scholarly journals Apoptosis, Annexin A5 and Anti-Annexin A5 Antibodies in The Antiphospholipid Syndrome

2013 ◽  
Vol 32 (2) ◽  
pp. 89-95 ◽  
Author(s):  
Mirjana Bećarević ◽  
Svetlana Ignjatović ◽  
Nada Majkić-Singh
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Imaging Techniques ◽  
Annexin A5 ◽  
Primary Antiphospholipid Syndrome ◽  
History Of ◽  
Recurrent Abortions ◽  
And Function

Summary It has been proposed that apoptosis is one of the mechanisms involved in the generation of antiphospholipid antibodies. The presence of antiphospholipid antibodies is the main laboratory criterion for a definite diagnosis of the antiphospholipid syndrome. Annexinopathies are disorders characterized by deregulation of annexins expression levels and function. Annexin A5 has been used as an agent for molecular imaging techniques (visualization of phosphatidylserineexpressing apoptotic cells) in vitro and in vivo in animal models and in patients (injection of human recombinant anxA5 into the patient‘s circulation). Although the determination of titers of anti-annexin A5 antibodies is not mandatory for the diagnosis of the antiphospholipid syndrome, it was reported that patients with primary antiphospholipid syndrome with a history of recurrent abortions had elevated titers of antiannexin A5 antibodies, while the presence of thromboses was not associated with elevated levels of these antibodies

scholarly journals Antiphospholipid Antibodies From Antiphospholipid Syndrome Patients Activate Endothelial Cells In Vitro and In Vivo

Circulation ◽  
1999 ◽  
Vol 99 (15) ◽  
pp. 1997-2002 ◽  
Author(s):  
Silvia S. Pierangeli ◽  
Margaret Colden-Stanfield ◽  
Xiaowei Liu ◽  
John H. Barker ◽  
Gary L. Anderson ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies

scholarly journals Development and Physiological Functions of the Lymphatic System - Insights from Genetic Studies of Lymphedema

2021 ◽  
Author(s):  
Silvia Martin-Almedina ◽  
Peter Mortimer ◽  
Pia Ostergaard
Keyword(s):  
Lymphatic System ◽  
Imaging Techniques ◽  
The Body ◽  
Genetic Studies ◽  
Disease Mechanisms ◽  
Primary Lymphedema ◽  
And Function ◽  
The Impact

Primary lymphedema is a long-term (chronic) condition characterized by tissue lymph retention and swelling that can affect any part of the body, although it usually develops in the arms or legs. Due to the relevant contribution of the lymphatic system to human physiology, while this review mainly focusses on the clinical and physiological aspects related to the regulation of fluid homeostasis and edema, clinicians need to know that the impact of lymphatic dysfunction with a genetic origin can be wide ranging. Lymphatic gene dysfunction can affect immune function so leading to infection; it can influence cancer development and spread; and it can determine fat transport so impacting on nutrition and obesity. Genetic studies and the development of imaging techniques for the assessment of lymphatic function have enabled the recognition of primary lymphedema as a heterogenic condition in terms of genetic causes and disease mechanisms. In this review, the known biological function of several genes crucial to the development and function of the lymphatic system are used as a basis for understanding normal lymphatic biology. The disease conditions originating from mutations in these genes are discussed together with a detailed clinical description of the phenotype and the up-to-date knowledge in terms of disease mechanisms acquired from in vitro and in vivo research models.

Pathogenic antiphospholipid antibody: an antigen-selected needle in a haystack

Blood ◽  
2004 ◽  
Vol 104 (6) ◽  
pp. 1711-1715 ◽  
Author(s):  
Patricia Lieby ◽  
Vincent Poindron ◽  
Stamatiki Roussi ◽  
Cyril Klein ◽  
Anne-Marie Knapp ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Germ Line ◽  
Annexin A5 ◽  
Antiphospholipid Antibody ◽  
Variable Regions ◽  
Anionic Phospholipids ◽  
Pregnant Mice

Abstract Antiphospholipid antibodies represent a heterogeneous group of autoantibodies directed against anionic phospholipids (PLs) usually linked to protein cofactors. Their presence during the antiphospholipid syndrome is associated with risks of thrombosis and fetal losses. Among 5 randomly selected monoclonal antiphospholipid antibodies, all originating from a single patient suffering from this autoimmune disease, only 1 induced fetal losses when passively injected into pregnant mice. Its antiphospholipid activity was dependent on annexin A5, and its variable regions contained mainly 3 replacement mutations. To clarify the role of these mutations in the pathogenicity of the antibody, they were in vitro reverted to the germ line configuration. The resulting “germ line” antibody reacted with multiple self-antigens and only partially lost its reactivity against PLs, but it was no more dependent on annexin A5 and, more importantly, was no more pathogenic. This study illustrates that the in vivo antigen-driven maturation process of natural autoreactive B cells can be responsible for pathogenicity. (Blood. 2004;104:1711-1715)

Optogenetics and Electrophysiology

2015 ◽  
Author(s):  
Hua-an Tseng ◽  
Richie E. Kohman ◽  
Xue Han
Keyword(s):  
Neural Coding ◽  
Neural Circuit ◽  
Imaging Techniques ◽  
Neural Signals ◽  
Molecular Sensors ◽  
Spatial And Temporal Scales ◽  
History Of ◽  
Optical Activation

Throughout the history of neuroscience, electrophysiological and imaging techniques have been utilized to observe neural signals at various spatial and temporal scales. However, it has been difficult to manipulate the activity of specific cells or neural circuits with the spatial and temporal resolutions relevant to neural coding. A novel technique called optogenetics, has recently been developed to control the activity of specific cells. This technique allows rapid and reversible optical activation or silencing of specific cells, which have been genetically transduced with light-sensitive molecules. The development of microbial opsin-based optogenetic molecular sensors has made optogenetics easily adaptable in various in vivo and in vitro preparations, and the technique has already been applied to understand neural circuit mechanisms of many behaviors and diseases. Here, we provide an introduction to optogenetics, the practical concerns in using the technique in vivo, and examples of applications that combine traditional electrophysiology techniques with optogenetics.

A Patient With Remote Heparin-Induced Thrombocytopenia and Antiphospholipid Syndrome Requiring Cardiopulmonary Bypass: Do Current Guidelines Apply?

2018 ◽  
Vol 23 (2) ◽  
pp. 256-260 ◽  
Author(s):  
Warsame Ibrahim ◽  
Hunter Nakia ◽  
Miller Stephen ◽  
Spiess Bruce ◽  
Whitson Bryan ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Unfractionated Heparin ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Artery Bypass ◽  
Inhibitory Effect ◽  
Heparin Induced Thrombocytopenia ◽  
History Of ◽  
Complex Decision Making

Anticoagulation for cardiopulmonary bypass (CPB) is required to prevent acute disseminated intravascular coagulation and clot formation within the bypass circuit. Unfractionated heparin is the standard anticoagulant for CPB due to its many advantages and long history of successful use. However, heparin has the unique drawback of triggering Heparin-PF4 (PF4) antibodies potentially leading to heparin-induced thrombocytopenia (HIT). We have limited data regarding reformation of antibodies if a patient has had a prior (remote) antibody production or full HIT. Patients with antiphospholipid antibodies undergoing CPB with unfractionated heparin have a high complication rate, even in the absence of HIT. Antiphospholipid antibodies have a multifaceted, cumulatively inhibitory effect on the normal anticoagulation armamentarium in vivo. Even more concerning is the possibility that antiphospholipid syndrome and HIT may be synergistic. We report a patient with risk factors for both thromboembolic (remote history of HIT and antiphospholipid syndrome) and hemorrhagic complications who underwent an aortic valve replacement and coronary artery bypass grafting on CPB using bivalirudin. We discuss the complex decision making regarding anticoagulant for CPB, particularly with regard to American College of Chest Physicians guidelines.

scholarly journals Extracellular Vesicles and Antiphospholipid Syndrome: State-of-the-Art and Future Challenges

2021 ◽  
Vol 22 (9) ◽  
pp. 4689
Author(s):  
Ula Štok ◽  
Saša Čučnik ◽  
Snežna Sodin-Šemrl ◽  
Polona Žigon
Keyword(s):  
Extracellular Vesicles ◽  
Antiphospholipid Syndrome ◽  
Autoimmune Disorder ◽  
In Vivo Models ◽  
Increased Risk ◽  
Future Challenges ◽  
History Of ◽  
Obstetric Aps

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thromboembolism, obstetric complications, and the presence of antiphospholipid antibodies (aPL). Extracellular vesicles (EVs) play a key role in intercellular communication and connectivity and are known to be involved in endothelial and vascular pathologies. Despite well-characterized in vitro and in vivo models of APS pathology, the field of EVs remains largely unexplored. This review recapitulates recent findings on the role of EVs in APS, focusing on their contribution to endothelial dysfunction. Several studies have found that APS patients with a history of thrombotic events have increased levels of EVs, particularly of endothelial origin. In obstetric APS, research on plasma levels of EVs is limited, but it appears that levels of EVs are increased. In general, there is evidence that EVs activate endothelial cells, exhibit proinflammatory and procoagulant effects, interact directly with cell receptors, and transfer biological material. Future studies on EVs in APS may provide new insights into APS pathology and reveal their potential as biomarkers to identify patients at increased risk.

scholarly journals Hyperhomocysteinemia and Smoking in Primary Antiphospholipid Syndrome

2009 ◽  
Vol 28 (3) ◽  
pp. 172-175
Author(s):  
Mirjana Bećarević ◽  
Duško Mirković ◽  
Nada Majkić-Singh
Keyword(s):  
Risk Factors ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Physical Inactivity ◽  
High Performance ◽  
Myocardial Infarctions ◽  
Modifiable Risk Factors ◽  
Primary Antiphospholipid Syndrome ◽  
History Of ◽  
Thrombotic Tendency

Hyperhomocysteinemia and Smoking in Primary Antiphospholipid SyndromeThe thrombotic tendency in antiphospholipid syndrome (APS) shares several pathways with atherosclerosis. Atherothrombosis (atherosclerosis superimposed with thromboses) is influenced by nonmodifiable and some modifiable risk factors (smoking, obesity, physical inactivity, alcohol abuse, hyperhomocysteinemia). Therefore, we investigated the association among clinical and serological features of patients with primary APS and potentially modifiable risk factors for the development of atherothrombosis. Also, we compared the analyzed parameters with those in control subjects. Homocysteine concentrations were detected by HPLC (high performance liquid chromatography), while antiphospholipid antibodies were detected by ELISA. Smokers had elevated levels of homocysteine (χ2= 6.22, p < 0.05). Independently of patients' age, the association between increased levels of homocysteine and history of myocardial infarctions was found (χ2= 4.61, p < 0.05). Hyperhomocysteinemia and smoking are the most important modifiable risk factors for atherothrombosis in primary APS.

scholarly journals Detecting apoptosis as a clinical endpoint for proof of a clinical principle

2020 ◽  
Author(s):  
Piero Zollet ◽  
Timothy E.Yap ◽  
M Francesca Cordeiro
Keyword(s):  
Drug Development ◽  
Therapeutic Response ◽  
Imaging Techniques ◽  
Brain Diseases ◽  
Promising Strategy ◽  
Sight Loss ◽  
Apoptosis Detection ◽  
Novel Therapeutic Strategies

The transparent eye media represent a window through which to observe changes occurring in the retina during pathological processes. In contrast to visualising the extent of neurodegenerative damage that has already occurred, imaging an active process such as apoptosis has the potential to report on disease progression and therefore the threat of irreversible functional loss in various eye and brain diseases. Early diagnosis in these conditions is an important unmet clinical need to avoid or delay irreversible sight loss. In this setting, apoptosis detection is a promising strategy with which to diagnose, provide prognosis, and monitor therapeutic response. Additionally, monitoring apoptosis in vitro and in vivo has been shown to be valuable for drug development in order to assess the efficacy of novel therapeutic strategies both in the pre-clinical and clinical setting. Detection of Apoptosing Retinal Cells (DARC) technology is to date the only tool of its kind to have been tested in clinical trials, with other new imaging techniques under investigation in the fields of neuroscience, ophthalmology and drug development. We summarize the transitioning of techniques detecting apoptosis from bench to bedside, along with the future possibilities they encase.

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