Natural killer cell dysfunction is a distinguishing feature of systemic onset juvenile rheumatoid arthritis and macrophage activation syndrome

Macrophage activation syndrome (MAS) has been reported in association with many rheumatic diseases, most commonly in systemic juvenile rheumatoid arthritis (sJRA). Clinically, MAS is similar to hemophagocytic lymphohistiocytosis (HLH), a genetic disorder with absent or depressed natural killer (NK) function. We have previously reported that, as in HLH, patients with MAS have profoundly decreased NK activity, suggesting that this abnormality might be relevant to the pathogenesis of the syndrome. Here we examined the extent of NK dysfunction across the spectrum of diseases that comprise juvenile rheumatoid arthritis (JRA). Peripheral blood mononuclear cells (PBMC) were collected from patients with pauciarticular (n = 4), polyarticular (n = 16), and systemic (n = 20) forms of JRA. NK cytolytic activity was measured after co-incubation of PBMC with the NK-sensitive K562 cell line. NK cells (CD56(+)/T cell receptor [TCR]-αβ(-)), NK T cells (CD56(+)/TCR-αβ(+)), and CD8(+ )T cells were also assessed for perforin and granzyme B expression by flow cytometry. Overall, NK cytolytic activity was significantly lower in patients with sJRA than in other JRA patients and controls. In a subgroup of patients with predominantly sJRA, NK cell activity was profoundly decreased: in 10 of 20 patients with sJRA and in only 1 of 20 patients with other JRA, levels of NK activity were below two standard deviations of pediatric controls (P = 0.002). Some decrease in perforin expression in NK cells and cytotoxic T lymphocytes was seen in patients within each of the JRA groups with no statistically significant differences. There was a profound decrease in the proportion of circulating CD56(bright )NK cells in three sJRA patients, a pattern similar to that previously observed in MAS and HLH. In conclusion, a subgroup of patients with JRA who have not yet had an episode of MAS showed decreased NK function and an absence of circulating CD56(bright )population, similar to the abnormalities observed in patients with MAS and HLH. This phenomenon was particularly common in the systemic form of JRA, a clinical entity strongly associated with MAS

МЕТОДИКА СИНТЕЗА КВАЗИДВУХПОЛОСОВЫХ СОГЛАСУЮЩИХ УСТРОЙСТВ

The article presents some findings on the potential of analytical methods for the synthesis of broadband matching circuits for solving nontrivial circuit engeneering problems. Nontriviality shows itself in the technique for the assignment of the frequency response model (approximation) for the broadband synthesis in cellular communication, when double-band antennas are essential. The frequency response model appears as the result of frequency transformation, which yields in the assignment of both bands at the very first stage of the synthesis. The bands’width and isolation between them may be controlled independently, which is the essential part of the frequency transformation. Such way offrequency response assignment allows the potential of the method, which is always restricted by a load, to find broader application. In these conditions the frequency response turns to a quasi-double and asymmetrical one due to finite isolation between bands. We also present the general approach to the synthesis, which incorporates both the frequency transformation and novel synthesis technique. The modified frequency transformation can be applied to all types oftraditional approximations of arbitrary orders in synthesizing broadband frequency-selective matching devices. The distinctive feature of this technique is in the use of generalized Darlington’s synthesis for solving the problems of broadband matching of resistances in a lumped element basis with the application of frequency reponses obtained through modified frequency transformation. We have also estimated the efficiency of the developed technique by comparison with the known results.В статье представлены результаты исследования потенциальных возможностей аналитических методов синтеза широкополосных согласующих устройств для решения некоторых нестандартных схемотехнических задач. Нестандартность проявляется в способе задания частотной характеристики при синтезе цепи согласования в таких системах, как сотовая связь, когда необходимо обеспечить работу антенны в двух диапазонах. Способ задания частотной характеристики заключается в использовании частотного преобразования, которое дает возможность на начальном этапе синтеза задавать полосы пропускания диапазонов. Существенными особенностями является возможность независимого управления полосами пропускания диапазонов в процессе синтеза и величиной их изоляции. Такой способ задания частотной характеристики позволяет в большей степени использовать потенциальные характеристики метода согласования, всегда ограниченные сопротивлением нагрузки. Частотная характеристика в этих условиях становится квазидвухполосовой и имеет асимметрию, обусловленную конечной изоляцией диапазонов. Выработана и представлена общая концепция подхода к синтезу, которая включает разработку как модифицированного частотного преобразования, так и новой методики синтеза согласующей цепи. Полученное в результате исследований модифицированное частотное преобразование можно применять для всех видов классических аппроксимирующих функций произвольного порядка, используемых в задачах синтеза широкополосных частотно-избирательных согласующих устройств. Особенность методики заключается в использовании обобщенного метода Дарлингтона для задач широкополосного согласования сопротивлений в сосредоточенном элементном базисе с применением частотных характеристик, полученных при помощи модифицированного преобразования частоты. Также произведена оценка эффективности разработанной методики путем сравнения с известными результатами

Immunomagnetic t-lymphocyte depletion (ITLD) of rat bone marrow using OX-19 monoclonal antibody

Graft versus host disease (GVHD) may be abrogated and host survival prolonged by in vitro depletion of T lymphocytes from bone marrow (BM) prior to allotransplantation. Using a mouse anti-rat pan T-lymphocyte monoclonal antibody (0×19) bound to monosized, magnetic, polymer beads, T lymphocytes were removed in vitro from normal bone marrow. The removal of the T lymphocytes was confirmed by flow cytometry. Injection of the T-lymphocyte-depleted bone marrow into fully allogeneic rats prevents the induction of GVHD and prolongs host survival. A highly efficient technique of T-lymphocyte depletion using rat bone marrow is described. It involves the binding of OX-19, a MoAb directed against all rat thy-mocytes and mature peripheral T lymphocytes, to monosized, magnetic polymer spheres. Magnetic separation of T lymphocytes after mixing the allogeneic bone marrow with the bead/OX-19 complex provides for a simple, rapid depletion of T lymphocytes from the bone marrow. In vitro studies using flow cytometry and the prevention of GVHD in a fully allogeneic rat bone marrow model have been used to demonstrate the effectiveness of the depletion procedure. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Defects of B-cell terminal differentiation in patients with type-1 Kabuki syndrome

Kabuki syndrome (KS) is a complex multi-system developmental disorder associated with mutation of genes encoding histone-modifying proteins. In addition to craniofacial, intellectual, and cardiac defects, KS is also characterized by humoral immune deficiency and autoimmune disease, yet no detailed molecular characterization of the KS-associated immune phenotype has previously been reported

Minimal change nephrotic syndrome after stem cell transplantation: a case report and literature review

Graft-versus-host disease is one of the most frequent complications occurring after haematopoietic stem cell transplantation. Recently, renal involvement has been described as a manifestation of chronic graft-versus-host disease. Immunosuppression seems to play a major role: clinical disease is triggered by its tapering and resolution is achieved with the resumption of the immunosuppressive therapy. Prognosis is apparently favourable, but long term follow up data are lacking

Sustained elevation of serum interleukin-18 and its association with hemophagocytic lymphohistiocytosis in XIAP deficiency

X-linked lymphoproliferative syndrome (XLP) is a rare primary immunodeficiency characterized by increased vulnerability to Epstein-Barr virus infection. XLP type 1 is caused by mutations in SH2D1A, whereas X-linked inhibitor of apoptosis (XIAP) encoded by XIAP/BIRC4 is mutated in XLP type 2. In XIAP deficiency, hemophagocytic lymphohistiocytosis (HLH) occurs more frequently and recurrence is common. However, the underlying mechanisms remain mostly unknown. We describe the characteristics of the cytokine profiles of serum samples from 10 XIAP-deficient patients. The concentration of interleukin (IL)-18 was strikingly elevated in the patients presented with HLH, and remained high after the recovery from HLH although levels of other pro-inflammatory cytokines approached the normal range. Longitudinal examination of two patients demonstrated marked exacerbation of IL-18 levels during every occasion of HLH. These findings may suggest the association between HLH susceptibility and high serum IL-18 levels in XIAP deficiency. © 2013 Elsevier Ltd. All rights reserved

The Helium and Carbon Isotope Characteristics of the Andean Convergent Margin

Subduction zones represent the interface between Earth’s interior (crust and mantle) and exterior (atmosphere and oceans), where carbon and other volatile elements are actively cycled between Earth reservoirs by plate tectonics. Helium is a sensitive tracer of volatile sources and can be used to deconvolute mantle and crustal sources in arcs; however it is not thought to be recycled into the mantle by subduction processes. In contrast, carbon is readily recycled, mostly in the form of carbon-rich sediments, and can thus be used to understand volatile delivery via subduction. Further, carbon is chemically-reactive and isotope fractionation can be used to determine the main processes controlling volatile movements within arc systems. Here, we report helium isotope and abundance data for 42 deeply-sourced fluid and gas samples from the Central Volcanic Zone (CVZ) and Southern Volcanic Zone (SVZ) of the Andean Convergent Margin (ACM). Data are used to assess the influence of subduction parameters (e.g., crustal thickness, subduction inputs, and convergence rate) on the composition of volatiles in surface volcanic fluid and gas emissions. He isotopes from the CVZ backarc range from 0.1 to 2.6 RA (n = 23), with the highest values in the Puna and the lowest in the Sub-Andean foreland fold-and-thrust belt. Atmosphere-corrected He isotopes from the SVZ range from 0.7 to 5.0 RA (n = 19). Taken together, these data reveal a clear southeastward increase in 3He/4He, with the highest values (in the SVZ) falling below the nominal range associated with pure upper mantle helium (8 ± 1 RA), approaching the mean He isotope value for arc gases of (5.4 ± 1.9 RA). Notably, the lowest values are found in the CVZ, suggesting more significant crustal inputs (i.e., assimilation of 4He) to the helium budget. The crustal thickness in the CVZ (up to 70 km) is significantly larger than in the SVZ, where it is just ∼40 km. We suggest that crustal thickness exerts a primary control on the extent of fluid-crust interaction, as helium and other volatiles rise through the upper plate in the ACM. We also report carbon isotopes from (n = 11) sites in the CVZ, where δ13C varies between −15.3‰ and −1.2‰ [vs. Vienna Pee Dee Belemnite (VPDB)] and CO2/3He values that vary by over two orders of magnitude (6.9 × 108–1.7 × 1011). In the SVZ, carbon isotope ratios are also reported from (n = 13) sites and vary between −17.2‰ and −4.1‰. CO2/3He values vary by over four orders of magnitude (4.7 × 107–1.7 × 1012). Low δ13C and CO2/3He values are consistent with CO2 removal (e.g., calcite precipitation and gas dissolution) in shallow hydrothermal systems. Carbon isotope fractionation modeling suggests that calcite precipitation occurs at temperatures coincident with the upper temperature limit for life (122°C), suggesting that biology may play a role in C-He systematics of arc-related volcanic fluid and gas emissions.Fil: Barry, P. H.. Woods Hole Oceanographic Institution; Estados UnidosFil: De Moor, J. M.. University of New Mexico; Estados Unidos. UNIVERSIDAD NACIONAL DE COSTA RICA (UNA);Fil: Chiodi, Agostina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Aguilera, F.. Universidad Católica del Norte; ChileFil: Hudak, M. R.. Woods Hole Oceanographic Institution; Estados UnidosFil: Bekaert, D. V.. Woods Hole Oceanographic Institution; Estados UnidosFil: Turner, S. J.. University of Massachussets; Estados UnidosFil: Curtice, J.. Woods Hole Oceanographic Institution; Estados UnidosFil: Seltzer, A. M.. Woods Hole Oceanographic Institution; Estados UnidosFil: Jessen, G. L.. Universidad Austral de Chile; ChileFil: Osses, E.. Universidad Austral de Chile; ChileFil: Blamey, J. M.. Universidad de Santiago de Chile; ChileFil: Amenábar, M. J.. Universidad de Santiago de Chile; ChileFil: Selci, M.. University Of Naples Federico Ii; ItaliaFil: Cascone, M.. University Of Naples Federico Ii; ItaliaFil: Bastianoni, A.. University Of Naples Federico Ii; ItaliaFil: Nakagawa, M.. Tokyo Institute Of Technology; JapónFil: Filipovich, Ruben Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Bustos, Emilce. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Schrenk, M. O.. Michigan State University; Estados UnidosFil: Buongiorno, J.. Maryville College; Estados UnidosFil: Ramírez, C. J.. Servicio Geológico Ambiental (segeoam); Costa RicaFil: Rogers, T. J.. University of Tennessee; Estados UnidosFil: Lloyd, K. G.. University of Tennessee; Estados UnidosFil: Giovannelli, D.. Institute Of Marine Biological Resources And Biotechno; Itali

Long-term complications and side effects after allogeneic hematopoietic stem cell transplantation: an update

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for various malignant and non-malignant diseases. Many patients have now been followed for two or three decades posttransplant and are presumed to be cured. With the tremendous advances achieved in terms of supportive care, it is reasonable to expect outcomes to improve steadily and consequently increasing numbers of transplant survivors will be facing life after the initial transplant experience. Although long-term allo-HSCT survivors generally enjoy good health, for many others, cure or control of the underlying disease is not accompanied by full restoration of health. The burden of long-term morbidity borne by allo-HSCT survivors is substantial, and long-term follow-up of patients who received allo-HSCT is now widely recommended. Immediate survival is no longer the sole concern after allo-HSCT. The goals should also include complete recovery of the overall health status with normal physical and psychological functioning. Long-term side effects after allo-HSCT include non-malignant organ or tissue dysfunction, changes in quality of life, infections related to abnormal immune reconstitution and secondary cancers. Many of these can be attributed to the deleterious effects of chronic graft-versus-host disease. The aims of this review are to provide an update on the recent research evidence in the field

Ancillary Therapy and Supportive Care of Chronic Graft-versus-Host Disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. Ancillary Therapy and Supportive Care Working Group Report

AbstractThe Ancillary Therapy and Supportive Care Working Group had 3 goals: (1) to establish guidelines for ancillary therapy and supportive care in chronic graft-versus-host disease (GVHD), including treatment for symptoms and recommendations for patient education, preventive measures, and appropriate follow-up; (2) to provide guidelines for the prevention and management of infections and other common complications of treatment for chronic GVHD; and (3) to highlight the areas with the greatest need for clinical research. The definition of “ancillary therapy and supportive care” embraces the most frequent immunosuppressive or anti-inflammatory interventions used with topical intent and any other interventions directed at organ-specific control of symptoms or complications resulting from GVHD and its therapy. Also included in the definition are educational, preventive, and psychosocial interventions with this same objective. Recommendations are organized according to the strength and quality of evidence supporting them and cover the most commonly involved organs, including the skin, mouth, female genital tract, eyes, gastrointestinal tract, and lungs. Recommendations are provided for prevention of infections, osteoporosis, and steroid myopathy and management of neurocognitive and psychosocial adverse effects related to chronic GVHD. Optimal care of patients with chronic GVHD often requires a multidisciplinary approach