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Jörg Fischer, Bernadette Eberlein, Christiane Hilger, Florian Eyer, Stephanie Eyerich, Markus Ollert, Tilo Biedermann
BACKGROUND: Antivenoms are mammalian immunoglobulins with the ability to neutralize snake venom components and to mitigate the progression of toxic effects. Immediate hypersensitivity to antivenoms often occurs during the first administration of these heterologous antibodies. A comparable clinical situation occurred after introduction of cetuximab, a chimeric mouse-human antibody, for cancer treatment. The carbohydrate epitope galactose-alpha-1,3-galactose, located on the Fab region of cetuximab, was identified as the target responsible for IgE reactivity...
October 24, 2016: Allergy
K V Firsov, A S Kotov
Fabry disease (Anderson-Fabry disease) is an X-linked recessive lysosomal storage disorder resulting from deficient activity of lysosomal hydrolase, alpha-galactosidase A (alpha-Gal A), which leads to progressive accumulation of globotriaosylceramide (Gb3) in various cells, predominantly endothelial and vascular smooth muscle cells, with clinical manifestations affecting major organs including the central nervous system. Manifestations of Fabry disease include progressive renal and cardiac insufficiency, neuropathic pain, stroke and cerebral disease, skin and gastrointestinal symptoms...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Scott P Commins
The syndrome of delayed allergic reactions to the carbohydrate galactose-alpha-1,3-galactose ("alpha-gal") has become increasingly recognized in allergy and immunology clinics regionally throughout the southeastern USA. Due to the increasing awareness of this unique food allergy, cases have been identified in the northeastern and central USA as well as in Central and South America, Europe, Asia, Scandinavia, and Australia. Clinically, alpha-gal allergy is characterized by reactions to non-primate mammalian meat (e...
September 2016: Current Allergy and Asthma Reports
Bishu Ganguly, Balaji Balasa, Lyubov Efros, Paul R Hinton, Stephen Hartman, Archana Thakur, Joanna M Xiong, Brian Schmidt, Randy R Robinson, Thierry Sornasse, Vladimir Vexler, James P Sheridan
The CD25-binding antibody daclizumab high-yield process (DAC HYP) is an interleukin (IL)-2 signal modulating antibody that shares primary amino acid sequence and CD25 binding affinity with Zenapax®, a distinct form of daclizumab, which was approved for the prevention of acute organ rejection in patients receiving renal transplants as part of an immunosuppressive regimen that includes cyclosporine and corticosteroids. Comparison of the physicochemical properties of the two antibody forms revealed the glycosylation profile of DAC HYP differs from Zenapax in both glycan distribution and the types of oligosaccharides, most notably high-mannose, galactosylated and galactose-alpha-1,3-galactose (alpha-Gal) oligosaccharides, resulting in a DAC HYP antibody material that is structurally distinct from Zenapax...
July 1, 2016: MAbs
E P Smorodin, B L Sergeyev
BACKGROUND: The serum levels of IgG antibodies reactive to glycoconjugates (TF, Tn and αGal) were found to be associated with prognosis of gastrointestinal cancer patients. AIM: To study the relation between the levels of serum antibodies to TF-pAA, Tn-PAA and αGal-PAA polyacrylamide-based glycoconjugates and survival in breast cancer. MATERIALS AND METHODS: The preoperative level of IgG antibodies was analysed in the serum of patients (n = 59) using ELISA with polyacrylamide-glycoconjugates namely, TF-pAA (amide-type), and ethanolamide-conjugates Tn-PAA and αGal-PAA...
June 2016: Experimental Oncology
Joseph Platz, Nicholas R Bonenfant, Franziska E Uhl, Amy L Coffey, Tristan McKnight, Charles Parsons, Dino Sokocevic, Zachary D Borg, Ying-Wai Lam, Bin Deng, Julia G Fields, Michael DeSarno, Roberto Loi, Andrew M Hoffman, John Bianchi, Brian Dacken, Thomas Petersen, Darcy E Wagner, Daniel J Weiss
BACKGROUND: A novel potential approach for lung transplantation could be to utilize xenogeneic decellularized pig lung scaffolds that are recellularized with human lung cells. However, pig tissues express several immunogenic proteins, notably galactosylated cell surface glycoproteins resulting from alpha 1,3 galactosyltransferase (α-gal) activity, that could conceivably prevent effective use. Use of lungs from α-gal knock out (α-gal KO) pigs presents a potential alternative and thus comparative de- and recellularization of wild-type and α-gal KO pig lungs was assessed...
August 2016: Tissue Engineering. Part C, Methods
Thomas A E Platts-Mills, Alexander J Schuyler, Elizabeth A Erwin, Scott P Commins, Judith A Woodfolk
Traditionally, the concept of allergy implied an abnormal response to an otherwise benign agent (eg, pollen or food), with an easily identifiable relationship between exposure and disease. However, there are syndromes in which the relationship between exposure to the relevant allergen and the "allergic" disease is not clear. In these cases the presence of specific IgE antibodies can play an important role in identifying the relevant allergen and provide a guide to therapy. Good examples include chronic asthma and exposure to perennial indoor allergens and asthma related to fungal infection...
June 2016: Journal of Allergy and Clinical Immunology
Robert B Hawkins, Helena L Frischtak, Irving L Kron, Ravi K Ghanta
We present the cases of two patients with bioprosthetic aortic valves who developed an allergy to alpha-gal. Each had premature degeneration of their bioprosthesis and demonstrated rapidly increasing transvalvular gradients after development of their allergy. Each underwent successful replacement with a mechanical aortic valve within 1-2 years of symptom onset. doi: 10.1111/jocs.12764 (J Card Surg 2016;31:446-448).
July 2016: Journal of Cardiac Surgery
J M García-Menaya, C Cordobés-Durán, J Gómez-Ulla, M A Zambonino, A C Mahecha, G M Chiarella, N Giangrande, P Bobadilla-González
No abstract text is available yet for this article.
2016: Journal of Investigational Allergology & Clinical Immunology
P Ulsemer, K Toutounian, G Kressel, C Goletz, J Schmidt, U Karsten, A Hahn, S Goletz
It is now generally accepted that the human body exists in close synergy with the gut microbiome and that this cross-talk plays an essential role in human health and disease. One facet from the many interactions between the microbiome and the immune system is the induction of natural antibodies to commensal bacterial glycans, such as blood group antigens, the alpha-Gal epitope or the Thomsen-Friedenreich (TFα) antigen. Since we have observed that certain species of the commensal genus Bacteroides express the TFα antigen, we examined whether the oral dietary supplementation of a pasteurised Bacteroides xylanisolvens strain might be able to enhance the level of natural anti-TFα antibodies in healthy adults...
September 2016: Beneficial Microbes
Onyinye I Iweala, A Wesley Burks
Food allergy is defined as an IgE-mediated hypersensitivity response to ingested food with allergic symptoms ranging from urticaria to life-threatening anaphylaxis. Food allergy is thought to develop because of (1) failed induction of tolerance upon initial exposure to food antigen or (2) breakdown of established tolerance to food antigen. We review current understanding of the pathogenesis, epidemiology, and natural history of food allergy, including the unconventional IgE-mediated food allergy to mammalian meat known as alpha-gal food allergy...
May 2016: Current Allergy and Asthma Reports
Saddam M Muthana, Jeffrey C Gildersleeve
Serum anti-glycan antibodies play important roles in many immune processes and are of particular interest as biomarkers for many diseases. Changes in anti-glycan antibodies can occur with the onset of disease or in response to stimuli such as pathogens and vaccination. Understanding relationships between anti-glycan antibody repertoires and genetic and environment factors is critical for basic research and clinical applications, but little information is available. In this study we evaluated the effects of age, race, gender, and blood type on anti-glycan antibody profiles in the serum of 135 healthy subjects...
2016: Scientific Reports
Jörg Fischer, Tilo Biedermann
The development of component-resolved diagnostics instead of whole extracts has brought about major advances in recent years. Particularly remarkable has been the identification of new disease entities based on the detection of IgE antibodies against specific individual components. In this context, delayed immediate-type hypersensitivity to red meat and innards plays a key role. This disorder is more common in German-speaking countries and likely still underdiagnosed. Affected individuals exhibit delayed type I reactions following the consumption of red meat or innards (responses to the latter are more rapid)...
January 2016: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
Kendall D Wagner, Matthew C Bell, Robert D Pesek, Joshua L Kennedy
Anaphylaxis and urticaria are commonly seen in both primary care and allergy clinics. Foods, drugs, and insects are frequent culprits for immediate reactions; however, the trigger for recurring and/or chronic episodes is often unclear. We present a 56-year-old male with recurrent symptoms of urticaria, angioedema, and anaphylaxis found to be triggered by sensitization to galactose-alpha 1, 3-galactose (alpha-gal), a novel food allergen.
November 2015: Journal of the Arkansas Medical Society
Christos Paliouras, Georgios Aperis, Foteini Lamprianou, Giorgos Ntetskas, Konstantinos Roufas, Polichronis Alivanis
Fabry disease is a rare X-linked lysosomal storage disorder of glycosphingolipids, caused by the partial or complete deficiency of the lysosomal enzyme alpha-galactosidase A (a-Gal A). The missense mutation pN215S usually causes a milder form of the disease with isolated cardiac involvement. We report a case of a male Fabry patient with the pN215S mutation and a generalized disease. He suffered a relapse in proteinuria which responded to increased doses of the administered recombinant enzyme. Individualization of enzyme replacement therapy must be considered in selected cases characterized by clinical deterioration...
November 2015: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
Anna Kulinich, Si Liu, Hong-Yu Ma, Yong-Mei Lv, Li Liu, Josef Voglmeir
Two putative α-D-galactosidases (α-GALs) belonging to glycosyl hydrolase family 27, and originating from the rather unexplored bacterial strain Pedobacter heparinus, were cloned and biochemically characterized. The recombinant enzymes designated as PhAGal729 and PhAGal2920 showed comparable biochemical properties: the optimum pH values were determined to be pH 5.0 and 5.5, and temperature optima lay between 30°C and 37°C, respectively. Both α-GALs were not dependent on the presence of divalent metal ions, and the addition of EDTA had no influence on enzymatic activity...
2015: Protein and Peptide Letters
Mari Suzuki, Nobuhiro Fujikake, Toshihide Takeuchi, Ayako Kohyama-Koganeya, Kazuki Nakajima, Yoshio Hirabayashi, Keiji Wada, Yoshitaka Nagai
Alpha-synuclein (αSyn) plays a central role in the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recent multicenter genetic studies have revealed that mutations in the glucocerebrosidase 1 (GBA1) gene, which are responsible for Gaucher's disease, are strong risk factors for PD and DLB. However, the mechanistic link between the functional loss of glucocerebrosidase (GCase) and the toxicity of αSyn in vivo is not fully understood. In this study, we employed Drosophila models to examine the effect of GCase deficiency on the neurotoxicity of αSyn and its molecular mechanism...
December 1, 2015: Human Molecular Genetics
A M Calamari, M Poppa, D Villalta, V Pravettoni
We report the case of a 55-year-old man who went into anaphylactic shock six hours after eating a meal containing meat. He reported having had several tick bites in months before the reaction. The serum specific IgE showed strong positivity to alpha-gal. This is clearly alpha-gal anaphylaxis with delayed onset after meat ingestion caused by tick bite, confirmed by alpha-gal IgE positivity.
September 2015: European Annals of Allergy and Clinical Immunology
Yeo Jin Jeon, Namhee Jung, Joo-Won Park, Hae-Young Park, Sung-Chul Jung
Fabry disease is a lysosomal storage disorder caused by deficiency of alpha-galactosidase A (α-gal A), which results in the deposition of globotriaosylceramide (Gb3) in the vascular endothelium. Globotriaosylsphingosine (lyso-Gb3), a deacylated Gb3, is also increased in the plasma of patients with Fabry disease. Renal fibrosis is a key feature of advanced Fabry disease patients. Therefore, we evaluated the association of Gb3 and lyso-Gb3 accumulation and the epithelial-mesenchymal transition (EMT) on tubular epithelial cells of the kidney...
2015: PloS One
Daniel Patschan, Katrin Schwarze, Elvira Henze, Susann Patschan, Gerhard Anton Müller
BACKGROUND: Autophagy enables cells to digest endogenous/exogenous waste products, thus potentially prolonging the cellular lifespan. Early endothelial progenitor cells (eEPCs) protect mice from ischemic acute kidney injury (AKI). The mid-term prognosis in AKI critically depends on vascular rarefication and interstitial fibrosis with the latter partly being induced by mesenchymal transdifferentiation of endothelial cells (EndoMT). This study aimed to determine the impact of eEPC preconditioning with different autophagy inducing agents [suberoylanilide hydroxamic acid (SAHA)/temsirolimus] in ischemic AKI...
October 2016: Journal of Nephrology
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