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Zdeněk Adam, Zita Chovancová, Markéta Nová, Pavel Fabian, Zdeněk Řehák, Renata Koukalová, Marek Slávik, Luděk Pour, Marta Krejčí, Aleš Čermák, Zdeněk Král, Jiří Mayer
A disease associated with immunoglobulin IgG4 is a rare unit with very variable symptoms. We describe the course and treatment of the disease in a patient who presented with multiple lymphadenopathy and infiltrates in the area of the retroperitoneum and pelvis and signs of chronic sclerosing pancreatitis. The disease was clinically manifested by a significant loss of weight, but also by a loss of perception of taste and smell. The diagnosis was made based on a high amount of IgG4 expressing plasma cells in the sampled tissue and an increased concentration of immunoglobulins of type IgG and mainly subclass IG4...
2018: Vnitr̆ní Lékar̆ství
Xue-Jie Li, Lei Yang, Dan Li, You-Ting Zhu, Qun Wang, Wei-Wei Li
The Down syndrome cell adhesion molecule (Dscam) gene is an extraordinary example of diversity that can produce thousands of isoforms and has so far been found only in insects and crustaceans. Cumulative evidence indicates that Dscam may contribute to the mechanistic foundations of specific immune responses in insects. However, the mechanism and functions of Dscam in relation to pathogens and immunity remain largely unknown. In this study, we identified the genome organization and alternative Dscam exons from Chinese mitten crab, Eriocheir sinensis ...
2018: Frontiers in Immunology
D M Paton
Atopic dermatitis (AD) is one of the most common skin disorders with a prevalence of about 20% in children and affecting adults in significant numbers. Moderate to severe AD significantly impairs a patient's quality of life with severe pruritus as a major issue that impairs sleep and contributes to major psychological disturbances. Detailed studies of its pathogenesis have revealed that immune mechanisms are involved including activation of T helper type 2 cells (Th2). Dupilumab is a fully human Ig4 monoclonal antibody directed against the interleukin-4 receptor subunit α (IL-4Rα) of IL-4 and IL-13 receptors...
September 2017: Drugs of Today
Galit Yom-Tov, Reut Barak, Omri Matalon, Mira Barda-Saad, Julia Guez-Haddad, Yarden Opatowsky
Robo receptors play pivotal roles in axonal guidance as well as in neurogenesis, angiogenesis, cell migration, and cancer progression and invasiveness. They are considered to be attractive drug targets for the treatment of cancer, ocular neovascular disorders, chronic kidney diseases, and more. Despite their great importance, the mechanisms by which Robo receptors switch from their "off" to "on" states remain obscure. One possibility involves a monomer-to-dimer or dimer-to-monomer transition that facilitates the recruitment and activation of enzymatic effectors to instigate intracellular signaling...
November 24, 2017: Journal of Molecular Biology
Melissa R Briones, Gabrielle A Morgan, Maria C Amoruso, Bahram Rahmani, Maura E Ryan, Lauren M Pachman
The study aimed to document the utility of the absolute number of natural killer cells as a biomarker in paediatric orbital myositis (OM). Extracted data from four children with OM included demographics, laboratory values, imaging and treatment response. Stored sera (-80°C) were tested for IgG4 levels in three cases and antibody to Coxsackie B in two cases. Their first symptom was at 14.4±1.2 years (mean±SD). At diagnosis three had creatine phosphokinase (CPK) of 97.3±44.2, aldolase of 8.5±2.8 (n=2), alanine aminotransferase (ALT) of 13±2...
2017: RMD Open
Yanelys Morera, Javier Sánchez, Mónica Bequet-Romero, Katty-Hind Selman-Housein, Ana de la Torre, Francisco Hernández-Bernal, Yenima Martín, Acralys Garabito, Jesús Piñero, Cimara Bermúdez, Josué de la Torre, Marta Ayala, Jorge V Gavilondo
CIGB-247 is a cancer therapeutic vaccine, based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, in combination with the adjuvant VSSP, a bacterially-derived adjuvant. The vaccine have demonstrated efficacy in several murine malignancy models. These studies supported the rationale for a phase I clinical trial where safety, tolerance, and immunogenicity of CIGB-247 was studied in patients with advanced solid tumors at three antigen dose level. Surviving individuals of this clinical trial were eligible to receive off-trial voluntary re-immunizations...
June 16, 2017: Vaccine
Deqiang Xiao, Yong Li, Huoling Luo, Yanfang Zhang, Xuejun Guo, Huimin Zheng, Qingmao Hu, Fucang Jia
PURPOSE: To compare the accuracy of a Kinect-Optical navigation system with an electromagnetic (EM) navigation system for percutaneous liver needle intervention. MATERIALS AND METHODS: Five beagles with nine artificial tumors were used for validation. The Veran IG4 EM navigation system and a custom-made Kinect-Optical navigation system were used. Needle insertions into each tumor were conducted with these two guidance methods. The target positioning error (TPE) and the time cost of the puncture procedures were evaluated...
February 20, 2017: Abdominal Radiology
Matti F Pronker, Suzanne Lemstra, Joost Snijder, Albert J R Heck, Dominique M E Thies-Weesie, R Jeroen Pasterkamp, Bert J C Janssen
Myelin-associated glycoprotein (MAG) is a myelin-expressed cell-adhesion and bi-directional signalling molecule. MAG maintains the myelin-axon spacing by interacting with specific neuronal glycolipids (gangliosides), inhibits axon regeneration and controls myelin formation. The mechanisms underlying MAG adhesion and signalling are unresolved. We present crystal structures of the MAG full ectodomain, which reveal an extended conformation of five Ig domains and a homodimeric arrangement involving membrane-proximal domains Ig4 and Ig5...
December 6, 2016: Nature Communications
Kerry M Goodman, Masahito Yamagata, Xiangshu Jin, Seetha Mannepalli, Phinikoula S Katsamba, Göran Ahlsén, Alina P Sergeeva, Barry Honig, Joshua R Sanes, Lawrence Shapiro
Sidekick (Sdk) 1 and 2 are related immunoglobulin superfamily cell adhesion proteins required for appropriate synaptic connections between specific subtypes of retinal neurons. Sdks mediate cell-cell adhesion with homophilic specificity that underlies their neuronal targeting function. Here we report crystal structures of Sdk1 and Sdk2 ectodomain regions, revealing similar homodimers mediated by the four N-terminal immunoglobulin domains (Ig1-4), arranged in a horseshoe conformation. These Ig1-4 horseshoes interact in a novel back-to-back orientation in both homodimers through Ig1:Ig2, Ig1:Ig1 and Ig3:Ig4 interactions...
September 19, 2016: ELife
Genevieve L Coe, Priscilla S Redd, Amy V Paschall, Chunwan Lu, Lilly Gu, Houjian Cai, Thomas Albers, Iryna O Lebedyeva, Kebin Liu
FasL-mediated cytotoxicity is one of the mechanisms that CTLs use to kill tumor cells. However, human colon carcinoma often deregulates the Fas signaling pathway to evade host cancer immune surveillance. We aimed at testing the hypothesis that novel ceramide analogs effectively modulate Fas function to sensitize colon carcinoma cells to FasL-induced apoptosis. We used rational design and synthesized twenty ceramide analogs as Fas function modulators. Five ceramide analogs, IG4, IG7, IG14, IG17, and IG19, exhibit low toxicity and potent activity in sensitization of human colon carcinoma cells to FasL-induced apoptosis...
August 4, 2016: Scientific Reports
T Flament, S Marchand-Adam, P Gatault, C Dupin, P Diot, L Guilleminault
INTRODUCTION: IgG4 has recently been a subject of great interest in human pathology. No data are available about the characteristics of asthma patients with elevated IgG4 levels. POPULATION AND METHODS: An observational study was conducted from January 2006 to March 2015 in a difficult-to-treat population of asthma patients. Twenty-six difficult-to-treat asthma patients with elevated serum IgG4 levels (IgG4/IgG ratio up to 10%) were compared with a control population of 98 difficult-to-treat asthma patients with normal serum IgG4...
March 2016: Respiratory Medicine
Kenji Otsuka, Mikako Ito, Bisei Ohkawara, Akio Masuda, Yu Kawakami, Ko Sahashi, Hiroshi Nishida, Naoki Mabuchi, Akemi Takano, Andrew G Engel, Kinji Ohno
MuSK antibody-positive myasthenia gravis (MuSK-MG) accounts for 5 to 15% of autoimmune MG. MuSK and LRP4 are coreceptors for agrin in the signaling pathway that causes clustering of acetylcholine receptor (AChR). MuSK also anchors the acetylcholinesterase (AChE)/collagen Q (ColQ) complex to the synaptic basal lamina. We previously reported that anti-MuSK antibodies (MuSK-IgG) block binding of ColQ to MuSK and cause partial endplate AChE deficiency in mice. We here analyzed the physiological significance of binding of ColQ to MuSK and block of this binding by MuSK-IgG...
2015: Scientific Reports
Takaya Oguchi, Masao Ota, Tetsuya Ito, Hideaki Hamano, Norikazu Arakura, Yoshihiko Katsuyama, Akira Meguro, Shigeyuki Kawa
Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis characterized by high serum IgG4 concentration and a variety of complicating extra-pancreatic lesions. In particular, lachrymal/salivary gland lesions tend to manifest in a highly active AIP disease state, and several genes are speculated to be associated with the onset of this complication. We therefore searched for candidate susceptibility genes related to lachrymal/salivary gland lesions in a genome-wide association study (GWAS) with the GeneChip Human Mapping 500k Array Set (Affymetrix, CA) that was followed by fine mapping of additional single nucleotide polymorphisms (SNPs) in strongly significant genes with TaqMan assays...
2015: PloS One
Andreia Noites, Rita Nunes, Ana Isabel Gouveia, Alexandra Mota, Cristina Melo, Ágata Viera, Nuno Adubeiro, José Mesquita Bastos
OBJECTIVE: To analyze the short- and long-term effects of microcurrent used with aerobic exercise on abdominal fat (visceral and subcutaneous). METHODS: Forty-two female students from a university population were randomly assigned into five group: intervention group (IG) 1 (n=9), IG2 (n=9), IG3 (n=7), IG4 (n=8), and placebo group (PG) (n=9). An intervention program of 10 sessions encompassing microcurrent and aerobic exercise (performed with a cycloergometer) was applied in all groups, with slightly differences between them...
April 2015: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
M Braig, N Pällmann, M Preukschas, D Steinemann, W Hofmann, A Gompf, T Streichert, T Braunschweig, M Copland, K L Rudolph, C Bokemeyer, S Koschmieder, A Schuppert, S Balabanov, T H Brümmendorf
Telomere biology is frequently associated with disease evolution in human cancer and dysfunctional telomeres have been demonstrated to contribute to genetic instability. In BCR-ABL(+) chronic myeloid leukemia (CML), accelerated telomere shortening has been shown to correlate with leukemia progression, risk score and response to treatment. Here, we demonstrate that proliferation of murine CML-like bone marrow cells strongly depends on telomere maintenance. CML-like cells of telomerase knockout mice with critically short telomeres (CML-iG4) are growth retarded and proliferation is terminally stalled by a robust senescent cell cycle arrest...
October 2014: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Robert Tweyongyere, Peter Naniima, Patrice A Mawa, Frances M Jones, Emily L Webb, Stephen Cose, David W Dunne, Alison M Elliott
INTRODUCTION: Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S...
2013: PLoS Neglected Tropical Diseases
T Watanabe, M Maruyama, T Ito, Y Fujinaga, Y Ozaki, M Maruyama, R Kodama, T Muraki, H Hamano, N Arakura, M Kadoya, S Suzuki, M Komatsu, H Shimojo, K Notohara, M Uchida, S Kawa
OBJECTIVES: Immunoglobulin (Ig)G4-related disease is a recently proposed systemic disorder that includes autoimmune pancreatitis (AIP), Mikulicz's disease, and various other organ lesions. In the present retrospective study, we examined whether thyroid lesions should also be included in IgG4-related disease (Ig4-RD) under the new term IgG4-related thyroiditis. METHOD: We enrolled 114 patients with Ig4-RD, including 92 patients with AIP, 15 patients with Mikulicz's disease, and seven patients with IgG4-related cholangitis, and analysed clinical findings, function, serum values of activity markers, computed tomography (CT) images, and histology of the thyroid gland...
2013: Scandinavian Journal of Rheumatology
Jean Mukherjee, Chase McCann, Kwasi Ofori, Julia Hill, Karen Baldwin, Charles B Shoemaker, Peter Harrison, Saul Tzipori
Botulinum neurotoxin (BoNT) is responsible for causing botulism, a potentially fatal disease characterized by paralysis of skeletal muscle. Existing specific treatments include polyclonal antisera derived from immunized humans or horses. Both preparations have similar drawbacks, including limited supply, risk of adverse effects and batch to batch variation. Here, we describe a panel of six highly protective sheep monoclonal antibodies (SMAbs) derived from sheep immunized with BoNT/A1 toxoid (SMAbs 2G11, 4F7) or BoNT/A1 heavy chain C-terminus (HcC) (SMAbs 1G4, 5E2, 5F7, 16F9) with or without subsequent challenge immunization with BoNT/A1 toxin...
December 2012: Toxins
Rania Ahmed, Safa Al-Shaikh, Mohammed Akhtar
More than a century has passed since the first description of Hashimoto thyroiditis (HT) as a clinicopathologic entity. HT is an autoimmune disease in which a breakdown of immune tolerance is caused by interplay of a variety of immunologic, genetic, and environmental factors. Thyrocyte injury resulting from environmental factors results in expression of new or hidden epitopes that leads to proliferation of autoreactive T and B cells. Infiltration of thyroid by these cells results in HT. In addition to the usual type of HT, several variants such as the fibrous type and Riedal thyroiditis are also recognized...
May 2012: Advances in Anatomic Pathology
M D Lopez, A Maudhuit, M J Pascual-Villalobos, D Poncelet
In recent studies, insecticide activity of a monoterpene, linalool, has been demonstrated, finding, however, limitations in application because of its rapid volatilization. Potential effectiveness of microcapsules and effects of various types of matrices on its stability as controlled-release systems for the slow volatilization of linalool to be applied as insecticide were evaluated. To study controlled-release, linalool was entrapped into microcapsules, inclusion complexes, and beads, obtained by different methods, inverse gelation (IG1, IG2, IG3, IG4, and IG5), oil-emulsion-entrapment (OEE), interfacial coacervation (INCO), and chemical precipitation (Cyc5 and Cyc10)...
February 8, 2012: Journal of Agricultural and Food Chemistry
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