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https://www.readbyqxmd.com/read/28548079/design-of-live-attenuated-bacterial-vaccines-based-on-d-glutamate-auxotrophy
#1
Maria P Cabral, Patricia García, Alejandro Beceiro, Carlos Rumbo, Astrid Pérez, Miriam Moscoso, Germán Bou
Vaccine development is a priority for global health due to the growing multidrug resistance in bacteria. D-glutamate synthesis is essential for bacterial cell wall formation. Here we present a strategy for generating effective bacterial whole-cell vaccines auxotrophic for D-glutamate. We apply this strategy to generate D-glutamate auxotrophic vaccines for three major pathogens, Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus. These bacterial vaccines show virulence attenuation and self-limited growth in mice, and elicit functional and cross-reactive antibodies, and cellular immunity...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28547661/targeting-sclerostin-in-postmenopausal-osteoporosis-focus-on-romosozumab-and-blosozumab
#2
Ian R Reid
Most current treatments for osteoporosis inhibit bone resorption and reduce total fracture numbers by about one-quarter. The identification of the osteocytic protein sclerostin as a potent regulator of bone turnover and bone density has led to the development of a new therapeutic class-agents that inhibit sclerostin activity, resulting in increased bone formation and reduced bone resorption. Romosozumab and blosozumab are monoclonal antibodies that bind to sclerostin, reducing its inhibition of Wnt signaling...
May 25, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28546233/a-case-of-confusion-paraneoplastic-encephalomyelitis-in-an-elderly-patient-suspected-of-having-urinary-tract-infection-associated-delirium
#3
Chris McKinnon, Simmie Manchanda
Acute confusion is a common symptom of physical illness in the older patient. In the majority, it is transient and resolves on treatment of precipitants. In a subset of patients, however, neurological decline is progressive, raising concern about a serious underlying cause. We describe the case of a 71-year-old woman who developed progressive cognitive impairment following insertion of a permanent pacemaker for sinoatrial arrests. An initial diagnosis of delirium secondary to a urinary tract infection was suspected; however, the patient became increasingly confused despite treatment...
May 24, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28545782/autoimmune-encephalopathy-for-psychiatrists-when-to-suspect-autoimmunity-and-what-to-do-next
#4
REVIEW
Mark Oldham
OBJECTIVE: To provide a critical review of autoimmune encephalopathy-broadly defined as neuropsychiatric features directly related to an autoimmune process-relevant for psychiatric practice. METHODS: We consulted rheumatology textbooks to define the scope of autoimmune conditions and identified recent reviews of rheumatic conditions, autoimmune vasculitis, and autoimmune encephalitis. We integrated these with primary reports to provide a clinically relevant overview of autoimmune encephalopathy...
May 2017: Psychosomatics
https://www.readbyqxmd.com/read/28543513/lc-ms-ms-isomeric-profiling-of-permethylated-n-glycans-derived-from-serum-haptoglobin-of-hepatocellular-carcinoma-hcc-and-cirrhotic-patients
#5
Yifan Huang, Shiyue Zhou, Jianhui Zhu, David M Lubman, Yehia Mechref
Early stage detection and cancer treatment demand the identification of reliable biomarkers. Over the past decades, efforts have been devoted to assess the variation of glycosylation level as well as the glycan structures of proteins in blood or serum, associated with the development and/or progression of several cancers, including liver. Herein, an LC-MS/MS-based analysis was conducted to define the glycosylation patterns of haptoglobin glycoprotein derived from sera collected from cirrhotic and hepatocellular carcinoma (HCC) patients...
May 25, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28540910/rituximab-induced-urticarial-dermatitis-during-the-treatment-of-membranous-nephropathy
#6
Radhika Chemmangattu Radhakrishnan, Gopal Basu, Renu E George, Harshad Parmar, Veerasami Tamilarasi
Rituximab is a monoclonal antibody directed against B cells and is being increasingly used for various renal indications. Acute dermatologic manifestations such as urticaria are well known to occur during rituximab infusion. Here, we report the case of a 53- year-old female who was treated with rituximab for membranous nephropathy and developed an exanthematous rash, which progressed with a further dose of rituximab and was diagnosed as urticarial dermatitis. A review of literature showed that urticarial dermatitis following rituximab therapy has been seldom reported and identification of this complication is very important to avoid giving further doses and thus, increasing the severity of lesions...
May 2017: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/28540859/case-report-serological-testing-interference-of-daratumumab-anti-cd38-therapy-in-multiple-myeloma
#7
Élodie Rabut, Annabelle Castro-Fernandez, Virginie Le Gall, Nihad Meknache
We report the case of a 54 years old patient monitored for a monoclonal IgG kappa light chain refractory relapsed multiple myeloma and receiving daratumumab immunotherapy. Daratumumab (DARA), a monoclonal anti-CD38 antibody, belongs to the new generation of immunotherapy in refractory relapse multiple myeloma which the medical pathologist should be aware of to avoid misinterpretation of biological tests performed for patients followed for this disease. By its IgG1K humanized monoclonal antibody backbone, DARA interferes in both serum protein electrophoresis and immunofixation by the presence of an alternate IgGK monoclonal peak, leading to a possible difficulty to assess treatment's response in monoclonal IgG kappa light chain myeloma...
June 1, 2017: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/28540842/reason-and-resolution-of-high-negative-control-beads-in-solid-phase-immunoassay
#8
Asmae Zerrouki, Sanae Ouadghiri, Nadia Benseffaj, Rachid Razine, Malika Essakalli
OBJECTIVES: The Luminex technology is the most sensitive diagnostic method for HLA antibody detection and identification. However, the interpretation of immunoassays is commonly affected by the artifact, and non-specific background. Sera from some patients show high negative control bead (NC) value, which makes assessing and interpretation of HLA antibodies difficult. In this study, we evaluated the effect of Adsorb Out reagent, dithiothreitol (DTT), and Ethylenediaminetetraacetic acid (EDTA) on the NC median fluorescence intensity value by comparing treated versus untreated patient sera...
May 22, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28540429/identification-of-markers-for-quiescent-pancreatic-stellate-cells-in-the-normal-human-pancreas
#9
Michael Friberg Bruun Nielsen, Michael Bau Mortensen, Sönke Detlefsen
Pancreatic stellate cells (PSCs) play a central role as source of fibrogenic cells in pancreatic cancer and chronic pancreatitis. In contrast to quiescent hepatic stellate cells (qHSCs), a specific marker for quiescent PSCs (qPSCs) that can be used in formalin-fixed and paraffin embedded (FFPE) normal human pancreatic tissue has not been identified. The aim of this study was to identify a marker enabling the identification of qPSCs in normal human FFPE pancreatic tissue. Immunohistochemical (IHC), double-IHC, immunofluorescence (IF) and double-IF analyses were carried out using a tissue microarray consisting of cores with normal human pancreatic tissue...
May 25, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28539448/virological-control-by-the-cd4-binding-site-antibody-n6-in-shiv-infected-rhesus-monkeys
#10
Boris Julg, Amarendra Pegu, Peter Abbink, Jinyan Liu, Amanda Brinkman, Katherine Molloy, Shanell Mojta, Abishek Chandrashekar, Katherine Callow, Keyun Wang, Xuejun Chen, Stephen D Schmidt, Jinghe Huang, Richard A Koup, Michael S Seaman, Brandon F Keele, John R Mascola, Mark Connors, Dan H Barouch
Passive immunotherapies against HIV-1 will most likely require broadly neutralizing antibodies (bnAb) with maximum breadth and potency to assure therapeutic efficacy. Recently, the novel CD4 binding site antibody N6 demonstrated extraordinary neutralization breadth and potency against large panels of cross clade pseudoviruses. We evaluated the in-vivo antiviral activity of N6-LS, alone or in combination with the established V3-glycan antibody PGT121, in chronically SHIV-SF162P3 infected macaques. A single dose of N6-LS suppressed plasma viral loads in 4 out of 5 animals at day 7 (mean 1...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28536381/antibody-drug-conjugates-for-cancer-therapy
#11
REVIEW
Adam C Parslow, Sagun Parakh, Fook-Thean Lee, Hui K Gan, Andrew M Scott
Antibody-drug conjugates (ADCs) take advantage of the specificity of a monoclonal antibody to deliver a linked cytotoxic agent directly into a tumour cell. The development of these compounds provides exciting opportunities for improvements in patient care. Here, we review the key issues impacting on the clinical success of ADCs in cancer therapy. Like many other developing therapeutic classes, there remain challenges in the design and optimisation of these compounds. As the clinical applications for ADCs continue to expand, key strategies to improve patient outcomes include better patient selection for treatment and the identification of mechanisms of therapy resistance...
July 11, 2016: Biomedicines
https://www.readbyqxmd.com/read/28536352/designing-the-sniper-improving-targeted-human-cytolytic-fusion-proteins-for-anti-cancer-therapy-via-molecular-simulation
#12
REVIEW
Anna Bochicchio, Sandra Jordaan, Valeria Losasso, Shivan Chetty, Rodrigo Casasnovas Perera, Emiliano Ippoliti, Stefan Barth, Paolo Carloni
Targeted human cytolytic fusion proteins (hCFPs) are humanized immunotoxins for selective treatment of different diseases including cancer. They are composed of a ligand specifically binding to target cells genetically linked to a human apoptosis-inducing enzyme. hCFPs target cancer cells via an antibody or derivative (scFv) specifically binding to e.g., tumor associated antigens (TAAs). After internalization and translocation of the enzyme from endocytosed endosomes, the human enzymes introduced into the cytosol are efficiently inducing apoptosis...
February 17, 2017: Biomedicines
https://www.readbyqxmd.com/read/28535267/the-plasma-and-mucosal-igm-iga-and-igg-responses-to-the-vibrio-cholerae-o1-protein-immunome-in-adults-with-cholera-in-bangladesh
#13
Richelle C Charles, Rie Nakajima, Li Liang, Al Jasinskas, Amanda Berger, Daniel T Leung, Meagan Kelly, Peng Xu, Pavol Kovác, Samantha R Giffen, James D Harbison, Fahima Chowdhury, Ashraful I Khan, Stephen B Calderwood, Taufiqur Rahman Bhuiyan, Jason B Harris, Philip L Felgner, Firdausi Qadri, Edward T Ryan
Background.: Cholera is a severe dehydrating illness of humans caused by toxigenic strains of Vibrio cholerae O1 or O139. Identification of immunogenic V. cholerae antigens could lead to a better understanding of protective immunity in human cholera. Methods.: We probed microarrays containing 3652 V. cholerae antigens with plasma and antibody-in-lymphocyte supernatant (ALS, a surrogate marker of mucosal immune responses) from patients with severe cholera caused by V...
May 23, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28534915/quantum-dot-based-sensitive-detection-of-disease-specific-exosome-in-serum
#14
Kseniia Boriachek, Md Nazmul Islam, Vinod Gopalan, Alfred K Lam, Nam-Trung Nguyen, Muhammad J A Shiddiky
Tumor-derived exosomes have emerged as promising cancer biomarkers due to their unique composition and functions. Herein, we report a stripping voltammetric immunoassay for the electrochemical detection of disease-specific exosomes using quantum dots as signal amplifiers. The assay involves three subsequent steps where bulk exosome populations are initially magnetically captured on magnetic beads by a generic tetraspanin antibody (e.g., CD9 or CD63) followed by the identification of disease-specific exosomes using cancer-related...
May 23, 2017: Analyst
https://www.readbyqxmd.com/read/28533998/ipilimumab-as-a-cause-of-severe-pan-colitis-and-colonic-perforation
#15
Raj Shah, Danielle Witt, Talal Asif, Fahad F Mir
Ipilimumab is a human monoclonal antibody that functions as a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor that is used to treat malignant melanoma. Due to ipilimumab's removal of immune regulation, specifically through the inactivation of CTLA-4, it is commonly associated with inflammatory and autoimmune events. Gastrointestinal (GI) related immune-related adverse events such as diarrhea occur in 29% of patients with 7.6% of patients specifically suffering from colitis. We describe a case of colonic perforation with ipilimumab use...
April 20, 2017: Curēus
https://www.readbyqxmd.com/read/28532666/transcription-of-immune-related-genes-in-solea-senegalensis-vaccinated-against-photobacterium-damselae-subsp-piscicida-identification-of-surrogates-of-protection
#16
J A Núñez-Díaz, I García de la Banda, C Lobo, M A Moriñigo, M C Balebona
Solea senegalensis is a flatfish with a great potential for aquaculture, but infectious diseases restrict its production, being this fish species highly susceptible to Photobacterium damselae subsp. piscicida (Phdp) infections. A better understanding of the mechanisms related to fish immune response is crucial for the development of effective approaches in disease management. In the present work, transcriptional changes of immune related genes have been evaluated in farmed S. senegalensis specimens vaccinated against Phdp by intraperitoneal injection (IP) and immersion (IM)...
May 19, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28530564/a-new-method-for-the-rapid-detection-of-atlantic-cod-gadus-morhua-pacific-cod-gadus-macrocephalus-alaska-pollock-gadus-chalcogrammus-and-ling-molva-molva-using-a-lateral-flow-dipstick-assay
#17
Ledicia Taboada, Ana Sánchez, Ricardo I Pérez-Martín, Carmen G Sotelo
Species-specific lateral flow dipstick (LFD) assays for the identification of Atlantic cod (Gadus morhua), Pacific cod (Gadus macrocephalus), Alaska pollock (Gadus chalcogrammus) and ling (Molva molva) in food products were developed. The method comprises a PCR system with four sets of specific primers, for each target species. This step was also devised to dual-labeling of PCR products with biotin and 6-FAM, which are then easily read on a lateral flow dipstick, upon which these products are immobilized by a fixed biotin-ligand and visualized with anti-FAM antibody-coated gold nanoparticles...
October 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28529974/a-glycosylphosphatidylinositol-anchored-carbonic-anhydrase-related-protein-of-toxoplasma-gondii-is-important-for-rhoptry-biogenesis-and-virulence
#18
Nathan M Chasen, Beejan Asady, Leandro Lemgruber, Rossiane C Vommaro, Jessica C Kissinger, Isabelle Coppens, Silvia N J Moreno
Carbonic anhydrase-related proteins (CARPs) have previously been described as catalytically inactive proteins closely related to α-carbonic anhydrases (α-CAs). These CARPs are found in animals (both vertebrates and invertebrates) and viruses as either independent proteins or domains of other proteins. We report here the identification of a new CARP (TgCA_RP) in the unicellular organism Toxoplasma gondii that is related to the recently described η-class CA found in Plasmodium falciparum. TgCA_RP is posttranslationally modified at its C terminus with a glycosylphosphatidylinositol anchor that is important for its localization in intracellular tachyzoites...
May 2017: MSphere
https://www.readbyqxmd.com/read/28529918/advances-in-dyslipidemia-management-for-prevention-of-atherosclerosis-pcsk9-monoclonal-antibody-therapy-and-beyond
#19
REVIEW
Nathan D Wong, Paul D Rosenblit, Robert S Greenfield
In 2003, select families with familial hypercholesterolemia were first identified to have gain-of-function mutations for proprotein convertase subtilisin kexin type 9 (PCSK9) followed, in 2006, by the identification of those with lifelong low levels of LDL-C and lowered atherosclerotic cardiovascular disease (ASCVD) risk who had loss-of-function PCSK9 mutations. These discoveries led to the rapid development of PSCK9-targeted monoclonal antibody (PCSK9 mAb) therapies and, in 2015, 2 'fully-humanized' PCSK9 mAbs (alirocumab and evolocumab) were marketed in the United States, Europe, and other countries...
April 2017: Cardiovascular Diagnosis and Therapy
https://www.readbyqxmd.com/read/28529904/mini-review-of-conventional-and-hypofractionated-radiation-therapy-combined-with-immunotherapy-for-non-small-cell-lung-cancer
#20
REVIEW
Allison M Campbell, Roy H Decker
A successful antitumoral response requires immunological activation as well as an antigenic pool capable of stimulating both the innate and the adaptive immune system. Recent advances in immunotherapy have been aimed at boosting the activation status of the innate and adaptive immune system, including cytokine administration, monoclonal antibodies engineered to target high yield elements in oncogenic signaling pathways, cancer vaccines, and checkpoint inhibitors. Herein, we examine the ways that radiation therapy induced cell death provides a pool of stimulus antigen, and draw parallels from the immunobiology of autoimmunity to explore how the immunogenicity of antigen derived from radiation-induced cell death might augment the antitumoral response...
April 2017: Translational Lung Cancer Research
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