Presence of paf-acether in human thymus

AbstractPaf-acether (paf) is a phospholipid mediator of inflammation endowed with major immunoregulatory properties. The present study demonstrates that human thymus contains large amounts of paf, as well as paf precursors. In addition, isolated thymic cells produced paf under ionophore stimulation. Paf from thymus exhibited the same biological and physicochemical properties as synthetic paf. The purity and molecular structure of paf from thymus were further characterized by reverse-phase HPLC and gas chromatography with electron-capture detection. These findings may have important implications since thymus microenvironment is essential in the proper development of bone marrow progenitors committed to the T cell lineage into thymocytes capable of emigrating to the periphery as functional T lymphocytes.Platelet-activating factor-acether; Thymu

Transplantation of Human Myoblasts in SCID Mice as a Potential Muscular Model for Myotonic Dystrophy

International audienceMyotonic dystrophy (DM), the most frequent hereditary myopathy in adults, is characterized clinically by muscle weakness, myotonia, and systemic symptoms. Although the specific genetic basis for DM has been established, less is known about the cellular defects responsible for its pleiotropic manifestations. DM pathogenesis studies are presently limited due to the absence of animal models. In the present study, we transplanted myoblasts of DM patients into the Tibialis anterior of Severe Combined Immunodeficient (SCID) mice to determine whether this approach could reproduce the muscular characteristics of DM. One to 4 months after transplantation, a variable number of innervated human muscle fibers, recognized by an antibody specific for the human dystrophin, were found in the transplanted muscles. The CTG expansion was retained in human muscle fibers as determined by Southern blot analysis. Although the histological characteristics of DM were absent in these fibers, electromyographic recording showed typical myotonic discharges in muscles transplanted with DM myoblasts. The specificity of the myotonic runs was demonstrated by its inhibition by apamin, a drug that specifically blocks DM myotonia. We conclude that transplantation of myoblasts from DM patients into SCID mice represents a potential in vivo model for basic studies of this disease

Molecular imaging predicts lack of T-DM1 response in advanced HER2-positive breast cancer (final results of ZEPHIR trial)

Abstract: Efficacy of the human epidermal growth factor receptor (HER)2-targeting trastuzumab emtansine (T-DM1) in breast cancer (BC) relies on HER2 status determined by immunohistochemistry or fluorescence in-situ hybridization. Heterogeneity in HER2 expression, however, generates interest in "whole-body" assessment of HER2 status using molecular imaging. We evaluated the role of HER2-targeted molecular imaging in detecting HER2-positive BC lesions and patients unlikely to respond to T-DM1. Patients underwent zirconium-89 (Zr-89) trastuzumab (HER2) PET/CT and [F-18]-2-fluoro-2-deoxy-D-glucose (FDG) PET/CT before T-DM1 initiation. Based on Zr-89-trastuzumab uptake, lesions were visually classified as HER2-positive (visible/high uptake) or HER2-negative (background/close to background activity). According to proportion of FDG-avid tumor load showing Zr-89-trastuzumab uptake (entire/dominant part or minor/no part), patients were classified as HER2-positive and HER2-negative, respectively. Out of 265 measurable lesions, 93 (35%) were HER2-negative, distributed among 42 of the 90 included patients. Of these, 18 (19%) lesions belonging to 11 patients responded anatomically (>30% decrease in axial diameter from baseline) after three T-DM1 cycles, resulting in an 81% negative predictive value (NPV) of the HER2 PET/CT. In combination with early metabolic response assessment on FDG PET/CT performed before the second T-DM1 cycle, NPVs of 91% and 100% were reached in predicting lesion-based and patient-based (RECIST1.1) response, respectively. Therefore, HER2 PET/CT, alone or in combination with early FDG PET/CT, can successfully identify BC lesions and patients with a low probability of clinical benefit from T-DM1

Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework.

Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines

Biological Stress Response Terminology: Integrating the Concepts of Adaptive Response and Preconditioning Stress Within a Hormetic Dose-Response Framework

Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose- response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.JRC.H.5-Rural, water and ecosystem resource

Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework.

Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines