Acute leukemia in association with Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) and malignancy occurring in the same individual is unusual and has generally been the subject of isolated case reports. To better define the occurrence of these events a registry of cases with synchronous or asynchronous LCH and malignancy was developed with the cooperation of the Histiocyte Society. In 1991 the Histiocyte Society surveyed its members requesting information on cases in which LCH was associated with malignancy. The questionnaire was mailed to all members of the society and specifically requested information on the clinical and laboratory features of the cases, disease evolution, and response to therapy. Retrospective reporting was allowed. With this initial data, an ongoing registry of LCH patients with associated malignancy was begun of such cases, including evolution and response to therapy. Twenty-seven patients were enrolled during the first year of the registry, of whom 4 patients had the association of LCH with a malignant lymphoma and 10 cases had an association of LCH with other types of solid tumor. The remaining 13 patients had the association of LCH with acute leukemia. In five cases, LCH was associated with acute lymphoblastic leukemia FAB L1 (ALL). In four cases the ALL preceded the LCH by 6 months to 1 year. In four of five patients the LCH was localized; in two instances the LCH was treated with chemotherapy. In all cases the leukemia was treated according to local standard ALL protocols and in one case autologous bone marrow transplantation (ABMT) was performed at relapse. Three patients are free of leukemia, one of whom has persistent localized LCH of the skin. Two patients died of the ALL, one of whom was free of the LCH at the time of death. In eight instances LCH was reported in association with acute myeloid leukemia (AML). Six of these patients had a generalized form of LCH. In seven the diagnosis of LCH preceded the diagnosis of leukemia by more than 2 years (median 4 years). In the remaining patient both diagnoses were made concurrently. In all seven cases in whom LCH was the initial diagnosis the treatment consisted of chemotherapy and/or radiotherapy. Seven patients died from the AML, five without evidence of LCH. The temporal patterns of the LCH-ALL and LCH-AML associations are distinct with ALL usually preceding the diagnosis of LCH and AML succeeding it. Such a pattern is suggestive that in cases of ALL the LCH may be a reactive process while in cases of AML occurring after LCH the primary LCH therapy may play an inductive role in the leukemia. © 1994 Wiley-Liss, Inc

From traumatic childhood to cocaine abuse: the critical function of the immune system

Background: Experiencing traumatic childhood is a risk factor for developing substance use disorder (SUD), but the mechanisms that underlie this relationship have not been determined. Adverse childhood experiences affect the immune system and the immune system mediates the effects of psychostimulants. However, whether this system is involved in the etiology of SUD in individuals who have experience early life stress is unknown. Methods:In this study, we performed a series of ex vivo and in vivo experiments in mice and humans to define the function of the immune system in the early-life stress-induced susceptibility to the neurobehavioral effects of cocaine. Results: We provide evidence that exposure to social-stress (S-S) at an early age permanently sensitizes the peripheral (splenocytes) and brain (microglia) immune responses to cocaine in mice. In the brain, microglial activation in the ventral tegmental area (VTA) of S-S mice was associated with functional alterations in dopaminergic neurotransmission, as measured by whole-cell voltage clamp recordings in dopamine (DA) neurons. Notably, preventing immune activation during the S-S exposure reverted the effects of DA in the VTA and the cocaine-induced behavioral phenotype to control levels. In humans, cocaine modulated Toll-like receptor 4-mediated innate immunity, an effect that was enhanced in cocaine addicts who had experienced a difficult childhood. Conclusions Collectively, our findings demonstrate that sensitization to cocaine in early-life-stressed individuals involves brain and peripheral immune responses and that this mechanism is shared between mice and humans

NarE: a novel ADP-ribosyltransferase from Neisseria meningitidis.

Mono ADP-ribosyltransferases (ADPRTs) are a class of functionally conserved enzymes present in prokaryotic and eukaryotic organisms. In bacteria, these enzymes often act as potent toxins and play an important role in pathogenesis. Here we report a profile-based computational approach that, assisted by secondary structure predictions, has allowed the identification of a previously undiscovered ADP-ribosyltransferase in Neisseria meningitidis (NarE). NarE shows structural homologies with E. coli heat-labile enterotoxin (LT) and cholera toxin (CT) and possesses ADP-ribosylating and NAD-glycohydrolase activities. As in the case of LT and CT, NarE catalyses the transfer of the ADP-ribose moiety to arginine residues. Despite the absence of a signal peptide, the protein is efficiently exported into the periplasm of Neisseria. The narE gene is present in 25 out of 43 strains analysed, is always present in ET-5 and Lineage 3 but absent in ET-37 and Cluster A4 hypervirulent lineages. When present, the gene is 100% conserved in sequence and is inserted upstream of and co-transcribed with the lipoamide dehydrogenase E3 gene. Possible roles in the pathogenesis of N. meningitidis are discussed

A Comparative Environmental Assessment for the Synthesis of 1,3-Oxazin-2-one by Metrics: Greenness Evaluation and Blind Spots

Alternative syntheses for the production of 3-benzyl-1,3-oxazinan-2-one are compared and evaluated employing green metrics. An environmental assessment has been performed using the algorithm recently developed by Andraos that takes into account the mass flows and the software EATOS that considers mass flows, environmental impacts of the substances involved, and waste produced. Strengths and critical spots of the environmental tools employed are also discussed. Data collected showed that the synthesis employing diethyl carbonate is the most promising one, having the lowest environmental impact

Expert consensus on dynamics of laboratory tests for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

Objective: To identify which laboratory tests that change over time are most valuable for the timely diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA). Methods: A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of experts was first asked to evaluate 115 profiles of patients with MAS, which included the values of laboratory tests at the pre-MAS visit and at MAS onset, and the change in values between the two time points. The experts were asked to choose the 5 laboratory tests in which change was most important for the diagnosis of MAS and to rank the 5 selected tests in order of importance. The relevance of change in laboratory parameters was further discussed and ranked by the same experts at a consensus conference. Results: Platelet count was the most frequently selected test, followed by ferritin level, aspartate aminotransferase (AST), white cell count, neutrophil count, and fibrinogen and erythrocyte sedimentation rate. Ferritin was most frequently assigned the highest score. At the end of the process, platelet count, ferritin level and AST were the laboratory tests in which the experts found change over time to be most important. Conclusions: We identified the laboratory tests in which change over time is most valuable for the early diagnosis of MAS in sJIA. The dynamics of laboratory values during the course of MAS should be further scrutinised in a prospective study in order to establish the optimal cut-off values for their variation

2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative

Objective To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). Methods A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA-associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Results Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (κ = 0.76). Conclusion We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies

Highly Selective Phosgene-Free Carbamoylation of Aniline by Dimethyl Carbonate under Continuous-Flow Conditions

Over the last 20 years organic carbamates have found numerous applications in pesticides, fungicides, herbicides, dyes, pharmaceuticals, cosmetics, and as protecting groups and intermediates for polyurethane synthesis. Recently, in order to avoid phosgene-based synthesis of carbamates, many environmentally benign and alternative pathways have been investigated. However, few examples of carbamoylation of aniline in continuous-flow apparatus have been reported. In this work, we report a high-yielding, dimethyl carbonate (DMC)-mediated carbamoylation of aniline in a fixed-bed continuously fed reactor employing basic zinc carbonate as catalyst. Several variables of the system have been investigated (i.e. molar ratio of reagents , flow rate, and reaction temperature) to optimize the operating conditions of the system

Chemical Behavior and Reaction Kinetics of Sulfur and Nitrogen Half-Mustard and Iprit Carbonate Analogues

Sulfur and nitrogen mustards are very toxic, yet versatile organic molecules with numerous applications. Herein, we report on a synthesis of a new class of green compounds, i.e., half-mustard and iprit carbonates, that result in new, unexplored, and safe molecules. Their chemical behavior with several nucleophiles and their reaction kinetics have been investigated

One-step hydrothermal synthesis of graphene decorated V2O5 nanobelts for enhanced electrochemical energy storage

Graphene-decorated V2O5 nanobelts (GVNBs) were synthesized via a low-temperature hydrothermal method in a single step. V2O5 nanobelts (VNBs) were formed in the presence of graphene oxide, a mild oxidant, which also enhanced the conductivity of GVNBs. From the electron energy loss spectroscopy analysis, the reduced graphene oxide (rGO) are inserted into the layered crystal structure of V2O5 nanobelts, which further confirmed the enhanced conductivity of the nanobelts. The electrochemical energy-storage capacity of GVNBs was investigated for supercapacitor applications. The specific capacitance of GVNBs was evaluated using cyclic voltammetry (CV) and charge/discharge (CD) studies. The GVNBs having V2O5-rich composite, namely, V(3)G(1) (VO/GO = 3:1), showed superior specific capacitance in comparison to the other composites (V(1)G(1) and V(1)G(3)) and the pure materials. Moreover, the V(3)G(1) composite showed excellent cyclic stability and the capacitance retention of about 82% was observed even after 5000 cycles.open

Immune signatures in human PBMCs of idiotypic vaccine for HCV-related lymphoproliferative disorders

Hepatitis C virus (HCV) is one of the major risk factors for chronic hepatitis, which may progress to cirrhosis and hepatocellular carcinoma, as well as for type II mixed cryoglobulinemia (MC), which may further evolve into an overt B-cell non-Hodgkin's lymphoma (NHL)