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The Effect of Axial Load in the Tibia on the Response of the 90 degrees Flexed Knee to Blunt Impacts with a Deformable Interface.

Lower extremity injuries are a frequent outcome of automotive accidents. While the lower extremity injury criterion is based on fracture of bone, most injuries are of less severity. Recent studies suggest microscopic, occult fractures that have been shown to be precursors of gross bone fractures, may occur in the kneecap (patella) for impacts with rigid and deformable interfaces due to excessive levels of patello-femoral contact pressure. One method of reducing this contact pressure for a 90 degrees flexed knee is to provide a parallel pathway for knee impact loads into the tibial tuberosity. Yet, blunt loads onto the tibial tuberosity can cause posterior drawer motion of the tibia, leading to injury or rupture of the posterior cruciate ligament (PCL). Recently studies have shown that axial loads in the tibia, which are measured during blunt loading on the knee in typical automobile crashes, can induce anterior drawer motion of the tibia and possibly help unload the PCL. The purpose of the current study was to explore the effect of combined anterior knee loading (AKL) and axial tibia loading (ATL), on response and injury for the 90 degrees flexed human knee. In repeated impacts with increasing ATL the stiffness of the knee to an AKL impact increased. For a 3 kN AKL, the stiffness of the knee increased approximately 26% when the ATL was increased from 0 kN to 2 kN. For 6 kN and 9 kN AKL, the stiffness was increased approximately 17% and 20%, respectively, when the ATL was increased from 0 kN (uniaxial) to 4 kN (biaxial). The effect, however, was not statistically significant at the 9 kN AKL level. The posterior tibial drawer was shown to increase with increased AKL and decrease with increased levels of ATL at an average of 0.3 mm per kN ATL for both the 3 kN and 6 kN ATL scenarios. For 9 kN AKL this drawer displacement was significantly reduced for biaxial versus uniaxial impacts, from 7.4+/-1.4 mm to 5.8+/-0.6 mm, respectively. Additionally, the percentage of the load carried by the tibial tuberosity increased with an ATL. For AKL impacts of 3, 6, and 9 kN, the percentage of load carried by the tibial tuberosity increased from 2.1% (range 0-19%) to 4.9% (0-36%), 2.1% (0-15%) to 6.9% (0-36%), and 8.7% (0-25%) to 12.7% (0-33%), respectively, between uniaxial and biaxial tests. The biaxial loading scenario also resulted in a reduction of the patello-femoral (PF) contact force as the ATL was increased. Ten knee impacts resulted in PCL tears at an average peak load of 12.7+/-2.4 kN in biaxial impacts (n=5) and 12.0+/-3.1 kN for uniaxial impacts (n=5). These PCL injured specimens had an average age of 62+/-11.3 years. The remaining specimens (n=11, 78+/-12.9 years of age) had bone fractures at approximately 8.9+/-3.1 kN. This study showed that combinations of compressive ATL and AKL reduced the PF contact force and had a stiffening effect on the response of the knee impacting a stiff but deformable interface. Furthermore, ATL reduced the posterior drawer of the tibia, which is the current basis for PCL injury in the knee, although it did not reduce the incidence of PCL injury in this study. While the current injury tolerance criterion reflects the vulnerability of the PCL to injury by limiting tibial drawer to 15 mm, the current dummy design does not incorporate the stiffening effect of an ATL that may occur at the same time as knee contact with an instrument panel during a typical automotive crash.

Journal Article↗

[Clinical study on the serum carcinoembryonic antigen, immunosuppressive acidic protein and C-reactive protein levels in patients with adult T cell leukemia].

Serum carcinoembryonic antigen (CEA), immunosuppressive acidic protein (IAP) and C-reactive protein (CRP) levels were measured in patients with adult T cell leukemia (ATL) in order to clarify their significance in this disease. Mean (+/- SD) serum CEA levels in 11 patients with acute ATL (3.1 +/- 1.3 ng/ml) and 7 patients with smoldering ATL (3.1 +/- 0.5 ng/ml) were significantly higher than in sera of 222 healthy controls (2.4 +/- 1.3 ng/ml). However, the levels in 7 patients with chronic ATL and healthy controls showed no differences. On the other hand, mean (+/- SD) serum IAP levels in patients with acute ATL (928 +/- 395 micrograms/ml), chronic ATL (487 +/- 125 micrograms/ml) and smoldering ATL (429 +/- 90 micrograms/ml) were significantly higher than in sera of healthy controls (359 +/- 103 micrograms/ml). However, the levels in patients with smoldering ATL and healthy controls showed no differences. Serum IAP levels in crisis in chronic and smoldering ATL were similar to those in patients with acute ATL. 85% of ATL patients with IAP levels above 500 micrograms/ml had CRP levels above 1+. Serum CEA, IAP and CRP levels were serially measured in a number of patients. Serum IAP and CRP levels reflected each patient's clinical course more than serum CEA levels. Overall the simultaneous measurements of serum CEA, IAP and CRP levels revealed a potential usefulness for determination of ATL subtype, and serum IAP and CRP levels may provide a way to evaluate the effectiveness of chemotherapy.

Adult↗

Cytotoxicity of interleukin 2-toxin toward lymphocytes from patients with adult T-cell leukemia.

The inhibitory effect of a diphtheria toxin-related interleukin 2 fusion protein, IL-2-toxin, on protein synthesis in adult T-cell leukemia/lymphoma (ATL) cells was examined in vitro. Peripheral blood ATL cells from 12 patients (six acute type, four chronic type, and two smoldering type ATL) and the lymph node cells from three ATL patients (two acute type and one lymphoma type ATL) were examined. At a concentration of 10(-8) M, IL-2-toxin inhibited protein synthesis by 60 to 98% in lymph node ATL cells, whereas protein synthesis in peripheral blood ATL cells was inhibited from 20 to 57% in acute type, and from 3 to 13% in chronic type. In contrast, IL-2-toxin had no measurable effect on T-cells from either patients with smoldering type ATL or normal controls. The cytopathic effects of IL-2-toxin were blocked by the addition of anti-CD25 monoclonal antibody, suggesting that the inhibition of protein synthesis in target cells was mediated by the IL-2 receptor (IL-2R). The degree of inhibition of protein synthesis, however, was not closely correlated with expression of CD25 antigen (low-affinity Mr 55,000 glycoprotein, IL-2R, Tac antigen) on ATL cells. There was an apparent correlation between the degree of inhibition and the rate of protein synthesis in ATL cells. We demonstrate that ATL cells from patients with acute or lymphoma type disease were more sensitive to IL-2-toxin than cells from chronic or smoldering disease. These findings suggest that the high affinity IL-2R present on acute and lymphoma type ATL cells may serve as a target for therapy with this recombinant chimeric toxin.

Adult↗

Adult T-cell leukemia/lymphoma in Jamaica and its relationship to human T-cell leukemia/lymphoma virus type I-associated lymphoproliferative disease.

We had shown previously that the prevalence of human T-cell leukemia/lymphoma virus type I (HTLV-I)-antibody positivity is high in Jamaican non-Hodgkin's lymphoma (NHL) patients and that virus-positive patients have the clinical features and poor prognosis of adult T-cell leukemia/lymphoma (ATL). Sixty-two % of 45 NHL patients diagnosed consecutively between 2/1/82 and 1/31/84 and studied prospectively were HTLV-I-antibody positive. Skin involvement (38%), hypercalcemia (44%), and leukemia (40%) were unusually prevalent and there was a strong association (p less than 0.05) with HTLV-I-antibody positivity. Fifty-two % of the patients had bone marrow infiltration, and 74% of these patients were HTLV-I-antibody positive (p = 0.06). Lymphadenopathy (96%), hepatomegaly (60%), and splenomegaly (25%) were detected with about the same frequency as in other series of NHL patients with advanced disease, and 61-88% of these patients were HTLV-I-antibody positive. Patients were classified into those with "typical ATL" (NHL associated with 2 of the 4 features i) hypercalcemia; ii) histologically proven skin infiltration; iii) leukemia; and iv) bone marrow infiltration, providing that the morphology of infiltrating or leukemic cells was characteristic of ATL; those "consistent with ATL" (NHL associated with 1 of these 4 features); and "non-ATL" (NHL without any of these 4 additional features). Thirty-two (71%) of the NHL patients were ATL patients, i.e., had features typical of or consistent with ATL, and 78% of these were HTLV-I-antibody positive. HTLV-I provirus was detected in tumour cells of all HTLV-I-antibody positive patients tested. Three (23%) of the non-ATL patients were HTLV-I-antibody positive. There was no correlation between histopathological features and the clinical classification or HTLV-I-antibody positivity. Median survival of ATL and non-ATL patients was 16 and 53 weeks. Although the disease was usually fulminant, 34% of the ATL patients had a subacute or chronic course. Skin involvement and leukemia were prominent in these patients. Hypercalcemia was the chief prognostic determinant. Median survival of hypercalcemic and normocalcemic ATL patients was 13 and 86 weeks (p less than 0.05). Hypercalcemia caused 10 deaths, infections 12, and death was due to tumour progression in 4 patients. Infections were usually due to pyogenic organisms and only 2 patients had systemic opportunistic infections. Six (27%) of 22 chronic lymphocytic leukemic (CLL) patients were HTLV-I-antibody positive.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Clinical features of adult T-cell leukemia].

Adult T-cell leukemia (ATL) is T-cell leukemic non Hodgkins' malignant lymphoma; 73 percent of 199 non Hodgkins' lymphomas were of T-cell origin, and 58 percent of these T-cell lymphomas were ATL in Nagasaki, Japan. ATL cells are mostly characteristic in the specific nuclear indentations. These cells have a commonly helper T-cell phenotype on the reaction to the Leu series monoclonal antibody, and the cells showed a suppressor function to normal B-cell differentiation by PWM. Miscellaneous infections, probably due to T-cell disfunction have been frequently experienced in ATL. Pulmonary infections, especially interstitial pneumonitis, were characteristic. Bone destraction through osteocrast proliferation was suggested to be the main cause of hypercalcemia. Many cases with familiar disposition have been found in ATL and T-ML, and 3 siblings having ATL and T-ML were presented. ATLA antibody was positive in all cases of ATL and 63 percent of T-ML. Positive rate of ATLA antibody in healthy spouses and siblings of ATL and T-ML patients was high. ATLA (antigen) on the mononuclear cells of almost all the ATL and ATLA antibody positive T-ML was positive. Peripheral blood mononuclear cells of 2 cases of mycosis fungoides were also positive for ATLA. Probably pre ATL cases with low grade leukocytosis and the presence of ATL cell like lymphocytes and positive rate of ATLA antibody and antigen of these cases were presented. By the chromosome study of 14 cases of ATL, chromosome aberrations of No. 2, 3 and 18 were frequently observed.

Adolescent↗

Homozygous deletions of the p15 (MTS2) and p16 (CDKN2/MTS1) genes in adult T-cell leukemia.

Adult T-cell leukemia (ATL) is associated with prior infection with human T-cell leukemia virus type I (HTLV-I). Twenty to 40 years often elapse from viral infection to overt ATL, suggesting that other genetic events must occur to produce frank leukemia. The p15 (MTS2) and p16 (CDKN2/MTS1) genes located on chromosome 9p have been implicated as candidate tumor-suppressor genes in several types of tumors. We examined for alterations of these genes in ATL using Southern blot and polymerase chain reaction-single-strand conformation polymorphism analyses. Both p15 and p16 genes were homozygously deleted in 4 of 23 acute/lymphomatous ATL (17%). An additional 3 (13%) and 4 (17%) acute/lymphomatous samples had hemizygous deletions in at least one exon of p15 and p16, respectively. One of 14 chronic ATL samples had a homozygously deleted p16 gene and another had a hemizygous deletion of p16. Neither homozygous nor hemizygous deletions of the p15 gene were found in chronic ATL. In total, 10 of 37 (27%) ATL samples had loss of the p15 and/or p16 genes. No point mutations of the p15 and p16 genes were found. The ATL patient with a homozygously deleted p16 in the chronic phase rapidly progressed to acute ATL and died within 6 months of the initial diagnosis. One instructive patient had no detectable deletion of the p15 and p16 genes during the chronic phase of ATL but had a homozygous deletions of both genes when she progressed to acute ATL. Our results suggest an association of p15/p16 deletions with development of acute ATL.

Acute Disease↗

Clinical significance of monocytosis and human monocytic colony-stimulating factor in patients with adult T-cell leukaemia/lymphoma.

We studied 79 patients with adult T-cell leukaemia/lymphoma (ATL) and 11 human T-lymphotropic virus-type I (HTLV-I-carriers to investigate the clinical significance of absolute monocyte counts in peripheral blood. Monocytosis was observed in 20% of ATL patients, but in none of the HTLV-I carriers. ATL patients with absolute monocyte counts above 1.5 x 10(9)/l had a poorer prognosis than those with counts less than 1.5 x 10(9)/l. We also investigated serum levels of human monocytic colony-stimulating factor (hM-CSF) in 7 ATL patients and 11 HTLV-I carriers at the time of diagnosis before chemotherapy, and also in 5 normal healthy individuals. The differences among the 3 groups were not statistically significant. However, markedly increased serum hM-CSF levels were found in 3 ATL patients who were considered to be in the accelerated phase of the disease and 2 of whom were previously diagnosed and had received chemotherapy. There was no correlation between serum hM-CSF level and absolute monocyte count in ATL patients or HTLV-I carriers. The results of hM-CSF assay of supernatants of cultured ATL cells revealed that the ATL cells did not produce hM-CSF themselves. In an ATL patient with pleural involvement, the pleural hM-CSF level was lower than the serum level. These facts indicate that absolute monocyte count is one of the prognostic factors in ATL and the source of the elevated hM-CSF level in some patients with ATL is not ATL cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Constitutive chemokine production results in activation of leukocyte function-associated antigen-1 on adult T-cell leukemia cells.

Adult T-cell leukemia (ATL) is characterized by massive infiltration of circulating ATL cells into a variety of tissues, a finding often associated with poor prognosis. Leukocyte migration from circulation into tissue depends on integrin-mediated adhesion to endothelium, and integrins are tightly regulated by several stimuli, such as inflammatory chemokines. However, the exact mechanisms that enhance adherence of leukemic cells to the endothelium and infiltration into tissues remain to be fully understood. We investigated the mechanisms of extravasation of leukemic cells using ATL cells and report the following novel features of endogenous chemokine-induced adhesion of ATL cells to the endothelium. ATL cells spontaneously adhered to endothelial cells without exogenous stimulation. Integrin leukocyte function-associated antigen-1 (LFA-1) on ATL cells was spontaneously activated. ATL cells produced high amounts of chemokines, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta. Adhesion of ATL cells to endothelial cells and the expression of activated form of LFA-1 were reduced by pretreatment with pertussis toxin, wortmannin, or anti-MIP-1alpha and MIP-1beta antibodies or transfection with antisense of MIP-1alpha or MIP-1beta. Spontaneous polymerization of cytoskeletal F-actin was observed in ATL cells, which was also inhibited by pertussis toxin and wortmannin. We propose that ATL cells adhere to endothelial cells through an adhesion cascade similar to normal leukocytes and that the chemokines produced by ATL cells are involved in triggering integrin LFA-1 through cytoskeletal rearrangement induced by G-protein-dependent activation of phosphoinositide 3-kinases in an autocrine manner. These events result in a strong adhesion of ATL cells to the endothelium and spontaneous transendothelial migration.

3-Phosphoinositide-Dependent Protein Kinases↗

Risk to verbal memory following anterior temporal lobectomy in patients with severe left-sided hippocampal sclerosis.

BACKGROUND: Previous investigations indicate low risk for memory loss following anterior temporal lobectomy (ATL) in patients with severe hippocampal sclerosis (HS) compared with patients with mild HS. However, these conclusions have been established primarily with group-level analyses. OBJECTIVE: To investigate individual base rate risk for verbal memory loss following ATL in patients who have pathologically verified mild, moderate, or severe HS. PATIENTS AND METHODS: One hundred fifteen patients with unilateral temporal lobe epilepsy (68 with left-sided and 47 with right-sided epilepsy) were included. Acquisition, retrieval, and recognition components of verbal memory, as measured by the California Verbal Learning Test, were assessed before and after ATL. Postoperatively, the degree of neuronal loss and reactive gliosis of the hippocampus was assessed via a 3-tiered rating system establishing mild, moderate, and severe pathologic features. Patients with preoperative magnetic resonance imaging-based evidence of lesions outside the mesial temporal area (side of surgical resection) were excluded. RESULTS: Neither seizure laterality nor severity of HS was associated with preoperative verbal memory performance. Postoperatively, the left-sided ATL group demonstrated significant decline across the acquisition (P<.01), retrival (P<.001), and recognition (P<.001) verbal memory components compared with the right-sided ATL group. Patients who underwent left-sided ATL and had mild HS displayed the largest magnitude and percentage proportion of postoperative decline across all verbal memory components. However, 28 (48%) of the 58 patients who underwent left-sided ATL and who had moderate and severe HS displayed statistically reliable declines on retrieval aspects of verbal memory. Most patients undergoing right-sided ATL, regardless of the extent of hippocampal pathologic features, displayed no postoperative memory change. CONCLUSIONS: Substantial individual heterogeneity of memory outcome exists across groups of patients undergoing ATL, with various degrees of pathologically verified HS. Patients undergoing left-sided ATL who have mild HS seem at greatest risk for broad-spectrum verbal memory decline. However, when examining outcome on a patient-by-patient basis, many patients undergoing left-sided ATL who have moderate to severe HS were also vulnerable to verbal memory loss. This risk seems selective to a retrieval-based aspect of verbal memory.

Adolescent↗

Peripheral T-cell lymphoma in Japan: recent progress.

T-lymphoma, including adult T-cell leukemia-lymphoma (ATL) accounted for 75% of non-Hodgkin's lymphoma in the Kyushu district of Japan and for 43% in the nation as a whole. Human T-cell leukemia/lymphoma virus type I (HTLV-I) is closely associated with ATL; however, 11 (7.5%) of 147 patients with ATL were HTLV-I negative. The cumulative percentage incidence of anti-HTLV-I seropositive ATL patients can be simply described by a Weibull model of the typical tear-off type, suggesting that ATL leukemogenesis may be the result of accumulation of approximately five critical events, most likely somatic mutations within HTLV-I-infected T-cells. ATL is still a difficult disease to treat successfully, while peripheral non-ATL T-lymphoma responded to standard chemotherapy in the same way as B-lymphoma. The disease entity of immunoblastic lymphadenopathy (IBL)-like T-lymphoma was also described. Morphological recognition of focal or sheetlike proliferation of atypical neoplastic pale cells and immunoblasts of T-cell nature were important findings for the diagnosis. Major prognostic factors differed greatly among ATL, peripheral non-ATL T-lymphoma and B-lymphoma. Pathology was not associated with treatment outcome and survival in T-cell diseases. These results indicate that the terms ATL, peripheral non-ATL T-lymphoma, and B-lymphoma should be used instead of the all-inclusive term non-Hodgkin's lymphoma, because of differences in cellular origin, clinical features, treatment outcome, prognosis, prognostic factors, chromosomal aberrations, and etiology.

Adult↗

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

Serum deoxythymidine kinase (TK) was measured in 15 patients with the acute type of adult T-cell leukemia (ATL), in 4 with chronic ATL, in 10 with lymphoma type ATL, in 9 with pre-ATL, in 11 with human T-cell leukemia virus type I (HTLV-I) associated with myelopathy (HAM) and in 19 HTLV-I carriers. All these patients were positive for anti-HTLV antibody. The level of TK in pretreatment serum was highest in acute ATL (15.6-1600 U/l, median 107 U/l). It was elevated in chronic ATL (5.4-55.0 U/l, median 37.6 U/l) and lymphoma ATL (6.8-316 U/l, median 16.8 U/l) but normal in pre-ATL (1.8-4.7 U/l, median 2.8 U/l), HAM (1.2-6.0 U/l, median 3.0 U/l) and HTLV-I carriers (1.1-4.6 U/l, median 2.3 U/l). Statistical examination revealed a significant difference between the levels of acute ATL and chronic ATL/lymphoma ATL. In the patients of this series, a close correlation between the level of TK and lactic dehydrogenase (LDH) was statistically present (p less than 0.01). These facts indicate that TK level is a useful indicator of the aggressiveness of ATL cells.

Acute Disease↗

Influence of propranolol, enalaprilat, verapamil, and caffeine on adenosine A(2A)-receptor-mediated coronary vasodilation.

OBJECTIVES: The study was done to determine the effects of propranolol, enalaprilat, verapamil, and caffeine on the vasodilatory properties of the adenosine A(2A)-receptor agonist ATL-146e (ATL). BACKGROUND: ATL is a new adenosine A(2A)-receptor agonist proposed as a vasodilator for myocardial stress perfusion imaging. Beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium blockers are commonly used for the treatment of coronary artery disease (CAD), and their effect on ATL-mediated vasodilation is unknown. Dietary intake of caffeine is also common. METHODS: In 19 anesthetized, open-chest dogs, hemodynamic responses to bolus injections of ATL (1.0 microg/kg) and adenosine (60 microg/kg) were recorded before and after administration of propranolol (1.0 mg/kg, ATL only), enalaprilat (0.3 mg/kg, ATL only), caffeine (5.0 mg/kg, ATL only), and verapamil (0.2 mg/kg bolus, ATL and adenosine). RESULTS: Neither propranolol nor enalaprilat attenuated the ATL-mediated vasodilation (225 +/- 86% and 237 +/- 67% increase, respectively, p = NS vs. control). Caffeine had an inhibitory effect (97 +/- 28% increase, p < 0.05 vs. control). Verapamil blunted both ATL- and adenosine-induced vasodilation (63 +/- 20% and 35 +/- 7%, respectively, p < 0.05 vs. baseline), and also inhibited the vasodilation induced by the adenosine triphosphate-sensitive potassium (K(ATP)) channel activator pinacidil. CONCLUSIONS: Beta-blockers and ACE inhibitors do not reduce the maximal coronary flow response to adenosine A(2A)-agonists, whereas verapamil attenuated this vasodilation through inhibition of K(ATP) channels. The inhibitory effect of verapamil and K(ATP) channel inhibitors like glybenclamide on pharmacologic stress using adenosine or adenosine A(2A)-receptor agonists should be evaluated in the clinical setting to determine their potential for reducing the sensitivity of CAD detection with perfusion imaging.

Adrenergic beta-Antagonists↗

Biosynthesis and Glycosylation of Antarlides, the Polyene Macrolides Possessing Androgen Receptor Antagonistic Activity.

Antarlides (ATLs) are tetraene macrolides discovered from Streptomyces spp. They demonstrated excellent antagonist activities toward mutated androgen receptors (ARs) related to the drug resistances in AR-targeted prostate cancer treatment. Herein, a biosynthetic gene cluster (BGC) of type I modular polyketide synthases (PKSs) from S. conglobatus ATCC 31005 was verified to be responsible for the biosynthesis of ATLs in the heterologous host S. lividans SBT5. The atl BGC was also activated in situ in S. conglobatus by equipping a strong promoter for the PKS genes operon. Unexpectedly, a new glycosylated product, ATL D1, was produced in the heterologous expression. ATL D1 was also generated in the S. conglobatus mutant bearing activated atl BGC through the introduction of a GT1 family glycosyltransferase gene mgt from S. lividans. Enzymatic analysis showed that the protein MGT catalyzed the glycosylation of ATL D to yield ATL D1 by attaching a &#x3b2;-d-glucose to the C11-hydroxyl position. Moreover, site-directed mutation of MGT resulted in an iterative glycosylation to yield ATL D2 bearing a disaccharide at the C11-hydroxyl. These results offer a platform for constructing efficient biosynthetic pathway of ATLs, and the O-glycosylation could be applied to improve the pharmaceutical properties of ATLs.

Glycosylation↗

Multiple gammac-receptor expression in adult T-cell leukemia.

Constitutive expression of the IL-2 receptor (IL-2R) on adult T-cell leukemia (ATL) cells and the presence of permanent IL-2-dependent ATL cell lines indicate that the signal transduction system via IL-2R is a key element for the development of this disease. IL-2R is a member of the common gamma-chain (gammac)-receptor family and shares gamma with IL-4R, IL-7R, IL-9R, and IL-15R. In addition to IL-2R, ATL cells express IL-15R and respond to IL-15. In the present study, we examined other members of this receptor family. ATL cells showed various levels of IL-4Ralpha (CD124) and IL-7Ralpha (CD127) expression, and responded to these cytokines. In contrast, ATL cells hardly responded to IL-9. As primary samples were a mixed population and the results may have been modified by contaminating normal cells, we used ATL cell lines as pure ATL cell populations. Here, we report that IL-2-dependent ATL cell lines also express IL-4Ralpha and respond to IL-4, which was verified by the activation of cytoplasmic transcriptional activator Stat6 protein. Moreover, a novel ATL cell line that grows stably in an IL-7-dependent manner was established from one of the cell lines, and IL-7 induced Stat5 activation in this cell line. These results indicated that ATL cells have the potential to express all gammac-receptors except IL-9R. Overlapping and switching of cytokine receptors supported the idea that ATL cells can rapidly select the appropriate gammac-receptor according to conditions.

Adult↗

Effect of the Advanced Trauma Life Support program on medical students' performance in simulated trauma patient management.

BACKGROUND: Part of the senior medical students' examination at the University of Toronto involves testing with simulated patient management. We compared the performance in these simulations of senior medical students who received Advanced Trauma Life Support (ATLS) training with those who did not receive ATLS training. METHODS: Thirty-two students (group I) completed a standard ATLS course, 12 students (group II) audited the ATLS course, and their performance in the trauma simulations was compared with 44 matched control students (group III) from the same class. Performance in the nontrauma patient simulation stations was also analyzed. The score on each station was standardized to a maximum of 20. The students were also graded on overall Approach (scale of 1 to 5) and pass status. RESULTS: The mean scores (+/-SD, *p < 0.05 compared with other groups) were as follows: Trauma Station, 17.5 +/- 1.02* for group I, 11.76 +/- 0.72* for group II, and 14.67 +/- 0.54* for group III; Nontrauma Station, 13.05 +/- 0.95 for group I, 12.25 +/- 0.72 for group II, and 11.88 +/- 0.80 for group III; Approach, 4.45 +/- 0.50* for group I, 2.09 +/- 0.60* for group II, 3.50 +/- 0.67* for group III. The ATLS-trained and ATLS-audit students had higher scores in the trauma stations than the control group, with the highest scores being in the ATLS-trained group. All ATLS-trained students passed with 62.5% honors and 37.5% passing grades. The ATLS-audit group had 33.3% honors and 66.6% passing grades, compared with the control group who had 84.09% pass, 9.09% borderline, and 6.82% failure in the trauma stations. CONCLUSIONS: The ATLS course, both complete and audit status, prepares students more appropriately for managing trauma patients as judged by trauma simulation scenarios. Consideration should be given for including ATLS as an integral part of the senior medical student curriculum.

Canada↗

Advanced trauma life support study: quality of diagnostic and therapeutic procedures.

BACKGROUND: The introduction of the ATLS course in The Netherlands in 1995 provided for an opportunity to compare data of trauma patients between a pre-ATLS and a post-ATLS period. MATERIALS AND METHODS: Over a 3-year period (May 1996 - September 1997 pre ATLS; December 1997-April 1999 post ATLS) 63 trauma patients with an AIS-ISS > or = 16 (n = 31, pre-ATLS and n = 32, post-ATLS) were prospectively studied in two community residency training (ACS Level III) hospitals. All diagnostic and therapeutic procedures were recorded by a video-camera and evaluated by a neutral faculty of six experienced ATLS trained specialists. RESULTS: Ten out of 14 interventions were performed qualitatively better in the post-ATLS group, while also the overall score was highly significantly better (4.2 pre-ATLS and 5.8 post-ATLS, p < 0.0001). CONCLUSION: Using the opinion of an expert team, this study identified a significantly lower number of patients with inadequate management.

Adult↗

Differences in IL-2 receptor levels between mycosis fungoides and cutaneous type adult T-cell leukemia/lymphoma in the early stages of the disease.

Skin lesions in mycosis fungoides (MF) and cutaneous-type adult T-cell leukemia/lymphoma (c-ATL) are sometimes difficult to differentiate. Our previous investigations showed that the alpha-chain of interleukin-2 receptor (IL-2R alpha) secretion is enhanced in both acute and chronic type ATL. This finding suggested increased levels of IL-2R alpha in c-ATL that might differentiate it from MF. In this study, we report several observations on IL-2R alpha levels in MF and c-ATL. 1) Plasma levels of IL-2R alpha determined by enzyme-linked immunosorbent assay were higher in patients with c-ATL (tumor group, 17,571 +/- 5,919 U/ml; non-tumor group, 4,546 +/- 1,788 U/ml) than those of patients with MF (tumor group, 2,352 +/- 861 U/ml; plaque group, 530 +/- 174 U/ml). 2) The percentages of IL-2R alpha-positive cells in skin lesions of c-ATL were 30.5 +/- 13.4% in the non-tumor group and 62.7 +/- 12.0% in the tumor group, which were significantly higher than those of MF, plaque group (12.7 +/- 5.9%), and tumor group (3.4 +/- 2.3%). 3) Further, there was a significant correlation between plasma IL-2R alpha levels and the number of IL-2R alpha-positive cells in skin lesions in patients with c-ATL (r = 0.654, p < 0.0001) and MF (r = 0.537, p < 0.01) on an individual basis; whereas no increased IL-2R alpha levels in peripheral blood mononuclear cells were observed in patients with either MF or c-ATL. 4) Skin lesions of c-ATL had much higher levels of IL-2R alpha genomic RNA than those of MF in their initial stages when measured by DNase/reverse transcription/polymerase chain reaction and liquid hybridization analysis. These findings suggest that increased plasma IL-2R alpha levels in patients with either MF or c-ATL may be linked to cellular IL-2R alpha levels in the skin lesions, and thus reflect the difference between MF and c-ATL.

Adult↗

Interleukin-4 induces proliferation of adult T-cell leukemia cells.

To evaluate the effect of IL-4 on the growth of leukemic cells from adult T-cell leukemia (ATL) patients (ATL cells) and determine whether the IL-4 autocrine mechanism is involved in the growth of ATL cells, we studied the proliferative response of ATL cells, from 11 patients, cultured in the presence or absence of IL-4 in vitro. Leukemic cells from 10 of the 11 patients examined proliferated in response to both IL-2 and IL-4 in a dose-dependent manner. The proliferative response to IL-4 was higher than that obtained with IL-2 in 8 patients. The expression of the IL-2 receptor (IL-2R) alpha alpha-chain in leukemic cells from some patients was also enhanced by IL-4. The IL-4 receptor was demonstrated by flow cytometry on the surface of ATL cells. Neither IL-4-induced proliferation of ATL cells nor IL-4-induced IL-2R expression on ATL cells was inhibited by anti-Tac or anti-IL-2 antibody and, therefore, these effects of IL-4 are considered independent of endogenous IL-2 activity. However, IL-2 and IL-4 were undetectable in the culture supernatants of ATL cells from any patient by enzyme-linked immunosorbent assay. Interferon-gamma (IFN-gamma) partially inhibited IL-2 or IL-4-induced proliferation of ATL cells. These results suggest that leukemic cells from ATL patients proliferate by an IL-2 or IL-4 paracrine mechanism in lymphoid tissue in vivo and that IFN-gamma inhibits IL-2- or IL-4-induced proliferation of ATL cells.

Aged↗