Differential modulation of immune recognition molecules by interleukin-7 in human acute leukaemias

Clinical animal models and in vitro data afford evidence for anti-leukaemia immunity. Many reports have underlined the interest of interleukin-7 (IL-7) use in cancer and its pivotal role in immune recognition. This cytokine, initially identified as a B cell growth factor, enhances the anti-tumour properties of immune effector cells via T lymphocyte activation, increased specific cytotoxicity and cytokine secretion. Nonetheless, few data are available regarding the effect of IL-7 on the expression at the leukaemia cell surface of molecules involved in the immune response, which defective expression could induce tolerance or anergy. This prompted us to study the effects of IL-7 on 20 cases of acute myeloid leukaemia (AML) and 9 cases of lymphoid leukaemia (ALL), in comparison with gamma-interferon, a potent inducer of immune regulation molecule expression. In AML and ALL, IL-7 increased MHC class I molecule expression, while class II molecules were weakly modified. The expression of the tumour necrosis factor family members CD40 and Fas/CD95, together with the adhesion molecules ICAM-1/CD54 and CD58/LFA-3, was also increased in both types of leukaemia. The IL-7 was an efficient inducer of B7-2/CD86 expression in AML and ALL, while increased expression of B7-1/CD80 was only observed in AML. In the corresponding, co-cultured T lymphocyte population, IL-7 more particularly increased B7-1/CD80 and CD58/LFA-3 expression. Finally, pre-incubation of leukaemic cells with IL-7 increased the proliferation of responding, normal allogenic T lymphocytes and their secretion of gamma-IFN and IL-2 in mixed the lymphocyte-tumour reaction. We concluded that IL-7 is efficient at increasing the membrane expression of molecules which are central for the development of the immune response, and at improving allogenic immune recognition. The clinical implications of such data require further in vivo investigation.     

Effects of helium-oxygen mixtures on endotracheal tubes: an in vitro study

QUESTION: To determine flow pattern and critical Reynolds numbers in endotracheal tubes submitted to different helium-oxygen mixtures under laboratory conditions. MATERIALS AND METHODS: Flow-pressure relationships were performed for seven endotracheal tubes (rectilinear position, entry length applied) with distal end open to atmosphere (predicted internal diameters: 6-9 mm). Nine helium-oxygen mixtures were tested, with FIHe varying from zero to 0.78 (increment: 10%). Nine flows were tested, with rates varying from 0.25 to 1.60 l s(-1) (increment: 0.15 l s(-1)). Gas flow resistance was calculated, and for each endotracheal tube, a Moody diagram was realised. Flow regime and critical Reynolds numbers were then determined (fully established laminar, nonestablished laminar, smooth turbulent, or rough). RESULTS: Even low concentration of helium in inspiratory mixture reduces endotracheal tubes resistance. Effect is maximal for high flows, small tube and high FIHe. Critical Reynolds numbers are inversely correlated to tube diameter. ANSWER: Under laboratory conditions, flow pattern in endotracheal tubes varies from fully established laminar to rough. Knowledge of the critical Reynolds numbers allows correct application of fluid mechanic formula when studying tube or gaseous mixture effects on respiratory mechanisms.     

Control and spread of Alligator Weed Alternanthera philoxeroides (Mart.) Griseb., in Australia: lessons for other regions

Biological control of alligator weed Alternanthera philoxeroides (Mart.) Griseb. has been successful in limiting growth in water in areas with mild or warm winters, but not on land. Until recently, herbicides have had very limited short term and no long term effectiveness. Several herbicides that now provide better control include: glyphosate over water, and metsulfuron and dichlobenil on land and in shallow water. The latter two are limited by lack of selectivity, contamination of water, and cost. Mechanical or manual control has provided local eradication of the weed at a few locations where infestations were small. Alligator weed is still spreading with new outbreaks on New South Wales, Australia (NSW) coastal beach areas and coastal river systems, and on inland waterbodies. Its use as a cultivated vegetable by some ethnic communities has resulted in many new locations in all eastern Australia states: Queensland to Tasmania. It is predicted that it will spread throughout much of coastal and inland southern Australia. The difficulties with management of this weed indicate that every effort should be made to prevent further invasion of wetlands and, in particular, its introduction to Africa, where it is predicted that all wetlands could support destructive levels of alligator weed growth.     

Interleukin-2 induces chemotactic deficiency in patients with onco hematologic malignancies and autologous bone marrow transplantation.

Unusual gram positive bacteremia has been reported in non granulopenic patients receiving recombinant human interleukin-2 (IL-2) suggesting a beneficial effect of anti gram positive prophylaxis in such patients. We report here studies on granulocyte functions examined during the course of high dose IL-2 therapy (16 to 24 million IU/m2/days for 11 to 18 days) administered during a period of 35 days in 14 patients including 4 solid tumors, 5 chronic myeloid leukemias, 4 recipients of autologous bone marrow transplant (ABMT) and 1 recipient of syngeneic bone marrow transplant. Neutrophils functions were studied before IL-2 administration (d 0), after the first cycle (d 8) and after the third cycle (d 36). Nylon fiber adherence, superoxide production, random migration, phagocytosis, nitroblue tetrazolium reduction, lysozyme and elastase release were not impaired significantly throughout therapy. However N-Formyl-Methionyl-Leucyl-Phenylalanine (FMLP) stimulated chemotaxis of granulocytes, normal before therapy, was significantly impaired as early at d 8 and severely inhibited at d 36 (p less than 0.001). Three septicemia, one corynebacteria parvum septicemia and two gram-negative septicemia despite normal neutrophil counts and oxacillin or Penicillin G plus Pefloxacin prophylaxis, occurred among the 14 patients studied. Although neutrophil functions were not more depressed in transplanted patients than in the other non transplanted patients, special attention should be paid to such patients in whom delayed immune reconstitution could increase the risk of sepsis.