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PubMed1990

Antiviral and antiproliferative activities of recombinant human interferon alpha 2, beta and gamma on HTLV-I and ATL cells in vitro.

ATL (Adult T cell leukemia) causes severe immune deficiency. Furthermore, aggravation of immune deficiency is a major problem in chemotherapy of ATL. In expectation of antiviral, antineoplastic and increasing immunological activity, several clinical trials of Interferons (IFNs) on ATL have been reported. However, as the effects have not been generally established, we investigated the in vitro effects of human recombinant interferon (rIFN) alpha 2, beta and gamma on both the infection of human T-cell lymphotropic virus type I (HTLV-I) to normal peripheral blood lymphocytes (PBL) and the growth of ATL cells. The induction of HTLV-I specific antigens on the surface of normal PBL cultured with HTLV-I in vitro was inhibited by the addition of rIFNs in a dose dependent manner. The rIFNs also had dose dependent suppressive effects on the proliferation of ATL cells and one of the ATL cell lines (MT-2). These suppressive effects of rIFNs were not due to a direct cytocidal activity, because rIFNs did not affect the viability of ATL cells at these concentrations. Such inhibitory concentrations (1 to 1000 U/ml) were within the ranges achievable in the blood of patients after the injection of rIFNs. This investigation suggests that rIFNs is applicable for the therapy of ATL.

Antineoplastic Agents↗
PubMed1990

Detection of preleukemic state of adult T-cell leukemia (pre-ATL) in HTLV-1 carriers.

The prevalence of the preleukemic state of adult T-cell leukemia (pre-ATL) was studied in Nagasaki prefecture, one of the endemic human T-lymphotropic virus type 1 (HTLV-1) areas in Japan. Pre-ATL cases have the monoclonal proliferation of abnormal lymphocytes, without signs of malignant proliferation or clinical signs and symptoms related to leukemia. HTLV-1 carriers who have monoclonal integration of HTLV-1 proviral DNA may be at high risk of developing ATL. Abnormal lymphocytes with either bilobular or large and chromatin-rich nuclei were found in 63/356 (17.7%) of HTLV-1 carriers among inhabitants. We analyzed DNA of peripheral lymphocytes from 108 carries with abnormal lymphocytes by Southern blot technique. Monoclonal integration of HTLV-1 has been detected in 12 cases (11.1%). These results lead to the conclusion that the prevalence rate of pre-ATL among all HTLV-1 carriers is about 2%. Pre-ATL is presumed to be the clinical stage which precedes ATL, although the possibility remains that the HTLV-1 carrier may develop symptoms of ATL directly, without going through the pre-ATL stage.

Adult↗
PubMed2002

Adenosine A2A analogue ATL-146e reduces systemic tumor necrosing factor-alpha and spinal cord capillary platelet-endothelial cell adhesion molecule-1 expression after spinal cord ischemia.

OBJECTIVE: Inflammation is likely a major contributor to spinal cord reperfusion injury after aortic reconstruction. Systemic 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), a selective adenosine A(2A) agonist, has been shown to reduce paralysis after spinal cord ischemia. We hypothesized that ATL-146e reduces cytokine production during spinal cord reperfusion, curtailing inflammation and decreasing spinal cord capillary platelet-endothelial cell adhesion molecule-1 (PECAM-1) expression. STUDY DESIGN: New Zealand White rabbits sustained spinal cord ischemia with 45-minute cross-clamping of the infrarenal aorta. One group of animals received intravenous ATL-146e at 0.06 microg/kg/min for 3 hours during reperfusion, beginning after 30 minutes of ischemia. A second group received saline solution vehicle alone for 3 hours, serving as an ischemic control. A third group served as sham-operated animals, undergoing laparotomy with anesthesia. Serum was assayed with enzyme-linked immunosorbent assay for tumor necrosing factor-alpha (TNF-alpha). Animals were allowed to recover for 48 hours and were evaluated for hind-limb motor function with the Tarlov (0 to 5) scoring system. At necropsy, animals from each group yielded spinal cords for immunohistochemical staining for PECAM-1. Data are expressed as mean +/- standard error of the mean, with statistical analysis with Student t test and Kruskal-Wallis nonparametric test. RESULTS: Markedly improved Tarlov scores were seen in rabbits with ATL-146e (P <.001) during spinal cord reperfusion as compared with ischemic control animals. A significant reduction was found in TNF-alpha in the sera of rabbits with ATL-146e infusion (P <.01) as compared with ischemic control animals. Significantly reduced endothelial PECAM-1 staining intensity (P <.05) was seen in microscopic spinal cord sections from rabbits with ATL-146e. CONCLUSION: ATL-146e, an adenosine A(2A) agonist, reduces spinal cord reperfusion injury. The mechanism of the protection may involve a reduction in circulating TNF-alpha during a critical 3-hour reperfusion interval and reduction in spinal cord endothelial PECAM-1 upregulation.

Animals↗
PubMed2000

Advanced Trauma Life Support (ATLS): necessary for emergency physicians?

A survey was conducted to determine differences in perspective towards Advanced Trauma Life Support (ATLS) between emergency medicine (EM) physicians and other specialties (OS), assess its value in the management of acute trauma, and identify areas in the course which could be revised or updated. The survey was devised and completed by physicians after ATLS. Of 26 course participants, there were 11 EM physicians (42%), four family practitioners (15%), four surgeons (15%), four internists (15%), two paediatricians (8%), and one anaesthesiologist (4%). Both groups found ATLS useful and relevant, and reported little deviation from their prior management of acute trauma. Unclear topics identified were airway, spine trauma, and burns/cold injury for EM, and head, abdominal, and paediatric trauma for OS. Significant differences were noted for the following: 91% EM vs. 13% OS felt ATLS could be shortened into a one-day course (p = 0.002), 64% EM vs. 7% OS thought the laboratory could be omitted (p = 0.003), and all (100%) EM vs. 60% OS believed the course could be taught by EM physicians as effectively as surgeons (p = 0.02). EM disagreed with OS over the proposed requirement that all EM physicians be required to take ATLS (2.0 +/- 0.2 vs. 3.5 +/- 0.4, p = 0.03). The EM group reported doing > 20 per year of airway, vascular, and thoracostomy procedures in their own practice, whereas OS did significantly fewer. ATLS may not be useful for EM practitioners actively involved in trauma care. Proposed changes from the EM perspective include shortening ATLS to one day, increased use of EM instructors, clarifying certain portions of the manual, and omitting the laboratory section or making it optional.

Adult↗
PubMed1985

Serum immunosuppressive acidic protein in adult T-cell leukaemia (ATL).

The availability of serum immunosuppressive acidic protein (IAP) as a marker of subtypes of adult T-cell leukaemia (ATL) was examined. Serum IAP levels were measured in 34 patients with ATL (18 typical, 9 atypical and 7 smoldering), 7 healthy carriers of ATLA antibody and 53 healthy controls. The mean value of serum IAP was significantly higher in patients with typical ATL (897.8 +/- 502.4 micrograms/ml) than in those with atypical ATL (426.7 +/- 106.6 micrograms/l), smoldering ATL (310.0 +/- 51.3 micrograms/ml), healthy carriers of ATLA antibody (302.9 +/- 39.5 micrograms/ml) and normal controls (350.5 +/- 73.2 micrograms/ml). Serial determinations of IAP revealed that the level was correlated with the clinical course in patients with ATL; there was a difference in the prognosis of patients with high and normal levels of IAP (P less than 0.05). Thus, routine measurement of serum IAP seems useful in differentiating typical, atypical and smoldering ATL and also in evaluating the prognosis of patients.

Adult↗
PubMed1997

Improved trauma management with advanced trauma life support (ATLS) training.

OBJECTIVE: To determine the value of advanced trauma life support (ATLS) training for medical staff in a major incident situation, based upon performance in a simulated exercise. METHODS: A major incident exercise was used to assess the management of trauma victims arriving in hospital suffering from multiple or life threatening injuries. The effect of ATLS training, or exposure to an abbreviated form of ATLS training, on the management of patients with simulated life threatening traumatic injuries was examined. The treatment offered by medical staff of different grades and varying exposure to ATLS training was compared. RESULTS: Medical staff who had undertaken ATLS training attained a higher number of ATLS key treatment objectives when treating the simulated trauma victims. CONCLUSION: Medical staff who have either undertaken the full ATLS course or an abbreviated form of the course were more effective in their management of the simulated trauma cases.

Education, Medical, Continuing↗
PubMed2004

Reduction of infarct size and postischemic inflammation from ATL-146e, a highly selective adenosine A2A receptor agonist, in reperfused canine myocardium.

Adenosine and adenosine A(2A) receptor agonists have been shown to limit myocardial infarct size when given at vasodilatory doses during reperfusion. This beneficial effect is thought to be due, in part, to stimulation of adenosine A(2A) receptors on inflammatory cells. The specific aims of this study were to determine whether the anti-inflammatory and cardioprotective properties of a novel adenosine A(2A) receptor agonist, ATL-146e (ATL), alone or in combination with the phosphodiesterase IV inhibitor rolipram would occur using very low, nonvasodilating doses. In a canine model of reperfused myocardial infarction, low-dose ATL given alone reduced infarct size by 45% (P < 0.05 vs. control). When ATL was combined with a very low dose of rolipram (0.001 microg.kg(-1).min(-1)), a marked reduction in P-selectin expression and neutrophil infiltration (51% lower; P < 0.001 vs. control) was seen and the infarct size reduction (58% lower; P < 0.01 vs. control) was greater than observed with ATL (45% lower; P < 0.05) or rolipram (33% lower; P < 0.05) alone. In conclusion, a low, nonvasodilating dose of ATL, a highly selective adenosine A(2A) receptor agonist, reduced infarct size after reperfusion. Furthermore, combining ATL and the phosphodiesterase IV inhibitor rolipram reduced infarct size even more than either agent alone. Such combination therapy may be beneficial clinically by potentiating cardioprotection after coronary reperfusion at doses far below those producing vasodilatation or side effects.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

[Adult T-cell leukemia (ATL)].

Adult T-cell leukemia (ATL) was first discovered and reported in Japan, where it has a high incidence in the southwest region. The retrovirus HTLV-I (human T-cell lymphotropic virus type I) is considered to be related to its etiology. In ATL endemic areas, HTLV-I carriers are found at a fairly high percentage even among healthy individuals. ATL shows diverse clinical features. It can be divided into 5 types (acute type, chronic type, smoldering type, crisis type, and lymphoma type). ATL cells originate from the CD4-positive subset of peripheral T cells; they show a characteristic notch in the nucleus and a lobulation tendency. ATL resists chemotherapy, and patients with acute and lymphoma types have quite a poor prognosis. A definite diagnosis of ATL is made by documenting the presence of HTLV-I proviral DNA in the DNA of tumor cells. HTLV-I infection is caused by transmission of live lymphocytes via three routes (from mother to children, from males to females, and by transfusion). Familial occurrence of ATL is frequently seen. HTLV-I infection is also seen in other countries, but its incidence is highest in Japan. It is thus an urgent task for Japanese physicians to eliminate HTLV-I infection.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1995

ATL cells recognize self class II HLA antigens: implication to leukemogenesis.

Adult T cell leukemia (ATL) cells show the decreased expression of T cell receptor (TCR)/CD3 complex on their surfaces in vivo. It is well known that excess amounts of antigen modulate TCR/CD3 complex on antigen-specific T lymphocytes. We hypothesized that antigen receptor of ATL cells was down-regulated with some antigenic stimulation in vivo, which might play an important role in leukemogenesis. In order to test this possibility, we studied whether the fresh ATL cells from three cases would respond to autologous and allogeneic lymphoid cell lines. In two of three cases, ATL cells could proliferate in the presence of autologous cell lines. In one case, this proliferation could be completely inhibited by anti-CD3 and anti-human leukocyte antigen (HLA)-DQ monoclonal antibodies, indicating that ATL cells recognized self HLA-DQ. In another case, the proliferation was suppressed by anti-CD3 and HLA-DR antibodies. These findings showed that ATL cells of some cases were derived from autoreactive T lymphocytes and such stimulation via TCR/CD3 complex plays an important role in the leukemogenesis of ATL in vivo.

Autoantigens↗
PubMed1996

Anatomic thoracoscopic lobectomy (ATL) without minithoracotomy: preliminary experience.

UNLABELLED: The purpose of this review is to outline our experience with a completely thoracoscopic approach to major pulmonary resection (lobectomy). There were 23 patients in this study selected by the usual criteria of resectability. The preoperative workup included chest x-ray, pulmonary function studies, computed tomography (CT) of the chest and abdomen, bronchoscopy, mediastinoscopy, and brain and bone scans in the majority of patients. ATL was attempted in 23 patients. In four patients the procedure was converted to the "open" approach for the following reasons: inability to identify the location of the primary lesion (two patients), obscurative bleeding (one patient), and inability to diagnose the pathology (one patient). The underlying pathology of the ATL group was as follows: bronchiolitis obliterans-organizing pneumonia = 1, granuloma = 2, non-small cell lung cancer = 14, solitary colonic metastases = 2. The breakdown by site of the 19 ATL resections is as follows: right upper lobe = 5, right middle lobe = 1, right lower lobe = 1, right upper and right middle lobes = 1, left upper lobe = 6, left lower lobe = 5. Group A patients (n = 11) were those who had no postoperative complications. Length of stay was short, ranging from 4 to 8 days, median 5 days. Group B patients (n = 8) had complications (prolonged air leak = 4, supplemental postoperative oxygen requirement = 3, pain control = 1) and stayed longer (range 10-21 days, median 13). There were no deaths, no blood transfusions, no chest tube reinsertions and no reoperations. The most significant complication in the ATL group was prolonged air leak in one patient (21 days). CONCLUSIONS: (a) ATL without minithoracotomy is feasible; (b) ATL has potential benefits in terms of reduction of pain and hospital stay; (c) ATL had better cosmetic and functional results.

Adult↗
PubMed1982

Antibodies to adult T-cell leukemia-virus-associated antigen (ATLA) in sera from patients with ATL and controls in Japan: a nation-wide sero-epidemiologic study.

A nation-wide sero-epidemiologic survey of adult T-cell leukemia virus (ATLV), detected es anti-ATLA (ATLV-associated antigen), was made in Japan. Sera from adult donors in 15 different locations were screened for anti-ATLA. High incidences (6 to 37%) of antibody-positive donors were found in seven regions, one in northern Japan, and the others in southwestern regions. These areas are ATLV-endemic areas corresponding to ATL-endemic areas. Examination of sera from healthy donors aged 6 to 80 years in ATL-endemic areas showed an age-dependent increase of seropositive donors with a maximum of about 30% at 40 years of age. Anti-ATLA was found in all but two of 142 patients with ATL. Anti-ATLA-positive patients with ATL were mainly found in ATLV-endemic areas, and only a few in ATL-nonendemic areas. Six patients with cutaneous T-cell lymphoma in ATLV-nonendemic areas gave a negative reaction for anti-ATLA. The geometric mean titer of anti-ATLA of patients with ATL was higher than that of healthy donors.

Adult↗
PubMed1993

Clinical, morphological and virological features of an HTLV-I-positive case of ATL in a white man from the Caucasus.

An HTLV-I-associated case of adult T-cell leukemia (ATL) was described in a 51-year-old white man, native from Georgia, the former U.S.S.R. Clinical manifestation of the disease (enlarged lymph nodes, bone marrow and peripheral blood changes, CNS-involvement, cutaneous lesions and hypercalcemia) as well as laboratory findings were recognized to be very similar to those frequently observed in ATL patients from endemic regions. Mature T-helper surface phenotype detected on peripheral blood lymphocytes of the patient (OKT3-, OKT4+ and OKT8-) and aggressive course of the disease were also in favour of classical type ATL developed in the patient. The HTLV-I antibody presence in an ATL patient was repeatedly confirmed by serological tests (Abbott HTLV-I EIA and Serodia HTLV-I), immunofluorescence and Western blot assay. The latter revealed the presence of a large spectrum of HTLV-I-specific antibodies (to p19, p24, p26, p28, p32, p36, pr53, gp21, gp46, gp62 and gp68 of HTLV-1). The HTLV-I-specific antibodies have also been detected in serum samples of the patient's wife and son. The presence of HTLV-I provirus in the primary ATL patient's PBL was clearly demonstrated by PCR and Southern blot analysis. This case, with the HTLV-I infections detected in two other family members, suggests that in Europe, HTLV-I-positive cases of ATL can occur in virus-infected local people with much wider distribution than that hitherto supposed.

Antibodies, Viral↗
PubMed1999

ATLS: a foundation for trauma training.

The Advanced Trauma Life Support (ATLS) course is sponsored by the American College of Surgeons Committee on Trauma. This course was developed to provide a consistent method of care for the resuscitation and evaluation of the injured patient. The ATLS course provides an easily remembered method for evaluating and treating the victim of a traumatic event. It also provides a scaffold for evaluation, treatment, education, and quality improvement of our ability to provide quality medical care to our patients. This article chronicles the past, present, and future of ATLS. The process of revising the ATLS course is reviewed. The changes recently introduced in the sixth edition of the ATLS course are highlighted. The worldwide growth of ATLS is acknowledged. The strength of this educational course remains the commitment to our primary goal of optimal care for the injured patient.

Curriculum↗
PubMed1996

Video assessment of trauma response: adherence to ATLS protocols.

A novel strategy using videotape recordings of initial trauma resuscitations was incorporated into the quality assurance program at a level 1 trauma center. Described are the process of taping the resuscitations, the multidisciplinary nature of the resuscitation team, the security measures taken to assure patient confidentiality, and the review process involved. The videotape review process was incorporated into a multidisciplinary educational trauma conference. The videotapes were used to evaluate the adherence to Advanced Trauma Life Support (ATLS) resuscitation protocols. Resident performance in six aspects of the ATLS resuscitation process were specifically highlighted on each videotape and graded for adherence to preestablished standards. The videotape process allowed an unblased, indisputable accurate documentation of the sequential application of the protocols of evaluation and resuscitation espoused in the ATLS course. We found 23% overall deviation from ATLS resuscitation principles, with at least one aspect of the resuscitation deviating from expected ATLS performance in 64% of the patients. In addition to documenting adherence to ATLS principles, this study illustrated the impact of the videotape review process on the education of eight senior residents in surgery.

Clinical Competence↗
PubMed2003

[5 years ATLS (Advanced Trauma Life Support) courses in Switzerland].

Five years ATLS (Advanced Trauma Life Support) in Switzerland are analysed, the problems are discussed and the changes during this period are demonstrated. ATLS Switzerland is a part of the Swiss surgical Society, introduced by the ATLS International Faculty in 1998. Switzerland with 4 official languages needs a special structure. For this reason a decentralisation of the courses was necessary with the need of five regional universities where ATLS courses are offered. Statistics of the rising amount of courses demonstrate the enormous rush for ATLS courses in our country. Three courses in 1998 where followed by six courses in 1999, up to 18 courses in 2002. 2001 was the first year with ATLS in the Swiss Army. Since 1.1.2003 Paul Martin Sutter, Biel ist the new National Director, successor of Domenic Scharplatz, Thusis.

Clinical Competence↗
PubMed1997

Extensive analysis of the retinoblastoma gene in adult T cell leukemia/lymphoma (ATL).

The retinoblastoma susceptibility gene (Rb) plays a key role in regulating the cell cycle in association with cyclins and cyclin-dependent kinases (CDKs). Alteration of the Rb gene as well as CDK inhibitors (CDKIs) leads to deregulated cellular growth which promotes cancer formation. We examined the genomic configuration of the entire Rb gene in 40 primary adult T cell leukemias/lymphomas (ATL) and two ATL cell lines by Southern blotting and also by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analyses. Homozygous loss of exon 1 was identified in one of 21 acute ATL, one of 15 chronic ATL, and none of four lymphomatous ATL samples. No point mutations were identified. Previously, we found that 10 of these same ATL samples had alterations of either p16(INK4A) (homozygous deletion) or p27(kip1) (homozygous deletion or point mutation). Although the numbers are very low, none of the samples with an aberrant Rb gene had an altered CDKI and vice versa, suggesting that both genes probably operate in a common pathway and alteration of either can provide these cells with a growth advantage.

Carrier Proteins↗
PubMed1996

Association of HTLV-I with autoimmune thyroiditis in patients with adult T-cell leukaemia (ATL) and in HTLV-I carriers.

OBJECTIVE: Human T-lymphotrophic virus type I (HTLV-I) is a retrovirus that causes adult T-cell leukaemia (ATL). This virus is associated with a variety of autoimmune disorders. The possible association between HTLV-I Infection and autoimmune thyroiditis has not been fully studied. We therefore evaluated anti-thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin antibodies (TGAb) in the sera of patients with ATL, carriers of HTLV-I, and in healthy control subjects to investigate the possible association between such infection and auto-immune thyroiditis. PATIENTS AND METHODS: Fifty-two ATL patients (21 males, 31 females; mean age 56.4 years) and 50 HTLV-I carriers (18 males, 32 females; mean age 56.7 years) were studied. The control subjects were 877 healthy adults (271 males, 606 females; mean age 54.8 years) who were negative for HTLV-I antibody. TPOAb, TGAb, thyroxine (T4) and thyrotrophin (TSH) were measured in serum using a radioimmunoassay kit. RESULTS: Positivity for thyroid autoantibodies (TPOAb and/or TGAb) was found in 21 of 52 ATL patients (40.4%), 15 of 50 HTLV-I carriers (30.0%), and 120 of 877 control subjects (13.7%). The difference between the HTLV-I-Infected and the control subjects was statistically significant (P < 0.005). Female control subjects had a significantly higher prevalence of positivity for thyroid autoantibodies than the males (17.3 vs 5.5%, P < 0.001). Carriers of HTLV-I and patients with ATL of each sex showed an equally high prevalence of positivity for thyroid autoantibodies. Of the subjects who were positive for thyroid autoantibody, 7.5% of control subjects, 19.0% of ATL patients, and 40.0% of HTLV-I carriers had hypothyroidism. A significant difference in this respect was noted between the HTLV-I infected subjects and the control subjects (P < 0.005). CONCLUSIONS: This study demonstrates a high prevalence of positivity for thyroid autoantibodies (TPOAb and/ or TGAb) in the adult T-cell leukaemia patients and the HTLV-I carriers. The adult T-cell leukaemia patients and the HTLV-I carriers each had a high prevalence of hypothyroidism. There was an association between HTLV-I infection and autoimmune thyroiditis.

Autoantibodies↗
PubMed1983

Polymorphism in Escherichia coli: rtl atl and gat regions behave as chromosomal alternatives.

Amongst forty wild strains of Escherichia coli, sixteen utilized galactitol (as did K12) and seven utilized ribitol (as did C) of which six utilized D-arabitol; none utilized all three polyols. Transduction of genes for ribitol utilization (rtl+) to strains able to utilize galactitol (gat+), whether K12 or wild strains, using wild strains and E. coli C as donors always resulted in loss of the galactitol phenotype. The genes for D-arabitol use (atl+) were always cotransduced with rtl+ in interstrain crosses. We confirm and extend the mapping of gat+ (Lengeler, 1977) and rtl+ atl+ (Reiner, 1975) in their respective hosts, K12 and C, by showing both regions to be 50% cotransducible with metG and 3% cotransducible with fpk. In reciprocal transductions, gat+ replaced rtl+ atl+. In partial diploids, rtl+ atl+ and gat+ regions did not interfere with each other's expression. Transfer of rtl+ from an Rtl+ Atl- donor by R plasmid (pE10)-mediated conjugation, gave Gat- transconjugants of K12 in which rtl+ and a kanamycin resistance gene were 100% cotransducible in the metG region of the chromosome. It is suggested that the rtl+ atl+ and gat+ genes (or parts of them) act as alternative, or mutually exclusive, regions in the chromosome. Possible reasons for the existence of alternative characters are discussed.

Chromosome Mapping↗