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At least 199 records · Page 11Linked to original sources
PubMed1989

ATL-derived factor (ADF), an IL-2 receptor/Tac inducer homologous to thioredoxin; possible involvement of dithiol-reduction in the IL-2 receptor induction.

HTLV-I transformed T cells not only express a large number of interleukin-2 receptors [IL-2R/p55(Tac)], but also produce a factor named ATL-derived factor (ADF) that augments the expression of IL-2R/p55(Tac). Based on a partial N-terminal amino acid sequence, complementary DNA (cDNA) clones for human and mouse ADF were isolated and sequenced. Recombinant ADF produced by COS-7 monkey kidney cells showed IL-2R/Tac inducing activity on YT cells, which are sensitive for ADF. ADF mRNA was strongly expressed in HTLV-I(+) T cells lines, but not in inactivated cells (THP-1, unstimulated PBMC). Furthermore, in normal human peripheral blood mononuclear cells, the expression of ADF mRNA was enhanced by mitogens or phorbol myristate acetate, suggesting a possible involvement of ADF in the lymphocyte activation. Homology analysis revealed an unexpected relationship between ADF and dithiol-reducing enzyme, thioredoxin, involved in many important biological reactions such as the conversion of ribonucleotides into deoxyribonucleotides, or the stabilization of glucocorticoid receptors. The biological significance of the generation of a redox potential in lymphocyte activation, and the possible involvement of dithiol reduction in the induction of IL-2R/Tac are discussed.

Amino Acid Sequence↗
PubMed2001

Comparison of performance 2 years after the old and new (interactive) ATLS courses.

BACKGROUND: We previously (1997) demonstrated superior clinical but similar cognitive performance after the new interactive compared to the old ATLS course. The present study is aimed at determining whether this difference was short term or maintained over time (2 years). MATERIALS AND METHODS: Two groups of 13 physicians out of the original 32 physicians were available for the study which compared performance in a 40-item MCQ examination on trauma topics and clinical performance in 4 trauma OSCE stations consisting of simulated trauma patients. Paired and unpaired t tests were used for within- and between-group comparisons, respectively, with P < 0.05 being considered statistically significant. Overall OSCE scores (maximum standard 20), adherence to priority scores (Priority, scale 1 to 7), and overall approach (Approach, scale 1 to 5) scores were analyzed. RESULTS: Values are means +/- SD; (+)-P < 0.05 compared to 1999; *P < 0.05 compared to old group [table in text]. CONCLUSIONS: Although knowledge base decreases similarly with time after both courses, the new interactive course participants maintained a consistently higher clinical skill performance level at 2 years.

Cognition↗
PubMed1990

Role of ATL-derived factor (ADF) in the normal and abnormal cellular activation: involvement of dithiol related reduction.

HTLV-I transformed T cells not only express a large number of interleukin-2 receptors (IL-2R/p55(Tac], but also produce an IL-2R/Tac inducer named ATL-derived factor (ADF). We have cloned the ADF cDNA and found that ADF production in human lymphocytes can be enhanced by cellular activators such as mitogens or phorbol esters. Recombinant ADF produced by E. coli was shown to have growth-promoting activity in combination with interleukin-2 or suboptimal mitogenic stimuli on several lymphoid cells including human PBMCs, besides the originally reported IL-2R/Tac inducing activity. Homology analysis revealed an unexpected structural relationship between ADF and dithiol-reducing enzyme, thioredoxin, which had been characterized originally in prokaryotic system. Recombinant ADF also has a reducing activity, suggesting the presence of still unknown features of ADF action in vivo. The requirement of dithiol reduction in the biological activities of ADF, together with the possible involvement of ADF production in the normal and abnormal activation of human cells are discussed.

Amino Acid Sequence↗
PubMed1997

Lipoxins and novel aspirin-triggered 15-epi-lipoxins (ATL): a jungle of cell-cell interactions or a therapeutic opportunity?

Lipid-derived mediators play critical roles in inflammation and other multicellular vascular processes, including atherosclerosis and thrombosis. The lipoxins (LXs) were first isolated in 1984, and have continued to show intriguing and potentially important biological roles. These compounds carry a trihydroxytetraene structure and are both structurally and functionally unique among arachidonic acid-derived bioactive products. The availability of synthetic materials for evaluation of bioactions as well as appropriate methods of detection to determine when and where LX are generated has, in recent studies, catapulted our understanding of the formation and actions of the lipoxins. This mini-review addresses new concepts in the formation and biological roles of these lipid-derived mediators and considers whether the lipoxins and the newly discovered aspirin-triggered lipoxins (ATL) represent novel approaches for therapeutic opportunities. Recent findings indicate that select cytokines and aspirin initiate and regulate LX biosynthetic events. These circuits involve cell-cell interfacing that facilitates transcellular events to form LX that display anti-inflammatory actions in both in vitro and in vivo models. These recent results suggest that LX biosynthetic circuits assemble to evoke anti-inflammatory actions and generate LX that can serve as "stop signals" in appropriate microenvironments.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Isolation and analysis of expression mechanisms of a rice gene, EL5, which shows structural similarity to ATL family from Arabidopsis, in response to N-acetylchitooligosaccharide elicitor.

Two rice cDNAs, EL5 and RRF1, were isolated and characterized. EL5 was responsive to N-acetylchitooligosaccharide, a biotic elicitor active in suspension-cultured rice cells. The structural specificity of the elicitor required for the expression of EL5 was consistent with other defense reactions observed in the experimental system, indicating that the elicitor signal to EL5 is transmitted through a single class of receptor-mediated recognition events. However, the intracellular signaling pathway to EL5 was distinct from those to other elicitor-responsive genes. Sequence analysis and alignment showed that a genomic sequence stored in rice genome databases in addition to EL5 and RRF1 belongs to the ATL family of RING-H2 finger motif proteins first isolated from Arabidopsis.

Journal Article↗
PubMed1986

Non epidermotropic cutaneous lymphoma ending in leukemia. A case of adult T cell lymphoma (ATL) in France?

A case of uncommon non Hodgkin malignant lymphoma with initial skin involvement is reported. The pathological pattern does not come under standard classifications. An aspect of non epidermotropic diffuse pleomorphic lymphoma is observed. In an immunological cell membrane study, the T-cell lineage of the malignant proliferation exhibited a very unusual pattern including the presence of the E rosette receptor and the expression of HLA-DR monomorphic determinant. This type of T cell malignant lymphoma can probably be included in the group of adult T cell leukemia/lymphoma (ATL) which is endemic in South Western Japan and occasionally observed in Western countries. The emergence of such cases in these countries raises important epidemiological questions.

Adult↗
PubMed2006

Cetilistat (ATL-962), a novel lipase inhibitor: a 12-week randomized, placebo-controlled study of weight reduction in obese patients.

OBJECTIVE: To determine the efficacy, safety and tolerability of cetilistat (ATL-962), a novel inhibitor of gastrointestinal (GI) lipases, in obese patients. DESIGN: Phase II, multicentre, randomized, placebo-controlled, parallel group study. Enrolled patients (N=442) were advised a hypocaloric diet (deficient by 500 kcal per day, 30% of calories from fat) for a 2-week run-in period. Patients who satisfied the entry criteria (N=371) continued on the hypocaloric diet and were randomized to either placebo or one of three different doses of cetilistat (60 mg three times daily t.i.d., 120 mg t.i.d. and 240 mg t.i.d.) for 12 weeks, followed by a 4-week post-treatment follow-up. Safety, tolerability and body weight were assessed, together with other parameters associated with obesity. OUTCOME MEASURES: The primary outcome measure was absolute change in body weight from baseline. Secondary outcomes included the proportion of patients achieving pre-defined weight loss targets, changes from baseline in waist circumference and in blood lipids. GI tolerability criteria were specifically assessed, as was safety. RESULTS: Treatment with cetilistat reduced mean body weight to similar extents at all doses, which were statistically significant compared with placebo (60 mg t.i.d. 3.3 kg, P<0.03; 120 mg t.i.d. 3.5 kg, P=0.02; 240 mg t.i.d. 4.1 kg, P<0.001). Total serum and low-density lipoprotein cholesterol levels were likewise significantly reduced by 3-11% at all doses of cetilistat. Cetilistat was well tolerated. The frequency of withdrawal owing to treatment-emergent adverse events was similar between cetilistat-treated groups (5.3-7.6%) and placebo (7.6%). Adverse events were generally mild to moderate in intensity, occurred on only one occasion and were mostly GI in nature. The incidence of GI adverse events was increased in the cetilistat-treated groups compared to placebo. However, those GI adverse events, such as flatus with discharge and oily spotting, only occurred in 1.8-2.8% of subjects in the cetilistat-treated groups. CONCLUSIONS: Cetilistat produced a clinically and statistically significant weight loss in obese patients in this short-term 12-week study. This was accompanied by significant improvements in other obesity-related parameters. Cetilistat treatment was well tolerated. The risk-benefit demonstrated in this study in terms of weight loss vs intolerable GI adverse effects shows that cetilistat merits further evaluation for the pharmacotherapy of obesity and related disorders.

Adult↗
PubMed2006

[Septic shock induced by Serratia marcescens complicating adult T-cell leukemia (ATL)].

A 75-year-old woman was admitted with fever of unknown origin and liver damage, and treated with prednisolone. Hypercalcemia appeared when of the dose of prednisolone was reduced, and human T-cell lymphotropic virus type-I (HTLV-I) proviral DNA was detected in the leukemic cells by Southern blot analysis, and a diagnosis of acute adult T-cell lymphoma (ATL) was made. After chemotherapy with sobuzoxane was started, she went into septic shock caused by multiple resistant Serratia marcesense, and was treated with PMX-DHP and antibiotics. Although ner general condition and her serum cytokine leyels improved, the septic shock became more severe, and the patient died. Serratia marcesense expreses lipopolysaccharide (LPS), a biologically active substance that is present in gram-negative bacteria. Exposure to LPS leads to activation of cytokines, including TNF-alpha, IL-1beta, IL-6, and IFN-gamma. After treatment with PMX-DHP, the patient's general condition improved, but she died of septic shock. Bacterial infection may be a life-threatening complication in the immunocompromised hosts and elderly patients, particularly when granulocytopenia has been induced by chemotherapy, and thus such these patients require careful management.

Aged↗
PubMed1998

[Israel's ATLS program: summary and outlook].

In recent years a vigorous effort has been made to improve quality of primary trauma care in Israel. Advanced trauma life support courses (ATLS) were given to physicians throughout the country, regardless of their specialties. In 7 years 4229 physicians participated in 202 courses with an average success rate of 76%. In the future, issues such as mandatory vs. voluntary training, language barriers, and continuous decline of knowledge should be addressed if momentum is to be maintained.

Curriculum↗
PubMed1997

Adult T cell leukemia (ATL)-derived factor/human thioredoxin prevents apoptosis of lymphoid cells induced by L-cystine and glutathione depletion: possible involvement of thiol-mediated redox regulation in apoptosis caused by pro-oxidant state.

Thiol compounds, such as L-cysteine and glutathione (GSH), play crucial roles in the regulation of lymphocyte proliferation. In this study, we analyzed the effect of L-cystine and GSH depletion on lymphocyte survival and investigated the regulatory roles of adult T cell leukemia (ATL)-derived factor (ADF)/human thioredoxin (hTRX) in relation to these low m.w. thiols. MT-1, MT-2, and Jurkat cells underwent apoptosis when cultured in the L-cystine- and GSH-free medium within 18 to 24 h. Dichlorofluorescin oxidation assay indicated that the apoptosis in MT-1 and MT-2 cells was preceded by an increase in the level of intracellular hydrogen peroxide (H2O2). The addition of catalase and recombinant ADF/hTRX (rADF) partially blocked the apoptosis in a dose-dependent manner. rADF has been also shown to enhance the internalization of L-cystine into MT-2 cells in a dose-dependent manner, whereas oxidized rADF or mutated rADF that has no insulin-reducing activity failed to do so. Furthermore, culture in the L-cystine- and GSH-free medium lowered the cellular GSH content of PHA blasts, which was restored dose-dependently by rADF. These data suggest that the inability to neutralize oxidative stress results in the apoptosis of lymphoid cells under L-cystine- and GSH-depleted conditions. The protective effects of rADF may be explained by direct scavenging action on H2O2 (catalase-like activity) or by indirect neutralizing effects on the pro-oxidant status through enhancing the L-cystine internalization and elevating the intracellular GSH content.

Apoptosis↗
PubMed1997

[ATLS course for surgery residents--should it be mandatory?].

Senior surgeons were asked about mandatory participation of general surgery residents in the advanced trauma life support (ATLS) course. Although trauma care in Israel is given by surgical residents, in the opinion of their senior mentors the course should continue to be mandatory for them.

Curriculum↗
PubMed1998

Aspirin-triggered 15-epi-lipoxin A4 (ATL) generation by human leukocytes and murine peritonitis exudates: development of a specific 15-epi-LXA4 ELISA.

Aspirin (ASA) triggers the formation of 15-epi-lipoxins (15-epi-LXs or ATL [ASA-triggered LX]), which are potent bioactive eicosanoids that may contribute to the therapeutic impact of ASA. To elucidate the role of these new compounds in vivo, it is essential to establish quick and sensitive detection methods. To this end, we prepared an enzyme-linked immunosorbent assay specific for 15-epi-LXA4 that proved to be highly sensitive (IC50 approximately 50 pg, minimum detection approximately 3.5 pg) and stereoselective. The amounts of 15-epi-LXA4 generated by human neutrophils from peripheral blood of healthy volunteers using this enzyme-linked immunosorbent assay were in agreement with those values obtained by liquid chromatography. Formation of 15-epi-LXA4 was cell ratio-dependent during THP-1 (a monocytic leukemia cell line)-neutrophil interactions with ASA-treated cells, and 15-epi-LXA4 was not detected with either cell type alone. Generation of 15-epi-LXA4 was also examined in murine peritonitis with ASA administration. Exudates from ASA-treated mice showed increased production of 15-epi-LXA4 that was diminished by indomethacin, a blocker of ASA-dependent acetylation of prostaglandin G/H synthase. A cytochrome P450 inhibitor administered in the presence of ASA did not prevent 15-epi-LXA4 formation, which suggests that P450 does not significantly contribute to formation of 15-epi-LXA4 in this murine model. These results indicate that the new enzyme-linked immunosorbent assay is both sensitive and selective for 15-epi-LXA4 and that 15-epi-LXA4 is produced by human leukocyte-leukocyte interactions. In addition, 15-epi-LXA4 is generated by inflammatory exudates when ASA is administered during murine peritonitis and when prostaglandin G/H synthase is upregulated and acetylated. This assay should provide rapid means to investigate 15-epi-LXA4 generation in both cellular and animal models.

Animals↗