Physiology of the Placenta
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
The basic structural unit of the human placenta is the chorionic villus. Blood enters the fetal side of the placenta from two umbilical arteries and returns to the fetus via a single umbilical vein. A variety of nutrients, waste products and toxins cross the placental barrier by simple diffusion, facilitated transport, active transport, endocytosis and bulk flow. The rates of blood flow in the maternal and fetal sides of the placenta have major importance for the maintenance of fetal oxygenation. Carbon dioxide can easily move across the layers of the placenta from the fetus to the mother because it is extremely soluble in biological membranes. The transfer of sodium and chloride ions across the human placenta is mainly by passive diffusion. The placenta contains enzymes that synthesize hormones such as oestrogen, progesterone, chorionic gonadotrophin and placental lactogen. The placenta is a selective immunological barrier as it permits transport of maternal Immunoglobulin G antibodies to provide passive immunity to the fetus.
Antibodies and Antisera
Lars-Inge Larsson in Immunocytochemistry: Theory and Practice, 2020
Nearly all antibodies used in immunocytochemistry and related techniques belong to the immunoglobulin G class, the remainder being IgM antibodies. In polyclonal antisera, antibody subpopulations of different specificities and different avidities occur. However, as polyclonal antisera vary so much in their biological properties, it is not possible to define a minimum dilution of them. Antibodies to single amino acids and related molecules may, however, differ in their reactivity with different chemical groups so that a variant of region-specific immunocytochemistry can be executed. Antibodies may therefore be used as either biochemically defined detection reagents in true immunocytochemical techniques or as anatomically defined immunohistological stains. Thus, many antisera contain antigen-antibody complexes, with the antigen component being introduced during the immunization or being of endogenous animal origin. In indirect immunocytochemical methods, which employ labeled antibodies or other labeled proteins as secondary detection reagents, the saturable mechanism could primarily cause unspecificity through binding of the second or third antibody.
Haematology
Michael McGhee in A Guide to Laboratory Investigations, 2019
There are a number of haematological conditions that must be referred to a consultant. The mean corpuscular volume may be normal in anaemia of chronic disease, uraemia, acute blood loss, myeloproliferative disorders and bone marrow infiltration, or where vitamin B 12 or folate deficiency are combined with iron deficiency or thalassaemia. Anti-cardiolipin immunoglobulin G is provided as an antibody against the beta-2 glycoprotein coagulation system. A significantly raised level is indicative of an increased risk of thrombosis, and is often found in autoimmune disease and in patients with recurrent miscarriages (more than three), and is thought to be due to placental thrombosis. Infection with the Epstein-Barr virus (human herpes type 4 virus) has been implicated in a wide spectrum of clinical diseases, ranging from glandular fever to lymphoma. Antiphospholipid syndrome may be suspected when a patient has suffered from venous thrombosis, or thrombophlebitis, arterial thrombosis or recurrent miscarriage and has antiphospholipid antibodies.
Necitumumab for the treatment of stage IV metastatic squamous non-small-cell lung cancer
Published in Expert Review of Respiratory Medicine, 2015
Paola Claudia Sacco, Paolo Maione, Antonio Rossi, Assunta Sgambato, Francesca Casaluce, Giovanni Palazzolo, Cesare Gridelli
Over the past two decades, progress in the treatment of patients with metastatic squamous non-small-cell lung cancer has been limited. The EGFR is involved in tumor progression and invasion and therefore it has become the target of several studies in lung cancer. Strategies to block this pathway are focused on the development of small molecule (tyrosine kinase inhibitor) and monoclonal antibodies (mAbs). Some mAbs have been studied in patients with advanced non-small-cell lung cancer. For the first time, a fully human immunoglobulin G (IMC-11F8), subclass 1 (IgG1) mAb targeting the EGFR, in combination with standard chemotherapy (cisplatin + gemcitabine), has been shown to increase overall survival in chemo-naïve patients with metastatic confirmed squamous cell histology.
Insights into the IgG heavy chain engineering patent landscape as applied to IgG4 antibody development
Published in mAbs, 2019
Christophe Dumet, Jérémy Pottier, Valérie Gouilleux-Gruart, Hervé Watier
Despite being the least abundant immunoglobulin G in human plasma, IgG4 are used therapeutically when weak effector functions are needed. The increase in engineered IgG4-based antibodies on the market led us to study the patent landscape of IgG4 Fc engineering, i.e., patents claiming modifications in the heavy chain. Thirty-seven relevant patent families were identified, comprising hundreds of IgG4 Fc variants focusing on removal of residual effector functions (since IgG4s bind to FcγRI and weakly to other FcγRs), half-life enhancement and IgG4 stability. Given the number of expired or soon to expire major patents in those 3 areas, companies developing blocking antibodies now have, or will in the near future, access to free tools to design silenced, half-life extended and stable IgG4 antibodies.
A sensitive electrochemical immunosensor based on poly(2-aminobenzylamine) film modified screen-printed carbon electrode for label-free detection of human immunoglobulin G
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Thitirat Putnin, Watthanachai Jumpathong, Rawiwan Laocharoensuk, Jaroon Jakmunee, Kontad Ounnunkad
This work focuses on fabricating poly(2-aminobenzylamine)-modified screen-printed carbon electrode as an electrochemical immunosensor for the label-free detection of human immunoglobulin G. To selectively detect immunoglobulin G, the anti-immunoglobulin G antibody with high affinity to immunoglobulin G was covalently linked with the amine group of poly(2-aminobenzylamine) film-deposited screen-printed carbon electrode. The selectivity for immunoglobulin G was subsequently assured by being challenged with redox-active interferences and adventitious adsorption did not significantly interfere the analyte signal. To obviate the use of costly secondary antibody, the [Fe(CN)6]4-/3- redox probe was instead applied to measure the number of human immunoglobulin G through the immunocomplex formation that is quantitatively related to the level of the differential pulse voltammetric current. The resulting immunosensor exhibited good sensitivity with the detection limit of 0.15 ng mL−1, limit of quantitation of 0.50 ng mL−1 and the linear range from 1.0 to 50 ng mL−1. Given those striking analytical performances and the affordability arising from using cheap screen-printed carbon electrode with label-free detection, the immunosensor serves as a promising model for the next-step development of a diagnostic tool.
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