Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy

The immune-mediated graft-versus-leukemia effect is important to prevent relapse after allogeneic progenitor cell transplantation. This process requires engraftment of donor immuno-competent cells. The objective of this study was to assess the feasibility of achieving engraftment of allogeneic peripheral blood or bone marrow progenitor cell after purine analog containing nonmyeloablative chemotherapy. Patients with advanced leukemia or myelodysplastic syndromes (MDS) who were not candidates for a conventional myeloablative therapy because of older age or organ dysfunction were eligible. All patients had an HLA-identical or one-antigen-mismatched related donor. Fifteen patients were treated (13 with acute myeloid leukemia and 2 with MDS). The median age was 59 years (range, 27 to 71 years). Twelve patients were either refractory to therapy or beyond first relapse. Eight patients received fludarabine at 30 mg/m2/d for 4 days with idarubicin at 12 mg/m2/d for 3 days and ara-c at 2 g/m2/d for 4 days (n = 7) or melphalan at 140 mg/m2/d (n = 1). Seven patients received 2-chloro-deoxyadenosine at 12 mg/m2/d for 5 days and ara-C 1 at g/m2/d for 5 days. Thirteen patients received allogeneic peripheral blood stem cells and 1 received bone marrow after chemotherapy. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methyl-prednisolone. Treatment was generally well tolerated, with only 1 death from multiorgan failure before receiving stem cells. Thirteen patients achieved a neutrophil count of greater than 0.5 x 10(9)/L a median of 10 days postinfusion (range, 8 to 17 days). Ten patients achieved platelet counts of 20 x 10(9)/L a median of 13 days after progenitor cell infusion (range, 7 to 78 days). Eight patients achieved complete remissions (bone marrow blasts were < 5% with neutrophil recovery and platelet transfusion independence) that lasted a median of 60 days posttransplantation (range, 34 to 170+ days). Acute GVHD grade > or = 2 occurred in 3 patients. Chimerism analysis of bone marrow cells in 6 of 8 patients achieving remission showed > or = 90% donor cells between 14 and 30 days postinfusion, and 3 of 4 patients remaining in remission between 60 and 90 days continued to have > or = 80% donor cells. We conclude that purine analog-containing nonmyeloablative regimens allow engraftment of HLA-compatible hematopoietic progenitor cells. This approach permits us to explore the graft-versus-leukemia effect without the toxicity of myeloablative therapy and warrants further study in patients with leukemia who are ineligible for conventional transplantation with myeloablative regimens either because of age or concurrent medical conditions.     

Larynx-associated lymphoid tissue (LALT) in young children

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) plays a central role in mucosal immunity. Whereas the characteristics and function of MALT in the intestine are well established, almost nothing is known about MALT in the larynx. METHODS: In this study we examined the morphology and the lymphocyte subset composition of MALT in the larynges of children who had died of sudden infant death or various defined traumatic or nontraumatic causes. RESULTS: Organized lymphoid tissue was found in the supraglottic parts of the larynx in nearly 80% of the children in both groups. This lymphoid tissue showed all morphological signs of MALT, such as typical lymphoid follicles with germinal centers, infiltration of the overlying epithelium by lymphocytes, and high endothelial venules (HEV). Thus we will use the term LALT (larynx-associated lymphoid tissue) to refer to this tissue. The lymphoid follicles of LALT contained mainly B lymphocytes with some CD4+ lymphocytes in the germinal centers. Remarkably, T lymphocytes of both subset types and B lymphocytes were observed in comparable numbers in the parafollicular area. CONCLUSIONS: We assume that LALT is a physiological structure of the larynx in young children. The morphology and the distribution of lymphocyte subsets are similar to those of MALT in the human gut. LALT may be a regular part of the mucosal immune system in young children with the role of respiratory inductive site for mucosal immunity.     

Microbeam RBS on flat panel displays

We have demonstrated the utility of microbeam-Rutherford BackScattering (μ-RBS) in spatially resolved studies of operational plasma effects on the interior surfaces of plasma flat panel displays manufactured by Photonics Imaging. The experiments were performed at the Sandia Nuclear microprobe using a 2.8 MeV He beam with an average beam spot size of less than 8 μm. The interior surface of the top panes of the flat panels is composed of approximately 800 nm of MgO on top of a 2000 nm thick PbO layer. μ-RBS of sample panels operated under varying conditions measured changes in the surface MgO film thickness due to plasma erosion and redeposition as accurately as ± 1.5 nm. The high accuracy in the MgO thickness measurement was achieved by inferring the MgO thickness from the shift of the Pb front edge in the RBS spectrum. An estimate for the thickness accuracy as a function of the acquired statistics is presented. The surface of the flat panels' bottom panes is also comprised of MgO on top of PbO. However, troughs 100 μm wide by 10 μm deep were partially filled with phosphor and cover the entire width of the surface. This leaves only 100 μm long sections of MgO within the trough exposed. Using μ-RBS, we were able to analyze the surface composition of these regions.     

Silver halide-containing photochromic powders of SiO2 sol–gel glass

In order to develop a photochromic powder, an SiO2-gel based on tetraethoxysilane (TEOS) was doped with AgNO3 or AgNO2. The dried gel pieces were pulverized and treated with aqueous or ethanolic halide solutions for growing silver halide microcrystals. Both the introduction of cuprous compounds such as CuBr, CuCl, Cu2O, Cu(CH3COO)2·H2O or sulphur-containing compounds and the formation of AgBrxCl1-x crystals lead to variations of photochromic properties. X-ray diffraction measurements indicate that the average diameters of silver halide microcrystals are limited to 70–110nm. Ultraviolet–visible spectroscopic investigations show the reversibility of the darkening/fading process. Cu+-containing samples exhibit a remarkable fading even at room temperature.     

Effect of dynamic strain ageing on the tensile properties of a modified 9Cr–1Mo steel

Tensile testing of a modified 9Cr–1Mo steel in two microstructural conditions (710T– normalized at 1100°C, tempered at 710°C, and 550T – normalized at 1100°C tempered at 550°C) in the temperature range 25–450°C, under strain rates of 2.3×10-5–2.3×10-3s-1, exhibited serrated flow curves, with serrations appearing almost at the onset of deformation and disappearing before ultimate strengths were attained. The serrated flow curves (characteristics of dynamic strain ageing) were accompanied by increased ultimate strengths, loss of ductility and negative strain-rate sensitivity, relative to the ambient temperature properties. However, the increase in ultimate strength and the reduction in ductility were much larger for 710T specimens, as compared to 550T ones. In the dynamic strain ageing regime, the work-hardenability of 710T specimens increased rapidly while that of 550T specimens remained practically unaffected. Based on the microstructural consideration and the observed activation energy of 45 kJ mol-1, it is proposed that serrations are initiated by a nitrogen atmosphere formation on the waiting dislocations by a pipe diffusion mechanism, and they disappear by diffusion to the precipitate sinks during deformation. Because the fine alloy carbide precipitates in 550T specimens are more effective sinks than those of 710T ones, they can cause much faster depletion of the atmosphere, resulting in a much smaller effect of dynamic strain ageing on the tensile properties of 550T specimens.     

The residential gateway

Burgeoning competition in telecommunications is multiplying the number of communications paths into the home-but a standard multinetwork connection could sort them out. Services going into the residence may enter over copper wires, hybrid fiber coax, RF transmission, fiber to the curb, or, most importantly, by any combination of these sources and structures. To have a successful market, residential customers must be able to move smoothly from one combination of these offerings to another so that the customers consider the move worthwhile. For this multinetwork-to-multiservice interconnection to have value, it must be simple, and that simplicity is the basis for the residential gateway concept. In other words, the substantial complexity of the interconnection must be hidden from the consumer. The concept is essentially the development of a set of interface standards between the broadband residential access networks and the communication services (the internal networks) required for the consumer's home     

Mathematical foundations for error estimation in numericalsolutions of integral equations in electromagnetics

The problem of error estimation in the numerical solution of integral equations that arise in electromagnetics is addressed. The direct method (Green's theorem or field approach) and the indirect method (layer ansatz or source approach) lead to well-known integral equations both of the first kind [electric field integral equations (EFIE)] and the second kind [magnetic field integral equations (MFIE)]. These equations are analyzed systematically in terms of the mapping properties of the integral operators. It is shown how the assumption that field quantities have finite energy leads naturally to describing the mapping properties in appropriate Sobolev spaces. These function spaces are demystified through simple examples which also are used to demonstrate the importance of knowing in which space the given data lives and in which space the solution should be sought. It is further shown how the method of moments (or Galerkin method) is formulated in these function spaces and how residual error can be used to estimate actual error in these spaces. The condition number of all of the impedance matrices that result from discretizing the integral equations, including first kind equations, is shown to be bounded when the elements are computed appropriately. Finally, the consequences of carrying out all computations in the space of square integrable functions, a particularly friendly Sobolev space, are explained