bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Endogenous Activated Protein C Attenuates Experimental Autoimmune Encephalomyelitis by Inducing Myeloid-Derived Suppressor Cells
Authors: Alabanza Leah M. , Esmon Naomi L. , Esmon Charles T. , Bynoe Margaret S.
Published: August 2013

Activated protein C (PC) is an anticoagulant involved in the interactions between the coagulation and immune systems. Activated PC has broad anti-inflammatory effects that are mediated through its ability to modulate leukocyte function and confer vascular barrier protection. We investigated the influence of activated PC on the pathogenesis of experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. We modulated activated PC levels in the circulation during EAE induction through systemic administration of a mAb against PC/activated PC (anti-PC). We initially hypothesized that inhibition of activated PC may result in a heightened inflammatory environment, leading to increased EAE pathogenesis. Contrary to this hypothesis, mice treated with anti-PC Ab (anti-PC mice) exhibited attenuated EAE. Interestingly, despite reduced disease severity and minimal pathogenic conditions in the CNS, anti-PC mice exhibited considerable leukocyte infiltration in the brain, comparable to control mice with severe EAE. Furthermore, CD4+ T cells were diminished in the periphery of anti-PC mice, whereas various CD11b+ populations were increased, notably the myeloid-derived suppressor cells (MDSCs), a CD11b+ subset characterized as potent T cell suppressors. MDSCs from anti-PC mice exhibited increased expression of T cell suppressive factors and effectively inhibited T cell proliferation. Overall, our findings show that activated PC inhibition affected EAE pathogenesis at multiple fronts, specifically increasing vascular barrier permeability, as evidenced by considerable leukocyte infiltration in the brain. Additionally, inhibition of activated PC modulated the functional responses of CD11b+ cells, leading to the expansion and increased activation of MDSCs, which are suppressive to the CD4+ T cells required for EAE progression, thereby resulting in attenuated EAE.
Multiple Checkpoint Breach of B Cell Tolerance in Rasgrp1-Deficient Mice
Authors: Bartlett Amber , Buhlmann Janet E. , Stone James , Lim Bing , Barrington Robert A.
Published: August 2013

Lymphopenic hosts offer propitious microenvironments for expansion of autoreactive B and T cells. Despite this, many lymphopenic hosts do not develop autoimmune disease, suggesting that additional factors are required for breaching self-tolerance in the setting of lymphopenia. Mice deficient in guanine nucleotide exchange factor Rasgrp1 develop a lymphoproliferative disorder with features of human systemic lupus erythematosus. Early in life, Rasgrp1-deficient mice have normal B cell numbers but are T lymphopenic, leading to defective homeostatic expansion of CD4 T cells. To investigate whether B cell–intrinsic mechanisms also contribute to autoimmunity, Rasgrp1-deficient mice were bred to mice containing a knockin autoreactive BCR transgene (564Igi), thereby allowing the fate of autoreactive B cells to be assessed. During B cell development, the frequency of receptor-edited 564Igi B cells was reduced in Rasrp1-deficient mice compared with Rasgrp1-sufficient littermate control mice, suggesting that tolerance was impaired. In addition, the number of 564Igi transitional B cells was increased in Rasgrp1-deficient mice compared with control mice. Immature 564Igi B cells in bone marrow and spleen lacking RasGRP1 expressed lower levels of Bim mRNA and protein, suggesting that autoreactive B cells elude clonal deletion during development. Concomitant with increased serum autoantibodies, Rasgrp1-deficient mice developed spontaneous germinal centers at 8–10 wk of age. The frequency and number of 564Igi B cells within these germinal centers were significantly increased in Rasgrp1-deficient mice relative to control mice. Taken together, these studies suggest that autoreactive B cells lacking Rasgrp1 break central and peripheral tolerance through both T cell–independent and –dependent mechanisms.
Lectin-like Receptor Ly49s3 on Dendritic Cells Contributes to the Differentiation of Regulatory T Cells in the Rat Thymus
Authors: Yamada Toshiyuki , Nanashima Naoki , Akita Miki , Shimizu Takeshi , Miura Takuya , Yamana Daisuke , Sawano Takeyuki , Sakurai Takuya , Tsuchida Shigeki
Published: August 2013

Naturally occurring regulatory T cells (nTregs), important for immune regulation and the maintenance of self-tolerance, develop in the thymus. The Hirosaki hairless rat (HHR), derived from the Sprague–Dawley rat (SDR), was shown to have decreased peripheral lymphocyte number, small thymus, and leukocyte infiltration in its dermis. In the HHR thymus, the medulla was underdeveloped and nTreg number was decreased. Array comparative genome hybridization revealed the deletion of an NK cell lectin-like receptor gene, Ly49s3, detecting MHC class I molecules on target cells, in the chromosome 4q42 region in HHRs. The gene was expressed in thymic conventional dendritic cells (cDCs) in SDRs, but not in HHRs. When CD4–single-positive or CD4+CD8−CD25− thymocytes were cultured with thymic cDCs, the expression of nTreg marker genes was lower when these cells were from HHRs than from SDRs, suggesting that HHR cDCs are deficient in the ability to induce and maintain nTreg differentiation. Expression of the genes was recovered when Ly49s3 was expressed on HHR thymic cDCs. Expression levels of MHC class II genes, presumably from cDCs, were parallel to those of nTreg marker genes in mixed-cell cultures. However, in the presence of an anti-MHC class I Ab, blocking interaction between Ly49s3 and MHC class I molecules, the expression of the former genes was upregulated, whereas the latter was downregulated. These results suggest that Ly49s3 contributes to nTreg regulation along with MHC class II molecules, whose effects alone are insufficient, and loss of Ly49s3 from thymic cDCs is the reason for the nTreg deficiency in HHRs.
Integrin-α FG-GAP Repeat-Containing Protein 2 Is Critical for Normal B Cell Differentiation and Controls Disease Development in a Lupus Model
Authors: Al-Shami Amin , Crisostomo Jeannette , Wilkins Carrie , Xu Nianhua , Humphries Juliane , Chang Wei C. , Anderson Stephen J. , Oravecz Tamas
Published: August 2013

The phenylalanyl-glycyl–glycyl-alanyl-prolyl (FG-GAP) domain plays an important role in protein–protein interactions, including interaction of integrins with their ligands. Integrin-α FG-GAP repeat-containing protein 2 (Itfg2) is a highly conserved protein in vertebrates that carries two FG-GAP domains, but its role in mammalian physiology is unknown. In this article, we show that Itfg2 is an intracellular protein and it plays a critical role in B cell differentiation and development of autoimmunity. Itfg2-deficient mice displayed a phenotype consistent with retention of B cells in the spleen and had a lower concentration of IgG in the blood when compared with wild-type littermates. Itfg2-deficient splenocytes also showed a defect in cell migration in vitro. After immunization with a thymus-dependent Ag, the absence of Itfg2 caused a shift in B cell maturation from the germinal centers to the extrafollicular regions of the spleen and blocked deposition of Ag-specific plasma cells in the bone marrow. In support of hematopoietic cell intrinsic activity of Itfg2, bone marrow transplantation of Itfg2-deficient cells was sufficient to impair germinal center development in wild-type mice. Furthermore, Itfg2 deficiency exacerbated development of autoimmune disease in MRL/lpr lupus-prone mice. These results identify Itfg2 as a novel contributor to B cell differentiation and a negative regulator of the autoimmune response during lupus.
Suppression of IL-12 Production by Tristetraprolin through Blocking NF-кB Nuclear Translocation
Authors: Gu Ling , Ning Huan , Qian Xuesong , Huang Qi , Hou Rong , Almourani Rajaa , Fu Mingui , Blackshear Perry J. , Liu Jianguo
Published: August 2013

Tristetraprolin (TTP), an mRNA-binding protein, plays a significant role in regulating the expression of adenylate-uridylate–rich elements containing mRNAs. Mice deficient of TTP (TTP−/−) develop a systemic autoimmune inflammatory syndrome characterized by cachexia, conjunctivitis, and dermatitis. IL-12 plays a crucial role in immune defense against infectious and malignant diseases. In this study, we found increased production of IL-12 during endotoxic shock and enhanced Th1 cells in TTP knockout mice. The levels of IL-12 p70 and p40 protein as well as p40 and p35 mRNA were also increased in activated macrophages deficient of TTP. In line with these findings, overexpression of TTP suppressed IL-12 p35 and p40 expression at the mRNA and promoter level, whereas it surprisingly had little effects on their mRNA stability. Our data showed that the inhibitory effects of TTP on p35 gene transcription were completely rescued by overexpression of NF-кB p65 and c-Rel but not by the p50 in activated macrophages. Our data further indicated that TTP acquired its inhibition on IL-12 expression through blocking nuclear translocation of NF-кB p65 and c-Rel while enhancing p50 upon stimulation. In summary, our study reveals a novel pathway through which TTP suppresses IL-12 production in macrophages, resulting in suppression of Th1 cell differentiation. This study may provide us with therapeutic targets for treatment of inflammatory and autoimmune disorders.
Recombinant Human IL-15 Trans-Presentation by B Leukemic Cells from Chronic Lymphocytic Leukemia Induces Autologous NK Cell Proliferation Leading to Improved Anti-CD20 Immunotherapy
Authors: Laprevotte Emilie , Voisin Gregory , Ysebaert Loïc , Klein Christian , Daugrois Camille , Laurent Guy , Fournie Jean-Jacques , Quillet-Mary Anne
Published: August 2013

Recombinant human IL-15 (rhIL-15) is one of the most promising cytokines for antitumor immunotherapy. In physiology IL-15 trans-presentation by accessory cells leads to pleiotropic activities, including activation of immune cells, such as NK cells. NK cells are largely involved in Ab-dependent cellular cytotoxicity mediated by therapeutic mAbs, such as rituximab, in chronic lymphocytic leukemia (CLL). Nevertheless, in CLL, Ab-dependent cellular cytotoxicity is relatively impaired by the low E:T ratio (NK/B leukemic cells). Thus, any strategy leading to an increase in NK cell number and activation status can offer new strategies for CLL treatment. To this end, we evaluated the effect of rhIL-15 on autologous NK cell stimulation in CLL samples. We show that rhIL-15 induces NK cell activation and proliferation, leading to improved B leukemic cell depletion. This phenomenon is significantly increased in the presence of anti-CD20 mAbs. In addition, the greater effect of obinutuzumab versus rituximab suggests a cooperative role between rhIL-15 signaling and CD16 signaling in the induction of NK cell proliferation. Moreover, rhIL-15–induced proliferation of autologous NK cells is strictly dependent on their interaction with B leukemic cells, identified in this study as new accessory cells for rhIL-15 trans-presentation. Thus, rhIL-15 is able to promote NK cell–based activity in Ab immunotherapy of CLL.
Macrophage-Derived IL-33 Is a Critical Factor for Placental Growth
Authors: Fock Valerie , Mairhofer Mario , Otti Gerlinde R. , Hiden Ursula , Spittler Andreas , Zeisler Harald , Fiala Christian , Knöfler Martin , Pollheimer Jürgen
Published: August 2013

IL-33, the most recently discovered member of the IL-1 superfamily and ligand for the transmembrane form of ST2 (ST2L), has been linked to several human pathologies including rheumatoid arthritis, asthma, and cardiovascular disease. Deregulated levels of soluble ST2, the natural IL-33 inhibitor, have been reported in sera of preeclamptic patients. However, the role of IL-33 during healthy pregnancy remains elusive. In the current study, IL-33 was detected in the culture supernatants of human placental and decidual macrophages, identifying them as a major source of secreted IL-33 in the uteroplacental unit. Because flow cytometry and immunofluorescence stainings revealed membranous ST2L expression on specific trophoblast populations, we hypothesized that IL-33 stimulates trophoblasts in a paracrine manner. Indeed, BrdU incorporation assays revealed that recombinant human IL-33 significantly increased proliferation of primary trophoblasts as well as of villous cytotrophoblasts and cell column trophoblasts in placental explant cultures. These effects were fully abolished upon addition of soluble ST2. Interestingly, Western blot and immunofluorescence analyses demonstrated that IL-33 activates AKT and ERK1/2 in primary trophoblasts and placental explants. Inhibitors against PI3K (LY294002) and MEK1/2 (UO126) efficiently blocked IL-33–induced proliferation in all model systems used. In summary, with IL-33, we define for the first time, to our knowledge, a macrophage-derived regulator of placental growth during early pregnancy.
CagA-Dependent Downregulation of B7-H2 Expression on Gastric Mucosa and Inhibition of Th17 Responses during Helicobacter pylori Infection
Authors: Lina Taslima T. , Pinchuk Irina V. , House Jennifer , Yamaoka Yoshio , Graham David Y. , Beswick Ellen J. , Reyes Victor E.
Published: August 2013

Gastric epithelial cells (GECs) are the primary target for Helicobacter pylori infection and may act as APCs regulating local T cell responses. We previously reported that H. pylori infection of GECs induces the expression of the T cell coinhibitory molecule B7-H1 on GECs. This process contributes to the hyporesponsiveness of CD4+ effector T cells and accumulation of regulatory T cells. In the present study, we investigated the impact of H. pylori cytotoxin-associated gene A (CagA) on the modulation of the expression of the T cell costimulator B7-H2 by GECs. B7-H2 is involved in promoting Th17 type responses. H. pylori infection downregulates B7-H2 expression by GECs in a CagA-dependent manner. IFN-γ, which is increased in the H. pylori–infected gastric mucosa, synergizes with H. pylori in downregulating B7-H2 expression by GECs. CagA-mediated modulation of B7-H2 on GECs involves p70 S6 kinase phosphorylation. The CagA-dependent B7-H2 downregulation in GECs correlates with a decrease in Th17 type responses in vitro and in vivo. Furthermore, CagA-dependent modulation of Th17 responses was inversely correlated with the H. pylori colonization levels in vivo. Our data suggest that CagA contributes to the ability of H. pylori to evade Th17-mediated clearance by modulating expression of B7-H2 and, thus, to the establishment of the H. pylori chronic infection.
Mycobacteria-Infected Dendritic Cells Attract Neutrophils That Produce IL-10 and Specifically Shut Down Th17 CD4 T Cells through Their IL-10 Receptor
Authors: Doz Emilie , Lombard Robin , Carreras Florence , Buzoni-Gatel Dominique , Winter Nathalie
Published: August 2013

Neutrophils participate in the control of mycobacterial infection both by directly eliminating bacilli and by interacting with macrophages and dendritic cells (DCs). Despite host defenses, slow-growing mycobacteria can persist in the host for decades, mostly inside macrophages and DCs, and eventually destroy tissues after exacerbated inflammation. IL-17A–driven neutrophil recruitment may participate in this process. We report that mouse bone marrow–derived DCs infected with live Mycobacterium bovis Bacillus Calmette-Guérin (BCG) produced large amounts of CXCL1 and CXCL2, and attracted neutrophils. After physical contact with DCs infected with live BCG, the neutrophils produced large quantities of the immunosuppressive cytokine IL-10 via the MyD88 and spleen tyrosine kinase pathways. The CD11b integrin was involved in this neutrophil–DC interaction and allowed IL-10 production. TCR OVA transgenic mice immunized with a BCG strain producing OVA mounted an OVA-specific Th17 and Th1 CD4 response. Interestingly, IL-10–producing neutrophils specifically shut down IL-17A production by Th17 CD4 cells, but not IFN-γ production by Th1 cells. This was due to Th17 CD4 cell–restricted expression of the receptor for IL-10. After neutrophil depletion, total mouse lung cells produced less IL-10 but more IL-17A; IFN-γ production was not affected. Therefore, we suggest that during mycobacterial infection, regulatory neutrophils are instructed by infected reservoir DCs to produce IL-10 that specifically targets IL-10Rα–expressing Th17 CD4 T cells. This could be important to control the otherwise exuberant Th17 response.
HLA-G5 Induces IL-4 Secretion Critical for Successful Pregnancy through Differential Expression of ILT2 Receptor on Decidual CD4+ T Cells and Macrophages
Authors: Lombardelli Letizia , Aguerre-Girr Maryse , Logiodice Federica , Kullolli Ornela , Casart Ysabel , Polgar Beata , Berrebi Alain , Romagnani Sergio , Maggi Enrico , Le Bouteiller Philippe , Piccinni Marie-Pierre
Published: August 2013

Successful pregnancy in humans has been associated with production of IL-4 by T cells at the feto–maternal interface. Soluble HLA-G5 produced by trophoblasts potentially controls the decidual T cell cytokine profile. We studied the effect of HLA-G5 on the cytokine profile of purified human macrophages and Ag-specific T cells in vitro. We demonstrated that HLA-G5 increased production of IL-12 by purified peripheral blood macrophages. Although IL-12 production by macrophages is known to induce IFN-γ production by CD4+ T cells, HLA-G5 increased production of IL-4 but not IFN-γ by CD4+ T cells after Ag presentation by macrophages. We found that this apparent paradox was due to the differential expression of the ILT2 HLA-G5 receptor on activated T cells and macrophages. This receptor was upregulated in the former and downregulated in the latter after Ag presentation and activation of both cell types. This observation was confirmed in situ, where decidual macrophages and T cells are continuously exposed to HLA-G5 produced locally and activated by trophoblast alloantigens. Freshly isolated decidua basalis macrophages expressed lower levels of ILT2 than peripheral blood macrophages from the same pregnant women. They did not spontaneously produce IL-12, whereas freshly isolated decidual CD4+ T cells expressed high levels of activation markers (CD25, HLA-DR, and CD69) as well as ILT2 and spontaneously produced IL-4 but not IFN-γ. Therefore, HLA-G5 could be responsible, at least in part, via its interaction with ILT2, for decidual T cell IL-4 production, known to be crucial for successful pregnancy.
Exacerbation of Allergen-Induced Eczema in TLR4- and TRIF-Deficient Mice
Authors: Brandt Eric B. , Gibson Aaron M. , Bass Stacey , Rydyznski Carolyn , Khurana Hershey Gurjit K.
Published: August 2013

Despite its presence on resident skin cells, the role of TLR4 in skin diseases remains poorly understood. This is highly significant because the skin biome is rich with potential TLR4 agonists. We aimed to establish the contribution of TLR4 to atopic dermatitis and determine the mechanism by which TLR4 acts in an experimental model of atopic dermatitis. MyD88, TLR4, or Toll–IL-1R domain-containing adapter-inducing IFN-β (TRIF)–deficient and wild-type mice were epicutaneously exposed to Aspergillus fumigatus allergen over 3 wk. Impaired skin barrier function was assessed by measuring transepidermal water loss (TEWL). Skin levels of innate and adaptive genes were quantified. In an experimental model of atopic dermatitis, TEWL, allergic sensitization, and epidermal thickness were increased following cutaneous allergen exposure, and these were further enhanced in the absence of TLR4. Increased allergen-induced skin levels of innate (S100A8/A9, IL-1β, TNF-α, and CXCL2) and Th17 genes (IL-17A and IL-17F) were observed in TLR4-deficient mice compared with wild-type mice. The absence of MyD88 alleviated disease (decreased TEWL, skin thickness, proinflammatory cytokines), whereas TRIF deficiency exacerbated disease. In conclusion, signaling through the TLR4 and TRIF pathways limits skin barrier dysfunction, cutaneous allergic sensitization, and proinflammatory cytokine production.
Cutting Edge: Mycobacterium tuberculosis but Not Nonvirulent Mycobacteria Inhibits IFN-β and AIM2 Inflammasome–Dependent IL-1β Production via Its ESX-1 Secretion System
Authors: Shah Swati , Bohsali Amro , Ahlbrand Sarah E. , Srinivasan Lalitha , Rathinam Vijay A. K. , Vogel Stefanie N. , Fitzgerald Katherine A. , Sutterwala Fayyaz S. , Briken Volker
Published: August 2013

Mycobacterium tuberculosis extracellular DNA gains access to the host cell cytosol via the ESX-1 secretion system. It is puzzling that this extracellular DNA of M. tuberculosis does not induce activation of the AIM2 inflammasome because AIM2 recognizes cytosolic DNA. In this study, we show that nonvirulent mycobacteria such as Mycobacterium smegmatis induce AIM2 inflammasome activation, which is dependent on their strong induction of IFN-β production. In contrast, M. tuberculosis, but not an ESX-1–deficient mutant, inhibits the AIM2 inflammasome activation induced by either M. smegmatis or transfected dsDNA. The inhibition does not involve changes in host cell AIM2 mRNA or protein levels but led to decreased activation of caspase-1. We furthermore demonstrate that M. tuberculosis inhibits IFN-β production and signaling, which was partially responsible for the inhibition of AIM2 activation. In conclusion, we report a novel immune evasion mechanism of M. tuberculosis that involves the ESX-1–dependent, direct or indirect, suppression of the host cell AIM2 inflammasome activation during infection.
TLR4 Signaling Shapes B Cell Dynamics via MyD88-Dependent Pathways and Rac GTPases
Authors: Barrio Laura , Saez de Guinoa Julia , Carrasco Yolanda R.
Published: August 2013

B cells use a plethora of TLR to recognize pathogen-derived ligands. These innate signals have an important function in the B cell adaptive immune response and modify their trafficking and tissue location. The direct role of TLR signaling on B cell dynamics nonetheless remains almost entirely unknown. In this study, we used a state-of-the-art two-dimensional model combined with real-time microscopy to study the effect of TLR4 stimulation on mouse B cell motility in response to chemokines. We show that a minimum stimulation period is necessary for TLR4 modification of B cell behavior. TLR4 stimulation increased B cell polarization, migration, and directionality; these increases were dependent on the MyD88 signaling pathway and did not require ERK or p38 MAPK activity downstream of TLR4. In addition, TLR4 stimulation enhanced Rac GTPase activity and promoted sustained Rac activation in response to chemokines. These results increase our understanding of the regulation of B cell dynamics by innate signals and the underlying molecular mechanisms.
Semantic Dementia Diagnosed by F-18 FDG PET/MRI: Co-registered Images
Authors: Jolepalem Prashant , Wu Dafang
Published: August 2013

We report a case of a 61-year-old male who presented with a sudden change in mental status. From a psychiatric standpoint, his symptoms were consistent with a bipolar disorder. A neurology consult raised suspicion for vascular dementia, given the sudden onset of symptoms; however, the magnetic resonance angiography (MRA) was unremarkable. The magnetic resonance imaging (MRI) had findings that were suggestive of both vascular and frontotemporal lobe dementia based on parenchymal atrophy and a lacunar infarct near the thalamus. However, by co-registering the magnetic resonance images with a subsequent fluorine-18 Fluorodeoxyglucose positron emission tomography (F-18 FDG PET), and combining the functional data with the anatomic appearance, the diagnosis was narrowed to semantic dementia, which is one of the lesser known subtypes of frontotemporal lobe dementia (FTD).
Multiple Osteolytic Lesions
Authors: Vinayachandran Divya , Sankarapandian Sathasivasubramanian
Published: August 2013

Several systemic diseases initially present with various oral manifestations. Investigation of these oral symptoms may at times lead to the diagnosis of grave underlying life-threatening conditions. We present one such case, where the patient manifested with gross enlargement of the mandible, along with lesions in the lower limbs. These lesions were the initial manifestation and on further investigations the patient was diagnosed with multiple myeloma.
Infected Dentigerous Cyst of Maxillary Sinus Arising from an Ectopic Third Molar
Authors: Guruprasad Yadavalli , Chauhan Dinesh Singh , Kura Umashankar
Published: August 2013

A dentigerous cyst or follicular cyst is a form of odontogenic cyst. It is believed that it forms during the development of the tooth and is associated with pressure exerted by the crown of an unerupted (or partially erupted) tooth on the fluid within the follicular space. Typically, dentigerous cysts are painless and discovered during routine radiographic examination. However, they may be large and result in a palpable mass. Additionally, as they grow they displace adjacent teeth. They almost exclusively occur in permanent dentition. The cyst is lined by stratified squamous non-keratinizing epithelium. About 70% of dentigerous cysts occur in the mandible and 30% in the maxilla. Dentigerous cysts associated with ectopic teeth within the maxillary sinus are very rare. We report radiologic and pathologic features in a rare case of infected dentigerous cyst of maxillary sinus arising from an ectopic third molar in a 21-year-old female patient.
The Failed Growth Economy, Stagnation, and Biophysical Limits to Growth
Authors: Klitgaard Kent A.
Published: August 2013

There are many indications that the era of economic degrowth has already begun, despite conscious policy efforts to maintain it. This indicated by a secular decline in the rate of GDP growth for essentially all OECD countries and many developing ones over the second half of the twentieth century. I believe that this phenomenon has occurred because the mature economies of the world have confronted a set of internal, or social, limits driven by the internal dynamics of capital accumulation and by approaching biophysical limits. These patterns are likely to continue. The purpose of this paper is to synthesize the literature on internal limits to capital accumulation and economic growth with the emerging literature on biophysical limits. Growth-oriented mainstream economics is incapable of analyzing adequately the historical conjuncture of the internal and biophysical limits. A study of heterodox political economy and institutional economics is needed in order to understand the transition to sustainability. The paper surveys prior theories of the internal limits to economic growth and synthesizes them with future potential limits imposed by the decrease in availability and increase in cost of high-quality resources, climate change and peak oil.
Novel Use of Intravenous Immunoglobulin G in Complement Factor H Missense Mutation: A Case Report
Authors: Neidich Alon B. , Neidich Eitan M. , Lee Andy , Nicoletta Julie , Rohrer Richard J. , Milner Lawrence S. , Cooper Jeffrey T.
Published: August 2013

A white girl presented at 8 months of age with thrombotic microangiopathy, followed by recurrent episodes of renal dysfunction, hemolysis, and thrombocytopenia, compatible with atypical hemolytic uremic syndrome. The episodes of the syndrome were treated by a combination of infusions of fresh frozen plasma, plasmapheresis, and continuous venovenous hemodialysis. Interval resolution occurred between episodes. At 2 years of age, prophylactic infusions of fresh frozen plasma were started between relapses, but this proved to be poorly protective; however, introduction of prophylactic intravenous gamma globulin at age 3.5 years resulted in prolonged remission (42 months). Serum levels of the third and fourth components of complement, total hemolytic complement, and complement factor H were normal. Results of the third component functional assay were low before and normalized after the start of immunoglobulin G prophylaxis. A missense mutation of complement factor H was identified. At 6 years of age, the patient underwent bilateral native nephrectomy and started long-term peritoneal dialysis, followed by a combined liver-kidney transplant at age 8 years. Four and a half years after transplant, she has excellent renal and liver graft function without recurrence of atypical hemolytic uremic syndrome.
Transplant Certification and Quality Assessment: Time to Take the Front Line?
Authors: Tuttle-Newhall Janet E. , Lentine Krista L. , Axelrod David , Ware Landon V. , Milton Jennifer , Schnitzler Mark A.
Published: August 2013

In the beginning of the past decade, a series of highly publicized events led the general public to question the ability of the transplant community to effectively police itself. Common to the events was the perception that insufficient regulation of the transplant community allowed both unintentional errors and, rarely, purposeful violations of policy, to affect the safety and justice of organ allocation and transplant practice. The goal of this article is to discuss the resulting regulatory responses to these events and to highlight one transplant center's experience with the current external review process. The potential benefits of using process control charts to prospectively monitoring a center's outcomes, as well as the benefits of implementing procedures that ensure the quality of publically reported data, are described. Specifically, the critical need for each center to understand the components, limitations, and implications of public outcome reporting and to define processes that promote real time self-evaluation and quality improvement are demonstrated.
The Swiss Transplant Cohort Study's Framework for Assessing Lifelong Psychosocial Factors in Solid-Organ Transplants
Authors: De Geest Sabina , Burkhalter Hanna , Berben Lut , Bogert Laura Jane , Denhaerynck Kris , Glass Tracy R. , Goetzmann Lutz , Kirsch Monika , Kiss Alexander , Koller Michael T. , Piot-Ziegler Chantal , Schmidt-Trucksäss Arno ,   For the Psychosocial Interest, Group, Swiss Transplantm, Cohort Study
Published: August 2013

Background

Understanding outcomes after transplant requires a biopsychosocial model that includes biomedical and psychosocial factors. The latter, to date, are assessed only in a limited way as part of transplant registries or cohort studies. The Swiss Transplant Cohort Study (STCS) is a nationwide open cohort study (starting May 2008) to systematically and prospectively assess psychosocial factors. This article describes the framework underpinning STCS's psychosocial assessment.

Methods

The STCS framework was adapted from the multidimensional conceptual perspective of Dew et al to describe transplant psychosocial domains and specific outcomes by adding a time perspective, a system perspective, and interaction among domains.

Results

We propose a multidimensional, multilevel biopsychosocial framework representing mutually influencing domains from before to after transplant, and exemplify each domain by factors included in STCS and their measurement. The transplant patient, centrally positioned, is described by clinical and sociodemographic characteristics (eg, socioeconomic status, educational, professional, and relationship status). The following psychosocial domains further describe the patient: (1) physical/functional (eg, perceived health status, sleep quality, daytime sleepiness), (2) psychological (eg, depression, stress), (3) behavioral (eg, medication adherence, smoking, drug use, physical activity, sun protection), (4) social (eg, work capacity/return to work), and (5) global quality of life. Factors associated with health care system level (eg, trust in transplant team) are also included in the model.

Conclusion

The STCS's psychosocial framework provides a basis for studying the interplay of biomedical, sociodemographic, psychosocial, behavioral, and health care system factors in view of transplant outcomes and therefore has the potential to guide biopsychosocial transplant research.
Families' Knowledge, Attitudes, and Experiences of the Tissue Donation Process
Authors: Luo Jingjing , Rothnie Alison , Sanderson Elaine , Smith Melissa , Cowie Anne , Musiello Toni
Published: August 2013

Context

Most existing research on the experiences of donor families has been focused on organ donation, with few studies pertaining specifically to the experiences of tissue donor families. Further investigation into tissue donation in Australia is needed in order to improve the process, support, and potential rate of tissue donation consent.

Objective

To assess the experiences of families of recent tissue donors, to compare changes in the tissue donation process with previously published research, and to identify areas for improvement.

Design

Cross-sectional survey by postal questionnaire.

Setting and Participants

Families who consented to tissue donation through DonateLife Western Australia (the coordinating organization for deceased organ and tissue donation in Western Australia) between 2004 and 2009 were invited to participate.

Main Outcome Measures

Donor families' experience, knowledge, and attitudes toward tissue donation and their satisfaction with the approach and quality/effectiveness of support services provided to donor families.

Results

One hundred one (39%) of the 256 questionnaires were completed. Most respondents were satisfied with how they were approached, whether by phone or in person. Most participants who received ongoing support after donation (91%) found it beneficial. Nearly half (46%) of respondents supported the use of tissue for research; however, only 28% could recall the topic being discussed at the time of donation. Only 40% of respondents knew of the differences between organ and tissue donation before the donation process. Overall, respondents rated the experience of donating tissue as positive.
Psychological Stress in Transplantation: A Unified Concept? What is Measured and How: A Literature Review
Authors: Rapo Christel , Piot-Ziegler Chantal
Published: August 2013

This article describes how the concept of stress is studied in the field of solid-organ transplantation. Sixty-five articles or reviews of scientific research on stress are analyzed. The question addressed was how stress is explored and defined in transplant research, as it is often referred to as affecting psychological and/or physical transplant outcomes.
Achievements and Barriers in the Organ Donation Process: A Critical Analysis of Donation Coordinators' Discourse
Authors: Mercado-Martínez Francisco J. , Díaz-Medina Blanca A. , Hernández-Ibarra Eduardo
Published: August 2013

Context

Donation coordinators play an important role in the success or failure of organ donation and transplant programs. Nevertheless, these professionals' perspectives and practices have hardly been explored, particularly in low- and middle-income countries.

Objective

To examine donation coordinators' discourse on the organ donation process and the barriers they perceive.

Design

A critical qualitative study was carried out in Guadalajara, Mexico.

Setting and Participants

Twelve donation coordinators from public and private hospitals participated.

Data Gathering and Analysis

Data were gathered by using semistructured interviews and critical discourse analysis.

Results

Participants indicated that partial results have been achieved in deceased organ donation. Concomitantly, multiple obstacles have adversely affected the process and outcomes: at the structural level, the fragmentation of the health system and the scarcity of financial and material resources; at the relational level, nonegalitarian relationships between coordinators and hospital personnel; at the ideational level, the transplant domain and its specialists overshadow the donation domain and its coordinators. Negative images are associated with donation coordinators.

Conclusions

Organ donation faces structural, relational, and ideational barriers; hence, complex interventions should be undertaken. Donation coordinators also should be recognized by the health system.
Respiratory Syncytial Virus and Pediatric Liver Transplant: One Center's Experience
Authors: Lerret Stacee , Mavis Alisha , Biank Vincent , Telega Grzegorz
Published: August 2013

Respiratory syncytial virus (RSV) is a ubiquitous virus responsible for acute infections of the respiratory tract in patients of all ages. RSV presents significant health risks to immunocompromised patients. Two patients, 1 before a liver transplant and 1 after a liver transplant, died of a severe RSV infection. Because of the high risk of death, we recommend expanding the criteria for palivizumab prophylaxis to 2 types of patients: (1) patients with chronic liver disease or who have received a liver transplant and are 24 months old or less and (2) transplant recipients with underlying pulmonary conditions who are less than 36 months old. Further research is indicated in pediatric solid-organ transplant centers to evaluate the effective management of RSV infection to prevent morbidity.
Attitudes of Australian Emergency Department Clinicians toward Organ and Tissue Donation: An Analysis of Cultural and Religious Influences
Authors: Weiland Tracey J. , Marck Claudia H. , Jelinek George A. , Neate Sandra L. , Hickey Bernadette B.
Published: August 2013

Objectives

To determine Australian emergency department clinicians' cultural and religious barriers to organ and tissue donation (OTD).

Method

A national cross-sectional survey of physicians and nurses working in Australian emergency departments. An online questionnaire of 133 items was delivered via e-mail.

Results

Responses were received from 599 of 2969 (20%) physicians and 212 of 1026 (21%) nurses. Respondents were generally representative of the colleges. Participants were from 26 cultures and 9 religious groups. Self-rated competence in OTD tasks was low for some minority groups: South American, Caribbean, and Pacific Islanders reported little competence in identifying, referring, and caring for potential donors, introducing OTD to families, and approaching distressed families. Those of Arabic, Jewish, North African, and Middle Eastern background reported low competence in referring and caring for potential donors and comforting distressed families. They reported low support for OTD after cardiac death, low familiarity with OTD processes after cardiac death, and poor familiarity with the coroner's process. Those of Southern Asian background reported low comfort in undertaking OTD processes, poor familiarity with the coroner's process, and low competence in caring for potential donors. Those of Islamic faith reported low competence in identifying potential donors, low support for OTD after cardiac death, and thought that the emergency department was an inappropriate location to identify potential donors. Those of Buddhist and Hindu faiths reported low competence in identifying potential donors. Respondent numbers for members of minority groups were low, thereby limiting the statistical accuracy of results.

Conclusions

Among clinicians working in Australian emergency departments, religion and culture may be barriers to facilitating OTD in emergency departments because of the perceptions and attitudes held by particular religious and cultural groups. Improving access to education may address these differences.
Successful Embolization of a Cytomegalovirus-Related Duodenal Ulcer in a Kidney-Pancreas Transplant Recipient
Authors: Ríos Antonio , Febrero Beatriz , Ramírez Pablo , Rodriguez Jose Manuel , Robles Ricardo , Bueno Francisco Sánchez , Medina José García , Capel Antonio , Parrilla Pascual
Published: August 2013

One of the complications that can occur in pancreas transplant is a massive intestinal hemorrhage, although such a hemorrhage is very rarely caused by ulcers due to cytomegalovirus infection. Treatment is fundamentally based on relaparatomy, although in some cases interventional radiology can be an efficient alternative because it allows the exact bleeding point to be located and therapeutic embolization to be performed. In this case, a man with diabetes type 1 who was given a simultaneous kidney-pancreas transplant had an ulcer due to cytomegalovirus infection develop in the duodenal graft (in the early postoperative period), causing a severe hemorrhage in the lower part of the gastrointestinal tract that was controlled via selective embolization of a branch of the pancreaticoduodenal artery.
Chagas Disease: A Proposal for Testing Policy for Solid-Organ Transplant in the United States
Authors: Wallace James A. , Miller Linda , Beavis Andrew , Baptista Carlos A. C.
Published: August 2013

Chagas disease is caused by the parasite Trypanosoma cruzi. The disease is difficult to detect because of the asymptomatic pathogenesis after infection. Chagas disease is endemic throughout much of Mexico, Central America, and South America, but human migration patterns are bringing the pathogen to the United States. The disease currently affects 16 to 18 million people with approximately 50000 deaths annually in these countries. In the United States, national screening of the blood supply was instituted in early 2007, and more than 1000 donors with T cruzi infection have been identified within the past 3 years of testing. It was observed that out of the 58 organ procurement organizations in the United States, only 4 required mandatory testing of every donor for Chagas disease. It was estimated that as of 2009, approximately 409 000 residents are living with Chagas disease, and in a 22-year span, approximately 300 patients may have contracted Chagas disease through transplant. Proposed solutions to the current testing method include automatic testing based on the medical social history questionnaire, testing of all recipients for Chagas disease, testing all persons of Latin descent, or testing of all organ donors.
Validation of a Single Item to Assess Daytime Sleepiness for the Swiss Transplant Cohort Study
Authors: Burkhalter Hanna , Wirz-Justice Anna , Cajochen Christian , Weaver Terri , Steiger Jürg , Fehr Thomas , Venzin Reto Martin , De Geest Sabina
Published: August 2013

Context

Daytime sleepiness in kidney transplant recipients has emerged as a potential predictor of impaired adherence to the immunosuppressive medication regimen. Thus there is a need to assess daytime sleepiness in clinical practice and transplant registries.

Objective

To evaluate the validity of a single-item measure of daytime sleepiness integrated in the Swiss Transplant Cohort Study (STCS), using the American Educational Research Association framework.

Methods

Using a cross-sectional design, we enrolled a convenience sample of 926 home-dwelling kidney transplant recipients (median age, 59.69 years; 25%-75% quartile [Q25-Q75], 50.27–59.69), 63% men; median time since transplant 9.42 years (Q25-Q75, 4.93–15.85). Daytime sleepiness was assessed by using a single item from the STCS and the 8 items of the validated Epworth Sleepiness Scale. Receiver operating characteristic curve analysis was used to determine the cutoff for the STCS daytime sleepiness item against the Epworth Sleepiness Scale score.

Results

Based on the receiver operating characteristic curve analysis, a score greater than 4 on the STCS daytime sleepiness item is recommended to detect daytime sleepiness. Content validity was high as all expert reviews were unanimous. Concurrent validity was moderate (Spearman ϱ, 0.531; P < .001) and convergent validity with depression and poor sleep quality although low, was significant (ϱ, 0.235; P < .001 and ϱ, 0.318, P= .002, respectively). For the group difference validity: kidney transplant recipients with moderate, severe, and extremely severe depressive symptom scores had 3.4, 4.3, and 5.9 times higher odds of having daytime sleepiness, respectively, as compared with recipients without depressive symptoms.

Conclusion

The accumulated evidence provided evidence for the validity of the STCS daytime sleepiness item as a simple screening scale for daytime sleepiness.
Gastrointestinal Bleeding in Patients with Ventricular Assist Devices: What Every Cardiac Nurse Should Know
Authors: Ballew Carole C. , Surratt Joe F. , Collins Tami L. , Shah Neeral
Published: August 2013

Patients with end-stage heart failure are increasingly being treated with implantation of a long-term ventricular assist device. As the use of these devices has grown, health care providers have been faced with managing clinically significant gastrointestinal bleeding in this population. Gastrointestinal bleeding is not uncommon and is reported to occur in 13% to 44% of patients treated with ventricular assist devices. Interestingly, because patients with ventricular assist devices are housed on units accustomed to managing the device, cardiac nurses are often asked about the management of gastrointestinal bleeding. This article describes the possible causes of, the array of diagnostic procedures for, and treatments for this complication. It is critical to develop an understanding of this topic so cardiac nurses can partner with other subspecialty groups to manage this population.
Lithium Chloride
Authors: Nowick James S. , Lutterbach Guido , Barbay J. Kent , He Wei , Liu Jinlin , Huang Liangbin
Published: July 2024

image

[

7447‐41‐8

]

LiCl
(MW 42.39)

InChI = 
1S/ClH.Li/h1H;/q;+1/p‐1

InChIKey = 
KWGKDLIKAYFUFQ‐UHFFFAOYSA‐M

(source of Cl
−
as nucleophile and ligand; weak Lewis acid that modifies the reactivity of enolates, lithium dialkylamides, and other Lewis bases)

Physical Data
: mp 605 °C; bp 1325–1360 °C;
d
2.068 g cm
−3
.

Solubility
: very sol H
2
O; sol methanol, ethanol, acetone, acetonitrile, THF, DMF, DMSO, HMPA.

Form Supplied in
: white solid, widely available.

Drying
: deliquescent; for most applications, drying at 150 °C for 3 h is sufficient; for higher purity, recrystallization from methanol, followed by drying at 140 °C/0.5 mmHg overnight, is recommended.

Handling, Storage, and Precautions
: of low toxicity; take directly from the oven when dryness is required.
1‐Chloro‐3,3‐Dimethylbenziodoxole
Authors: Thai‐Savard Léa
Published: July 2024

image

[69352‐04‐1]

C
9
H
10
ClIO

(MW 296.53)

InChI = 
1S/C9H10ClIO/c1‐9(2)7‐5‐3‐4‐6‐8(7)11(10)12‐9/h3‐6H,1‐2H3

InChIKey = 
HEBYOYIIQNKPGQ‐UHFFFAOYSA‐N

(key intermediate for hypervalent iodine(III) compounds)

Physical Data
: 178.5–180.0 °C.

Solubility
: dichloromethane, carbon tetrachloride, ethyl acetate, pentane, and most organic solvents.

Form Supplied in
: yellow powder, commercially available.

Analysis of Reagent Purity
:
1
H NMR (300 MHz, CDCl
3
, 23 °C) δ 7.79 (m, 1
H
), 7.99 (ddd,
J
 = 8.6, 7.2, and 1.6 Hz, 1
H
), and 8.23 (ddd,
J
 = 14.0, 8.0, and 1.3 Hz, 2
H
).
13
C NMR (75.5 MHz, CDCl
3
, 23 °C) δ 117.1, 126.9, 128.8, 131.9, 133.4, 136.6, and 167.2.

Preparative Method
: chlorination of 2‐iodobenzoic acid using trichloroisocyanuric acid (TCICA) (eq 1).

1

image

A 3 L, three‐necked, round‐bottom flask equipped with a magnetic stirring bar, gas inlet, Dimroth condenser, and drop funnel with pressure‐equalizing side arm was charged, under argon with solid 2‐iodobenzoic acid (200 g, 0.790 mol), and anhydrous MeCN (1.5 L) was added. The resulting stirred suspension was heated to 75 °C in an oil bath. The dropping funnel was charged with a solution of trichloroisocyanuric acid (63.7 g, 0.266 mol) in anhydrous MeCN (300 mL). The solution of trichloroisocyanuric acid was dropped into the vigorously stirring reaction mixture within 5 min. The reaction mixture was refluxed for an additional 5 min. The reaction media was vacuum filtered over an oven‐preheated, sintered‐glass funnel with a tightly packed pad of Celite (1 cm thick), and the filter cake was rinsed with additional hot MeCN (100–200 mL). The combined filtrates were evaporated to near‐dryness, and the resulting yellow solid was filtered over a sintered‐glass funnel and washed with a small amount of cold MeCN. The mother liquor from filtration was partially concentrated, giving a second crop of crystals. The combined crops were dried for 2 h under high vacuum to give 1‐chloro‐3,3‐dimethylbenziodoxole (223 g, 89%) as free‐flowing light‐yellow crystals.

Purification
: recrystallization in acetonitrile.

Handling, Storage, and Precautions
: air stable.