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https://www.readbyqxmd.com/read/27562362/repeat-exposure-to-group-a-streptococcal-m-protein-exacerbates-cardiac-damage-in-a-rat-model-of-rheumatic-heart-disease
#1
Davina Gorton, Suchandan Sikder, Natasha L Williams, Lisa Chilton, Catherine M Rush, Brenda L Govan, Madeleine W Cunningham, Natkunam Ketheesan
Rheumatic fever and rheumatic heart disease (RF/RHD) develop following repeated infection with group A streptococci (GAS). We used the Rat Autoimmune Valvulitis (RAV) model of RF/RHD to demonstrate that repetitive booster immunization with GAS-derived recombinant M protein (rM5) resulted in an enhanced anti-cardiac myosin antibody response that may contribute to the breaking of immune tolerance leading to RF/RHD and increased infiltration of heart valves by mononuclear cells. With each boost, more inflammatory cells were observed infiltrating heart tissue which could lead to severe cardiac damage...
August 25, 2016: Autoimmunity
https://www.readbyqxmd.com/read/27541593/preclinical-immunogenicity-and-safety-of-a-group-a-streptococcal-m-protein-based-vaccine-candidate
#2
Michael R Batzloff, Anne Fane, Davina Gorton, Manisha Pandey, Tania Rivera-Hernandez, Ainslie Calcutt, Grace Yeung, Jon Hartas, Linda Johnson, Catherine M Rush, James McCarthy, Natkunam Ketheesan, Michael F Good
Streptococcus pyogenes (group A streptococcus, GAS) causes a wide range of clinical manifestations ranging from mild self-limiting pyoderma to invasive diseases such as sepsis. Also of concern are the post-infectious immune-mediated diseases including rheumatic heart disease. The development of a vaccine against GAS would have a large health impact on populations at risk of these diseases. However, there is a lack of suitable models for the safety evaluation of vaccines with respect to post-infectious complications...
August 19, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27433366/triple-valvulopathy-and-jaccoud-s-arthropathy-a-case-report-and-literature-review
#3
Ali Naderi Mahabadi, Bassam Alhaddad, Stanley Ballou
Cardiac involvement is fairly common in patients with systemic lupus erythematosus (SLE). It may involve all layers of the heart and coronary arteries as well as the heart valves. We report an extremely rare presentation of valvulitis and valvular dysfunction associated with systemic lupus erythematosus. This is the first case of lupus valvulitis which required three mechanical prosthetic valve replacements with disease recurrence leading to a fatal outcome. This is, in our point of view, the consequence of aggressive natural history of the disease and perhaps late diagnosis and treatment of underlying SLE which was unsuccessful...
2016: Case Reports in Rheumatology
https://www.readbyqxmd.com/read/27310707/predicted-coverage-and-immuno-safety-of-a-recombinant-c-repeat-region-based-streptococcus-pyogenes-vaccine-candidate
#4
Celia McNeilly, Samantha Cosh, Therese Vu, Jemma Nichols, Anna Henningham, Andreas Hofmann, Anne Fane, Pierre R Smeesters, Catherine M Rush, Louise M Hafner, Natkuman Ketheesan, Kadaba S Sriprakash, David J McMillan
The C-terminal region of the M-protein of Streptococcus pyogenes is a major target for vaccine development. The major feature is the C-repeat region, consisting of 35-42 amino acid repeat units that display high but not perfect identity. SV1 is a S. pyogenes vaccine candidate that incorporates five 14mer amino acid sequences (called J14i variants) from differing C-repeat units in a single recombinant construct. Here we show that the J14i variants chosen for inclusion in SV1 are the most common variants in a dataset of 176 unique M-proteins...
2016: PloS One
https://www.readbyqxmd.com/read/27122431/sudden-death-due-to-undiagnosed-rheumatic-heart-disease-in-a-child
#5
Camille Rérolle, Maxime Faisant, Thierry Lefrancq, Pauline Saint-Martin
We report the case of a 5-year-old boy who died from complications of rheumatic heart disease with atypical presentation. He was hospitalized for recent inflammatory and neurological symptoms. He was diagnosed with viral encephalitis. He died the day after he was discharged. The macroscopic autopsy findings were unremarkable. Histology revealed typical rheumatic heart disease. Neuropathology showed cerebral infarction due to an embolic event linked with the rheumatic valvulitis. The cause of death was determined as heart failure due to rheumatic heart disease secondary to an undiagnosed acute rheumatic fever...
May 2016: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/26681305/pulmonary-artery-dilation-and-right-ventricular-function-in-acute-kawasaki-disease
#6
Fujito Numano, Chisato Shimizu, Adriana H Tremoulet, Dan Dyar, Jane C Burns, Beth F Printz
Coronary artery inflammation and aneurysm formation are the most common complications of Kawasaki disease (KD). Valvulitis and myocarditis are also well described and may lead to valvar regurgitation and left ventricular dysfunction. However, functional changes in the right heart have rarely been reported. We noted several acute KD patients with dilated pulmonary arteries (PA) and thus sought to systematically characterize PA size and right-heart function in an unselected cohort of KD patients cared for at a single clinical center...
March 2016: Pediatric Cardiology
https://www.readbyqxmd.com/read/25560735/mitral-valve-geometry-in-paediatric-rheumatic-mitral-regurgitation
#7
Michael Yeong, Marcus Silbery, Kirsten Finucane, Nigel J Wilson, Thomas L Gentles
Rheumatic mitral valve disease is associated with valvulitis and valvular regurgitation; however, the effect of the rheumatic process on the mitral valve geometry and function is not well understood. To assess mitral valve annulus remodelling in rheumatic mitral valve disease, 16 subjects aged 6-15 years with rheumatic mitral valve regurgitation [MR] [6 mild or moderate (Group 1), 10 severe (Group 2)] and 7 age- and body size-matched normal controls with adequate trans-thoracic echocardiograms were recruited...
April 2015: Pediatric Cardiology
https://www.readbyqxmd.com/read/25414841/animal-models-to-investigate-the-pathogenesis-of-rheumatic-heart-disease
#8
REVIEW
Catherine M Rush, Brenda L Govan, Suchandan Sikder, Natasha L Williams, Natkunam Ketheesan
Rheumatic fever (RF) and rheumatic heart disease (RHD) are sequelae of group A streptococcal (GAS) infection. Although an autoimmune process has long been considered to be responsible for the initiation of RF/RHD, it is only in the last few decades that the mechanisms involved in the pathogenesis of the inflammatory condition have been unraveled partly due to experimentation on animal models. RF/RHD is a uniquely human condition and modeling this disease in animals is challenging. Antibody and T cell responses to recombinant GAS M protein (rM) and the subsequent interactions with cardiac tissue have been predominantly investigated using a rat autoimmune valvulitis model...
2014: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/25282330/percutaneous-valvulation-of-failing-fontan-rationale-acute-effects-and-follow-up
#9
Sophie Malekzadeh-Milani, Magalie Ladouceur, Laurence Iserin, Younes Boudjemline
BACKGROUND: Fontan circulation is fragile and unfavourable evolution is frequent. Fontan physiology largely depends on respiration and gravity. The hypothesis for valvulation is that valvulation of the circuit reduces the effects of respiration and the proclive position, and increases anterograde flow towards the systemic circulation, with increasing exercise capacity and benefits for enteropathy. Because it originates from the bovine jugular vein, the Melody(®) valve (Medtronic, Minneapolis, MN, USA) is naturally designed to work in a low-pressure environment...
November 2014: Archives of Cardiovascular Diseases
https://www.readbyqxmd.com/read/25218009/results-of-transcatheter-pulmonary-valvulation-in-native-or-patched-right-ventricular-outflow-tracts
#10
Sophie Malekzadeh-Milani, Magalie Ladouceur, Sarah Cohen, Laurence Iserin, Younes Boudjemline
BACKGROUND: Although widely accepted worldwide, indications for percutaneous valve replacement are limited to treatment of dysfunction of prosthetic conduits inserted in the right ventricular outflow tract (RVOT). There has been little evaluation of the use of the Melody(®) valve for patched non-circular pulmonary pathways. AIM: To evaluate the outcomes of Melody valve insertion in patients with a patched non-circular RVOT. METHODS: We analysed procedural and outcomes data from 34 patients who underwent Melody valve implantation for a non-circular RVOT...
November 2014: Archives of Cardiovascular Diseases
https://www.readbyqxmd.com/read/24939149/pathologic-findings-in-native-infective-endocarditis
#11
Jennifer A Collins, Yang Zhang, Allen P Burke
BACKGROUND: There are few studies on the histologic findings in native infective endocarditis, especially regarding mimics of autoimmune valvulitis. METHODS: We prospectively studied 106 surgical specimens from 95 patients with a clinical diagnosis of infective endocarditis on native valves, and compared gross and histologic findings with culture results, underlying valve disease, risk factors and time interval from symptom onset to surgical intervention. RESULTS: There were 41 (39%) aortic, 33 (31%) mitral, 9 (9%) tricuspid, 1(...
December 2014: Pathology, Research and Practice
https://www.readbyqxmd.com/read/24659312/evaluation-of-echogenicity-of-the-heart-in-kawasaki-disease
#12
Hazumu Nagata, Kenichiro Yamamura, Kiyoshi Uike, Yasutaka Nakashima, Yuichiro Hirata, Eiji Morihana, Yumi Mizuno, Shiro Ishikawa, Toshiro Hara
Pathologic studies of the heart in patients with Kawasaki disease (KD) revealed vasculitis, valvulitis, myocarditis, and pericarditis. However, there have been no studies on the quantitative determination of multi-site echogenicity of the heart in KD patients. It is also undetermined whether the degree of echogenicity of each site of the heart in patients with KD might be related to the response to intravenous immunoglobulin (IVIG) treatment. In 81 KD patients and 30 control subjects, we prospectively analyzed echogenicity of the heart...
August 2014: European Journal of Pediatrics
https://www.readbyqxmd.com/read/24346820/identification-of-streptococcal-m-protein-cardiopathogenic-epitopes-in-experimental-autoimmune-valvulitis
#13
Christine A Kirvan, Jeffrey E Galvin, Silvia Hilt, Stanley Kosanke, Madeleine W Cunningham
The M protein of rheumatogenic group A streptococci induces carditis and valvulitis in Lewis rats and may play a role in pathogenesis of rheumatic heart disease. To identify the epitopes of M5 protein that produce valvulitis, synthetic peptides spanning A, B, and C repeat regions contained within the extracellular domain of the streptococcal M5 protein were investigated. A repeat region peptides NT4, NT5/6, and NT7 induced valvulitis similar to the intact pepsin fragment of M5 protein. T cell lines from rats with valvulitis recognized M5 peptides NT5/6 and NT6...
March 2014: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/23564686/autoimmune-myocarditis-valvulitis-and-cardiomyopathy
#14
Jennifer M Myers, DeLisa Fairweather, Sally A Huber, Madeleine W Cunningham
Myocarditis and valvulitis are inflammatory diseases affecting myocardium and valve. Myocarditis, a viral-induced disease of myocardium, may lead to dilated cardiomyopathy and loss of heart function. Valvulitis leads to deformed heart valves and altered blood flow in rheumatic heart disease. Animal models recapitulating these diseases are important in understanding the human condition. Cardiac myosin is a major autoantigen in heart, and antibodies and T cells to cardiac myosin are evident in inflammatory heart diseases...
2013: Current Protocols in Immunology
https://www.readbyqxmd.com/read/23129897/prognostic-value-of-clinical-and-doppler-echocardiographic-findings-in-children-and-adolescents-with-significant-rheumatic-valvular-disease
#15
Fátima Derlene da Rocha Araújo, Eugênio Marcos Andrade Goulart, Zilda Maria Alves Meira
INTRODUCTION: The diagnosis of acute rheumatic fever (RF) is based on clinical findings. However, during the chronic phase of the disease, the clinical approach is not sufficient for the follow-up of the patients and the Doppler echocardiography is a tool for the diagnosis of cardiac involvement. Prognostic variables that influence long-term outcomes are not well known. METHODS: 462 patients with RF according to Jones criteria were studied, and followed-up from the initial attack to 13...
July 2012: Annals of Pediatric Cardiology
https://www.readbyqxmd.com/read/22737215/augmented-tlr2-expression-on-monocytes-in-both-human-kawasaki-disease-and-a-mouse-model-of-coronary-arteritis
#16
I-Chun Lin, Ho-Chang Kuo, Ying-Jui Lin, Feng-Shen Wang, Lin Wang, Shun-Chen Huang, Shao-Ju Chien, Chien-Fu Huang, Chih-Lu Wang, Hong-Ren Yu, Rong-Fu Chen, Kuender D Yang
BACKGROUND: Kawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis. METHODS: Recruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009...
2012: PloS One
https://www.readbyqxmd.com/read/21801375/the-accuracy-of-echocardiography-versus-surgical-and-pathological-classification-of-patients-with-ruptured-mitral-chordae-tendineae-a-large-study-in-a-chinese-cardiovascular-center
#17
COMPARATIVE STUDY
Weichun Wu, Xiaoliang Luo, Linlin Wang, Xin Sun, Yong Jiang, Shunwei Huo, Dalou Tu, Zhigang Bai, Hao Wang
BACKGROUND: The accuracy of echocardiography versus surgical and pathological classification of patients with ruptured mitral chordae tendineae (RMCT) has not yet been investigated with a large study. METHODS: Clinical, hemodynamic, surgical, and pathological findings were reviewed for 242 patients with a preoperative diagnosis of RMCT that required mitral valvular surgery. Subjects were consecutive in-patients at Fuwai Hospital in 2002-2008. Patients were evaluated by thoracic echocardiography (TTE) and transesophageal echocardiography (TEE)...
2011: Journal of Cardiothoracic Surgery
https://www.readbyqxmd.com/read/20921914/fulminant-valvulitis-from-acute-rheumatic-fever-successful-use-of-extracorporeal-support
#18
Frankie E Crain, Nga Pham, Scott F Wagoner, Peter T Rycus, Kevin O Maher, James D Fortenberry
OBJECTIVE: To describe an unusual case of fulminant rheumatic fever presenting acutely as severe respiratory failure managed with extracorporeal membrane oxygenation and ultimately valve replacement while on extracorporeal membrane oxygenation. DESIGN: Case report. SETTING: Large quaternary care pediatric intensive care unit. PATIENT: A 6-yr-old female with profound respiratory failure found to be due to mitral valve dysfunction stemming from acute fulminant rheumatic fever...
May 2011: Pediatric Critical Care Medicine
https://www.readbyqxmd.com/read/20206182/an-alternative-technique-for-the-induction-of-autoimmune-valvulitis-in-a-rat-model-of-rheumatic-heart-disease
#19
D Gorton, S Blyth, J G Gorton, B Govan, N Ketheesan
We currently use a rat model in our investigations into human rheumatic heart disease (RHD). This model traditionally involves footpad immunization with antigen emulsified in complete Freund's adjuvant (CFA). Trials to find an alternative adjuvant to CFA which produced a Th1 type response in the rats resulting in carditis were unsuccessful. However, hock immunization was found to produce the desired valvular pathology without the adverse inflammatory side-effects associated with CFA. We therefore consider the hock an ideal site for immunization, particularly when using CFA...
April 15, 2010: Journal of Immunological Methods
https://www.readbyqxmd.com/read/20093488/left-sided-cardiac-valvulitis-in-tristetraprolin-deficient-mice-the-role-of-tumor-necrosis-factor-alpha
#20
Sanjukta Ghosh, Mark J Hoenerhoff, Natasha Clayton, Page Myers, Deborah J Stumpo, Robert R Maronpot, Perry J Blackshear
Inflammation may play a role in the etiology of both degenerative and rheumatic cardiac valve diseases. We report here that mice deficient in tristetraprolin (TTP), a protein with known anti-inflammatory functions, develop severe left-sided cardiac valvulitis. TTP is an mRNA binding protein that inhibits inflammation by destabilizing the mRNA encoding tumor necrosis factor alpha (TNF). This leads in turn to a TNF-excess syndrome characterized by systemic inflammation. Evaluation of hearts from TTP-/- mice demonstrated gross thickening of the mitral and aortic but not the tricuspid or pulmonary valves, accompanied by inflammatory cell infiltrates...
March 2010: American Journal of Pathology
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