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Search Results: 1 - 10 of 444 matches for " Bernadette Rojkovich "
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Safety, pharmacokinetics, and biologic activity of pateclizumab, a novel monoclonal antibody targeting lymphotoxin α: results of a phase I randomized, placebo-controlled trial
Brinda Emu, Diana Luca, Carolyn Offutt, Jane L Grogan, Bernadette Rojkovich, Marna B Williams, Meina T Tang, Jim Xiao, June H Lee, John C Davis
Arthritis Research & Therapy , 2012, DOI: 10.1186/ar3554
Abstract: The single ascending dose (SAD) phase in patients with stable RA consisted of six cohorts (4:1 active:placebo at 0.3 mg/kg IV, 1.0 mg/kg IV, 1.0 mg/kg SC, 3.0 mg/kg IV, 3.0 mg/kg SC, and 5.0 mg/kg IV; n = 5/cohort). In the multiple ascending dose (MAD) phase, patients with prespecified RA disease activity received three doses of pateclizumab or placebo (4:1) every 2 weeks (1.0 mg/kg SC, n = 10; 3.0 mg/kg SC, n = 20; or 5.0 mg/kg IV, n = 5). Safety and tolerability were assessed throughout, and clinical activity was determined after three doses (Week 6).We observed no serious adverse events (AEs) or dose-limiting toxicities, and the majority of AEs were mild to moderate. The pharmacokinetic profiles were linear, and clearance was independent of dose. Reductions in levels of serum CXCL13 were observed, supporting the biologic activity of pateclizumab on the LTα pathway. Patients receiving pateclizumab in the 3.0 mg/kg MAD group (3.0 mg/kg SC) demonstrated ACR20, ACR50, and ACR70 response rates at week 6 of 75%, 56% and 25%, respectively, compared with 57%, 29%, and 0% in the placebo group. The median Disease Activity Score in 28 joints, C-reactive protein, reduction was 28% for pateclizumab, versus 8.4% for placebo.Pateclizumabwas generally well-tolerated in RA patients. Preliminary evidence of clinical activity was observed in active RA patients at the dose level targeted for clinical effect.Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease associated with progressive joint damage, pain, fatigue, and disability. Despite advances in the treatment of RA, a significant proportion of patients do not achieve an adequate clinical response upon treatment with available therapies, and less than half of patients who do respond to therapy achieve complete remission [1]. Current biologic treatment options for the management of RA often target the proinflammatory cytokine TNF-α; however, these agents are associated with safety concerns, such as increased ri
TGFβ Activated Kinase 1 (TAK1) at the Crossroad of B Cell Receptor and Toll-Like Receptor 9 Signaling Pathways in Human B Cells
Dániel Szili, Zsuzsanna Bankó, Eszter Angéla Tóth, Gy?rgy Nagy, Bernadette Rojkovich, Tamás Gáti, Melinda Simon, Zoltán Hérincs, Gabriella Sármay
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096381
Abstract: B cell development and activation are regulated by combined signals mediated by the B cell receptor (BCR), receptors for the B-cell activating factor of the tumor necrosis factor family (BAFF-R) and the innate receptor, Toll-like receptor 9 (TLR9). However, the underlying mechanisms by which these signals cooperate in human B cells remain unclear. Our aim was to elucidate the key signaling molecules at the crossroads of BCR, BAFF-R and TLR9 mediated pathways and to follow the functional consequences of costimulation.Therefore we stimulated purified human B cells by combinations of anti-Ig, B-cell activating factor of the tumor necrosis factor family (BAFF) and the TLR9 agonist, CpG oligodeoxynucleotide. Phosphorylation status of various signaling molecules, B cell proliferation, cytokine secretion, plasma blast generation and the frequency of IgG producing cells were investigated. We have found that BCR induced signals cooperate with BAFF-R- and TLR9-mediated signals at different levels of cell activation. BCR and BAFF- as well as TLR9 and BAFF-mediated signals cooperate at NFκB activation, while BCR and TLR9 synergistically costimulate mitogen activated protein kinases (MAPKs), ERK, JNK and p38. We show here for the first time that the MAP3K7 (TGF beta activated kinase, TAK1) is responsible for the synergistic costimulation of B cells by BCR and TLR9, resulting in an enhanced cell proliferation, plasma blast generation, cytokine and antibody production. Specific inhibitor of TAK1 as well as knocking down TAK1 by siRNA abrogates the synergistic signals. We conclude that TAK1 is a key regulator of receptor crosstalk between BCR and TLR9, thus plays a critical role in B cell development and activation.
Bead Arrays for Antibody and Complement Profiling Reveal Joint Contribution of Antibody Isotypes to C3 Deposition
Burcu Ayoglu, Eszter Szarka, Krisztina Huber, Anita Orosz, Fruzsina Babos, Anna Magyar, Ferenc Hudecz, Bernadette Rojkovich, Tamás Gáti, Gy?rgy Nagy, Jochen M. Schwenk, Gabriella Sármay, József Prechl, Peter Nilsson, Krisztián Papp
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096403
Abstract: The development of antigen arrays has provided researchers with great tools to identify reactivities against self or foreign antigens from body fluids. Yet, these approaches mostly do not address antibody isotypes and their effector functions even though these are key points for a more detailed understanding of disease processes. Here, we present a bead array-based assay for a multiplexed determination of antigen-specific antibody levels in parallel with their properties for complement activation. We measured the deposition of C3 fragments from serum samples to reflect the degree of complement activation via all three complement activation pathways. We utilized the assay on a bead array containing native and citrullinated peptide antigens to investigate the levels of IgG, IgM and IgA autoantibodies along with their complement activating properties in serum samples of 41 rheumatoid arthritis patients and 40 controls. Our analysis revealed significantly higher IgG reactivity against the citrullinated fibrinogen β and filaggrin peptides as well as an IgA reactivity that was exclusive for citrullinated fibrinogen β peptide and C3 deposition in rheumatoid arthritis patients. In addition, we characterized the humoral immune response against the viral EBNA-1 antigen to demonstrate the applicability of this assay beyond autoimmune conditions. We observed that particular buffer compositions were demanded for separate measurement of antibody reactivity and complement activation, as detection of antigen-antibody complexes appeared to be masked due to C3 deposition. We also found that rheumatoid factors of IgM isotype altered C3 deposition and introduced false-positive reactivities against EBNA-1 antigen. In conclusion, the presented bead-based assay setup can be utilized to profile antibody reactivities and immune-complex induced complement activation in a high-throughput manner and could facilitate the understanding and diagnosis of several diseases where complement activation plays role in the pathomechanism.
Suicide, Mental Illness and Maori People  [PDF]
Said Shahtahmasebi, Bernadette Cassidy
Open Journal of Social Sciences (JSS) , 2014, DOI: 10.4236/jss.2014.28014
Abstract: Globally, authorities and “experts” continually assert that suicide is a major public health concern and it is preventable. However, decades of suicide prevention strategies have seen “more of the same” action plans but no change in the upward suicide trend. Therefore, the current suicide prevention model is less relevant to indigenous and minority populations with a high suicide rate. Current suicide statistics for Maori, New Zealand’s indigenous population are unacceptably high. The Maori suicide rate is about 19 per 100,000 roughly averaging about 104 deaths per year over the last six years. Maori claim that before colonisation suicide was non-existent. There is certainly evidence to support such a claim. e.g., historical suicide data suggested that the number of Maori youth suicide deaths was less than five until the 1970s and 1980s. Maori now have the dubious honour of having the highest rates of mortality and morbidity outcomes, including higher rates of suicide. Neither Maori nor the authorities responded with an action plan when suicide numbers spiked in 1960 and 1967. Subsequently, the number of suicides rose sharply to over one hundred where they stayed. It is plausible that exposure to Western ideals as well as social insensitivity to Maori beliefs and needs may have led to a cultural dealignment during the1960s and 1970s. This cultural shift also may be due to the application of a Western model of suicide prevention based on mental illness. The Western model does not work in preventing suicide and conflicts with indigenous cultures.
Nasopharyngeal carcinoma
Bernadette Brennan
Orphanet Journal of Rare Diseases , 2006, DOI: 10.1186/1750-1172-1-23
Abstract: Nasopharyngeal carcinoma (NPC) is a tumor arising from the epithelial cells that cover the surface and line the nasopharynx. NPC was first described as a separate entity by Regaud and Schmincke in 1921 [1,2]. Approximately one third of nasopharyngeal carcinomas of the undifferentiated type are diagnosed in adolescents or young adults. Although rare, NPC accounts for one third of childhood nasopharyngeal neoplasms (data from USA) [3].The annual incidence of NPC in the UK is 0.25 per million (age standardized, age 0–14 years), 0.1 per million at age 0–9 years and 0.8 per million at age 10–14 years. It seems reasonable to assume, on the basis of England and Wales cancer registry data, that at least 80% of nasopharyngeal cancers at age 15–19 years are carcinomas. This suggests an incidence of 1 to 2 per million for NPC at age 15–19 years.In comparison with other countries, the incidence in the UK is low. In particular, in Tunisia the incidence is relatively high [4]. In southern parts of China, Southeast Asia, the Mediterranean basin and Alaska the incidence of NPC is moderately elevated; an incidence of 2 per million of NPC in China has been reported [5]. In other countries, for example in India, the incidence is comparable to that in the UK at 0.9 per million. Furthermore, the younger age peak in the second decade found in India [6], is also found in the UK [7].NPC is the commonest epithelial cancer in adults. The detection of nuclear antigen associated with Epstein-Barr virus (EBNA) and viral DNA in NPC type 2 and 3, has revealed that EBV can infect epithelial cells and is associated with their transformation [8]. The etiology of NPC (particularly the endemic form) seems to follow a multi-step process, in which EBV, ethnic background, and environmental carcinogens all seem to play an important role.Lo et al. showed that EBV DNA was detectable in the plasma samples of 96% of patients with non-keratinizing NPC, compared with only 7% in controls [9]. More importantly, E
Liste des acquisitions de la bibliothèque de Géographie
Bernadette Joseph
EchoGéo , 2008,
Abstract: AfriqueRandriamananoro-Rabesahala Charlotte Liliane, Ambohimanga-Rova : approche anthropologique de la civilisation merina (Madagascar), Paris, Le Publieur, 2006.Duponnois Lacombe, La brousse, le champ et la jachère au Burkina Faso, Paris, L'Harmattan, 2007.Fondja Wandji Yris D., Le Cameroun et la question énergétique : analyse, bilan et perspectives Paris, Budapest, Kinshasa [etc.], L'Harmattan, 2007.Ouedraogo Moussa, La communalisation en milieu rural les élus locaux peuvent-ils relever le ...
Nouvelles Acquisitions de la bibliothèque de Géographie
Bernadette Joseph
EchoGéo , 2008,
Abstract: AfriqueExploitation et gestion durable des forêts en Afrique Centrale : la quête de la durabilité, Paris, L'Harmattan, 2007.FAY, KONé, QUIMINAL, Décentralisation et pouvoirs en Afrique : en contrepoint, modèles territoriaux fran ais, Paris, IRD éditions, 2006.GASCON, Alain, Sur les hautes terres comme au ciel : identités et territoires en éthiopie, Paris, Publications de la Sorbonne, 2006.GOULOU, Jean-Richard Armand, Infrasructuctures de transport et de communication au Congo-Brazzaville, Par...
Kenyan refugees included in transitional justice processes
Bernadette Iyodu
Forced Migration Review , 2011,
Abstract: In the complex relationship between forced migration and transitional justice, a visit by the Kenyan Truth, Justice and Reconciliation Commission to a refugee settlement in Uganda seems to mark a significant step…
The role of culture in mentoring
Bernadette Ludwig
Forced Migration Review , 2012,
Abstract: Mentors from the same cultural background can play an important role in supporting young refugees and their families.
THE SORBS – AN ETHNIC GROUP, WHICH STRUGGLES FOR SURVIVAL
Bernadette Jonda
Studia Humanistyczne (Kraków. 2003) , 2011,
Abstract: The following article deals with the current situation of the Sorbs – a Slavic ethnic group leaving in Lusatia, which is a region belonging to former East Germany. The development of this ethnic group – starting from the end of the 19th Century and considering both Nazi times and former East Germany situation – will be shown. The article discusses on the one hand the attempts to maintain the Sorbian language, among others due to the activities of the Language Centre WITAJ, and on the other hand it stresses the consequences of the brown coal mining in the region of Lusatia. In addition, the attitudeof German natives towards the Sorbs is analysed. On basis of the own research conducted by the author in the year 2010 near the Sorbian town Slepo (ger. Schleife), dilemmas of the local people, who feel dependent on energy concern Vattenfall, are shown. Although the concern guarantees work places, it also jeopardizes the existence of local people’s houses and the cultivation of the Sorbian tradition. The coal mines destroy the natural and social environment. More and more villages are demolished and social networks are being broken by people’s displacements. The current situation makes the Sorbs even more cautious about their own culture and motivates them to fight for their cultural survival.
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