Muscular dystrophies, dilated cardiomyopathy, lipodystrophy and neuropathy: the nuclear connection

2002 ◽  
Vol 4 (17) ◽  
pp. 1-21 ◽  
Author(s):  
Stephen L. Maidment ◽  
Juliet A. Ellis
Keyword(s):  
Dilated Cardiomyopathy ◽  
Nuclear Proteins ◽  
Muscular Dystrophies ◽  
Lamin A ◽  
Cell Integrity ◽  
Distinct Disease ◽  
Life Threatening ◽  
And Function ◽  
Disease Understanding

An understanding of muscle structure and function is central to improving our knowledge of the group of muscle diseases referred to as muscular dystrophies. These diseases involve a progressive weakening and wasting of skeletal muscle, which can be associated with life-threatening cardiac arrhythmias. The vast majority of these diseases arise from defects in either cytoskeletal or structural proteins, resulting in a breakdown of muscle cell integrity. However, mutations in two nuclear proteins – emerin and lamin A/C – have also been demonstrated to give rise to a muscular dystrophy phenotype. In addition, mutations in lamin A/C can give rise to a dilated cardiomyopathy, a lipodystrophy or a neuropathy. It is far from clear how mutations in nuclear proteins can result in a dystrophy, or cause more than one clinically distinct disease. Understanding the functional role of nuclear proteins in causing these diseases will therefore provide novel insights into muscle function, and should hopefully provide new directions for treatment.

Molecular signatures of Emery–Dreifuss muscular dystrophy

2008 ◽  
Vol 36 (6) ◽  
pp. 1354-1358 ◽  
Author(s):  
Matthew A. Wheeler ◽  
Juliet A. Ellis
Keyword(s):  
Muscular Dystrophy ◽  
Dilated Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Autosomal Dominant ◽  
Signalling Pathways ◽  
Lamin A ◽  
Degenerative Diseases ◽  
Hypertrophic Growth ◽  
Genes Encoding

Mutations in genes encoding the nuclear envelope proteins emerin and lamin A/C lead to a range of tissue-specific degenerative diseases. These include dilated cardiomyopathy, limb-girdle muscular dystrophy and X-linked and autosomal dominant EDMD (Emery–Dreifuss muscular dystrophy). The molecular mechanisms underlying these disorders are poorly understood; however, recent work using animal models has identified a number of signalling pathways that are altered in response to the deletion of either emerin or lamin A/C or expression of Lmna mutants found in patients with laminopathies. A distinguishing feature of patients with EDMD is the association of a dilated cardiomyopathy with conduction defects. In the present article, we describe several of the pathways altered in response to an EDMD phenotype, which are known to be key mediators of hypertrophic growth, and focus on a possible role of an emerin–β-catenin interaction in the pathogenesis of this disease.

scholarly journals The role of Asprosin in patients with dilated cardiomyopathy

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ming-Shien Wen ◽  
Chao-Yung Wang ◽  
Jih-Kai Yeh ◽  
Chun-Chi Chen ◽  
Ming-Lung Tsai ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Mitochondrial Respiration ◽  
Cardiovascular Events ◽  
Molecular Mechanisms ◽  
Major Adverse Cardiovascular Events ◽  
Study Cohort ◽  
Protective Mechanisms ◽  
Mitochondrial Functions ◽  
And Function

Abstract Background Asprosin is a novel fasting glucogenic adipokine discovered in 2016. Asprosin induces rapid glucose releases from the liver. However, its molecular mechanisms and function are still unclear. Adaptation of energy substrates from fatty acid to glucose is recently considered a novel therapeutic target in heart failure treatment. We hypothesized that the asprosin is able to modulate cardiac mitochondrial functions and has important prognostic implications in dilated cardiomyopathy (DCM) patients. Methods We prospectively enrolled 50 patients (86% male, mean age 55 ± 13 years) with DCM and followed their 5-year major adverse cardiovascular events from 2012 to 2017. Comparing with healthy individuals, DCM patients had higher asprosin levels (191.2 versus 79.7 ng/mL, P < 0.01). Results During the 5-year follow-up in the study cohort, 16 (32.0%) patients experienced adverse cardiovascular events. Patients with lower asprosin levels (< 210 ng/mL) were associated with increased risks of adverse clinical outcomes with a hazard ratio of 7.94 (95% CI 1.88–33.50, P = 0.005) when compared patients with higher asprosin levels (≥ 210 ng/mL). Using cardiomyoblasts as a cellular model, we showed that asprosin prevented hypoxia-induced cell death and enhanced mitochondrial respiration and proton leak under hypoxia. Conclusions In patients with DCM, elevated plasma asprosin levels are associated with less adverse cardiovascular events in five years. The underlying protective mechanisms of asprosin may be linked to its functions relating to enhanced mitochondrial respiration under hypoxia.

HMGN dynamics and chromatin function

2003 ◽  
Vol 81 (3) ◽  
pp. 113-122 ◽  
Author(s):  
Frédéric Catez ◽  
Jae-Hwan Lim ◽  
Robert Hock ◽  
Yuri V Postnikov ◽  
Michael Bustin
Keyword(s):  
Binding Sites ◽  
Protein Composition ◽  
Nuclear Proteins ◽  
Chromatin Interactions ◽  
Binding Partners ◽  
Nucleosomal Dna ◽  
Transient Interactions ◽  
And Function ◽  
Nucleosome Binding

Recent studies indicate that most nuclear proteins, including histone H1 and HMG are highly mobile and their interaction with chromatin is transient. These findings suggest that the structure of chromatin is dynamic and the protein composition at any particular chromatin site is not fixed. Here we discuss how the dynamic behavior of the nucleosome binding HMGN proteins affects the structure and function of chromatin. The high intranuclear mobility of HMGN insures adequate supply of protein throughout the nucleus and serves to target these proteins to their binding sites. Transient interactions of the proteins with nucleosomes destabilize the higher order chromatin, enhance the access to nucleosomal DNA, and impart flexibility to the chromatin fiber. While roaming the nucleus, the HMGN proteins encounter binding partners and form metastable multiprotein complexes, which modulate their chromatin interactions. Studies with HMGN proteins underscore the important role of protein dynamics in chromatin function.Key words: HMG, nuclear proteins, chromatin, HMGN.

Intensive cardiovascular care units: structure, organization, and staffing

2021 ◽  
pp. 11-24
Author(s):  
Eric Bonnefoy-Cudraz ◽  
Tom Quinn
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Acute Myocardial Infarction ◽  
Working Group ◽  
Life Threatening ◽  
Coronary Care ◽  
The 1960S ◽  
And Function ◽  
Cardiovascular Care

The nature and complexity of acute cardiovascular care has changed markedly since the early days of the coronary care unit (CCU), introduced in the 1960s to prevent and treat life threatening arrhythmias associated with acute myocardial infarction. In the present day, the patient population is older, has more multimorbidity, comprises a range of conditions alongside critical cardiovascular disease and associated multi-organ failure, requiring increasingly sophisticated management. To reflect this, the Acute Cardiovascular Care Association (ACCA) published a comprehensive update of recommendations in 2018, developed by a multinational working group of experts. These recommendations, which inform this chapter, address the definition, structure, organisation and function of the contemporary intensive cardiovascular care unit (ICCU). Reflecting the modern casemix, three levels of acuity of care are described, and corresponding requirements for ICCU organisation defined. Recommendations on ICCU staffing (medical, nursing and allied professions), equipment and architecture, are presented, alongside considerations of the role of the ICCU within the wider hospital and cardiovascular care network.

The epidermal keratinocyte as a model for the study of gene regulation and cell differentiation

1997 ◽  
Vol 77 (2) ◽  
pp. 397-424 ◽  
Author(s):  
R. L. Eckert ◽  
J. F. Crish ◽  
N. A. Robinson
Keyword(s):  
Gene Regulation ◽  
Current Knowledge ◽  
Keratinocyte Differentiation ◽  
Marker Genes ◽  
Epidermal Keratinocyte ◽  
Major Cell Type ◽  
Life Threatening ◽  
Exogenous Agents ◽  
And Function

The epidermis is a dynamic, continually renewing structure that provides the organism with a life-sustaining interface with the environment. The major cell type of the epidermis, the epidermal keratinocyte, undergoes a complex and carefully choreographed program of differentiation. Aberrations in this process result in the genesis of a variety of debilitating and life-threatening diseases. In the present paper, we discuss the keratinocyte differentiation program and the exogenous agents that regulate differentiation. We describe the marker genes that have been utilized to study the process of gene regulation in epidermis. We describe the keratin proteins and studies that have identified keratin mutations that cause epidermal disease. We present recent information on regulation of keratinocyte gene expression and attempt to summarize current knowledge on the role of transcription factors in this process. We also discuss the process of cornified envelope assembly and the structure and function of the proteins that are thought to be precursors of this structure.

scholarly journals Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C–deficient mice

2004 ◽  
Vol 113 (3) ◽  
pp. 357-369 ◽  
Author(s):  
Vesna Nikolova ◽  
Christiana Leimena ◽  
Aisling C. McMahon ◽  
Ju Chiat Tan ◽  
Suchitra Chandar ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Nuclear Structure ◽  
Structure And Function ◽  
Lamin A ◽  
And Function ◽  
Deficient Mice

scholarly journals Role of CT scan in evaluation and management of intestinal obstruction

2017 ◽  
Vol 4 (7) ◽  
pp. 2257
Author(s):  
Gaurav Baid ◽  
Manohar Lal Dawan ◽  
Ashok Parmar
Keyword(s):  
Intestinal Obstruction ◽  
Common Symptom ◽  
Inclusion Criteria ◽  
X Ray ◽  
Pain Abdomen ◽  
Ct Findings ◽  
Life Threatening ◽  
Study Population ◽  
And Function

Background: Intestinal obstruction is one of the most common diseases in abdominal surgery. It can slowly lead to changes in intestinal structure and function, and in extreme cases it can be life-threatening. CT allows imaging of the abdominal contents outside the lumen, because of this advantage, the nature and site of the obstruction, especially extraluminal or intramural process, can be established.Methods: Prospective Hospital Based study. From January 2016 to November 2016 (11 months). 50 Patients presenting to Department of Surgery, whether in OPD or Emergency, with complaints suggestive of intestinal obstruction with in study duration eligible as per inclusion criteria will be included in the study.Results: In present study Majority (52.0%) of study population belonged to 41-60 years age group. The most common symptom was pain abdomen (94%). Majority (66%) patients showed multiple air fluid level on X-ray. In CT imaging, maximum 36% presented with dilated bowel loops. 86% were diagnosed as sub-acute intestinal obstruction, in USG. In present study, 60% patients were treated by surgery. Majority of patients (86.67%) CT findings matched with perop/ intraoperative findings. Accurate CT findings were helpful in guiding patient management. In our study, CT had the sensitivity of 86.67%, Specificity75%.Conclusions: Management decisions in intestinal obstruction remain notoriously difficult, relying on a combination of clinical and imaging factors to help stratify patients into conservative or surgical treatment.

scholarly journals Macrophages in bacterial lung diseases: phenotype and functions (review)

2019 ◽  
Vol 18 (1) ◽  
pp. 142-154
Author(s):  
E. G. Churina ◽  
A. V. Sitnikova ◽  
O. I. Urazova ◽  
S. P. Chumakova ◽  
M. V. Vins ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Literature Review ◽  
Lung Diseases ◽  
Functional Heterogeneity ◽  
Protective Function ◽  
Immunoregulatory Cells ◽  
Macrophage Plasticity ◽  
And Function ◽  
Disease Understanding

This literature review is devoted to the analysis of the role of macrophages in the immunopathogenesis of infectious lung diseases of bacterial etiology. The article summarizes information about the origin of macrophages, their phenotypic and functional heterogeneity. The mechanisms of impaired protective function of innate immunity are associated with the polarization of the program of maturation and activation of macrophages in the direction to tolerogenic or immunoregulatory cells with phenotype of M2. Alveolar macrophages perform a variety of functions (from pro-inflammatory to regenerative) in the development of inflammation in the respiratory organs. Their inherent plasticity suggests that the same macrophages can change their phenotype and function depending on the microenvironment in the inflammatory focus at different stages of the disease. Understanding the mechanisms that regulate macrophage plasticity will be an important step towards realizing the potential of personalized immunomodulatory therapy.

scholarly journals The Role of Co-Stimulatory Molecules in Chagas Disease

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 200 ◽  
Author(s):  
Bruna Pinto ◽  
Nayara Medeiros ◽  
Tereza Fontes-Cal ◽  
Isabela Naziazeno ◽  
Rodrigo Correa-Oliveira ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Latin American ◽  
Clinical Symptoms ◽  
Adaptive Immune Response ◽  
Chronic Phase ◽  
T Cell Response ◽  
Life Threatening ◽  
And Function ◽  
The Relationship

Chagas disease, caused by Trypanosoma cruzi, is a potentially life-threatening tropical disease endemic to Latin American countries that affects approximately 8 million people. In the chronic phase of the disease, individuals are classified as belonging to the indeterminate clinical form or to the cardiac and/or digestive forms when clinical symptoms are apparent. The relationship between monocytes and lymphocytes may be an important point to help clarify the complexity that surrounds the clinical symptoms of the chronic phase of Chagas disease. The co-stimulatory signals are essential to determining the magnitude of T cell response to the antigen. The signals are known to determine the regulation of subsequent adaptive immune response. However, little is known about the expression and function of these molecules in Chagas disease. Therefore, this review aims to discuss the possible role of main pathways of co-stimulatory molecule-receptor interactions in this pathology that could be crucial to understand the disease dynamics.

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