model compared with the use of local doses in infinitesimal compartments in the ATL model. The ATP concept introduces an empirical scaling of the cross-section from subcellular to cellular response. The ATL concept inherently requires a critical adjustment of parameters handling the high local dose region near the track centre. The models predict proton survival curves reasonably well but neither shows good agreement with experimental data over the entire range of proton energy and absorbed dose considered. CONCLUSION: Designed for heavy ion applications, the models show weaknesses in the prediction of proton radiation effects. Amorphous track models are based on assumptions about the properties of the biological target and the radiation field that can be questioned. In particular, the assumption of subtargets and the multitarget/single-hit response function on one hand and the parameterization of radial dose and high dose cellular response on the other hand leave question marks.

Animals↗
PubMed2002

Arsenic trioxide induces apoptosis in HTLV-I infected T-cell lines and fresh adult T-cell leukemia cells through CD95 or tumor necrosis factor alpha receptor independent caspase activation.

Arsenic trioxide (As2O3) has been reported to induce apoptosis in human T-cell leukemia virus type-I (HTLV-I) infected T-cell lines and fresh adult T-cell leukemia (ATL) cells and to induce G1 phase accumulation in HTLV-I infected T-cell lines. The present study aimed to clarify the pathway of As2O3-induced apoptosis in HTLV-I infected T-cell lines, MT-1 and MT-2, and fresh ATL cells separated from peripheral blood of patients with acute or chronic type ATL. Cells were treated up to 72 h at clinically tolerable concentrations of As2O3 (1-2 micromol/l) shown to be safe in patients with acute promyelocytic leukemia (APL). Activation of caspases 3, 8, and 9, loss of mitochondrial transmembrane potential and cleavage of poly (adenosine diphosphate-ribose) polymerase (PARP) were observed during As2O3 treatment. Furthermore, prior exposure to a broad-spectrum caspase inhibitor blocked As2O3-induced apoptosis but not G1 phase accumulation. While pre-treatment with a CD95 receptor-blocking antibody (Ab) or a TNF-alpha neutralizing Ab did not show such inhibitions in these cells. In conclusion, As2O3 induces apoptosis in HTLV-I infected T-cell lines and fresh ATL cells through CD95 or TNF-alpha receptor independent caspase activation.

Antineoplastic Agents↗
PubMed1985

Origin of human T-lymphotrophic virus I-positive T cell lines in adult T cell leukemia. Analysis of T cell receptor gene rearrangement.

Using the clone-specific rearrangement of the T cell receptor gene as the genetic marker of the clonotype, we analyzed the clonal origin of the interleukin 2 (IL-2)-dependent human T-lymphotrophic virus I (HTLV-I)-positive T cell lines established from various adult T cell leukemia (ATL) patients. From a patient with chronic ATL, whose leukemic cells proliferated in vitro in response to IL-2, we repeatedly established leukemic T cell clones having the same rearrangement profile of the T beta chain gene as the leukemic cells. By contrast, established cell lines from acute ATL patients had different beta chain gene rearrangements from those of the leukemic cells. These HTLV-I+ T cell lines might not be the direct progeny of the leukemic cells, but that of T cells infected either in vivo or in vitro. These IL-2-reactive nonleukemic T cells might have been selected in vitro, because their leukemic cells failed to respond to IL-2, despite the expression of IL-2 receptor. The analysis of the T cell receptor gene rearrangement may give a new approach for the elucidation of the mechanism of leukemogenesis and the origin of the HTLV-I+ T cell lines in ATL.

Acute Disease↗
PubMed2000

Activation of lipoxin A(4) receptors by aspirin-triggered lipoxins and select peptides evokes ligand-specific responses in inflammation.

Lipoxin (LX) A(4) and aspirin-triggered LX (ATL) are endogenous lipids that regulate leukocyte trafficking via specific LXA(4) receptors (ALXRs) and mediate antiinflammation and resolution. ATL analogues dramatically inhibited human neutrophil (polymorphonuclear leukocyte [PMN]) responses evoked by a potent necrotactic peptide derived from mitochondria as well as a rogue synthetic chemotactic peptide. These bioactive lipid analogues and small peptides each selectively competed for specific (3)H-LXA(4) binding with recombinant human ALXR, and its N-glycosylation proved essential for peptide but not LXA(4) recognition. Chimeric receptors constructed from receptors with opposing functions, namely ALXR and leukotriene B(4) receptors (BLTs), revealed that the seventh transmembrane segment and adjacent regions of ALXR are essential for LXA(4) recognition, and additional regions of ALXR are required for high affinity binding of the peptide ligands. Together, these findings are the first to indicate that a single seven-transmembrane receptor can switch recognition as well as function with certain chemotactic peptides to inhibitory with ATL and LX (lipid ligands). Moreover, they suggest that ALXR activation by LX or ATL can protect the host from potentially deleterious PMN responses associated with innate immunity as well as direct effector responses in tissue injury by recognition of peptide fragments.

Animals↗
PubMed2001

Characterization of the importance of Staphylococcus epidermidis autolysin and polysaccharide intercellular adhesin in the pathogenesis of intravascular catheter-associated infection in a rat model.

A rat central venous catheter (CVC) infection model was used to assess the importance of the proteinacious autolysin (AtlE) and the polysaccharide intercellular adhesin (PIA) in the pathogenesis of Staphylococcus epidermidis CVC-associated infection. Wild-type (wt) S. epidermidis O-47 was significantly more likely to cause a CVC infection than was either of the isogenic mutant strains (AtlE-negative [O-47mut1] or PIA-negative [O-47mut2]). Bacteria were retrieved from the explanted catheters of 87.5% of rats inoculated with S. epidermidis O-47, compared with 25% of rats challenged with either S. epidermidis O-47mut1 or O-47mut2 (P=.007). Peripheral bacteremia was documented in 75% of rats challenged with S. epidermidis O-47, compared with 12.5% and 25% challenged with O-47mut1 and O-47mut2, respectively (P=.009). Metastatic disease was more common in rats inoculated with wt S. epidermidis, compared with AtlE- or PIA-deficient mutants. These results confirm the importance of initial adherence, associated with AtlE, and biofilm production, mediated by PIA, in the pathogenesis of S. epidermidis experimental CVC infection.

Animals↗
PubMed2003

Expression of biofilm-associated genes in Staphylococcus epidermidis during in vitro and in vivo foreign body infections.

The expression of the genes icaA, icaC, aap, and atlE--with a putative role in the pathogenesis of Staphylococcus epidermidis foreign body infections--and of mecA and 3 housekeeping genes (gmk, tpi, and hsp60) was examined in vitro and in vivo. In vitro expression levels of ica, atlE, and gmk were higher in sessile than in planktonic bacteria. Exposure to foreign bodies in vitro and in vivo induced a sharp increase in ica expression that was followed by a progressive decrease. The in vivo expression of aap and mecA was high during early but low during late foreign body infections. The in vivo expression of atlE and gmk remained relatively high and stable. In conclusion, biofilm genes encoding for structural elements are mainly expressed during early foreign body infections. The ica genes are associated with initial colonization but not with persistence. The constant expression of atlE and gmk may indicate a role during the entire course of foreign body infections.

Animals↗
PubMed1996

Gene therapy for adult T cell leukemia using human immunodeficiency virus vector carrying the thymidine kinase gene of herpes simplex virus type 1.

Adult T cell leukemia/lymphoma (ATL) is derived from CD4+ T cells and has a poor prognosis because of its resistance to chemotherapy. To evaluate the effectiveness of gene therapy for ATL, the effect of ganciclovir on ATL cell lines transfected with the thymidine kinase gene of herpes simplex virus type 1 (HSV-TK) was analyzed. To transfer the HSV-TK gene to ATL cells, a human immunodeficiency virus (HIV) vector that has specific infectivity to CD4+ cells was used. HSV-TK was inserted into the long terminal repeats of HIV-1 and driven by the SL3 promoter HXBSL3TK. HXBSL3TK was co-transfected with HXBCAT as a reporter into MT2 or HUT102 cells by DEAE-dextran. The cells were incubated with ganciclovir, and chloramphenicol acetyltransferase (CAT) activity was analyzed. The CAT activity of the MT2 cells and HUT102 cells transfected with HXBSL3TK decreased dose-dependently with ganciclovir. HXBSL3TK was also co-transfected into COS cells with an HIV-1 packaging vector that has gag, pol, and env driven by a cytomegalovirus promoter. The supernatant was transferred to MT2 cells or Raji cells and incubated with ganciclovir. Ninety percent of the MT2 cells transduced by HXBSL3TK and incubated with ganciclovir were killed, but Raji cells were not killed. In addition, HXBTK that expresses the HSV-TK gene and Tat gene driven by the LTR of HIV-1 was constructed. HXBTK had a higher expression of the HSV-TK gene and higher sensitivity to ganciclovir than did HXBSL3TK.

Animals↗
PubMed1994

Lymphokine receptors: a target for immunotherapy of lymphomas.

Lymphoma cells often express lymphokine receptors that provide a target for therapy. For example, malignant cells of patients with HTLV-1-associated adult T-cell leukemia/lymphoma (ATL) express IL-2 receptors. In contrast, normal resting cells do not express the IL-2 receptors identified by the anti-Tac monoclonal antibody. Using the unmodified anti-Tac monoclonal antibody, one-third of the 19 patients treated with ATL have undergone a remission. However, unmodified murine monoclonal antibodies are limited by their immunogenicity and their poor effector functions. To address these issues, we used genetic engineering to produce humanized anti-Tac that contains the complementarity-determining regions from the mouse with the remainder of the antibody derived from human IgG1-kappa. Humanized anti-Tac is dramatically less immunogenic than the murine versions and, in contrast to the parent antibody, manifests antibody-dependent cellular cytotoxicity with human mononuclear cells. To enhance its effector function, anti-Tac was armed with toxins or with alpha- and beta-emitting radionuclides. In a clinical trial with 90Y-anti-Tac, 11 of the 17 patients with ATL underwent a partial or sustained complete remission. Thus, the clinical application of lymphokine-receptor-directed therapy provides a new perspective for treatment of certain lymphomas, including HTLV-1-associated ATL.

Antibodies, Monoclonal↗
PubMed2006

Commensal isolates of methicillin-resistant Staphylococcus epidermidis are also well equipped to produce biofilm on polystyrene surfaces.

OBJECTIVES: To study biofilm production and to detect icaAD, atlE and aap genes in 137 isolates of methicillin-resistant Staphylococcus epidermidis (MRSE) obtained from healthy individuals from the community (35 isolates), from hospitalized patients at the Antônio Pedro University Hospital (25 isolates) and from individuals from a home-care system (HCS; 77 isolates). METHODS: Biofilm production was determined in vitro using polystyrene inert surfaces. icaAD, atlE and aap genes were detected using PCR. Hybridization experiments were also carried out to confirm some PCR results. Antimicrobial susceptibility testing was carried out using the NCCLS methods. RESULTS: Although many of the commensal MRSE isolates produced biofilms, the percentage of biofilm producers was significantly higher (P = 0.0107) among hospital isolates (76%) than among isolates from the community (60%) and from the HCS (57%). An association was observed between multiresistance and biofilm production for isolates obtained from healthy individuals from the community and from household contacts from the HCS (P < 0.0001). The concomitant presence of the ica operon and atlE and aap genes was associated with the strong biofilm-producer phenotype (P < 0.0001). CONCLUSION: Because many of the commensal MRSE isolates obtained from nares produced biofilms and carried icaAD, aap and atlE genes, biofilms or such genetic elements should not be used as markers for clinical significance. The biofilm environment seems to increase genetic exchanges and hence may contribute to multiresistance phenotypes.

Anti-Bacterial Agents↗
PubMed1986

Double-blind comparison of the beta 1-selectivity of single doses of bisoprolol and atenolol.

The beta 1-adrenoceptor selectivity of bisoprolol (BPL) was investigated using the forearm circulation of eight healthy subjects. Each subject was studied twice, with at least 10 days in between each investigation. A brachial artery was cannulated for intra-arterial (i.a.) monitoring of blood pressure and for i.a. infusion of isoproterenol (ISO) and epinephrine (EPI). ISO was given in doses of 0.02-0.10-0.40 and 1.20 ng/kg/min, for 3 min per dose. After 20 min rest, EPI was infused in doses of 0.08 and 2.0 ng/kg/min for 6 min per dose. Subsequently, the subjects received an oral dose of either 20 mg BPL or 100 mg atenolol (ATL), and 2 h later, the ISO and EPI infusions were repeated. Forearm blood flow was measured by venous occlusion strain-gauge plethysmography. ISO produced a dose-dependent vasodilatation, whereas the response to EPI varied between individuals. After administration of BPL and ATL, the ISO dose-response curves were shifted to the right by 2.8 and 2.6 times, respectively (both p less than 0.01). Both beta-blockers influenced the vascular effect of EPI in the direction of vasoconstriction. However, this was only significant for ATL (p less than 0.05). From the latter observation it is concluded that BPL is slightly more beta 1-adrenoceptor-selective than ATL, using the forearm vascular bed.

Adrenergic beta-Antagonists↗
PubMed2002

Adenosine A2A analogue improves neurologic outcome after spinal cord trauma in the rabbit.

BACKGROUND: ATL-146e, an adenosine A2A agonist, reduces paralysis after spinal cord ischemia-reperfusion. We hypothesized that systemic ATL-146e could improve neurologic outcome after blunt spinal cord trauma. METHODS: Twenty rabbits survived a thoracic spinal cord impact of 30 g-cm. One group received 0.06 microg/kg/min ATL-146e for the first 3 hours after impact (A2A group), whereas a second group received saline carrier (T/C group). Neurologic outcome was measured using the Tarlov scale (0-5). Histologic sections from the A2A and T/C groups were compared for neuronal viability. RESULTS: There was significant improvement in Tarlov scores of A2A animals compared with T/C animals at 12 hours (p = 0.007), with a trend toward improvement at 36 (p = 0.08) and 48 (p = 0.09) hours after injury. There was decreased neuronal attrition in A2A animals (p = 0.06). CONCLUSION: Systemic ATL-146e given after spinal cord trauma results in improved neurologic outcome. Adenosine A2A agonists may hold promise as a rapidly acting alternative to steroids in the early treatment of the spinal cord injured patient.

Animals↗
PubMed1996

Adult T-cell leukemia/lymphoma in Jamaica: 1986-1995.

Adult T-cell leukemia/lymphoma (ATL) is the commonest lymphoid malignancy in adult Jamaicans, reflecting the role of the causative agent, human T-cell lymphotrophic virus type I (HTLV-I), in altering the pattern of non-Hodgkin lymphoma in an endemic area. A total of 126 cases of ATL were registered in Jamaica between January 1985 and July 1995. There were 65 male and 61 female patients (male-female ratio, 1:1), with a mean age of 43 years (17-85 years). The majority of cases were acute subtype (46.8%), followed by lymphoma (27%), chronic (20.6%), and smoldering (5.6%) types. The disease is associated with a high mortality, with only five of the 126 patients currently alive. The median survival rate is 20 weeks. The epidemiologic, clinical, and laboratory features are similar to those reported in Japan and Brazil, except that the mean age of patients, identical in Jamaica and Brazil (43 years), is 11 years younger than that in Japan (54 years). Given the theory that ATL develops after a long incubation period after early life exposure to HTLV-I facilitated by mother-to-child transmission via breast milk, and the fact that mothers of ATL patients have a high incidence of HTLV-I seropositivity, it would appear that reduction in the incidence of this disease could be achieved by methods aimed at preventing this mode of transmission.

Adolescent↗
PubMed2002

Lipid-derived mediators in endogenous anti-inflammation and resolution: lipoxins and aspirin-triggered 15-epi-lipoxins.

It is well appreciated that lipid-derived mediators play key roles in inflammation and many other physiologic responses where multicellular processes are involved. Among them, lipoxins (LX) and aspirin-triggered LX (ATL) evoke actions of interest in a range of physiologic and pathophysiologic processes, and these two series have emerged as founding members of the first class of lipid/chemical mediators "switched on" in the resolution phase of an inflammatory reaction. These unique compounds possess a trihydroxytetraene structure and are both structurally and functionally distinct among the many groups of lipid-derived bioactive mediators. LXA4 and 15-epi-LXA4 (a member of the ATL series) display leukocyte-selective actions that enable them to serve as endogenous "stop signals" in multicellular events in that they modulate adherence, transmigration, and chemotaxis. Both LXA4 and 15-epi-LXA elicit these responses via a G protein-coupled receptor (GPCR), termed ALXR, identified in human and murine tissues. Among eicosanoids, ALXR is stereoselective for LXA4 (5S,6R,15S-trihydroxy-7,9,13- trans-11-cis-eicosatetraenoic acid). Its aspirin-triggered 15 R epimer (15-epi-LXA4) and their bioactive stable analogs act in the subnanomolar to nanomolar range in human cellular systems and murine models of acute inflammation and reperfusion. ALXR also has the ability to interact with a wide panel of small peptides that give different signaling responses in vitro than LXA4 or its analogs, suggesting that ALXR is capable of serving as a multirecognition receptor in immune responses. Characterization of ALXR and development of metabolically stable LX and ATL analogs that are mimetics rapidly advanced our appreciation of the mechanism of LX actions and the potential utility of these counter-regulatory biocircuits in the quest to control local inflammatory events. In this on-line update, LX and ATL biosynthesis and the LXA4 specific receptor, termed ALXR, are reviewed with a focus on their roles in inflammation and resolution with respect to pharmacology, molecular biology, and signal transduction in several cell types and animal models investigated thus far.

Animals↗
PubMed2000

Crusted (Norwegian) scabies in a patient with smoldering adult T-cell leukemia.

Crusted (Norwegian) scabies is described in a patient with smoldering adult T-cell leukemia (ATL). The patient is an 84-year-old Japanese woman who presented with widespread scaling over the trunk and limbs and crusted lesions on the scalp and ears. Microscopical examination of scrapings from the scalp and ears showed extraordinarily large numbers of scabies mites. The white blood cell count was 5.1 x 10(9)/L with 6% abnormal lymphocytes with mature nuclei that showed convolution and lobulation. Anti-HTLV-I antibodies were positive. Southern blot analysis revealed that the cellular DNA extracted from this patient's peripheral blood cells, digested with Pst I, showed the same pattern of provirus genome as the DNA from ATL patients. A diagnosis of crusted scabies with smoldering ATL was made. It is possible that crusted scabies could be an opportunistic infection and a pre-diagnostic sign of ATL.

Aged↗
PubMed2004

A case of multifocal lupus vulgaris that preceded pulmonary tuberculosis in an immune compromised patient.

We describe the rare case of a Japanese male with multifocal lupus vulgaris that preceded asymptomatic pulmonary tuberculosis and adult T-cell leukemia/lymphoma (ATL). He visited our hospital with multiple reddish plaques and erythema of 4-12 months duration. A skin biopsy revealed non-caseating epithelioid granulomas. Mycobacterium tuberculosis was detected by polymerase chain reaction (PCR)-hybridization from a skin biopsy specimen and was also isolated from a culture of the skin biopsy sample. The result of chest roentogenography was compatible with pulmonary tuberculosis. In addition, the diagnosis of ATL was based upon the presence of atypical lymphocytes with convoluted nuclei in his peripheral blood and a positive anti-ATL antibody reaction. Cases of cutaneous tuberculosis presenting with unusual clinical features may be on the increase, accompanying the spread of tuberculosis in immunosuppressed patients, including those with ATL and acquired immunodeficiency syndrome (AIDS).

Acquired Immunodeficiency Syndrome↗
PubMed1989

Antibodies against p40tax gene product of human T-lymphotropic virus type-I (HTLV-I) under various conditions of HTLV-I infection.

We investigated antibodies against pX gene product, p40tax, by ELISA using recombinant p40tax protein in HTLV-I seropositive carriers as well as patients with adult T cell leukemia (ATL) and HTLV-I-associated myelopathy (HAM). Seventy (49.0%) out of 143 HTLV-I healthy carriers were found to be positive for antibody against p40tax antigen and the follow-up samples at two-year intervals revealed constant reactivity by ELISA in each carrier. The onset of antibody production was delayed 4 to 12 weeks as compared with anti-HTLV-I in primary infection cases. The anti-p40tax-positive rate (90%) in HAM patients was significantly higher than that of healthy carriers, acute and chronic ATL patients and their family members. Furthermore, HAM patients and a few healthy carriers showed high reactivities by ELISA. Children from mothers with anti-p40tax showed a higher anti-HTLV-I-positive rate than that of children from mothers without anti-p40tax (54.5% versus 12.5%). Two men without anti-p40tax and one female with low anti-p40tax developed ATL during follow-up studies. These results suggest that HTLV-I carriers could be divided into 2 or 3 sub-populations according to antibody response to p40tax. A smaller population with anti-p40tax, especially a high antibody reactivity, could have a high risk of developing HAM and of transmission from mother to child. In addition, ATL may occur in a population with low or absent anti-p40tax.

Carrier State↗
PubMed1989

Adult T-cell leukemia in spouses.

A married couple who developed adult T-cell leukemia (ATL) is described. The husband presented with acute ATL and died soon after admission in spite of aggressive chemotherapy, and his wife, who is diagnosed as smoldering ATL, has been followed in the out-patient clinic. The couple had serum antibodies against human T-cell leukemia virus type I (HTLV-I) and the monoclonal integration of HTLV-I proviral DNA in their lymphocytes. The patients described represent the first reported example of ATL in a married couple.

Female↗