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tissue cross reactivity

Margaret-Ann M Nelson, Zachariah J Builta, T Blake Monroe, Jonathan A Doorn, Ethan J Anderson
Oxidative deamination of norepinephrine (NE) and dopamine (DA) by monoamine oxidase (MAO) generates the catecholaldehydes 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL) and 3,4-dihydroxyphenylacetaldehyde (DOPAL), respectively, and H2 O2 . Catecholaldehydes are highly reactive electrophiles that have been implicated as causal factors in the etiology of neurodegenerative diseases and cardiac injury from ischemia and diabetes. The reactivity of both catechol and aldehyde groups enables the catecholaldehdyes to cross-link proteins and other biological molecules...
September 6, 2018: Amino Acids
Rakesh Sit, Zrinka Kovarik, Nikolina Macek-Hrvat, Suzana Zunec, Carol Green, Valery Fokin, K Barry Sharpless, Zoran Radic', Palmer Taylor
In the development of antidotal therapy for treatment of organophosphate exposure from pesticides used in agriculture and nerve agents used insidiously in terrorism, the methylpyridinium aldoximes have received primary attention, since their development by I.B. Wilson in the 1950's. Yet, these agents, by virtue of their quaternary structures, are limited in crossing the blood-brain barrier and require administration parenterally to achieve full distribution in the body. Oximes lacking cationic charges or presenting a tertiary amine have been considered as alternatives...
September 6, 2018: Journal of Pharmacology and Experimental Therapeutics
Milla Pietiäinen, John M Liljestrand, Elisa Kopra, Pirkko J Pussinen
Clinical periodontitis is associated with an increased risk for cardiovascular diseases (CVDs) through systemic inflammation as the etiopathogenic link. Whether the oral microbiota, especially its quality, quantity, serology, and virulence factors, plays a role in atherogenesis is not clarified. Patients with periodontitis are exposed to bacteria and their products, which have access to the circulation directly through inflamed oral tissues and indirectly (via saliva) through the gastrointestinal tract, resulting in systemic inflammatory and immunologic responses...
October 2018: European Journal of Oral Sciences
Ratchaneewan Khiaosa-Ard, Qendrim Zebeli
Dietary shifts play an important role in decreased longevity in ruminant livestock. Ruminants evolved as cellulose fermenters adapt to fiber-rich diets. Instead, high-producing ruminants nowadays are commonly fed with grain-based diets to increase intake and productivity. Such diets, however, trade off the health of the animal. One negative aspect of such feeding is related to elevated levels of bacterial endotoxin (lipopolysaccharide, LPS) in the gut lumen and the likelihood of LPS translocation across the gut causing systemic and local (tissue) inflammation with consequences for production and longevity...
August 24, 2018: Research in Veterinary Science
John L Vahle
This article summarizes a continuing education presentation on immunogenicity that was part of a continuing education course entitled, "Clinical Pathology of Biotherapeutics." Immunogenicity of a biotherapeutic can have diverse impacts including altered systemic exposure and pharmacologic responses and, in a fraction of the cases, safety concerns including cross-reactive neutralization of endogenous proteins or sequela related to immune complex disease (ICD). In most cases, immune complexes are readily cleared from circulation; however, based on physiochemical properties, insoluble complexes form, activate complement, and deposit in tissues...
August 29, 2018: Toxicologic Pathology
Milind Machhindra Patil, Sreejith Parameswaran, Sadishkumar Kamalanathan, Jaya Prakash Sahoo, Karthik Balachandran, Sitanshu Sekhar Kar
Both chronic kidney disease (CKD) and hypothyroidism are associated with decreased serum irisin level. The presence of hypothyroidism may influence serum irisin level in CKD patients. The objective of this study was to evaluate the effect of hypothyroidism on serum irisin level in patients with nondiabetic CKD. Two hundred nondiabetic CKD patients aged between 18 and 65 years with glomerular filtration rate <60 mL/min/1.73 m2 were included in this study. Forty-three (21.5%) patients had hypothyroidism (overt and subclinical both)...
July 2018: Saudi Journal of Kidney Diseases and Transplantation
Liliana R Loureiro, Diana P Sousa, Dylan Ferreira, Wengang Chai, Luís Lima, Carina Pereira, Carla B Lopes, Viviana G Correia, Lisete M Silva, Chunxia Li, Lúcio Lara Santos, José Alexandre Ferreira, Ana Barbas, Angelina S Palma, Carlos Novo, Paula A Videira
Incomplete O-glycosylation is a feature associated with malignancy resulting in the expression of truncated glycans such as the sialyl-Tn (STn) antigen. Despite all the progress in the development of potential anti-cancer antibodies, their application is frequently hindered by low specificities and cross-reactivity. In this study, a novel anti-STn monoclonal antibody named L2A5 was developed by hybridoma technology. Flow cytometry analysis showed that L2A5 specifically binds to sialylated structures on the cell surface of STn-expressing breast and bladder cancer cell lines...
August 15, 2018: Scientific Reports
Taizo Mori, Nao Suzuki-Yamazaki, Satoshi Takaki
Lnk/Sh2b3 is an adaptor protein that negatively regulates cytokine signaling in lymphohematopoiesis. A missense variant within the LNK/SH2B3 gene has been reported to be a risk variant for several autoimmune diseases, including diabetes. We found that glucose tolerance and insulin responses were impaired in Lnk-/- mice. Moreover, immune cells such as group 1 innate lymphoid cells (G1-ILCs), CD8+ T cells, and M1 macrophages accumulated in adipose tissue. When Lnk-/- mice were crossed with Il15-/- mice or depleted of G1-ILCs but not CD8+ T cells, glucose intolerance and adipose inflammation were ameliorated...
August 14, 2018: Cell Reports
Yumi Matsushita, Naoki Kitamura, Masashi Higuchi, Yoshinao Z Hosaka, Izumi Shibuya
Ten pairs of protrusions, called accessory lobes (ALs), exist at the lateral sides of the avian lumbosacral spinal cord. Histological evidence indicates that neuron-like cells gather in the ALs, and behavioral evidence suggests that the ALs act as a sensory organ of equilibrium during bipedal walking. Recently, using an electrophysiological method, we reported that cells showing Na+ currents and action potentials exist among cells that were dissociated from the ALs. However, it was unclear which isoforms of the voltage-gated sodium channel (VGSC) are expressed in the ALs and whether cells having neuronal morphology in the ALs express VGSCs...
2018: Biomedical Research
Hongdou Luo, Jiejie Zhuang, Piaopiao Hu, Wei Ye, Shanshan Chen, Yulian Pang, Ningfeng Li, Cong Deng, Xu Zhang
Purpose: Resveratrol has been shown to enhance the survival of retinal ganglion cells (RGCs) following ischemia-reperfusion (I/R) injury for glaucoma. However, the precise mechanisms for resveratrol's protective effects are still unclear. The aim of this study is to determine whether resveratrol can inhibit RGC apoptosis, retinal gliosis, and inflammation, all of which are critical events in retinal degeneration following I/R injury. Methods: Right retinal ischemia was induced in adult male Sprague Dawley rats by increasing intraocular pressure to 110 mm Hg for 60 minutes, and the left eyes maintained at normal pressure serve as the control...
August 1, 2018: Investigative Ophthalmology & Visual Science
Jowita Samanta Niczyporuk, Hanna Czekaj
Fowl adenoviruses (FAdVs) are the causative agents of multietiological syndromes and diseases in poultry flocks. During a routine diagnostic examination, two FAdVs strains were isolated. Molecular typing of these isolates based on the partial loop L1 HVR1-4 region of the hexon gene sequence revealed the presence of different FAdV isolates: 1/A-61/11z (GenBank accession number KX247012, APP94082), and 8a/E-6/12j (GenBank accession number: KP890032, ALB00550), and comparative genome analysis indicated small differences between these two viruses...
July 31, 2018: Archives of Virology
David A Eavarone, Linah Al-Alem, Alexey Lugovskoy, Jillian M Prendergast, Rawan I Nazer, Jenna N Stein, Daniel T Dransfield, Jeff Behrens, Bo R Rueda
The expression of Sialyl-Tn (STn) in tumors is associated with metastatic disease, poor prognosis, and reduced overall survival. STn is expressed on ovarian cancer biomarkers including CA-125 (MUC16) and MUC1, and elevated serum levels of STn in ovarian cancer patients correlate with lower five-year survival rates. In the current study, we humanized novel anti-STn antibodies and demonstrated the retention of nanomolar (nM) target affinity while maintaining STn antigen selectivity. STn antibodies conjugated to Monomethyl Auristatin E (MMAE-ADCs) demonstrated in vitro cytotoxicity specific to STn-expressing ovarian cancer cell lines and tumor growth inhibition in vivo with both ovarian cancer cell line- and patient-derived xenograft models...
2018: PloS One
M Bobinac, T Ćelić, I Vukelić, J Španjol, N Rubinić, D Bobinac
Spinal cord ischemia-reperfusion injury (IRI) results in overproduction of reactive oxygen species leading to tissue oxidative stress which impacts the neuronal network in the spinal cord as well as glial cells. We investigated the expression of Nuclear factor erythroid 2-related factor 2 (Nrf2) in neurons and glial cells after occlusion of the abdominal aorta followed by IRI as well as the time-dependent expression of Nrf2 in the same cells. The experimental method of transient aortic occlusion was carried out on rats by cross-clamping of the abdominal aorta for 45 minutes...
July 2018: Journal of Biological Regulators and Homeostatic Agents
Do Thi Hoang Kim, Duong Tuan Bao, Hyun Park, Nguyen Minh Ngoc, Seon-Ju Yeo
Zika virus (ZIKV) has been identified as a cause of adverse outcomes of pregnancy, including microcephaly and other congenital diseases. Most people infected with ZIKV do not show any symptoms. Development of a method to discriminate dengue virus (DENV) and ZIKV infections has been challenging, and efficient assays for patient management are limited, attributable to high levels of cross-reactivity among co-circulating Flaviviruses . Thus, there is an urgent need for a specific high-throughput diagnostic assay to discriminate ZIKV infections from other Flavivirus infections...
2018: Theranostics
Anke Schlüter, Anja K Eckstein, Alexandra Brenzel, Mareike Horstmann, Stephan Lang, Utta Berchner-Pfannschmidt, J Paul Banga, Salvador Diaz-Cano
Objectives: Experimental models of Graves hyperthyroid disease accompanied by Graves orbitopathy (GO) can be efficiently induced in susceptible inbred strains of mice by immunization by electroporation of heterologous human TSH receptor (TSHR) A-subunit plasmid. The interrelated pathological findings in the thyroid glands of Graves disease (GD) that explain the core changes classically include diffuse follicular hyperplasia and multifocal mild lymphocytic infiltrate. However, the relative contributions of different thyroid tissue components (colloid, follicular cells, and stroma) have not been previously evaluated...
June 2018: European Thyroid Journal
Chun-Heng Kuo, Jung-Nan Wei, Chung-Yi Yang, Horng-Yih Ou, Hung-Tsung Wu, Kang-Chih Fan, Shu-Huei Wang, Cyue-Huei Hua, Ching-Hsiang Hsiao, Mei-Kuei Lee, Hung-Yuan Li
BACKGROUND/OBJECTIVES: Vascular adhesion protein-1 (VAP-1) can enhance tissue glucose uptake in cell studies and normalize hyperglycemia in animal studies. However, serum VAP-1 concentration (sVAP-1) is higher in subjects with diabetes in cross-sectional studies. In this cohort study, we test our hypothesis that sVAP-1 is increased in prediabetes to counteract hyperglycemia and is associated with incident diabetes negatively. SUBJECTS/METHODS: From 2006 to 2012, 600 subjects without diabetes from Taiwan Lifestyle Study were included and followed regularly...
July 18, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Cristina Anna Gallelli, Silvio Calcagnini, Adele Romano, Justyna Barbara Koczwara, Marialuisa de Ceglia, Donatella Dante, Rosanna Villani, Anna Maria Giudetti, Tommaso Cassano, Silvana Gaetani
Growing evidence supports the pivotal role played by oxidative stress in tissue injury development, thus resulting in several pathologies including cardiovascular, renal, neuropsychiatric, and neurodegenerative disorders, all characterized by an altered oxidative status. Reactive oxygen and nitrogen species and lipid peroxidation-derived reactive aldehydes including acrolein, malondialdehyde, and 4-hydroxy-2-nonenal, among others, are the main responsible for cellular and tissue damages occurring in redox-dependent processes...
July 18, 2018: Antioxidants (Basel, Switzerland)
Xinyan Bi, Yi Ting Loo, Shalini Ponnalagu, Christiani Jeyakumar Henry
BACKGROUND AND AIMS: High-sensitivity C-reactive protein (hs CRP) has emerged as an inflammatory biomarker to predict metabolic syndrome. Here, we investigate the association of hs CRP with metabolic variables and determine the risks for elevated hs CRP levels in healthy Singaporean adults. METHODS: We conducted a cross-sectional study of 225 participants (104 men). The levels of hs CRP and fasting lipid parameters were analyzed by COBAS. Body composition was determined with dual-energy X-ray absorptiometry...
August 23, 2018: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
Melania Spadaro, Stephan Winklmeier, Eduardo Beltrán, Caterina Macrini, Romana Höftberger, Elisabeth Schuh, Franziska S Thaler, Lisa-Ann Gerdes, Sarah Laurent, Ramona Gerhards, Simone Brändle, Klaus Dornmair, Constanze Breithaupt, Markus Krumbholz, Markus Moser, Gurumoorthy Kirshnamoorthy, Frits Kamp, Dieter Jenne, Reinhard Hohlfeld, Tania Kümpfel, Hans Lassmann, Naoto Kawakami, Edgar Meinl
OBJECTIVE: Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) occur in a proportion of patients with inflammatory demyelinating diseases of the CNS. We analyzed their pathogenic activity by affinity-purifying these Abs from patients and transferring them to experimental animals. METHODS: Patients with Abs to MOG were identified by cell-based assay. We determined the cross-reactivity to rodent MOG and determined the recognized MOG-epitopes. We produced the correctly folded extracellular domain of MOG and affinity-purified MOG-specific Abs from the blood of patients...
July 16, 2018: Annals of Neurology
Ahreum Lee, Yong C Kim, Keumjin Baek, Jehan Alam, Yun S Choi, Yaeeun Rheu, Yoo Jin Shin, Sungtae Kim, Hyun-Duck Kim, Yeong W Song, Youngnim Choi
Autoantibodies against alpha-enolase (ENO1) are often detected in various infectious and autoimmune diseases. Anti-ENO1 antibody titers were reported to be associated with the severity of periodontitis in patients with rheumatoid arthritis. Because the enolase of the periodontal pathogen Treponema denticola (TdEno) has the highest homology with ENO1 among the enolases of human-associated bacteria, we hypothesized that anti-ENO1 autoantibodies produced during the immune response to TdEno may contribute to the progression of periodontitis and tested it in human and mouse systems...
2018: Virulence
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