scholarly journals ANCA-Associated Vasculitides and Hematologic Malignancies: Lessons from the Past and Future Perspectives

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Marco Folci ◽  
Giacomo Ramponi ◽  
Dana Shiffer ◽  
Aurora Zumbo ◽  
Michele Agosti ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Hematologic Malignancy ◽  
Hematologic Malignancies ◽  
Future Perspectives ◽  
The Past ◽  
Anca Associated Vasculitis ◽  
Uncommon Presentation ◽  
Immunotherapy Target ◽  
And Function

The purpose of this paper is to collect and summarize all evidences relating to an association between ANCA-associated vasculitides (AAVs) and hematologic malignancies, in the form of either a paraneoplastic vasculitis or leukemias and lymphomas developing on a preexisting vasculitis. Additionally, the role of cyclophosphamide in vasculitis treatment has been assessed and compared to rituximab. Paraneoplastic AAV seems to be an uncommon presentation of hemopathies. Hematologic malignancy risk in AAV is more likely to be increased by cyclophosphamide, although not yet definitely proven. Furthermore, the pathogenesis of ANCA-associated vasculitis has been reviewed with particular emphasis on the role of proteinase 3 (PR3) in fuelling granulomatosis with polyangiitis (GPA) inflammation. PR3 is a bactericidal protein expressed by neutrophilic granules and on their plasma membrane. Derangements in its expression and function have been linked to leukemias and GPA alike. PR3-derived PR1 peptide is being studied as an immunotherapy target in leukemia and multiple myeloma. This study is aimed at bringing together various evidences from the field of immunological and hematological research, at exposing contradictions, and at revealing novel insights on the association between ANCA-associated vasculitis and hematologic malignancies.

scholarly journals Update in the Management of ANCA-Associated Vasculitis: Recent Developments and Future Perspectives

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Karla N. Samman ◽  
Carolyn Ross ◽  
Christian Pagnoux ◽  
Jean-Paul Makhzoum
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Microscopic Polyangiitis ◽  
Future Perspectives ◽  
Significant Progress ◽  
Treatment Algorithms ◽  
The Past ◽  
Anca Associated Vasculitis ◽  
Recent Developments ◽  
Maintenance Of Remission ◽  
Made In

Significant progress has been made in the treatment of ANCA-associated vasculitides (AAV), notably in granulomatosis with polyangiitis and microscopic polyangiitis. Over the past few years, many innovative studies have changed the way we now induce and maintain remission in AAV; achieving remission while limiting treatment toxicity is the key. This article provides an in-depth, up-to-date summary of recent trials and suggests treatment algorithms for induction and maintenance of remission based on the latest guidelines. Future possible therapies in AAV will also be discussed.

scholarly journals ANCA Status or Clinical Phenotype — What Counts More?

2021 ◽  
Vol 23 (6) ◽  
Author(s):  
Martin Windpessl ◽  
Erica L. Bettac ◽  
Philipp Gauckler ◽  
Jae Il Shin ◽  
Duvuru Geetha ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Granulomatosis With Polyangiitis ◽  
Clinical Phenotype ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Cardiovascular Death ◽  
Genetic Associations ◽  
Ongoing Debate ◽  
The Past ◽  
Anca Associated Vasculitis

Abstract Purpose of Review There is ongoing debate concerning the classification of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. That is, whether classification should be based on the serotype (proteinase 3 (PR3)- or myeloperoxidase (MPO)-ANCA) or on the clinical phenotype (granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)). To add clarity, this review focused on integration of the most recent literature. Recent Findings Large clinical trials have provided evidence that a serology-based risk assessment for relapses is more predictive than distinction based on the phenotype. Research conducted in the past decade indicated that a serology-based approach more closely resembles the genetic associations, the clinical presentation (i.e., lung involvement), biomarker biology, treatment response, and is also predicting comorbidities (such as cardiovascular death). Summary Our review highlights that a serology-based approach could replace a phenotype-based approach to classify ANCA-associated vasculitides. In future, clinical trials and observational studies will presumably focus on this distinction and, as such, translate into a “personalized medicine.”

scholarly journals Immunosuppressive Mechanisms of Regulatory B Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Diego Catalán ◽  
Miguel Andrés Mansilla ◽  
Ashley Ferrier ◽  
Lilian Soto ◽  
Kristine Oleinika ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Metabolic Diseases ◽  
Inflammatory Responses ◽  
Surface Proteins ◽  
Regulatory B Cells ◽  
Cell Surface Proteins ◽  
The Past ◽  
And Function

Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting ongoing immune responses and reestablishing immune homeostasis. The important role of Bregs in restraining the pathology associated with exacerbated inflammatory responses in autoimmunity and graft rejection has been consistently demonstrated, while more recent studies have suggested a role for this population in other immune-related conditions, such as infections, allergy, cancer, and chronic metabolic diseases. Initial studies identified IL-10 as the hallmark of Breg function; nevertheless, the past decade has seen the discovery of other molecules utilized by human and murine B cells to regulate immune responses. This new arsenal includes other anti-inflammatory cytokines such IL-35 and TGF-β, as well as cell surface proteins like CD1d and PD-L1. In this review, we examine the main suppressive mechanisms employed by these novel Breg populations. We also discuss recent evidence that helps to unravel previously unknown aspects of the phenotype, development, activation, and function of IL-10-producing Bregs, incorporating an overview on those questions that remain obscure.

Role of PET in Diagnosis and Risk Assessment in Patients with Known or Suspected CAD

2015 ◽  
Author(s):  
Brian A. Mc Ardle ◽  
Jennifer M. Renaud ◽  
Robert A. deKemp ◽  
Rob S. B. Beanlands
Keyword(s):  
Myocardial Perfusion ◽  
Diagnostic Accuracy ◽  
Lower Cost ◽  
Image Artifacts ◽  
Cardiac Pet ◽  
The Past ◽  
Pet Myocardial Perfusion Imaging ◽  
Patient Radiation Exposure ◽  
And Function

Cardiac PET enables evaluation of multiple aspects of myocardial perfusion, metabolism, cell signaling and function that are of value both for diagnosis and prognostication in patients with known or suspected CAD and its use has increased in the past three decades. PET myocardial perfusion imaging (MPI) offers several technological advantages over SPECT including; higher photon energy, higher count sensitivity, more consistent attenuation correction and the ability to measure myocardial blood flow in absolute terms. These result in faster imaging times, lower patient radiation exposure and increased diagnostic accuracy. However the availability of PET MPI remains limited, predominantly due to expense. Efforts are underway to expand the use of PET MPI beyond larger centers, with lower-cost scanners and more widely available radiotracers. In this chapter we describe the latest advances in PET camera technology and image reconstruction as well as potential image artifacts specific to PET MPI. We go on to discuss diagnostic accuracy and prognostic value of PET MPI as well as its role in clinical practice.

scholarly journals Endocrine Significance of SARS-CoV-2’s Reliance on ACE2

Endocrinology ◽  
2020 ◽  
Vol 161 (9) ◽  
Author(s):  
Eric Lazartigues ◽  
Mirza Muhammad Fahd Qadir ◽  
Franck Mauvais-Jarvis
Keyword(s):  
Potential Role ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Global Impact ◽  
The Past ◽  
And Function ◽  
Endocrine Tissues

Abstract The current COVID-19 pandemic is the most disruptive event in the past 50 years, with a global impact on health care and world economies. It is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a coronavirus that uses angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. ACE2 is a transmembrane carboxypeptidase and member of the renin-angiotensin system. This mini-review summarizes the main findings regarding ACE2 expression and function in endocrine tissues. We discuss rapidly evolving knowledge on the potential role of ACE2 and SARS coronaviruses in endocrinology and the development of diabetes mellitus, hypogonadism, and pituitary and thyroid diseases.

Indigenous approaches to the past: ‘Creative histories’ at the Hyde Park Barracks, Sydney

2020 ◽  
Vol 9 (1) ◽  
pp. 83-102 ◽  
Author(s):  
Kiera Lindsey
Keyword(s):  
Visual Art ◽  
The Other ◽  
Cultural Relations ◽  
Form And Function ◽  
The Past ◽  
Cultural Responses ◽  
And Function ◽  
The Way

This article discusses a recent art project created by the Wiradjuri and Kamilaroi artist Jonathon Jones, which was commissioned to commemorate the opening of the revitalized Hyde Park Barracks in Sydney in early 2020. Jones’ work involves a dramatic installation of red and white crushed stones laid throughout the grounds of the barracks, merging the image of the emu footprint with that of the English broad convict arrow to ‘consider Australia’s layered history and contemporary cultural relations’. This work was accompanied by a ‘specially-curated programme’ of performances, workshops, storytelling and Artist Talks. Together, these elements were designed to unpack how certain ‘stories determine the ways we came together as a nation’. As one of the speakers of the Artist Talk’s programme, I had a unique opportunity to experiment with what colleagues and I have been calling ‘Creative histories’ in reference to the way some artists and historians are choosing to communicate their research about the past in ways that experiment with form and function and push disciplinary or generic boundaries. This article reflects upon how these two distinct creative history projects – one visual art, the other performative – renegotiate the complex and contested pasts of the Hyde Park Barracks. I suggest that both examples speak to the role of memory and creativity in shaping cultural responses to Australia’s colonial past, while Jones' programme illustrates how Indigenous artists and academics are making a profound intervention into contemporary understandings of how history is ‘done’ in Australia.

scholarly journals The Future of International Legal Scholarship: Some Thoughts on ‘Practice’, ‘Growth’, and ‘Dissemination’

2013 ◽  
Vol 27 (1) ◽  
pp. 1-10 ◽  
Author(s):  
CARSTEN STAHN ◽  
ERIC DE BRABANDERE
Keyword(s):  
International Law ◽  
Legal Discourse ◽  
Legal Scholarship ◽  
Self Reflection ◽  
The Past ◽  
Niche Area ◽  
And Function ◽  
Changing Role ◽  
Role And Function

Like international legal scholarship, LJIL is in transition. Our colleagues, Larissa van den Herik and Jean d'Aspremont, who have shaped much of the role and plural identity of the journal over the past decade, in collaboration with our different sections, have passed leadership on to us, the new team of (co-)editors-in-chief. This editorial reflects on the changing role and function of scholarship in international law, a theme important to our predecessors and ourselves. This is to some extent a niche area. It has not received much attention in discourse. With some notable exceptions, legal journals are typically reluctant to address overarching meta-issues of discourse, i.e. issues of production of scholarship, the role of journals vis-à-vis other media, or the broader direction of the development of international legal scholarship. Such issues might be perceived as non-scientific by some. We feel that it is important to include such dimensions, including critical self-reflection on our discipline, in international legal discourse.

scholarly journals Investigating the Subcortical Route to the Amygdala Across Species and in Disordered Fear Responses

2019 ◽  
Vol 13 ◽  
pp. 117906951984644 ◽  
Author(s):  
Jessica McFadyen
Keyword(s):  
Visual Information ◽  
Sensory Input ◽  
Cortical Circuits ◽  
Temporal Area ◽  
Middle Temporal ◽  
Directional Flow ◽  
The Past ◽  
And Function ◽  
Anatomical Evidence

Over the past few decades, evidence has come to light that there is a rapid subcortical shortcut that transmits visual information to the amygdala, effectively bypassing the visual cortex. This pathway purportedly runs from the superior colliculus to the amygdala via the pulvinar, and thus presents a methodological challenge to study noninvasively in the human brain. Here, we present our recent work where we reliably reconstructed the white matter structure and directional flow of neural signal along this pathway in over 600 healthy young adults. Critically, we found structure-function relationships for the pulvinar-amygdala connection, where people with greater fibre density had stronger functional neural coupling and were also better at recognising fearful facial expressions. These results tie together recent anatomical evidence from other visual primates with very recent optogenetic research on rodents demonstrating a functional role of this pathway in producing fear responses. Here, we discuss how this pathway might operate alongside other thalamo-cortical circuits (such as pulvinar to middle temporal area) and how its structure and function may change according to the sensory input it receives. This newly established circuit might play a potentially important role in autism and/or anxiety disorders.

Progress in ultrastructural and molecular analysis of the nuclear matrix

1992 ◽  
Vol 50 (1) ◽  
pp. 508-509
Author(s):  
Edward G. Fey
Keyword(s):  
Electron Microscopy ◽  
Nuclear Matrix ◽  
Structure And Function ◽  
Matrix Proteins ◽  
Rna Transcription ◽  
Nuclear Matrix Proteins ◽  
The Past ◽  
And Function

In the past few years, considerable advances have been made regarding the structure and function of the nuclear matrix. In the first half of this presentation, the field of nuclear matrix research will be summarized. Emphasis will be placed on those studies where molecular interactions are demonstrated in situ utilizing high resolution light and/or electron microscopy. Studies demonstrating the role of the nuclear matrix in DNA synthesis and replication, RNA transcription and processing, and the binding of matrix attachment regions to specific nuclear matrix proteins will be summarized.

Judicial Activism and Judicial Independence: Implications of the Charter of Rights and Freedoms for the Reference Procedure and Judicial Service on Commissions of Inquiry.

1990 ◽  
Vol 5 ◽  
pp. 95-110
Author(s):  
Kenneth M. Holland
Keyword(s):  
Civil Rights ◽  
Judicial Independence ◽  
Royal Commission ◽  
Supreme Court Of Canada ◽  
The Past ◽  
The Supreme Court ◽  
Commissions Of Inquiry ◽  
And Function ◽  
Fundamental Values

Over the past five years the Supreme Court of Canada has addressed on three occasions the implications of the 1982Charter of Rights and Freedomsfor the principle of judicial independence. The justices agree that the Court's new role as guardian of constitutionally entrenched civil rights and liberties demands an expansion in its immunity from legislative and executive influence. The hoary principle of judicial independence can no longer be confined to such individual elements as security of salary and tenure but must encompass an institutional element, “reflected in [a court's] institutional or administrative relationships to the executive and legislative branches of government.” The “modern understanding of judicial independence,” according to Chief Justice Brian Dickson, recognizes that the Canadian judiciary is no longer confined to the resolution of disputes in individual cases but plays the role of “protector of theConstitutionand the fundamental values embodied in it—rule of law, fundamental justice, equality, preservation of the democratic process, to name perhaps the most important.” It is not enough, therefore, to ensure the impartiality of judges in individual cases. Courts must “be completely separate in ‘authority and function’ from all other branches of government.” Accordingly, the Court ruled in a 1989 case that a royal commission of inquiry cannot compel judges involved in a matter being investigated to testify as to the reasons for their judicial decision.

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