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Sample records for acute lymphocytic myocarditis

  1. Acute viral myocarditis

    PubMed Central

    Dennert, Robert; Crijns, Harry J.; Heymans, Stephane

    2008-01-01

    Acute myocarditis is one of the most challenging diagnosis in cardiology. At present, no diagnostic gold standard is generally accepted, due to the insensitivity of traditional diagnostic tests. This leads to the need for new diagnostic approaches, which resulted in the emergence of new molecular tests and a more detailed immunohistochemical analysis of endomyocardial biopsies. Recent findings using these new diagnostic tests resulted in increased interest in inflammatory cardiomyopathies and a better understanding of its pathophysiology, the recognition in overlap of virus-mediated damage, inflammation, and autoimmune dysregulation. Novel results also pointed towards a broader spectrum of viral genomes responsible for acute myocarditis, indicating a shift of enterovirus and adenovirus to parvovirus B19 and human herpes virus 6. The present review proposes a general diagnostic approach, focuses on the viral aetiology and associated autoimmune processes, and reviews treatment options for patients with acute viral myocarditis. PMID:18617482

  2. Infant acute myocarditis mimicking acute myocardial infarction

    PubMed Central

    Tilouche, Samia; Masmoudi, Tasnim; Sahnoun, Maha; Chkirbène, Youssef; Mestiri, Sarra; Boughamoura, Lamia; Ben Dhiab, Mohamed; Souguir, Mohamed Kamel

    2016-01-01

    Myocarditis is an inflammatory disease of the myocardium with heterogeneous clinical manifestations and progression. In clinical practice, although there are many methods of diagnosis of acute myocarditis, the diagnosis remains an embarrassing dilemma for clinicians. The authors report the case of 9-month-old infant who was brought to the Pediatric Emergency Department with sudden onset dyspnea. Examination disclosed heart failure and resuscitation was undertaken. The electrocardiogram showed an ST segment elevation in the anterolateral leads with a mirror image. Cardiac enzyme tests revealed a significant elevation of troponin and creatine phosphokinase levels. A diagnosis of acute myocardial infarction was made, and heparin therapy was prescribed. The infant died on the third day after admission with cardiogenic shock. The autopsy showed dilatation of the ventricles and massive edema of the lungs. Histological examinations of myocardium samples revealed the presence of a marked lymphocytic infiltrate dissociating myocardiocytes. Death was attributed to acute myocarditis. The authors call attention to the difficulties of differential diagnosis between acute myocarditis and acute myocardial infarction especially in children, and to the important therapeutic implications of a correct diagnosis. PMID:28210569

  3. Improving outcomes of acute myocarditis in children.

    PubMed

    Di Filippo, Sylvie

    2016-01-01

    Acute viral myocarditis may impair prognosis in children of all ages. Its true incidence is underestimated because of heterogeneity of presentation and outcome. Patients may either recover or progress to chronic cardiomyopathy or death. Improving short-term and long-term prognosis is challenging but can probably be achieved by new diagnostic techniques and novel targeted therapies. The objectives of this review are: (1) to detail the current state of knowledge of the pathophysiological mechanisms of acute myocarditis; (2) to provide an update on diagnostic tools such as magnetic resonance imaging and endomyocardial biopsy; and (3) to present new insights in therapeutic strategies, targeted therapies and management of fulminant cases. Options for improving outcomes in acute myocarditis in the pediatric population are discussed.

  4. Acute myocarditis triggering coronary spasm and mimicking acute myocardial infarction

    PubMed Central

    Kumar, Andreas; Bagur, Rodrigo; Béliveau, Patrick; Potvin, Jean-Michel; Levesque, Pierre; Fillion, Nancy; Tremblay, Benoit; Larose, Éric; Gaudreault, Valérie

    2014-01-01

    A 24-year-old healthy man consulted to our center because of typical on-and-off chest-pain and an electrocardiogram showing ST-segment elevation in inferior leads. An urgent coronary angiography showed angiographically normal coronary arteries. Cardiovascular magnetic resonance imaging confirmed acute myocarditis. Although acute myocarditis triggering coronary spasm is an uncommon association, it is important to recognize it, particularly for the management for those patients presenting with ST-segment elevation and suspect myocardial infarction and angiographically normal coronary arteries. The present report highlights the role of cardiovascular magnetic resonance imaging to identify acute myocarditis as the underlying cause. PMID:25276306

  5. Acute myocarditis triggering coronary spasm and mimicking acute myocardial infarction.

    PubMed

    Kumar, Andreas; Bagur, Rodrigo; Béliveau, Patrick; Potvin, Jean-Michel; Levesque, Pierre; Fillion, Nancy; Tremblay, Benoit; Larose, Eric; Gaudreault, Valérie

    2014-09-26

    A 24-year-old healthy man consulted to our center because of typical on-and-off chest-pain and an electrocardiogram showing ST-segment elevation in inferior leads. An urgent coronary angiography showed angiographically normal coronary arteries. Cardiovascular magnetic resonance imaging confirmed acute myocarditis. Although acute myocarditis triggering coronary spasm is an uncommon association, it is important to recognize it, particularly for the management for those patients presenting with ST-segment elevation and suspect myocardial infarction and angiographically normal coronary arteries. The present report highlights the role of cardiovascular magnetic resonance imaging to identify acute myocarditis as the underlying cause.

  6. Acute Lymphocytic Leukemia

    MedlinePlus

    ... hard for blood to do its work. In acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, there are too ... of white blood cells called lymphocytes or lymphoblasts. ALL is the most common type of cancer in ...

  7. Myocarditis

    MedlinePlus

    ... and diagnosis of myocarditis in adults. http://www.uptodate.com/home. Accessed Sept. 2, 2015. Cooper LT. ... and prognosis of myocarditis in adults. http://www.uptodate.com/home. Accessed Sept. 2, 2015. Cooper LT. ...

  8. Acute myocarditis associated with novel Middle east respiratory syndrome coronavirus.

    PubMed

    Alhogbani, Tariq

    2016-01-01

    The novel Middle east respiratory syndrome coronavirus (MeRS-CoV) has been identified as a cause of pneumonia; however, it has not been reported as a cause of acute myocarditis. A 60-year-old man presented with pneumonia and congestive heart failure. On the first day of admission, he was found to have an elevated troponin-l level and severe global left ventricular systolic dysfunction on echo-cardiography. The serum creatinine level was found mildly elevated. Chest radiography revealed in the lower lung fields accentuated bronchovascular lung markings and multiple small patchy opacities. Laboratory tests were negative for viruses known to cause myocarditis. Sputum sample was positive for MeRS-CoV. Cardiovascular magnetic resonance revealed evidence of acute myocarditis. the patient had all criteria specified by the international Consensus Group on CMR in Myocarditis that make a clinical suspicion for acute myocarditis. this was the first case that demonstrated that MeRS-CoV may cause acute myocarditis and acute-onset heart failure.

  9. Outcome of acute fulminant myocarditis in children

    PubMed Central

    Amabile, N; Fraisse, A; Bouvenot, J; Chetaille, P; Ovaert, C

    2006-01-01

    Objectives To highlight clinical features and outcome of acute fulminant myocarditis (AFM) in children. Methods Diagnostic criteria were (1) the presence of severe and acute heart failure; (2) left ventricular dysfunction on echocardiography; (3) recent history of viral illness; and (4) no history of cardiomyopathy. Results Eleven children were included between 1998 and 2003, at a median age of 1 (0 to 9) year. Their mean left ventricular ejection fraction (LVEF) was 22 (SD 9)% at presentation. A virus was identified in five patients: human parvovirus B19 (n  =  2), Epstein–Barr (n  =  1), varicella zoster (n  =  1), and coxsackie (n = 1). The median intensive care unit course was 13 (2–34) days. Intravenous inotropic support was required by nine patients and eight were mechanically ventilated. All patients received corticosteroid, associated with intravenous immunoglobulin in seven. Five patients experienced cardiocirculatory arrest that was successfully resuscitated in four. At a median follow up of 58.7 (33.8–83.1) months, the 10 survivors are asymptomatic with normalised LVEF. Conclusion Despite a severe presentation, the outcome of AFM is favourable. Aggressive symptomatic management is warranted and heart transplantation should be considered only when maximal supportive therapy does not lead to improvement. PMID:16449512

  10. Acute right ventricular myocarditis presenting with chest pain and syncope

    PubMed Central

    Mancio, Jennifer; Bettencourt, Nuno; Oliveira, Marco; Pires-Morais, Gustavo; Ribeiro, Vasco Gama

    2013-01-01

    Myocarditis is assumed to involve both ventricles equally. Right ventricular predominant involvement is rarely described. A case of acute viral right ventricular myocarditis presenting with chest pain and syncope, grade 3 atrioventricular block, right ventricular dilatation and free wall hypokinesia is reported. Cardiac MRI showed late enhancement of the right ventricular free wall without involvement of the left ventricle. Anti-Coxsackie A9 virus neutralising IgM-type antibodies titre was elevated. This case emphasises that manifestations of myocarditis can be limited to the right ventricle and should be considered in the differential diagnosis of right ventricular enlargement. PMID:24096068

  11. Fulminant lymphocytic myocarditis associated with orbital myositis and diaphragmatic paralysis.

    PubMed

    Kwon, Oh Hong; Kim, Mi-Na; Kim, Su-A; Seok, Hung Youl; Park, Seong-Mi; Kim, Byung-Jo; Kim, Chul-Hwan; Shim, Wan-Joo; Shim, Ju Sung; Lee, Min-Gu

    2016-01-01

    Although the clinical presentation of myocarditis is very diverse, ranging from mild dyspnea to hemodynamic collapse, myocarditis accompanied with extracardiac myositis is extremely rare. We report a single case of fulminant myocarditis associated with orbital myositis and diaphragmatic paralysis in a 40-year-old man, which was successfully managed by immunosuppressive therapy with steroid.

  12. Diagnostic relevance of humoral and cell-mediated immune reactions in patients with acute viral myocarditis.

    PubMed Central

    Maisch, B; Trostel-Soeder, R; Stechemesser, E; Berg, P A; Kochsiek, K

    1982-01-01

    Sera of 177 patients with acute myocarditis (10 coxsackie B 3/4, four influenza, four mumps, 15 cytomegalovirus, 144 undefined) were tested by indirect immunofluorescence for autoantibodies against heart and skeletal muscle and vital or air-dried adult cardiocytes. Antibody-dependent cytolysis, lymphocytotoxicity and antibody-dependent cellular lymphocytotoxicity were assessed using viral adult rat cardiocytes as target cells. Muscle-specific anti-sarcolemmal antibodies of the anti-myolemmal type--often associated with non-organ-specific anti-endothelial antibodies--were demonstrated in nine out of 10 patients with coxsackie B, in all patients with influenza and mumps and in 65 out of 144 patients with undefined myocarditis. In contrast, 13 out of 15 patients with cytomegalovirus myocarditis lacked anti-sarcolemmal antibodies but had low titre anti-inter fibrillary antibodies instead. In the presence of complement, anti-myolemmal antibodies induced cytolysis of vital cardiocytes, whereas hepatocytes remained unaffected. Titres of anti-myolemmal antibodies correlated with the degree of cardiocytolysis. The anti-myolemmal immunofluorescent pattern and the cytolytic serum activity could be absorbed with the respective viral antigens suggesting that these antibodies cross-react with moieties of the virus itself and may be both diagnostic and aetiological markers in acute viral myocarditis. Lymphocyte-mediated cytotoxicity against heterologous cardiac target cells could not be observed in our patients with myocarditis of proven viral aetiology. However, lymphocyte-mediated cytotoxicity was demonstrated in 10 ASA-positive and one ASA-negative patient with myocarditis of unknown origin. ASA-positive sera blocked lymphocytotoxicity in three of these patients. PMID:6288291

  13. What Is Acute Lymphocytic Leukemia (ALL)?

    MedlinePlus

    ... Adults About Acute Lymphocytic Leukemia (ALL) What Is Acute Lymphocytic Leukemia? Cancer starts when cells in the body begin ... Acute Lymphocytic Leukemia Research and Treatment? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  14. Targeted Therapy for Acute Lymphocytic Leukemia

    MedlinePlus

    ... Adults Treating Acute Lymphocytic Leukemia Targeted Therapy for Acute Lymphocytic Leukemia In recent years, new drugs that target specific ... Typical Treatment of Acute Lymphocytic Leukemia More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  15. Acute nonrheumatic streptococcal myocarditis resembling ST-elevation acute myocardial infarction in a young patient

    PubMed Central

    Jurado, Margarita; Porres-Aguilar, Mateo; Olivas-Chacon, Cristina; Porres-Muñoz, Mateo; Mukherjee, Debabrata; Taveras, Juan

    2015-01-01

    Acute myocarditis can be induced by various concomitant disease processes including infections. Most of these cases are viral in origin; however, bacterial infections are also implicated to a lesser degree. Group A streptococcus is a frequent culprit in bacterial-induced myocarditis. Its diagnosis is suspected by the presence of signs and symptoms of rheumatic fever as established by the Jones criteria. The development and refinement of current diagnostic tools has improved our ability to identify specific pathogens. It has been found that group A streptococcus may be responsible for more cases of infection-induced acute myocarditis than previously thought, and often without the clinical features of rheumatic fever. We present the case of a 43-year-old man hospitalized with chest pain that was initially diagnosed as an acute ST-elevation myocardial infarction. Further evaluation confirmed that his chief complaint was due to acute nonrheumatic streptococcal myocarditis. PMID:25829649

  16. Acute nonrheumatic streptococcal myocarditis resembling ST-elevation acute myocardial infarction in a young patient.

    PubMed

    Aguirre, Jose L; Jurado, Margarita; Porres-Aguilar, Mateo; Olivas-Chacon, Cristina; Porres-Muñoz, Mateo; Mukherjee, Debabrata; Taveras, Juan

    2015-04-01

    Acute myocarditis can be induced by various concomitant disease processes including infections. Most of these cases are viral in origin; however, bacterial infections are also implicated to a lesser degree. Group A streptococcus is a frequent culprit in bacterial-induced myocarditis. Its diagnosis is suspected by the presence of signs and symptoms of rheumatic fever as established by the Jones criteria. The development and refinement of current diagnostic tools has improved our ability to identify specific pathogens. It has been found that group A streptococcus may be responsible for more cases of infection-induced acute myocarditis than previously thought, and often without the clinical features of rheumatic fever. We present the case of a 43-year-old man hospitalized with chest pain that was initially diagnosed as an acute ST-elevation myocardial infarction. Further evaluation confirmed that his chief complaint was due to acute nonrheumatic streptococcal myocarditis.

  17. Myocarditis.

    PubMed

    Fung, Gabriel; Luo, Honglin; Qiu, Ye; Yang, Decheng; McManus, Bruce

    2016-02-05

    Viral myocarditis remains a prominent infectious-inflammatory disease for patients throughout the lifespan. The condition presents several challenges including varied modes of clinical presentation, a range of timepoints when patients come to attention, a diversity of approaches to diagnosis, a spectrum of clinical courses, and unsettled perspectives on therapeutics in different patient settings and in the face of different viral pathogens. In this review, we examine current knowledge about viral heart disease and especially provide information on evolving understanding of mechanisms of disease and efforts by investigators to identify and evaluate potential therapeutic avenues for intervention.

  18. Murine heart gene expression during acute Chagasic myocarditis

    PubMed Central

    Henao-Martínez, Andrés F.; Parra-Henao, Gabriel

    2015-01-01

    Chagas disease is transmitted by the parasite, Trypanosoma cruzi. Acute infection is characterized by acute myocarditis, although it is largely asymptomatic. Initial cardiac insult could be a determinant to the posterior development of chronic Chagasic cardiomyopathy, usually after 10 years in only approximately 30% of chronically infected patients. Herein, we characterized the acute gene expression profiling in heart tissue of two strains of mice infected with T. cruzi (tulahuen strain) at 4 weeks and their respective controls. Gene sequence data are available at NCBI under GEO accession number: GSE63847. The output of the genes expression suggests differences in involvement of protein kinase B (AKT), NCAM1, HLA-DRA, and ubiquitin C genes networks. These gene activation differences may correlate with myocardial contractility during the acute infection. PMID:26484182

  19. What Are the Key Statistics about Acute Lymphocytic Leukemia?

    MedlinePlus

    ... Leukemia (ALL) What Are the Key Statistics About Acute Lymphocytic Leukemia? The American Cancer Society’s estimates for acute lymphocytic ... Acute Lymphocytic Leukemia Research and Treatment? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  20. Rare Presentation of Lupus Myocarditis With Acute Heart Failure-A Case Report.

    PubMed

    Malhotra, Gurveen; Chua, Serafin; Kodumuri, Vamsi; Sivaraman, Sivashankar; Ramdass, Priya

    Systemic lupus erythematosus is an autoimmune disease with diffuse organ involvement. The cardiac complications include pericarditis, myocarditis, pulmonary hypertension, coronary vasculitis, and Libman-Sacks endocarditis. Symptomatic lupus myocarditis presenting with left ventricular dysfunction, acute heart failure, and pulmonary edema, although rare, is a life-threatening complication. We report the occurrence of acute lupus myocarditis in a 38-year-old postpartum female who had a cesarean section a week before presentation for preeclampsia. Initially she was managed for pneumonia but later found to have acute pericarditis and myocarditis related to systemic lupus erythematosus. She had a complicated hospital course including acute respiratory failure and cardiogenic shock. She was started on pulse dose steroids besides the treatment for heart failure and had a dramatic improvement within days.

  1. Recurrent Acute Nonrheumatic Streptococcal Myocarditis Mimicking STEMI in a Young Adult

    PubMed Central

    2014-01-01

    Myocarditis consists of an inflammation of the cardiac muscle, definitively diagnosed by endomyocardial biopsy. The causal agents are primarily infectious: in developed countries, viruses appear to be the main cause, whereas in developing countries rheumatic carditis, Chagas disease, and HIV are frequent causes. Furthermore, myocarditis can be indirectly induced by an infectious agent and occurs following a latency period during which antibodies are created. Typically, myocarditis observed in rheumatic fever related to group A streptococcal (GAS) infection occurs after 2- to 3-week period of latency. In other instances, myocarditis can occur within few days following a streptococcal infection; thus, it does not fit the criteria for rheumatic fever. Myocarditis classically presents as acute heart failure, and can also be manifested by tachyarrhythmia or chest pain. Likewise, GAS-related myocarditis reportedly mimics myocardial infarction (MI) with typical chest pain, electrocardiograph changes, and troponin elevation. Here we describe a case of recurrent myocarditis, 5 years apart, with clinical presentation imitating an acute MI in an otherwise healthy 37-year-old man. Both episodes occurred 3 days after GAS pharyngitis and resolved quickly following medical treatment. PMID:24963417

  2. What Should You Ask Your Doctor about Acute Lymphocytic Leukemia?

    MedlinePlus

    ... Types What Should You Ask Your Doctor About Acute Lymphocytic Leukemia? It is important to have frank, honest discussions ... Your Doctor About Acute Lymphocytic Leukemia? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  3. Acute myocarditis with normal wall motion detected with 2D speckle tracking echocardiography

    PubMed Central

    Niel, Johannes; Aichinger, Josef; Ebner, Christian

    2016-01-01

    Summary We present the case of a 26-year-old male with acute tonsillitis who was referred for coronary angiography because of chest pain, elevated cardiac biomarkers, and biphasic T waves. The patient had no cardiovascular risk factors. Echocardiography showed no wall motion abnormalities and no pericardial effusion. 2D speckle tracking revealed distinct decreased regional peak longitudinal systolic strain in the lateral and posterior walls. Ischemic disease was extremely unlikely in view of his young age, negative family history regarding coronary artery disease, and lack of regional wall motion abnormalities on the conventional 2D echocardiogram. Coronary angiography was deferred as myocarditis was suspected. To confirm the diagnosis, cardiac magnetic resonance tomography (MRT) was performed, showing subepicardial delayed hyperenhancement in the lateral and posterior walls correlating closely with the strain pattern obtained by 2D speckle tracking echocardiography. With a working diagnosis of acute myocarditis associated with acute tonsillitis, we prescribed antibiotics and nonsteroidal anti-inflammatory drugs. The patient’s clinical signs resolved along with normalization of serum creatine kinase (CK) levels, and the patient was discharged on the third day after admission. Learning points Acute myocarditis can mimic acute coronary syndromes.Conventional 2D echocardiography lacks specific features for detection of subtle regional wall motion abnormalities.2D speckle tracking expands the scope of echocardiography in identifying myocardial dysfunction derived from edema in acute myocarditis. PMID:27249814

  4. Percutaneous extracorporeal membrane oxygenation for cardiogenic shock due to acute fulminant myocarditis.

    PubMed

    Fayssoil, Abdallah; Nardi, Olivier; Orlikowski, David; Combes, Alain; Chastre, Jean; Annane, Djillali

    2010-02-01

    Percutaneous extracorporeal membrane oxygenation is an invasive technique that provides emergent circulatory support for patients with cardiogenic shock. We report a favorable outcome of an acute fulminant myocarditis in a 25-year-old myasthenia patient with cardiogenic shock supported by percutaneous extracorporeal membrane oxygenation.

  5. Ultra-low dose comprehensive cardiac CT imaging in a patient with acute myocarditis.

    PubMed

    Tröbs, Monique; Brand, Michael; Achenbach, Stephan; Marwan, Mohamed

    2014-01-01

    The ability of contrast-enhanced CT to detect "late enhancement" in a fashion similar to magnetic resonance imaging has been previously reported. We report a case of acute myocarditis with coronary CT angiography as well as "late enhancement" imaging with ultra-low effective radiation dose.

  6. ST-segment elevation mimicking myocardial infarction after hydrochloric acid ingestion: Acute caustic myocarditis.

    PubMed

    San Antonio, Rodolfo; Pujol López, Margarida; Perea, Rosario Jesús; Sabaté, Manel

    ST-segment elevation after hydrochloric acid ingestion has barely been described in the literature, without identification of its causal mechanism. We hypothesize that acute caustic myocarditis, by direct contact between necrotic upper gastrointestinal tract and pericardium may induce the ECG findings.

  7. A case report of lethal post-viral lymphocytic myocarditis with exclusive location in the right ventricle.

    PubMed

    Crudele, Graziano Domenico Luigi; Amadasi, Alberto; Marasciuolo, Laura; Rancati, Alessandra; Gentile, Guendalina; Zoja, Riccardo

    2016-03-01

    The inflammatory involvement of vital organs may represent a dangerous and life-threatening situation: in particular, the inflammation of the myocardial tissue of the heart may lead to severe consequences since the clinical history of the disease may be completely asymptomatic, any clinical sign may be lacking, thus preventing correct diagnosis and treatment. This may occur even in the case of myocarditis and may lead to unexpected death whose cause can be assessable only by means of a thorough histopathological examination. The article reports the case of 61-year old female who developed a flu-like syndrome with very few symptoms, followed by sudden death in three weeks. The autopsy and following histopathological investigations identified the cause of death in a post-viral lymphocytic myocarditis, probably related to the previous infectious disease, and alternative causes (as arrhythmic ventricular dysplasia, vasculitis, sarcoidosis and giant cell myocarditis) were excluded. The exclusive location in the right ventricle was a peculiar finding. The case highlights the importance of the myocardium of the right ventricle, a tissue which is often less considered even in histopathological surveys. The exclusive location of myocarditis in the right ventricle is a rare event but in this case fully responsible for death.

  8. Role of the innate immune system in acute viral myocarditis.

    PubMed

    Huang, Chien-Hua; Vallejo, Jesus G; Kollias, George; Mann, Douglas L

    2009-05-01

    Although the adaptive immune system is thought to play an important role in the pathogenesis of viral myocarditis, the role of the innate immune system has not been well defined. To address this deficiency, we employed a unique line of mice that harbor a genomic "knock in" of a mutated TNF gene lacking the AU rich element (TNF(ARE/ARE)) that is critical for TNF mRNA stability and translation, in order to examine the contribution of the innate immune system in encephalomyocarditis-induced myocarditis (EMCV). Heterozygous mice (TNF(ARE/+)) were infected with 500 plaque-forming units of EMCV. TNF(ARE/+)mice had a significantly higher 14-day mortality and myocardial inflammation when compared to littermate control mice. Virologic studies showed that the viral load at 14 days was significantly lower in the hearts of TNF(ARE/+) mice. TNF(ARE/+) mice had an exaggerated proinflammatory cytokine and chemokine response in the heart following EMCV infection. Modulation of the innate immune response in TNF(ARE/+) mice by the late administration of prednisolone resulted in a significant improvement in survival and decreased cardiac inflammation, whereas early administration of prednisolone resulted in a blunted innate response and increased mortality in littermate control mice. Viewed together, these data suggest that the duration and degree of activation of the innate immune system plays a critical role in determining host outcomes in experimental viral myocarditis.

  9. Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

    PubMed Central

    Gotzhein, Frauke; Escher, Felicitas; Blankenberg, Stefan; Westermann, Dirk

    2017-01-01

    Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice. PMID:28352641

  10. Macrophages and galectin 3 play critical roles in CVB3-induced murine acute myocarditis and chronic fibrosis.

    PubMed

    Jaquenod De Giusti, Carolina; Ure, Agustín E; Rivadeneyra, Leonardo; Schattner, Mirta; Gomez, Ricardo M

    2015-08-01

    Macrophage influx and galectin 3 production have been suggested as major players driving acute inflammation and chronic fibrosis in many diseases. However, their involvement in the pathogenesis of viral myocarditis and subsequent cardiomyopathy are unknown. Our aim was to characterise the role of macrophages and galectin 3 on survival, clinical course, viral burden, acute pathology, and chronic fibrosis in coxsackievirus B3 (CVB3)-induced myocarditis. Our results showed that C3H/HeJ mice infected with CVB3 and depleted of macrophages by liposome-encapsulated clodronate treatment compared with infected untreated mice presented higher viral titres but reduced acute myocarditis and chronic fibrosis, compared with untreated infected mice. Increased galectin 3 transcriptional and translational expression levels correlated with CVB3 infection in macrophages and in non-depleted mice. Disruption of the galectin 3 gene did not affect viral titres but reduced acute myocarditis and chronic fibrosis compared with C57BL/6J wild-type mice. Similar results were observed after pharmacological inhibition of galectin 3 with N-acetyl-d-lactosamine in C3H/HeJ mice. Our results showed a critical role of macrophages and their galectin 3 in controlling acute viral-induced cardiac injury and the subsequent fibrosis. Moreover, the fact that pharmacological inhibition of galectin 3 induced similar results to macrophage depletion regarding the degree of acute cardiac inflammation and chronic fibrosis opens up the possibility of new pharmacological strategies for viral myocarditis.

  11. How Is Acute Lymphocytic Leukemia Classified?

    MedlinePlus

    ... Adults Early Detection, Diagnosis, and Types How Is Acute Lymphocytic Leukemia Classified? Most types of cancers are assigned numbered ... ALL are now named as follows: B-cell ALL Early pre-B ALL (also called pro-B ...

  12. How Is Acute Lymphocytic Leukemia Diagnosed?

    MedlinePlus

    ... Adults Early Detection, Diagnosis, and Types How Is Acute Lymphocytic Leukemia Diagnosed? Certain signs and symptoms can suggest that ... described below. Tests used to diagnose and classify ALL If your doctor thinks you have leukemia, he ...

  13. Successful clearance of human parainfluenza virus type 2 viraemia with intravenous ribavirin and immunoglobulin in a patient with acute myocarditis.

    PubMed

    Kalimuddin, Shirin; Sessions, October M; Hou, Yan'An; Ooi, Eng Eong; Sim, David; Cumaraswamy, Sivathasan; Tan, Teing Ee; Lai, Siang Hui; Low, Chian Yong

    2013-01-01

    Human parainfluenza virus (HPIV) infection as an aetiology of acute viral myocarditis is rare, with only few cases reported in the literature to date. Here we report a case of fulminant HPIV-2 myocarditis in a 47 year-old man with viraemia who was successfully treated with intravenous ribavirin and intravenous immunoglobulin (IVIG). There are currently no recommendations on the treatment of HPIV myocarditis. We are, to our knowledge, the first to report a patient with a documented HPIV-2 viraemia that subsequently cleared after the initiation of antiviral therapy. Although it is difficult to definitively attribute the patient's clinical improvement to ribavirin or IVIG alone, our case does suggest that clinicians may wish to consider initiating ribavirin and IVIG in patients with HPIV myocarditis and persistent viraemia not responding to supportive measures alone.

  14. In vivo T2* weighted MRI visualizes cardiac lesions in murine models of acute and chronic viral myocarditis

    PubMed Central

    Helluy, Xavier; Sauter, Martina; Ye, Yu-Xiang; Lykowsky, Gunthard; Kreutner, Jakob; Yilmaz, Ali; Jahns, Roland; Boivin, Valerie; Kandolf, Reinhard; Jakob, Peter M.; Hiller, Karl-Heinz; Klingel, Karin

    2017-01-01

    Objective Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis. Results Here we present the discovery of a novel endogenous T2* MRI contrast of myocardial lesions in murine models of acute and chronic CVB3 myocarditis. The evaluation of infected hearts ex vivo and in vivo by 3D T2w and T2*w MRI allowed direct localization of virus-induced myocardial lesions without any MRI tracer or contrast agent. T2*w weighted MRI is able to detect both small cardiac lesions of acute myocarditis and larger necrotic areas at later stages of chronic myocarditis, which was confirmed by spatial correlation of MRI hypointensity in myocardium with myocardial lesions histologically. Additional in vivo and ex vivo MRI analysis proved that the contrast mechanism was due to a strong paramagnetic tissue alteration in the vicinity of myocardial lesions, effectively pointing towards iron deposits as the primary contributor of contrast. The evaluation of the biological origin of the MR contrast by specific histological staining and transmission electron microscopy revealed that impaired iron metabolism primarily in mitochondria caused iron deposits within necrotic myocytes, which induces strong magnetic susceptibility in myocardial lesions and results in strong T2* contrast. Conclusion This T2*w MRI technique provides a fast and sensitive diagnostic tool to determine the patterns and the severity of acute and chronic enteroviral myocarditis and the precise

  15. Rapidly fatal community-acquired pneumonia due to Klebsiella pneumoniae complicated with acute myocarditis and accelerated idioventricular rhythm.

    PubMed

    Chuang, Tzu-Yi; Lin, Chou-Jui; Lee, Shih-Wei; Chuang, Chun-Pin; Jong, Yuh-Shiun; Chen, Wen-Jone; Hsueh, Po-Ren

    2012-08-01

    We describe a previously healthy 52-year-old man with rapidly fatal community-acquired pneumonia caused by Klebsiella pneumoniae. The patient developed acute renal dysfunction, accelerated idioventricular rhythm (acute myocarditis), lactic acidosis and septic shock. He died within 15 hours after admission despite intravenous levofloxacin (750 mg daily) and aggressive medical treatment.

  16. Acute Fulminant Myocarditis Successfully Bridged to Recovery with Left Ventricular Assist Device and Complicated by Flail Mitral Valve

    PubMed Central

    Duyuler, Pınar Türker; Duyuler, Serkan; Şahan, Ekrem; Küçüker, Şeref Alp

    2016-01-01

    Acute fulminant myocarditis is a life-threatening inflammatory disease of the myocardium characterized by the rapid deterioration of the hemodynamic status of the affected individual. With prompt recognition and appropriate management, complete recovery of ventricular function is likely within a few weeks. We introduce a 28-year-old man with acute fulminant myocarditis, who experienced circulatory collapse following acute angina and dyspnea. The patient had high troponin levels with low ejection fraction and normal coronary arteries. He was successfully bridged to recovery with a left ventricular assist device but was complicated by flail mitral valve. Perioperative myocardial biopsy was also compatible with myocarditis. At 4 months’ follow-up, the patient was stable with functional capacity I according to the New York Heart Association’s classification. A possible mechanism for this very rare complication is the rupture of the chordal structure secondary to the fragility of an inflamed subvalvular apparatus stretched by a recovered ventricle. PMID:27403189

  17. Lymphocyte populations in acute viral gastroenteritis.

    PubMed Central

    Dolin, R; Reichman, R C; Fauci, A S

    1976-01-01

    Viral gastroenteritis was induced in 16 of 24 normal volunteers after oral administration of either the Norwalk or Hawaii agents. Clinical illness lasted for 24 to 48 h and resolved spontaneously. During acute illness, a transient lymphopenia was noted which involved all lymphocyte subpopulations (thymus-and bone marrow-derived, and null cells). No circulating lymphocytotoxins were detected, and the lymphocytes remaining in the circulation responded normally to mitogenic stimuli. The acute lymphopenia occurred at the time that mononuclear cell infiltration of the jejunal mucosa has been noted. These findings are consistent with the occurrence of a redistribution of circulating lymphocytes during acute illness, with accumulation of lymphocytes at the site of infection in the gut. PMID:1085751

  18. Coxsackievirus B3 Directly Induced Th17 Cell Differentiation by Inhibiting Nup98 Expression in Patients with Acute Viral Myocarditis

    PubMed Central

    Long, Qi; Liao, Yu-Hua; Xie, Yu; Liang, Wei; Cheng, Xiang; Yuan, Jing; Yu, Miao

    2016-01-01

    Th17 cells play a key role in the progression of coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC). However, the direct effect of virus on Th17 cell differentiation is still unknown. Recently, nucleoporin (Nup) 98 has been proved to be associated with lymphocyte differentiation. Therefore, we investigated whether Nup98 mediated Th17 cell differentiation in AVMC. In our study, patients with AVMC and healthy controls were recruited. The results showed that CVB3 could enter into the CD4+ T cells in AVMC patients and healthy controls. After transfecting purified CD4+ T cells with CVB3 in vitro, the Th17 cell frequency, IL-17 secretion, and RORγT synthesis were increased while the Nup98 levels were decreased. Furthermore, down-regulating Nup98 expression by siRNA-Nup98 in CD4+ T cells resulted in the elevated Th17 cell frequency and IL-17 secretion, along with enhanced levels of RORγT, dissociative p300/CBP, and acetylated Stat3. Up-regulation of Nup98 expression by pcDNA3.1-Nup98 showed the opposite effects. Our results suggested that CVB3 directly induced CD4+ T cell differentiation into Th17 cells by inhibiting Nup98 expression, representing a therapeutic target in AVMC. PMID:28018858

  19. [Human chronic chagasic myocarditis: quantitative study of CD4+ and CD8+ lymphocytes in inflammatory exudates].

    PubMed

    Tostes Júnior, S; Lopes, E R; Pereira, F E; Chapadeiro, E

    1994-01-01

    Myocardial exsudate CD4+ and CD8+ lymphocytes were counted in transmural left ventricular free wall frozen sections taken from 10 necropsied chronic cardiac chagasic patients. The cells were labeled with monoclonal antibodies using a streptavidin-biotin technique. We counted: 1) lymphocytes in the total exsudate (LTE) and, separately, 2) the lymphocytes touching or very near to myocells (LTVNM). Lymphocytes were considered very near whenever their own nuclear shortest nuclear diameter was larger than their distance from myocells. CD8+ lymphocytes were more numerous than CD4+ lymphocytes, especially among the LTVNM. The LTE CD4/CD8 ratio was 0.37 +/- 0.20, but the LTVNM CD4/CD8 ratio was smaller (0.23 +/- 0.11). Among the LTE, 34 +/- 11% of CD8+ (against 24 +/- 12% of CD4+) were LTVNM. All these differences were statistically significant. Both subtypes of T-lymphocytes were found to have an intimate relationship with both ruptured and unruptured myocells, and parasites were not seen. These findings are in accordance with the idea that the myocardial cell lesions in the cardiac form of human Chagas' disease are mediated mainly by T-cytotoxic lymphocytes.

  20. Proinflammatory Effects of Interferon Gamma in Mouse Adenovirus 1 Myocarditis

    PubMed Central

    McCarthy, Mary K.; Procario, Megan C.; Twisselmann, Nele; Wilkinson, J. Erby; Archambeau, Ashley J.; Michele, Daniel E.; Day, Sharlene M.

    2014-01-01

    ABSTRACT Adenoviruses are frequent causes of pediatric myocarditis. Little is known about the pathogenesis of adenovirus myocarditis, and the species specificity of human adenoviruses has limited the development of animal models, which is a significant barrier to strategies for prevention or treatment. We have developed a mouse model of myocarditis following mouse adenovirus 1 (MAV-1) infection to study the pathogenic mechanisms of this important cause of pediatric myocarditis. Following intranasal infection of neonatal C57BL/6 mice, we detected viral replication and induction of interferon gamma (IFN-γ) in the hearts of infected mice. MAV-1 caused myocyte necrosis and induced substantial cellular inflammation that was composed predominantly of CD3+ T lymphocytes. Depletion of IFN-γ during acute infection reduced cardiac inflammation in MAV-1-infected mice without affecting viral replication. We observed decreased contractility during acute infection of neonatal mice, and persistent viral infection in the heart was associated with cardiac remodeling and hypertrophy in adulthood. IFN-γ is a proinflammatory mediator during adenovirus-induced myocarditis, and persistent adenovirus infection may contribute to ongoing cardiac dysfunction. IMPORTANCE Studying the pathogenesis of myocarditis caused by different viruses is essential in order to characterize both virus-specific and generalized factors that contribute to disease. Very little is known about the pathogenesis of adenovirus myocarditis, which is a significant impediment to the development of treatment or prevention strategies. We used MAV-1 to establish a mouse model of human adenovirus myocarditis, providing the means to study host and pathogen factors contributing to adenovirus-induced cardiac disease during acute and persistent infection. The MAV-1 model will enable fundamental studies of viral myocarditis, including IFN-γ modulation as a therapeutic strategy. PMID:25320326

  1. New Echocardiographic Findings Correlate with Intramyocardial Inflammation in Endomyocardial Biopsies of Patients with Acute Myocarditis and Inflammatory Cardiomyopathy

    PubMed Central

    Escher, Felicitas; Kasner, Mario; Kühl, Uwe; Heymer, Johannes; Wilkenshoff, Ursula; Tschöpe, Carsten; Schultheiss, Heinz-Peter

    2013-01-01

    Background. The diagnosis of acute myocarditis (AMC) and inflammatory cardiomyopathy (DCMi) can be difficult. Speckle tracking echocardiography with accurate assessments of regional contractility could have an outstanding importance for the diagnosis. Methods and Results. N = 25 patients with clinically diagnosed AMC who underwent endomyocardial biopsies (EMBs) were studied prospectively. Speckle tracking imaging was examined at the beginning and during a mean follow-up period of 6.2 months. In the acute phase patients had markedly decreased left ventricular (LV) systolic function (mean LV ejection fraction (LVEF) 40.4 ± 10.3%). At follow-up in n = 8 patients, inflammation persists, correlating with a significantly reduced fractional shortening (FS, 21.5 ± 6.0%) in contrast to those without inflammation in EMB (FS 32.1 ± 7.1%, P < 0.05). All AMC patients showed a reduction in global systolic longitudinal strain (LS, −8.36 ± −3.47%) and strain rate (LSR, 0.53 ± 0.29 1/s). At follow-up, LS and LRS were significantly lower in patients with inflammation, in contrast to patients without inflammation (−9.4 ± 1.4 versus −16.8 ± 2.0%, P < 0.0001; 0.78 ± 0.4 versus 1.3 ± 0.3 1/s). LSR and LS correlate significantly with lymphocytic infiltrates (for CD3 r = 0.7, P < 0.0001, and LFA-1 r = 0.8, P < 0.0001). Conclusion. Speckle tracking echocardiography is a useful adjunctive assisting tool for evaluation over the course of intramyocardial inflammation in patients with AMC and DCMi. PMID:23576857

  2. Myocarditis (image)

    MedlinePlus

    Myocarditis is inflammation and weakness of the heart muscle usually caused by a viral infection that reaches ... the influenza (flu) virus, Coxsackie virus, and adenovirus. Myocarditis can damage the heart muscle causing it to ...

  3. Acute necrotizing eosinophilic myocarditis in a patient taking Garcinia cambogia extract successfully treated with high-dose corticosteroids.

    PubMed

    Allen, Scott F; Godley, Robert W; Evron, Joshua M; Heider, Amer; Nicklas, John M; Thomas, Michael P

    2014-12-01

    A previously healthy 48-year-old woman was evaluated for lightheadedness and chest heaviness 2 weeks after starting the herbal supplement Garcinia cambogia. She was found to be hypotensive and had an elevated serum troponin level. The patient had a progressive clinical decline, ultimately experiencing fulminant heart failure and sustained ventricular arrhythmias, which required extracorporeal membrane oxygenation support. Endomyocardial biopsy results were consistent with acute necrotizing eosinophilic myocarditis (ANEM). High-dose corticosteroids were initiated promptly and her condition rapidly improved, with almost complete cardiac recovery 1 week later. In conclusion, we have described a case of ANEM associated with the use of Garcinia cambogia extract.

  4. What Are the Risk Factors for Acute Lymphocytic Leukemia?

    MedlinePlus

    ... and Prevention What Are the Risk Factors for Acute Lymphocytic Leukemia? A risk factor is something that affects your ... this is unknown. Having an identical twin with ALL Someone who has an identical twin who develops ...

  5. Myocarditis - pediatric

    MedlinePlus

    ... enable JavaScript. Pediatric myocarditis is inflammation of the heart muscle in an infant or young child. Causes Myocarditis is rare in ... the infection. This can lead to symptoms of heart failure. ... to detect. However, in newborns and infants, symptoms may sometimes appear suddenly. Symptoms may include: ...

  6. Arrhythmias in viral myocarditis and pericarditis.

    PubMed

    Baksi, A John; Kanaganayagam, G Sunthar; Prasad, Sanjay K

    2015-06-01

    Acute viral myocarditis and acute pericarditis are self-limiting conditions that run a benign course and that may not involve symptoms that lead to medical assessment. However, ventricular arrhythmia is frequent in viral myocarditis. Myocarditis is thought to account for a large proportion of sudden cardiac deaths in young people without prior structural heart disease. Identification of acute myocarditis either with or without pericarditis is therefore important. However, therapeutic interventions are limited and nonspecific. Identifying those at greatest risk of a life-threatening arrhythmia is critical to reducing the mortality. This review summarizes current understanding of this challenging area in which many questions remain.

  7. Targeted Therapy for Acute Autoimmune Myocarditis with Nano-Sized Liposomal FK506 in Rats

    PubMed Central

    Matsuzaki, Takashi; Araki, Ryo; Tsuchida, Shota; Thanikachalam, Punniyakoti V.; Fukuta, Tatsuya; Asai, Tomohiro; Yamato, Masaki; Sanada, Shoji; Asanuma, Hiroshi; Asano, Yoshihiro; Asakura, Masanori; Hanawa, Haruo; Hao, Hiroyuki; Oku, Naoto; Takashima, Seiji; Kitakaze, Masafumi; Sakata, Yasushi; Minamino, Tetsuo

    2016-01-01

    Immunosuppressive agents are used for the treatment of immune-mediated myocarditis; however, the need to develop a more effective therapeutic approach remains. Nano-sized liposomes may accumulate in and selectively deliver drugs to an inflammatory lesion with enhanced vascular permeability. The aims of this study were to investigate the distribution of liposomal FK506, an immunosuppressive drug encapsulated within liposomes, and the drug’s effects on cardiac function in a rat experimental autoimmune myocarditis (EAM) model. We prepared polyethylene glycol-modified liposomal FK506 (mean diameter: 109.5 ± 4.4 nm). We induced EAM by immunization with porcine myosin and assessed the tissue distribution of the nano-sized beads and liposomal FK506 in this model. After liposomal or free FK506 was administered on days 14 and 17 after immunization, the cytokine expression in the rat hearts along with the histological findings and hemodynamic parameters were determined on day 21. Ex vivo fluorescent imaging revealed that intravenously administered fluorescent-labeled nano-sized beads had accumulated in myocarditic but not normal hearts on day 14 after immunization and thereafter. Compared to the administration of free FK506, FK506 levels were increased in both the plasma and hearts of EAM rats when liposomal FK506 was administered. The administration of liposomal FK506 markedly suppressed the expression of cytokines, such as interferon-γ and tumor necrosis factor-α, and reduced inflammation and fibrosis in the myocardium on day 21 compared to free FK506. The administration of liposomal FK506 also markedly ameliorated cardiac dysfunction on day 21 compared to free FK506. Nano-sized liposomes may be a promising drug delivery system for targeting myocarditic hearts with cardioprotective agents. PMID:27501378

  8. What's New in Adult Acute Lymphocytic Leukemia (ALL) in Adults Research?

    MedlinePlus

    ... in Adults About Acute Lymphocytic Leukemia (ALL) What’s New in Acute Lymphocytic Leukemia Research and Treatment? Researchers ... have the Philadelphia chromosome. Gene expression profiling This new lab technique is being studied to help identify ...

  9. Peripheral blood T and B lymphocytes during acute rheumatic fever.

    PubMed Central

    Lueker, R D; Abdin, Z H; Williams, R C

    1975-01-01

    Proportions and total numbers of thymus-derived (T) and bone marrow-derived (B) peripheral blood lymphocytes were studied in 53 patients with acute rheumatic fever, diagnosed on the basis of modifified Jones criteria. An elevation in both proportions and absolute numbers of cells bearing surface Ig was found in most patients, particularly during the first 7 days after onset. Conversely, T-cell proportions and numbers were often found to be depressed early in the acue phases of rheumatic fever. Proportions of cells bearing surface Ig did not correlate with another B-cell marker, the aggregated gamma globulin receptor, suggesting that such cells bearing surface Ig were not all B lymphocytes. Incuvation for 20 h at 37 per cent C of cells showing high proportions of surface Ig-bearing surface Ig in both normal and rheumatic fever subjects, although there was no appreciable increment in proportions of lymphocytes expressing T-cell markers. Patients with initial attacks showed higher percentages and total numbers of Ig-bearing lymphocytes (P smaller than 0.01) than did those with rneumatic fever recurrences. Elevations in numbers and proportions of peripheral blood lymphocytes bearing Ig appeared to correlate with the relative acute nature of the rheumatic fever attack. PMID:1091658

  10. Acute lymphocytic leukemia recurring in the spinal epidural space.

    PubMed

    Higashida, Tetsuhiro; Kawasaki, Takashi; Sakata, Katsumi; Tanabe, Yutaka; Kanno, Hiroshi; Yamamoto, Isao

    2007-08-01

    A 27-year-old man presented with a very rare spinal epidural mass associated with recurrence of acute lymphocytic leukemia (ALL) manifesting as acute progressive neurological deficits. The patient presented with shoulder pain and ambulatory difficulties 3 years after remission of ALL treated by bone marrow transplantation. Magnetic resonance imaging revealed an epidural mass extending from C-7 to T-3, which compressed the cord and extended to the intervertebral foramen along the roots. After decompression surgery, the symptoms dramatically improved. Histological examination showed clusters of immature lymphocytes consistent with recurrence of leukemia, so chemotherapy and radiation therapy were carried out. At 1 year after the operation, no local mass expansion or systemic progression of leukemia had occurred. Leukemic mass must be considered in the differential diagnosis of spinal epidural mass, even in patients with ALL.

  11. Silencing MicroRNA-155 Attenuates Cardiac Injury and Dysfunction in Viral Myocarditis via Promotion of M2 Phenotype Polarization of Macrophages.

    PubMed

    Zhang, Yingying; Zhang, Mengying; Li, Xueqin; Tang, Zongsheng; Wang, Xiangmin; Zhong, Min; Suo, Qifeng; Zhang, Yao; Lv, Kun

    2016-03-02

    Macrophage infiltration is a hallmark feature of viral myocarditis. As studies have shown that microRNA-155 regulates the differentiation of macrophages, we aimed to investigate the role of microRNA-155 in VM. We report that silencing microRNA-155 protects mice from coxsackievirus B3 induced myocarditis. We found that microRNA-155 expression was upregulated and localized primarily in heart-infiltrating macrophages and CD4(+) T lymphocytes during acute myocarditis. In contrast with wildtype (WT) mice, microRNA-155(-/-) mice developed attenuated viral myocarditis, which was characterized by decreased cardiac inflammation and decreased intracardiac CD45(+) leukocytes. Hearts of microRNA-155(-/-) mice expressed decreased levels of the IFN-γ and increased levels of the cytokines IL-4 and IL-13. Although total CD4(+) and regulatory T cells were unchanged in miR-155(-/-) spleen proportionally, the activation of T cells and CD4(+) T cell proliferation in miR-155(-/-) mice were significantly decreased. Beyond the acute phase, microRNA-15(5-/-) mice had reduced mortality and improved cardiac function during 5 weeks of follow-up. Moreover, silencing microRNA-155 led to increased levels of alternatively-activated macrophages (M2) and decreased levels of classically-activated macrophages (M1) in the heart. Combined, our studies suggest that microRNA-155 confers susceptibility to viral myocarditis by affecting macrophage polarization, and thus may be a potential therapeutic target for viral myocarditis.

  12. Myocarditis along with acute ischaemic cerebellar, pontine and lacunar infarction following viper bite.

    PubMed

    Bhatt, Alok; Menon, Aravind Ajakumar; Bhat, Rama; Ramamoorthi, Kusugodlu

    2013-09-06

    Cerebrovascular complications are rare following viper bites. A 65-year-old man presented with loss of consciousness and developed haemiparesis following a viper bite. Coagulation parameters were severely deranged. MRI showed acute ischaemic infarction on the left side in the precentral and postcentral gyrus, hemipons and cerebellum. Troponin T was elevated and transient left bundle branch block was seen. The patient had a good outcome following treatment with Anti Snake Venom and supportive therapy. Possible mechanisms of infarction are discussed.

  13. Myocardial imaging. Coxsackie myocarditis

    SciTech Connect

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-09-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1.

  14. Overview on chronic viral cardiomyopathy/chronic myocarditis.

    PubMed

    Schultheiss, H P; Kühl, U

    2006-01-01

    Myocarditis is most often induced by cardiotropic viruses and often resolves with minimal cardiac remodelling and without discernable prognostic impact. Acute myocarditis has a highly diverse clinical presentation (asymptomatic, infarct-like presentation, atrioventricular (AV)-block, atrial fibrillation, sudden death due to ventricular tachycardia, fulminant myocarditis with severely depressed contractility). Progression of myocarditis to its sequela, dilated cardiomyopathy (DCM), has been documented in 20% of cases and is pathogenically linked to chronic inflammation and viral persistence. Persistence of cardiotropic viruses (enterovirus, adenovirus) constitutes one of the predominant aetiological factors in DCM. Additionally, circulating autoantibodies to distinct cardiac autoantigens have been described in patients with DCM, providing evidence for autoimmune involvement. Since clinical complaints of myocarditis and DCM are unspecific, a positive effect of any specific therapy depends on an accurate biopsy-based diagnosis and characterization of the patients with histological, immunohistological and molecular biological methods (PCR), which have developed into sensitive tools for the detection of different viruses, active viral replication, and myocardial inflammation. The immunohistochemical characterization of infiltrates has supported a new era in the diagnosis of myocardial inflammation compared with the Dallas criteria, which has led to a new entity of secondary cardiomyopathies acknowledged by the WHO, the inflammatory cardiomyopathies (DCMi). Immunohistochemically quantified lymphocytes significantly better reflect troponin levels and correlate with findings by anti-myosin scintigraphy compared with the histological analysis. Furthermore, the orchestrated induction of endothelial cell adhesion molecules (CAMs) in 65% of DCM patients has confirmed that CAM induction is a prerequisite for lymphocytic infiltration in DCMi. The combination of these

  15. Unexpected hazard of illegal immigration: Outbreak of viral myocarditis exacerbated by confinement and deprivation in a shipboard cargo container.

    PubMed

    Li, Melissa K; Beck, Melinda A; Shi, Qing; Harruff, Richard C

    2004-06-01

    We present a group of 18 illegal immigrant stowaways who arrived in a shipboard cargo container suffering from gastroenteritis, dehydration, and malnutrition and showing evidence of viral myocarditis in 3 of 4 fatalities. Our investigation included an evaluation of the 2-week ocean voyage, analysis of medical records and laboratory results of the survivors, autopsies on the decedents, and viral studies on their heart tissue. Of 3 stowaways who died shipboard, 2 showed lymphocytic myocarditis and 1 could not be evaluated histologically due to decomposition. A fourth stowaway died 4 months after arrival with dilated cardiomyopathy and lymphocytic myocarditis. Reverse-transcriptase polymerase chain reaction and nucleotide sequencing of viral isolates from the decedents' heart tissues demonstrated Coxsackie virus B3 genome. We believe that these cases represent an outbreak of viral myocarditis, exacerbated by acute dehydration and malnutrition, due to confinement within the shipping container. Our evidence indicates that close confinement promoted the spread of the virus, and nutritional deprivation increased the stowaways' vulnerability. Furthermore, our observations support the conclusion, based on experimental studies, that nutritionally induced oxidative stress increased the virulence of the etiologic viral agent. In summary, these cases represent a potential infectious disease hazard of illegal immigration.

  16. Cranial radiation in childhood acute lymphocytic leukemia. Neuropsychologic sequelae

    SciTech Connect

    Whitt, J.K.; Wells, R.J.; Lauria, M.M.; Wilhelm, C.L.; McMillan, C.W.

    1984-08-01

    A battery of neuropsychologic tests was administered ''blindly'' to 18 children with acute lymphocytic leukemia (ALL) who had been randomly assigned to treatment regimens with or without cranial radiation. These children were all in complete continuous remission for more than 3 1/2 years and were no longer receiving therapy. The results indicated no substantial differences between groups as a function of radiation therapy. However, decreased neuropsychologic performance was found when the entire sample was compared with population norms. These data do not support the hypothesis that cranial radiation therapy is responsible for the neuropsychologic sequelae seen in these survivors of ALL. Post hoc multiple regression analysis indicated that parental education levels accounted for more of the neuropsychologic variability seen in these children than other factors such as age at diagnosis, type of therapy, or sex of child.

  17. L-asparaginase and venous thromboembolism in acute lymphocytic leukemia.

    PubMed

    Goyal, Gaurav; Bhatt, Vijaya Raj

    2015-01-01

    The occurrence of venous thromboembolism (VTE) in acute lymphocytic leukemia patients receiving L-asparaginase therapy may cause significant morbidity, neurological sequela and possibly worse outcomes. The prophylactic use of antithrombin infusion (to keep antithrombin activity >60%) or low molecular weight heparin (LMWH) may reduce the risk of VTE. The decision to continue L-asparaginase therapy after the development of VTE should be based on anticipated benefits, severity of VTE and the ability to continue therapeutic anticoagulation. In patients receiving asparaginase rechallenge, the use of therapeutic LMWH, monitoring of anti-Xa level and antithrombin level are important. Novel oral anticoagulants are not dependent on antithrombin level, hence offer theoretical advantages over LMWH for the prevention and therapy of asparaginase-related VTE.

  18. A Pitfall in the Diagnosis of Eosinophilic Myocarditis in a Patient who Received Steroid Therapy

    PubMed Central

    Watanabe, Yusuke; Wada, Hiroshi; Sakakura, Kenichi; Fujita, Hideo; Momomura, Shin-ichi

    2017-01-01

    Eosinophilic myocarditis is a rare form of myocardial inflammation that is characterized by the infiltration of eosinophilic cells into the myocardium. The clinical symptoms of eosinophilic myocarditis are similar to those of acute coronary syndrome, and eosinophilic myocarditis sometimes occurs in combination with bronchial asthma. We herein present a case of eosinophilic myocarditis in which additional time was required to make a definitive diagnosis because the patient received steroid therapy. The diagnosis of eosinophilic myocarditis is challenging, especially when a patient has other inflammatory diseases, such as bronchial asthma. We should pay attention to the possibility that steroid therapy may mask the presentation of eosinophilic myocarditis. PMID:28090045

  19. Lymphocyte aromatic hydrocarbon responsiveness in acute leukemia of childhood

    SciTech Connect

    Blumer, J.L.; Dunn, R.; Esterhay, M.D.; Yamashita, T.S.; Gross, S.

    1981-12-01

    Aryl hydrocarbon hydroxylase (AHH) activity and inducibility were examined in mitogen-stimulated cultured lymphocytes from children with acute leukemia in remission, with nonleukemic malignancies, and with no family or personal history of malignant disease. Neither morphological differences nor differences in mitogen responsivelness were observed among the three sources of cells studied. Levels of constitutive and dibenzanthracene-induced AHH activity were found to be similar among the three groups by analysis of variance. However, when results were analyzed in terms of inducibility ratios, it was found that cells from leukemic children were significantly less inducible (p < 0.005) than cells from unaffected children or children with nonleukemic malignancies. The reason for this difference became apparent when statistical criteria were employed for the phenotypic separation of individuals who were highly aromatic hydrocarbon responsive and minimally responsive. A significantly larger proportion (p < 0.001) of leukemic children than unaffected children or children with nonleukemic malignancy were found to be minimally aromatic hydrocarbon responsive. Moreover, in patients with acute lymphoblastic leukemia relapsing while on therapy, longer durations of the first remission were correlated (r = 0.63, p < 0.05) with the highly inducible AHH phenotype.

  20. Decitabine and Valproic Acid in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2013-09-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. Autoimmune myocarditis: a clinical entity.

    PubMed Central

    Dragatakis, L. N.; Klassen, J.; Hüttner, I.; Fraser, D. G.; Poirier, N. L.; Klassen, G. A.

    1979-01-01

    In a case of myocarditis electron microscopic and immunoflourescent studies of a transmural myocardial biopsy specimen indicated an autoimmune process. Extensive inflammatory cell infiltration, immunoglobulin and complement deposition along the sarcolemma and in the interstitium, and capillary endothelial injury were found. After a short course of immunosuppressive therapy the inflammatory process was replaced by collagenous scarring and lymphocytic depletion; the blood vessels were then normal. Earlier therapy in such cases may be lifesaving. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 PMID:427670

  2. MUMPS MYOCARDITIS: A FORGOTTEN DISEASE?

    PubMed

    Hussain, Sheraz; Zahid, Mohammad Faizan; Rahman, Arshalooz Jamila; Ahmed, Mehnaz Atiq; Ibrahim, Shahnaz Hamid

    2016-01-01

    Mumps is an acute viral illness that follows a self-limiting course but up to 10% of cases have a complicated course with the involvement of other organ systems. Myocarditis is reported as a complication but the incidence has greatly fallen ever since the development of the mumps vaccine. A child presented to our department with parotid swelling and fever. Persistent tachycardia with irregular pulse led to further cardiac work up which showed decreased ejection fraction and raised serum cardiac enzymes, indicating myocardial damage. With ionotropic agents and supportive care, there was complete normalization of ejection fraction and serum cardiac enzyme levels. He was discharged within a week of admission. This case highlights the importance of suspecting myocarditis in the setting of mumps, a diagnosis that precludes early suspicion in mumps patients suffering from cardiac symptoms not explained by other potential aetiologies. Early suspicion and timely supportive care are essential to ensure favourable outcomes.

  3. Anti-inflammatory role of obestatin in autoimmune myocarditis.

    PubMed

    Pamukcu, Ozge; Baykan, Ali; Bayram, Latife Cakir; Narin, Figen; Cetin, Nazmi; Narin, Nazmi; Argun, Mustafa; Ozyurt, Abdullah; Uzum, Kazim

    2016-01-01

    Obestatin is a popular endogeneous peptide, known to have an autoimmune regulatory effect on energy metabolism and the gastrointestinal system. Studies regarding the anti-inflammatory effects of obestatin are scarce. The aim of this study was to show the anti-inflammatory effect of obestatin in an experimental model of autoimmune myocarditis in rats. Experimental autoimmune myocarditis was induced in Lewis rats by immunization with subcutaneous administration of porcine cardiac myosin, twice at 7-day intervals. Intraperitoneal pretreatment with obestatin (50 μg/kg) was started before the induction of myocarditis and continued for 3 weeks. The severity of myocarditis was evidenced by clinical, echocardiographic and histological findings. In addition, by-products of neutrophil activation, lipid peroxidation, inflammatory and anti-inflammatory cytokines were measured in serum. Obestatin significantly ameliorated the clinical and histopathological severity of autoimmune myocarditis. Therapeutic effects of obestatin in myocarditis were associated with reduced lipid peroxidation, suppression of polymorphonuclear leukocyte infiltration and enhancement of glutathione synthesis, inhibition of serum inflammatory and activation of anti-inflammatory cytokines. Histopathologically, the left ventricle was significantly dilated, and its wall thickened, along with widespread lymphocytic and histocytic infiltration. The myocardium was severely infiltrated with relatively large mononuclear cells. These histopathological changes were observed in lesser degrees in obestatin-treated rats. This study demonstrated a novel anti-inflammatory effect of obestatin in an experimental model of autoimmune myocarditis. Consequently, obestatin administration may represent a promising therapeutic approach for myocarditis and dilated cardiomyopathy in the future.

  4. Lymphocyte surface markers in acute rheumatic fever and post-streptococcal acute glomerulonephritis.

    PubMed Central

    Williams, R C; Zabriskie, J B; Mahros, F; Hassaballa, F; Abdin, Z H

    1977-01-01

    Lymphocyte cell-surface markers were examined in forty children with acute rheumatic fever (ARF) and twelve with acute post-streptococal glomerulonephritis (AGN) and compared to thirty-six normal controls of similar age. Cell-surface-marker studies included surface Ig using fluorescein-labelled F(ab)2 anti-F(AB')2, IgG aggregate binding cells, and EAC rosettes. T cells were identified both as 'active' rosettes and total E-binding cells. Proportions and absolute numbers of cells bearing surface Ig and Fc receptors were elevated in subjects with AGN (Pless than0-01-0-5), whereas proportions of cells producing EAC rosettes were diminished. Patients with acute rheumatic carditis or chorea showed a substantial elevation in proportions and numbers of active T-cell rosettes (Pless than0-01). Streptococcal antigen binding cells capable of forming rosettes with autologous cells coated with group A streptococcal membranes were elevated in the acute phase of both rheumatic fever and acute glomerulonephritis(Pless than0-01). The majority of such cells were removed by passage over insolubilized Ig-anti-IgG columns and appeared to be B cells. PMID:300301

  5. Fas ligand-expressing lymphocytes enhance alveolar macrophage apoptosis in the resolution of acute pulmonary inflammation

    PubMed Central

    Barthel, Lea; Bednarek, Joseph M.; Yunt, Zulma X.; Henson, Peter M.; Janssen, William J.

    2014-01-01

    Apoptosis of alveolar macrophages and their subsequent clearance by neighboring phagocytes are necessary steps in the resolution of acute pulmonary inflammation. We have recently identified that activation of the Fas death receptor on the cell surface of macrophages drives macrophage apoptosis. However, the source of the cognate ligand for Fas (FasL) responsible for induction of alveolar macrophage apoptosis is not defined. Given their known role in the resolution of inflammation and ability to induce macrophage apoptosis ex vivo, we hypothesized that T lymphocytes represented a critical source of FasL. To address this hypothesis, C57BL/6J and lymphocyte-deficient (Rag-1−/−) mice were exposed to intratracheal lipopolysaccharide to induce pulmonary inflammation. Furthermore, utilizing mice expressing nonfunctional FasL, we adoptively transferred donor lymphocytes into inflamed lymphocyte-deficient mice to characterize the effect of lymphocyte-derived FasL on alveolar macrophage apoptosis in the resolution of inflammation. Herein, evidence is presented that lymphocytes expressing FasL enhance alveolar macrophage apoptosis during the resolution of LPS-induced inflammation. Moreover, lymphocyte induction of alveolar macrophage apoptosis results in contraction of the alveolar macrophage pool, which occurs in a FasL-dependent manner. Specifically, FasL-expressing CD8+ T lymphocytes potently induce alveolar macrophage apoptosis and contraction of the alveolar macrophage pool. Together, these studies identify a novel role for CD8+ T lymphocytes in the resolution of acute pulmonary inflammation. PMID:24838751

  6. Gallium-positive Lyme disease myocarditis

    SciTech Connect

    Alpert, L.I.; Welch, P.; Fisher, N.

    1985-09-01

    In the course of a work-up for fever of unknown origin associated with intermittent arrhythmias, a gallium scan was performed which revealed diffuse myocardial uptake. The diagnosis of Lyme disease myocarditis subsequently was confirmed by serologic titers. One month following recovery from the acute illness, the abnormal myocardial uptake completely resolved.

  7. Sudden death of a child due to pyogenic bacterial myocarditis.

    PubMed

    Sikary, Asit K; Mridha, Asit R; Behera, Chittaranjan

    2016-01-01

    Bacterial myocarditis is an uncommon condition and only a few fatal cases in adults are reported in the scientific literature. Death from acute bacterial myocarditis in children is extremely rare. We report an unusual case of fatal bacterial myocarditis in a seven-year-old girl, who had a history of cough for a month and fever for two days. She was given symptomatic treatment by a local physician without suspecting her clinical condition. Her condition rapidly deteriorated and she was brought in dead to the hospital. Autopsy revealed pyogenic bacterial myocarditis associated with bilateral lobar pneumonia caused by Gram-positive cocci. Death from bacterial myocarditis can be prevented by early diagnosis and appropriate antibiotics.

  8. Oxidative stress and myocarditis.

    PubMed

    Tada, Yuko; Suzuki, Jun-Ichi

    2016-01-01

    Reactive oxygen species (ROS) such as superoxide anion and hydrogen peroxide are produced highly in myocarditis. ROS, which not only act as effectors for pathogen killing but also mediate signal transduction in the stress responsive pathways, are closely related with both innate and adaptive immunity. On the other hand, oxidative stress overwhelming the capacity of anti-oxidative system generated in severe inflammation has been suggested to damage tissues and exacerbate inflammation. Oxidative stress worsens the autoimmunological process of myocarditis, and suppression of the anti-oxidative system and long-lasting oxidative stress could be one of the pathological mechanisms of cardiac remodeling leading to inflammatory cardiomyopathy. Oxidative stress is considered to be one of the promising treatment targets of myocarditis. Evidences of anti-oxidative treatments in myocarditis have not been fully established. Basic strategies of anti-oxidative treatments include inhibition of ROS production, activation of anti-oxidative enzymes and elimination of generated free radicals. ROS are produced by mitochondrial respiratory chain reactions and enzymes including NADPH oxidases, cyclooxygenase, and xanthine oxidase. Other systems involved in inflammation and stress response, such as NF-κB, Nrf2/Keap1, and neurohumoral factors also influence oxidative stress in myocarditis. The efficacy of anti-oxidative treatments could also depend on the etiology and the phases of myocarditis. We review in this article the pathological significance of ROS and oxidative stress, and the potential anti-oxidative treatments in myocarditis.

  9. Cardioprotective effects of sarcolemmal and mitochondrial K-ATP channel openers in an experimental model of autoimmune myocarditis. Role of the reduction in calcium overload during acute heart failure.

    PubMed

    Niwano, Shinichi; Hirasawa, Shoji; Niwano, Hiroe; Sasaki, Sae; Masuda, Ray; Sato, Kiyotaka; Masuda, Takashi; Izumi, Tohru

    2012-01-01

    It has been reported that K-ATP channel openers have a cardioprotective effect in acute ischemia as a pharmacological preconditioning effect. In the present study, the chronic effects of clinical K-ATP channel openers, ie, nicorandil (Nic) and mexiletine (Mex), on cardiac function were evaluated in a rat model of experimental autoimmune myocarditis (EAM). Nicorandil (3 or 10 mg/kg/day) or Mex (10 or 25 mg/kg/day) was administered to the EAM rats, and the effects were compared with those in untreated EAM rats (control EAM) and sham rats without EAM on day 21 (acute phase) or day 60 (chronic phase). In the acute phase, the control EAM rats exhibited a reduced left ventricular ejection fraction (LVEF) and prolonged monophasic action potential duration (MAPD). Neither drug had an affect on the LVEF or degree of myocarditis, but Mex 25 mg suppressed the MAPD prolongation. In the chronic phase, EAM+Nic and EAM+Mex 25 mg exhibited a higher LVEF than the control EAM. Although the control EAM exhibited sustained MAPD prolongation, the other groups showed recovery of the MAPD in the chronic phase. The mitochondorial redox state was lower in the control EAM than in the sham, and EAM+Nic exhibited a similar level of the redox state as the sham in the chronic phase. Nicorandil exhibited a cardioprotective effect through the protection of mitochondrial function. Mexiletine exhibited a cardioprotective effect possibly through a reduction in the calcium overload by shortening the MAPD in the acute phase.

  10. B Cell Acute Lymphocytic Leukemia Presenting as a Bile Duct Stricture Diagnosed With Cholangioscopy

    PubMed Central

    Bartel, Michael J.; Jiang, Liuyan; Lukens, Frank

    2016-01-01

    Indeterminate biliary strictures represent a diagnostic challenge requiring further work-up, which encompasses a variety of diagnostic modalities. We report a very rare case of B-cell acute lymphocytic leukemia presenting as a biliary stricture following remission of acute myeloid leukemia, which was initially treated with allogenic stem cell transplant. After multiple diagnostic modalities were implemented with no success, the use of cholangioscopy-guided biopsies was the key for the final diagnosis. PMID:27807569

  11. Hypersensitivity myocarditis confirmed by cardiac magnetic resonance imaging and endomyocardial biopsy.

    PubMed

    Park, Yumi; Ahn, Sung Gyun; Ko, Anna; Ra, Sang Ho; Cha, Jaehwang; Jee, Yong Gwan; Lee, Ji Hyun

    2014-03-01

    Myocarditis often occurs due to viral infections and postviral immune-mediated responses. Hypersensitivity myocarditis is a rare form of myocarditis. Numerous drugs can induce myocarditis, which is typically reversible after withdrawal of the causative agent. Here, we report a case of hypersensitivity myocarditis that was probably triggered by amoxicillin and that resolved completely with heart failure management as well as discontinuation of the drug. A 68-year-old woman presented with acute chest pain mimicking acute coronary syndromes, but the coronary angiography was normal. A recent history of taking medications, skin rash, and peripheral eosinophilia suggested a diagnosis of hypersensitivity myocarditis, which was confirmed by cardiac magnetic resonance imaging and endomyocardial biopsy.

  12. AIM2 co-immunization favors specific multifunctional CD8(+) T cell induction and ameliorates coxsackievirus B3-induced chronic myocarditis.

    PubMed

    Chai, Dafei; Yue, Yan; Xu, Wei; Dong, Chunsheng; Xiong, Sidong

    2015-07-01

    Coxsackievirus B3 (CVB3) infection can cause acute myocarditis and chronic myocarditis, leading to dilated cardiomyopathy (DCM) with no effective therapeutic strategy. Therefore, we investigated the potential of absent in melanoma 2 (AIM2) to enhance the therapeutic efficacy of DNA vaccine against CVB3-induced chronic myocarditis. Mice were infected with CVB3 and then intranasally immunized with chitosan-pcDNA3.1 (mock), chitosan-pAIM2 (CS-pAIM2), chitosan-pVP1 (CS-pVP1), or chitosan-pAIM2 plus chitosan-pVP1 (CS-pAIM2/CS-pVP1) at 7, 21, and 35d. Therapeutic efficacies of various vaccines were evaluated at day 56d. Compared with CS-pVP1 immunization, CS-pAIM2/CS-pVP1 co-immunization significantly increased survival rate, improved cardiac function, as well as decreased myocardial injury and fibrosis, this result indicated that CVB3-induced chronic myocarditis was alleviated. CVB3-specific T lymphocyte proliferation and cytotoxic T lymphocyte responses of the CS-pAIM2/CS-pVP1 co-immunization group were also increased. More interestingly, CS-pAIM2/CS-pVP1 co-immunization could facilitate CVB3-specific multifunctional CD8(+) T cell induction in the intestinal mucosa, and this induction was closely correlated with myocardial scores, this result indicated that CS-pAIM2/CS-pVP1 vaccine exhibits therapeutic efficacy by enhancing multifunctional CD8(+) T cells. This study may represent a novel therapy for CVB3-induced chronic myocarditis.

  13. Diagnosis of Large Granular Lymphocytic Leukemia in a Patient Previously Treated for Acute Myeloblastic Leukemia

    PubMed Central

    Bozdag, Sinem Civriz; Namdaroglu, Sinem; Kayikci, Omur; Kaygusuz, Gülsah; Demiriz, Itir; Cinarsoy, Murat; Tekgunduz, Emre; Altuntas, Fevzi

    2013-01-01

    Large granular lymphocytic (LGL) leukemia is a lymphoproliferative disease characterized by the clonal expansion of cytotoxic T or natural killer cells. We report on a patient diagnosed with T-cell LGL leukemia two years after the achievement of hematologic remission for acute myeloblastic leukemia. PMID:24416499

  14. Natural killer T cells: innate lymphocytes positioned as a bridge between acute and chronic inflammation?

    PubMed Central

    Fox, Lisa; Hegde, Subramanya

    2010-01-01

    Natural killer T cells are an innate population of T lymphocytes that recognize antigens derived from host lipids and glycolipids. In this review, we focus on how these unique T cells are positioned to influence both acute and chronic inflammatory processes through their early recruitment to sites of inflammation, interactions with myeloid antigen presenting cells, and recognition of lipids associated with inflammation. PMID:20850561

  15. Hyperglycemia during induction therapy is associated with increased infectious complications in childhood acute lymphocytic leukemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Children with acute lymphocytic leukemia (ALL) are at high risk for developing hyperglycemia. Hyperglycemic adult ALL patients have shorter remissions, more infections, and increased mortality. No corresponding data are available in children. We hypothesized that children with ALL who become hypergl...

  16. Current treatment options in (peri)myocarditis and inflammatory cardiomyopathy.

    PubMed

    Maisch, B; Pankuweit, S

    2012-09-01

    In inflammatory dilated cardiomyopathy and myocarditis there is--apart from heart failure and antiarrhythmic therapies--no alternative to an aetiologically driven specific treatment. Prerequisite are noninvasive and invasive biomarkers including endomyocardial biopsy and PCR on cardiotropic agents. This review deals with the different etiologies of myocarditis and inflammatory cardiomyopathy including the genetic background, the predisposition for heart failure and inflammation. It analyses the epidemiologic shift in pathogenetic agents in the last 20 years, the role of innate and aquired immunity including the T- and B-cell driven immune responses. The phases and clinical faces of myocarditis are summarized. Up-to-date information on current treatment options starting with heart failure and antiarrhythmic therapy are provided. Although inflammation can resolve spontaneously, specific treatment directed to the causative aetiology is often required. For fulminant, acute and chronic autoreactive myocarditis immunosuppressive treatment is beneficial, while for viral cardiomyopathy and myocarditis ivIg can resolve inflammation and is as successful as interferon therapy in enteroviral and adenoviral myocarditis. For Parvo B19 and HHV6 myocarditis eradication of the virus is still a problem by any of these treatment options. Finally, the potential of stem cell therapy has to be tested in future trials. In virus-negative, autoreactive perimyocardial disease a locoregional approach with intrapericardial instillation of high local doses of triamcinolone acetate has been shown to be highly efficient and with few systemic side-effects.

  17. Fatal Epstein-Barr virus myocarditis in a child with repetitive myocarditis.

    PubMed

    Hebert, M M; Yu, C; Towbin, J A; Rogers, B B

    1995-01-01

    Fatal Epstein-Barr virus (EBV) myocarditis occurred in a 9-year-old female with a history of two prior discrete episodes of myocarditis, the first associated with chicken pox and the second of undetermined origin. Serologic studies during the fatal episode were characteristic of acute EBV infection, and EBV genome was detected by polymerase chain reaction (PCR) amplification of DNA extracted from autopsy heart and liver. PCRs for enteroviruses and cardiac viral culture were negative. An intense mononuclear cell infiltrate in the myocardium consisted entirely of T cells, without identifiable B cells. Human leukocyte antigen HLA-DR analysis using frozen tissue obtained postmortem revealed antigens DR4 and DR13. DR4 is associated with some autoimmune disorders, as well as idiopathic dilated cardiomyopathy. We postulate that an aberrant immune response, possibly associated with the DR4 locus, was responsible for the repetitive episodes of myocarditis in this patient.

  18. Influenza A virus infection complicated by fatal myocarditis.

    PubMed

    Nolte, K B; Alakija, P; Oty, G; Shaw, M W; Subbarao, K; Guarner, J; Shieh, W J; Dawson, J E; Morken, T; Cox, N J; Zaki, S R

    2000-12-01

    Influenza virus typically causes a febrile respiratory illness, but it can present with a variety of other clinical manifestations. We report a fatal case of myocarditis associated with influenza A infection. A previously healthy 11-year-old girl had malaise and fever for approximately 1 week before a sudden, witnessed fatal collapse at home. Autopsy revealed a pericardial effusion, a mixed lymphocytic and neutrophilic myocarditis, a mild lymphocytic interstitial pneumonia, focal bronchial/bronchiolar mucosal necrosis, and histologic changes consistent with asthma. Infection with influenza A (H3N2) was confirmed by virus isolation from a postmortem nasopharyngeal swab. Attempts to isolate virus from heart and lung tissue were unsuccessful. Immunohistochemical tests directed against influenza A antigens and in situ hybridization for influenza A genetic material demonstrated positive staining in bronchial epithelial cells, whereas heart sections were negative. Sudden death is a rare complication of influenza and may be caused by myocarditis. Forensic pathologists should be aware that postmortem nasopharyngeal swabs for viral culture and immunohistochemical or in situ hybridization procedures on lung tissue might be necessary to achieve a diagnosis. Because neither culturable virus nor influenza viral antigen could be identified in heart tissue, the pathogenesis of influenza myocarditis in this case is unlikely to be the result of direct infection of myocardium by the virus. The risk factors for developing myocarditis during an influenza infection are unknown.

  19. Beneficial effects of low-dose benidipine in acute autoimmune myocarditis: suppressive effects on inflammatory cytokines and inducible nitric oxide synthase.

    PubMed

    Yuan, Zuyi; Kishimoto, Chiharu; Shioji, Keisuke

    2003-06-01

    Excessive production of nitric oxide (NO) by inducible NO synthase (iNOS) contributes to the progression of myocardial damage in myocarditis. Some dihydropyridine calcium channel blockers reportedly inhibit NO production and proinflammatory cytokines and the present study sought to clarify if a low dose of benidipine, a novel dihydropyridine calcium channel blocker, would ameliorate experimental autoimmune myocarditis (EAM). Rats with or without myocarditis were administered oral benidipine at a dose of 3 mg. kg(-1). day(-1) for 3 weeks. Low-dose benidipine did not decrease blood pressure significantly compared with the untreated group, but markedly reduced the severity of myocarditis. Myocardial interleukin-1beta (IL-1beta) expression and IL-1beta-positive cells were significantly less in rats with EAM that were treated with low-dose benidipine compared with untreated rats. Also, myocardial iNOS expression and iNOS-positive cells were markedly reduced in in the treated rats compared with the untreated group. Furthermore, myocardial NO production and nitrotyrosine expression were suppressed by the treatment in rats with EAM. The cardioprotection of low-dose benidipine may be caused by suppression of inflammatory cytokines and inhibition of NO production.

  20. Sleep disruption and its effect on lymphocyte redeployment following an acute bout of exercise.

    PubMed

    Ingram, Lesley A; Simpson, Richard J; Malone, Eva; Florida-James, Geraint D

    2015-07-01

    Sleep disruption and deprivation are common in contemporary society and have been linked with poor health, decreased job performance and increased life-stress. The rapid redeployment of lymphocytes between the blood and tissues is an archetypal feature of the acute stress response, but it is not known if short-term perturbations in sleep architecture affect lymphocyte redeployment. We examined the effects of a disrupted night sleep on the exercise-induced redeployment of lymphocytes and their subtypes. 10 healthy male cyclists performed 1h of cycling at a fixed power output on an indoor cycle ergometer, following a night of undisrupted sleep (US) or a night of disrupted sleep (DS). Blood was collected before, immediately after and 1h after exercise completion. Lymphocytes and their subtypes were enumerated using direct immunofluorescence assays and 4-colour flow cytometry. DS was associated with elevated concentrations of total lymphocytes and CD3(-)/CD56(+) NK-cells. Although not affecting baseline levels, DS augmented the exercise-induced redeployment of CD8(+) T-cells, with the naïve/early differentiated subtypes (KLRG1(-)/CD45RA(+)) being affected most. While the mobilisation of cytotoxic lymphocyte subsets (NK cells, CD8(+) T-cells γδ T-cells), tended to be larger in response to exercise following DS, their enhanced egress at 1h post-exercise was more marked. This occurred despite similar serum cortisol and catecholamine levels between the US and DS trials. NK-cells redeployed with exercise after DS retained their expression of perforin and Granzyme-B indicating that DS did not affect NK-cell 'arming'. Our findings indicate that short-term changes in sleep architecture may 'prime' the immune system and cause minor enhancements in lymphocyte trafficking in response to acute dynamic exercise.

  1. Viral myocarditis--diagnosis, treatment options, and current controversies.

    PubMed

    Pollack, Ari; Kontorovich, Amy R; Fuster, Valentin; Dec, G William

    2015-11-01

    Myocarditis--a frequent cause of dilated cardiomyopathy and sudden cardiac death--typically results from cardiotropic viral infection followed by active inflammatory destruction of the myocardium. Characterization of this disease has been hampered by its heterogeneous clinical presentations and diverse aetiologies. Advances in cardiac MRI and molecular detection of viruses by endomyocardial biopsy have improved our ability to diagnose and understand the pathophysiological mechanisms of this elusive disease. However, therapeutic options are currently limited for both the acute and chronic phases of myocarditis. Several randomized, controlled trials have demonstrated potential benefit with immunosuppressive and immunomodulatory therapies, but further investigations are warranted. In this Review, we explore the pathophysiology, natural history, and modes of diagnosis of myocarditis, as well as evidence-based treatment strategies. As novel imaging techniques and human in vitro models of the disease emerge, the landscape of therapies for myocarditis is poised to improve.

  2. Novel biomarkers for patients with idiopathic acute anterior uveitis: neutrophil to lymphocyte ratio and platelet to lymphocyte ratio

    PubMed Central

    Ozgonul, Cem; Sertoglu, Erdim; Ayyildiz, Onder; Mumcuoglu, Tarkan; Kucukevcilioglu, Murat; Gokce, Gokcen; Durukan, Ali Hakan

    2017-01-01

    AIM To assess the levels of the neutrophil to lymphocyte ratio (N/L) and the platelet to lymphocyte ratio (P/L) in patients with idiopathic acute anterior uveitis (AAU) and to compare with healthy controls. METHODS Thirty-six male patients with idiopathic AAU and 36 male healthy subjects were enrolled in this retrospective study. Complete ophthalmological examination and complete blood count measurements results of all subjects were evaluated. RESULTS There was a significant difference in N/L and P/L between idiopathic AAU and control groups (P=0.006, P=0.022). Also, correlation analysis revealed a significant correlation between C-reactive protein (CRP) and N/L (P=0.002; r=0.461). CONCLUSION Our study for the first time provides evidence of N/L and P/L may be useful biomarkers in patients with idiopathic AAU. N/L is correlated with CRP, so it can be a useful biomarker to predict the prognosis in idiopathic AAU. PMID:28251086

  3. Myocarditis in Clinical Practice.

    PubMed

    Sinagra, Gianfranco; Anzini, Marco; Pereira, Naveen L; Bussani, Rossana; Finocchiaro, Gherardo; Bartunek, Jozef; Merlo, Marco

    2016-09-01

    Myocarditis is a polymorphic disease characterized by great variability in clinical presentation and evolution. Patients presenting with severe left ventricular dysfunction and life-threatening arrhythmias represent a demanding challenge for the clinician. Modern techniques of cardiovascular imaging and the exhaustive molecular evaluation of the myocardium with endomyocardial biopsy have provided valuable insight into the pathophysiology of this disease, and several clinical registries have unraveled the disease's long-term evolution and prognosis. However, uncertainties persist in crucial practical issues in the management of patients. This article critically reviews current information for evidence-based management, offering a rational and practical approach to patients with myocarditis. For this review, we searched the PubMed and MEDLINE databases for articles published from January 1, 1980, through December 31, 2015, using the following terms: myocarditis, inflammatory cardiomyopathy, and endomyocardial biopsy. Articles were selected for inclusion if they represented primary data or were review articles published in high-impact journals. In particular, a risk-oriented approach is proposed. The different patterns of presentation of myocarditis are classified as low-, intermediate-, and high-risk syndromes according to the most recent evidence on prognosis, clinical findings, and both invasive and noninvasive testing, and appropriate management strategies are proposed for each risk class.

  4. A single black ulcer in a child with acute lymphocytic leukemia*

    PubMed Central

    Vestita, Michelangelo; Filoni, Angela; Santoro, Nicola; Arcamone, Gianpaolo; Bonamonte, Domenico

    2016-01-01

    Ecthyma gangrenosum is an uncommon dermatological manifestation characterized by round, indurated ulcers with a central necrotic black eschar and surrounding erythema. This report describes the case of a 5-year-old girl, affected by acute lymphocytic leukemia, presenting with a black eschar on her right thigh. Such lesions should always be correctly identified to avoid potentially fatal bacteraemia. Furthermore, because of its similar clinical presentation, cutaneous anthrax must be ruled out. PMID:28099607

  5. Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-12-08

    CD19-Positive Neoplastic Cells Present; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

  6. Update on Myocarditis and Inflammatory Cardiomyopathy: Reemergence of Endomyocardial Biopsy.

    PubMed

    Dominguez, Fernando; Kühl, Uwe; Pieske, Burkert; Garcia-Pavia, Pablo; Tschöpe, Carsten

    2016-02-01

    Myocarditis is defined as an inflammatory disease of the heart muscle and is an important cause of acute heart failure, sudden death, and dilated cardiomyopathy. Viruses account for most cases of myocarditis or inflammatory cardiomyopathy, which could induce an immune response causing inflammation even when the pathogen has been cleared. Other etiologic agents responsible for myocarditis include drugs, toxic substances, or autoimmune conditions. In the last few years, advances in noninvasive techniques such as cardiac magnetic resonance have been very useful in supporting diagnosis of myocarditis, but toxic, infectious-inflammatory, infiltrative, or autoimmune processes occur at a cellular level and only endomyocardial biopsy can establish the nature of the etiological agent. Furthermore, after the generalization of immunohistochemical and viral genome detection techniques, endomyocardial biopsy provides a definitive etiological diagnosis that can lead to specific treatments such as antiviral or immunosuppressive therapy. Endomyocardial biopsy is not commonly performed for the diagnosis of myocarditis due to safety reasons, but both right- and left endomyocardial biopsies have very low complication rates when performed by experienced operators. This document provides a state-of-the-art review of myocarditis and inflammatory cardiomyopathy, with special focus on the role of endomyocardial biopsy to establish specific treatments.

  7. Recent advances and novel treatment paradigms in acute lymphocytic leukemia

    PubMed Central

    Papadantonakis, Nikolaos; Advani, Anjali S.

    2016-01-01

    This is an exciting time in the treatment of acute lymphoblastic leukemia (ALL) given the advances in the relapsed/refractory setting. The development of antibody treatments (including antibody drug conjugates with toxins) offers a different treatment approach compared with conventional chemotherapy regimens. Moreover, the use of bispecific T-cell-engager antibodies (BiTEs) such as blinatumomab harness the cytotoxic activity of T cells against CD19-positive lymphoblasts. Another strategy involves the use of chimeric antigen receptor (CAR) T cells. CAR T cells have demonstrated promising results in the relapsed/refractory setting. However, the use of BiTEs and CAR T cells is also associated with a distinct set of adverse reactions that must be taken into account by the treating physician. Apart from the above strategies, the use of other targeted therapies has attracted interest. Namely, the discovery of the Philadelphia (Ph)-like signature in children and young adults with ALL has led to the use of tyrosine kinase inhibitors (TKI) in these patients. The different drugs and strategies that are being tested in the relapsed/refractory ALL setting pose a unique challenge in identifying the optimum sequence of treatment and determining which approaches should be considered for frontline treatment. PMID:27695616

  8. TandemHeart as a Bridge to Recovery in Legionella Myocarditis.

    PubMed

    Briceño, David F; Fernando, Rajeev R; Nathan, Sriram; Loyalka, Pranav; Kar, Biswajit; Gregoric, Igor D

    2015-08-01

    Legionnaires' disease is the designation for pneumonia caused by the Legionella species. Among the rare extrapulmonary manifestations, cardiac involvement is most prevalent, in the forms of myocarditis, pericarditis, postcardiotomy syndrome, and prosthetic valve endocarditis. Mechanical circulatory support has proved to be a safe and effective bridge to myocardial recovery in patients with acute fulminant myocarditis; however, to our knowledge, this support has not been used in infectious myocarditis specifically related to Legionellosis. We describe a case of Legionella myocarditis associated with acute left ventricular dysfunction and repolarization abnormalities in a 48-year-old man. The patient fully recovered after left ventricular unloading with use of a TandemHeart percutaneous ventricular assist device. In addition, we review the English-language medical literature on Legionella myocarditis and focus on cardiac outcomes.

  9. Viral Myocarditis and Dilated Cardiomyopathy: Etiology and Pathogenesis.

    PubMed

    Huber, Sally A

    2016-01-01

    Myocarditis is an inflammation of the myocardium which often follows microbial infections and is a significant cause of sudden unexpected death in the young (<40 years of age) and an underlying cause of dilated cardiomyopathy. Although histologically, the disease is usually associated with infiltration of the myocardium with either eosinophils or leukocytes, use of immunosuppression is controversial outside of giant cell myocarditis and has been found to be of limited value in lymphocytic myocarditis. The relatively limited response might reflect the need for host immunity to control persistent virus infection in the heart which may be the predominant cause of the chronic myocarditis and dilated cardiomyopathy. Treating the persistent virus infection with interferon-beta improved cardiac function in a clinical trial. However, classic immunosuppressive drugs, such as cyclosporine A and cyclophosphamide, are not effective against all types of immunity and experimental myocarditis models have shown that certain immunopathogenic forms of the disease are resistant to these immunosuppressive agents. Understanding the molecular mechanisms underlying the pathogenesis of this disease and the various infectious agents which can cause it will be essential for developing effective therapeutic agents.

  10. Fas-FasL expression and myocardial cell apoptosis in patients with viral myocarditis.

    PubMed

    Huang, T F; Wu, X H; Wang, X; Lu, I J

    2016-06-20

    The aim of the current study was to investigate Fas and FasL expression and myocardial cell apoptosis in viral myocarditis patients. Human heart specimens were selected from patients who were autopsied between February 2012 and February 2015; of these, 25 patients were diagnosed with viral myocarditis. Another 15 cases with no diagnosis of myocarditis were selected for the control group. All tissue specimens were divided into two parts, one for reverse transcription-polymerase chain reaction analysis and the other for immunohistochemical and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analyses. In situ detection of apoptosis was performed by the TUNEL method, which revealed that myocardial cells from the viral myocarditis group exhibited significant apoptosis, whereas no apoptotic cells were observed in the control group. The number of cells staining positive for Fas and FasL protein in the viral myocarditis group was significantly higher than that in the control group (P < 0.05). There was also a correlation between Fas and FasL protein expression levels and scores (r = 0.92, P < 0.05). The mRNA expression of Fas and FasL was significantly higher in the viral myocarditis group than in the control group (P < 0.05). In conclusion, the Fas-FasL system may be involved in the pathogenesis of viral myocarditis. Furthermore, cytotoxic T lymphocytes may mediate cardiac muscle cells apoptosis via Fas-FasL signaling, and thus participate in the pathogenesis of viral myocarditis.

  11. Method of automating of the separation of blasts and lymphocytes in the diagnosis of acute myeloid leukemia

    NASA Astrophysics Data System (ADS)

    Blindar, V. N.; Nikitaev, V. G.; Polyakov, E. V.; Matveeva, I. I.

    2017-01-01

    The work deals with the separation of the lymphocytes of healthy patients from blasts of patients with acute myeloblastic leukemia (different variants of the disease). In this study the evaluation of textural characteristics has been done for nuclei of blood cells for cells classification and for the determination of a variant of acute myeloblastic leukemia.

  12. Case report: Concomitant Chronic Lymphocytic Leukaemia and Cytogenetically Normal de novo Acute Leukaemia in a Patient.

    PubMed

    Kajtár, Béla; Rajnics, Péter; Egyed, Miklós; Alizadeh, Hussain

    2015-01-01

    The simultaneous occurrence of acute myeloid leukaemia with untreated chronic lymphocytic leukemia is extremely rare. We report a case of a 74-year-old man who was evaluated for macrocytic anaemia. Based on the morphology and immunophenotyping analysis of peripheral blood, a diagnosis of chronic lymphocytic leukemia was established. Subsequently, the bone marrow examination revealed the presence of two distinct, coexisting CLL and AML clones. Cytogenetic and molecular genetic analysis detected deletion 13q14.3 and unmutated immunoglobulin variable heavy-chain in the CLL clone, only. The AML and CLL clones did not share clonality, and the AML did not involve the peripheral blood. A diagnosis of cytogenetically normal de novo AML occurring concurrently with untreated CLL has not been reported previously in English literature.

  13. Clinical and experimental aspects of viral myocarditis.

    PubMed Central

    Leslie, K; Blay, R; Haisch, C; Lodge, A; Weller, A; Huber, S

    1989-01-01

    Picornaviruses are frequently implicated as the etiological agents of acute myocarditis. This association is based historically on serological evidence of rising antibody titers to specific pathogens and more recently on identification of viral genomic material in endocardial biopsy specimens through in situ hybridization. Only rarely is infectious virus isolated from either the patient or the heart during periods of maximum myocardial inflammation and injury. Thus, despite a probable viral etiology, much interest centers on the role of the immune system in cardiac damage and the likelihood that the infection triggers an autoimmune response to heart-specific antigens. Heart-reactive antibodies and T cells are found in most myocarditis patients, and immunosuppressive therapy has proven beneficial in many, though not all, cases. Furthermore, murine models of coxsackievirus group B type 3-induced myocarditis also demonstrate that virus infection initiates autoimmunity and that these autoimmune effectors are predominately responsible for tissue injury. How virus-host interactions overcome presumed self-tolerance to heart antigens is discussed, and evidence supporting various theories of virus-initiated autoimmunity and disease pathogenesis are delineated. PMID:2650861

  14. Effects of competition on acute phase proteins and lymphocyte subpopulations - oxidative stress markers in eventing horses.

    PubMed

    Valle, E; Zanatta, R; Odetti, P; Traverso, N; Furfaro, A; Bergero, D; Badino, P; Girardi, C; Miniscalco, B; Bergagna, S; Tarantola, M; Intorre, L; Odore, R

    2015-10-01

    The aim of the study was to evaluate markers of the acute phase response (APR) in eventing horses by measuring acute phase proteins (APP) (haptoglobin, Hp, and serum amyloid A, SAA), lysozyme, protein adducts such as pentosidine-like adducts (PENT), malondialdehyde adducts (MDA), hydroxynonenal adducts (HNE) and total advanced glycation/glycoxidation end products (AGEs), complete blood count and lymphocyte subpopulations (CD4+, CD8+ and CD21+) both at rest and at the end of an eventing competition. Blood samples were collected from eight Warmblood horses (medium age 10 ± 3) during an official national 2-day event competition at rest (R) and 10 min after the arrival of the cross-country test on the second day. Exercise caused a significant increase in red blood cell number, haemoglobin, packed cell volume, neutrophils, white blood cell and lymphocyte number; however, these values remained within the normal range. The CD4+ and CD8+ cells significantly increased, whereas the CD21+ lymphocytes decreased; a significant increase in serum SAA, lysozyme and protein carbonyl derivates was also observed. Two-day event causes significant changes in APR markers such as lysozyme, protein carbonyl derivates (HNE, AGEs, PENT) and lymphocyte subpopulations. The data support the hypothesis that 2-day event may alter significantly APR markers. Limitations of the study were the relatively small sample size and sampling time conditioned by the official regulations of the event. Therefore, further studies are needed to investigate the time required for recovery to basal values in order to define the possible effects on the immune function of the athlete horse.

  15. Glioblastoma multiforme following cranial irradiation and chemotherapy for acute lymphocytic leukaemia. Report of 3 cases.

    PubMed

    Menon, R; Muzumdar, D; Shah, A; Goel, A

    2007-01-01

    The most common secondary neoplasms which occur following cranial radiation therapy are sarcoma and meningioma. The occurrence of glioblastoma multiforme following radiation and chemotherapy in acute lymphocytic leukaemia (ALL) is rare. We report 3 cases of glioblastoma multiforme in children developing 11-72 months following completion of chemotherapy/radiotherapy for ALL. The exact cause for the development of glioblastoma multiforme following therapy for ALL is not clear. A genetic predisposition may be essential for the occurrence of such a highly malignant primary brain tumour in leukaemia patients, irrespective of radiation and/or chemotherapy. The pathogenesis and surgical management are discussed, and the literature on the subject is reviewed.

  16. The impact of cranial irradiation on the growth of children with acute lymphocytic leukemia

    SciTech Connect

    Wells, R.J.; Foster, M.B.; D'Ercole, A.J.; McMillan, C.W.

    1983-01-01

    Heights, height velocities, weights, and weight velocities were measured serially in 21 patients with acute lymphocytic leukemia (ALL) who had survived three to five years in continuous complete remission. These patients were assigned randomly to treatment regimens that varied according to whether cranial irradiation was used. Patients receiving cranial irradiation had lower height velocities during therapy than normal subjects and patients not receiving cranial irradiation. Twenty-two other children with ALL, who were irradiated but not randomized, exhibited similar alterations in growth. These results indicate that cranial irradiation, and not leukemia or antileukemia chemotherapy, causes reduced growth.

  17. Myocarditis induced by coxsackie B3 virus in mature mice.

    PubMed

    Jaśkiewicz, K; Mrozińska, B

    1975-01-01

    Forty female mice during breast-feeding were infected intraperitoneally with coxackie B3 virus. Gross and microscopic examination of the hearts of the mice 7, 20, 44 and 120 days after infection revealed myocarditis typical of the acute stage of the disease, not reported previously, and gradually increasing intensity of immunologic changes in the chronic stage.

  18. Cellular immune mechanisms in Coxsackievirus group B, type 3 induced myocarditis in Balb/C mice

    SciTech Connect

    Huber, S.A.; Job, L.P.

    1983-01-01

    Coxsackie B viruses are a common cause of viral myocarditis in humans. A murine model of the human disease has been developed using Coxsackievirus group B, type 3 and inbred Balb/c mice. Infection of T lymphocyte deficient mice does not result in significant myocarditis indicating the importance of T cells in this disease. The virus can be isolated from the hearts of T cell deficient and normal mice in equal concentrations. Virus elimination presumably is mediated by virus specific neutralizing antibody induced in both groups. T lymphocytes, natural killer cells and macrophage obtained from normal virus infected mice are all capable of lysing myofibers in vitro. Maximum lysis is obtained with the cytolytic T cells. When these cell populations or Coxsackievirus immune antibody were adoptively transferred into T lymphocyte deficient animals infected with the virus, only animals given T cells developed significant myocarditis.

  19. [Endomyocardial biopsy should be performed in selected patients with suspected myocarditis].

    PubMed

    Ammirati, Enrico; Cipriani, Manlio; Bonacina, Edgardo; Garascia, Andrea; Oliva, Fabrizio

    2015-10-01

    Endomyocardial biopsy (EMB) is the gold standard for the diagnosis of myocarditis. Patients with clinical presentation consistent with myocarditis and acute heart failure should undergo EMB, in particular to exclude giant-cell myocarditis or necrotizing eosinophilic myocarditis that are life-threatening conditions. The indication for EMB is debatable in case of suspected myocarditis with infarct-like presentation and preserved left ventricular ejection fraction. In fact, in this group of patients the prognosis is fairly good, and the clinical advantage to reach a histological diagnosis by means of an invasive procedure with potential complications such as EMB is limited. In this article we discuss the indication for EMB in the light of current guidelines based on existing consensus documents.

  20. Coxsackievirus B3 induces viral myocarditis by upregulating toll-like receptor 4 expression.

    PubMed

    Zhao, Zhao; Cai, Tian-Zhi; Lu, Yan; Liu, Wen-Jun; Cheng, Man-Li; Ji, Yu-Qiang

    2015-04-01

    In the present study, we investigated the potential pathogenesis of coxsackievirus B3 (CVB3)-induced viral myocarditis and the promising protective effect of silencing RNA (small interfering RNA, siRNA). One hundred and twenty mice were included in the study, and 30 mice were intraperitoneally inoculated with CVB3 to establish an acute viral myocarditis model. The survival rate was observed for the CVB3-infected mouse model (MOD), and myocardial injury was examined by HE (hematoxylin and eosin) staining assay. Real-time PCR (RT-PCR) and Western blot assay were selected to detect the toll-like receptor 4 (TLR4) expression in myocardial tissues. The TLR4 gene was silenced for the MOD mice, and the effects of this treatment were observed. The results indicate that the expression of TLR4 mRNA and the protein significantly and persistently increased during the progression of CVB3-induced myocarditis. The activities of cardiac enzymes including CK, LDH, AST, and CK-MB were also enhanced in CVB3-induced myocardial tissues. Interestingly, when the TLR4 gene was silenced, the CVB3-induced TLR4 production was significantly decreased and the severity of myocarditis was significantly lessened. In conclusion, CVB3 may induce viral myocarditis by upregulating toll-like receptor 4 expression. The viral myocarditis can be ameliorated by silencing the TLR4 gene in the CVB3 viral myocarditis model, which may be a feasible therapeutic method for treatment of viral myocarditis.

  1. Comparative study of quality of life of adult survivors of childhood acute lymphocytic leukemia and Wilms’ tumor

    PubMed Central

    de Souza, Clélia Marta Casellato; Cristofani, Lilian Maria; Cornacchioni, Ana Lucia Beltrati; Odone, Vicente; Kuczynski, Evelyn

    2015-01-01

    Abstract Objective To analyze and compare the health-related quality of life of adult survivors of acute lymphocytic leukemia and Wilms’ tumor amongst themselves and in relation to healthy participants. Methods Ninety participants aged above 18 years were selected and divided into three groups, each comprising 30 individuals. The Control Group was composed of physically healthy subjects, with no cancer history; and there were two experimental groups: those diagnosed as acute lymphocytic leukemia, and those as Wilms’ Tumor. Quality of life was assessed over the telephone, using the Medical Outcomes Study 36-Item Short Form Health Survey. Results Male survivors presented with better results as compared to female survivors and controls in the Vitality domain, for acute lymphocytic leukemia (p=0.042) and Wilms’ tumor (p=0.013). For acute lymphocytic leukemia survivors, in Social aspects (p=0.031), Mental health (p=0.041), and Emotional aspects (p=0.040), the latter also for survivors of Wilms’ tumor (p=0.040). The best results related to the Functional capacity domain were recorded for the experimental group that had a late diagnosis of acute lymphocytic leukemia. There were significant differences between groups except for the Social and Emotional domains for self-perceived health, with positive responses that characterized their health as good, very good, and excellent. Conclusion Survivors of acute lymphocytic leukemia showed no evidence of relevant impairment of health-related quality of life. The Medical Outcomes Study 36-Item Short Form Health Survey (via telephone) can be a resource to access and evaluate survivors. PMID:26537509

  2. Heart muscle performance after experimental viral myocarditis.

    PubMed Central

    Adesanya, C O; Goldberg, A H; Phear, W P; Thorp, K A; Young, N A; Abelmann, W H

    1976-01-01

    As part of an inquiry into possible antecedents of idiopathic cardiomyopathy, acute experimental coxsackie virus myocarditis was studied for late structural and functional sequelae. Myocarditis was induced in 12- and 22-day-old hamsters by inoculation with coxsackie virus B3. Early viremia occurred, followed by virus replication in heart muscle. Maximum peak developed tension (Tpd) of isometrically contracting isolated heart muscle was depressed 17 and 43% in the animals inoculated at 12 days, and studied 18 and 90 days later, respectively, as compared to their uninoculated controls. In both infected groups, less muscle stretch was required to reach the length at which Tpd was produced. Animals studied 180 days after inoculation did not differ from controls. The muscles from animals inoculated at 22 days of age and studied 18 days later showed a 15% depression of Tpd compared to their controls. Glycerinated muscles from this infected group developed 50% less tension than their controls. The muscles of hamsters inoculated with virus at 22 days and studied 90 and 180 days later showed no change in Tpd. The data suggest that contractility and compliance of heart muscle are decreased 18 days after inoculation, but recover by 90 days if the animals are inoculated at age 22 days. However, if the animals are inoculated at a younger age (12 days), depression of myocardial performance persists for at least an additional 90 days. It is concluded that the inflammatory stage of experimental acute coxsackie virus B3 myocarditis in the Syrian golden hamster may be followed by residual alterations in contractile proteins and myocardial function. PMID:1249200

  3. A Case of Fulminant Myocarditis With Preceding Repeated Episodes of Congestive Heart Failure

    PubMed Central

    Tada, Yuko; Uto, Kenta; Wada, Hiroshi; Sakakura, Ken-ichi; Suzuki, Jun-ichi; Nishikawa, Toshio; Ako, Junya; Momomura, Shin-ichi

    2013-01-01

    We report a rare case of fulminant myocarditis that was considered to have smoldered for a few months before it finally exteriorized. An 80-year-old man had had two episodes of mild congestive heart failure with preserved ejection function (HFPEF) within 3 months before he was finally admitted for the treatment of rapidly progressive heart failure. Cardiac function deteriorated remarkably on the final admission. Extracorporeal cardiopulmonary support was used because of pump failure and conduction disability, however, the patient died on the 16th day. Endomyocardial biopsy revealed numerous inflammatory infiltrates in myocardium compatible with fulminant myocarditis. However, advanced fibrosis and increased number of B lymphocytes and plasma cells found in the present case were not typical for fulminant myocarditis. Considering several distinctive findings in clinical and laboratory findings together, two preceding HFPEF episodes were highly likely to be associated with myocarditis.

  4. Idiopathic giant cell myocarditis in childhood: A case report.

    PubMed

    Pehlivan, Sultan; Akçan, Ramazan; Heybet, Eyup Ruşen; Cavlak, Mehmet; Pehlivan, Ali

    2016-03-01

    Idiopathic giant cell myocarditis is a rare entity of unknown origin, which causes sudden death in more than half of the affected patients. It is rarely seen in childhood, and might result in death due to heart failure and ventricular arrhythmias. Idiopathic giant cell myocarditis is mostly diagnosed at autopsy incidentally. Here we present a rare case of childhood idiopathic giant cell myocarditis. A 10-year old boy found dead in his bed in the morning. Interview with family members revealed death the boy was in good health conditions apart from being overweight. At autopsy, external examination was completely normal. Internal examination revealed normal findings; the heart was 297g and macroscopically normal. No traces of any toxic agents detected in complete toxicological analyses. Areas characterized with granulomatous lesions, lymphocytes, histiocytes, and multinucleated giant cells were observed in myocardium at histopathological examination. No necrosis was observed in granulomatous areas. Tuberculosis was negative in the PCR assays. There were no signs indicative of fungal infection, and clinical status of the case was not compatible with the sarcoidosis. In this respect death was attributed to idiopathic giant cell myocarditis.

  5. Native T1 Mapping Demonstrating Apical Thrombi in Eosinophilic Myocarditis Associated with Churg-Strauss Syndrome

    PubMed Central

    Beck, Kyongmin Sarah; Jeong, Soh Yong; Lee, Kyo Young; Chang, Kiyuk

    2016-01-01

    Eosinophilic myocarditis is a disease characterized by eosinophilic infiltration of the myocardium, consisting of acute necrotic stage, thrombotic stage, and fibrotic stage. Although T1 mapping has been increasingly used in various cardiac pathologies, there has been no report of T1 mapping in eosinophilic myocarditis. We report a case of 75-year-old female with eosinophilic myocarditis, whose cardiac magnetic resonance imaging included native T1 mapping, in which apical thrombi were distinctly seen as areas with decreased T1 values, next to areas of inflammation seen as increased T1 value in subendocardium. PMID:27826352

  6. Total artificial heart implantation for biventricular failure due to eosinophilic myocarditis.

    PubMed

    Kawabori, Masashi; Kurihara, Chitaru; Miller, Yair; Heck, Kent A; Bogaev, Roberta C; Civitello, Andrew B; Cohn, William E; Frazier, O H; Morgan, Jeffrey A

    2017-03-27

    Idiopathic hypereosinophilic syndrome is a condition of unknown etiology characterized by proliferation of eosinophils and their infiltration into tissues. Although cardiac involvement is rare, eosinophilic myocarditis can lead to life-threating fulminant congestive heart failure. Treatment of patients with eosinophilic myocarditis is challenging as heart failure can be caused by biventricular dysfunction. To our knowledge, this is the first case reported in the literature describing a patient with acute severe biventricular heart failure caused by eosinophilic myocarditis with mural left ventricular apical thrombus who was successfully treated with implantation of a total artificial heart as a bridge to heart transplant.

  7. A reduced lymphocyte ratio as an early marker for predicting acute pancreatitis

    PubMed Central

    Qi, Xiuzhong; Yang, Fangyong; Huang, Haitao; Du, Yiqi; Chen, Yan; Wang, Meitang; Zhu, Dezeng; Yue, Xiaoqiang; Wang, Lina

    2017-01-01

    The early diagnosis and severity grading for acute pancreatitis (AP) are difficult to determine because of the complexity and differences in disease process. To date, few studies have investigated the role of lymphocyte ratio (LR) in AP. Therefore, the objective of the present study was to investigate the prognostic value of LR as an indicator in AP, as well as determine an optimal cut-off value for the severity prediction. There were two hundred four patients involved in this study, ninety-two of whom had severe acute pancreatitis (SAP). The LR was analyzed on admission and correlated with severity, which was determined using the Atlanta classification. The optimal cut-off value for LR was generated using receiving operator characteristic (ROC) curves. The results showed that the LR in the SAP group decreased significantly compared to the mild acute pancreatitis (MAP) group (8.82 vs. 13.43). The optimal cut-off value obtained from ROC curves was 0.081, with a sensitivity of 80.4%, a specificity of 53.3%, a positive likelihood ratio of 1.722, and a negative likelihood ratio of 0.368. In conclusion, the LR is obviously related to the condition of AP patients and is valuable for the differential diagnosis of SAP in early stages of AP. PMID:28266603

  8. Fulminant myocarditis owing to high-dose interleukin-2 therapy for metastatic melanoma

    PubMed Central

    Thavendiranathan, P; Verhaert, D; Kendra, K L; Raman, S V

    2011-01-01

    High-dose interleukin-2 (IL-2) therapy may cause acute myocarditis characterised by diffuse myocardial involvement and occasionally fulminant heart failure. Cardiac MRI (CMRI) provides a comprehensive assessment of myocardial function, inflammation and injury in a single examination and has shown value in the diagnosis of myocarditis. We report a case of a 54-year-old male with metastatic melanoma who developed acute severe myocarditis with fulminant heart failure after high-dose IL-2 therapy. CMRI using a combination of T2 weighted imaging and T1 weighted late post-gadolinium enhancement techniques played a key role in establishing the diagnosis. To our knowledge we present the first case report of the combined use of T1 and T2 weighted CMRI techniques to diagnose IL-2 induced myocarditis. PMID:21511746

  9. Initial absolute lymphocyte count as a prognostic factor for outcome in acute myeloid leukemia.

    PubMed

    Le Jeune, Caroline; Bertoli, Sarah; Elhamri, Mohamed; Vergez, Francois; Borel, Cecile; Huguet, Françoise; Michallet, Mauricette; Dumontet, Charles; Recher, Christian; Thomas, Xavier

    2014-04-01

    The absolute lymphocyte count (ALC) at presentation has been associated with survival in various malignancies. However, its prognostic value in acute myeloid leukemia (AML) has not been established. In a series of 1702 newly diagnosed patients with AML, we evaluated the prognostic value of ALC at diagnosis with regard to induction chemotherapy response, disease-free survival (DFS) and overall survival (OS). Low initial ALC (< 1 × 10(9)/L) appeared as a poor prognostic factor for DFS (p = 0.01) and OS (p = 0.02), while higher ALC (> 4.5 × 10(9)/L) showed a lower response rate after one (p = 0.004) or two induction chemotherapy courses (p = 0.01). However, ALC did not appear as an independent predictor of outcome in a multivariate analysis model also including age, cytogenetics and white blood cell count. Examination of lymphocyte subsets is warranted to specify the relationship between ALC at diagnosis and clinical outcome in AML.

  10. Lymphocyte distribution in mouse submandibular lymph nodes in response to acute treadmill exercise.

    PubMed

    Quadrilatero, J; Boudreau, J; Hoffman-Goetz, L

    2003-10-01

    The submandibular lymph nodes (LN), part of the nasal-associated lymphoid tissue (NALT), are involved in local immune responses in the eye, upper respiratory tract (URT), and oral mucosa. Although athletes have been reported to be at increased risk for URT and ocular infections, little is known about the impact of exercise on LN included in the NALT. The purpose of this study was to examine the impact of intense acute exercise on submandibular lymphocyte distribution. Female C57BL/6 mice were randomly assigned to a nonexercised control condition or a single session of treadmill exercise (32 m.min-1, 8 degrees grade for 90 min) and sacrificed immediately, 2, and 24 h after exercise. Running resulted in a significant increase in plasma corticosterone immediately following exercise compared with other times (p < 0.001). Percentages and total numbers of CD3+ and CD4+CD8- T lymphocytes in submandibular LN were significantly lower 24 h after exercise compared with controls. The percentage of pan-NK and CD19+ B cells increased immediately and 24 h after exercise, respectively, but the total numbers were not affected. The results suggest that decreased percentages and absolute numbers of T cells in submandibular LN following a single session of intense exercise may be partially mediated by increased corticosterone concentrations and may have consequences for ocular health among athletes.

  11. Myocarditis in Patients With Antisynthetase Syndrome: Prevalence, Presentation, and Outcomes.

    PubMed

    Dieval, Céline; Deligny, Christophe; Meyer, Alain; Cluzel, Philippe; Champtiaux, Nicolas; Lefevre, Guillaume; Saadoun, David; Sibilia, Jean; Pellegrin, Jean-Luc; Hachulla, Eric; Benveniste, Olivier; Hervier, Baptiste

    2015-07-01

    Antisynthetase syndrome (aSS) corresponds to an overlapping inflammatory myopathy identified by various myositis-specific autoantibodies (directed against tRNA-synthetases). Myocardial involvement in this condition is poorly described.From a registry of 352 aSS patients, 12 cases of myocarditis were retrospectively identified on the basis of an unexplained increase in troponin T/I levels associated with either suggestive cardiac magnetic resonance imaging (MRI) findings, nonsignificant coronary artery abnormalities or positive endomyocardial biopsy.The prevalence of myocarditis in aSS is 3.4% and was not linked to any autoantibody specificity: anti-Jo1 (n = 8), anti-PL7 (n = 3), and anti-PL12 (n = 1). Myocarditis was a part of the first aSS manifestations in 42% of the cases and was asymptomatic (n = 2) or revealed by an acute (n = 4) or a subacute (n = 6) cardiac failure. It should be noted that myocarditis was always associated with an active myositis. When performed (n = 11), cardiac MRI revealed a late hypersignal in the T1-images in 73% of the cases (n = 8). Half of the patients required intensive care. Ten patients (83%) received dedicated cardiotropic drugs. Steroids and at least 1 immunosuppressive drug were given in all cases. After a median follow-up of 11 months (range 0-84) 9 (75%) patients recovered whereas 3 (25%) developed a chronic cardiac insufficiency. No patient died.The prevalence of myocarditis in aSS is similar to that of other inflammatory myopathies. Although the prognosis is relatively good, myocarditis is a severe condition and should be carefully considered as a possible manifestation in active aSS patients.

  12. Survival after acute lymphocytic leukaemia: effects of socioeconomic status and geographic region

    PubMed Central

    Schillinger, J.; Grosclaude, P.; Honjo, S.; Quinn, M.; Sloggett, A.; Coleman, M.

    1999-01-01

    National cancer registry data, linked to an areal measure of material deprivation, were used to explore possible socioeconomic and regional variation in the survival of children (0-14 years) diagnosed with acute lymphocytic leukaemia (ALL) in England and Wales from 1971 to 1990. Survival analysis and Poisson regression were used to estimate observed (crude) survival probabilities and the adjusted hazard of death. There was little evidence of a socioeconomic gradient in survival. Regional differences in survival were observed over time. These differences were most pronounced in the first six months after diagnosis, and may be attributable to differential access to centralised paediatric oncology services or treatment protocols, or to the artefact of variations in regional cancer registry practice. Similar analyses should be repeated for other, less treatable childhood cancers. The results of this study can be used to help identify ways of reducing regional variation in survival.

 PMID:10086933

  13. Combination chemotherapy for marrow relapse in children and adolescents with acute lymphocytic leukaemia.

    PubMed

    Amadori, S; Spiriti, M A; Meloni, G; Pacilli, L; Papa, G; Mandelli, F

    1981-04-01

    38 children with acute lymphocytic leukaemia (ALL) in haematologic relapse were retreated with vincristine, daunomycin and prednisone (VPD) together with intrathecal methotrexate and prednisone, followed by asparaginase in those patients not in complete remission after 4 weeks. The overall complete remission (CR) rate was 79%; asparaginase was needed to achieve CR in 7 of the 30 responding patients. The median duration of second remission was only 36 weeks, but 6 out of 15 children receiving the COAP-POMP-CART consolidation regimen remain in continuous second remission after 37-260 weeks; 3 of them are currently off all therapy. It is concluded that a prolonged second remission can be achieved in children with ALL in bone marrow relapse by combining intensive chemotherapy with the prevention of meningeal leukaemia.

  14. Acute sinusitis and blindness as the first presentation of chronic lymphocytic leukaemia.

    PubMed

    Lim, K H; Thomas, G; van Beers, E J; Hosman, A E; Mourits, M P; van Noesel, C J M; Kater, A P; Reinartz, S M

    2014-12-01

    Chronic lymphocytic leukaemia (CLL) is the most frequent form of leukaemia among adults in the Western world, presenting at a median age of 65 years. The diagnosis is usually made incidentally during routine blood examination while the disease is still in its early phase. We report a case of blindness of 24 hours due to acute sinusitis based on CLL localisation in a patient with undiagnosed CLL. Emergency endoscopic sinus surgery and intra- and extra-ocular orbital decompression were performed. The sinusitis resolved after surgery and intravenous antibiotics. Her vision improved within 24 hours and eventually recovered completely after six months. Her CLL remained in an indolent state, needing no active treatment. This case illustrates that blindness from a lymphoproliferative disorder may be treated with emergency endoscopic sinus surgery instead of conventional chemotherapy in order to salvage the vision first, even if the vision is lost for more than 24 hours.

  15. Acute lymphocytic leukemia mimicking spondyloarthritis in an adolescent: A case report and review of the literature

    PubMed Central

    XU, DANYI; XU, GUANHUA; XU, LIQIN; CAO, HENG; XU, BEI; CHEN, WEIQIAN; SUN, CHUANYIN; YUE, LIHUAN; LIN, JIN

    2016-01-01

    The present study describes the case of an 18-year-old adolescent male exhibiting acute lymphocytic leukemia (ALL), complicated by the onset of the symptom of sacroiliitis mimicking spondyloarthritis. Atypical features including an enlarged spleen, poor effects of non-steroidal anti-inflammatory drug therapy, low levels of hemoglobin, a low platelet count, a low neutrophil count and increased levels of monocytes, indicated the possibility of hematological malignancy. Bone marrow examination confirmed the diagnosis of ALL. The patient received chemotherapy and the symptoms were dramatically relieved. To the best of our knowledge, the current study reports the second published case of a patient with ALL presenting with sacroiliitis. Sacroiliitis as an onset manifestation of ALL may result in misdiagnosis, therefore, a differential diagnosis is essential when atypical features are present. PMID:26893708

  16. Organ irradiation and combination chemotherapy in treatment of acute lymphocytic leukaemia in children.

    PubMed Central

    Lanzkowsky, P; Shende, A; Aral, I; Saluja, G

    1975-01-01

    Lanzkowsky, P., Shende, A., Aral, I., Saluja, G. (1975). Archives of Disease in Childhood, 50, 685. Organ irradiation and combination chemotherapy in treatment of acute lymphocytic leukaemia in children. A total of 30 consecutive children with acute lymphocytic leukaemia (ALL) were treated from June 1971 until December 1974. Remission was induced with the use of vincristine and prednisone. After induction of remission, cranial irradiation and intrathecal methotrexate were given. Then the liver, spleen, and kidney were irradiated and 6-mercaptopurine, cyclophosphamide, and methotrexate were administered during the maintenance phase. Pulsed doses of vincristine and prednisone were administered at 10- to 12-week intervals. The patients were subdivided into two groups based on their initial white blood cell (WBC) counts: a standard risk group with an initial WBC count of less than 25 000/mm3 (25 X 10(9)/1) and a high risk group with an initial WBC count greater than 25 000/mm3 (25 X 10(9)/1). Of the 30 children entered in this study one standard risk patient died in the induction phase before attaining remission. Analysis of the results is therefore based on the remaining 29 patients, 22 standard risk and 7 high risk patients, who attained complete remission. Survival rates in continuous remission were found to be 43% of the high risk group, 88% for the standard risk group, and 77% for the combined group. Analysis of the data indicates that this therapy is unsatisfactory in high risk ALL. The results to date of this therapy for standard risk are sufficiently encouraging to continue its use in this subgroup of patients. PMID:1059384

  17. Myocarditis in patients with subarachnoid hemorrhage: A histopathologic study.

    PubMed

    van der Bilt, Ivo A C; Vendeville, Jean-Paul; van de Hoef, Tim P; Begieneman, Mark P V; Lagrand, Wim K; Kros, Johan M; Wilde, Arthur A M; Rinkel, Gabriel J E; Niessen, Hans W M

    2016-04-01

    Cardiac abnormalities after subarachnoid hemorrhage (SAH) such as electrocardiographic changes, echocardiographic wall motion abnormalities, and elevated troponin levels are independently associated with a poor prognosis. They are caused by catecholaminergic stress coinciding with influx of inflammatory cells into the heart. These abnormalities could be a sign of a myocarditis, potentially giving insight in pathophysiology and treatment options. These inflammatory cells are insufficiently characterized, and it is unknown whether myocarditis is associated with SAH. Myocardium of 25 patients who died of SAH and 18 controls was stained with antibodies identifying macrophages (CD68), lymphocytes (CD45), and neutrophil granulocytes (myeloperoxidase). Myocytolysis was visualized using complement staining (C3d). CD31 was used to identify putative thrombi. We used Mann-Whitney U testing for analysis. In the myocardium of SAH patients, the amount of myeloperoxidase-positive (P < .005), CD45-positive (P < .0005), and CD68-positive (P < .0005) cells was significantly higher compared to controls. Thrombi in intramyocardial arteries were found in 22 SAH patients and 1 control. Myocytolysis was found in 6 SAH patients but not in controls. Myocarditis, consisting of an influx of neutrophil granulocytes, lymphocytes, and macrophages, coinciding with myocytolysis and thrombi in intramyocardial arteries, occurs in patients with SAH but not in controls. These findings might explain the cardiac abnormalities after SAH and may have implications for treatment.

  18. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-08-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Secondary Acute Myeloid Leukemia; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma

  19. The role of neutrophil lymphocyte ratio to leverage the differential diagnosis of familial Mediterranean fever attack and acute appendicitis

    PubMed Central

    Kucuk, Adem; Erol, Mehmet Fatih; Senel, Soner; Eroler, Emir; Yumun, Havvanur Alparslan; Uslu, Ali Ugur; Erol, Asiye Mukaddes; Tihan, Deniz; Duman, Ugur; Kucukkartallar, Tevfik; Solak, Yalcin

    2016-01-01

    Background/Aims: Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever and diffuse abdominal pain. The primary concern with this presentation is to distinguish it from acute appendicitis promptly. Thus, we aimed to evaluate the role of neutrophil lymphocyte ratio (NLR) to leverage the differential diagnosis of acute FMF attack with histologically proven appendicitis. Methods: Twenty-three patients with histologically confirmed acute appendicitis and 88 patients with acute attack of FMF were included in the study. NLR, C-reactive protein and other hematologic parameters were compared between the groups. Results: Neutrophil to lymphocyte ratio was significantly higher in patients with acute appendicitis compared to the FMF attack group (8.24 ± 6.31 vs. 4.16 ± 2.44, p = 0.007). The performance of NLR in diagnosing acute appendicitis with receiver operating characteristic analysis with a cut-off value of 4.03 were; 78% sensitivity, 62% specificity, and area under the curve 0.760 (95% confidence interval, 0.655 to 0.8655; p < 0.001). Conclusions: This study showed that NLR, the simple and readily available inflammatory marker may have a useful role in distinguishing acute FMF attack from acute appendicitis. PMID:26864298

  20. Acute exercise mobilises CD8+ T lymphocytes exhibiting an effector-memory phenotype.

    PubMed

    Campbell, John P; Riddell, Natalie E; Burns, Victoria E; Turner, Mark; van Zanten, Jet J C S Veldhuijzen; Drayson, Mark T; Bosch, Jos A

    2009-08-01

    An acute bout of exercise evokes mobilisation of lymphocytes into the bloodstream, which can be largely attributed to increases in CD8+ T lymphocytes (CD8TLs) and natural killer (NK) cells. Evidence further suggests that, even within these lymphocyte subsets, there is preferential mobilisation of cells that share certain functional and phenotypic characteristics, such as high cytotoxicity, low proliferative ability, and high tissue-migrating potential. These features are characteristic of effector-memory CD8TL subsets. The current study therefore investigated the effect of exercise on these newly-identified subsets. Thirteen healthy and physically active males (mean+/-SD: age 20.9+/-1.5 yr) attended three sessions: a control session (no exercise); cycling at 35% Watt(max) (low intensity exercise); and 85% Watt(max) (high intensity exercise). Each bout lasted 20 min. Blood samples were obtained before exercise, during the final min of exercise, and +15, and +60 min post-exercise. CD8TLs were classified into naïve, central memory (CM), effector-memory (EM), and CD45RA+ effector-memory (RAEM) using combinations of the cell surface markers CCR7, CD27, CD62L, CD57, and CD45RA. In parallel, the phenotypically distinct CD56(bright) 'regulatory' and CD56(dim) 'cytotoxic' NK subsets were quantified. The results show a strong differential mobilisation of CD8TL subsets (RAEM>EM>CM>naïve); during high intensity exercise the greatest increase was observed for RAEM CD8Tls (+450%) and the smallest for naïve cells (+84%). Similarly, CD56(dim) NK cells (+995%) were mobilised to a greater extent than CD56(bright) (+153%) NK cells. In conclusion, memory CD8TL that exhibit a high effector and tissue-migrating potential are preferentially mobilised during exercise. This finding unifies a range of independent observations regarding exercise-induced phenotypic and functional changes in circulating lymphocytes. The selective mobilisation of cytotoxic tissue-migrating subsets, both

  1. B Lymphocytes Differentially Influence Acute and Chronic Allograft Rejection in Mice1

    PubMed Central

    DiLillo, David J.; Griffiths, Robert; Seshan, Surya V.; Magro, Cynthia M.; Ruiz, Phillip; Coffman, Thomas M.; Tedder, Thomas F.

    2013-01-01

    The relative contributions of B lymphocytes and plasma cells during allograft rejection remain unclear. Therefore, the effects of B cell depletion on acute cardiac rejection, chronic renal rejection, and skin graft rejection were compared using CD20 or CD19 mAbs. Both CD20 and CD19 mAbs effectively depleted mature B cells, while CD19 mAb treatment depleted plasmablasts and some plasma cells. B cell depletion did not affect acute cardiac allograft rejection, although CD19 mAb treatment prevented allograft-specific IgG production. Strikingly, CD19 mAb treatment significantly reduced renal allograft rejection and abrogated allograft-specific IgG development, while CD20 mAb treatment did not. By contrast, B cell depletion exacerbated skin allograft rejection and augmented the proliferation of adoptively transferred alloantigen-specific CD4+ T cells, demonstrating that B cells can also negatively regulate allograft rejection. Thereby, B cells can either positively or negatively regulate allograft rejection depending on the nature of the allograft and the intensity of the rejection response. Moreover, CD19 mAb may represent a new approach for depleting both B cells and plasma cells to concomitantly impair T cell activation, inhibit the generation of new allograft-specific Abs, or reduce preexisting allograft-specific Ab levels in transplant patients. PMID:21248259

  2. TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis

    PubMed Central

    Baijer, Jan; Déchamps, Nathalie; Perdry, Hervé; Morales, Pablo; Kerns, Sarah; Vasilescu, Alexandre; Baulande, Sylvain; Azria, David; Roméo, Paul Henri; Schmitz, Annette

    2016-01-01

    Sensitivity of T4 effector-memory (T4EM) lymphocytes to radiation-induced apoptosis shows heritability compatible with a Mendelian mode of transmission. Using gene expression studies and flow cytometry, we show a higher TNF-Related Apoptosis Inducing Ligand (TRAIL/TNFSF10) mRNA level and a higher level of membrane bound TRAIL (mTRAIL) on radiosensitive compared to radioresistant T4EM lymphocytes. Functionally, we show that mTRAIL mediates a pro-apoptotic autocrine signaling after irradiation of T4EM lymphocytes linking mTRAIL expression to T4EM radiosensitivity. Using single marker and multimarker Family-Based Association Testing, we identified 3 SNPs in the TRAIL gene that are significantly associated with T4EM lymphocytes radiosensitivity. Among these 3 SNPs, two are also associated with acute and subacute dermatitis after radiotherapy in breast cancer indicating that T4EM lymphocytes radiosensitivity may be used to predict response to radiotherapy. Altogether, these results show that mTRAIL level regulates the response of T4EM lymphocytes to ionizing radiation and suggest that TRAIL/TNFSF10 genetic variants hold promise as markers of individual radiosensitivity. PMID:26982083

  3. [The differentiation of human peripheral blood lymphocytes by immunological methods. III. Results in acute lymphoblastic leukemia (author's transl)].

    PubMed

    Pathouli, C; Michlmayr, G; Huber, C; Kurz, R; Haas, H; Resch, R; Falkensammer, M; Abbrederis, K; Huber, H; Braunsteiner, H

    1977-07-01

    In 47 patients with acute lymphoblastic leukemia surface markers were evaluated on mononuclear cells of the peripheral blood as well as in some cases on bone marrow lymphocytes. The lymphocytes were characterized by their binding capacity for sheep red blood cells, the demonstration of Fc-receptors, complement receptors as well as surface immunoglobulins. In 6 of 23 untreated patients the blasts bound sheep red blood cells spontaneously (T-ALL), in two of these six cases the lymphoblasts had simultaneously receptors for complement. In a further patients the lymphoblasts had complement- and Fc-receptors. The blasts of 16 of 23 patients were negative in respect to the markers tested (O-ALL). By comparing two groups of patients--one with positive cells, one unreactive--the clinical features differed: the marker positive group showed a predominance of male patients, 5 of 7 patients had a massive mediastinal mass and the remission rate was lower than in the group with positive blasts. 24 patients in remission under maintance treatment had a decreased percentage of rosette forming lymphocytes as well as lymphocytes with surface immunoglobulins and Fc-receptors. There existed some correlation between the percentage of rosette forming lymphocytes and the clinical course: patients with complications had lower percentages of rosette forming lymphocytes than patients with a favourable course.

  4. Reversible myocarditis after spider bite

    PubMed Central

    Kara, Hasan; Ak, Ahmet; Bayir, Aysegul; Avci, Ahmet

    2013-01-01

    Black widow spiders (Latrodectus tredecimguttatus) are poisonous spiders endemic in Turkey. Latrodectus bites may cause myocarditis with increased cardiac enzymes. We treated two men (aged 20 and 33 years) who had myocarditis after black spider bites with leucocytosis and elevated levels of troponin I, creatine kinase and creatine kinase-MB fraction. Both patients had normal results on an ECG, and one patient had abnormal echocardiography with minimal left ventricular wall movement disorder. Both patients were hospitalised in the intensive care unit and treated with intravenous fluids, analgesics, spasmolytic drugs, tetanus prophylaxis and cardiac monitoring. The levels of troponin I, creatine kinase and creatine kinase-MB fraction improved, and the patients were discharged home on the third and fifth hospital day without complications. Myocarditis after a Latrodectus bite is rare, but may be associated with serious complications. Therefore, in regions endemic with Latrodectus spiders, prudent treatment of spider bites may include cardiac evaluation and monitoring. PMID:23572268

  5. Reversible myocarditis after spider bite.

    PubMed

    Kara, Hasan; Ak, Ahmet; Bayir, Aysegul; Avci, Ahmet

    2013-04-08

    Black widow spiders (Latrodectus tredecimguttatus) are poisonous spiders endemic in Turkey. Latrodectus bites may cause myocarditis with increased cardiac enzymes. We treated two men (aged 20 and 33 years) who had myocarditis after black spider bites with leucocytosis and elevated levels of troponin I, creatine kinase and creatine kinase-MB fraction. Both patients had normal results on an ECG, and one patient had abnormal echocardiography with minimal left ventricular wall movement disorder. Both patients were hospitalised in the intensive care unit and treated with intravenous fluids, analgesics, spasmolytic drugs, tetanus prophylaxis and cardiac monitoring. The levels of troponin I, creatine kinase and creatine kinase-MB fraction improved, and the patients were discharged home on the third and fifth hospital day without complications. Myocarditis after a Latrodectus bite is rare, but may be associated with serious complications. Therefore, in regions endemic with Latrodectus spiders, prudent treatment of spider bites may include cardiac evaluation and monitoring.

  6. Unusual Presentation of Listerial Myocarditis and the Diagnostic Value of Cardiac Magnetic Resonance

    PubMed Central

    Ladani, Amit P.; Vaghasia, Nishit; Generalovich, Thomas

    2015-01-01

    Listeria monocytogenes is an infrequent cause of bacterial myocarditis. Myocarditis without evidence of endocarditis is even rarer. Management in such cases involves early diagnosis, antibiotic therapy, and emergency treatment of arrhythmias. We report the case of a 47-year-old man who presented with features of acute ST-segment-elevation myocardial infarction complicated by ventricular tachycardia that necessitated urgent electrical cardioversion. Contrast-enhanced cardiac magnetic resonance images revealed hypertrophy, necrosis, and a mass that was determined to be an abscess caused by L. monocytogenes. Antibiotic treatment led to resolution of the listerial myocarditis. In addition to reporting our patient's case, we discuss the comparative advantages of cardiac magnetic resonance versus transthoracic echocardiography in characterizing myocarditis, upon presentation and in follow-up evaluation. PMID:26175642

  7. Unusual presentation of listerial myocarditis and the diagnostic value of cardiac magnetic resonance.

    PubMed

    Ladani, Amit P; Biswas, Abhishek; Vaghasia, Nishit; Generalovich, Thomas

    2015-06-01

    Listeria monocytogenes is an infrequent cause of bacterial myocarditis. Myocarditis without evidence of endocarditis is even rarer. Management in such cases involves early diagnosis, antibiotic therapy, and emergency treatment of arrhythmias. We report the case of a 47-year-old man who presented with features of acute ST-segment-elevation myocardial infarction complicated by ventricular tachycardia that necessitated urgent electrical cardioversion. Contrast-enhanced cardiac magnetic resonance images revealed hypertrophy, necrosis, and a mass that was determined to be an abscess caused by L. monocytogenes. Antibiotic treatment led to resolution of the listerial myocarditis. In addition to reporting our patient's case, we discuss the comparative advantages of cardiac magnetic resonance versus transthoracic echocardiography in characterizing myocarditis, upon presentation and in follow-up evaluation.

  8. The effects of prophylactic treatment of the central nervous system on the intellectual functioning of children with acute lymphocytic leukemia

    SciTech Connect

    Moss, H.A.; Nannis, E.D.; Poplack, D.G.

    1981-07-01

    The effect of central nervous system prophylaxis (cranial radiation and intrathecal chemotherapy) on intellectual function was studied in 24 children with acute lymphocytic leukemia. The Wechsler Intelligence tests were administered to these children and to a sample of their healthy siblings, who served as a comparison group. The mean Full Scale lQ was 98.6 for the patients and 112.5 for the sibling controls (p less than 0.001 level). Those patients who received central nervous system preventive treatment at a young age exhibited a greater decrement in intellectual abilities than did patients who were older when they received this treatment. In contrast, leukemia patients who had not received central nervous system prophylaxis had IQs that did not differ statistically from those of their siblings. These data suggest that central nervous system prophylaxis may have an adverse effect on the intellectual capability of children with acute lymphocytic leukemia.

  9. Brugada pattern in toxic myocarditis due to severe aluminum phosphide poisoning.

    PubMed

    Nayyar, Sachin; Nair, Mohan

    2009-11-01

    Brugada pattern electrocardiogram (ECG) unmasking can occur due to various drugs. There are old reports of the acute infarction pattern in aluminum phosphide (rodenticide)-related toxic myocarditis. The given case illustrates the Brugada pattern and various other ECG abnormalities in a patient with this poisoning. The old reported cases of the acute infarction pattern are also likely the Brugada pattern.

  10. Glioblastoma multiforme following prophylactic cranial irradiation and intrathecal methotrexate in a child with acute lymphocytic leukemia. [. gamma. rays; infants

    SciTech Connect

    Chung, C.K.; Stryker, J.A.; Cruse, R.; Vannuci, R.; Towfighi, J.

    1981-06-01

    Cases of radiation-induced glioma in humans are extremely rare. A 2-year-old boy with acute lymphocytic leukemia had received prophylactic cranial irradiation (2400 rad/2 1/2 weeks) and intrathecal methotrexate. Five years later he developed a glioblastoma multiforme on the left cerebral hemisphere while the leukemia was in remission. This is the first reported association of these disorders. It is possible that the glioma may have been induced by radiation and/or chemotherapy.

  11. Overshoot phenomenon of phytohemagglutinin response after chemotherapy and its relationship to remission in acute non-lymphocytic leukemia.

    PubMed

    Harada, M; Mori, T; Kodo, H; Ishino, C; Matsue, K; Hattori, K

    1979-02-01

    To define the relationship between cell-mediated immunity and responses to chemotherapy or prognosis, delayed cutaneous hypersensitivity, E- and active E-rosette tests, and mitogenic responses of lymphocytes were examined in 15 patients with acute nonlymphocytic leukemia. Its results indicated that cell-mediated immunity before remission induction chemotherapy did not correlate with the outcome of treatment. In contrast, delayed cutaneous hypersensitivity and mitogenic response tested after remission induction correlated with therepeutic effect. Further a "rebound" or overshoot of phytohemagglutinin responsiveness was observed in patients achieving remission. Serial studies on cell-mediated immunity may be useful for predicting therapuetic efficacy and prognosis in patients with acute leukemia.

  12. Meningosis prophylaxis with intrathecal /sup 198/Au-colloid and methotrexate in childhood acute lymphocytic leukemia

    SciTech Connect

    Metz, O.; Stoll, W.; Plenert, W.

    1982-01-15

    Since 1972, telecobalt irradiation plus intrathecal methotrexate (ITMTX) has been successfully replaced in Jena by intrathecal colloidal radioactive gold (/sup 198/Au) plus ITMTX for meningosis prophylaxis in leukemia. Seventy-three children with acute lymphocytic leukemia (ALL) were given 1.24-4.89 mCi (45.8-181 MBq) of colloidal 198Au IT after successful initiation of remission. During cytostatic therapy, the following relapses occurred: meningosis leucaemica, five patients (6.8%); bone-marrow relapse and the meningosis leucaemica, one patient; and bone-marrow relapse, 20 patients (27.4%). In 18 children, combination chemotherapy was terminated after two and a half or three years of treatment. After that time, one meningeal relapse and six bone-marrow relapses occurred. Within the first 24 hours after application of radioactive gold, headaches, vomiting, and fever occurred in less than 10% of the children. An apathy syndrome, leukecephalopathy, or severe infections, were not observed in a single case. Radioactive gold spreads in the subarachnoid space and is phagocytized by the arachnoidea. The tumoricide effect extends selectively over the space of distribution of the latent meningosis leucaemia. The cerebral parenchyma remains unaffected by radiation. Thus, radioactive gold may be preferable to telecobalt irradiation in preventing central nervous system leukemia.

  13. Elevated lymphocyte count at time of acute myeloid leukemia diagnosis is associated with shorter remission.

    PubMed

    Bar, Merav; Othus, Megan; Park, Hanahlyn M; Sandhu, Vicky; Chen, Xueyan; Wood, Brent L; Estey, Elihu

    2015-01-01

    In solid tumors, decreased absolute lymphocyte count (ALC) at diagnosis was found to be associated with poorer outcome, but there is only limited data on the impact of ALC in acute myeloid leukemia (AML). In this study we evaluated the prognostic value of ALC on outcome in 259 adult patients with AML who responded to induction therapy. Higher than normal ALC at diagnosis was associated with shorter remission (HR 4.06; p < 0.001), and decreased relapse free and overall survival (HR 3.47; p < 0.001 and HR 3.85; p < 0.001 respectively). Flow cytometry showed low frequency of natural killer (NK) cells and high frequency of CD4+ T cells (which includes the subset of T regulatory cells) in the high ALC group. Low frequency of NK cells and potentially high frequency of inhibitory T regulatory cells may result in weaker immune responses against residual leukemia and may explain the poorer outcome of the high ALC group.

  14. DR3 regulation of apoptosis of naive T-lymphocytes in children with acute infectious mononucleosis.

    PubMed

    Filatova, Elena Nikolaevna; Anisenkova, Elena Viktorovna; Presnyakova, Nataliya Borisovna; Utkin, Oleg Vladimirovich

    2016-09-01

    Acute infectious mononucleosis (AIM) is a widespread viral disease that mostly affects children. Development of AIM is accompanied by a change in the ratio of immune cells. This is provided by means of different biological processes including the regulation of apoptosis of naive T-cells. One of the potential regulators of apoptosis of T-lymphocytes is a death receptor 3 (DR3). We have studied the role of DR3 in the regulation of apoptosis of naive CD4(+) (nTh) and CD8(+) (nCTL) T-cells in healthy children and children with AIM. In healthy children as well as in children with AIM, the activation of DR3 is accompanied by inhibition of apoptosis of nTh. In healthy children, the stimulation of DR3 resulted in the increase in apoptosis of nCTL. On the contrary, in children with AIM, the level of apoptosis of nCTL decreased after DR3 activation, which is a positive contribution to the antiviral immune response. In children with AIM, nCTL are characterized by reduced level of apoptosis as compared with healthy children. These results indicate that DR3 can be involved in the reduction of sensitivity of nCTL to apoptosis in children with AIM.

  15. Neutrophil-To-Lymphocyte Ratio Predicts 3-Month Outcome of Acute Ischemic Stroke.

    PubMed

    Qun, Sen; Tang, Yan; Sun, Jing; Liu, Zhaoxia; Wu, Juncang; Zhang, Ji; Guo, Jidong; Xu, Zhiqiang; Zhang, Dan; Chen, Zhengxu; Hu, Fuyong; Xu, Xingshun; Ge, Wei

    2017-04-01

    Increasing evidences have demonstrated that inflammation is involved in the mechanisms of acute ischemic stroke (AIS). As an important and easy-to-measure inflammatory marker, neutrophil-to-lymphocyte ratio (NLR) shows a high association with mortality in patients with stroke in recent studies. In this study, we evaluated the prognostic role of NLR in patients with AIS. One hundred forty-three patients with AIS were enrolled. Clinical data were collected and the NLR was calculated from the admission blood work. The patients were followed up for 3 months after stroke onset. The occurrence of death and the major disability at 3 months after onset were end points in this study. Modified Rankin Scale score ≥3 was considered as poor outcome. In this study, 75 patients (52%) had poor outcome. We used binary logistic regression model to evaluate risk factor for poor outcome of AIS and found that the NLR was independently associated with the poor outcome of 3 months (P < 0.001). The optimal cutoff value for NLR as a predictor for 3-month outcome was 2.995. Therefore, in our study, high NLRs inversely predicted 3-month outcome in patients with AIS.

  16. Immunopathological Features of Canine Myocarditis Associated with Leishmania infantum Infection.

    PubMed

    Costagliola, Alessandro; Piegari, Giuseppe; Otrocka-Domagala, Iwona; Ciccarelli, Davide; Iovane, Valentina; Oliva, Gaetano; Russo, Valeria; Rinaldi, Laura; Papparella, Serenella; Paciello, Orlando

    2016-01-01

    Myocarditis associated with infectious diseases may occur in dogs, including those caused by the protozoa Neospora caninum, Trypanosoma cruzi, Babesia canis, and Hepatozoon canis. However, although cardiac disease due to Leishmania infection has also been documented, the immunopathological features of myocarditis have not been reported so far. The aim of this study was to examine the types of cellular infiltrates and expression of MHC classes I and II in myocardial samples obtained at necropsy from 15 dogs with an established intravitam diagnosis of visceral leishmaniasis. Pathological features of myocardium were characterized by hyaline degeneration of cardiomyocytes, necrosis, and infiltration of mononuclear inflammatory cells consisting of lymphocytes and macrophages, sometimes with perivascular pattern; fibrosis was also present in various degrees. Immunophenotyping of inflammatory cells was performed by immunohistochemistry on cryostat sections obtained from the heart of the infected dogs. The predominant leukocyte population was CD8+ with a fewer number of CD4+ cells. Many cardiomyocytes expressed MHC classes I and II on the sarcolemma. Leishmania amastigote forms were not detected within macrophages or any other cell of the examined samples. Our study provided evidence that myocarditis in canine visceral leishmaniasis might be related to immunological alterations associated with Leishmania infection.

  17. Immunopathological Features of Canine Myocarditis Associated with Leishmania infantum Infection

    PubMed Central

    Piegari, Giuseppe; Otrocka-Domagala, Iwona; Ciccarelli, Davide; Iovane, Valentina; Oliva, Gaetano; Russo, Valeria; Rinaldi, Laura; Papparella, Serenella; Paciello, Orlando

    2016-01-01

    Myocarditis associated with infectious diseases may occur in dogs, including those caused by the protozoa Neospora caninum, Trypanosoma cruzi, Babesia canis, and Hepatozoon canis. However, although cardiac disease due to Leishmania infection has also been documented, the immunopathological features of myocarditis have not been reported so far. The aim of this study was to examine the types of cellular infiltrates and expression of MHC classes I and II in myocardial samples obtained at necropsy from 15 dogs with an established intravitam diagnosis of visceral leishmaniasis. Pathological features of myocardium were characterized by hyaline degeneration of cardiomyocytes, necrosis, and infiltration of mononuclear inflammatory cells consisting of lymphocytes and macrophages, sometimes with perivascular pattern; fibrosis was also present in various degrees. Immunophenotyping of inflammatory cells was performed by immunohistochemistry on cryostat sections obtained from the heart of the infected dogs. The predominant leukocyte population was CD8+ with a fewer number of CD4+ cells. Many cardiomyocytes expressed MHC classes I and II on the sarcolemma. Leishmania amastigote forms were not detected within macrophages or any other cell of the examined samples. Our study provided evidence that myocarditis in canine visceral leishmaniasis might be related to immunological alterations associated with Leishmania infection. PMID:27413751

  18. Fructus Amomi Cardamomi Extract Inhibit Coxsackievirus-B3 Induced Myocarditis in Murine Myocarditis Model.

    PubMed

    Lee, Yun-Gyeong; Park, Jung-Ho; Jeon, Eun-Seok; Kim, Jin-Hee; Lim, Byung-Kwan

    2016-11-28

    Coxsackievirus B3 (CVB3) is the main cause of acute myocarditis and dilated cardiomyopathy. Plant extracts are considered as useful materials to develop new antiviral drugs. We had previously selected candidate plant extracts, which showed anti-inflammatory effects. We examined the antiviral effects by using a HeLa cell survival assay. Among these extracts, we chose the Amomi Cardamomi (Amomi) extract, which showed strong antiviral effect and preserved cell survival in CVB3 infection. We investigated the mechanisms underlying the ability of Amomi extract to inhibit CVB3 infection and replication. HeLa cells were infected by CVB3 with or without Amomi extract. Erk and Akt activities, and their correlation with virus replication were observed. Live virus titers in cell supernatants and viral positive- and negative-strand RNA amplification were measured. Amomi extract significantly increased HeLa cell survival in different concentrations (100-10 µg/ml). CVB3 capsid protein VP1 expression (76%) and viral protease 2A-induced eIF4G1 cleavage (70%) were significantly decreased in Amomi extract (100 µg/ml) treated cells. The levels of positive- (20%) and negative-strand (80%) RNA were dramatically decreased compared with the control, as revealed by reverse transcription-PCR. In addition, Amomi extract improved mice survival (51% vs 26%) and dramatically reduced heart inflammation in a CVB3-induced myocarditis mouse model. These results suggested that Amomi extract significantly inhibited Enterovirus replication and myocarditis damage. Amomi may be developed as a therapeutic drug for Enterovirus.

  19. BIRC3 alterations in chronic and B-cell acute lymphocytic leukemia patients

    PubMed Central

    ALHOURANI, EYAD; OTHMAN, MONEEB A.K.; MELO, JOANA B.; CARREIRA, ISABEL M.; GRYGALEWICZ, BEATA; VUJIĆ, DRAGANA; ZECEVIĆ, ZELJKO; JOKSIĆ, GORDANA; GLASER, ANITA; POHLE, BEATE; SCHLIE, CORDULA; HAUKE, SVEN; LIEHR, THOMAS

    2016-01-01

    Deletions within chromosome 11q22-23, are considered among the most common chromosomal aberrations in chronic lymphocytic leukemia (CLL), and are associated with a poor outcome. In addition to the ataxia telangiectasia mutated (ATM) gene, the baculoviral IAP repeat-containing 3 (BIRC3) gene is also located in the region. BIRC3 encodes a negative regulator of the non-canonical nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) protein. Disruption of BIRC3 is known to be restricted to CLL fludarabine-refractory patients. The aim of the present study was to determine the frequency of copy number changes of BIRC3 and to assess its association with two known predictors of negative CLL outcome, ATM and tumor protein 53 (TP53) gene deletions. To evaluate the specificity of BIRC3 alterations to CLL, BIRC3 copy numbers were assessed in 117 CLL patients in addition to 45 B-cell acute lymphocytic leukemia (B-ALL) patients. A commercially available multiplex ligation dependent probe amplification kit, which includes four probes for the detection of TP53 and four probes for ATM gene region, was applied. Interphase-directed fluorescence in situ hybridization was used to apply commercially available probes for BIRC3, ATM and TP53. High resolution array-comparative genomic hybridization was conducted in selected cases. Genetic abnormalities of BIRC3 were detected in 23/117 (~20%) of CLL and 2/45 (~4%) of B-ALL cases. Overall, 20 patients with CLL and 1 with B-ALL possessed a BIRC3 deletion, whilst 3 patients with CLL and 1 with B-ALL harbored a BIRC3 duplication. All patients with an ATM deletion also carried a BIRC3 deletion. Only 2 CLL cases possessed deletions in BIRC3, ATM and TP53 simultaneously. Evidently, the deletion or duplication of BIRC3 may be observed rarely in B-ALL patients. BIRC3 duplication may occur in CLL patients, for which the prognosis requires additional studies in the future. The likelihood that TP53 deletions occur simultaneously with

  20. Evaluation of In-111 labeled lymphocytes in an acute rejection model

    SciTech Connect

    Schauwecker, D.S.; Leapman, S.B.; Siddiqui, A.R.; Filo, R.S.; Smith, P.G.; Forney, M.N.

    1983-01-01

    Four days after surgery, canine renal allografts were studied with 290-500 microCi of In-111/10(8) lymphocytes. All transplants were visualized, implying that it may not be necessary to harvest large numbers of lymphocytes from immunosuppressed patients. On the day of renal transplant, a second set of dogs were injected with 80-150 microCi of In-111/10(8) lymphocytes. No delayed visualization could be seen 2-4 days later when rejection commenced. Cellular damage, even at this lower level of labeling, may require injection of labeled lymphocytes after the onset of the rejection process in order to visualize the rejection organ.

  1. Clinical and pathologic findings of myocarditis in two families with dilated cardiomyopathy

    SciTech Connect

    O'Connell, J.B.; Fowles, R.E.; Robinson, J.A.; Subramanian, R.; Henkin, R.E.; Gunnar, R.M.

    1984-01-01

    The use of endomyocardial biopsy and gallium-67 scans in patients with dilated cardiomyopathy (DCM) has demonstrated the presence of myocardial inflammation in a subset of patients. A family with DCM was studied with endomyocardial biopsy and gallium-67 scanning; both identified the presence of myocarditis in the proband. Evaluation of histologic sections from deceased family members revealed myocarditis as the principal pathologic finding. This patient identified during life demonstrated a defect in suppressor lymphocytic function and improved with immunosuppressive therapy. A second family with DCM was discovered when postmortem examination of the proband and his father's heart showed myocarditis. A living sibling was identified with asymptomatic myocardial dysfunction. Longitudinal follow-up of surviving members of both families are in progress. This study indicates that thorough diagnostic evaluation of all patients with familial DCM should be pursued to identify subgroups with potentially treatable inflammation.

  2. The ratio of absolute lymphocyte count at interim of therapy to absolute lymphocyte count at diagnosis predicts survival in childhood B-lineage acute lymphoblastic leukemia.

    PubMed

    Cheng, Yuping; Luo, Zebin; Yang, Shilong; Jia, Ming; Zhao, Haizhao; Xu, Weiqun; Tang, Yongmin

    2015-02-01

    Absolute lymphocyte count (ALC) after therapy has been reported to be an independent prognostic factor for clinical outcome in leukemia. This study mainly analyzed ALC at interim of therapy on day 22 (ALC-22) and the ratio of ALC-22 to ALC at diagnosis (ALC-0) on the impact of survival and the relation of ALC to lymphocyte subsets in 119 pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients. Univariate analysis revealed that ALC-22/ALC-0 ratio <10% was significantly associated with inferior overall survival (OS) (hazard ratio (HR)=12.24, P=0.0014) and event-free survival (EFS) (HR=3.3, P=0.0046). In multivariate analysis, ALC-22/ALC-0 ratio remained an independent prognostic factor for OS (HR=6.92, P=0.0181) and EFS (HR=2.78, P=0.0329) after adjusting for age, white blood cell (WBC) count and minimal residual disease (MRD) status. A Spearman correlation test showed that CD3+ T cells had a negative correlation with ALC-0 (r=-0.7204, P<0.0001) and a positive correlation with ALC-22 (r=0.5061, P=0.0071). These data suggest that ALC-22/ALC-0 ratio may serve as a more effective biomarker to predict survival in pediatric B-ALL and ALC is mainly associated with CD3+ T cells.

  3. Platelet-to-lymphocyte ratio but not neutrophil-to-lymphocyte ratio predicts high on-treatment platelet reactivity in clopidogrel-treated patients with acute coronary syndrome

    PubMed Central

    Efe, Edem; Kocayiğit, Ibrahim; Türker, Pabuccu Mustafa; Murat, Küçükukur; Erkan, Alpaslan; Sedat, Taş; Alper, Çil; Necati, Aksoy Murat; Gökhan, Vural Mustafa; Bahri, Akdeniz

    2016-01-01

    Objectives: Dual antiplatelet therapy (DAPT), consisting of clopidogrel and aspirin, is the main-stay treatment of acute coronary syndromes (ACS). However, major adverse cardiovascular events may occur even in patients undergoing DAPT, and this has been related to the variable pharmacodynamic efficacy of these drugs, especially clopidogrel. Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are novel inflammatory markers for cardiovascular risk stratification, which may reflect an inflammatory state and thus high on-treatment platelet reactivity (HPR). Methods: We investigated the usefulness of PLR and NLR in predicting HPR in clopidogrel-treated patients with ACS. A total of 244 patients were enrolled in this study, and 43 of them were nonresponsive to clopidogrel. Results: Logistic regression analysis indicated that PLR was significantly associated with HPR (P < 0.001). Using a cutoff level of 331, PLR predicted HPR with a sensitivity of 73% and a specificity of 69% (odds ratio: 376.15, 95% confidence interval = 37.813–3741.728 P < 0.001, receiver operating characteristic curve: 0.885). Conclusions: We suggest that more attention should be paid to the PLR values of these patients on admission to identify individuals who may not benefit from clopidogrel during the course of ACS. PMID:27756943

  4. Salivary Lymphocyte Responses Follwing Acute Anaerobic Exercise In A Cool Environment.

    PubMed

    Carlson, Lara A; Lawrence, Michael A; LeCavalier, Kaylee; Koch, Alexander J

    2016-08-16

    The purpose of this study was to examine the impact of anaerobic training on salivary lymphocytes (s-LYMPH), and further determine whether these responses differ between cool vs. thermoneutral environments. Nine lightly clothed (∼0.3 clo) volunteers (7/2 women/men: age 21 ± 1 y; height 168.7 ± 7.3 cm; weight 66.4 ± 8.4 kg; body fat 20.6 ± 7.6%) completed speed, agility, and quickness (SAQ) sessions in both warm (18.9°C, Biddeford, Maine, USA) and cool (10.4°C, Thorsmörk, Iceland) temperatures. SAQ sessions consisted of three trials of 20 m sprints, 40 m sprints, t-tests, and box drills, and two 300-yd shuttle runs in both conditions. Saliva samples via passive drool were collected at baseline, immediately postexercise, and after 2 h of recovery. s-LYMPH increased (p<0.001) immediately postexercise, followed by a decrease (p<0.001) below baseline values after 2 h of recovery in both environments. s-LYMPH counts were lower (p<0.001) for the cool environment than for the thermoneutral environment. s-LYMPH counts increased postexercise, followed by a decrease after 2 h of recovery in regardless of environment. Acute anaerobic exercise induced transient changes in s-LYMPH counts similar to that observed in peripheral blood. Compared to baseline measures, changes in s-LYMPH were of a smaller magnitude following exercise in the cool environment as compared to thermoneutral. In summary, there is no indication that exercise in the cool environment presented a greater challenge to the subjects' immunity. Rather, these data indicate exercise in a cool environment produces smaller fluctuations in salivary immune cells as compared to resting levels.

  5. Tobacco Smoke and Risk of Childhood Acute Non-Lymphocytic Leukemia: Findings from the SETIL Study

    PubMed Central

    Mattioli, Stefano; Farioli, Andrea; Legittimo, Patrizia; Miligi, Lucia; Benvenuti, Alessandra; Ranucci, Alessandra; Salvan, Alberto; Rondelli, Roberto; Magnani, Corrado

    2014-01-01

    Background Parental smoking and exposure of the mother or the child to environmental tobacco smoke (ETS) as risk factors for Acute non-Lymphocytic Leukemia (AnLL) were investigated. Methods Incident cases of childhood AnLL were enrolled in 14 Italian Regions during 1998–2001. We estimated odds ratios (OR) and 95% confidence intervals (95%CI) conducting logistic regression models including 82 cases of AnLL and 1,044 controls. Inverse probability weighting was applied adjusting for: age; sex; provenience; birth order; birth weight; breastfeeding; parental educational level age, birth year, and occupational exposure to benzene. Results Paternal smoke in the conception period was associated with AnLL (OR for ≥11 cigarettes/day  = 1.79, 95% CI 1.01–3.15; P trend 0.05). An apparent effect modification by maternal age was identified: only children of mothers aged below 30 presented increased risks. We found weak statistical evidence of an association of AnLL with maternal exposure to ETS (OR for exposure>3 hours/day  = 1.85, 95%CI 0.97–3.52; P trend 0.07). No association was observed between AnLL and either maternal smoking during pregnancy or child exposure to ETS. Conclusions This study is consistent with the hypothesis that paternal smoke is associated with AnLL. We observed statistical evidence of an association between maternal exposure to ETS and AnLL, but believe bias might have inflated our estimates. PMID:25401754

  6. Absolute Lymphocyte Count (ALC) after Induction Treatment Predicts Survival of Pediatric Patients with Acute Lymphoblastic Leukemia.

    PubMed

    Farkas, Tamas; Müller, Judit; Erdelyi, Daniel J; Csoka, Monika; Kovacs, Gabor T

    2017-01-30

    Absolute Lymphocyte Count (ALC) has been recently established as a prognostic factor of survival in pediatric Acute Lymphoblastic Leukemia (ALL). A retrospective analysis of 132 patients treated according the BFM - ALLIC 2002 protocol was performed in a single institution. A possible association between ALC values and Overall Survival (OS) or Event-Free Survival (EFS) was evaluated at multiple time points during induction chemotherapy. ALC higher than 350 cells/μL measured on the 33th day of induction was associated with better Overall- and Event-Free Survival in both Kaplan-Meier (OS 88.6% vs. 40%; p < 0.001 / EFS 81.6% vs. 30%; p < 0.001) and Cox regression (OS HR 8.77 (3.31-23.28); p < 0.001) and EFS HR 6.61 (2.79-15.63); p < 0.001) analyses. There was no association between survival and measured ALC values from earlier time points (day of diagnosis, days 8 and 15) of induction therapy. Patients with low ALC values tend to have higher risk (MR or HR groups) and a higher age at diagnosis (>10 years). With help of day 33 ALC values of 350 cells/μL cutoff it was possible to refine day 33 flow cytometry (FC) Minimal Residual Disease (MRD) results within the negative cohort: higher ALC values were significantly associated with better survival. ALC on day 33 (350 cells/μL) remained prognostic for OS and EFS in multivariate analysis after adjusting it for age, cytogenetics, immunophenotype and FC MRD of induction day 33. According to these findings ALC on day 33 of induction is a strong predictor of survival in pediatric ALL.

  7. A DPP-4 inhibitor suppresses fibrosis and inflammation on experimental autoimmune myocarditis in mice.

    PubMed

    Hirakawa, Hiroyuki; Zempo, Hirofumi; Ogawa, Masahito; Watanabe, Ryo; Suzuki, Jun-Ichi; Akazawa, Hiroshi; Komuro, Issei; Isobe, Mitsuaki

    2015-01-01

    Myocarditis is a critical inflammatory disorder which causes life-threatening conditions. No specific or effective treatment has been established. DPP-4 inhibitors have salutary effects not only on type 2 diabetes but also on certain cardiovascular diseases. However, the role of a DPP-4 inhibitor on myocarditis has not been investigated. To clarify the effects of a DPP-4 inhibitor on myocarditis, we used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. EAM mice were assigned to the following groups: EAM mice group treated with a DPP-4 inhibitor (linagliptin) (n = 19) and those untreated (n = 22). Pathological analysis revealed that the myocardial fibrosis area ratio in the treated group was significantly lower than in the untreated group. RT-PCR analysis demonstrated that the levels of mRNA expression of IL-2, TNF-α, IL-1β and IL-6 were significantly lower in the treated group than in the untreated group. Lymphocyte proliferation assay showed that treatment with the DPP-4 inhibitor had no effect on antigen-induced spleen cell proliferation. Administration of the DPP-4 inhibitor remarkably suppressed cardiac fibrosis and reduced inflammatory cytokine gene expression in EAM mice. Thus, the agents present in DPP-4 inhibitors may be useful to treat and/or prevent clinical myocarditis.

  8. Pathological Substratum for a Case of Fulminant Myocarditis Treated with Extracorporeal Membrane Oxygenation and Subsequent Heart Transplantation.

    PubMed

    Kim, In Ae; Yang, Hyun Suk; Kim, Wan Seop; Chee, Hyun Keun

    2015-09-01

    Fulminant myocarditis has been defined as the clinical manifestation of cardiac inflammation with rapid-onset heart failure and cardiogenic shock. We report on the case of a 23-yr-old woman with pathology-proven fulminant lymphocytic myocarditis presenting shock with elevated cardiac troponin I and ST segments in V1-2, following sustained ventricular tachycardia and a complete atrioventricular block. About 55 min of intensive cardio-pulmonary resuscitation, with extracorporeal membrane oxygenation support, bridged the patient to orthotopic heart transplantation. The explanted heart revealed diffuse lymphocytic infiltration and myocyte necrosis in all four cardiac chamber walls. Aggressive mechanical circulatory support may be an essential bridge for recovery or even transplantation in patients with fulminant myocarditis with shock.

  9. Myocarditis in Mediterranean spotted fever: a case report and a review of the literature

    PubMed Central

    Siracusa, Lucia; Trizzino, Marcello; Gioè, Claudia; Giammanco, Anna; Cascio, Antonio

    2016-01-01

    Introduction: Mediterranean spotted fever (MSF) is a tick-borne acute febrile disease caused by Rickettsia conorii. Most cases follow a benign course, with a case fatality rate of 3–7 % among hospitalized patients. Complications are described mainly in adult patients and include hepatic, renal, neurological and cardiac impairment. Among cardiac complications, pericarditis, myocarditis and heart rhythm disorders are uncommon complications in MSF and only a few cases have been reported in the literature. Case Presentation: We describe a new case of acute myocarditis complicating MSF in an immunocompetent adult patient without risk factors for severe MSF. Conclusion: Myocarditis is an uncommon but severe complication of MSF. Clinicians should be aware of a possible cardiac involvement in patients with MSF. Close monitoring and an aggressive approach are essential to reduce mortality rates of MSF. PMID:28348768

  10. Lymphodepletion followed by donor lymphocyte infusion (DLI) causes significantly more acute graft-versus-host disease than DLI alone

    PubMed Central

    Weisdorf, Daniel J.; Burns, Linda J.; Slungaard, Arne; Wagner, John E.; Verneris, Michael R.; Cooley, Sarah; Wangen, Rosanna; Fautsch, Susan K.; Nicklow, Roby; DeFor, Todd; Blazar, Bruce R.

    2007-01-01

    Donor lymphocyte infusions (DLIs) can produce lasting remissions in patients with relapsed chronic myeloid leukemia (CML), but are less effective in non-CML diseases. We hypothesized that lymphodepletion, achieved with cyclophosphamide (Cy) and fludarabine (Flu), would promote in vivo expansion of the infused lymphocytes enhancing their immunologic effects. Fifteen patients with relapsed non-CML disease who received Cy/Flu/DLI were compared with 63 controls who received DLI without chemotherapy. Only the patients receiving Cy/Flu/DLI became lymphopenic at the time of DLI. Compared with controls, patients who received Cy/Flu/DLI developed significantly more grades II to IV (60% vs 24%, P = .01) and grades III to IV acute graft-versus-host disease (GVHD) (47% vs 14%, P = .01) with greater GVHD lethality. In Cy/Flu/DLI patients, T-cell proliferation was elevated at 14 days after DLI. Although these data suggest that chemotherapy-induced lymphodepletion enhances activation of donor lymphocytes, the toxicity needs to be managed before testing whether better disease control can be achieved. This trial was registered at www.clinicaltrials.gov as no. NCT00303693 and www.cancer.gov/clinicaltrials as no. NCT00167180. PMID:17579184

  11. Lymphodepletion followed by donor lymphocyte infusion (DLI) causes significantly more acute graft-versus-host disease than DLI alone.

    PubMed

    Miller, Jeffrey S; Weisdorf, Daniel J; Burns, Linda J; Slungaard, Arne; Wagner, John E; Verneris, Michael R; Cooley, Sarah; Wangen, Rosanna; Fautsch, Susan K; Nicklow, Roby; Defor, Todd; Blazar, Bruce R

    2007-10-01

    Donor lymphocyte infusions (DLIs) can produce lasting remissions in patients with relapsed chronic myeloid leukemia (CML), but are less effective in non-CML diseases. We hypothesized that lymphodepletion, achieved with cyclophosphamide (Cy) and fludarabine (Flu), would promote in vivo expansion of the infused lymphocytes enhancing their immunologic effects. Fifteen patients with relapsed non-CML disease who received Cy/Flu/DLI were compared with 63 controls who received DLI without chemotherapy. Only the patients receiving Cy/Flu/DLI became lymphopenic at the time of DLI. Compared with controls, patients who received Cy/Flu/DLI developed significantly more grades II to IV (60% vs 24%, P = .01) and grades III to IV acute graft-versus-host disease (GVHD) (47% vs 14%, P = .01) with greater GVHD lethality. In Cy/Flu/DLI patients, T-cell proliferation was elevated at 14 days after DLI. Although these data suggest that chemotherapy-induced lymphodepletion enhances activation of donor lymphocytes, the toxicity needs to be managed before testing whether better disease control can be achieved. This trial was registered at www.clinicaltrials.gov as no. NCT00303693 and www.cancer.gov/clinicaltrials as no. NCT00167180.

  12. A Case of Clozapine-Induced Myocarditis in a Young Patient with Bipolar Disorder

    PubMed Central

    Cohen, Ronny; Lysenko, Alla; Mallet, Thierry; Mirrer, Brooks; Gale, Michael; Loarte, Pablo; McCue, Robert

    2015-01-01

    We present a case of drug-induced myocarditis manifesting as acute heart failure in a young patient with bipolar disorder being treated for depression. The case describes a 20-year-old man being treated in the psychiatry ward for worsening depression when he started complaining of chest pain and shortness of breath. His list of medications included clozapine, lithium, lorazepam, and haloperidol. The main findings on physical examination were tachycardia, low-grade fever, crackles in both lung bases on auscultation, and the absence of any notable edema. Abnormal labs included a troponin of 0.9, with a CK of 245 and CK-MB of 3.1. An ECG revealed sinus tachycardia and left anterior fascicular block (LAFB). An echocardiogram revealed global hypokinesis, severe left ventricular dysfunction with an ejection fraction estimated at 20%. The patient had an admitting diagnosis of acute left ventricular systolic dysfunction likely secondary to drug-induced myocarditis (suspect clozapine) versus acute coronary syndrome. He was managed conservatively and transferred to another facility for endomyocardial biopsy confirming myocarditis. This case is an example of one of the most typical presentations of suspected drug-induced acute myocarditis and will hopefully prompt the reader to think of this underdiagnosed entity in the right clinical setting. PMID:26413355

  13. Myocarditis, Disseminated Infection, and Early Viral Persistence Following Experimental Coxsackievirus B Infection of Cynomolgus Monkeys

    PubMed Central

    Cammock, Cheryl E.; Halnon, Nancy J.; Skoczylas, Jill; Blanchard, James; Bohm, Rudolf; Miller, Christopher J.; Lai, Chi; Krogstad, Paul A.

    2013-01-01

    Coxsackievirus B (CVB) infection is a common cause of acute viral myocarditis. The clinical presentation of myocarditis caused by this enterovirus is highly variable, ranging from mildly symptoms to complete hemodynamic collapse. These variations in initial symptoms and in the immediate and long term outcomes of this disease have impeded development of effective treatment strategies. Nine cynomolgus monkeys were inoculated with myocarditic strains of CVB. Virological studies performed up to 28 days post-inoculation demonstrated the development of neutralizing antibody in all animals, and the presence of CVB in plasma. High dose intravenous inoculation (n = 2) resulted in severe disseminated disease, while low dose intravenous (n = 6) or oral infection (1 animal) resulted in clinically unapparent infection. Transient, minor, echocardiographic abnormalities were noted in several animals, but no animals displayed signs of significant acute cardiac failure. Although viremia rapidly resolved, signs of myocardial inflammation and injury were observed in all animals at the time of necropsy, and CVB was detected in postmortem myocardial specimens up to 28 days PI. This non-human primate system replicates many features of illness in acute coxsackievirus myocarditis and demonstrates that myocardial involvement may be common in enteroviral infection; it may provide a model system for testing of treatment strategies for enteroviral infections and acute coxsackievirus myocarditis. PMID:24040287

  14. Three hematologic malignancies in the same patient: chronic lymphocytic leukemia, followed by chronic myeloid leukemia and acute myeloid leukemia.

    PubMed

    Fattizzo, Bruno; Radice, Tommaso; Cattaneo, Daniele; Pomati, Mauro; Barcellini, Wilma; Iurlo, Alessandra

    2014-01-01

    The co-existence of both chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) have been described in a few cases, either simultaneously or subsequently presenting. We report an unusual case of three he-matological malignancies in the same patient: CLL, CML, and acute myeloid leukemia (AML). None of the three malignancies shared the same origin, since the marrow sample was negative for BCR-ABL1 transcript at the time of CLL diagnosis, CLL was in remission at CML diagnosis, and CML was in complete cytogenetic response at AML onset, indicating that this was not a blast crisis. Background: Chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) are the most common proliferative disorders in Western countries, with an incidence of 4.2/100,000/year and 1-1.5/100,000/year, respectively. The co-existence of both CML and CLL is an extremely rare event, even if it has been described in a few cases, either simultaneously or subsequently presenting. Above all, the presence of more than two different hematologic neoplasms has not been described in literature so far. In the present study we report a particular case of a CLL patient, who first developed CML and then acute myeloid leukemia (AML).

  15. [Lymphocyte metabolism in patients with acute pancreatitis with different genotypes of GSTM1 and GSTT1 genes].

    PubMed

    Markova, E V; Zotova, N V; Savchenko, A A; Titova, N M; Slepov, E V; Cherdantsev, D V; Konovalenko, A N

    2006-01-01

    In this study, we have investigated correlation between enzymatic activity of NAD(P)-dependent dehydrogenases of lymphocytes and polymorphic variants of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genes in the group of unrelated patients with acute pancreatitis in comparison with healthy Russians from Krasnoyarsk. Thus, genotype GSTM1 0/0 is the marker of predisposition to the acute pancreatitis, wheras polymorphism of the GSTT1 gene is not involved in the development of the pancreatitis, at least in our group. The bioluminescence analysis showed statistically significant decrease of the levels of G3PD, NAD(+)MDH and the increase of NADH(+)LDH, NAD(+)GDH, NADH(+)GDH in lymphocytes of pancreatic group. Development of pancreatitis in patients with different genotypes GSTM1 and GSTT1 genes showed the rearrangement of the basic intracellular processes: dominance of a plastic metabolism in the patients with GSTM1--deletions and predominance of energetic processes at GSTT1 0 - pancreatitis.

  16. Multi-state analysis illustrates treatment success after stem cell transplantation for acute myeloid leukemia followed by donor lymphocyte infusion.

    PubMed

    Eefting, Matthias; de Wreede, Liesbeth C; Halkes, Constantijn J M; von dem Borne, Peter A; Kersting, Sabina; Marijt, Erik W A; Veelken, Hendrik; Putter, Hein; Schetelig, Johannes; Falkenburg, J H Frederik

    2016-04-01

    In the field of hematopoietic stem cell transplantation, the common approach is to focus outcome analyses on time to relapse and death, without assessing the impact of post-transplant interventions. We investigated whether a multi-state model would give insight into the events after transplantation in a cohort of patients who were transplanted using a strategy including scheduled donor lymphocyte infusions. Seventy-eight consecutive patients who underwent myeloablative T-cell depleted allogeneic stem cell transplantation for acute myeloid leukemia or myelodysplastic syndrome were studied. We constructed a multi-state model to analyze the impact of donor lymphocyte infusion and graft-versus-host disease on the probabilities of relapse and non-relapse mortality over time. Based on this model we introduced a new measure for outcome after transplantation which we called 'treatment success': being alive without relapse and immunosuppression for graft-versus-host disease. All relevant clinical events were implemented into the multi-state model and were denoted treatment success or failure (either transient or permanent). Both relapse and non-relapse mortality were causes of failure of comparable magnitude. Whereas relapse was the dominant cause of failure from the transplantation state, its rate was reduced after graft-versus-host disease, and especially after donor lymphocyte infusion. The long-term probability of treatment success was approximately 40%. This probability was increased after donor lymphocyte infusion. Our multi-state model helps to interpret the impact of post-transplantation interventions and clinical events on failure and treatment success, thus extracting more information from observational data.

  17. Regulation of T lymphocyte apoptotic markers is associated to cell activation during the acute phase of dengue.

    PubMed

    Torrentes-Carvalho, Amanda; Marinho, Cintia Ferreira; de Oliveira-Pinto, Luzia Maria; de Oliveira, Débora Batista; Damasco, Paulo Vieira; Cunha, Rivaldo Venâncio; de Souza, Luiz José; de Azeredo, Elzinandes Leal; Kubelka, Claire Fernandes

    2014-05-01

    Dengue fever, a public health problem in Brazil, may present severe clinical manifestations as result of an increased vascular permeability and coagulation disorders. T cell activation is a critical event for an effective immune response against infection, including the production of cytokines. We aim to reveal mechanisms that modulate the virus-cell interaction, with an emphasis on cell death. Apoptosis is involved in lymphocyte homeostasis, contributes to the clearance of virus-infected cells but also may play a role in the pathogenesis. Phosphatidylserine exposure on CD8T lymphocytes from dengue patients support early apoptotic processes and loss of genomic integrity, observed by DNA fragmentation in T lymphocytes and indicating late apoptosis. These T cells express activation and cytotoxic phenotypes as revealed by CD29 and CD107a upregulation. Higher frequencies of CD95 were detected in T lymphocytes mainly in those with the cytotoxic profile (CD107a+) and lower levels of anti-apoptotic molecule Bcl-2, suggesting that both CD4+ and CD8+ T cell subsets are more susceptible to apoptosis during acute dengue. The analysis of apoptosis-related protein expression profile showed that not only molecules with pro- but also those with anti-apoptotic functions are overexpressed, indicating that survival mechanisms could be possibly protecting cells against apoptosis caused by viral, immune, oxidative and/or genotoxic stresses. These observations led us to propose that in dengue patients there is an association between T cell susceptibility to apoptosis and the activation state. The mechanisms for understanding the immunopathogenesis during dengue infection are discussed.

  18. Drugs Targeting the Canonical NF-κB Pathway to Treat Viral and Autoimmune Myocarditis.

    PubMed

    Valaperti, Alan

    2016-01-01

    Myocarditis, which is commonly known as heart inflammation, is a multifaceted disease that includes at least three phases. The host's immune system is mostly active during the first viral and the second autoimmune phase, when several inflammatory pathways are activated. One of the pivotal transcription factors that regulate immune responses is the nuclear factor kappa B (NF-κB). If, on one side, the acute response to heart injury activates the production of inflammatory cytokines to protect and limit host damage, on the other side sustained and long-term inflammation is one of the leading causes of cardiac hypertrophy and chronic heart failure. An update on the current knowledge of inhibitors and treatments that limit excessive inflammation in experimental and viral autoimmune myocarditis, and therapeutic approaches to cure patients with myocarditis, are described and discussed in this review.

  19. Idiopathic Giant Cell Myocarditis: A Case Report

    PubMed Central

    Kumari M.K., Kalpana; Mysorekar, Vijaya V.; S., Praveen

    2012-01-01

    Giant-cell myocarditis is a disease of relatively young, predominantly healthy adults. The patients usually die of heart failure and ventricular arrhythmia unless a cardiac transplantation is performed. We are reporting here an autopsy case of idiopathic giant cell myocarditis with no symptoms in a 27-year old -worker who died suddenly. The purpose of this report was to emphasize that idiopathic giant cell myocarditis was a rare disease and that it could exist in the absence of any symptomatic heart disease. PMID:23205365

  20. Usefulness of immunosuppression for giant cell myocarditis.

    PubMed

    Cooper, Leslie T; Hare, Joshua M; Tazelaar, Henry D; Edwards, William D; Starling, Randall C; Deng, Mario C; Menon, Santosh; Mullen, G Martin; Jaski, Brian; Bailey, Kent R; Cunningham, Madeleine W; Dec, G William

    2008-12-01

    Giant cell myocarditis (GCM) is a rare and highly lethal disorder. The only multicenter case series with treatment data lacked cardiac function assessments and had a retrospective design. We conducted a prospective, multicenter study of immunosuppression including cyclosporine and steroids for acute, microscopically-confirmed GCM. From June 1999 to June 2005 in a standard protocol, 11 subjects received high dose steroids and cyclosporine, and 9 subjects received muromonab-CD3. In these, 7 of 11 were women, the mean age was 60 +/- 15 years, and the mean time from symptom onset to presentation was 27 +/- 33 days. During 1 year of treatment, 1 subject died of respiratory complications on day 178, and 2 subjects received heart transplantations on days 2 and 27, respectively. Serial endomyocardial biopsies revealed that after 4 weeks of treatment the degree of necrosis, cellular inflammation, and giant cells decreased (p = 0.001). One patient who completed the trial subsequently died of a fatal GCM recurrence after withdrawal of immunosuppression. Her case demonstrates for the first time that there is a risk of recurrent, sometimes fatal, GCM after cessation of immunosuppression. In conclusion, this prospective study of immunosuppression for GCM confirms retrospective case reports that such therapy improves long-term survival. Additionally, withdrawal of immunosuppression can be associated with fatal GCM recurrence.

  1. Characterization of Benign Myocarditis Using Quantitative Delayed-Enhancement Imaging Based on Molli T1 Mapping.

    PubMed

    Toussaint, Marcel; Gilles, Raymond J; Azzabou, Noura; Marty, Benjamin; Vignaud, Alexandre; Greiser, Andreas; Carlier, Pierre G

    2015-10-01

    Delayed contrast enhancement after injection of a gadolinium-chelate (Gd-chelate) is a reference imaging method to detect myocardial tissue changes. Its localization within the thickness of the myocardial wall allows differentiating various pathological processes such as myocardial infarction (MI), inflammatory myocarditis, and cardiomyopathies. The aim of the study was first to characterize benign myocarditis using quantitative delayed-enhancement imaging and then to investigate whether the measure of the extracellular volume fraction (ECV) can be used to discriminate between MI and myocarditis.In 6 patients with acute benign myocarditis (32.2 ± 13.8 year-old, subepicardial late gadolinium enhancement [LGE]) and 18 patients with MI (52.3 ± 10.9 year-old, subendocardial/transmural LGE), myocardial T1 was determined using the Modified Look-Locker Imaging (MOLLI) sequence at 3 Tesla before and after Gd-chelate injection. T1 values were compared in LGE and normal regions of the myocardium. The myocardial T1 values were normalized to the T1 of blood, and the ECV was calculated from T1 values of myocardium and blood pre- and post-Gd injection.In both myocarditis and MI, the T1 was lower in LGE regions than in normal regions of the left ventricle. T1 of LGE areas was significantly higher in myocarditis than in MI (446.8 ± 45.8 vs 360.5 ± 66.9 ms, P = 0.003) and ECV was lower in myocarditis than in MI (34.5 ± 3.3 vs 53.8 ± 13.0 %, P = 0.004).Both inflammatory process and chronic fibrosis induce LGE (subepicardial in myocarditis and subendocardial in MI). The present study demonstrates that the determination of T1 and ECV is able to differentiate the 2 histological patterns.Further investigation will indicate whether the severity of ECV changes might help refine the predictive risk of LGE in myocarditis.

  2. Immunohistochemical diagnosis of myocarditis on (infantile) autopsy material: Does it improve the diagnosis?

    PubMed

    Grasmeyer, Sarah; Madea, Burkhard

    2015-06-01

    The standard for the histopathologic diagnosis of myocarditis has been the Dallas criteria. Recently, immunohistochemical studies that include the specification and quantification of interstitial inflammatory cells have been proposed as the diagnostic approach for myocarditis. Cut-off limits regarding inflammatory cell numbers for the positive diagnosis of myocarditis have been recommended. However, it is unclear whether these can be applied to postmortem tissues or to infants, as they were established from endomyocardial biopsies and for adults. Nevertheless, cut-off limits for the postmortem diagnosis of myocarditis in the first year of life have been proposed. Studies using these cut-off limits identified myocarditis in a high percentage of presumed sudden infant death syndrome (SIDS) cases. These results were re-evaluated by the present study, which examined heart specimens from infants less than 1 year of age. The study had a test group of 92 SIDS cases and a control group of 15. Myocardial tissue was examined from eight standardized locations, stained with hematoxylin-eosin and for three different immunohistochemical reagents (LCA for leukocytes, CD68 for macrophages, CD45-RO for T-lymphocytes). Histopathological assessment of the number of inflammatory cells was carried out on an aggregate of 80 mm(2) of myocardial tissue per case. Myocarditis, based on the Dallas criteria, was histologically diagnosed in only two cases. Immunohistochemical quantification revealed elevated cell counts in the SIDS group for LCA and CD45-RO. However, those differences were neither statistically significant nor clinically relevant as the mean cell counts per mm(2) were low. The density of inflammatory cells differed considerably from section to section and even within single sections. Therefore the commonly used arithmetic mean value was not diagnostically relevant, suggesting cut-off values based on the arithmetic mean value as recommended in the literature, cannot be regarded

  3. Pre-acute hepadnaviral infection is associated with activation-induced apoptotic death of lymphocytes in the woodchuck (Marmota monax) model of hepatitis B.

    PubMed

    Gujar, Shashi A; Jenkins, Adam K M; Macparland, Sonya A; Michalak, Tomasz I

    2010-09-01

    Woodchucks (Marmota monax) infected with woodchuck hepatitis virus (WHV) represent a highly valuable immunopathogenic model of hepatitis B virus (HBV) infection. Both WHV and HBV are noncytopathic hepadnaviruses which induce a strong but delayed virus-specific cellular immune response believed to be a cause of hepatitis. The reason behind this postponement is not well understood and its dissection in the woodchuck model has been hampered by the lack of appropriate research tools. In this study, we applied an assay for the simultaneous detection of cell apoptosis and proliferation to determine the fate of T lymphocytes after WHV infection leading to acute hepatitis. The results revealed that pre-acute WHV infection is associated with the significantly heightened susceptibility of T lymphocytes to activation-induced apoptotic death. This suggests that T lymphocyte function is compromised very early in the course of hepadnaviral infection and this may directly contribute to the postponement of virus-specific T cell response.

  4. Absolute lymphocyte count is associated with minimal residual disease level in childhood B-cell precursor acute lymphoblastic leukemia.

    PubMed

    Shen, Hong-Qiang; Feng, Jian-Hua; Tang, Yong-Min; Song, Hua; Yang, Shi-Long; Shi, Shu-Wen; Xu, Wei-Qun

    2013-06-01

    The prognostic value of absolute lymphocyte count (ALC) has been a recent matter of debate in childhood acute lymphoblastic leukemia (ALL). In the current study, ALCs at the time of diagnosis (ALC-0), after 7 days of initial therapy (ALC-8) and at interim of the induction therapy (ALC-22) were examined in Chinese children with B-cell precursor (BCP) ALL and correlated with the level of minimal residual disease (MRD) at day 22 of induction therapy. Medical and laboratory records of 140 patients diagnosed with childhood BCP ALL were retrieved and analyzed. ALC-22 is significantly correlated with MRD level at day 22 of therapy and can be a good prognostic factor for childhood BCP-ALL. Furthermore, lymphocyte count at initial diagnosis is correlated with MRD level at day 22 in childhood BCP-ALL with the immnunophenotype of CD19(pos)/CD10(pos)/CD34(pos)/CD45(neg) and role as a new prognostic factor was determined.

  5. An evaluation of diagnostic techniques utilized in the initial workup of pediatric patients with acute lymphocytic leukemia.

    PubMed

    Kuntz, D J; Leonard, J C; Nitschke, R M; Vanhoutte, J J; Wilson, D A; Basmadjian, G P

    1984-07-01

    The records of 32 pediatric patients with acute lymphocytic leukemia (ALL) were reviewed to evaluate the role of various diagnostic techniques used to assess the extent of extramedullary disease. Our findings indicate that adequate screening for hepatosplenomegaly is obtained by clinical assessment and for bone and renal involvement by bone scintigraphy including concomitant renal imaging. We recommend that radiographs be restricted to scintigraphically abnormal areas and/or sites of bone pain. Liver-spleen scintigraphy, gallium studies, intravenous pyelography, and ultrasound studies of the abdomen and pelvis should be utilized only to answer specific clinical questions. Evaluation in this manner reduces both radiation exposure and patient expense, while it adequately defines the extent of disease in these organs.

  6. Myocarditis

    MedlinePlus

    ... may also be done to help make the diagnosis. Other tests that may be needed include: Blood ... biopsy (the most accurate way to confirm the diagnosis, but not always needed) Special tests to check ...

  7. Acute lacunar infarcts in CLIPPERS: is the chronic infiltrative lymphocytic perivascular disease process to blame?

    PubMed

    Saigal, Gaurav; Quencer, Robert

    2013-12-01

    CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is a recently described chronic inflammatory disorder involving the brainstem with characteristic imaging findings. Since it was originally described in 2002, only a handful of cases have been reported in the literature. We describe two additional cases of CLIPPERS with characteristic clinical and radiological findings. Besides the previously described MR findings, one of the cases also demonstrated multiple basal ganglia lacunar infarcts, a finding which has not been previously reported. We hypothesize that the lacunar infarcts are caused by this chronic infiltrative perivascular disease process.

  8. Acute Lacunar Infarcts in CLIPPERS: Is the Chronic Infiltrative Lymphocytic Perivascular Disease Process to Blame?

    PubMed Central

    Saigal, Gaurav; Quencer, Robert

    2013-01-01

    Summary CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is a recently described chronic inflammatory disorder involving the brainstem with characteristic imaging findings. Since it was originally described in 2002, only a handful of cases have been reported in the literature. We describe two additional cases of CLIPPERS with characteristic clinical and radiological findings. Besides the previously described MR findings, one of the cases also demonstrated multiple basal ganglia lacunar infarcts, a finding which has not been previously reported. We hypothesize that the lacunar infarcts are caused by this chronic infiltrative perivascular disease process. PMID:24355180

  9. Apigenin Attenuates Experimental Autoimmune Myocarditis by Modulating Th1/Th2 Cytokine Balance in Mice.

    PubMed

    Zhang, Shouxin; Liu, Xiaoyan; Sun, Chengming; Yang, Jun; Wang, Lihong; Liu, Jie; Gong, Lei; Jing, Yanyan

    2016-04-01

    This study aims to investigate the protective effect of apigenin on the development of experimental autoimmune myocarditis (EAM) and the underlying mechanisms. An EAM model was induced in BALB/c mice by the injection of porcine cardiac myosin. Apigenin was orally administered from day 1 to 21. The severity of myocarditis was assessed by determination of heart weight/body weight ratio (HW/BW) and histopathological evaluation. Echocardiography was conducted to evaluate the cardiac function and heart structure. Antigen-specific T cell proliferation responses to cardiac myosin were evaluated by the lymphocyte proliferation assay. ELISA was used to determine serum levels of type 1 helper (Th1) and Th2 cytokines. Apigenin treatment significantly decreased HW/BW. Histopathologic analysis showed that the infiltration of inflammatory cells was reduced significantly by apigenin treatment. Meanwhile, apigenin administration effectively ameliorated autoimmune myocarditis-induced cardiac hypertrophy and cardiac dysfunction as well as inhibited lymphocyte proliferation in mice immunized with myosin. Furthermore, Th1 cytokines tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-2 (IL-2) were significantly downregulated, while Th2 cytokines IL-4 and IL-10 were markedly upregulated. The results indicated that apigenin can alleviate EAM due to its immunomodulatory reactions in modification of helper T cell balance.

  10. Alterations in creatine metabolism observed in experimental autoimmune myocarditis using ex vivo proton magic angle spinning MRS.

    PubMed

    Muench, Frédéric; Retel, Joren; Jeuthe, Sarah; O h-Ici, Darach; van Rossum, Barth; Wassilew, Katharina; Schmerler, Patrick; Kuehne, Titus; Berger, Felix; Oschkinat, Hartmut; Messroghli, Daniel R

    2015-12-01

    Experimental autoimmune myocarditis (EAM) in rodents is an accepted model of myocarditis and dilated cardiomyopathy (DCM). Altered metabolism is thought to play an important role in the pathogenesis of DCM and heart failure (HF). Study of the metabolism may provide new diagnostic information and insights into the mechanisms of myocarditis and HF. Proton MRS ((1)H-MRS) has not yet been used to study the changes occurring in myocarditis and subsequent HF. We aimed to explore the changes in creatine metabolism using this model and compare them with the findings in healthy animals. Myocardial function of male young Lewis rats with EAM was quantified by performing left ventricular ejection fraction (LVEF) analysis in short-axis cine images throughout the whole heart. Inflammatory cellular infiltrate was assessed by immunohistochemistry. Myocardial tissue was analyzed using ex vivo proton magic angle spinning MRS ((1)H-MAS-MRS). Myocarditis was confirmed histologically by the presence of an inflammatory cellular infiltrate and CD68 positive staining. A significant increase in the metabolic ratio of Tau/tCr (taurine/total creatine) obtained by (1)H-MAS-MRS was observed in myocarditis compared with healthy controls (21 d acute EAM, 4.38 (±0.23); 21 d control, 2.84 (±0.08); 35 d chronic EAM, 4.47 (±0.83); 35 d control, 2.59 (±0.38); P < 0.001). LVEF was reduced in diseased animals (EAM, 55.2% (±11.3%); control, 72.6% (±3.8%); P < 0.01) and correlated with Tau/tCr ratio (R = 0.937, P < 0.001). Metabolic alterations occur acutely with the development of myocarditis. Myocardial Tau/tCr ratio as detected by (1)H-MRS correlates with LVEF and is able to differentiate between healthy myocardium and myocardium from rats with EAM.

  11. Concurrent nephrotic syndrome and acute renal failure caused by chronic lymphocytic leukemia (CLL): a case report and literature review.

    PubMed

    Dou, Xianrui; Hu, Haitang; Ju, Yongle; Liu, Yongdong; Kang, Kaifu; Zhou, Shufeng; Chen, Wenfang

    2011-10-13

    Kidney injury associated with lymphocytic leukemia (CLL) is typically caused by direct tumor infiltration which occasionally results in acute renal failure. Glomerular involvement presenting as proteinuria or even nephrotic syndrome is exceptionally rare. Here we report a case of 54-year-old male CLL patient with nephrotic syndrome and renal failure. The lymph node biopsy confirmed that the patients had CLL with remarkable immunoglobulin light chain amyloid deposition. The renal biopsy demonstrated the concurrence of AL amyloidosis and neoplastic infiltration. Combined treatment of fludarabine, cyclophosphamide and rituximab resulted in remission of CLL, as well as the renal disfunction and nephrotic syndrome, without recurrence during a 12-month follow-up. To our knowledge, this is the first case of CLL patient showing the nephrotic syndrome and acute renal failure caused by AL amyloidosis and neoplastic infiltration. Though AL amyloidosis caused by plasma cell dyscrasia usually responses poorly to chemotherapy, this patient exhibited a satisfactory clinical outcome due to successful inhibition of the production of amylodogenic light chains by combined chemotherapy.

  12. Immunotherapy of acute leukemia by chimeric antigen receptor-modified lymphocytes using an improved Sleeping Beauty transposon platform

    PubMed Central

    Magnani, Chiara F.; Turazzi, Nice; Benedicenti, Fabrizio; Calabria, Andrea; Tenderini, Erika; Tettamanti, Sarah; Attianese, Greta M.P. Giordano; Cooper, Laurence J.N.; Aiuti, Alessandro; Montini, Eugenio; Biondi, Andrea; Biagi, Ettore

    2016-01-01

    Chimeric antigen receptor (CAR)-modified T-cell adoptive immunotherapy is a remarkable therapeutic option proven effective in the treatment of hematological malignancies. In order to optimize cell manufacturing, we sought to develop a novel clinical-grade protocol to obtain CAR-modified cytokine-induced killer cells (CIKs) using the Sleeping Beauty (SB) transposon system. Administration of irradiated PBMCs overcame cell death of stimulating cells induced by non-viral transfection, enabling robust gene transfer together with efficient T-cell expansion. Upon single stimulation, we reached an average of 60% expression of CD123- and CD19- specific 3rd generation CARs (CD28/OX40/TCRzeta). Furthermore, modified cells displayed persistence of cell subsets with memory phenotype, specific and effective lytic activity against leukemic cell lines and primary blasts, cytokine secretion, and proliferation. Adoptive transfer of CD123.CAR or CD19.CAR lymphocytes led to a significant anti-tumor response against acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) disseminated diseases in NSG mice. Notably, we found no evidence of integration enrichment near cancer genes and transposase expression at the end of the differentiation. Taken all together, our findings describe a novel donor-derived non-viral CAR approach that may widen the repertoire of available methods for T cell-based immunotherapy. PMID:27323395

  13. Immunotherapy of acute leukemia by chimeric antigen receptor-modified lymphocytes using an improved Sleeping Beauty transposon platform.

    PubMed

    Magnani, Chiara F; Turazzi, Nice; Benedicenti, Fabrizio; Calabria, Andrea; Tenderini, Erika; Tettamanti, Sarah; Giordano Attianese, Greta M P; Cooper, Laurence J N; Aiuti, Alessandro; Montini, Eugenio; Biondi, Andrea; Biagi, Ettore

    2016-08-09

    Chimeric antigen receptor (CAR)-modified T-cell adoptive immunotherapy is a remarkable therapeutic option proven effective in the treatment of hematological malignancies. In order to optimize cell manufacturing, we sought to develop a novel clinical-grade protocol to obtain CAR-modified cytokine-induced killer cells (CIKs) using the Sleeping Beauty (SB) transposon system. Administration of irradiated PBMCs overcame cell death of stimulating cells induced by non-viral transfection, enabling robust gene transfer together with efficient T-cell expansion. Upon single stimulation, we reached an average of 60% expression of CD123- and CD19- specific 3rd generation CARs (CD28/OX40/TCRzeta). Furthermore, modified cells displayed persistence of cell subsets with memory phenotype, specific and effective lytic activity against leukemic cell lines and primary blasts, cytokine secretion, and proliferation. Adoptive transfer of CD123.CAR or CD19.CAR lymphocytes led to a significant anti-tumor response against acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) disseminated diseases in NSG mice. Notably, we found no evidence of integration enrichment near cancer genes and transposase expression at the end of the differentiation. Taken all together, our findings describe a novel donor-derived non-viral CAR approach that may widen the repertoire of available methods for T cell-based immunotherapy.

  14. Effects of proton and gamma radiation on lymphocyte populations and acute response to antigen

    NASA Technical Reports Server (NTRS)

    Kajioka, E. H.; Gheorghe, C.; Andres, M. L.; Abell, G. A.; Folz-Holbeck, J.; Slater, J. M.; Nelson, G. A.; Gridley, D. S.

    1999-01-01

    BACKGROUND: The clinical use of proton radiation in the management of cancer, as well as benign disorders, is rapidly increasing. The major goal of this study was to compare the effects of proton and gamma (60Co) radiation on cell-mediated and humoral immunological parameters. MATERIALS AND METHODS: C57BL/6 mice were exposed to a single dose of 3 Gray (Gy) protons or gamma-rays and intraperitoneally injected 1 day later with sheep red blood cells (sRBC). On 4, 10, 15, and 29 days after exposure, subsets from each group were euthanised; nonirradiated controls (with and without sRBC injection) were included. Body and relative spleen weights, leukocyte counts, spontaneous blastogenesis, lymphocyte populations, and anti-sRBC titers were evaluated. RESULTS: The data showed significant depression (p < 0.05) in nearly all assays on days 4 and 10 after irradiation. B lymphocytes (CD19+) were the most radiosensitive, although reconstitution back to normal levels was observed by day 15. T cell (CD3+) and T helper cell (CD4+) recovery was evident by day 29, whereas the T cytotoxic cell (CD8+) count remained significantly below normal. Natural killer cells (NK1.1+) were relatively radioresistant. Anti-sRBC antibody production was slow and low titers were obtained after irradiation. No significant differences were noted between the two types of radiation. CONCLUSIONS: Taken together, the data show that whole-body irradiation with protons or gamma-rays, at the dose employed, results in marked, but transient, immunosuppression. However, at the time points of testing and with the assays used, little or no differences were found between the two forms of radiation.

  15. Coxsackievirus-induced chronic myocarditis in murine models.

    PubMed

    Gauntt, C J; Tracy, S M; Chapman, N; Wood, H J; Kolbeck, P C; Karaganis, A G; Winfrey, C L; Cunningham, M W

    1995-12-01

    Challenge of several murine strains with two highly myocarditic variants of coxsackievirus B3 (CVB3) induced acute and chronic myocarditis, detectable at 21 and 45 days post-inoculation (p.i.). In-situ hybridization of coronal heart sections showing chronic inflammation with a radiolabelled CVB3 probe detected viral genomic RNA at day 7 p.i. but rarely at 21 or 45 days p.i., suggesting few murine heart cells actively replicate virus during chronic myocardial inflammation. Data will be presented that favour an alternative hypothesis, i.e. autoimmune responses to shared epitopes among CVB3 proteins, cardiac myosin and myocardial cell surface proteins (molecular mimicry) can affect the severity of chronic inflammation. Mice inoculated with human cardiac myosin (HM) prior to a CVB3m challenge develop less myocarditis than mice inoculated with virus only, suggesting that antibodies stimulated by HM bind virus, reduce the virus burden and provide protection. Mice inoculated with HM only develop non-neutralizing antibodies against purified CVB3m particles. Several strains of mice inoculated with specific synthetic peptides of HM produce antibodies against CVB3m and/or develop cardiomyopathy. Thus antigen-challenged mice can produce antibodies which cross-react among CVB3m HM or cardiac cells to protect or exacerbate heart disease.

  16. Immune-mediated and autoimmune myocarditis: clinical presentation, diagnosis and management.

    PubMed

    Caforio, Alida L P; Marcolongo, Renzo; Jahns, Roland; Fu, Michael; Felix, Stephan B; Iliceto, S

    2013-11-01

    According to the current WHO classification of cardiomyopathies, myocarditis is an inflammatory disease of the myocardium and is diagnosed by endomyocardial biopsy using established histological, immunological and immunohistochemical criteria; it may be idiopathic, infectious or autoimmune and may heal or lead to dilated cardiomyopathy (DCM). DCM is characterized by dilatation and impaired contraction of the left or both ventricles; it may be idiopathic, familial/genetic, viral and/or immune. The diagnosis of DCM requires exclusion of known, specific causes of heart failure, including coronary artery disease. On endomyocardial biopsy, there is myocyte loss, compensatory hypertrophy, fibrous tissue and immunohistochemical findings consistent with chronic inflammation (myocarditis) in 30-40 % of cases. In a patient subset, myocarditis and DCM represent the acute and chronic stages of an inflammatory disease of the myocardium, which can be viral, post-infectious immune or primarily organ-specific autoimmune. Here, we review the clinical presentation, etiopathogenetic diagnostic criteria, and management of immune-mediated and autoimmune myocarditis.

  17. Zinc finger antiviral protein inhibits coxsackievirus B3 virus replication and protects against viral myocarditis.

    PubMed

    Li, Min; Yan, Kepeng; Wei, Lin; Yang, Jie; Lu, Chenyu; Xiong, Fei; Zheng, Chunfu; Xu, Wei

    2015-11-01

    The host Zinc finger antiviral protein (ZAP) has been reported exhibiting antiviral activity against positive-stranded RNA viruses (Togaviridae), negative-stranded RNA viruses (Filoviridae) and retroviruses (Retroviridae). However, whether ZAP restricts the infection of enterovirus and the development of enterovirus mediated disease remains unknown. Here, we reported the antiviral properties of ZAP against coxsackievirus B3 (CVB3), a single-stranded RNA virus of the Enterovirus genus within the Picornaviridae as a major causative agent of viral myocarditis (VMC). We found that the expression of ZAP was significantly induced after CVB3 infection in heart tissues of VMC mice. ZAP potently inhibited CVB3 replication in cells after infection, while overexpression of ZAP in mice significantly increased the resistance to CVB3 replication and viral myocarditis by significantly reducing cardiac inflammatory cytokine production. The ZAP-responsive elements (ZREs) were mapped to the 3'UTR and 5'UTR of viral RNA. Taken together, ZAP confers resistance to CVB3 infection via directly targeting viral RNA and protects mice from acute myocarditis by suppressing viral replication and cardiac inflammatory cytokine production. Our finding further expands ZAP's range of viral targets, and suggests ZAP as a potential therapeutic target for viral myocarditis caused by CVB3.

  18. Increase in Th17 and T-reg lymphocytes and decrease of IL22 correlate with the recovery phase of acute EAE in rat.

    PubMed

    Almolda, Beatriz; Costa, Manuela; Montoya, Maria; González, Berta; Castellano, Bernardo

    2011-01-01

    Experimental autoimmune encephalomyelitis (EAE), a well-established model of multiple sclerosis, is characterised by microglial activation and lymphocyte infiltration. Induction of EAE in Lewis rats produces an acute monophasic disease characterised by a single peak of disability followed by a spontaneous and complete recovery and a subsequent tolerance to further immunizations. In the current study we have performed a detailed analysis of the dynamics of different lymphocyte populations and cytokine profile along the induction, peak, recovery and post-recovery phases in this paradigm. MBP-injected rats were sacrificed attending exclusively to their clinical score, and the different populations of T-lymphocytes as well as the dynamics of different pro- and anti-inflammatory cytokines were analysed in the spinal cord by flow cytometry, immunohistochemistry and ELISA. Our results revealed that, during the induction and peak phases, in parallel to an increase in symptomatology, the number of CD3+ and CD4+ cells increased progressively, showing a Th1 phenotype, but unexpectedly during recovery, although clinical signs progressively decreased, the number and proportion of CD3+ and CD4+ populations remained unaltered. Interestingly, during this recovery phase, we observed a marked decrease of Th1 and an important increase in Th17 and T-reg cells. Moreover, our results indicate a specific cytokine expression profile along the EAE course characterized by no changes of IL10 and IL17 levels, decrease of IL21 on the peak, and high IL22 levels during the induction and peak phases that markedly decrease during recovery. In summary, these results revealed the existence of a specific pattern of lymphocyte infiltration and cytokine secretion along the different phases of the acute EAE model in Lewis rat that differs from those already described in chronic or relapsing-remitting mouse models, where Th17-cells were found mostly during the peak, suggesting a specific role of these

  19. Increase in Th17 and T-reg Lymphocytes and Decrease of IL22 Correlate with the Recovery Phase of Acute EAE IN Rat

    PubMed Central

    Almolda, Beatriz; Costa, Manuela; Montoya, Maria; González, Berta; Castellano, Bernardo

    2011-01-01

    Experimental autoimmune encephalomyelitis (EAE), a well-established model of multiple sclerosis, is characterised by microglial activation and lymphocyte infiltration. Induction of EAE in Lewis rats produces an acute monophasic disease characterised by a single peak of disability followed by a spontaneous and complete recovery and a subsequent tolerance to further immunizations. In the current study we have performed a detailed analysis of the dynamics of different lymphocyte populations and cytokine profile along the induction, peak, recovery and post-recovery phases in this paradigm. MBP-injected rats were sacrificed attending exclusively to their clinical score, and the different populations of T-lymphocytes as well as the dynamics of different pro- and anti-inflammatory cytokines were analysed in the spinal cord by flow cytometry, immunohistochemistry and ELISA. Our results revealed that, during the induction and peak phases, in parallel to an increase in symptomatology, the number of CD3+ and CD4+ cells increased progressively, showing a Th1 phenotype, but unexpectedly during recovery, although clinical signs progressively decreased, the number and proportion of CD3+ and CD4+ populations remained unaltered. Interestingly, during this recovery phase, we observed a marked decrease of Th1 and an important increase in Th17 and T-reg cells. Moreover, our results indicate a specific cytokine expression profile along the EAE course characterized by no changes of IL10 and IL17 levels, decrease of IL21 on the peak, and high IL22 levels during the induction and peak phases that markedly decrease during recovery. In summary, these results revealed the existence of a specific pattern of lymphocyte infiltration and cytokine secretion along the different phases of the acute EAE model in Lewis rat that differs from those already described in chronic or relapsing-remitting mouse models, where Th17-cells were found mostly during the peak, suggesting a specific role of these

  20. Low CD4/CD8 T lymphocyte ratio in acute myocardial infarction.

    PubMed Central

    Syrjälä, H; Surcel, H M; Ilonen, J

    1991-01-01

    T lymphocyte subsets were analysed using monoclonal antibodies and flow cytometry to determine whether myocardial infarction and cardiopulmonary resuscitation induce changes in these. Groups of 11 infarct patients and 10 patients with past cardiopulmonary resuscitation were compared with 11 age- and sex-matched controls and 12 sepsis patients. The differences in the CD4/CD8 ratios between the four groups were significant (F = 7.71, P = 0.001). The infarct patients had lower CD4/CD8 ratios (mean +/- s.d. 0.83 +/- 0.43) than the control (2.12 +/- 1.13; P = 0.001) or sepsis cases (1.76 +/- 1.05; P = 0.004), but their ratios did not differ from those of the resuscitation group (0.93 +/- 0.79, P = 0.84). The latter group also had lower ratios than the control (P = 0.003) and sepsis groups (P = 0.013). Most infarct patients had an on admission inverted CD4/CD8 ratio which usually returned to normal in the next 2 days. A permanently low CD4/CD8 ratio may be a poor sign prognostically after both myocardial infarction and resuscitation. PMID:1899632

  1. Demographic, clinical and pathological features of sudden deaths due to myocarditis: Results from a state-wide population-based autopsy study.

    PubMed

    Li, Liliang; Zhang, Yang; Burke, Allen; Xue, Aimin; Zhao, Ziqin; Fowler, David; Shen, Yiwen; Li, Ling

    2017-03-01

    Causes of sudden cardiac deaths have been widely reported with limited data focused specifically on myocarditis. A retrospective review of cases from the Office of the Chief Medical Examiner (OCME), State of Maryland yielded a total of 103 sudden unexpected deaths (SUDs) due to myocarditis (0.17% of all SUDs and 0.70% of autopsied SUDs) from 2005 through 2014. Most deaths occurred in patients <30 years of age with a male:female ratio 1.3:1. Of the 103 cases, 45 (43.7%) patients were witnessed collapsed. Four deaths occurred during exertion, such as exercising at the gym or performing heavy physical work, and 2 deaths were associated with emotional stress. The common cardiac macroscopic findings included ventricular dilatation (39.8%), mild coronary stenosis (17.5%), mottled myocardial appearance (15.5%), and myocardial fibrosis (10.7%). The histological classification of myocarditis was based on the predominant type of inflammatory cell infiltration. In our study group, lymphocytic myocarditis was most common, accounting for 56 cases (54.4%), followed by neutrophilic (32 cases, 31.7%), eosinophilic (13 cases, 12.6%) and giant cell type (2 cases, 1.9%). Microscopic examination revealed myocyte necrosis in 69 cases (67.0%) and interstitial or perivascular fibrosis in 48 cases (46.6%). The percentage of myocyte necrosis was 75.0% (42/58 cases) in lymphocytic, 65.6% (21/31 cases) in neutrophilic, 30.8% (4/13 cases) in eosinophilic, and 100% (2/2 cases) in giant cell myocarditis. Determination of myocarditis as cause of death continues to present a major challenge to forensic pathologists, because histopathologic findings can be subtle and the diagnosis of myocarditis remains difficult.

  2. Kinetics of indium-111-labeled leukemic cells in patients with acute non-lymphocytic leukemia

    SciTech Connect

    Suzuki, Y.; Yamauchi, K.

    1984-01-01

    The kinetics of autologous leukemic cells labeled with In-111 oxine were studied in 5 patients with acute myeloblastic leukemia (AML) and one patient with acute premyelocytic leukemia (APL), and kinetics of OKM1 monoclonal antibody-treated leukemic cells were studied in one patient with acute monoblastic leukemia (AMoL). Recoveries of 33.7 +- 23.3%(range, 22.0 to 48.1%) were achieved at 10min after injection of In-111 oxine labeled leukemic cells in AML and APL patients. However, in a patient with AMoL recovery of 12.3% was only achieved at 10min after injection of OKM1-treated leukemic cells. Clearance of the activity from blood was rapid up to one in all patients. The clearance curve of the activity in 5 AML patients showed a hump or a plateau from one to 5hr after injection of labeled leukemic cells. In APL patient and AMoL patient, however, this hump or plateau was not noted. In AML and APL patients the activity over the spleen was higher than that of over the liver at from 30min to 3hr after and showed a plateau or gradual rising thereafter. In a patient with AMoL, the hepatic activity was higher than the splenic activity at 30min after, but thereafter the latter became higher than the former. Liver activity curves showed transient fall at 3hr after and then gradual uprising in all patients. In a patient with APL, high activity was noted over the kidneys. This rose to a maximum after 3hr and then decreased rapidly. Since In-111 oxine stays firmly attached to the cells in spite of the possibility of radiation damage in a long-term survey, it seems an ideal label for studying leukemic cell kinetics.

  3. Thallium-201 myocardial perfusion imaging in myocarditis

    SciTech Connect

    Tamaki, N.; Yonekura, Y.; Kadota, K.; Kambara, H.; Torizuka, K.

    1985-08-01

    TI-201 myocardial perfusion imaging was performed in six patients with clinically documented myocarditis. Each case manifested electrocardiographic abnormalities with elevation of serum cardiac enzymes and no significant stenosis of the coronary arteries observed on angiogram. Resting TI-201 images were visually assessed by three observers. Focal perfusion defects were observed in three cases (50%), among which two showed multiple perfusion defects. Emission computed tomography using TI-201 clearly delineated multifocal lesions in the first case. On the other hand, no significant perfusion defects were noted in the remaining three cases. Thus, myocarditis should be considered as one of the disease entities that may produce perfusion defects on TI-201 myocardial imaging.

  4. Effect of acute maximal exercise on lymphocyte subgroups in type 1 diabetes.

    PubMed

    Salman, F; Erten, G; Unal, M; Kiran, B; Salman, S; Deniz, G; Yilmaz, M T; Kayserilioglu, A; Dinccag, N

    2008-03-01

    The essential therapy of diabetes mellitus includes medical nutrition therapy (MNT), exercise and medical therapy. Exercise, besides its metabolic effects, has positive influence on the immune system, but some forms of exercise may cause trauma for muscle and skeletal systems, they may also support negative effects on the immune system. Nineteen type 1 diabetic patients (mean age 22.1 +/- 2.8 yrs), followed by Diabetes Outpatient Clinic and twenty age matched male control subjects were included into the study, to demonstrate the effects of maximal, acute exercise on the immune system. The exercise test was performed according to Bruce protocol on treadmill. In diabetic subjects, increased CD19 and CD23 expressions were observed before exercise. In both groups (diabetic/control) CD3, CD4 expressions and CD4/CD8 ratio were decreased following the exercise, however expression of natural killer (NK) cells increased. Compared to type 1 diabetic patients healthy subjects had longer acute exercise that caused the increased level of CD8 expression, however type 1 diabetic patients did not show any difference. These results indicate that submaximal aerobic exercise might be recommended for type 1 diabetics without any complications because of its positive reflection on metabolic control and no negative effects on the immune system.

  5. Transformation of myocarditis and inflammatory cardiomyopathy to idiopathic dilated cardiomyopathy: facts and fiction.

    PubMed

    Figulla, Hans R

    2004-05-01

    There is broad evidence that enteroviruses and adenoviruses can induce an acute inflammation of the myocardium without cardiac dysfunction (i.e. myocarditis) or with cardiac dysfunction (i.e. inflammatory cardiomyopathy) that can transform to a virus-negative dilated cardiomyopathy. In the adult patient neither other viruses (parvo-B 19 virus, hepatitis C virus, cytomegalovirus) nor post-infection autoimmunity are likely to induce idiopathic dilated cardiomyopathy.

  6. Gene expression analysis during recovery process indicates the mechanism for innate immune injury and repair from Coxsackievirus B3-induced myocarditis.

    PubMed

    Yao, Hai-Lan; Song, Juan; Sun, Peng; Song, Qin-Qin; Sheng, Lin-Jun; Chi, Miao-Miao; Han, Jun

    2016-02-02

    To investigate the innate immune injury and repair mechanism during recovery from Coxsackievirus B3 (CVB3) induced myocarditis, we established an acute viral myocarditis recovery model by infecting BALB/c mice with CVB3. Histopathological examination of cardiac tissues after infection showed a gradual increase of myocardial injury to the maximum degree at 8 dpi (days post infection), followed by a recovery process with reduced viral replication. We also measured expression changes of innate immune genes in heart after 4, 8 and 12 days of infection using innate immune real-time PCR array. The results showed expression alterations in many Pattern Recognition Receptors (PRRs) genes upon CVB3 infection, which activated multiple important signaling pathways during recovery process. The expression of TLRs, RLRs, PKR and cytokines were strongly induced and reached the peak at 4 dpi in early myocarditis stage, followed by a gradual reduction in recovery stage, during which the levels were even lower than normal at 12 dpi. The strong correlation between cardiac histopathology score and chemokine expression level suggested that the chemokines might play a role in pathological changes during early myocarditis stage. In addition, we also found that both cell survival signaling pathways (AKT1, p38MAPK) and antiviral signaling pathways (IKKα/β/ε) were activated and promoted the recovery during late myocarditis stage. Altogether, our observations improved the understanding of formation and progression of the pathological lesions, as well as the repair mechanism for acute viral myocarditis.

  7. [Myocarditis in a cachectic female, nonsteroidal anti-inflammatory drugs abuser, in a course of progressive systemic sclerosis].

    PubMed

    Wozakowska-Kapłon, Beata; Gorczyca, Iwona; Maciejowska-Roge, Maria

    2009-11-01

    A case of 70-year-old cachectic female, nonsteroid anti-inflammatory drugs abuser, with progressive systemic sclerosis, who was admitted to our hospital due to joint pain and fatigue is presented. During hospitalisation the patient developed symptoms of acute myocarditis. Angiography of coronary arteries did not reveal narrowing of the vessels. Alimentary supplementation and therapy for heart failure (diuretics, vasodilators, angiotensin-converting enzyme inhibitor and beta-blocker) were used. In repeated echocardiography examinations ejection fraction systematically improved and hemodynamic stabilisation was obtained. Scleroderma, malnutrition, toxicity of nonsteroid anti-inflammatory drugs and infectious agents were considered as a cause of myocarditis.

  8. Myocarditis and inflammatory cardiomyopathy: from diagnosis to treatment.

    PubMed

    Escher, Felicitas; Tschöepe, Carsten; Lassner, Dirk; Schultheiss, Heinz-Peter

    2015-12-01

    Based on the definition in the European Society of Cardiology statement, myocarditis is an inflammatory disease of the myocardium diagnosed by established histological, immunological, and immunohistochemical criteria, whereas inflammatory cardiomyopathy is myocarditis in association with cardiac dysfunction. Actual incidences of myocarditis and CMi are difficult to determine. Studies addressing the issue of sudden cardiac death in young people report a highly variable autopsy prevalence of myocarditis, ranging from 2-42% of cases. Similarly, biopsy-proven myocarditis has been reported in 9-16% of adult patients with unexplained nonischemic dilated cardiomyopathy (DCM). In up to 30% of cases, biopsy-proven myocarditis can progress to DCM and is associated with a poor prognosis. Prognosis in myocarditis patients also varies according to underlying etiology.

  9. Absolute lymphocyte count at the end of induction therapy is a prognostic factor in childhood acute lymphoblastic leukemia.

    PubMed

    Hirase, Satoshi; Hasegawa, Daiichiro; Takahashi, Hironobu; Moriwaki, Kensuke; Saito, Atsuro; Kozaki, Aiko; Ishida, Toshiaki; Yanai, Tomoko; Kawasaki, Keiichiro; Yamamoto, Nobuyuki; Kubokawa, Ikuko; Mori, Takeshi; Hayakawa, Akira; Nishimura, Noriyuki; Nishio, Hisahide; Iijima, Kazumoto; Kosaka, Yoshiyuki

    2015-11-01

    Recent studies have reported that the absolute lymphocyte count (ALC) during induction therapy is predictive of treatment outcome in de novo acute lymphoblastic leukemia (ALL); however, the significance of ALC on outcomes remains controversial. In the present study, we assessed the significance of ALC at day 29 (ALC-29), the end of induction therapy, on outcomes in our Japanese cohort. The outcomes of 141 patients aged ≤18 years with newly diagnosed ALL who were enrolled on the JACLS ALL-02 at our hospitals were analyzed in terms of ALC-29. Patients with ALC-29 ≥750/μL (n = 81) had a superior 5-year EFS (95.2 ± 2.7 vs 84.3 ± 4.8 %, P = 0.016) and OS (100 vs 87.0 ± 4.7 %, P = 0.0062). A multivariate analysis identified ALC-29 ≥750/μL as a significant predictor of improved EFS and OS after controlling for confounding factors. A multiple linear regression model revealed a significant inverse relationship between the percentage of blasts in bone marrow on day 15 and ALC-29 (P = 0.005). These results indicate that ALC is a simple prognostic factor in childhood ALL, and, thus, has the potential to refine current risk algorithms.

  10. [Radiation-induced intracranial osteosarcoma after radiation for acute lymphocytic leukemia associated with Li-Fraumeni syndrome].

    PubMed

    Yoshimura, Junichi; Natsumeda, Manabu; Nishihira, Yasushi; Nishiyama, Kenichi; Saito, Akihiko; Okamoto, Kouichirou; Takahashi, Hitoshi; Fujii, Yukihiko

    2013-06-01

    A 28-year-old man presented with osteosarcoma of the occipital bone 16 years after 24 Gy of craniospinal irradiation for acute lymphocytic leukemia. The tumor had both intra- and extra-cranial components. However, the affected skull appeared to be normal on imaging because of permeative infiltration by the tumor. Subtotal resection was achieved and the tumor was verified histologically as an osteosarcoma. The residual tumor soon showed remarkable enlargement and disseminated to the spinal cord. Both of the enlarged and disseminated tumor masses were treated by surgical intervention and chemotherapy. However, the patient deteriorated due to the tumor regrowth and died 11 months after the initial diagnosis. This patient had previously developed a leukemia, a colon cancer, a rectal cancer and a hepatocellular carcinoma. His brother also died of leukemia. The patient had a heterozygous TP53 germ-line mutation of codon 248 in the exon 7. In conclusion, we consider the present tumor to be a rare example of radiation-induced skull osteosarcoma in a member of the cancer-prone family with TP53 germ-line mutation which is associated with Li-Fraumeni syndrome.

  11. Health-Related Quality of Life, Depression, Anxiety, and Self-Image in Acute Lymphocytic Leukemia Survivors

    PubMed Central

    Baytan, Birol; Aşut, Çiğdem; Çırpan Kantarcıoğlu, Arzu; Sezgin Evim, Melike; Güneş, Adalet Meral

    2016-01-01

    Objective: With increasing survival rates in childhood acute lymphocytic leukemia (ALL), the long-term side effects of treatment have become important. Our aim was to investigate health-related quality of life, depression, anxiety, and self-image among ALL survivors. Materials and Methods: Fifty patients diagnosed with ALL and their siblings were enrolled. The Kovacs Children’s Depression Inventory, State-Trait Anxiety Inventory, Offer Self-Image Questionnaire, and Pediatric Quality of Life InventoryTM were used for collecting data. ANOVA tests were used to determine if there were any significant differences between groups. Results: ALL survivors had higher depression, more anxiety symptoms, lower quality of life, and more negative self-image when compared to their siblings. Conclusion: Continuous diagnostic and interventional mental health services might be necessary for possible emotional side effects of treatment during and after the treatment. Rehabilitation and follow-up programs should be implemented for children during and after treatment for ALL. PMID:27094799

  12. Regulation of HIF-1α signaling and chemoresistance in acute lymphocytic leukemia under hypoxic conditions of the bone marrow microenvironment

    PubMed Central

    Frolova, Olga; Samudio, Ismael; Benito, Juliana Maria; Jacamo, Rodrigo; Kornblau, Steven M.; Markovic, Ana; Schober, Wendy; Lu, Hongbo; Qiu, Yi Hua; Buglio, Daniela; McQueen, Teresa; Pierce, Sherry; Shpall, Elizabeth; Konoplev, Sergej; Thomas, Deborah; Kantarjian, Hagop; Lock, Richard; Andreeff, Michael; Konopleva, Marina

    2012-01-01

    Overcoming resistance to chemotherapy is the main therapeutic challenge in the treatment of acute lymphocytic leukemia (ALL). Interactions between leukemia cells and the microenvironment promote leukemia cell survival and confer resistance to chemotherapy. Hypoxia is an integral component of bone marrow (BM) microenvironment. Hypoxia-inducible factor-1α (HIF-1), a key regulator of the cellular response to hypoxia, regulates cell growth and metabolic adaptation to hypoxia. HIF-1α expression, analyzed by Reverse Phase Protein Arrays in 92 specimens from newly diagnosed patients with pre-B-ALL, had a negative prognostic impact on survival (p = 0.0025). Inhibition of HIF-1α expression by locked mRNA antagonist (LNA) promoted chemosensitivity under hypoxic conditions, while pharmacological or genetic stabilization of HIF-1α under normoxia inhibited cell growth and reduced apoptosis induction by chemotherapeutic agents. Co-culture of pre-B ALL or REH cells with BM-derived mesenchymal stem cells (MSC) under hypoxia resulted in further induction of HIF-1α protein and acquisition of the glycolytic phenotype, in part via stroma-induced AKT/mTOR signaling. mTOR blockade with everolimus reduced HIF-1α expression, diminished glucose uptake and glycolytic rate and partially restored the chemosensitivity of ALL cells under hypoxia/stroma co-cultures. Hence, mTOR inhibition or blockade of HIF-1α-mediated signaling may play an important role in chemosensitization of ALL cells under hypoxic conditions of the BM microenvironment. PMID:22785211

  13. Platelet to lymphocyte ratio in the prediction of adverse outcomes after acute coronary syndrome: a meta-analysis

    PubMed Central

    Li, Wenzhang; Liu, Qianqian; Tang, Yin

    2017-01-01

    Recent studies have shown platelet to lymphocyte ratio (PLR) to be a potential inflammatory marker in cardiovascular diseases. We performed a meta-analysis to systematically evaluate the prognostic role of PLR in acute coronary syndrome (ACS). A comprehensive literature search up to May 18, 2016 was conducted from PUBMED, EMBASE and Web of science to identify related studies. The risk ratio (RR) with 95% confidence interval (CI) was extracted or calculated for effect estimates. Totally ten studies involving 8932 patients diagnosed with ACS were included in our research. We demonstrated that patients with higher PLR level had significantly higher risk of in-hospital adverse outcomes (RR = 2.24, 95%CI = 1.81–2.77) and long-term adverse outcomes (RR = 2.32, 95%CI = 1.64–3.28). Sensitivity analyses confirmed the stability of our results. We didn’t detect significant publication bias by Begg’s and Egger’s test (p > 0.05). In conclusion, our meta-analysis revealed that PLR is promising biomarker in predicting worse prognosis in ACS patients. The results should be validated by future large-scale, standard investigations. PMID:28071752

  14. In vitro chemosensitivity testing of leukemic cells: prediction of response to chemotherapy in patients with acute non-lymphocytic leukemia.

    PubMed

    Santini, V; Bernabei, P A; Silvestro, L; Dal Pozzo, O; Bezzini, R; Viano, I; Gattei, V; Saccardi, R; Ferrini, P R

    1989-01-01

    The in vitro chemosensitivity to daunorubicin and cytosine arabinoside of blast cells derived from 35 patients affected by acute non-lymphocytic leukemia was assessed by a semiautomated tetrazolium-based colorimetric assay, by the use of p-iodonitrotetrazolium violet. The results of the in vitro testing were then compared a posteriori to clinical outcome of patients, who followed a schedule of therapy which always included the drugs tested in vitro. Three dosages of drugs were employed to allow the determination of a dose-response curve, which was obtained for all the patients. The data collected in INT assay correlated with the clinical sensitivity of patients, evaluated in terms of achievement of complete remission. For the dosage of ARA-C 500 ng/ml it was possible to establish a significant cutoff between responders and non-responders to therapy, while an acceptable distribution of sensitivity/resistance prediction was found for DNR 500 ng/ml and 5 micrograms/ml. Present results, together with rapid and easy execution of the test, encourage the use of INT assay in screening leukemic patients' sensitivity to antiblastic drugs before treatment or, in case of resistance to classical chemotherapy, in detecting individual sensitivity to alternative drugs.

  15. Upregulation of ICOS on CD43+ CD4+ murine small intestinal intraepithelial lymphocytes during acute reovirus infection

    SciTech Connect

    Montufar-Solis, Dina; Garza, Tomas; Teng, B.-B.; Klein, John R. . E-mail: john.r.klein@uth.tmc.edu

    2006-04-14

    Murine intestinal intraepithelial lymphocytes (IELs) can be classified according to expression of a CD43 glycoform recognized by the S7 monoclonal antibody. In this study, we examined the response of S7+ and S7- IELs in mice during acute reovirus serotype 3 (Dearing strain) infection, which was confirmed by virus-specific real-time PCR. In vivo proliferation increased significantly for both S7- and S7+ IELs on day 4 post-infection as determined by BrdU incorporation; however, expression of the inducible costimulatory (ICOS) molecule, which peaked on day 7 post-infection, was upregulated on S7+ CD4+ T cells, most of which were CD4+8- IELs. In vitro ICOS stimulation by syngeneic peritoneal macrophages induced IFN-{gamma} secretion from IELs from day 7 infected mice, and was suppressed by treatment with anti-ICOS mAb. Additionally, IFN-{gamma} mRNA increased in CD4+ IELs on day 6 post-infection. These findings indicate that S7- and S7+ IELs are differentially mobilized during the immune response to reovirus infection; that the regulated expression of ICOS is associated with S7+ IELs; and that stimulation of IELs through ICOS enhances IFN-{gamma} synthesis during infection.

  16. Non‐tumour bone marrow lymphocytes correlate with improved overall survival in childhood acute lymphoblastic leukaemia

    PubMed Central

    Edwin, Claire; Dean, Joanne; Bonnett, Laura; Phillips, Kate

    2016-01-01

    Abstract Composition of tumour immune cell infiltrates correlates with response to treatment and overall survival (OS) in several cancer settings. We retrospectively examined immune cells present in diagnostic bone marrow aspirates from paediatric patients with B‐cell acute lymphoblastic leukaemia. Our analysis identified a sub‐group (∼30% of patients) with >2.37% CD20 and >6.05% CD7 expression, which had 100% OS, and a sub‐group (∼30% of patients) with ≤2.37% CD20 and ≤6.05% CD7 expression at increased risk of treatment failure (66.7% OS, P < 0.05). Immune cell infiltrate at diagnosis may predict treatment response and could provide a means to enhance immediate treatment risk stratification. PMID:27348401

  17. Protection against Acute Hepatocellular Injury Afforded by Liver Fibrosis Is Independent of T Lymphocytes

    PubMed Central

    Lacoste, Benoit; Raymond, Valérie-Ann; Lapierre, Pascal; Bilodeau, Marc

    2016-01-01

    Collagen produced during the process of liver fibrosis can induce a hepatocellular protective response through ERK1 signalling. However, the influence of T cells and associated cytokine production on this protection is unknown. In addition, athymic mice are frequently used in hepatocellular carcinoma xenograft experiments but current methods limit our ability to study the impact of liver fibrosis in this setting due to high mortality. Therefore, a mouse model of liver fibrosis lacking T cells was developed using Foxn1 nu/nu mice and progressive oral administration of thioacetamide (TAA) [0.01–0.02%] in drinking water. Fibrosis developed over a period of 16 weeks (alpha-SMA positive area: 20.0 ± 2.2%, preCol1a1 mRNA expression: 11.7 ± 4.1 fold changes, hydroxyproline content: 1041.2 ± 77μg/g of liver) at levels comparable to that of BALB/c mice that received intraperitoneal TAA injections [200 μg/g of body weight (bw)] (alpha-SMA positive area: 20.9 ± 2.9%, preCol1a1 mRNA expression: 13.1 ± 2.3 fold changes, hydroxyproline content: 931.6 ± 14.8μg/g of liver). No mortality was observed. Athymic mice showed phosphorylation of ERK1/2 during fibrogenesis (control 0.03 ± 0.01 vs 16 weeks 0.22 ± 0.06AU; P<0.05). The fibrosis-induced hepatoprotection against cytotoxic agents, as assessed histologically and by serum AST levels, was not affected by the absence of circulating T cells (anti-Fas JO2 [0.5μg/g bw] for 6h (fibrotic 4665 ± 2596 vs non-fibrotic 13953 ± 2260 U/L; P<0.05), APAP [750 mg/kg bw] for 6 hours (fibrotic 292 ± 66 U/L vs non-fibrotic 4086 ± 2205; P<0.01) and CCl4 [0.5mL/Kg bw] for 24h (fibrotic 888 ± 268 vs non-fibrotic 15673 ± 2782 U/L; P<0.001)). In conclusion, liver fibrosis can be induced in athymic Foxn1 nu/nu mice without early mortality. Liver fibrosis leads to ERK1/2 phosphorylation. Finally, circulating T lymphocytes and associated cytokines are not involved in the hepatocellular protection afforded by liver fibrosis. PMID

  18. Association of cytotoxic T-lymphocyte antigen 4 +49A/G gene polymorphism with acute rejection risk in renal transplantation.

    PubMed

    Yang, Chun-Hua; Chen, Xue-Xia; Chen, Li; Zheng, Dong-Hua; Liu, Qiong-Shan; Xie, Wen-Feng

    2017-03-23

    The conclusions on the association between cytotoxic T-lymphocyte antigen 4 (CTLA4) +49A/G gene polymorphism and acute rejection risk in renal transplantation are still debated. This meta-analysis was performed to update the association between CTLA4 +49A/G and acute rejection risk in renal transplantation. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Fourteen reports were included into this meta-analysis for the association of CTLA4 A/G gene polymorphism and acute rejection risk in renal transplantation, consisting of 962 acute rejection patients and 2084 non-acute rejection controls. The association between CTLA4 G allele/GG genotype and acute rejection risk in renal transplantation was found in this meta-analysis (G allele: OR=1.21, 95% CI: 1.03-1.44, P=.02; GG genotype: OR=1.37, 95% CI: 1.10-1.69, P=.004). However, the AA genotype was not associated with acute rejection risk in renal transplantation. In conclusion, CTLA4 G allele/GG genotype is associated with the acute rejection risk in renal transplantation.

  19. Paralysis caused by acute myelitis in Theiler's murine encephalomyelitis virus strain GD VII infection is induced by CD4+ lymphocytes infiltrating the spinal cord.

    PubMed

    Kohanawa, M; Asano, M; Min, Y; Minagawa, T; Nakane, A

    1995-09-01

    Intravenous infection by Theiler's murine encephalomyelitis virus strain GD VII causes acute encephalomyelitis and paralysis in infected mice. However, nude mice and cyclophosphamide-treated ddY mice did not show paralysis when they were able to survive until day 20 post-infection (p.i.). Of ddY mice infected with 5 x 10(7) p.f.u./mouse, 70-80% showed symptoms of paralysis on day 20 p.i. The viral titres in the brain and spinal cord in infected mice were not significantly different between paralytic and non-paralytic mice. In all of the mice infected with the virus, CD4+ lymphocytes and CD8+ lymphocytes had infiltrated the brain on days 10, 12, 14 and 20 p.i. as demonstrated by flow cytometric analysis. In contrast, few T lymphocytes infiltrated the spinal cord in the non-paralytic mice. Administration of an anti-CD4 monoclonal antibody (MAb) or anti-T cell receptor-alpha beta MAb on day 6 p.i. inhibited paralysis until day 20 p.i., though 20% of the MAb-treated mice and 80% of the control mice showed paralysis. Administration of anti-CD8 MAb was not effective in the suppression of paralysis. The MAb treatment did not significantly augment viral replication in the spinal cord, although the viral titres in the brain of the MAb-treated mice increased significantly. After the transfer of spleen cells from infected C3H mice, the recipient mice infected with a small amount of the virus showed paralysis, though uninfected mice did not. This transfer could be blocked by CD4+ lymphocyte depletion of the donor mice. These results indicate that paralysis caused by acute myelitis in Theiler's virus strain GD VII infection is induced by CD4+ lymphocytes infiltrating the spinal cord.

  20. Myocarditis associated with reovirus in turkey poults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Myocarditis associated with reovirus was diagnosed in 17 day-old male turkey poults based on virus isolation, reverse transcript – polymerase chain reaction (RT-PCR), demonstration of reovirus antigen in the cytoplasm of mononuclear inflammatory cells and myocytes in the heart by immunohistochemistr...

  1. Myocarditis associated with Reovirus in Turkey Poults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Myocarditis associated with Reovirus in Turkey Poults H. L. ShivaprasadA, M. S. FrancaA, P. R. WoolcockA, R. NordhausenB, M. DayC and M. Pantin-JackwoodC California Animal Health and Food Safety Laboratory System, AFresno and BDavis Branches, University of California, Davis, 2789 South Orange Av...

  2. Outcomes for Patients with Chronic Lymphocytic Leukemia (CLL) and Acute Leukemia or Myelodysplastic Syndrome

    PubMed Central

    Tambaro, Francesco Paolo; Garcia-Manero, Guillermo; O’Brien, Susan M.; Faderl, Stefan H.; Ferrajoli, Alessandra; Burger, Jan A.; Pierce, Sherry; Wang, Xuemei; Do, Kim-Anh; Kantarjian, Hagop M.; Keating, Michael J.; Wierda, William G.

    2016-01-01

    Acute leukemia (AL) and myelodysplastic syndrome (MDS) are uncommon in CLL. We retrospectively identified 95 patients with CLL also diagnosed with AL (n=38) or MDS (n=57), either concurrently (n=5) or subsequent (n=90) to CLL diagnosis and report their outcomes. Median number of CLL treatments prior to AL and MDS was 2(0–9) and 1(0–8), respectively; the most common regimen was purine analogue combined with alkylating agent±CD20 mAb. Twelve had no prior CLL treatment. Among 38 with AL, 33 had AML, 3 had ALL (1Ph+), 1 had biphenotypic, and 1 had extramedullary (bladder) AML. Unfavorable AML karyotype was noted in 26, intermediate-risk in 7. There was no association between survival from AL and number of prior CLL regimens or karyotype. Expression of CD7 on blasts was associated with shorter survival. Among MDS cases, all IPSS were represented; karyotype was unfavorable in 36, intermediate in 6, and favorable in 12 patients; 10 experienced transformation to AML. Shorter survival from MDS correlated with higher-risk IPSS, poor-risk karyotype, and increased number of prior CLL treatments. Overall, outcomes for patients with CLL subsequently diagnosed with AL or MDS were poor; AL/MDS occurred without prior CLL treatment. Effective therapies for these patients are desperately needed. PMID:26290497

  3. Two case reports of severe myocarditis associated with the initiation of dolutegravir treatment in HIV patients

    PubMed Central

    Mahlab-Guri, Keren; Asher, Ilan; Rosenberg-Bezalel, Shira; Elbirt, Daniel; Burke, Michael; Sthoeger, Zev M.

    2016-01-01

    Abstract Rationale: The integrase inhibitor dolutegravir is now recommended as first-line treatment for HIV. A single case of myocarditis after treatment with dolutegravir was reported in the FLAMINGO trial. We present here 2 cases of severe myocarditis that occurred shortly after the initiation of dolutegravir treatment. Patients concerns: The first case is a 45-year-old female who developed severe congestive heart failure and died, weeks after the initiation of dolutegravir treatment (for simplification of her antiretroviral regimen). The second case was a 51-year-old male who presented with effort dyspnea 3 weeks after the initiation of dolutegravir treatment and was later diagnosed as severe congestive heart failure. The treatment was changed and the patient survived, but he still suffers from severe heart failure with functional impairment. Diagnosis and Outcome: Patient 1 died, patient 2 suffers from severe heart failure. Lessons: We discuss here the possible relationship between the initiation of dolutegravir treatment and the development of lymphocytic myocarditis in our patients, and we suggest a possible mechanism. PMID:27893693

  4. Healthy CD4+ T lymphocytes are not affected by targeted therapies against the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia

    PubMed Central

    Martelli, Alberto M.; Zauli, Giorgio; Ultimo, Simona; McCubrey, James A.; Gonelli, Arianna; Marisi, Giorgia; Ulivi, Paola; Capitani, Silvano; Neri, Luca M.

    2016-01-01

    An attractive molecular target for novel anti-cancer therapies is the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway which is commonly deregulated in many types of cancer. Nevertheless, the effects of PI3K/Akt/mTOR inhibitors on T lymphocytes, a key component of immune responses, have been seldom explored. In this study we investigated the effects on human CD4+ T-cells of a panel of PI3K/Akt/mTOR inhibitors: BGT226, Torin-2, MK-2206, and ZSTK474. We also assessed their efficacy against two acute leukemia T cell lines. T lymphocytes were stimulated with phytohemagglutinin. Inhibitor effects on cell cycle and apoptosis were analyzed by flow cytometry, while cytotoxicity was assessed by MTT assays. In addition, the activation status of the pathway as well as induction of autophagy were analyzed by Western blotting. Quiescent healthy T lymphocytes were unaffected by the drugs whereas mitogen-stimulated lymphocytes as well as leukemic cell lines displayed a cell cycle block, caspase-dependent apoptosis, and dephosphorylation of key components of the signaling pathway. Autophagy was also induced in proliferating lymphocytes and in JURKAT and MOLT-4 cell lines. When autophagy was inhibited by 3-methyladenine or Bafilomycin A1, drug cytotoxicity was increased, indicating that autophagy is a protective mechanism. Therefore, our findings suggest that PI3K/Akt/mTOR inhibitors preserve lymphocyte viability. This is a valuable result to be taken into account when selecting drugs for targeted cancer therapy in order to minimize detrimental effects on immune function. PMID:27494886

  5. Mixed T Lymphocyte Chimerism after Allogeneic Hematopoietic Transplantation Is Predictive for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    PubMed

    Lee, Hans C; Saliba, Rima M; Rondon, Gabriela; Chen, Julianne; Charafeddine, Yasmeen; Medeiros, L Jeffrey; Alatrash, Gheath; Andersson, Borje S; Popat, Uday; Kebriaei, Partow; Ciurea, Stefan; Oran, Betul; Shpall, Elizabeth; Champlin, Richard

    2015-11-01

    Chimerism testing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represents a promising tool for predicting disease relapse, although its precise role in this setting remains unclear. We investigated the predictive value of T lymphocyte chimerism analysis at 90 to 120 days after allo-HSCT in 378 patients with AML/MDS who underwent busulfan/fludarabine-based myeloablative preparative regimens. Of 265 (70%) patients with available T lymphocyte chimerism data, 43% of patients in first or second complete remission (CR1/CR2) at the time of transplantation had complete (100%) donor T lymphocytes at day +90 to +120 compared with 60% of patients in the non-CR1/CR2 cohort (P = .005). In CR1/CR2 patients, donor T lymphocyte chimerism ≤ 85% at day +90 to +120 was associated with a higher frequency of 3-year disease progression (29%; 95% confidence interval [CI], 18% to 46% versus 15%; 95% CI, 9% to 23%; hazard ratio [HR], 2.1; P = .04). However, in the more advanced, non-CR1/CR2 cohort, mixed T lymphocyte chimerism was not associated with relapse (37%; 95% CI, 20% to 66% versus 34%; 95% CI, 25% to 47%; HR, 1.3; P = .60). These findings demonstrate that early T lymphocyte chimerism testing at day +90 to +120 is a useful approach for predicting AML/MDS disease recurrence in patients in CR1/CR2 at the time of transplantation.

  6. Lymphocyte subpopulations and suppressor cell activity in acute polyradiculoneuritis (Guillain-Barré syndrome).

    PubMed Central

    Hughes, R A; Aslan, S; Gray, I A

    1983-01-01

    Ficoll-Triosil separated peripheral blood mononuclear (PBM) cells were analysed by fluorescent microscopy with Ortho monoclonal antisera to T cells (OKT3+) helper cells (OKT4+) and suppressor cytotoxic cells (OKT8+) and with polyclonal antiserum to surface immunoglobulin. Twenty-five normal subjects, 16 patients with acute polyradiculoneuritis (Guillain-Barré syndrome, AP) and 10 patients with other neurological diseases were studied. The percentages of OKT3+, OKT4+ and immunoglobulin bearing cells were similar in the three patient groups but the percentage of OKT8+ cells was reduced to 13.5 +/- 4.1 (mean +/- s.d.) compared with 19.4 +/- 4.9 in the normal subjects and 18.5 +/- 3.1 in the patients with other neurological diseases. The ratio of OKT4+/OKT8+ cells was correspondingly increased to 3.5 +/- 2.1 compared with 2.1 +/- 0.5 in the normal subjects and 2.1 +/- 0.4 in the patients with other neurological diseases. In one test of suppressor cell function Con A incubated mitomycin treated PBM cells were added to autologous PBM cells stimulated with Con A to compare the degree of suppression with that produced by control incubated mitomycin treated cells (Con A suppression test). In a second test of suppressor cell function short lived suppressor cell (SLS) activity was assayed by comparing PBM stimulation by Con A added at the start of culture with that produced by Con A added after 24 hr. Neither test revealed any significant differences between AP patients and control subjects. PMID:6221841

  7. Acute exposure to 930 MHz CW electromagnetic radiation in vitro affects reactive oxygen species level in rat lymphocytes treated by iron ions.

    PubMed

    Zmyślony, Marek; Politanski, Piotr; Rajkowska, Elzbieta; Szymczak, Wieslaw; Jajte, Jolanta

    2004-07-01

    The aim of this study was to test the hypothesis that the 930 MHz continuous wave (CW) electromagnetic field, which is the carrier of signals emitted by cellular phones, affects the reactive oxygen species (ROS) level in living cells. Rat lymphocytes were used in the experiments. A portion of the lymphocytes was treated with iron ions to induce oxidative processes. Exposures to electromagnetic radiation (power density 5 W/m2, theoretical calculated SAR = 1.5 W/kg) were performed within a GTEM cell. Intracellular ROS were measured by the fluorescent probe dichlorofluorescin diacetate (DCF-DA). The results show that acute (5 and 15 min) exposure does not affect the number of produced ROS. If, however, FeCl2 with final concentration 10 microg/ml was added to the lymphocyte suspensions to stimulate ROS production, after both durations of exposure, the magnitude of fluorescence (ROS level during the experiment) was significantly greater in the exposed lymphocytes. The character of the changes in the number of free radicals observed in our experiments was qualitatively compatible with the theoretical prediction from the model of electromagnetic radiation effect on radical pairs.

  8. Coxsackie Myocarditis and Hepatitis with Reactivated Epstein-Bar Virus (EBV): A Case Report

    PubMed Central

    Atti, Varunsiri; Anderson, Nathan M.; Day, Mathew B.

    2017-01-01

    Patient: Female, 57 Final Diagnosis: Coxsackie myocarditis and hepatitis Symptoms: Fever • headache • general malaise • sob. Medication: — Clinical Procedure: Echocardiography • cardiac MRI Specialty: Cardiology Objective: Unusual clinical course Background: Myocarditis, defined as inflammation of myocardial tissue of the heart, is an uncommon cardiac presentation and is due to a variety of causes. It affects 1% of the US population, 50% of which is caused by coxsackie B virus. Cardiac tissue is the prime target, and destruction of myocardium results in cardiac failure with fluid overload. Case Report: Our patient was a 57-year-old woman with fever, headache, neck pain, and generalized malaise. Her white blood cell count was 13×103 cells/mm3. Interestingly, lumbar puncture ruled out meningitis. An echocardiogram to evaluate elevated troponin revealed an ejection fraction of 30% with severe left ventricular global hypokinesis without valvular vegetations consistent with new-onset systolic heart failure. Cardiac MRI showed a small pericardial effusion with bilateral pleural effusion. As she continued to be febrile, a viral panel was ordered, revealing coxsackie B4 antibody titer of 1: 640 (reference: >1: 32 indicates recent infection) with positive Epstein-Barr virus deoxyribonucleic acid by PCR, consistent with viral myocarditis. Conclusions: Coxsackie B virus myocarditis is rarely recognized and reported by the general internist in clinical practice, so we would like present our experience with an interesting clinical presentation of the viral prodrome. An estimated 95% people in the US are infected with Epstein-Barr virus by adulthood, but it remains dormant in memory B lymphocytes. Recirculation of these B cells in lymphoid tissue stimulated by antigens, which in our case is coxsackie B virus; they differentiate into plasma cells, and the production of Z Epstein-Barr replication activator protein (ZEBRA) increases viral replication, thus explaining the

  9. Long-term follow-up on cardiac function following fulminant myocarditis requiring percutaneous extracorporeal cardiopulmonary support.

    PubMed

    Ishida, Kohki; Wada, Hiroshi; Sakakura, Kenichi; Kubo, Norifumi; Ikeda, Nahoko; Sugawara, Yoshitaka; Ako, Junya; Momomura, Shin-ichi

    2013-01-01

    Fulminant myocarditis is a rapidly progressive, life-threatening disease with severe impairment of systolic left ventricle function in the acute phase. However, the long-term prognosis of patients who survive the acute phase with percutaneous extracorporeal cardiopulmonary support (PCPS) is not established. The purpose of this study was to elucidate the long-term follow-up on chronic cardiac function and long-term outcome. Twenty consecutive patients with fulminant myocarditis in the acute phase supported by PCPS were enrolled between January 1995 and March 2010. Echocardiography was performed at least three times; acute phase (within 3 days from onset), predischarge (days 3-30), and chronic phase (>6 months, 2.67 ± 2.19 years, mean ± SD). The clinical events were queried by their medical record and questionnaires. Eight patients (40%) died in the acute phase. The time course of ejection fraction (%) by echocardiography was 22.7 ± 9.8, 53.1 ± 7.2, and 57.2 ± 9.6 in acute, predischarge, and chronic phase, respectively. Diastolic dimension (mm) was 46.8 ± 7.4, 51.3 ± 2.9, and 50.4 ± 1.8, and systolic dimension (mm) was 41.4 ± 7.7, 36.8 ± 4.0, and 35.2 ± 3.3 in acute, predischarge, and chronic phase, respectively. There was no recurrence or admission related to heart failure during the follow-up period. The cardiac function of patients with fulminant myocarditis recovers rapidly during their stay in hospital. The cardiac function of predischarge patients remains unchanged in the chronic phase. The long-term survival of fulminant myocarditis appears favorable in the chronic phase.

  10. Low-Dose Inorganic Mercury Increases Severity and Frequency of Chronic Coxsackievirus-Induced Autoimmune Myocarditis in Mice

    PubMed Central

    Nyland, Jennifer F.; Fairweather, DeLisa; Shirley, Devon L.; Davis, Sarah E.; Rose, Noel R.; Silbergeld, Ellen K.

    2012-01-01

    Mercury is a widespread environmental contaminant with neurotoxic impacts that have been observed over a range of exposures. In addition, there is increasing evidence that inorganic mercury (iHg) and organic mercury (including methyl mercury) have a range of immunotoxic effects, including immune suppression and induction of autoimmunity. In this study, we investigated the effect of iHg on a model of autoimmune heart disease in mice induced by infection with coxsackievirus B3 (CVB3). We examined the role of timing of iHg exposure on disease; in some experiments, mice were pretreated with iHg (200 μg/kg, every other day for 15 days) before disease induction with virus inoculation, and in others, they were treated with iHg after the acute (viral) phase of disease but before the development of dilated cardiomyopathy (DCM). iHg alone had no effect on heart pathology. Pretreatment with iHg before CVB3 infection significantly increased the severity of chronic myocarditis and DCM compared with control animals receiving vehicle alone. In contrast, treatment with iHg after acute myocarditis did not affect the severity of chronic disease. The increased chronic myocarditis, fibrosis, and DCM induced by iHg pretreatment were not due to increased viral replication in the heart, which was unaltered by iHg treatment. iHg pretreatment induced a macrophage infiltrate and mixed cytokine response in the heart during acute myocarditis, including significantly increased interleukin (IL)-12, IL-17, interferon-γ, and tumor necrosis factor-α levels. IL-17 levels were also significantly increased in the spleen during chronic disease. Thus, we show for the first time that low-dose Hg exposure increases chronic myocarditis and DCM in a murine model. PMID:21984480

  11. Gonococcaemia with arthritis, dermatitis and myocarditis

    PubMed Central

    Fraser, H. S.; Figueroa, J. P.; James, O. B. O'L.; Liburd, A. L.; Nicholson, G. A.; Whitbourne, F.; Alleyne, G. A. O.

    1974-01-01

    Six cases of gonococcaemia seen at the University Hospital of the West Indies are described. All presented with polyarthritis and all but one had skin lesions. They varied widely in severity and chronicity and included one case with rigors and myocarditis. Emphasis is placed on the diagnostic value of the scanty skin lesions, and the importance of repeated examination of cervical swabs. ImagesFig. 1 PMID:4219856

  12. MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia

    ClinicalTrials.gov

    2016-09-20

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  13. Cacao polyphenols ameliorate autoimmune myocarditis in mice.

    PubMed

    Zempo, Hirofumi; Suzuki, Jun-ichi; Watanabe, Ryo; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Komuro, Issei; Isobe, Mitsuaki

    2016-04-01

    Myocarditis is a clinically severe disease; however, no effective treatment has been established. The aim of this study was to determine whether cacao bean (Theobroma cacao) polyphenols ameliorate autoimmune myocarditis. We used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. Mice with induced EAM were treated with a cacao polyphenol extract (CPE, n=12) or vehicle (n=12). On day 21, hearts were harvested and analyzed. Elevated heart weight to body weight and fibrotic area ratios as well as high cardiac cell infiltration were observed in the vehicle-treated EAM mice. However, these increases were significantly suppressed in the CPE-treated mice. Reverse transcriptase-PCR revealed that mRNA expressions of interleukin (Il)-1β, Il-6, E-selectin, vascular cell adhesion molecule-1 and collagen type 1 were lower in the CPE group compared with the vehicle group. The mRNA expressions of nicotinamide adenine dinucleotide phosphate-oxidase (Nox)2 and Nox4 were increased in the vehicle-treated EAM hearts, although CPE treatment did not significantly suppress the transcription levels. However, compared with vehicle treatment of EAM hearts, CPE treatment significantly suppressed hydrogen peroxide concentrations. Cardiac myeloperoxidase activity, the intensity of dihydroethidium staining and the phosphorylation of nuclear factor-κB p65 were also lower in the CPE group compared with the vehicle group. Our data suggest that CPE ameliorates EAM in mice. CPE is a promising dietary supplement to suppress cardiovascular inflammation and oxidative stress.

  14. Sudden unexpected death related to enterovirus myocarditis: histopathology, immunohistochemistry and molecular pathology diagnosis at post-mortem

    PubMed Central

    2012-01-01

    Background Viral myocarditis is a major cause of sudden unexpected death in children and young adults. Until recently, coxsackievirus B3 (CVB3) has been the most commonly implicated virus in myocarditis. At present, no standard diagnosis is generally accepted due to the insensitivity of traditional diagnostic tests. This has prompted health professionals to seek new diagnostic approaches, which resulted in the emergence of new molecular pathological tests and a more detailed immunohistochemical and histopathological analysis. When supplemented with immunohistochemistry and molecular pathology, conventional histopathology may provide important clues regarding myocarditis underlying etiology. Methods This study is based on post-mortem samples from sudden unexpected death victims and controls who were investigated prospectively. Immunohistochemical investigations for the detection of the enteroviral capsid protein VP1 and the characterization and quantification of myocardial inflammatory reactions as well as molecular pathological methods for enteroviral genome detection were performed. Results Overall, 48 sudden unexpected death victims were enrolled. As for controls, 37 cases of unnatural traffic accident victims were studied. Enterovirus was detected in 6 sudden unexpected death cases (12.5 %). The control samples were completely enterovirus negative. Furthermore, the enteroviral capsid protein VP1 in the myocardium was detected in enterovirus-positive cases revealed by means of reverse transcriptase-polymerase chain reaction (RT-PCR). Unlike control samples, immunohistochemical investigations showed a significant presence of T and B lymphocytes in sudden unexpected death victims. Conclusions Our findings demonstrate clearly a higher prevalence of viral myocarditis in cases of sudden unexpected death compared to control subjects, suggesting that coxsackie B enterovirus may contribute to myocarditis pathogenesis significantly. PMID:22966951

  15. Acute Lymphocytic Leukemia

    MedlinePlus

    ... the best course of action? What are the alternatives to the primary approach that you're suggesting? ... my insurance cover it? Is there a generic alternative to the medicine you're prescribing me? Are ...

  16. Acute lymphocytic leukemia (ALL)

    MedlinePlus

    ... made. Life-threatening symptoms can occur as normal blood counts drop. Causes Most of the time, no clear cause can be found for ALL. The following factors may play a role in the development of all types of leukemia: Certain chromosome problems Exposure to radiation, ...

  17. The relationship between neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and thrombolysis in myocardial infarction risk score in patients with ST elevation acute myocardial infarction before primary coronary intervention

    PubMed Central

    Ertaş, Faruk; Bilik, Mehmet Zihni; Akıl, Mehmet Ata; Özyurtlu, Ferhat; Aydın, Mesut; Oylumlu, Mustafa; Polat, Nihat; Yüksel, Murat; Yıldız, Abdulkadir; Kaya, Hasan; Akyüz, Abdurrahman; Ayçiçek, Hilal; Özbek, Mehmet; Toprak, Nizamettin

    2015-01-01

    Introduction The thrombolysis in myocardial infarction (TIMI) risk score is calculated as the sum of independent predictors of mortality and ischemic events in ST elevation acute myocardial infarction (STEMI). Several studies show that the neutrophil to lymphocyte ratio (NLR) is a prognostic inflammatory marker. In preliminary studies, platelet to lymphocyte ratio (PLR) has been proposed as a pro-thrombotic marker. The relationship between NLR, PLR and TIMI risk score for STEMI has never been studied. Aim To evaluate the association between TIMI-STEMI risk score and NLR, PLR and other biochemical indices in STEMI. Material and methods In this retrospective study, we evaluated 390 patients who presented with STEMI within 12 h of symptom onset. Patients were grouped according to low and high TIMI risk scores. Results We enrolled 390 patients (mean age 61.9 ±13.6 years; 73% were men). The NLR, platelet distribution width (PDW) and uric acid level (UA) were significantly associated with a high TIMI-STEMI risk score (p = 0.016, p = 0.008, p = 0.030, respectively), but PLR was not associated with a high TIMI-STEMI risk score. Left ventricular ejection fraction was an independent predictor of TIMI-STEMI risk score. A cut-off point of TIMI-STEMI score of > 4 predicted in-hospital mortality (sensitivity 75%, specificity 70%, p < 0.001). We found that NLR, PDW, and UA level were associated with TIMI-STEMI risk score. Conclusions Neutrophil to lymphocyte ratio, PDW and UA level are convenient, inexpensive and reproducible biomarkers for STEMI prognosis before primary angioplasty when these indicators are combined with the TIMI-STEMI risk score. We believe that these significant findings can guide further clinical practice. PMID:26161105

  18. [EFFECT OF 4-METHYLPYRAZOLE ON IMMUNE RESPONSE, FUNCTION OF Th1 AND Th2 LYMPHOCYTES, AND CYTOKINE CONCENTRATION IN RAT BLOOD AFTER ACUTE METHANOL POISONING].

    PubMed

    Zabrodskii, P F; Maslyakov, V V; Gromov, M S

    2016-01-01

    It was established in experiments on noninbred albino rats that the acute intoxication with methanol (1.0 LD50) decreased cellular and humoral immune responses, Th2-lymphocyte activity (to a greater extent as compared to the function of Th1 cells), reduced the blood concentration of immunoregulatory (IFN-g, IL-2, IL-4) and proinflammatory (TNF, IL-1b, IL-6) cytokines on the average by 36.5% (p < 0.05), and did not affect the content of anti-inflammatory cytokines (IL-10, IL-13). Methanol antidote 4-methylpyrazole (non-competitive inhibitor of alcohol dehydrogenase) administered upon acute intoxication with methanol at a dose of 1.0 DL50 partially reduces the intoxication-induced suppression of humoral and cellular immune response, activity of T-helper cells, and production of IL-4 and restores blood levels of TNF, IL-1b, IFN-γ, IL-4, IL-2, IL-6 to the control values.

  19. Early lymphocyte recovery predicts superior overall survival after unmanipulated haploidentical blood and marrow transplant for myelodysplastic syndrome and acute myeloid leukemia evolving from myelodysplastic syndrome.

    PubMed

    Chang, Ying-Jun; Zhao, Xiang-Yu; Xu, Lan-Ping; Liu, Dai-Hong; Liu, Kai-Yan; Chen, Yu-Hong; Wang, Yu; Zhang, Xiao-Hui; Zhao, Xiao-Su; Han, Wei; Chen, Huan; Wang, Feng-Rong; Lv, Meng; Huang, Xiao-Jun

    2013-12-01

    We investigated whether early lymphocyte recovery, after unmanipulated, haploidentical, blood and marrow transplant (HBMT), affected clinical outcomes in 78 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia evolving from MDS. Lymphocyte recovery was based on the absolute lymphocyte count on day 30 (ALC-30). Patients with high ALC-30 (≥ 300 cells/μL) had lower relapse rates (13.8% vs. 35.5%, p = 0.049) and lower incidence of bacterial infections (3.4% vs. 25.8%, p = 0.015) than those with low ALC-30 values. Multivariate analysis showed that a high ALC-30 was associated with improved overall survival (OS, hazard ratio [HR]: 0.099, 95% confidence interval [CI]: 0.029-0.337; p < 0.0001), improved leukemia-free survival (HR: 0.245, 95% CI: 0.112-0.539; p < 0.0001), lower relapse rate (HR: 0.096, 95% CI: 0.011-0.827; p = 0.033) and lower transplant-related mortality (TRM, HR: 0.073, 95% CI: 0.016-0.324; p = 0.001). Combinations of three mismatches in the human leukocyte antigen loci were associated with a higher TRM (HR: 5.026, 95% CI: 1.392-18.173; p = 0.014). Our results suggest that the ALC-30 can predict a favorable OS after unmanipulated HBMT.

  20. A case report and literature review of Churg–Strauss syndrome presenting with myocarditis

    PubMed Central

    Qiao, Lu; Gao, Dengfeng

    2016-01-01

    Abstract Background: Churg–Strauss syndrome (CSS) is a multisystem disorder characterized by asthma, prominent peripheral blood eosinophilia, and vasculitis signs. Case summary: Here we report a case of CSS presenting with acute myocarditis and heart failure and review the literature on CSS with cardiac involvement. A 59-year-old man with general fatigue, numbness of limbs, and a 2-year history of asthma was admitted to the department of orthopedics. Eosinophilia, history of asthma, lung infiltrates, peripheral neurological damage, and myocarditis suggested the diagnosis of CSS. Transthoracic echocardiography revealed a dilated hypokinetic left ventricle (left ventricular ejection fraction ∼40%) with mild segmental abnormalities in the septal and apical segments. Conclusion: By reviewing the present case reports, we concluded that (1) the younger age of CSS, the greater occurrence rate of complicating myocarditis and the poorer prognosis; (2) female CSS patients are older than male patients; (3) patients with cardiac involvement usually have a history of severe asthma; (4) markedly increased eosinophil count suggests a potential diagnosis of CSS (when the count increases to 20% of white blood cell counts or 8.1 × 109/L, eosinophils start to infiltrate into myocardium); and (5) negative ANCA status is associated with heart disease in CSS. PMID:28002315

  1. Interleukin-1 Receptor Blockade Rescues Myocarditis-Associated End-Stage Heart Failure

    PubMed Central

    Cavalli, Giulio; Foppoli, Marco; Cabrini, Luca; Dinarello, Charles A.; Tresoldi, Moreno; Dagna, Lorenzo

    2017-01-01

    Support measures currently represent the mainstay of treatment for fulminant myocarditis, while effective and safe anti-inflammatory therapies remain an unmet clinical need. However, clinical and experimental evidence indicates that inhibition of the pro-inflammatory cytokine interleukin 1 (IL-1) is effective against both myocardial inflammation and contractile dysfunction. We thus evaluated treatment with the IL-1 receptor antagonist anakinra in a case of heart failure secondary to fulminant myocarditis. A 65-year-old man with T cell lymphoma developed fulminant myocarditis presenting with severe biventricular failure and cardiogenic shock requiring admittance to the intensive care unit and mechanical circulatory and respiratory support. Specifically, acute heart failure and cardiogenic shock were initially treated with non-invasive ventilation and mechanical circulatory support with an intra-aortic balloon pump. Nevertheless, cardiac function deteriorated further, and there were no signs of improvement. Treatment with anakinra, the recombinant form of the naturally occurring IL-1 receptor antagonist, was started at a standard subcutaneous dose of 100 mg/day. We observed a dramatic clinical improvement within 24 h of initiating anakinra. Prompt, progressive amelioration of cardiac function allowed weaning from mechanical circulatory and respiratory support within 72 h of anakinra administration. Recent studies point at inhibition of IL-1 activity as an attractive treatment option for both myocardial inflammation and contractile dysfunction. Furthermore, IL-1 receptor blockade with anakinra is characterized by an extremely rapid onset of action and remarkable safety and may thus be suitable for the treatment of patients critically ill with myocarditis. PMID:28232838

  2. Inhalant-Abuse Myocarditis Diagnosed by Cardiac Magnetic Resonance

    PubMed Central

    Rao, Krishnasree; Matulevicius, Susan

    2016-01-01

    Multiple reports of toxic myocarditis from inhalant abuse have been reported. We now report the case of a 23-year-old man found to have toxic myocarditis from inhalation of a hydrocarbon. The diagnosis was made by means of cardiac magnetic resonance imaging with delayed enhancement. The use of cardiac magnetic resonance to diagnose myocarditis has become increasingly common in clinical medicine, although there is not a universally accepted criterion for diagnosis. We appear to be the first to document a case of toxic myocarditis diagnosed by cardiac magnetic resonance. In patients with a history of drug abuse who present with clinical findings that suggest myocarditis or pericarditis, cardiac magnetic resonance can be considered to support the diagnosis. PMID:27303242

  3. Strain difference in rats with experimental giant cell myocarditis.

    PubMed

    Shioji, K; Kishimoto, C; Nakayama, Y; Sasayama, S

    2000-04-01

    Immunogenetic mechanisms may be involved in the pathogenesis of myocarditis and dilated cardiomyopathy. The present study investigated the incidence, histopathology and histocompatibility characteristics of experimental giant cell myocarditis in various strains of rats. Experimental giant cell myocarditis was induced by immunization with porcine cardiac myosin in Lewis (RT-1(l)), Dahl (DIR/Eis) (RT-1(l)), Fisher (RT-1(lv 1)) rats, but not in Dahl (DIS/Eis) (RT-1(l)) or Brown Norway (RT-1(n)). Myocarditis was most severe in the Lewis rats and their heart weight/body weight ratio was significantly higher than that of control rats immunized with Freund's complete adjuvant alone. In conclusion, this study provides evidence that the expression and severity of experimental giant cell myocarditis may be determined mainly by genetic factors, including both major histocompatibility complex genes as well as other genes, which may be controlled by an immune mechanism.

  4. Virus myocarditis in a 1-month-old boy presenting as two types of paroxysmal supraventricular tachycardia.

    PubMed

    Fujita, Shuhei; Futatani, Takeshi; Kubo, Tatsuya; Itamochi, Masae; Yachi, Yusuke; Iwasaki, Hidenori; Shimao, Ayako; Ina, Shihomi; Higashiyama, Hiroyuki; Igarashi, Noboru; Hatasaki, Kiyoshi

    2017-04-12

    Herein we describe the case of a 1-month-old boy with acute viral myocarditis, who presented with two kinds of paroxysmal supraventricular tachycardia, and who was cured after medical treatment. He was brought to the emergency room with poor feeding due to fever. On the third day of hospitalization, a narrow QRS tachycardia (180-200 beats/min) was detected. Echocardiography showed a high echoic area at the atrial septum around the atrioventricular node. The patient was clinically diagnosed with acute myocarditis. The narrow QRS tachycardia was diagnosed as incessant junctional ectopic tachycardia. The patient was treated with propranolol and landiolol. The frequency of the tachycardia decreased, but a different narrow QRS tachycardia was detected on the 15th day of hospitalization on electrocardiogram (220 beats/min), which was ascribed to atrioventricular nodal re-entrant tachycardia. Atenolol was effective for the tachycardia. At 2 years follow up, cardiac function was normal and tachycardia had not recurred.

  5. Fatal pyogranulomatous myocarditis in 10 Boxer puppies.

    PubMed

    Detmer, Susan E; Bouljihad, Mostafa; Hayden, David W; Schefers, Jeremy M; Armien, Anibal; Wünschmann, Arno

    2016-03-01

    Over a period of 5 years, 10 pure-bred Boxer puppies, 9-16 weeks old, were presented with a history of sudden death and were diagnosed with pyogranulomatous myocarditis. The myocarditis was characterized by a mixed infiltrate composed predominantly of neutrophils and macrophages. In our retrospective study, original case records and archived materials were examined. All dogs were positive for Borrelia burgdorferi on immunohistochemistry (IHC). There was no evidence of infectious agents in formalin-fixed, paraffin-embedded (FFPE) heart tissue sections stained with hematoxylin and eosin, Ziehl-Neelsen, Gram, Grocott methenamine silver, Warthin-Starry, Von Kossa, and Steiner-Chapman stains. IHC for Chlamydia sp., Toxoplasma gondii, Neospora caninum, West Nile virus, and canine parvovirus also yielded a negative result in all dogs. Polymerase chain reaction testing for vector-borne pathogens on heart tissue from 9 of the dogs (1 frozen and 8 FFPE samples) yielded positive results for 1 dog with B. burgdorferi as well as Anaplasma phagocytophilum in another dog. Subsequently, 2 additional cases were found in a French Bulldog and a French Bulldog-Beagle mix that had identical morphology, test results, age, and seasonality to these 10 Boxer dogs. The similarities in the seasonality, signalment of the affected dogs, and the gross and microscopic lesions suggest a common etiology. Positive IHC and morphologic similarities to human Lyme carditis indicate that B. burgdorferi is likely the agent involved. An additional consideration for these cases is the possibility of a breed-specific autoimmune myocarditis or potential predisposition for cardiopathogenic agents in young Boxers.

  6. Lymphocyte-depleting induction therapy lowers the risk of acute rejection in African American pediatric kidney transplant recipients.

    PubMed

    Crowson, Cole N; Reed, Rhiannon D; Shelton, Brittany A; MacLennan, Paul A; Locke, Jayme E

    2017-02-01

    The use of lymphocyte-depleting induction immunosuppression has been associated with a reduction in risk of AR after KT among adult recipients, particularly among high-risk subgroups such as AAs. However, data on induction regimen and AR risk are lacking among pediatric KT recipients. We examined outcomes among 7884 first-time pediatric KT recipients using SRTR data (2000-2014). Characteristics were compared across race using Wilcoxon rank-sum tests for continuous and chi-square tests for categorical variables. Risk of AR was estimated using modified Poisson regression, stratified by recipient race, adjusting for recipient age, gender, BMI, primary diagnosis, number of HLA mismatches, maintenance immunosuppression, and donor type. Risk of AR within 1 year was lower in AA recipients receiving lymphocyte-depleting induction (ATG or alemtuzumab; RR, 0.66; 95% CI, 0.52-0.83 P < .001) compared to AA recipients receiving anti-IL-2 receptor antibody induction. This difference was not seen in non-AA recipients receiving lymphocyte-depleting induction (RR, 0.93; 95% CI, 0.81-1.06, P = .26) compared to IL-2 induction. These findings support a role for lymphocyte-depleting induction agents in AA pediatric patients undergoing KT and continued use of IL-2 inhibitor induction in non-AA pediatric KT recipients.

  7. Two-dimensional speckle-tracking-derived segmental peak systolic longitudinal strain identifies regional myocardial involvement in patients with myocarditis and normal global left ventricular systolic function.

    PubMed

    Uppu, Santosh C; Shah, Amee; Weigand, Justin; Nielsen, James C; Ko, H Helen; Parness, Ira A; Srivastava, Shubhika

    2015-06-01

    The presence of myocardial late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) imaging in concert with electrocardiography and elevated biomarkers helps support the diagnosis of acute myocarditis. Two-dimensional echocardiography is limited to global and qualitative regional function assessment and may not contribute to the diagnosis, especially in the presence of normal LV systolic function. Two-dimensional speckle-tracking (2D-STE)-derived segmental peak systolic (pkS) longitudinal strain (LS) may identify segmental myocardial involvement in myocarditis. We sought to identify an association between segmental pkS, LGE, and troponin levels in patients with myocarditis. Retrospective analysis of myocardial segmental function by 2D-STE segmental strain was compared to the presence of LGE and admission peak troponin levels in patients with acute myocarditis and preserved global LV systolic function. American Heart Association 17-segment model was used for comparison between imaging modalities. Global function was assessed by m-mode-derived shortening fraction (SF). Descriptive statistics and regression analysis were utilized. Forty-four CMRs performed to evaluate for myocarditis were identified. Of the 44, 10 patients, median age 17.5 years (14-18.5 years) and median SF 35 % (28-44 %), had paired CMR and 2D-STE data for analysis, and 161/170 segments could be analyzed by both methods for comparison. PkS LS was decreased in 51 % of segments that were positive for LGE with average pkS of -14.7 %. Segmental pkS LS abnormalities were present in all but one patient who had abnormal pkS circumferential strain. Global pkS LS was decreased in patients with myocarditis. There is a moderate correlation between decreased pkS LS and the presence of LGE by CMR, 2D-STE for myocardial involvement in acute myocarditis can serve as an useful noninvasive adjunct to the existing tests used for the diagnosis of acute myocarditis and might have a role in prognostication.

  8. Eosinophilic Myocarditis due to Toxocariasis: Not a Rare Cause

    PubMed Central

    Shibazaki, Shunichi; Eguchi, Shunsuke; Endo, Takashi; Wakabayashi, Tadamasa; Araki, Makoto; Gu, Yoshiaki; Imai, Taku; Asano, Kouji; Taniuchi, Norihide

    2016-01-01

    Myocarditis is a clinically important disease because of the high mortality. From the perspective of treatment strategy, eosinophilic myocarditis should be distinguished from other types of myocarditis. Toxocariasis, caused by Toxocara canis or Toxocara cati, is known as a cause of eosinophilic myocarditis but is considered rare. As it is an unpopular disease, eosinophilic myocarditis due to toxocariasis may be underdiagnosed. We experienced two cases of eosinophilic myocarditis due to toxocariasis from different geographical areas in quick succession between 2013 and 2014. Case 1 is 32-year-old man. Case 2 is 66-year-old woman. In both cases, diagnosis was done by endomyocardial biopsy and IgG-ELISA against Toxocara excretory-secretory antigen. Only a corticosteroid was used in Case  1, whereas a corticosteroid and albendazole were used in Case  2 as induction therapy. Both patients recovered. Albendazole was also used in Case  1 to prevent recurrence after induction therapy. Eosinophilic myocarditis by toxocariasis may in actuality not be a rare disease, and corticosteroid is an effective drug as induction therapy even before use of albendazole. PMID:27123346

  9. Inducible nitric oxide synthase in the myocard.

    PubMed

    Buchwalow, I B; Schulze, W; Karczewski, P; Kostic, M M; Wallukat, G; Morwinski, R; Krause, E G; Müller, J; Paul, M; Slezak, J; Luft, F C; Haller, H

    2001-01-01

    Recognition of significance of nitric oxide synthases (NOS) in cardiovascular regulations has led to intensive research and development of therapies focused on NOS as potential therapeutic targets. However, the NOS isoform profile of cardiac tissue and subcellular localization of NOS isoforms remain a matter of debate. The aim of this study was to investigate the localization of an inducible NOS isoform (NOS2) in cardiomyocytes. Employing a novel immunocytochemical technique of a catalyzed reporter deposition system with tyramide and electron microscopical immunocytochemistry complemented with Western blotting and RT-PCR, we detected NOS2 both in rat neonatal and adult cultured cardiomyocytes and in the normal myocard of adult rats as well as in the human myocard of patients with dilative cardiomyopathy. NOS2 was targeted predominantly to a particulate component of the cardiomyocyte--along contractile fibers, in the plasma membrane including T-tubules, as well as in the nuclear envelope, mitochondria and Golgi complex. Our results point to an involvement of NOS2 in maintaining cardiac homeostasis and contradict to the notion that NOS2 is expressed in cardiac tissue only in response to various physiological and pathogenic factors. NOS2 targeting to mitochondria and contractile fibers suggests a relationship of NO with contractile function and energy production in the cardiac muscle.

  10. Pathology of Toxoplasma myocarditis in acquired immunodeficiency syndrome.

    PubMed

    Sahasrabudhe, Neil S; Jadhav, M V; Deshmukh, S D; Holla, V V

    2003-10-01

    Involvement of the myocardium by Toxoplasma gondii is seen in patients of acquired immunodeficiency syndrome (AIDS), mostly in association with toxoplasma encephalitis. Only few patients die as a direct result of cardiac dysfunction. Clinico-pathological findings of three cases of toxoplasma myocarditis are reported, one of which presented and died due to massive pericardial effusion. All cases showed diffuse myocarditis with parasites on histopathological examination. Incidence of toxoplasma myocarditis in patients dying with AIDS was 8.3% (3 out of 36 cases).

  11. Myocarditis in sibling boxer puppies associated with Citrobacter koseri infection.

    PubMed

    Cassidy, J P; Callanan, J J; McCarthy, G; O'Mahony, M C

    2002-05-01

    Two sibling Boxer puppies presented with severe suppurative myocarditis in the absence of additional disseminated suppurative foci. The identification of gram-negative bacteria within areas of myocarditis in both puppies and the pure growth of large numbers of Citrobacter koseri from the myocardial lesions in one of the dogs were consistent with a bacterial etiology. The fact that C. koseri is an opportunist pathogen suggested intercurrent immunosuppression. The finding of a concomitant bacterial myocarditis in two canine siblings is novel. The case is also unusual in that syncope could be related to the myocardial injury.

  12. Acute exercise boosts cell proliferation and the heat shock response in lymphocytes: correlation with cytokine production and extracellular-to-intracellular HSP70 ratio.

    PubMed

    Heck, Thiago Gomes; Scomazzon, Sofia Pizzato; Nunes, Patrícia Renck; Schöler, Cinthia Maria; da Silva, Gustavo Stumpf; Bittencourt, Aline; Faccioni-Heuser, Maria Cristina; Krause, Mauricio; Bazotte, Roberto Barbosa; Curi, Rui; Homem de Bittencourt, Paulo Ivo

    2017-03-01

    Exercise stimulates immune responses, but the appropriate "doses" for such achievements are unsettled. Conversely, in metabolic tissues, exercise improves the heat shock (HS) response, a universal cytoprotective response to proteostasis challenges that are centred on the expression of the 70-kDa family of intracellular heat shock proteins (iHSP70), which are anti-inflammatory. Concurrently, exercise triggers the export of HSP70 towards the extracellular milieu (eHSP70), where they work as pro-inflammatory cytokines. As the HS response is severely compromised in chronic degenerative diseases of inflammatory nature, we wondered whether acute exercise bouts of different intensities could alter the HS response of lymphocytes from secondary lymphoid organs and whether this would be related to immunoinflammatory responses. Adult male Wistar rats swam for 20 min at low, moderate, high or strenuous intensities as per an overload in tail base. Controls remained at rest under the same conditions. Afterwards, mesenteric lymph node lymphocytes were assessed for the potency of the HS response (42 °C for 2 h), NF-κB binding activity, mitogen-stimulated proliferation and cytokine production. Exercise stimulated cell proliferation in an "inverted-U" fashion peaking at moderate load, which was paralleled by suppression of NF-κB activation and nuclear location, and followed by enhanced HS response in relation to non-exercised animals. Comparative levels of eHSP70 to iHSP70 (H-index) matched IL-2/IL-10 ratios. We conclude that exercise, in a workload-dependent way, stimulates immunoinflammatory performance of lymphocytes of tissues far from the circulation and this is associated with H-index of stress response, which is useful to assess training status and immunosurveillance balance.

  13. Myeloid Antigen-positive T Cell Acute Lymphocytic Leukemia with t(14;18) and Trisomy 10: Report of a Case and Literature Review.

    PubMed

    Lin, Guoqiang; Liu, Limin; Zhao, Guangsheng; Si, Yejun; Zhang, Xingxia; Sun, Yumei; Lu, Shuhua; Zhang, Yanming

    2015-08-01

    The chromosomal translocation t(14;18)(q32;q21) is commonly associated with neoplasms of follicular center cell origin and has also been reported in cases of chronic lymphocytic leukemia. However, T cell acute lymphoblastic (or lymphocytic) leukemia (T-ALL) with t(14;18)(q32;q21) has been rarely reported. Here, we report a case of myeloid antigen-positive T-ALL (My+T-ALL) with t(14;18)(q32;q21) and trisomy 10. This is the first reported case of My+T-ALL (L2) with such chromosomal abnormalities. Other published de novo ALL cases, with t(14;18)(q32;q21) and without a documented history of lymphoma, are summarized and reviewed in this report. The patient in this study was treated with remission induction therapy and intensive chemotherapy, followed by maintenance therapy. As of this writing, he has remained in remission for more than 3 years and has presented a better clinical outcome compared with other reported adult ALL patients with t(14;18)(q32;q21).

  14. miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221.

    PubMed

    Kotani, Ai; Ha, Daon; Hsieh, James; Rao, Prakash K; Schotte, Diana; den Boer, Monique L; Armstrong, Scott A; Lodish, Harvey F

    2009-11-05

    MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA) are small noncoding RNAs that posttranscriptionally regulate expression of target mRNAs. Our analysis of previously published data showed that expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down-regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and miR-221 is implicated in glucocorticoid resistance and that restoration of their levels is a potentially promising therapeutic in MLL-AF4 ALL.

  15. Myocarditis in puppies: clinical, pathological and virological findings.

    PubMed

    Gagnon, A N; Crowe, S P; Allen, D G; Downey, R S

    1980-07-01

    The clinical, pathological and virological findings in puppies affected with myocarditis are reported. A parvo-like virus was isolated from pooled heart specimens, which is similar to the virus isolated from gastroenteritis cases.

  16. Diagnostic Approach to Myocarditis Mimicking Myocardial Infarction at Initial Presentation

    PubMed Central

    Basman, Craig; Agrawal, Pratik R.; McRee, Chad; Saravolatz, Louis; Chen-Scarabelli, Carol; Scarabelli, Tiziano M.

    2016-01-01

    We present a case of a 35-year-old male patient with a 12-hour history of sudden-onset, crushing chest pain and associated complaints of profuse diaphoresis, nausea and vomiting. The patient was transferred to our institution from an outside hospital for evaluation and possible emergent catheterization. Left heart catheterization was conclusive for normal coronary arteries and a ventriculogram revealed a left ventricular ejection fraction of approximately 45%. Due to a suspicion of myocarditis based on clinical history, pertinent serology tests were ordered, which were found to be negative. Cardiac magnetic resonance on delayed enhancement imaging showed typical sub-epicardial enhancement in a pattern most consistent with myocarditis. The patient was eventually diagnosed with myocarditis and discharged home later, without needing a myocardial biopsy. We present and discuss here the indications of myocardial biopsy and compare the relative utility of cardiac magnetic resonance imaging in formulating the diagnosis of myocarditis. PMID:28197294

  17. Fatal Dengue Myocarditis despite the Use of Extracorporeal Membrane Oxygenation

    PubMed Central

    2016-01-01

    Dengue is an important mosquitoes-borne viral disease which is endemic in tropics and subtropics region. Rapid spreading of disease to previously unaffected region was found in recent years. Atypical manifestations, such as myocarditis, were reported during large outbreak. There is a wide range of clinical manifestations of cardiac involvement in dengue, but rarely fatal. Here we reported a case of fulminant dengue myocarditis in fatal outcome despite cardiac mechanical support. PMID:28018687

  18. Effect of Increased Neutrophil-to-Lymphocyte Ratio (NLR) and Decreased Mean Platelet Volume (MPV) Values on Inflammation in Acute Mania

    PubMed Central

    MAYDA, Hasan; AHSEN, Ahmet; BAĞCIOĞLU, Erman; ÖZTÜRK, Ahmet; BAHÇECİ, Bülent; SOYUÇOK, Etem; BAŞPINAR, Erol; ULU, Memnune Sena

    2016-01-01

    Introduction The neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV) are simple, low-cost, and useful inflammatory markers detected in routine complete blood count (CBC), and their use has recently become widespread. In this study, we aimed to investigate the presence of an inflammatory state in manic patients on the basis of NLR and MPV values. Methods This retrospective study was performed on 76 patients with acute mania who were admitted to the Inpatients Psychiatry Clinic of Afyon Kocatepe University Hospital in Turkey. Diagnoses were based on Diagnostic and Statistical Manuel of Mental disorder (DSM-IV). The control group consisted of 74 healthy individuals recruited from the community. They were age- and sex-matched with the study group. Results NLR values of the manic patient group were 2.2±1.4 and those of the control group were 1.6±0.5. NLR values were significantly higher (p=0.004) and MPV values were significantly lower in the manic patient group than in the control group (10.0±1.2 vs. 10.9±2.3, p=0.027). Conclusion Increased NLR and decreased MPV levels may reflect inflammation in manic patients, and inflammation may play a role in the complex pathophysiology of acute mania. PMID:28360805

  19. Moesin is activated in cardiomyocytes in experimental autoimmune myocarditis and mediates cytoskeletal reorganization with protrusion formation.

    PubMed

    Miyawaki, Akimitsu; Mitsuhara, Yusuke; Orimoto, Aya; Nakayasu, Yusuke; Tsunoda, Shin-Ichi; Obana, Masanori; Maeda, Makiko; Nakayama, Hiroyuki; Yoshioka, Yasuo; Tsutsumi, Yasuo; Fujio, Yasushi

    2016-08-01

    Acute myocarditis is a self-limiting disease. Most patients with myocarditis recover without cardiac dysfunction in spite of limited capacity of myocardial regeneration. Therefore, to address intrinsic reparative machinery of inflamed hearts, we investigated the cellular dynamics of cardiomyocytes in response to inflammation using experimental autoimmune myocarditis (EAM) model. EAM was induced by immunization of BALB/c mice with α-myosin heavy chain peptides twice. The inflammatory reaction was evoked with myocardial damage with the peak at 3 wk after the first immunization (EAM3w). Morphological and functional restoration started from EAM3w, when active protrusion formation, a critical process of myocardial healing, was observed in cardiomyocytes. Shotgun proteomics revealed that cytoskeletal proteins were preferentially increased in cardiomyocytes at EAM3w, compared with preimmunized (EAM0w) hearts, and that moesin was the most remarkably upregulated among them. Immunoblot analyses demonstrated that the expression of both total and phosphorylated moesin was upregulated in isolated cardiomyocytes from EAM3w hearts. Immunofluorescence staining showed that moesin was localized at cardiomyocyte protrusions at EAM3w. Adenoviral vectors expressing wild-type, constitutively active and inactive form of moesin (wtMoesin, caMoesin, and iaMoesin, respectively) were transfected in neonatal rat cardiomyocytes. The overexpression of wtMoesin and caMoesin resulted in protrusion formation, while not iaMoesin. Finally, we found that cardiomyocyte protrusions were accompanied by cell-cell contact formation. The expression of moesin was upregulated in cardiomyocytes under inflammation, inducing protrusion formation in a phosphorylation-dependent fashion. Moesin signal could be a novel therapeutic target that stimulates myocardial repair by promoting contact formation of cardiomyocytes.

  20. An Anti-Interleukin-2 Receptor Drug Attenuates T- Helper 1 Lymphocytes-Mediated Inflammation in an Acute Model of Endotoxin-Induced Uveitis

    PubMed Central

    Navea, Amparo; Almansa, Inmaculada; Muriach, María; Bosch-Morell, Francisco

    2014-01-01

    The aim of the present study was to evaluate the anti-inflammatory efficacy of Daclizumab, an anti-interleukin-2 receptor drug, in an experimental uveitis model upon a subcutaneous injection of lipopolysaccharide into Lewis rats, a valuable model for ocular acute inflammatory processes. The integrity of the blood-aqueous barrier was assessed 24 h after endotoxin-induced uveitis by evaluating two parameters: cell count and protein concentration in aqueous humors. The histopathology of all the ocular structures (cornea, lens, sclera, choroid, retina, uvea, and anterior and posterior chambers) was also considered. Enzyme-linked immunosorbent assays of the aqueous humor samples were performed to quantify the levels of the different chemokine and cytokine proteins. Similarly, a biochemical analysis of oxidative stress-related markers was also assessed. The inflammation observed in the anterior chamber of the eyes when Daclizumab was administered with endotoxin was largely prevented since the aqueous humor protein concentration substantially lowered concomitantly with a significant reduction in the uveal and vitreous histopathological grading. Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon-γ, also significantly reduced with related anti-oxidant systems recovery. Daclizumab treatment in endotoxin-induced uveitis reduced Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon gamma, by about 60–70% and presented a preventive role in endotoxin-induced oxidative stress. This antioxidant protective effect of Daclizumab may be related to several of the observed Daclizumab effects in our study, including IL-6 cytokine regulatory properties and a substantial concomitant drop in INFγ. Concurrently, Daclizumab treatment triggered a significant reduction in both the uveal histopathological grading and protein concentration in aqueous humors, but not in cellular infiltration. PMID:24595020

  1. Cellular and humoral immune reactions in chronic active liver disease. II. Lymphocyte subsets and viral antigens in liver biopsies of patients with acute and chronic hepatitis B.

    PubMed Central

    Eggink, H F; Houthoff, H J; Huitema, S; Wolters, G; Poppema, S; Gips, C H

    1984-01-01

    The characteristics and distribution of the inflammatory infiltrate in liver biopsies of 25 patients with hepatitis B viral (HBV) infection were studied in relation to the distribution and expression of HBV antigens. Mononuclear subsets were characterized with monoclonal (OKT, OKM, Leu) antibodies to surface antigens. For the demonstration of viral antigens directly conjugated antibodies to surface (HBsAg), core (HBcAg) and 'e' (HBeAg) antigen were used. For the study of mutual relations all methods were performed on serial cut tissue sections. In chronic active hepatitis B (CAH-B, n = 12) OKT8+ lymphocytes of T cell origin were the only cell type present in areas with liver cell degeneration and T cell cytotoxicity appears to be the only immune mechanism. In chronic persistent hepatitis B (CPH-B, n = 7) the only conspicuous feature was the presence of many Leu 3+ lymphocytes of the helper/inducer population in the portal tracts. In acute hepatitis B (AHB, n = 6) OKT8+ cells of non-T origin (OKT1-,3-) and Leu 7+ cells of presumed natural killer (NK) potential predominated in the areas with liver cell necrosis, and non-T cell cytotoxicity appears to be the predominant immune mechanism. In none of these disease entities a positive spatial relation could be established between the cytotoxic cells and the demonstrable expression of HBV antigens in hepatocytes. It is concluded that differences in immunological reaction pattern may explain the different course in the three forms of HBV infection studied. Images Fig. 1 Fig. 2 PMID:6713726

  2. Intracellular viral localization in murine coxsackievirus-B3 myocarditis. Ultrastructural study by electron microscopic in situ hybridization.

    PubMed Central

    Ukimura, A.; Deguchi, H.; Kitaura, Y.; Fujioka, S.; Hirasawa, M.; Kawamura, K.; Hirai, K.

    1997-01-01

    Group B Coxsackieviruses are a common cause of myocarditis. To detect the viral genome and its localization in the myocardium, we examined C3H/He mice with Coxsackievirus B3 (CVB3) myocarditis on days 5, 8, and 14 after inoculation by the reverse transcriptase polymerase chain reaction and by in situ hybridization. Sense and antisense CVB3 RNA were detected in the myocardium of all mice up to day 14 by reverse transcriptase polymerase chain reaction. Light microscopic in situ hybridization with a cDNA probe for CVB3 showed clusters of positive signals in the areas of myocardial necrosis and cell infiltration. With electron microscopic in situ hybridization, CVB3 RNA was detected in the cytoplasm of cardiocytes, between the myofibrils, near the mitochondria, and in tubular or vesicular structures. Viral RNA was also detected in necrotic debris, in the cytoplasm of macrophages, and in the cytoplasm of interstitial fibroblasts. These findings suggest that CVB3 RNA is replicated in the cytoplasm of cardiocytes, transferred into tubular or vesicular structures, released into the interstitium, and phagocytosed by macrophages. Some positive signals were also detected in the cytoplasm of cardiocytes showing close contact with infiltrating lymphocytes, suggesting that the lymphocytes recognized virus-infected cardiocytes and caused cell-mediated immune cardiocyte damage. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 PMID:9176398

  3. The mtDNA nt7778 G/T polymorphism augments formation of lymphocytic foci but does not aggravate cerulein-induced acute pancreatitis in mice.

    PubMed

    Müller, Sarah; Krüger, Burkhard; Lange, Falko; Bock, Cristin N; Nizze, Horst; Glass, Änne; Ibrahim, Saleh M; Jaster, Robert

    2014-01-01

    A polymorphism in the ATP synthase 8 (ATP8) gene of the murine mitochondrial genome, G-to-T transversion at position 7778, has been suggested to increase susceptibility to multiple autoimmune diseases, including autoimmune pancreatitis (AIP). The polymorphism also induces mitochondrial reactive oxygen species generation, secretory dysfunction and β-cell mass adaptation. Here, we have used two conplastic mouse strains, C57BL/6N-mtAKR/J (B6-mtAKR; nt7778 G; control) and C57BL/6N-mtFVB/N (B6-mtFVB; nt7778 T), to address the question if the polymorphism also affects the course of cerulein-induced acute pancreatitis in mice. Therefore, two age groups of mice (3 and 12-month-old, respectively) were subjected to up to 7 injections of the secretagogue cerulein (50 µg/kg body weight) at hourly intervals. Disease severity was assessed at time points from 3 hours to 7 days based on pancreatic histopathology, serum levels of α-amylase and activities of myeloperoxidase (MPO) in lung tissue. A comparison of cerulein-induced pancreatic tissue damage and increases of α-amylase and MPO activities showed no differences between the age-matched groups of both strains. Interestingly, histological evaluation of pancreatic tissue of both untreated and cerulein-treated B6-mtAKR and B6-mtFVB mice also revealed the presence of infiltrates of immune cells surrounding ducts and vessels; a finding that is compatible with an early stage of AIP. After recovery from cerulein-induced pancreatitis (day 7 after the injections), 12-month-old B6-mtFVB mice but not B6-mtAKR mice displayed aggravated lymphocytic lesions. A comparison of 12-month-old mice with other age groups of both strains revealed that lymphocytic foci were largely absent in 3-month-old mice, while 24-month-old mice were more affected. Together, our data suggest that the mtDNA nt7778 G/T polymorphism does not aggravate cerulein-induced acute pancreatitis. Autoimmune-like lesions, however, may progress faster if additional tissue

  4. Nucleic acid distribution pattern as a possible biomarker for metabolic activities of neoplastic cells: a digitally-aided fluorescence microscopy study on normal and neoplastic lymphocytes of acute and chronic canine lymphocytic leukemia

    PubMed Central

    Isitor, Godwin N; Campbell, Mervyn; Nayak, Shivananda B

    2009-01-01

    Background Metabolic states of neoplastic cells are increasingly being relied upon for diagnostic and prognostic assessment of neoplastic conditions. The nucleic acid distribution pattern of cells in general, in terms of degree of condensation of the nuclear chromatin and overall spread of the nucleic acid within the nuclear and cytoplasmic compartments, can reflect the metabolic state of the cell. This simple but logical concept appears not be put into consideration to date as numerous attempts are being made towards formulating reliable biomarkers for rapid diagnosis, prognosis and subsequent therapeutic interventions for neoplastic conditions. We comparatively evaluated nucleic acid distribution patterns of normal lymphocytes and neoplastic cells of lymphocytic lineage, employing light and fluorescence microscopy procedures, as well as digital imaging analytical methods. Results The results demonstrate distinctiveness in the pattern of nucleic acid distribution for the normal lymphocytes and three lymphocytic neoplastic cell-types of canine lymphocytic leukemia that are categorized as small, intermediate and large neoplastic lymphocytes. Variably-shaped cytoplasmic processes laden with single-stranded nucleic acids (SSNA) were observed for the small and intermediate-sized neoplastic lymphocytes, compared with large neoplastic lymphocytes and the normal lymphocytes; the latter two categories of cells being virtually devoid of similar processes. Prominent cytoplasmic and nuclear clumps of SSNA, indicative of a higher rate of metabolic activity, were also observed within the neoplastic cells compared with fewer and narrower SSNA of the normal cells. Conclusion The comparative relative increases of SSNA in cytoplasmic processes and other cellular areas of small and intermediate-sized neoplastic lymphocytes is reflective of greater metabolic activity in neoplastic cells in general compared with their normal cellular counterparts. PMID:19432993

  5. Use of the Impella 5.0 Device as a Bridge to Recovery in Adult Fulminant Viral Myocarditis.

    PubMed

    Burns, Daniel J P; Quantz, Mackenzie A

    2015-01-01

    We present a case of a 48-year-old female patient successfully bridged to recovery with the Impella 5.0 microaxial pump (Abiomed, Danvers, MA USA) after presenting with cardiogenic shock secondary to acute fulminant viral myocarditis. After 1 week of flu-like symptoms, the patient presented to her community emergency department with chest pain and hypotension. A diagnosis of inferior ST elevation myocardial infarction was made; subsequent angiography demonstrated normal coronary arteries and a left ventricular ejection fraction of 10%. A provisional diagnosis of viral myocarditis was made. As her condition deteriorated further, she underwent insertion of an Impella 5.0 after failure of supportive medical therapy. Myocardial recovery occurred, and the Impella was removed after 1 week. After a prolonged cardiac intensive care unit stay requiring temporary hemodialysis, the patient recovered sufficiently to tolerate device explant, transfer to the recovery ward, and ultimate discharge home. This case report highlights the benefit of mechanical circulatory support in a patient with cardiogenic shock from viral myocarditis as well as some of the complications that can occur in this critically ill subset of patients.

  6. Autonomic Nervous System in Viral Myocarditis: Pathophysiology and Therapy.

    PubMed

    Cheng, Zheng; Li-Sha, Ge; Yue-Chun, Li

    2016-01-01

    Myocarditis, which is caused by viral infection, can lead to heart failure, malignant arrhythmias, and even sudden cardiac death in young patients. It is also one of the most important causes of dilated cardiomyopathy worldwide. Although remarkable advances in diagnosis and understanding of pathophysiological mechanisms of viral myocarditis have been gained during recent years, no standard treatment strategies have been defined as yet. Fortunately, recent studies present some evidence that immunomodulating therapy is effective for myocarditis. The immunomodulatory effect of the autonomic nervous system has raised considerable interest over recent decades. Studying the influence on the inflammation and immune system of the sympathetic and parasympathetic nervous systems will not only increase our understanding of the mechanism of disease but could also lead to the identification of potential new therapies for viral myocarditis. Studies have shown that the immunomodulating effect of the sympathetic and parasympathetic nervous system is realized by the release of neurotransmitters to their corresponding receptors (catecholamine for α or β adrenergic receptor, acetylcholine for α7 nicotinic acetylcholinergic receptor). This review will discuss the current knowledge of the roles of both the sympathetic and parasympathetic nervous system in inflammation, with a special focus on their roles in viral myocarditis.

  7. Interrupted development of dentition in children receiving bone marrow transplantation for acute lymphocytic Leukemia: a case series.

    PubMed

    Rowland, Chris; Kaste, Sue; Owens, Amber

    2013-01-01

    This case series depicts dental anomalies that may develop in children who have undergone bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL). The most common finding in these patients was root stunting; other abnormalities included microdontia, hypodontia, taurodontia, caries, enamel pearls, and pulpal calcification. Recognition of these adverse effects of BMT on odontogenesis, as demonstrated on panoramic radiograph images, will allow healthcare providers to explain to parents and patients the possible dental outcomes associated with BMT and to optimize their dental health regimen.

  8. Trametes versicolor Protein YZP Activates Regulatory B Lymphocytes – Gene Identification through De Novo Assembly and Function Analysis in a Murine Acute Colitis Model

    PubMed Central

    Kuan, Yen-Chou; Wu, Ying-Jou; Hung, Chih-Liang; Sheu, Fuu

    2013-01-01

    Background Trametes versicolor (Yun-Zhi) is a medicinal fungus used as a chemotherapy co-treatment to enhance anti-tumor immunity. Although the efficacies of T. versicolor extracts have been documented, the active ingredients and mechanisms underlying the actions of these extracts remain uncharacterized. Results We purified a new protein, YZP, from the fruiting bodies of T. versicolor and identified the gene encoding YZP using RNA-seq and de novo assembly technologies. YZP is a 12-kDa non-glycosylated protein comprising 139 amino acids, including an 18-amino acids signal peptide. YZP induced a greater than 60-fold increase in IL-10 secretion in mice B lymphocytes; moreover, YZP specifically triggered the differentiation of CD1d+ B cells into IL-10-producing regulatory B cells (Bregs) and enhanced the expression of CD1d. YZP-induced B cells suppressed approximately 40% of the LPS-activated macrophage production of inflammatory cytokines in a mixed leukocyte reaction and significantly alleviated the disease activity and colonic inflammation in a DSS-induced acute colitis murine model. Furthermore, YZP activated Breg function via interaction with TLR2 and TLR4 and up-regulation of the TLR-mediated signaling pathway. Conclusions We purified a novel Breg-stimulating protein, YZP, from T. versicolor and developed an advanced approach combining RNA-seq and de novo assembly technologies.to clone its gene. We demonstrated that YZP activated CD1d+ Breg differentiation through TLR2/4-mediated signaling pathway, and the YZP-stimulated B cells exhibited anti-inflammatory efficacies in vitro and in murine acute colitis models. PMID:24019869

  9. Isolation of CD4-independent primary human immunodeficiency virus type 1 isolates that are syncytium inducing and acutely cytopathic for CD8+ lymphocytes.

    PubMed

    Zerhouni, Bouchra; Nelson, Julie A E; Saha, Kunal

    2004-02-01

    Previous studies have established the existence of CD4-independent simian immunodeficiency virus, human immunodeficiency virus type 2 (HIV-2), and laboratory strains of HIV-1. However, whether CD4-independent viruses may also exist in HIV-1-infected patients has remained unclear. We have recently reported the isolation of viruses from an AIDS patient that were able to infect CD8(+) cells independent of CD4, using CD8 as a receptor. Using a similar approach, here we examined viruses from 12 randomly selected patients (obtained from the AIDS Research and Reference Program, National Institutes of Health) for the presence of CD4-independent HIV-1. CD4-independent variants were isolated from infected CD8(+) cells from the viral quasispecies of 7 of 12 patients. The CD4-independent isolates were able to infect primary CD8(+) cells as well as a CD4(-) CD8(+) T-cell line. Soluble CD4 and blocking anti-CD4 or -CD8 antibody had no effect on infection of CD8(+) cells. Remarkably, two of the seven CD4-independent isolates, but not their parental bulk viruses, induced syncytia and caused acute death of infected CD8(+) cells. Some of the CD4-independent variants were also able to infect U87 cells that were negative for CD4, CD8, and common HIV coreceptors, suggesting a novel entry mechanism for these isolates. The CD4-independent isolates were derived from adults and children infected with subtypes A, B, and D. Although no common motif for CD4 independence was found, novel sequence changes were observed in critical areas of the envelopes of the CD4-independent viruses. These results demonstrate that HIV-1-infected patients can frequently harbor viruses that are able to mediate CD4-independent infection of CD8(+) cells. In addition, this study also provides evidence of primary HIV-1 variants that are syncytium inducing and acutely cytopathic for CD8(+) lymphocytes.

  10. [Cardiogenic shock after ingestion of amphetamines on a ground of Mycoplasma myocarditis].

    PubMed

    Berger, K; Hérault, M-C; Danel, V; Vincent, F; Jacquot, C

    2008-03-01

    Amphetamines are considered as narcotics in France. Their use induces modifications of the central nervous system and of the cardiovascular, respiratory and urinary systems by a sympathomimetic indirect effect. Here is reported the observation of a young woman who absorbed amphetamines causing a cardiogenic shock on a ground of acute myocarditis. The constitution of haemodynamic, respiratory and neurologic distresses lead to the endotracheal intubation of the patient. The haemodynamic status remaining shaky, despite the use of vasoactive drugs, a circulatory assistance by intra-aortic counter pulsation balloon was carried out. The initial echocardiography showed a left ventricular ejection fraction lower than 20%. Amphetamine's toxicity mechanisms still remain complicated; on cardiovascular plan, some cases of coronary artery spasm have been described. The coronarography, not accomplished immediately, was normal. Toxicological samples revealed an abnormally high amphetamines concentration. The severity of the cardiac attack was amplified by a Mycoplasma pneumoniae myocarditis. There was a positive evolution in eight days. Intoxication and infection can difficultly be dissociated in this case of cardiogenic shock.

  11. Bioinformatics Multivariate Analysis Determined a Set of Phase-Specific Biomarker Candidates in a Novel Mouse Model for Viral Myocarditis

    PubMed Central

    Omura, Seiichi; Kawai, Eiichiro; Sato, Fumitaka; Martinez, Nicholas E.; Chaitanya, Ganta V.; Rollyson, Phoebe A.; Cvek, Urska; Trutschl, Marjan; Alexander, J. Steven; Tsunoda, Ikuo

    2015-01-01

    Background Myocarditis is an inflammatory disease of the cardiac muscle and is mainly caused by viral infections. Viral myocarditis has been proposed to be divided into 3 phases: the acute viral phase, the subacute immune phase, and the chronic cardiac remodeling phase. Although individualized therapy should be applied depending on the phase, no clinical or experimental studies have found biomarkers that distinguish between the 3 phases. Theiler’s murine encephalomyelitis virus belongs to the genus Cardiovirus and can cause myocarditis in susceptible mouse strains. Methods and Results Using this novel model for viral myocarditis induced with Theiler’s murine encephalomyelitis virus, we conducted multivariate analysis including echocardiography, serum troponin and viral RNA titration, and microarray to identify the biomarker candidates that can discriminate the 3 phases. Using C3H mice infected with Theiler’s murine encephalomyelitis virus on 4, 7, and 60 days post infection, we conducted bioinformatics analyses, including principal component analysis and k-means clustering of microarray data, because our traditional cardiac and serum assays, including 2-way comparison of microarray data, did not lead to the identification of a single biomarker. Principal component analysis separated heart samples clearly between the groups of 4, 7, and 60 days post infection. Representative genes contributing to the separation were as follows: 4 and 7 days post infection, innate immunity–related genes, such as Irf7 and Cxcl9; 7 and 60 days post infection, acquired immunity–related genes, such as Cd3g and H2-Aa; and cardiac remodeling–related genes, such as Mmp12 and Gpnmb. Conclusions Sets of molecules, not single molecules, identified by unsupervised principal component analysis, were found to be useful as phase-specific biomarkers. PMID:25031303

  12. Malignant ventricular arrhythmias in chronic chagasic myocarditis.

    PubMed

    Chiale, P A; Halpern, M S; Nau, G J; Przybylski, J; Tambussi, A M; Lázzari, J O; Elizari, M V; Rosenbaum, M B

    1982-03-01

    We studied 28 cases of chronic chagasic myocarditis (CCM) with frequent ventricular arrhythmias. Two-hundred and three conventional ECGs recorded during 3 months showed ventricular extrasystoles (VE) ranging between 0.2 and 6 per ten beats in 100%; multiform VE in 97.04%; couplets in 79.31%; ventricular tachycardia (VT) in 42.85%; and R on T in 21.67%. A 24-hour continuous recording showed that VE ranged between 3780 and 61733 (mean 16618 +/- 2627); multiform VE and couplets were present in 100% of patients, and VT was present in 78.5%. In 16 patients (group I) the frequency of VE was persistently high, without diurnal variation; 11 patients showed sustained reduction during sleeping hours and only one showed an increase during night sleep (group II). Even in group II, VE never disappeared for periods longer than 10 minutes. In five patients, four 24-hour recordings were obtained at weekly intervals, and in five other patients a second 24-hour recording was performed 10 to 24 months later. The remarkable frequency, persistence and low variability of ventricular arrhythmias in CCM suggest that such arrhythmias can be used as a most stable, reliable, but highly demanding model for testing the efficacy of antiarrhythmic drugs.

  13. Bone marrow mesenchymal stromal cells affect the cell cycle arrest effect of genotoxic agents on acute lymphocytic leukemia cells via p21 down-regulation.

    PubMed

    Zhang, Yiran; Hu, Kaimin; Hu, Yongxian; Liu, Lizhen; Wang, Binsheng; Huang, He

    2014-09-01

    The effect of bone marrow microenvironment on the cell cycle of acute lymphocytic leukemia (ALL) and the underlying mechanism has not been elucidated. In this study, we found that in normal condition, bone marrow mesenchymal stromal cells (BM-MSCs) had no significant effect on the cell cycle and apoptosis of ALL; in the condition when the cell cycle of ALL was blocked by genotoxic agents, BM-MSCs could increase the S-phase cell ratio and decrease the G2/M phase ratio of ALL. Besides, BM-MSCs could protect ALL cells from drug-induced apoptosis. Then, we proved that BM-MSCs affect the cell cycle arrest effect of genotoxic agents on ALL cells via p21 down-regulation. Moreover, our results indicated that activation of Wnt/β-catenin and Erk pathways might be involved in the BM-MSC-induced down-regulation of p21 in ALL cells. Targeting microenvironment-related signaling pathway may therefore be a potential novel approach for ALL therapy.

  14. Low blood lymphocyte count at 30 days post transplant predicts worse acute GVHD and survival but not relapse in a large retrospective cohort.

    PubMed

    Gul, Z; Van Meter, E; Abidi, M; Ditah, I; Abdul-Hussein, M; Deol, A; Ayash, L; Lum, L G; Waller, E K; Ratanatharathorn, V; Uberti, J; Al-Kadhimi, Z

    2015-03-01

    Multiple reports have shown that low absolute lymphocyte count at day 30 (ALC30) after allogeneic hematopoietic SCT (AHSCT) is associated with higher risk of disease relapse and worse OS. However, these reports included heterogeneous populations with different grafts and GVHD prophylaxis. Therefore, we retrospectively evaluated the association of ALC30 with transplant outcomes in a cohort of 381 consecutive patients who underwent AHSCT between 2005 and 2010 and received T-replete PBSC grafts and Tacrolimus/Mycophenolate combination as GVHD prophylaxis. Median follow-up was 57 months. Lower ALC30 (⩽400 × 10(6)/L) was associated with lower OS and increased nonrelapse mortality (NRM) for the whole cohort as well as for recipients of SD and UD grafts separately. Lower ALC30 was associated with more severe acute GVHD (aGVHD; III-IV) for the entire cohort as well as for the SD and UD groups. No association was found between lower ALC30 and relapse. Pretransplant factors associated with lower ALC30 were: unrelated donors; HLA mismatch; older donors; lower recipient age; and lower CD34+ cell dose. In this large retrospective study, ALC30⩽400 × 10(6)/L was associated with worse OS, increased NRM and severe aGVHD.

  15. Role of peripheral blood minimum residual disease at day 8 of induction therapy in high-risk pediatric patients with acute lymphocytic leukemia

    PubMed Central

    Salina, Thais Ditolvo da Costa; Ferreira, Yvelise Antunes; Alves, Eliana Brasil; Ferreira, Cristina Motta; De Paula, Erich Vinícius; Mira, Marcelo Távora; Passos, Leny da Mota

    2016-01-01

    Risk stratification and treatment intensification, based on minimal residual disease (MRD) mensurement, changed the prognosis of pediatric patients with acute lymphocytic leukemia (ALL). The main aim of this study was to investigate whether peripheral blood (PB) MRD measurement at day 8 (D8) could predict the risk stratification category determined by bone marrow (BM) MRD at day 15 (D15). The study was performed prospectively, in a cohort of 40 children with B-lineage ALL, adopting the protocol of the Brazilian Cooperative Group of the Treatment Childhood Leukemia (GBTLI-2009). MRD was detected by flow cytometry (FC) using a simplifed panel that can reliably identify MRD at early phases of induction therapy. Upon diagnosis, the proportion of low and high-risk patients, was 24:16 (60%:40%). The main result of our study demonstrated the potential of D8 MRD in anticipating of week the risk stratification of high-risk patients as determined by D15 BM MRD. In these patients D8 MRD level of 1% was able to segregate high risk fast responders from high risk slow responders (p = 0.0097). This result could represent an opportunity for early treatment intensification, as already performed in some protocols. PMID:27526794

  16. Comparison of intermediate-dose methotrexate with cranial irradiation for the post-induction treatment of acute lymphocytic leukemia in children

    SciTech Connect

    Freeman, A.I.; Weinberg, V.; Brecher, M.L.

    1983-03-03

    We compared two regimens with respect to their ability to prolong disease-free survival in 506 children and adolescents with acute lymphocytic leukemia. All responders to induction therapy were randomized to treatment with 2400 rad of cranial irradiation plus intrathecal methotrexate or to treatment with intermediate-dose methotrexate plus intrathecal methotrexate, as prophylaxis for involvement of the central nervous system and other sanctuary areas. Patients were then treated with a standard maintenance regimen. Complete responders were stratified into either standard-risk or increased-risk groups on the basis of age and white-cell count at presentation. Among patients with standard risk, hematologic relapses occurred in 9 of 117 given methotrexate and 24 of 120 given irradiation (P less than 0.01). The rate of central-nervous-system relapse was higher in the methotrexate group (23 of 117) than in the irradiation group (8 of 120) (P . 0.01). Among patients with increased risk, radiation offered greater protection to the central nervous system than methotrexate (P . 0.03); there was no difference in the rate of hematologic relapse. In both risk strata the frequency of testicular relapse was significantly lower in the methotrexate group (1 patient) than the radiation group (10 patients) (P . 0.01). Methotrexate offered better protection against systemic relapse in standard-risk patients and better protection against testicular relapse overall, but it offered less protection against relapses in the central nervous system than cranial irradiation.

  17. Effect of the Polymorphism of Folylpolyglutamate Synthetase on Treatment of High-Dose Methotrexate in Pediatric Patients with Acute Lymphocytic Leukemia

    PubMed Central

    Huang, Zhen; Tong, Hong-Fei; Li, Yuan; Qian, Jiang-Chao; Wang, Ju-Xiang; Wang, Zhe; Ruan, Ji-Chen

    2016-01-01

    Background The aim of this study was to investigate the association of the polymorphism of folylpolyglutamate synthetase (FPGS) with the dynamic plasma concentration of methotrexate (MTX) in pediatric patients with acute lymphocytic leukemia (ALL), as well as the prognosis. Material/Methods 57 ALL patients and 31 age and sex-matched children (control) were included in this study. Polymerase chain reaction-restriction fragment length polymorphism was performed for the analysis of the genotype of FPGS rs1544105 and high-performance liquid chromatography for measurement of MTX plasma concentration after 24-h and 44-h treatment. Overall survival was analyzed by Kaplan-Meier method. Results No differences were observed between patients and controls regarding the distribution frequency of genotype and alleles of rs1544105. Patients carrying AA genotype had a significantly higher plasma concentration of MTX after 24 h than those carrying GG or GA (P<0.05) and no differences were found after 44 h. Kaplan-Meier survival analysis showed a longer median survival time in patients with AA than other genotypes with significant difference in overall survival. Conclusions Polymorphism of FPGS rs1544105 might be used as an effective approach for prediction of the treatment outcome of MTX. PMID:27987364

  18. Coxsackievirus-induced disease. CD4+ cells initiate both myocarditis and pancreatitis in DBA/2 mice.

    PubMed Central

    Blay, R.; Simpson, K.; Leslie, K.; Huber, S.

    1989-01-01

    DBA/2 male mice inoculated intraperitoneally with 1.8 X 10(5) plaque-forming units (PFU) coxsackievirus B-3 (CVB3) showed extensive inflammatory cell infiltration of the myocardium and acinar tissue of the pancreas in 7 days. Selective depletion of T lymphocyte subpopulations indicated that CD4 cells were either completely or partially responsible for cell damage in both organs. Other organs such as the liver were infected and contained virus titers equivalent to those seen in the heart and pancreas but showed no apparent tissue injury. The role of the CD4 cell was confirmed by positive selection of either T cell subpopulation from CVB3-immune lymphocytes in vitro and adoptive transfer of these cells into T cell-deficient (thymectomized, irradiated, bone marrow reconstituted, TXBM) DBA/2 recipients. Lymphocytes from CVB3-infected donor mice were adsorbed to myocyte, skin fibroblast, or liver vascular endothelial cell (VEC) monolayers. The adherent population was retrieved and adoptively transferred into uninfected syngeneic recipients. When killed 7 days later, the animals receiving unfractionated immune lymphocytes or cells eluted from heart monolayers developed both myocarditis and pancreatitis. Anti-Thy 1.2 and C' treatment of the unfractionated cells completely abrogated transfer of disease. Cells eluted from either fibroblast or liver VEC monolayers showed no pathogenicity. Adsorption of immune cells to heart monolayers in the presence of anti-IAd (class II major histocompatibility complex antigen, MHC) inhibited attachment of the pathogenic T cell, whereas anti KdDd (a class I MHC antigen) had no effect. Images Figure 1 PMID:2573284

  19. Clozapine-induced hypersensitivity myocarditis presenting as sudden cardiac death

    PubMed Central

    Balla, Sudarshan; Aggarwal, Kul

    2016-01-01

    Hypersensitivity myocarditis is a rare but serious adverse effect of clozapine, a commonly used psychiatric drug. We report the case of sudden cardiac death from clozapine-induced hypersensitivity myocarditis diagnosed at autopsy. A 54-year-old Caucasian male on clozapine therapy for bipolar disorder presented with a sudden onset of shortness of breath. Laboratory studies were significant for elevated N-terminal prohormone of brain natriuretic peptide. During his hospital stay, the patient died of sudden cardiac arrest from ventricular tachycardia. The autopsy revealed hypersensitivity myocarditis, which usually occurs in the first 4 weeks after the initiation of clozapine. A 4-week monitoring protocol, including laboratory assessment of troponin and C-reactive protein, may assist in the early diagnosis of this potentially fatal condition. PMID:28210568

  20. Acquired Cell-Mediated Immunodepression in Acute Chagas' Disease

    PubMed Central

    Teixeira, Antonio R. L.; Teixeira, Glória; Macêdo, Vanize; Prata, Aluizio

    1978-01-01

    In this study two groups of patients with acute Chagas' disease were identified. Group one consisted of five patients with apparent acute Chagas' disease. These patients showed symptoms and signals of an acute illness, such as high fever and enlarged spleen. One of these patients developed severe myocarditis and heart failure. Group two consisted of seven patients with inapparent acute Chagas' disease. This was a nonclinical entity, not perceived by the patient who did not seek medical care. The diagnosis was made by the shift of a serologic test which indicates the presence of immunoglobulin M antibodies to Trypanosoma cruzi. The patients with apparent acute Chagas' disease showed positive delayed-type skin response to T. cruzi antigen. Also, their leukocytes showed significant inhibition of migration in the presence of this antigen. By contrast, the patients with the inapparent acute Chagas' disease did not show positive delayed-type skin response to T. cruzi antigen and no significant inhibition was observed when their cells migrated in the presence of this antigen. Of interest, none of these patients was capable of developing contact sensitivity to 2,4-dinitrochlorobenzene. However, three out of five patients with the apparent acute disease and all the normal control subjects showed positive contact reaction after sensitization to this drug. The results of these experiments would suggest that the thymus-derived (T)-lymphocyte function is depressed in patients with the clinically inapparent acute Chagas' disease. This immunodepression seems to be acquired in the course of the T. cruzi infection because all patients showed positive delayed-type skin response to at least one ubiquitous microbial extract, thus indicating previously normal T-cell function. We hypothesize that T. cruzi antigens may directly stimulate T cells with the concomitant release of factors that might become supressive for T-cell responses. Furthermore, the suppressive effect might interfere

  1. [Fetal death caused by myocarditis and isolated congenital auriculoventricular block].

    PubMed

    Herreman, G; Ferme, I; Morel, S; Batisse, J; Vuon, N P; Meyer, O

    1985-09-07

    A 26-year old woman gave birth, at term, to a child with isolated complete heart block. A second pregnancy was interrupted by foetal death. Among other immunological abnormalities, this young woman had an antibody resembling the anti-SS-B antibody. At pathological examination the foetus' heart was found to be free of malformation but presented with subacute myocarditis associated with microcalcifications of the conductive tissue. Such findings suggest that an incipient myocarditis may either result in foetal death or lead to fibrosis of conduction pathways with isolated complete heart block.

  2. Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Lymphocytic or Myelogenous Leukemia

    ClinicalTrials.gov

    2017-03-13

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  3. Virus-induced Transient Bone Marrow Aplasia: Major Role of Interferon-α/β during Acute Infection with the Noncytopathic Lymphocytic Choriomeningitis Virus

    PubMed Central

    Binder, Daniel; Fehr, Jörg; Hengartner, Hans; Zinkernagel, Rolf M.

    1997-01-01

    The hematologic consequences of infection with the noncytopathic lymphocytic choriomeningitis virus (LCMV) were studied in wild-type mice with inherent variations in their interferon (IFN)-α/β responder ability and in mutant mice lacking α/β (IFN-α/β R0/0) or γ IFN (IFN-γ R0/0) receptors. During the first week of infection, wild type mice demonstrated a transient pancytopenia. Within a given genetic background, the extent of the blood cell abnormalities did not correlate with the virulence of the LCMV isolate but variations were detected between different mouse strains; they were found to depend on their IFN-α/β responder phenotype. Whereas IFN-γ R0/0 mice were comparable to wild-type mice, IFN-α/β R0/0 mice exhibited unchanged peripheral blood values during acute LCMV infection. In parallel, the bone marrow (BM) cellularity, the pluripotential and committed progenitor compartments were up to 30-fold reduced in wild type and IFN-γ R0/0, but remained unchanged in IFN-α/β R0/0 mice. Viral titers in BM 3 d after LCMV infection were similar in these mice, but antigen localization was different. Viral antigen was predominantly confined to stromal BM in normal mice and IFN-γ R0/0 knockouts, whereas, in IFN-α/β R0/0 mice, LCMV was detected in >90% of megakaryocytes and 10–15% of myeloid precursors, but not in erythroblasts. Although IFN-α/β efficiently prevented viral replication in potentially susceptible hematopoietic cells, even in overwhelming LCMV infection, unlimited virus multiplication in platelet and myeloid precursors in IFN-α/β R0/0 mice did not interfere with the number of circulating blood cells. Natural killer (NK) cell expansion and activity in the BM was comparable on day 3 after infection in mutant and control mice. Adaptive immune responses did not play a major role because comparable kinetics of LCMV-induced pancytopenia and transient depletion of the pluripotential and committed progenitor compartments were observed in CD80

  4. Two-Stage, In Silico Deconvolution of the Lymphocyte Compartment of the Peripheral Whole Blood Transcriptome in the Context of Acute Kidney Allograft Rejection

    PubMed Central

    Shannon, Casey P.; Balshaw, Robert; Ng, Raymond T.; Wilson-McManus, Janet E.; Keown, Paul; McMaster, Robert; McManus, Bruce M.; Landsberg, David; Isbel, Nicole M.; Knoll, Greg; Tebbutt, Scott J.

    2014-01-01

    Acute rejection is a major complication of solid organ transplantation that prevents the long-term assimilation of the allograft. Various populations of lymphocytes are principal mediators of this process, infiltrating graft tissues and driving cell-mediated cytotoxicity. Understanding the lymphocyte-specific biology associated with rejection is therefore critical. Measuring genome-wide changes in transcript abundance in peripheral whole blood cells can deliver a comprehensive view of the status of the immune system. The heterogeneous nature of the tissue significantly affects the sensitivity and interpretability of traditional analyses, however. Experimental separation of cell types is an obvious solution, but is often impractical and, more worrying, may affect expression, leading to spurious results. Statistical deconvolution of the cell type-specific signal is an attractive alternative, but existing approaches still present some challenges, particularly in a clinical research setting. Obtaining time-matched sample composition to biologically interesting, phenotypically homogeneous cell sub-populations is costly and adds significant complexity to study design. We used a two-stage, in silico deconvolution approach that first predicts sample composition to biologically meaningful and homogeneous leukocyte sub-populations, and then performs cell type-specific differential expression analysis in these same sub-populations, from peripheral whole blood expression data. We applied this approach to a peripheral whole blood expression study of kidney allograft rejection. The patterns of differential composition uncovered are consistent with previous studies carried out using flow cytometry and provide a relevant biological context when interpreting cell type-specific differential expression results. We identified cell type-specific differential expression in a variety of leukocyte sub-populations at the time of rejection. The tissue-specificity of these differentially

  5. Preliminary evidence for lymphocyte distribution differences at rest and after acute psychological stress in PTSD-symptomatic women.

    PubMed

    Glover, Dorie A; Steele, Amber C; Stuber, Margaret L; Fahey, John L

    2005-05-01

    This study investigated circulating natural killer (NK), CD4+ and CD8+ cells in response to acute psychological challenge among mothers of child cancer survivors with and without posttraumatic stress symptoms (PTSS). Control mothers of healthy children (n=9) were compared to 17 cancer mothers with (PTSS: n=9) and without PTSS (No PTSS: n=7) under conditions of rest, after a generic stressor (MAT: mental arithmetic task) and a personalized stressor (script-driven trauma imagery), and after recovery from each stressor. Results indicate the PTSS group had higher percentage CD4+ and lower CD8+ levels than non-symptomatic women and blunted NK reactivity to generic challenge. Multiple regression analyses indicated PTSS effects were independent of self-reported distress. Contrary to expectations, cancer mothers without PTSS were not significantly different from controls on tonic or phasic immune outcomes. Also unlike predictions, reactivity to challenge was greatest to the non-social MAT stressor compared to the personalized challenge for all groups. Conclusions are constrained by study limitations (e.g., small sample size and potential phase order effects). Nonetheless, results are consistent with an emerging literature on PTSS-associated immune differences and further suggest these effects may be distinct from that associated with subjective distress more generally.

  6. Characterization of the Myocarditis during the worst outbreak of dengue infection in China.

    PubMed

    Li, Yingying; Hu, Zhongwei; Huang, Yuli; Li, Jianping; Hong, Wenxin; Qin, Zhihui; Tong, Yuwei; Li, Jinglong; Lv, Mingfang; Li, Meiyu; Zheng, Xiaoke; Hu, Jun; Hua, Jinghai; Zhang, Fuchun; Xu, Ding-Li

    2016-07-01

    Myocarditis is a common complication of severe dengue infection. However, data about prevalence and characterization of myocarditis in dengue are still lacking. In 2014, the worst outbreak of dengue in the last two decades in China occurred. In this study, we described the clinical and laboratory diagnostic features of dengue with myocarditis. Totally, 1782 diagnosed dengue patients were admitted from August to October, 2014, all of whom were subjected to electrocardiogram, ultrasound cardiogram, and cardiac enzyme test. About 201 cases of dengue patients were diagnosed with myocarditis and the prevalence of myocarditis in hospitalized dengue was 11.28%. The prevalence of myocarditis in nonsevere dengue with warning signs and severe dengue [NSD(WS+)/SD] and nonsevere dengue without warning signs [NSD(WS-)] was 46.66% and 9.72%, respectively. The NSD(WS+)/SD patients with myocarditis presented with higher incidence of cardiac symptoms, supraventricular tachycardia (14.29% vs. 0%, P < 0.001), atrial fibrillation (25.71% vs. 10.24%, P = 0.019) and heart failure compared with NSD (WS-) patients with myocarditis. About 150 cases of dengue patients without myocarditis in the same period of time in department of Cardiology were recruited as control group. The proportion of NSD(WS+)/SD in dengue patients with and without myocarditis was 17.41% and 2.53%, respectively. Dengue patients with myocarditis experienced longer hospital stay than those without myocarditis (7.17 ± 4.64 vs. 5.98 ± 2.69, P = 0.008). There was no difference between patients with and without myocarditis in the proportion of symptoms, auxiliary methods abnormality, arrhythmia, and heart failure on the discharge day. Our study demonstrates the prevalence of myocarditis in worst outbreak of dengue in China was 11.28% and the incidence of myocarditis increased with the severity of dengue. The NSD(WS+)/SD patients with myocarditis presented with higher incidence of cardiac complication compared

  7. Presence of Antigen-Experienced T Cells with Low Grade of Differentiation and Proliferative Potential in Chronic Chagas Disease Myocarditis

    PubMed Central

    Cabeza-Meckert, Patricia; Viotti, Rodolfo; Garelli, Fernando; Favaloro, Liliana E.; Favaloro, Roberto R.; Laguens, Rubén; Laucella, Susana A.

    2014-01-01

    Background The main consequence of chronic Trypanosoma cruzi infection is the development of myocarditis in approximately 20–30% of infected individuals but not until 10–20 years after the initial infection. We have previously shown that circulating interferon-γ-secreting T cells responsive to Trypanosoma cruzi antigens in chronic Chagas disease patients display a low grade of differentiation and the frequency of these T lymphocytes decreases along with the severity of heart disease. This study thought to explore the expression of inhibitory receptors, transcription factors of type 1 or regulatory T cells, and markers of T cell differentiation, immunosenescence or active cell cycle in cardiac explants from patients with advanced Chagas disease myocarditis. Methodology/Principal Findings The expression of different markers for T and B cells as well as for macrophages was evaluated by immunohistochemistry and immunofluorescence techniques in cardiac explants from patients with advanced chronic Chagas disease submitted to heart transplantation. Most infiltrating cells displayed markers of antigen-experienced T cells (CD3+, CD4+, CD8+, CD45RO+) with a low grade of differentiation (CD27+, CD57−, CD45RA−, PD-1−). A skewed T helper1/T cytotoxic 1 profile was supported by the expression of T-bet; whereas FOXP3+ cells were scarce and located only in areas of severe myocarditis. In addition, a significant proliferative capacity of CD3+ T cells, assessed by Ki67 staining, was found. Conclusions/Significance The quality of T cell responses and immunoregulatory mechanisms might determine the pattern of the cellular response and the severity of disease in chronic Trypanosoma cruzi infection. PMID:25144227

  8. Diagnosis of myocarditis: Current state and future perspectives.

    PubMed

    Biesbroek, P Stefan; Beek, Aernout M; Germans, Tjeerd; Niessen, Hans W M; van Rossum, Albert C

    2015-07-15

    Myocarditis, i.e. inflammation of the myocardium, is one of the leading causes of sudden cardiac death (SCD) and dilated cardiomyopathy (DCM) in young adults, and is an important cause of symptoms such as chest pain, dyspnea and palpitations. The pathophysiological process of disease progression leading to DCM involves an ongoing inflammation as a result of a viral-induced auto-immune response or a persisting viral infection. It is therefore crucial to detect the disease early in its course and prevent persisting inflammation that may lead to DCM and end-stage heart failure. Because of the highly variable clinical presentation, ranging from mild symptoms to severe heart failure, and the limited available diagnostic tools, the evaluation of patients with suspected myocarditis represents an important clinical dilemma in cardiology. New approaches for the diagnosis of myocarditis are needed in order to improve recognition, to help unravel its pathophysiology, and to develop new therapeutic strategies to treat the disease. In this review, we give a comprehensive overview of the current diagnostic strategies for patients with suspected myocarditis, and demonstrate several new techniques that may help to improve the diagnostic work-up.

  9. Case report: A presumptive case of vaccinia myocarditis.

    PubMed

    Guerdan, Bruce R; Shumway, Gail Janet

    2004-11-01

    A 26-year-old male medical technician who received the smallpox (vaccinia) vaccination developed a clinical case of myocarditis 11 days after vaccination. The medical literature has little information on this complication of vaccination. The individual was admitted for evaluation and pain control. At discharge, he appeared to have had no long-term effects and has returned to duty.

  10. Giant cell myocarditis mimicking idiopathic fascicular ventricular tachycardia.

    PubMed

    Weidenbach, Michael; Springer, Tina; Daehnert, Ingo; Klingel, Karin; Doll, Susanne; Janousek, Jan

    2008-02-01

    We report an adolescent with giant cell myocarditis (GCM) mimicking tachycardia-induced cardiomyopathy. His electrocardiogram (ECG) was typical for an incessant form of fascicular ventricular tachycardia. The patient rapidly deteriorated and required support using extracorporeal membrane oxygenation (ECMO). Biopsy revealed GCM with massive myocyte necrosis. He was successfully heart transplanted 6 days after admission.

  11. Comparison of outcomes after donor lymphocyte infusion with or without prior chemotherapy for minimal residual disease in acute leukemia/myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Mo, Xiao-Dong; Zhang, Xiao-Hui; Xu, Lan-Ping; Wang, Yu; Yan, Chen-Hua; Chen, Huan; Chen, Yu-Hong; Han, Wei; Wang, Feng-Rong; Wang, Jing-Zhi; Liu, Kai-Yan; Huang, Xiao-Jun

    2017-03-11

    The efficacy of donor lymphocyte infusion (DLI) without chemotherapy was investigated and compared with that of chemotherapy prior to DLI (Chemo-DLI) in patients who were minimal residual disease (MRD)-positive after allogeneic hematopoietic stem cell transplantation (HSCT). We enrolled 115 consecutive patients who received either DLI (n = 20) or Chemo-DLI (n = 95) during the same period. For each DLI recipient, three recipients matched for age at the HSCT, underlying diseases, and the year of the HSCT were randomly selected from the Chemo-DLI cohort (n = 60). The 2-year cumulative incidence of severe acute graft-versus-host disease (GVHD) and chronic GVHD was comparable between the groups. Fifteen (75.0%) and 47 (78.3%) patients in the DLI and Chemo-DLI groups turned MRD-negative, respectively. The 2-year cumulative incidences of relapse and non-relapse mortality after intervention were 30.7 versus 39.6% (P = 0.582) and 10.3 versus 6.0% (P = 0.508) in the DLI and Chemo-DLI groups, respectively. The 2-year probabilities of disease-free, overall, and GVHD-free/relapse-free survival after preemptive intervention were 58.9 versus 54.3% (P = 0.862), 69.3 versus 78.1% (P = 0.361), and 44.4 versus 35.1% (P = 0.489) in the DLI and Chemo-DLI groups, respectively. In multivariate analysis, the intervention method did not significantly influence the clinical outcomes. In summary, preemptive DLI alone may be effective for patients who are MRD-positive and may be a potential alternative for patients who refuse or are unable to receive Chemo-DLI after HSCT.

  12. Palifermin and Chlorhexidine Mouthwashes in Prevention of Chemotherapy-Induced Mucositis in Children with Acute Lymphocytic Leukemia: a Randomized Controlled Trial

    PubMed Central

    Gholizadeh, Narges; Mehdipoor, Masoumeh; Sajadi, Hasan; Moosavi, Mahdieh-Sadat

    2016-01-01

    Statement of the Problem: Over the past three decades, significant improvements have been achieved in the survival of children with cancer. However, the considerable morbidity which occurs as a result of chemotherapy often restricts the treatment intensity. One of the important dose-limiting and costly adverse effects of cancer therapy is mucositis. Children with hematological malignancies are greatly at risk of developing mucositis. Purpose: This study aimed to assess the effectiveness of palifermin in preventing mucositis in children with acute lymphocytic leukemia (ALL) who undergo chemotherapy. Materials and Method: In this clinical trial, 90 children with ALL were randomized to receive chlorhexidine (n=45) or palifermin (n=45). One group received 60 μg/ kg/ day palifermin as an intravenous bolus once daily for 3 days before and 3 days after the chemotherapy. Chlorhexidine mouthwash was administered once daily for 3 days before and 3 days after the chemotherapy. The world health organization (WHO) oral toxicity scale was employed for grading the mucositis. The data were analyzed by using two-way ANOVA. Results: The two groups were matched for age and gender. The study groups were significantly different in terms of mucositis grading (P values after 1 and 2 week therapy were 0.00). Palifermin decreased the incidence and severity of chemotherapy-induced mucositis. Conclusion: Palifermin reduces the oral mucositis in children with ALL. Several mechanisms of action are suggested for keratinocyte growth factor (such as palifermin) including promotion of cell proliferation and cytoprotection, restraining the apoptosis, and changing the cytokine profile. PMID:27942550

  13. [Clinical efficacy of decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen on elderly patients with high risk myelodysplastic syndrome and acute myeloid leukemia].

    PubMed

    Dou, Li-Ping; Jing, Yu; Wang, Quan-Shun; Mei, Jun-Hui; Yu, Li

    2013-06-01

    This study was aimed to observe the clinical efficacy and adverse effects of decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen on elderly patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Five elderly patients with MDS and AML were treated with decitabine plus improved CAG chemotherapy and donor peripheral lymphocyte infusion regimen. Examinations on liver and renal function, electrocardiogram and bone marrow analysis were performed before and after treatment, and adverse effects were observed. The results indicated that after a course of treatment by decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen, the total effective rate was 100%, and 4 patients (80%) achieved complete remission, 1 patient achieved partial remission. The dominant clinical adverse effect was bone marrow depression, the median time of neutrophil>0.5×10(9)/L and platelet>20×10(9)/L was 15 d and 16 d respectively for patients without previous MDS. It is concluded that decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen may be effective with less adverse effects for elderly primary AML and high risk MDS patients, it is a promising therapeutic methods and worthy to deeply study.

  14. Trial of Donor Lymphocyte Infusion (DLI) and Activated DLI Following Relapse After Allogeneic Stem Cell Transplant

    ClinicalTrials.gov

    2016-12-01

    Chronic Myelogenous Leukemia; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma; Hodgkin's Disease; Multiple Myeloma; Chronic Lymphocytic Leukemia

  15. Gallium-67 imaging in patients with dilated cardiomyopathy and biopsy-proven myocarditis

    SciTech Connect

    O'Connell, J.B.; Henkin, R.E.; Robinson, J.A.; Subramanian, R.; Scanlon, P.J.; Gunnar, R.M.

    1984-07-01

    Current standards for detection of myocarditis in a clinical setting rely on endomyocardial biopsy for accurate diagnosis. With this technique a subset of patients with dilated cardiomyopathy show unsuspected myocarditis histologically. Endomyocardial biopsy, despite its specificity, may lack sensitivity due to sampling error if the inflammation is patchy or focal. Therefore, inflammation-sensitive radioisotopic imaging may be a useful adjunct in the diagnosis of myocarditis. This study was designed to evaluate the applicability of gallium-67 (67Ga) myocardial imaging as an adjunct to endomyocardial biopsy in the diagnosis of myocarditis. Sixty-eight consecutive patients referred for evaluation of dilated cardiomyopathy underwent 71 parallel studies with 67Ga imaging and biopsies that served as the basis of comparison for this study. Histologic myocarditis was identified in 8% of biopsy specimens. Clinical and hemodynamic parameters could not be used to predict the presence of myocarditis. Five of six biopsy samples (87%) with myocarditis showed dense 67Ga uptake, whereas only nine of 65 negative biopsy samples (14%) were paired with equivocally positive 67Ga scans. The single patient with myocarditis and no myocardial 67Ga uptake had dense mediastinal lymph node uptake that may have obscured cardiac uptake. The incidence of myocarditis on biopsy with a positive 67Ga scan was 36% (5/14); however, the incidence of myocarditis with a negative 67Ga scan was only 1.8% (1/57). Follow-up scans for three patients showed close correlation of 67Ga uptake with myocarditis on biopsy. In conclusion 67Ga may be a useful screening test for identifying patients with a high yield of myocarditis on biopsy, and serial scans may eliminate the need for frequent biopsies in patients with proven myocarditis.

  16. Recent Toxoplasmosis Infection With Acute Myopericarditis and Persistent Troponin Elevation in an Immunocompetent Patient

    PubMed Central

    Roubille, François; Roubille, Camille; Lattuca, Benoît; Gervasoni, Richard; Vernhet-Kovacsik, Hélène; Leclercq, Florence

    2012-01-01

    Although often considered as "begnin", acute infections in young healthy adults can lead to heart inflammation, including acute myocarditis. We report a rare case of myopericarditis in a young immunocompetent adult, in the context of recent toxoplasmosis infection. Clinical presentation was common acute pericarditis, but with risk biomarkers: high troponin I levels and multiple inflammation-compatible images on MR-scan. Diagnosis of myopericarditis was established. In spite of spontaneous favourable clinical evolution, troponin remained elevated. MR-scan is shown; acute myocarditis in the context of an acute toxoplasmosis infection is discussed.

  17. Patterns and clinical manifestations of tuberculous myocarditis: a systematic review of cases.

    PubMed

    Michira, Brian Nyasani; Alkizim, Faraj Omar; Matheka, Duncan Mwangangi

    2015-01-01

    Tuberculosis is a rare cause of myocarditis. It is however associated with a high mortality when it occurs and is often diagnosed at post-mortem. Tuberculous myocarditis prevalence in males is twice that in females. Most of the reported cases of tuberculous myocarditis are predominantly in immunocompetent patients. Out of the reported fatalities (sudden cardiac deaths), eighty one percent (81%) occur in the 'young' patients (below 45years). Antituberculosis drug therapy does not appear to offer mortality benefit against sudden cardiac deaths.

  18. 11C-Methionine PET of Myocardial Inflammation in a Rat Model of Experimental Autoimmune Myocarditis.

    PubMed

    Maya, Yoshifumi; Werner, Rudolf A; Schütz, Claudia; Wakabayashi, Hiroshi; Samnick, Samuel; Lapa, Constantin; Zechmeister, Christina; Jahns, Roland; Jahns, Valérie; Higuchi, Takahiro

    2016-12-01

    Myocarditis represents a major cause of dilated cardiomyopathy and sudden cardiac death in younger adults. Currently, definitive diagnosis of myocarditis requires endomyocardial biopsy, which is highly invasive and has the drawback of variable sensitivity due to inherent sampling error. Therefore, reliable noninvasive methods to detect and monitor cardiac inflammation are clinically relevant. In this study, we explored the potential of radiolabeled methionine to assess myocardial inflammatory activity in a rat model of experimental autoimmune myocarditis (EAM).

  19. Recent advances in the management of autoimmune myocarditis: insights from animal studies.

    PubMed

    Tajiri, Kazuko; Yasutomi, Yasuhiro; Aonuma, Kazutaka

    2016-01-01

    A growing body of evidence has been accumulating to demonstrate that human myocarditis and dilated cardiomyopathy involve a complex interaction with autoimmunity triggered by cardiotropic microbial infections. Animal experiments have provided direct evidence that infections with a particular microbe can incite autoimmune myocarditis, and this autoimmune response can be mimicked by immunization with the cardiac autoantigen, α- myosin. Animal models greatly advanced our understanding of the molecular mechanisms of myocarditis, and various novel therapeutic strategies have been reported during the last two decades. In this review we present animal models of autoimmune myocarditis and describe the outlook of possible drug targets by showing the latest findings from animal studies.

  20. [Myocarditis in the differential diagnosis of cardiomyopathies. Endomyocardial biopsy or MRI?].

    PubMed

    Besler, C; Schuler, G; Lurz, P

    2015-06-01

    Myocarditis is an inflammatory disease of the heart muscle commonly caused by viral pathogens. Dilated cardiomyopathy is a major long-term sequela of myocarditis and at least in part related to post-viral immune-mediated responses. Establishing a diagnosis of myocarditis represents a major challenge because of the variable clinical picture and the lack of readily available, non-invasive diagnostic tests. In recent years, cardiac magnetic resonance imaging (cMRI) has emerged as a promising additional diagnostic tool in patients with suspected myocarditis: cMRI not only provides important insights into structural and functional abnormalities of the heart but relevant tissue pathologies can also be visualized. The diagnostic accuracy of three tissue criteria, i.e. the edema ratio, early gadolinium enhancement ratio and late gadolinium enhancement, has been characterized in several studies. Endomyocardial biopsy (EMB) is widely considered to be the reference standard for diagnosis of myocarditis. Although limited by sampling error, EMB is the only diagnostic procedure that can be used to confirm myocarditis. Laboratory analyses of EMB may provide information about specific causes of myocarditis and are, at least in part, of prognostic relevance. In a subset of patients the results of EMB may guide therapeutic decision-making. Additional efforts are needed in cardiac imaging, molecular characterization of EMB and evaluation of serum biomarkers to improve the diagnostic work-up in patients with suspected myocarditis and to identify potential novel targets for a cause-specific therapy of myocarditis.

  1. Relevance of Molecular Mimicry in the Mediation of Infectious Myocarditis

    PubMed Central

    Massilamany, Chandirasegaran; Huber, Sally A.; Cunningham, Madeleine W.

    2014-01-01

    Heart disease, the leading cause of death in humans, is estimated to affect one in four American adults in some form. One predominant cause of heart failure in young adults is myocarditis, which can lead to the development of dilated cardiomyopathy, a major indication for heart transplantation. Environmental microbes, including viruses, bacteria, and fungi that are otherwise innocuous, have the potential to induce inflammatory heart disease. As the list is growing, it is critical to determine the mechanisms by which microbes can trigger heart autoimmunity and, importantly, to identify their target antigens. This is especially true as microbes showing structural similarities with the cardiac antigens can predispose to heart autoimmunity by generating cross-reactive immune responses. In this review, we discuss the relevance of molecular mimicry in the mediation of infectious myocarditis. PMID:24263348

  2. [Bioenergetics of the myocardiocytes in infectious-allergic myocarditis].

    PubMed

    Odinokova, V A; Smirnov, V B; Gurevich, M A

    1989-01-01

    The role of myoglobin in myocardial bio-energetics was analyzed in cases of infectious-allergic myocarditis (38 endomyocardial biopsies and 18 autopsies). Myoglobin content is found to be directly related to the severity of the disease and the degree of circulatory compensation or decompensation. In conditions of progressive muscular cell dystrophy, an abrupt drop in myoglobin, detectable around the A discs, can be seen. In hypertrophic myocardiocytes of compensated circulation, myoglobin is detected as distinctly outlined large and small granules.

  3. Nitric oxide synthase in experimental autoimmune myocarditis dysfunction.

    PubMed

    Goren, N; Leiros, C P; Sterin-Borda, L; Borda, E

    1998-11-01

    This study reports the expression of inducible nitric oxide synthase (NOS) in heart from autoimmune myocarditis mice associated with an alteration in their contractile behavior. By mean of the production of [U-14C]citrulline from [U-14C]arginine and immunoblot assay, the expression of iNOS was demonstrated in autoimmune atria that was normally absent. The iNOS activity decreased with administration of dexamethasone and in mice treated with monoclonal anti-interferon-gamma antibody (anti-IFN-gamma mAb). The inhibitors of protein kinase C activity (staurosporine) but not calcium/calmodulin (trifluoperazine) attenuated the iNOS activity. Moreover, autoimmune atria presented contractile alterations (lower values of dF/dt than control). The in vivo treatment with inhibitors of NOS activity or anti-IFN-gamma mAb or dexamethasone improved the contractile activity of autoimmune atria with no change in the contractility of normal atria. The results suggest that the infiltrative cells in myocarditis heart have a potential role in cardiac dysfunction by production of IFN-gamma and subsequent expression of iNOS, that in turn alter the contractile behavior of the heart. The data indicate that cytokines induced activation of L-arginine nitric oxide pathway in myocarditis atria leading to contractile dysfunction.

  4. Frequent epigenetic inactivation of KIBRA, an upstream member of the Salvador/Warts/Hippo (SWH) tumor suppressor network, is associated with specific genetic event in B-cell acute lymphocytic leukemia.

    PubMed

    Hill, Victoria K; Dunwell, Thomas L; Catchpoole, Daniel; Krex, Dietmar; Brini, Anna T; Griffiths, Mike; Craddock, Charles; Maher, Eamonn R; Latif, Farida

    2011-03-01

    The WW-domain containing protein KIBRA has recently been identified as a new member of the Salvador/Warts/Hippo (SWH) pathway in Drosophila and is shown to act as a tumor suppressor gene in Drosophila. This pathway is conserved in humans and members of the pathway have been shown to act as tumor suppressor genes in mammalian systems. We determined the methylation status of the 5' CpG island associated with the KIBRA gene in human cancers. In a large panel of cancer cell lines representing common epithelial cancers KIBRA was unmethylated. But in pediatric acute lymphocytic leukemia (ALL) cell lines KIBRA showed frequent hypermethylation and silencing of gene expression, which could be reversed by treatment with 5-aza-2'-deoxycytidine. In ALL patient samples KIBRA was methylated in 70% B-ALL but was methylated in < 20% T-ALL leukemia (p = 0.0019). In B-ALL KIBRA methylation was associated with ETV6/RUNX1 [t(12;21) (p13;q22)] chromosomal translocation (p = 0.0082) phenotype, suggesting that KIBRA may play an important role in t(12;21) leukemogenesis. In ALL paired samples at diagnosis and remission KIBRA methylation was seen in diagnostic but not in any of the remission samples accompanied by loss of KIBRA expression in disease state compared to patients in remission. Hence KIBRA methylation occurs frequently in B-cell acute lymphocytic leukemia but not in epithelial cancers and is linked to specific genetic event in B-ALL.

  5. Early lymphocyte recovery at 28 d post-transplant is predictive of reduced risk of relapse in patients with acute myeloid leukemia transplanted with peripheral blood stem cell grafts.

    PubMed

    Michelis, Fotios V; Messner, Hans A; Loach, David; Uhm, Jieun; Gupta, Vikas; Lipton, Jeffrey H; Seftel, Matthew D; Kuruvilla, John; Kim, Dennis D

    2014-10-01

    Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for acute myeloid leukemia (AML). Impact of lymphocyte recovery on post-transplant outcomes has been suggested but reports are conflicting. We evaluated the impact of lymphocyte recovery at 28 d post-HCT in 191 AML patients using peripheral blood stem cells as graft. Patients were divided into those with absolute lymphocyte count (ALC) ≥ 0.5 × 10(9) /L (n = 111, 58%; high ALC group) and those with ALC < 0.5 × 10(9) /L (n = 80, 42%; low ALC group), at day 28 post-transplant. With a median follow-up of 49 months, overall survival (OS) was significantly improved in the high ALC group (59% at 3 yr) vs. patients with low ALC (40% at 3 yr, P = 0.03). Cumulative incidence of relapse (CIR) was significantly lower in the high ALC group (16% at 3 yr) vs. low ALC group (36% at 3 yr, P = 0.001). Multivariable analysis for CIR demonstrated high ALC group as an independent factor decreasing relapse risk (P = 0.03, HR = 0.49, 95% CI = 0.26-0.92). Multivariable analysis for OS and non-relapse mortality did not demonstrate ALC ≥ 0.5 × 10(9) /L at 28 d post-transplant to be predictive. We conclude that lymphocyte recovery with ALC ≥ 0.5 × 10(9) /L at day 28 post-transplant is associated with less relapse in AML patients undergoing allogeneic peripheral blood HCT, but without survival benefit.

  6. Reduced-energy diet improves survival of obese KKAy mice with viral myocarditis: induction of cardiac adiponectin expression.

    PubMed

    Kanda, Tsugiyasu; Saegusa, Seiichiro; Takahashi, Takashi; Sumino, Hiroyuki; Morimoto, Shigeto; Nakahashi, Takeshi; Iwai, Kunimitsu; Matsumoto, Masayuki

    2007-07-31

    Obesity is an important risk factor for heart disease. Whether weight loss affects the severity of heart failure induced by viral myocarditis is a matter of debate. We hypothesized that weight loss could improve cardiac dysfunction by inducing cardiac expression of a cardioprotective cytokine, adiponectin. We examined the relationship between weight loss by food restriction and heart failure due to viral myocarditis in obese KKAy mice. We intraperitoneally injected encephalomyocarditis virus (500 plaque-forming units/mouse) into KKAy mice fed ad libitum as a control (CF) or 60% restriction of that eaten by ad libitum (RF). The 14-day survival rate was 0% in FF, whereas it was 23% in RF (P<0.01). Heart weight/body weight ratio in RF was lower than that in FF on day 5 after viral inoculation (P<0.05). Histological scores for myocardial necrosis and inflammation on day 5 were significantly lower in RF than in FF (P<0.05). Circulating adiponectin level on day 0 was significantly elevated in RF compared with that in FF (32+9 vs. 22+2 microg/mL, P<0.05). Comparative expression of cardiac adiponectin mRNA in RF was significantly higher than that in FF (5.1+0.3 vs. 1+0.2, P<0.05). Cardiac tumor necrosis factor-alpha (TNF-alpha) mRNA in RF was significantly decreased compared with that in FF on day 5 (P<0.05). Cardiac expression of nuclear factor kappa B was reduced and that of peroxisome proliferator-activated receptor gamma mRNA was increased in RF in comparison with FF on day 0. Cardiac adiponectin mRNA was negatively correlated with cardiac TNF-alpha mRNA (r=-0.555; P=0.0097). Weight loss improved the survival and myocardial damage in obese mice with viral myocarditis, with cardiac induction of adiponectin. The induction of adiponectin might provide benefit through a cardioprotective effect against acute heart failure due to viral myocarditis in obese subjects.

  7. Viral myocarditis: potential defense mechanisms within the cardiomyocyte against virus infection

    PubMed Central

    Yajima, Toshitaka

    2011-01-01

    Virus infection can inflict significant damage on cardiomyocytes through direct injury and secondary immune reactions, leading to myocarditis and dilated cardiomyopathy. While viral myocarditis or cardiomyopathy is a complication of systemic infection of cardiotropic viruses, most individuals infected with the viruses do not develop significant cardiac disease. However, some individuals proceed to develop severe virus-mediated heart disease. Recent studies have shown that viral infection of cardiomyocytes is required for the development of myocarditis and subsequent cardiomyopathy. This suggests that viral infection of cardiomyocytes can be an important step that determines the pathogenesis of viral myocarditis during systemic infection. Accordingly, this article focuses on potential defense mechanisms within the cardiomyocyte against virus infection. Understanding of the cardiomyocyte defense against invading viruses may give us novel insights into the pathophysiology of viral myocarditis, and enable us to develop innovative strategies of diagnosis and treatment for this challenging clinical entity. PMID:21585262

  8. Current Diagnostic and Therapeutic Aspects of Eosinophilic Myocarditis

    PubMed Central

    Kuchynka, Petr; Palecek, Tomas; Masek, Martin; Cerny, Vladimir; Lambert, Lukas; Vitkova, Ivana; Linhart, Ales

    2016-01-01

    Eosinophilic myocarditis (EM) represents a rare form of myocardial inflammation with very heterogeneous aetiology. In developed countries, the most prevalent causes of EM are hypersensitivity or allergic reactions, as well as hematological diseases leading to eosinophilia. The disease may have a variable clinical presentation, ranging from asymptomatic forms to life-threatening conditions. Most patients with EM have marked eosinophilia in peripheral blood. Endomyocardial biopsy needs to be performed in most cases in order to establish a definitive diagnosis of EM. The therapy depends on the underlying aetiology. Immunosuppressive therapy represents the treatment mainstay in the majority of EM forms. PMID:26885504

  9. Quantitative MRI myocarditis analysis by a PCA-based object recognition algorithm

    NASA Astrophysics Data System (ADS)

    Romano, Rocco; Acernese, Fausto; Giordano, Gerardo; De Giorgi, Igino; Orientale, Antonio; Babino, Giovanni; Barone, Fabrizio

    2016-03-01

    Magnetic Resonance Imaging (MRI) has shown promising results in diagnosing myocarditis that can be qualitatively observed as enhanced pixels on the cardiac muscles images. In this paper, a quantitative MRI Myocarditis Analysis is proposed. Analysis consists in introducing a myocarditis index, defined as the ratio between enhanced pixels, representing an inflammation, and the total pixels of myocardial muscle. In order to recognize and quantify enhanced pixels, a PCA-based recognition algorithm is used. The algorithm, implemented in Matlab, was tested by examining a group of 12 patients, referred to MRI with presumptive, clinical diagnosis of myocarditis. To assess intra- and interobserver variability, two observers blindly analyzed data related to the 12 patients by delimiting myocardial region and selecting enhanced pixels. After 10 days the same observers redid the analysis. The obtained myocarditis indexes were compared to an ordinal variable (values in the 1 - 5 range) that represented the blind assessment of myocarditis seriousness given by two radiologists on the base of the patient case histories. Results show that there is a significant correlation (P < 0:001; r = 0:96) between myocarditis indexes and the radiologists' clinical judgments. Furthermore, a good intraobserver and interobserver reproducibility was obtained.

  10. Evidence of canine distemper and suggestion of preceding parvovirus-myocarditis in a Eurasian badger (Meles meles).

    PubMed

    Burtscher, Hugo; Url, Angelika

    2007-03-01

    An approximately 1.5-yr-old free-ranging male Eurasian badger (Meles meles) from the eastern part of Austria had macroscopic and microscopic lesions consistent with canine distemper virus infection, including nonsuppurative meningoencephalitis, interstitial pneumonia with accumulation of macrophages in alveoli that contained intranuclear inclusion bodies, vesicular exanthema of the ventral abdomen, and atrophy of lymphoid tissues. Canine distemper virus-antigen was demonstrable in a variety of organs by using immunohistology. In addition, there were widespread areas of fibrosis in the myocardium that were rich in collagen and paucicellular. Because such changes are comparable with sequelae of the acute cardiac form of canine parvovirus (CPV) infection in dogs, it was speculated that this badger may have experienced CPV myocarditis as a cub but that the corresponding antigen or DNA was not detectable due to resolution of the disease.

  11. Evidence for a protective role of tumor necrosis factor in the acute phase of Trypanosoma cruzi infection in mice.

    PubMed Central

    Lima, E C; Garcia, I; Vicentelli, M H; Vassalli, P; Minoprio, P

    1997-01-01

    A possible role for tumor necrosis factor (TNF) alpha during Trypanosoma cruzi infection was explored by using transgenic mice expressing in blood high levels of a soluble TNFR1-FcIgG3 fusion protein, which neutralizes the effects of TNF in vivo. Nontransgenic littermates were used as controls. The transgenic mice showed high susceptibility to T. cruzi infection. Inocula sublethal for control mice resulted in over 80% mortality associated with higher levels of parasites in the blood. In histological sections of the hearts of transgenic mice, large parasitic clusters without inflammatory cell infiltrates around the parasites were seen, while smaller parasitic clusters associated with leukocytes were seen in control mice. No difference in specific antibody response or lymphocyte composition of the spleen was found between transgenic and control mice, although the unresponsiveness of spleen cells to concanavalin A stimulation in vitro, typical of the acute phase of T. cruzi infection, was less pronounced in transgenic mice. Infected transgenic mice produced higher levels of gamma interferon than did control mice. These results confirm that TNF is involved in mechanisms leading to parasite clearance and protection from death in the acute phase of T. cruzi infection. More importantly, the data reveal that TNF is necessary for the establishment of effective tissue inflammation and parasite load control in acute experimental Chagas' disease myocarditis. PMID:9009297

  12. Novel biphasic role for lymphocytes revealed during resolving inflammation

    PubMed Central

    Rajakariar, Ravindra; Lawrence, Toby; Bystrom, Jonas; Hilliard, Mark; Colville-Nash, Paul; Bellingan, Geoff; Fitzgerald, Desmond; Yaqoob, Muhammad M.

    2008-01-01

    Acute inflammation is traditionally described as the influx of polymorphonuclear leukocytes (PMNs) followed by monocyte-derived macrophages, leading to resolution. This is a classic view, and despite subpopulations of lymphocytes possessing innate immune-regulatory properties, seldom is their role in acute inflammation and its resolution discussed. To redress this we show, using lymphocyte-deficient RAG1−/− mice, that peritoneal T/B lymphocytes control PMN trafficking by regulating cytokine synthesis. Once inflammation ensues in normal mice, lymphocytes disappear in response to DP1 receptor activation by prostaglandin D2. However, upon resolution, lymphocytes repopulate the cavity comprising B1, natural killer (NK), γ/δ T, CD4+/CD25+, and B2 cells. Repopulating lymphocytes are dispensable for resolution, as inflammation in RAG1−/− and wild-type mice resolve uniformly. However, repopulating lymphocytes are critical for modulating responses to superinfection. Thus, in chronic granulomatous disease using gp91phox−/− mice, not only is resolution delayed compared with wild-type, but there is a failure of lymphocyte re-appearance predisposing to exaggerated immune responses upon secondary challenge that is rescued by resolution-phase lymphocytes. In conclusion, as lymphocyte repopulation is also evident in human peritonitis, we hereby describe a transition in T/B cells from acute inflammation to resolution, with a central role in modulating the severity of early onset and orchestrating responses to secondary infection. PMID:18218853

  13. Myocardial changes in acute Trypanosoma cruzi infection. Ultrastructural evidence of immune damage and the role of microangiopathy.

    PubMed Central

    Andrade, Z. A.; Andrade, S. G.; Correa, R.; Sadigursky, M.; Ferrans, V. J.

    1994-01-01

    Histological and ultrastructural studies of the hearts of dogs sacrificed 18 to 26 days after intraperitoneal inoculation with 4 x 10(5) blood forms of the 12 SF strain of Trypanosoma cruzi/kg of body weight disclosed myocarditis characterized by parasitic invasion of some myocytes, damage and necrosis of nonparasitized myocytes, and interstitial infiltration by mononuclear cells. Nonparasitized myocytes showed alterations ranging from mild edema to severe myocytolysis. These changes often were accompanied by contacts of myocytes with lymphocytes (both granular and agranular) and macrophages. These contacts were characterized by focal loss of the myocyte basement membrane and close approximation of the plasma membranes of the two cells. Contacts between lymphocytes and capillary endothelial cells were also frequent. Platelet aggregates and fibrin microthrombi were observed in some capillaries. Our findings suggest that immune effector cells play a major role in the pathogenesis of the myocyte damage and the microangiopathy in acute Chagas' disease. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:8203476

  14. Verapamil ameliorates the clinical and pathological course of murine myocarditis.

    PubMed Central

    Dong, R; Liu, P; Wee, L; Butany, J; Sole, M J

    1992-01-01

    The effects of the calcium channel blocking agent, verapamil, were studied in a murine model of viral myocarditis. Three groups of 8-wk-old DBA/2 mice (n = 25 each) were inoculated with 10 plaque-forming units of encephalomyocarditis virus and randomized to three treatment regimens. Group 1 mice received verapamil intraperitoneally (5 mg/kg per d) for 7 d before infection, followed by verapamil orally (mean dose of 3.5 mg/mouse per d) in drinking water during infection. Group 2 mice received only verapamil orally starting on day 4 after infection, coincident with peak viremia. Group 3 (infected control) received no verapamil in regular drinking water after viral inoculation. Additional control animals were studied in group 4 (n = 21), consisting of uninfected control animals receiving intraperitoneal and oral verapamil at doses identical to group 1, and in group 5 (n = 21), consisting of uninfected and untreated controls. Animals were randomly killed from each group (n = 7) at 7, 14, and 28 d after infection. Routine histology was performed blindly on an apical slice of each heart and semi-quantitatively graded for inflammation, necrosis, calcification, and fibrosis on a scale of 0-4. Digital planimetry was performed to measure the absolute and relative areas of inflammation and necrosis. The pretreated animals in group 1 showed marked reduction in inflammation and necrosis (score of 3.7 +/- 1.4 vs. 8.7 +/- 2.0 in group 3 on day 14, P < 0.05) and were indistinguishable from the posttreated group 2 mice (score of 4.0 +/- 1.5 vs. 8.7 +/- 2.0 in group 3 on day 14, P < 0.05). All the uninfected control animals (groups 4 and 5) showed no myocardial lesions whether treated with verapamil or not. Quantitative planimetry confirmed decreased inflammation and necrosis (2.0 +/- 3.3% in group 1 and 3.5 +/- 3.1% in group 2 vs. 21.9 +/- 22.6% in group 3 on day 14). Untreated infected hearts injected with liquid silicone rubber exhibited extensive areas of focal microvascular

  15. Near-fatal myocarditis complicating typhoid fever in a traveler returning from Nepal.

    PubMed

    Palombo, Michal; Margalit-Yehuda, Reuma; Leshem, Eyal; Sidi, Yechezkel; Schwartz, Eli

    2013-01-01

    We report a 27-year-old traveler who returned from Nepal suffering from typhoid fever. His disease was complicated by life-threatening myocarditis and ventricular fibrillation, a rare manifestation in travelers.

  16. A Case of Fetal Parvovirus B19 Myocarditis That Caused Terminal Heart Failure

    PubMed Central

    2014-01-01

    Parvovirus B19 is a well-established cause of fetal anemia and nonimmune fetal hydrops in pregnancy. Fetal parvovirus infection can cause severe destruction of erythroid progenitor cells, resulting in fetal anemia, hydrops, and intrauterine death. However, viral myocarditis with subsequent heart failure is another possible mechanism for hydrops formation as viral infection of fetal myocardial cells has been reported in postmortem examinations. We herein report a case of fetal cardiomegaly and massive pericardial effusion secondary to myocarditis as a result of parvovirus B19 infection. The case developed hydrops as consequence of severe anemia and experienced terminal heart failure, which led to the fetus dying an intrauterine death at 22 weeks of gestation. This case demonstrates that there may be an association between myocarditis caused by intrauterine parvovirus B19 infection and a poor outcome. The presence of viral myocarditis may be the determining prognostic factor in that situation. PMID:25328731

  17. The organisms reported to cause infective myocarditis and pericarditis in England and Wales.

    PubMed

    Fairley, C K; Ryan, M; Wall, P G; Weinberg, J

    1996-05-01

    It is difficult to acquire an overall perspective of the range of organisms responsible for infective myocarditis or pericarditis, and their relative importance, as most studies have involved only case reports or case series of a single organism. This study analyses reports to the Communicable Disease Surveillance Centre, of the Public Health Laboratory Service. Reports where myocarditis or pericarditis was included as the main clinical features between 1990 and 1993 were studied. Between 1990 and 1993, 368 cases of myocarditis and/or pericarditis were reported to CDSC. Viruses were reported to cause 253 (69%) cases, bacteria were responsible for 49 (13%) cases, mycoplasma for 32 (9%) cases, chlamydia for 16 (4%) cases and Mycobacterium tuberculosis for nine (2%) cases. Infection with coxsackie B virus was most frequently associated with a mixed picture of myo/pericarditis, whereas influenzae virus was associated with pericarditis or myocarditis alone. This information will provide clinicians with details of the more likely pathogens responsible for these conditions.

  18. High cardiac troponin I plasma concentration in a calf with myocarditis

    PubMed Central

    Karapinar, Tolga; Dabak, Durrin Ozlem; Kuloglu, Tuncay; Bulut, Hakan

    2010-01-01

    A 15-day-old Brown Swiss calf, whose dam had suffered from foot-and-mouth disease, was presented with a history of depression and failure to suckle. The calf had an irregular cardiac rhythm and increased plasma cardiac troponin I (cTnI) detected with a commercial human immunoassay. The calf died the following day and myocarditis was detected. The cTnI assay may be useful in diagnosis of myocarditis in cattle. PMID:20592829

  19. [Endomyocardial biopsy should be performed in every patient with suspected myocarditis].

    PubMed

    Testolina, Martina; Schiavo, Alessandro; Marcolongo, Renzo; Iliceto, Sabino

    2015-10-01

    The diagnosis of myocarditis is difficult because there is no pathognomonic clinical presentation and the disease may mimic other non-inflammatory diseases. Thus, current classifications on cardiomyopathies (e.g., the World Health Organization and the International Society and Federation of Cardiology [WHO/ISFC], the European Society of Cardiology [ESC], and the 2013 Expert Myocarditis ESC Task Force) define myocarditis as an inflammatory disease of the myocardium, which is diagnosed on endomyocardial biopsy (EMB) based upon histological, immunological, immunohistochemical and molecular tools. This will identify etiology, and differentiate between infectious, mainly viral, and non-infectious, immune-mediated forms. The term "inflammatory cardiomyopathy" may be applied in biopsy-proven myocarditis with associated left, right or biventricular dysfunction. Myocarditis may resolve spontaneously, relapse or become chronic progressing to dilated cardiomyopathy, death or heart transplantation. The 2013 Myocarditis ESC Task Force consensus document recommends consideration of EMB and selective coronary angiography in all patients with clinically suspected myocarditis according to the Task Force criteria. It is recommended that EMB analysis includes not only histology (Dallas criteria), but also immunohistology and detection of the genome of infectious agents by molecular tools. EMB should be performed by expert teams. The rationale for this diagnostic effort is the availability of a wide range of immunosuppressive or immunomodulatory agents that, as shown in systemic extracardiac autoimmune disease and in many clinical studies, can be used in infection-negative myocarditis patients to stop or at least stabilize chronic cardiac tissue damage mediated by the immune system, and thus prevent fibrosis and progression to irreversible end-stage dilated cardiomyopathy.

  20. [Thiamine diphosphate level and metabolism in allergic myocarditis and treatment with peloid].

    PubMed

    Leus, N F

    1986-01-01

    Enzymatic systems involved in thiamin metabolism were studied in experimental allergic myocarditis. Development of inflammation in myocardium was accompanied by a distinct activation of thiamin pyrophosphatase which catalyzed the most important step responsible for deterioration of the coenzyme functions. The stabilizing effect of peloid on the intracellular pool and compartmentalization of thiamin in myocarditis involved equilibration of the anabolic and catabolic reactions in the coenzyme metabolism, mainly due to selective inhibition of the thiamin pyrophosphatase activity stimulated under these conditions.

  1. Ventricular aneurysms complicating coxsackievirus group B, types 1 and 4 murine myocarditis.

    PubMed

    El-Khatib, M R; Chason, J L; Lerner, A M

    1979-02-01

    Suckling Swiss Webster mice were inoculated with 10(4)TCD50 of coxsackieviruses, group B types 1 or 4. Virulent necrotizing myocarditis resulted in 185 infected mice. Of the latter group, three (14.3%) nurslings on the 17th and 23rd day after inoculations had left ventricular aneurysms postmortem. None of 61 concurrently matched control mice developed aneurysms. Ventricular aneurysm is a suggested but previously undocumented complication of murine, and possibly human necrotizing transmural coxsackievirus myocarditis.

  2. Successful early diagnosis and treatment in a case of Toxocara canis-induced eosinophilic myocarditis with eosinophil-rich pericardial effusion.

    PubMed

    Sangen, Hideto; Tanabe, Jun; Takano, Hitoshi; Shimizu, Wataru

    2015-09-03

    Fulminant myocarditis can become fatal if left untreated. Treatments for most types of myocarditis, including mechanical support, are limited. However, immediate systemic corticosteroids are known to be effective against eosinophilic myocarditis; therefore, prompt diagnosis of this disease is crucial. Unfortunately, the standard diagnostic tool for myocarditis, endomyocardial biopsy, does not provide immediate histopathological findings. Thus, a rapid diagnostic tool for identifying types of myocarditis is urgently required. We report here the first case of Toxocara canis-induced eosinophilic fulminant myocarditis which was diagnosed based on eosinophil-rich pericardial effusion where the patient recovered with early corticosteroid therapy.

  3. Percutaneous cardioscopy of the left ventricle in patients with myocarditis

    NASA Astrophysics Data System (ADS)

    Uchida, Yasumi; Tomaru, Takanobu; Nakamura, Fumitaka; Oshima, Tomomitsu; Fujimori, Yoshiharu; Hirose, Junichi

    1992-08-01

    The morphology and function of the cardiac chambers have been evaluated clinically using cineventriculography, computed tomography, magnetic resonance imaging, and endomyocardial biopsy. Excluding the invasive technique of biopsy where tissue is actually removed, these other non-invasive techniques reveal only indirect evidence of endocardial and subendocardial pathology and, therefore, allow the potential for misdiagnosis from insufficient data. Fiberoptic examinations, as recently demonstrated in coronary, pulmonary, and peripheral vessels, allow direct observation of pathology otherwise unobtainable. Recently, similar techniques have been applied to examine the cardiac chambers of dogs and the right heart of humans. In this study, we examine the feasibility and safety of percutaneous fiberoptic cardioscopy of the left ventricle in patients with myocarditis.

  4. Fatal myocarditis-associated Bartonella quintana endocarditis: a case report

    PubMed Central

    2009-01-01

    Introduction Bartonella spp. infection is not rare and must be considered with great care in patients with suspected infective endocarditis, particularly if regular blood cultures remain sterile. Management of these infections requires knowledge of the identification and treatment of these bacteria. Case presentation A 50-year-old Senegalese man was admitted to our Department of Cardiac Surgery with a culture-negative endocarditis. Despite valvular surgery and adequate antibiotic treatment, recurrence of the endocarditis was observed on the prosthetic mitral valve. Heart failure required circulatory support. Weaning off the circulatory support could not be attempted owing to the absence of heart recovery. Bacteriological diagnosis of Bartonella quintana endocarditis was performed by molecular methods retrospectively after the death of the patient. Conclusions This case report underlines the severity and difficulty of the diagnosis of Bartonella quintana endocarditis. The clinical picture suggested possible Bartonella quintana associated myocarditis, a feature that should be considered in new cases. PMID:19830188

  5. Eosinophil-derived IL-4 drives progression of myocarditis to inflammatory dilated cardiomyopathy.

    PubMed

    Diny, Nicola L; Baldeviano, G Christian; Talor, Monica V; Barin, Jobert G; Ong, SuFey; Bedja, Djahida; Hays, Allison G; Gilotra, Nisha A; Coppens, Isabelle; Rose, Noel R; Čiháková, Daniela

    2017-04-03

    Inflammatory dilated cardiomyopathy (DCMi) is a major cause of heart failure in children and young adults. DCMi develops in up to 30% of myocarditis patients, but the mechanisms involved in disease progression are poorly understood. Patients with eosinophilia frequently develop cardiomyopathies. In this study, we used the experimental autoimmune myocarditis (EAM) model to determine the role of eosinophils in myocarditis and DCMi. Eosinophils were dispensable for myocarditis induction but were required for progression to DCMi. Eosinophil-deficient ΔdblGATA1 mice, in contrast to WT mice, showed no signs of heart failure by echocardiography. Induction of EAM in hypereosinophilic IL-5Tg mice resulted in eosinophilic myocarditis with severe ventricular and atrial inflammation, which progressed to severe DCMi. This was not a direct effect of IL-5, as IL-5TgΔdblGATA1 mice were protected from DCMi, whereas IL-5(-/-) mice exhibited DCMi comparable with WT mice. Eosinophils drove progression to DCMi through their production of IL-4. Our experiments showed eosinophils were the major IL-4-expressing cell type in the heart during EAM, IL-4(-/-) mice were protected from DCMi like ΔdblGATA1 mice, and eosinophil-specific IL-4 deletion resulted in improved heart function. In conclusion, eosinophils drive progression of myocarditis to DCMi, cause severe DCMi when present in large numbers, and mediate this process through IL-4.

  6. An MRI myocarditis index defined by a PCA-based object recognition algorithm

    NASA Astrophysics Data System (ADS)

    Romano, Rocco; De Giorgi, Igino; Acernese, Fausto; Giordano, Gerardo; Orientale, Antonio; Babino, Giovanni; Barone, Fabrizio

    2015-03-01

    Magnetic Resonance Imaging (MRI) has shown promising results in diagnosing myocarditis that can be qualitatively observed as enhanced pixels on the cardiac muscles images. In this paper, a myocarditis index, defined as the ratio between enhanced pixels, representing an inflammation, and the total pixels of myocardial muscle, is presented. In order to recognize and quantify enhanced pixels, a PCA-based recognition algorithm is used. The algorithm, implemented in Matlab, was tested by examining a group of 10 patients, referred to MRI with presumptive, clinical diagnosis of myocarditis. To assess intra- and interobserver variability, two observers blindly analyzed data related to the 10 patients by delimiting myocardial region and selecting enhanced pixels. After 5 days the same observers redid the analysis. The obtained myocarditis indexes were compared to an ordinal variable (values in the 1 - 5 range) that represented the blind assessment of myocarditis seriousness given by two radiologists on the base of the patient case histories. Results show that there is a significant correlation (P < 0:001; r = 0:94) between myocarditis indexes and the radiologists' clinical judgments. Furthermore, a good intraobserver and interobserver reproducibility was obtained.

  7. A retrospective study: cardiac MRI of fulminant myocarditis in children—can we evaluate the short-term outcomes?

    PubMed Central

    Wang, Haipeng; Zhao, Bin; Jia, Haipeng; Gao, Fei; Zhao, Junyu

    2016-01-01

    Background Fulminant myocarditis (FM) is an inflammatory disease of the myocardium that results in ventricular systolic dysfunction and causes acute-onset heart failure. Cardiac magnetic resonance (CMR) has become the primary noninvasive tool for the diagnosis and evaluation of myocarditis. The aim of our study was to assess the CMR findings at different course of FM and the short-term outcomes of fulminant myocarditis (FM) in children. Methods Eight FM children with CMR examinations were included in our study. Initial baseline CMR was performed 10 days (range, 7–20 days) after onset of FM and follow-up CMR after 55 days (range, 33–75 days). Cardiac morphology and function and myocardial tissue characterization at baseline and follow-up CMR were compared using paired T-test and Mann–Whitney U test. The clinical data and initial CMR findings were also compared to predict short-term outcomes. Results The median age of eight FM children was 8.5 years old (range, 3–14). The initial CMR findings were most common with early gadolinium enhancement (EGE, 100%), followed by signal increasing on T2WI and late gadolinium enhancement (LGE, 87.5%), increased septal thickness (75.0%) and increased left ventricle ejection fraction (LVEF, 50.0%). Only three LGE (37.5%), one signal increasing on T2WI (12.5%) and one increased LVEF (12.5%) were found at follow-up. Statistically significant differences were found between initial and follow-up CMR abnormalities in the septal thickness, left ventricular end-diastolic diameter (LVEDD), end-systolic volume (ESV), LVEF, left ventricular mass, T2 ratio and LGE area (P = 0.011, P = 0.042, P = 0.016, P = 0.001, P = 0.003, P = 0.011, P = 0.020). The children with full recovery performed higher incidence of III° atrioventricular block (AVB, five cases VS 0 case) and smaller LGE area (104.0 ± 14.5 mm2 VS 138.0 ± 25.2 mm2) at baseline CMR. Discussion The CMR findings of FM in children were characteristic and

  8. Comparison of Clinical Presentation of Acute Myocarditis Following Smallpox Vaccination to Acute Coronary Syndromes in Patients

    DTIC Science & Technology

    2005-05-15

    echocardiographic re- sults in 8.2 Previous studies of viral myocardi- tis mimicking myocardial infarction have focused on enteroviruses , adeno- viruses, and...infarction. Am Heart J 1988; 115:768–776. 3. Baboonian C, Treasure T. Meta-analysis of the association of enteroviruses with human heart disease. Heart 1997;78

  9. T-lymphocyte subpopulations in uveitis.

    PubMed Central

    Murray, P. I.; Dinning, W. J.; Rahi, A. H.

    1984-01-01

    Following an inconclusive study of differential lymphocyte counts in uveitis in which the peripheral blood was examined only once in the course of each case a longitudinal study has been carried out in patients with acute anterior uveitis. Venous blood lymphocytes were examined at intervals throughout the course of the illness, from presentation until six months later. No changes in E-rosetting T cells or total lymphocyte values have been found, nor any variations from normal in the helper (OKT4)/suppressor (OKT8) T-cell ratio. Random studies performed in a sample of patients with heterochromic cyclitis have also failed to reveal consistent abnormalities in peripheral blood lymphocyte parameters. PMID:6236843

  10. Erdheim-Chester disease with rare radiological features in a 14-year old girl with pre-B Acute Lymphocytic Leukemia and Diabetes mellitus

    PubMed Central

    Krishna, Varanasi Venkata Rama; James, Teo Eu Leong Harvey; Chang, Kenneth Tou En; Yen, Soh Shui

    2014-01-01

    We report a case of a 14 year-old girl with Diabetes Mellitus who was in remission with pre-B cell Acute Lymphoblastic Leukemia and subsequently diagnosed with Erdheim-Chester disease. Erdheim-Chester disease is a non-Langerhans cell histiocytosis and is very rare in children. In addition, the radiological features of the lesions are atypical and have not been reported in children. There is no known association between the three conditions and this is the first reported case in the literature. A literature review of Erdheim-Chester disease will be performed. PMID:25426240

  11. Right Cervical Vagotomy Aggravates Viral Myocarditis in Mice Via the Cholinergic Anti-inflammatory Pathway

    PubMed Central

    Li-Sha, Ge; Xing-Xing, Chen; Lian-Pin, Wu; De-Pu, Zhou; Xiao-Wei, Li; Jia-Feng, Lin; Yue-Chun, Li

    2017-01-01

    The autonomic nervous system dysfunction with increased sympathetic activity and withdrawal of vagal activity may play an important role in the pathogenesis of viral myocarditis. The vagus nerve can modulate the immune response and control inflammation through a ‘cholinergic anti-inflammatory pathway’ dependent on the α7-nicotinic acetylcholine receptor (α7nAChR). Although the role of β-adrenergic stimulation on viral myocarditis has been investigated in our pervious studies, the direct effect of vagal tone in this setting has not been yet studied. Therefore, in the present study, we investigated the effects of cervical vagotomy in a murine model of viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of right cervical vagotomy and nAChR agonist nicotine on echocardiography, myocardial histopathology, viral RNA, and proinflammatory cytokine levels were studied. We found that right cervical vagotomy inhibited the cholinergic anti-inflammatory pathway, aggravated myocardial lesions, up-regulated the expression of TNF-α, IL-1β, and IL-6, and worsened the impaired left ventricular function in murine viral myocarditis, and these changes were reversed by co-treatment with nicotine by activating the cholinergic anti-inflammatory pathway. These results indicate that vagal nerve plays an important role in mediating the anti-inflammatory effect in viral myocarditis, and that cholinergic stimulation with nicotine also plays its peripheral anti-inflammatory role relying on α7nAChR, without requirement for the integrity of vagal nerve in the model. The findings suggest that vagus nerve stimulation mediated inhibition of the inflammatory processes likely provide important benefits in myocarditis treatment. PMID:28197102

  12. Increased Echogenicity and Radiodense Foci on Echocardiogram and MicroCT in Murine Myocarditis

    PubMed Central

    Dalton, Nancy D.; Gu, Yusu; Chao, Chieh-Ju; Peterson, Kirk L.; Knowlton, Kirk U.

    2016-01-01

    Objectives To address the question as to whether echocardiographic and/or microcomputed tomography (microCT) analysis can be utilized to assess the extent of Coxsackie B virus (CVB) induced myocarditis in the absence of left ventricular dysfunction in the mouse. Background Viral myocarditis is a significant clinical problem with associated inflammation of the myocardium and myocardial injury. Murine models of myocarditis are commonly used to study the pathophysiology of the disease, but methods for imaging the mouse myocardium have been limited to echocardiographic assessment of ventricular dysfunction and, to a lesser extent, MRI imaging. Methods Using a murine model of myocarditis, we used both echocardiography and microCT to assess the extent of myocardial involvement in murine myocarditis using both wild-type mice and CVB cleavage-resistant dystrophin knock-in mice. Results Areas of increased echogenicity were only observed in the myocardium of Coxsackie B virus infected mice. These echocardiographic abnormalities correlated with the extent of von Kossa staining (a marker of membrane permeability), inflammation, and fibrosis. Given that calcium phosphate uptake as imaged by von Kossa staining might also be visualized using microCT, we utilized microCT imaging which allowed for high-resolution, 3-dimensional images of radiodensities that likely represent calcium phosphate uptake. As with echocardiography, only mice infected with Coxsackie B virus displayed abnormal accumulation of calcium within individual myocytes indicating increased membrane permeability only upon exposure to virus. Conclusions These studies demonstrate new, quantitative, and semi-quantitative imaging approaches for the assessment of myocardial involvement in the setting of viral myocarditis in the commonly utilized mouse model of viral myocarditis. PMID:27486657

  13. Novel immunodominant peptide presentation strategy: a featured HLA-A*2402-restricted cytotoxic T-lymphocyte epitope stabilized by intrachain hydrogen bonds from severe acute respiratory syndrome coronavirus nucleocapsid protein.

    PubMed

    Liu, Jun; Wu, Peng; Gao, Feng; Qi, Jianxun; Kawana-Tachikawa, Ai; Xie, Jing; Vavricka, Christopher J; Iwamoto, Aikichi; Li, Taisheng; Gao, George F

    2010-11-01

    Antigenic peptides recognized by virus-specific cytotoxic T lymphocytes (CTLs) are presented by major histocompatibility complex (MHC; or human leukocyte antigen [HLA] in humans) molecules, and the peptide selection and presentation strategy of the host has been studied to guide our understanding of cellular immunity and vaccine development. Here, a severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid (N) protein-derived CTL epitope, N1 (QFKDNVILL), restricted by HLA-A*2402 was identified by a series of in vitro studies, including a computer-assisted algorithm for prediction, stabilization of the peptide by co-refolding with HLA-A*2402 heavy chain and β(2)-microglobulin (β(2)m), and T2-A24 cell binding. Consequently, the antigenicity of the peptide was confirmed by enzyme-linked immunospot (ELISPOT), proliferation assays, and HLA-peptide complex tetramer staining using peripheral blood mononuclear cells (PBMCs) from donors who had recovered from SARS donors. Furthermore, the crystal structure of HLA-A*2402 complexed with peptide N1 was determined, and the featured peptide was characterized with two unexpected intrachain hydrogen bonds which augment the central residues to bulge out of the binding groove. This may contribute to the T-cell receptor (TCR) interaction, showing a host immunodominant peptide presentation strategy. Meanwhile, a rapid and efficient strategy is presented for the determination of naturally presented CTL epitopes in the context of given HLA alleles of interest from long immunogenic overlapping peptides.

  14. A novel mutation in the miR-128b gene reduces miRNA processing and leads to glucocorticoid resistance of MLL-AF4 acute lymphocytic leukemia cells.

    PubMed

    Kotani, Ai; Ha, Daon; Schotte, Diana; den Boer, Monique L; Armstrong, Scott A; Lodish, Harvey F

    2010-03-15

    MLL-AF4 acute lymphocytic leukemia has a poor prognosis, and the mechanisms by which these leukemias develop are not understood despite intensive research based on well-known concepts and methods. MicroRNAs (miRNAs) are a new class of small noncoding RNAs that post-transcriptionally regulate expression of target mRNA transcripts. We recently reported that ectopic expression of miR-128b together with miR-221, two of the miRNAs downregulated in MLL-AF4 ALL, restores glucocorticoid resistance through downregulation of the MLL-AF4 chimeric fusion proteins MLL-AF4 and AF4-MLL that are generated by chromosomal translocation t(4;11). Here we report the identification of new mutations in miR-128b in RS4;11 cells, derived from MLL-AF4 ALL patient. One novel mutation significantly reduces the processing of miR-128b. Finally, this base change occurs in a primary MLL-AF4 ALL sample as an acquired mutation. These results demonstrate that the novel mutation in miR-128b in MLL-AF4 ALL alters the processing of miR-128b and that the resultant downregulation of mature miR-128b contributes to glucocorticoid resistance through the failure to downregulate the fusion oncogenes.

  15. Allogeneic stem cell transplantation for adult Philadelphia chromosome-negative acute lymphocytic leukemia: comparable survival rates but different risk factors between related and unrelated transplantation in first complete remission.

    PubMed

    Nishiwaki, Satoshi; Inamoto, Yoshihiro; Sakamaki, Hisashi; Kurokawa, Mineo; Iida, Hiroatsu; Ogawa, Hiroyasu; Fukuda, Takahiro; Ozawa, Yukiyasu; Kobayashi, Naoki; Kasai, Masanobu; Mori, Takehiko; Iwato, Koji; Yoshida, Takashi; Onizuka, Makoto; Kawa, Keisei; Morishima, Yasuo; Suzuki, Ritsuro; Atsuta, Yoshiko; Miyamura, Koichi

    2010-11-18

    To identify factors to improve the outcomes of related and unrelated allogeneic stem cell transplantations (allo-SCT) for Philadelphia chromosome-negative acute lymphocytic leukemia (Ph(-) ALL) in the first complete remission (CR1), we retrospectively analyzed 1139 Ph(-) ALL patients using the registry data, particularly the details of 641 patients transplanted in CR1. Overall survival was significantly superior among patients transplanted in CR1, but no significant difference was observed between related and unrelated allo-SCTs (related vs unrelated: 65% vs 62% at 4 years, respectively; P = .19). Among patients transplanted in CR1, relapse rates were significantly higher in related allo-SCT compared with unrelated allo-SCT, and multivariate analysis demonstrated that less than 6 months from diagnosis to allo-SCT alone was associated with relapse. On the other hand, nonrelapse mortality (NRM) was significantly higher in unrelated allo-SCT compared with related allo-SCT, and multivariate analysis demonstrated that 10 months or longer from diagnosis to allo-SCT, human leukocyte antigen mismatch, and abnormal karyotype were associated with NRM. In conclusion, our study showed comparable survival rates but different relapse rates, NRM rates, and risk factors between related and unrelated allo-SCTs. After a close consideration of these factors, the outcome of allo-SCT for adult Ph(-) ALL in CR1 could be improved.

  16. Biventricular support using a centrifugal pump in a 6 year old with fulminant myocarditis.

    PubMed

    Kehara, Hiromu; Takano, Tamaki; Terasaki, Takamitsu; Okada, Kenji

    2016-12-01

    We experienced a case of ventricular assist with both a pulsatile-flow and a continuous-flow pump in a pediatric patient, and herein report the clinical course and characteristics of the pumps. A 6-year-old female was diagnosed with fulminant myocarditis and transferred to our hospital for mechanical support. After 12 days of extracorporeal membrane oxygenation, we implanted a left ventricular assist device (LVAD) and a right ventricular assist device (RVAD) using centrifugal Gyro pumps with a membrane oxygenator in a paracorporeal fashion. The membrane oxygenator was removed on postoperative day (POD) 4, and the patient was weaned from the respirator on POD 6. The LVAD was exchanged on POD 13 and 17, and the RVAD was exchanged on POD 14 because of thrombus formation inside the pumps. The RVAD was removed on POD 25. On POD 32, the patient experienced cerebral infarction and the centrifugal Gyro pump was switched to an extracorporeal pulsatile pump. No thromboembolic event occurred after pump conversion, although continuous administration of vasodilators was required to avoid hypertension. She underwent successfully heart transplantation in the USA after 8 months of ventricular support. A centrifugal pump is considered useful for pediatric patients, as pump flow and blood pressure can be relatively easily controlled in the postoperative acute phase compared with the pulsatile pump. However, special care should be taken to monitor for thrombus formation when support length becomes longer than 13 days, and a switch to a pulsatile pump should be considered once the hemodynamic status stabilizes.

  17. Changes in cell death of peripheral blood lymphocytes isolated from children with acute lymphoblastic leukemia upon stimulation with 7 Hz, 30 mT pulsed electromagnetic field.

    PubMed

    Kaszuba-Zwoińska, Jolanta; Ćwiklińska, Magdalena; Balwierz, Walentyna; Chorobik, Paulina; Nowak, Bernadeta; Wójcik-Piotrowicz, Karolina; Ziomber, Agata; Malina-Novak, Kinga; Zaraska, Wiesław; Thor, Piotr J

    2015-03-01

    Pulsed electromagnetic field (PEMF) influenced the viability of proliferating in vitro peripheral blood mononuclear cells (PBMCs) isolated from Crohn's disease patients as well as acute myeloblastic leukemia (AML) patients by induction of cell death, but did not cause any vital changes in cells from healthy donors. Experiments with lymphoid U937 and monocytic MonoMac6 cell lines have shown a protective effect of PEMF on the death process in cells treated with death inducers. The aim of the current study was to investigate the influence of PEMF on native proliferating leukocytes originating from newly diagnosed acute lymphoblastic leukemia (ALL) patients. The effects of exposure to PEMF were studied in PBMCs from 20 children with ALL. PBMCs were stimulated with three doses of PEMF (7 Hz, 30 mT) for 4 h each with 24 h intervals. After the last stimulation, the cells were double stained with annexin V and propidium iodide dye to estimate viability by flow cytometric analysis. The results indicated an increase of annexin V positive as well as double stained annexin V and propidium iodide positive cells after exposure to threefold PEMF stimulation. A low-frequency pulsed electromagnetic field induces cell death in native proliferating cells isolated from ALL patients. The increased vulnerability of proliferating PBMCs to PEMF-induced interactions may be potentially applied in the therapy of ALL. The analysis of expression of apoptosis-related genes revealed changes in mRNA of some genes engaged in the intrinsic apoptotic pathway belonging to the Bcl-2 family and the pathway with apoptosis-inducing factor (AIF) abundance upon PEMF stimulation of PBMCs.

  18. Cardiac myosin-Th17 responses promote heart failure in human myocarditis

    PubMed Central

    Myers, Jennifer M.; Cooper, Leslie T.; Kem, David C.; Stavrakis, Stavros; Kosanke, Stanley D.; Shevach, Ethan M.; Fairweather, DeLisa; Stoner, Julie A.; Cox, Carol J.; Cunningham, Madeleine W.

    2016-01-01

    In human myocarditis and its sequela dilated cardiomyopathy (DCM), the mechanisms and immune phenotype governing disease and subsequent heart failure are not known. Here, we identified a Th17 cell immunophenotype of human myocarditis/DCM with elevated CD4+IL17+ T cells and Th17-promoting cytokines IL-6, TGF-β, and IL-23 as well as GM-CSF–secreting CD4+ T cells. The Th17 phenotype was linked with the effects of cardiac myosin on CD14+ monocytes, TLR2, and heart failure. Persistent heart failure was associated with high percentages of IL-17–producing T cells and IL-17–promoting cytokines, and the myocarditis/DCM phenotype included significantly low percentages of FOXP3+ Tregs, which may contribute to disease severity. We demonstrate a potentially novel mechanism in human myocarditis/DCM in which TLR2 peptide ligands from human cardiac myosin stimulated exaggerated Th17-related cytokines including TGF-β, IL-6, and IL-23 from myocarditic CD14+ monocytes in vitro, and an anti-TLR2 antibody abrogated the cytokine response. Our translational study explains how an immune phenotype may be initiated by cardiac myosin TLR ligand stimulation of monocytes to generate Th17-promoting cytokines and development of pathogenic Th17 cells in human myocarditis and heart failure, and provides a rationale for targeting IL-17A as a therapeutic option. PMID:27366791

  19. Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1) as a Biomarker in the Mouse Model of Experimental Autoimmune Myocarditis (EAM)

    PubMed Central

    Grabmaier, U.; Kania, G.; Kreiner, J.; Grabmeier, J.; Uhl, A.; Huber, B. C.; Lackermair, K.; Herbach, N.; Todica, A.; Eriksson, U.; Weckbach, L. T.; Brunner, S.

    2016-01-01

    Vascular cell adhesion molecule-1 (VCAM-1) is strongly upregulated in hearts of mice with coxsackie virus-induced as well as in patients with viral infection-triggered dilated cardiomyopathy. Nevertheless, the role of its soluble form as a biomarker in inflammatory heart diseases remains unclear. Therefore, we investigated whether plasma levels of soluble VCAM-1 (sVCAM-1) directly correlated with disease activity and progression of cardiac dysfunction in the mouse model of experimental autoimmune myocarditis (EAM). EAM was induced by immunization of BALB/c mice with heart-specific myosin-alpha heavy chain peptide together with complete Freund`s adjuvant. ELISA revealed strong expression of cardiac VCAM-1 (cVCAM-1) throughout the course of EAM in immunized mice compared to control animals. Furthermore, sVCAM-1 was elevated in the plasma of immunized compared to control mice at acute and chronic stages of the disease. sVCAM-1 did not correlate with the degree of acute cardiac inflammation analyzed by histology or cardiac cytokine expression investigated by ELISA. Nevertheless, heart to body weight ratio correlated significantly with sVCAM-1 at chronic stages of EAM. Cardiac systolic dysfunction studied with positron emission tomography indicated a weak relationship with sVCAM-1 at the chronic stage of the disease. Our data provide evidence that plasma levels of sVCAM-1 are elevated throughout all stages of the disease but showed no strong correlation with the severity of EAM. PMID:27501319

  20. Novel application of a percutaneous left ventricular assist device as a bridge to transplant in a paediatric patient with severe heart failure due to viral myocarditis.

    PubMed

    Perry, Paul; David, Elizabeth; Atkins, Broadus; Raff, Gary

    2017-03-01

    A 13-year obese female with suspected viral myocarditis presented with acute decompensated heart failure. Due to her body habitus, she was a poor candidate for immediate heart transplantation. A peripherally inserted left ventricular assist device (LVAD) was implanted via the right axillary artery. Following device insertion the patient experienced rapid improvement in symptoms. The LVAD provided effective left ventricular unloading for 50 days, promoting myocardial recovery and maintaining excellent patient performance status. The device placement strategy allowed for a high level of activity including completion of school-work and participation in a weight loss program. The patient achieved a 28-pound weight loss, thus improving candidacy for transplantation. Removal of the device was well tolerated and post-removal echocardiography revealed an improvement in the left ventricular ejection fraction (LVEF) from 21% at baseline to 38% after device removal. This case represents a successful application of a peripherally inserted LVAD as a bridge to transplant in a pediatric patient with severe heart failure due to suspected viral myocarditis. For select patients with this condition, a transaxillary LVAD should be considered as a therapeutic option as it is well tolerated and provides effective left ventricle unloading to promote myocardial recovery and maintain performance status.

  1. Cinnamaldehyde Derivatives Inhibited Coxsackievirus B3-Induced Viral Myocarditis.

    PubMed

    Li, Xiao-Qiang; Liu, Xiao-Xiao; Wang, Xue-Ying; Xie, Yan-Hua; Yang, Qian; Liu, Xin-Xin; Ding, Yuan-Yuan; Cao, Wei; Wang, Si-Wang

    2016-10-17

    The chemical property of cinnamaldehyde is unstable in vivo, although early experiments have shown its obvious therapeutic effects on viral myocarditis (VMC). To overcome this problem, we used cinnamaldehyde as a leading compound to synthesize derivatives. Five derivatives of cinnamaldehyde were synthesized: 4-methylcinnamaldehyde (1), 4-chlorocinnamaldehyde (2), 4-methoxycinnamaldehyde (3), α-bromo-4-methylcinnamaldehyde (4), and α-bromo-4-chlorocinnamaldehyde (5). Neonatal rat cardiomyocytes and HeLa cells infected by coxsackievirus B3 (CVB3) were used to evaluate their antiviral and cytotoxic effects. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. Among the derivatives, compound 4 and 5 inhibited the CVB3 in HeLa cells with the half-maximal inhibitory concentrations values of 11.38 ± 2.22 μM and 2.12 ± 0.37 μM, respectively. The 50% toxic concentrations of compound 4 and 5-treated cells were 39-fold and 87-fold higher than in the cinnamaldehyde group. Compound 4 and 5 effectively reduced the viral titers and cardiac pathological changes in a dose-dependent manner. In addition, compound 4 and 5 significantly inhibited the secretion, mRNA and protein expressions of inflammatory cytokines TNF-α, IL-1β and IL-6 in CVB3-infected cardiomyocytes, indicating that brominated cinnamaldehyde not only improved the anti-vital activities for VMC, but also had potent anti-inflammatory effects in cardiomyocytes induced by CVB3.

  2. Learning from myocarditis: mimicry, chaos and black holes

    PubMed Central

    Rose, Noel R.

    2014-01-01

    Autoimmune myocarditis and its sequel, dilated cardiomyopathy, are major causes of heart failure, especially in children and young adults. We have developed animal models to investigate their pathogenesis by infecting genetically susceptible mice with coxsackievirus B3 or by immunizing them with cardiac myosin or its immunodominant peptide. A number of valuable lessons have emerged from our study of this paradigm of an infection-induced autoimmune disease. We understand more clearly how natural autoimmunity, as an important component of normal physiology, must be recalibrated regularly due to changes caused by infection or other internal and external stimuli. A new normal homeostatic platform will be established based on its evolutionary fitness. A loss of homeostasis with out-of-control normal autoimmunity leads to autoimmune disease. It is signified early on by a spread of an adaptive autoimmune response to novel epitopes and neighboring antigens. The progression from infection to normal, well-balanced autoimmunity to autoimmune disease and on to irreversible damage is a complex, step-wise process. Yet, chaos theory provides hope that the pattern is potentially predictable. Infection-induced autoimmune disease represents a sequence of events heading for a train wreck at the end of the line. Our aim in autoimmune disease research must be to stop the train before this happens. PMID:24904749

  3. Apolizumab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2013-07-15

    Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Small Lymphocytic Lymphoma

  4. Direct interaction of Ikaros and Foxp1 modulates expression of the G protein-coupled receptor G2A in B-lymphocytes and acute lymphoblastic leukemia

    PubMed Central

    Roman-Trufero, Mónica; Sabbattini, Pierangela; Ferreiros-Vidal, Isabel; Gerrard, Gareth; Asnafi, Vahid; Macintyre, Elizabeth; Merkenschlager, Matthias; Dillon, Niall

    2016-01-01

    Ikaros and Foxp1 are transcription factors that play key roles in normal lymphopoiesis and lymphoid malignancies. We describe a novel physical and functional interaction between the proteins, which requires the central zinc finger domain of Ikaros. The Ikaros-Foxp1 interaction is abolished by deletion of this region, which corresponds to the IK6 isoform that is commonly associated with high-risk acute lymphoblastic leukemia (ALL). We also identify the Gpr132 gene, which encodes the orphan G protein-coupled receptor G2A, as a novel target for Foxp1. Increased expression of Foxp1 enhanced Gpr132 transcription and caused cell cycle changes, including G2 arrest. Co-expression of wild-type Ikaros, but not IK6, displaced Foxp1 binding from the Gpr132 gene, reversed the increase in Gpr132 expression and inhibited G2 arrest. Analysis of primary ALL samples revealed a significant increase in GPR132 expression in IKZF1-deleted BCR-ABL negative patients, suggesting that levels of wild-type Ikaros may influence the regulation of G2A in B-ALL. Our results reveal a novel effect of Ikaros haploinsufficiency on Foxp1 functioning, and identify G2A as a potential modulator of the cell cycle in Ikaros-deleted B-ALL. PMID:27588474

  5. Acute Chagas' disease (Trypanosomiasis americana) in acquired immunodeficiency syndrome: report of two cases.

    PubMed

    Oddó, D; Casanova, M; Acuña, G; Ballesteros, J; Morales, B

    1992-01-01

    Two heterosexual men, aged 31 and 40 years, with the acquired immunodeficiency syndrome and presenting with the acute form of Chagas' disease are reported. The first patient, a carrier of hemophilia A, was treated for 20 years with Chilean and Brazilian cryoprecipitates. This patient acquired both diseases through this medium. The second patient, an inhabitant of northern Chile (fourth region), was allegedly bitten by Triatoma infestans and was an intravenous drug addict. The hemophilic patient presented with a neurologic syndrome; a brain biopsy showed a necrotizing encephalitis with an obliterative angiitis and abundant macrophages. The second patient developed intractable congestive heart failure; necropsy showed a dilated myocarditis with rupture of myofibers and an inflammatory infiltrate rich in plasma cells, lymphocytes, and macrophages. Using light and electron microscopy, abundant amastigotes of Trypanosoma cruzi were seen in brain tissue, especially in the cytoplasm of macrophages, as well as in some myocardial fibers. In both cases, determination of anti-T cruzi antibodies (indirect hemagglutination technique) and xenodiagnosis were positive.

  6. Lymphocyte Functions in Microgravity

    NASA Technical Reports Server (NTRS)

    Pellis, Neal R.; Risin, Diane; Sundaresan, A.; Cooper, D.; Dawson, David L. (Technical Monitor)

    1999-01-01

    To understand the mechanism of immunity impairment in space it is important to analyze the direct effects of space-related conditions on different lymphocytes functions. Since 1992, we are investigating the effect of modeled and true microgravity (MG) on numerous lymphocyte functions. We had shown that modeled (MMG) and true microgravity inhibit lymphocyte locomotion through type I collagen. Modeled microgravity also suppresses polyclonal and antigen-specific lymphocyte activation. Polyclonal activation of lymphocytes prior to exposure to MMG abrogates the MG-induced inhibition of lymphocyte locomotion. The relationship between activation deficits and the loss of locomotion in MG was investigated using PKC activation by phorbol ester (PMA) and calcium ionophore (ionomycin). Direct activation of PKC by PMA substantially restored the MMG-inhibited lymphocyte locomotion and PHA-induced lymphocyte activation lonomycin by itself did not restore either locomotion or activation of the lymphocytes, indicating that these changes are not related to the impairment in the calcium flux in MMG. Treatment of lymphocytes with PMA before exposure to MMG prevented the loss of locomotion. It was observed that DNA synthesis is not necessary for restoration of locomotion since mitomicin C treated and untreated cells recovered their locomotion to the same level after PKC activation. Our recent data indicate that microgravity may selectively effect the expression of novel Ca2+ independent isoforms of PKC, in particularly PKC sigma and delta. This provides a new insight in understanding of the mechanisms of MG-sensitive cellular functions.

  7. Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2014-10-30

    Hematopoietic/Lymphoid Cancer; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  8. Mast Cell Inhibition Attenuates Myocardial Damage, Adverse Remodeling and Dysfunction during Fulminant Myocarditis in Rat

    PubMed Central

    Mina, Yair; Rinkevich-Shop, Shunit; Konen, Eli; Goitein, Orly; Kushnir, Tammar; Epstein, Frederick H.; Feinberg, Micha S.; Leor, Jonathan; Landa-Rouben, Natalie

    2013-01-01

    Background Myocarditis is a life-threatening heart disease characterized by myocardial inflammation, necrosis and chronic fibrosis. While mast cell inhibition has been suggested to prevents fibrosis in rat myocarditis, little is known about its effectiveness in attenuating cardiac remodeling and dysfunction in myocarditis. Thus, we sought to test the hypothesis that mast cell inhibition will attenuate the inflammatory reaction and associated left ventricular (LV) remodeling and dysfunction after fulminant autoimmune myocarditis. Methods and Results To induce experimental autoimmune myocarditis, we immunized 30 rats with porcine cardiac myosin twice at a 7-day interval. On day 8 animals were randomized into treatment either with an intraperitoneal (IP) injection of 25mg/kg of cromolyn sodium (n=13), or an equivalent volume (~0.5ml IP) of normal saline (n=11). All animals were scanned by serial echocardiography studies before treatment (baseline echocardiogram) and after 20 days of cromolyn sodium (28 days after immunization). Furthermore, serial cardiac magnetic resonance was performed in a subgroup of 12 animals. After 20 days of treatment (28 days from first immunization), hearts were harvested for histopathological analysis. By echocardiography, cromolyn sodium prevented LV dilatation and attenuated LV dysfunction, compared with controls. Postmortem analysis of hearts showed that cromolyn sodium reduced myocardial fibrosis, as well as the number and size of cardiac mast cells in the inflamed myocardium, compared with controls. Conclusions Our study suggests that mast cell inhibition with cromolyn sodium attenuates adverse LV remodeling and dysfunction in myocarditis. This mechanism-based therapy is clinically relevant and could improve the outcome of patients at risk for inflammatory cardiomyopathy and heart failure. PMID:23172937

  9. Involvement of NLRP3 inflammasome in CVB3-induced viral myocarditis.

    PubMed

    Wang, Yan; Gao, Bo; Xiong, Sidong

    2014-11-15

    Viral myocarditis, which is most prevalently caused by coxsackievirus B3 (CVB3) infection, is a serious clinical condition characterized by cardiac inflammation. Inflammasome plays an essential role in the regulation of diverse inflammatory responses by serving as a platform for caspase-1 activation and caspase-1-dependent proteolytic maturation and secretion of IL-1β. Although inflammasome has been reported to be crucial for the development of many inflammatory diseases, its role in the pathogenesis of viral myocarditis is still elusive. The present study aims to investigate whether CVB3 infection activates inflammasome and whether the activation of inflammasome contributes to CVB3-induced myocarditis. Our results showed that CVB3 infection induced inflammasome activation both in vitro and in vivo. With the inhibition of inflammasome activation, the severity of CVB3-induced myocarditis was significantly alleviated as evidenced by less weight loss, decreased serological indexes of creatine kinase and creatinekinase-MB activities, as well as less severe myocardial injury. Of importance, echocardiography results showed that inhibition of inflammasome activation also efficiently improved cardiac function as revealed by enhanced left ventricular ejection fraction and left ventricular fractional shortening. Despite that CVB3 infection significantly increased the expression of both retinoic acid-inducible gene 1 and NOD-like receptor family, pyrin domain containing 3 (NLRP3) in cardiac myocytes, CVB3-induced inflammasome activation was NLRP3-, but not retinoic acid-inducible gene 1, dependent. Further study showed that reactive oxygen species production and K(+) efflux were critical for the activation of NLRP3 inflammasome upon CVB3 infection. Collectively, our study demonstrated a crucial role of the NLRP3 inflammasome in the pathogenesis of CVB3-induced myocarditis, and modulation of inflammasome activation might represent a promising therapeutic strategy for viral

  10. The Protective Effects of Ivabradine in Preventing Progression from Viral Myocarditis to Dilated Cardiomyopathy

    PubMed Central

    Yue-Chun, Li; Guang-Yi, Chen; Li-Sha, Ge; Chao, Xing; Xinqiao, Tian; Cong, Lin; Xiao-Ya, Dai; Xiangjun, Yang

    2016-01-01

    To study the beneficial effects of ivabradine in dilated cardiomyopathy (DCM) mice, which evolved from coxsackievirus B3-induced chronic viral myocarditis. Four-to-five-week-old male balb/c mice were inoculated intraperitoneally with coxsackievirus B3 (Strain Nancy) on days 1, 14, and 28. The day of the first virus inoculation was defined as day 1. Thirty-five days later, the surviving chronic viral myocarditis mice were divided randomly into two groups, a treatment group and an untreated group. Ivabradine was administered by gavage for 30 consecutive days in the treatment group, and the untreated group was administered normal saline. Masson’s trichrome stain was used to evaluate the fibrosis degree in myocardial tissue. The expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), collagen I, collagen III and p38-MAPK signaling pathway proteins were detected by Western blot. Electrocardiogram was used to investigate the heart rate and rhythm. The thickness of the ventricular septum and left ventricular posterior wall, left ventricular end diastolic dimension, left ventricular end systolic dimension, left ventricular ejection fractions and fractional shortening were studied by echocardiography. Compared with the untreated chronic viral myocarditis mice, ivabradine significantly increased the survival rate, attenuated the myocardial lesions and fibrosis, improved the impairment of the left ventricular function, diminished the heart dimension, decreased the production of collagen I and collagen III, reduced the expression of the proinflammatory cytokines TNF-α, IL-1β, and IL-6, and lowered the production of phospho-p38 MAPK. The findings indicate the therapeutic effect of ivabradine in preventing the progression from viral myocarditis to DCM in mice with chronic viral myocarditis induced by coxsackievirus B3, is associated with inhibition of the p38 MAPK pathway, downregulated inflammatory responses and decreased

  11. Characterization of a murine model of myocarditis induced by a reactivated coxsackievirus B3.

    PubMed Central

    Zhang, H.; Yousef, G. E.; Ouyang, X.; Archard, L. C.

    1994-01-01

    A transfection-reactivated Coxsackievirus B3 (rCVB3), from a full-length cDNA clone of Nancy strain, has previously been shown to be as cardiovirulent as the wild-type virus. Myocarditis induced by this genetically defined virus was compared in SWR mice with the traditional Balb/c model. SWR mice inoculated with rCVB3 developed more severe myocarditis but less severe pancreatitis than Balb/c mice. In contrast to the poor general health and frequent mortality of Balb/c mice following CVB3 infection, the body weight of SWR mice was not affected by CVB3 inoculation and no mortality occurred at titres of 10(2)-10(7) plaque forming units (PFU). Typical myocarditis developed in SWR mice 7 days post infection. Myocarditic foci consisting of necrotic myocardial fibres and mononuclear cell infiltrates resolved by day 30, similar to that observed in Balb/c. However, SWR mice were more sensitive to rCVB3-induced myocarditis than were Balb/c mice: mild myocarditis was induced (4/4) by as low as 10(2) PFU of the virus (ID50 < 10(1.5) PFU), and more severe myocarditis was seen at higher PFU of virus in a dose-dependent manner. The SWR model was tested with attenuated variants derived from cardiovirulent rCVB3. The ID50 for myocarditis was 10(7) PFU for a large plaque-size attenuant and 10(6) PFU for a minute plaque-size attenuant, indicating loss of cardiovirulence by a factor of more than 10(4)-10(5). rCVB3-induced SWR mouse is a sensitive and reliable model for myocarditis. It is useful in assessing the cardiovirulence of different CVB3 variants and evaluating the efficacies of anti-viral therapies. It will allow follow-up study after high dose infection with cardiovirulent rCVB3. Images Figure 1 Figure 2 p104-a Figure 4 p106-a Figure 5 PMID:8199011

  12. Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacitidine and donor lymphocyte infusions--a retrospective multicenter analysis from the German Cooperative Transplant Study Group.

    PubMed

    Schroeder, Thomas; Rachlis, Elena; Bug, Gesine; Stelljes, Matthias; Klein, Stefan; Steckel, Nina Kristin; Wolf, Dominik; Ringhoffer, Mark; Czibere, Akos; Nachtkamp, Kathrin; Dienst, Ariane; Kondakci, Mustafa; Stadler, Michael; Platzbecker, Uwe; Uharek, Lutz; Luft, Thomas; Fenk, Roland; Germing, Ulrich; Bornhäuser, Martin; Kröger, Nicolaus; Beelen, Dietrich W; Haas, Rainer; Kobbe, Guido

    2015-04-01

    To expand the current knowledge about azacitidine (Aza) and donor lymphocyte infusions (DLI) as salvage therapy for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to identify predictors for response and survival, we retrospectively analyzed data of 154 patients with acute myeloid leukemia (AML, n = 124), myelodysplastic (MDS, n = 28), or myeloproliferative syndrome (n = 2). All patients received a median number of 4 courses of Aza (range, 4 to 14) and DLI were administered to 105 patients (68%; median number of DLI, 2; range, 1 to 7). Complete and partial remission rates were 27% and 6%, respectively, resulting in an overall response rate of 33%. Multivariate analysis identified molecular-only relapse (hazard ratio [HR], 9.4; 95% confidence interval [CI], 2.0 to 43.5; P = .004) and diagnosis of MDS (HR, 4.1; 95% CI, 1.4 to 12.2; P = .011) as predictors for complete remission. Overall survival (OS) at 2 years was 29% ± 4%. Molecular-only relapse (HR, .14; 95% CI, .03 to .59; P = .007), diagnosis of MDS (HR, .33; 95% CI, .16 to .67; P = .002), and bone marrow blasts <13% (HR, .54; 95% CI, .32 to .91; P = .021) were associated with better OS. Accordingly, 2-year OS rate was higher in MDS patients (66% ± 10%, P = .001) and correlated with disease burden in patients with AML. In summary, Aza and DLI is an effective and well-tolerated treatment option for patients with relapse after allo-HSCT, in particular those with MDS or AML and low disease burden. The latter finding emphasizes the importance of stringent disease monitoring and early intervention.

  13. Time course of gene expression in rat experimental autoimmune myocarditis.

    PubMed

    Hanawa, Haruo; Abe, Satoru; Hayashi, Manabu; Yoshida, Tsuyoshi; Yoshida, Kaori; Shiono, Takaaki; Fuse, Koichi; Ito, Masahiro; Tachikawa, Hitoshi; Kashimura, Takeshi; Okura, Yuji; Kato, Kiminori; Kodama, Makoto; Maruyama, Seitaro; Yamamoto, Tadashi; Aizawa, Yoshifusa

    2002-12-01

    Genetic responses that characterize experimental autoimmune myocarditis (EAM) have not yet been determined. To investigate gene expression in the myocardium of EAM, absolute copy numbers of 44 mRNA species [calcium-handling proteins, contractile proteins, natriuretic peptides (NPs), cytokines, chemokines, growth factors, renin-angiotensin-aldosterone (RAA) system, endothelins (ETs) and extracellular matrix] in synthesized cDNA from a fixed quantity of total heart RNA were assessed using real-time reverse-transcriptase PCR at days 0, 14, 21 and 28 after immunization. alpha-Cardiac myosin showed a 26.3-fold decrease and beta-cardiac myosin a 3.75-fold increase at day 14. Atrial NP and brain NP increased 47.7- and 6.35-fold at days 21 and 14 respectively. Angiotensin II type 1 receptor, angiotensin-converting enzyme and ET1 increased 22.3-fold at day 21, 6.30-fold at day 21 and 16.8-fold at day 14 respectively. Aldosterone receptor decreased 2.15-fold at day 14, but aldosterone synthetase was detected only at days 14 and 21. Interleukin (IL)-2, IL-10, interferon-gamma and monocyte chemo-attractant protein-1 increased 9.08-fold at day 14, 398-fold at day 21, 43.1-fold at day 14 and 142-fold at day 14 respectively. Collagen type 3, collagen type 1 and fibronectin increased 34.6-, 1.74- and 44.4-fold respectively at day 21. Interestingly, osteopontin showed a 4540-fold increase and it was the highest mRNA of all at day 14. An isoform of cardiac myosin and NP are dramatically changed in EAM. RAA system and ET expressions are changed differently during the EAM time course. Cytokine, chemokine and extracellular matrix greatly increase and, in particular, large numbers of osteopontin mRNA are expressed in early EAM.

  14. FATE OF THE LYMPHOCYTE

    PubMed Central

    Bunting, C. H.; Huston, John

    1921-01-01

    Although the count of circulating lymphocytes in the blood stream remains constant, more lymphocytes enter the blood from the thoracic duct during 24 hours than are present in the blood at any one time. This excess of lymphocytes is not destroyed in the blood stream. The cells migrate from the blood vessels into the mucous membranes and through them to their surface. This occurs chiefly in the gastrointestinal tract, and it is apparently in the mucosa and especially within the intestinal lumen that the function of the lymphocyte is normally performed. PMID:19868519

  15. In vivo delivery of interleukin-35 relieves coxsackievirus-B3-induced viral myocarditis by inhibiting Th17 cells.

    PubMed

    Hu, Yadong; Dong, Chunsheng; Yue, Yan; Xiong, Sidong

    2014-09-01

    Interleukin (IL)-35 is a new member of the IL-12 cytokine family. The suppressive role of IL-35 in the immune response to parasitic and bacterial infections and in autoimmunity has been demonstrated in terms of its anti-inflammatory properties. However, the functional role of IL-35 in viral myocarditis has not been investigated. In this study, IL-35 expression was measured in heart tissues with coxsackievirus B3 (CVB3)-induced myocarditis. It was significantly reduced in the late stage of viral infection and correlated negatively with disease severity. To examine the therapeutic role of IL-35 in viral myocarditis, an IL-35-expressing plasmid (pIL-35-FC) was packaged with polyethyleneimine and delivered intraperitoneally to BALB/c male mice before and after CVB3 infection. The severity of myocarditis was assessed 7 days after infection. The in vivo delivery of IL-35 significantly ameliorated the severity of viral myocarditis, reflected in an increased survival rate and increased bodyweights, and reduced serum creatine kinase (CK) and CK-MB activities, cardiac pathological scores, and viral replication. We also show that the overexpression of IL-35 reduced splenic Th17 cells and Th17-related proinflammatory cytokines in heart tissues. In conclusion, our data indicate that IL-35 effectively protects the myocardium from the pathogenesis of CVB3-induced viral myocarditis, which may be attributable to reduced Th17 production. This suggests that supplementation with IL-35 could be a novel therapeutic treatment for viral myocarditis.

  16. High Frequency of Detection by PCR of Viral Nucleic Acid in The Blood of Infants Presenting with Clinical Myocarditis.

    PubMed

    Simpson, Kathleen E; Storch, Gregory A; Lee, Caroline K; Ward, Kent E; Danon, Saar; Simon, Catherine M; Delaney, Jeffrey W; Tong, Alan; Canter, Charles E

    2016-02-01

    Specific viruses are associated with pediatric myocarditis, but the prevalence of viral DNAemia detected by blood polymerase chain reaction (PCR) is unknown. We evaluated the prevalence of known cardiotropic viruses (enterovirus, adenovirus, human herpesvirus 6, and parvovirus B19) in children with clinical myocarditis (n = 21). Results were compared to pediatric controls with similar viral PCR testing. The majority of positive PCR (89 %) was noted in children ≤12 months of age at diagnosis compared to older children. Infant myocarditis patients (8/10) had increased the prevalence of PCR positivity compared to infant pediatric controls (4/114) (p < 0.0001). Other than age, patient characteristics at diagnosis were similar between PCR-positive and PCR-negative patients. Both PCR-negative myocarditis infants had clinical recovery at follow-up. Of the PCR-positive myocarditis infants, 4 had clinical recovery, 2 developed chronic cardiomyopathy, 1 underwent heart transplant, and 1 died. Infants with clinical myocarditis have a high rate of blood viral positivity, which is higher compared to older children with myocarditis and healthy infant controls. Age-related differences in PCR positivity may be due to differences in host and/or virus characteristics. Our findings suggest that viral blood PCR may be a useful diagnostic tool and identify patients who would potentially benefit from virus-specific therapy.

  17. Transmissible endoplasmic reticulum stress from myocardiocytes to macrophages is pivotal for the pathogenesis of CVB3-induced viral myocarditis

    PubMed Central

    Zhang, Hui; Yue, Yan; Sun, Tianle; Wu, Xuejie; Xiong, Sidong

    2017-01-01

    Infiltrating macrophages have been proven as a pivotal pathological inflammatory cell subset in coxsackievirus B3 (CVB3) induced viral myocarditis. However, the mechanisms underlying the initiation and promotion of macrophage pro-inflammatory responses are still blur. We previously reported that cardiac ER stress contributed to CVB3-induced myocarditis by augmenting inflammation. In this study, we focused on the influence of ER stress on the macrophage inflammatory responses in the viral myocarditis. We found that ER stress was robustly induced in the cardiac infiltrating macrophages from CVB3-infected mice, and robustly facilitated the production of pro-inflammatory cytokines (IL-6, IL-12, MCP-1 and IP-10). Consistently, adoptive transfer of ER stressed macrophages significantly worsened the viral myocarditis; while transfer of ER stress-inhibited macrophages obviously alleviated the myocarditis. To our surprise, this significantly activated ER stress was not directly caused by the virus stimulation, but was transferred from the CVB3-infected, ER stressed myocardiocytes via soluble molecules in a TLR2, 4-independent way. In the present study, we reported that the transmissible ER stress from the infected myocardiocytes to macrophages could augment the pro-inflammatory responses and promoted the pathogenesis of viral myocarditis. Blocking ER stress transmission, instead of inhibiting its initiation, may represent novel therapeutic strategies against viral myocarditis. PMID:28176833

  18. In situ immune autoradiographic identification of cells in heart tissues of mice with coxsackievirus B3-induced myocarditis

    SciTech Connect

    Godeny, E.K.; Gauntt, C.J.

    1987-11-01

    In adolescent CD-1 male mice inoculated with a myocarditic coxsackievirus B3 (CVB3m) acute focal lesions containing necrotic myocytes, infiltrating mononuclear cells, and fibroblasts develop. With the use of an in situ immune autoradiographic method with rat monoclonal antibodies (MAb) and an /sup 35/S-labeled antibody, viral antigens were detected outside of lesions. Macrophages, T lymphocytes, and natural killer (NK) cells were identified within myocarditic lesions during the acute phase of the disease. Macrophages detected by anti-Mac-1 MAb were in focal areas within myocarditic lesions on Days 4-7 after inoculation. T lymphocytes were detected in myocarditic lesions on Days 4-10, with MAb to Thy-1 and Lyt-1 antigens showing diffuse reaction patterns, suggesting random distribution of these cells in lesions. Focal areas of reactivity were detected with MAbs to L3T4 and Lyt-2 antigens, suggesting clusters of helper and cytotoxic/suppressor T lymphocytes, respectively. NK cells were presumptively detected by asialo GM1 surface marker in lesions at all times. The presence of activated NK cells in lesions was confirmed by assay of mechanically dissociated heart tissues on Day 8. These data describe the temporal sequence and identity of leukocytes entering into CVB3-induced focal myocarditic lesions during the acute phase of disease in CD-1 mice.

  19. Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2013-07-01

    B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  20. Argonaute proteins in cardiac tissue contribute to the heart injury during viral myocarditis.

    PubMed

    Sun, Shougang; Ma, Jialiang; Zhang, Quan; Wang, Qiongying; Zhou, Lei; Bai, Feng; Hu, Hao; Chang, Peng; Yu, Jing; Gao, Bingren

    2016-01-01

    MicroRNAs (miRNAs) are a group of short, noncoding, regulatory RNA molecules the dysregulation of which contributes to the pathogenesis of myocarditis. Argonaute proteins are essential components of miRNA-induced silencing complex and play important roles during miRNA biogenesis and function. However, the expression pattern of four AGO family members has not yet been detected in the coxsackievirus B3 (CVB3)-induced myocarditis tissue samples. In this study, we detected the expression of four AGOs in the CVB3-infected mouse heart tissues and found that AGO1 and AGO3 up-regulated significantly at 4 and 8h after CVB3 infection. Further in vitro research indicated that up-regulated AGO1 and AGO3 are related to the down-regulated TNFAIP3, which is a negative regulator of NF-κB pathway. Subsequently, we confirmed that TNFAIP3 is a direct target of miR-19a/b, and during CVB3 infection, the expression of miR-19a/b and miR-125a/b is not significantly changed. TNFAIP3 level is mainly reduced by up-regulated AGO1 and AGO3. This research sheds light on the relationship between overexpressed AGO proteins and CVB3-induced myocarditis, and this provides potential therapeutic target for viral myocarditis.

  1. Case of a healthy infant born following antenatal enterovirus myocarditis and hydrops.

    PubMed

    Bonnin, Aurore; Tassin, Mikael; Vauloup-Fellous, Christelle; Letamendia, Emmanuelle; Stos, Bertrand; Bonnet, Damien; Gajdos, Vincent; Mabille, Mylène; Benachi, Alexandra

    2014-11-01

    Fetal hydrops and myocarditis were diagnosed in a woman at 32 weeks of gestation (WG). Transplacental enterovirus infection was suspected because all other causes of myocarditis and hydrops were excluded, it was during an endemic period, and there was a setting of maternal infection (fever a few days before). We opted for in utero treatment because of the risk of resuscitating a neonate with myocarditis and hydrops. We administered dexamethasone 12mg twice for pulmonary maturation and presumed it would partially improve the myocarditis. Fetal arrhythmia was noted at 35 WG and we decided to deliver the infant as postnatal treatment of the heart disorder would be more effective. RT-PCR (ARGENE(®)) showed that the neonate's throat and anal tissues and cord blood sampled on the day of birth contained enterovirus ribonucleic acid and coxsackievirus B5, as did the mother's anal sample. Laboratory tests, heart MRI and probably brain MRI indicated neonatal enterovirus infection. Findings were normal at two-year follow-up.

  2. Genetic and antigenic characterisation of Bungowannah virus, a novel pestivirus causing myocarditis in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In June 2003 a syndrome of sudden death in sucker pigs, an elevation in the proportion of stillborn foetuses, increased preweaning losses and to a lesser extent increased mummification rates was recognised on a property in NSW, Australia [1]. This disease has been described as the porcine myocarditi...

  3. Anévrysme ventriculaire gauche et communication interventriculaire compliquant un infarctus du myocarde

    PubMed Central

    Belkhadir, Mohammed; MoutakiAllah, Younes; Raissouni, Zainab; Abdou, Abdessamad; Bamous, Mehdi; Nya, Fouad; Atmani, Noureddine; Houssa, Mahdi Ait; El Bekkali, Youssef; Boulahya, Abdellatif

    2014-01-01

    L'association d'une communication interventriculaire post infarctus du myocarde et d'un anévrysme du ventricule gauche chez un même patient est extrêmement rare et survient habituellement durant la première semaine qui suit un infarctus du myocarde. Nous rapportons le cas insolite d'un patient âgé de 63 ans, admis pour choc cardiogénique en rapport avec une communication inter ventriculaire apicale et un anévrysme ventriculaire gauche causés par un infarctus du myocarde antérieur. La correction chirurgicale a consisté en une fermeture du défect septal par un patch en dacron via une ventriculotomie gauche associée à une anévrysectomie et un mono pontage coronaire. Cette observation illustre d'une part la rareté de l'association communication inter ventriculaire-anévrysme ventriculaire gauche post infarctus du myocarde, et d'autre part l'efficacité du traitement chirurgical qui reste la seule option salvatrice pour cette pathologie. PMID:25328617

  4. Lenalidomide and Vaccine Therapy in Treating Patients With Early-Stage Asymptomatic Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2016-12-26

    Chronic Lymphocytic Leukemia; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma

  5. Lymphocyte emperipolesis revisited

    PubMed Central

    Sandilands, G. P.; Reid, Fiona M.; Gray, Kathleen G.; Anderson, J. R.

    1978-01-01

    A surprisingly high proportion of antibody (IgG) sensitized Chang liver cells apparently contained one or more intracytoplasmic human peripheral blood lymphocytes following a period of contact at 37°. Since various technical factors were found to influence this phenomenon of lymphocyte `emperipolesis', optimum conditions were selected for use in a standard quantitative in vitro assay. Lymphocytes from normal individuals varied considerably in their ability to participate in emperipolesis; an observation which suggested that a particular lymphocyte subpopulation may be involved. Preliminary characterization of emperipoletic cells indicated that they are Fc receptor bearing, non-T lymphocytes. The significance of these findings in relation to immune mechanisms is discussed. ImagesFigure 1Figure 2 PMID:312253

  6. Pentostatin and Lymphocyte Infusion in Preventing Graft Rejection in Patients Who Have Undergone Donor Stem Cell Transplant

    ClinicalTrials.gov

    2016-02-29

    Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Graft Versus Host Disease; Hodgkin Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Plasma Cell Myeloma; Waldenstrom Macroglobulinemia

  7. Cannabidiol Limits T Cell–Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation

    PubMed Central

    Lee, Wen-Shin; Erdelyi, Katalin; Matyas, Csaba; Mukhopadhyay, Partha; Varga, Zoltan V; Liaudet, Lucas; Hask’, György; ’iháková, Daniela; Mechoulam, Raphael; Pacher, Pal

    2016-01-01

    Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen. Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis. Cannabidiol (CBD) is a nonpsychoactive constituent of marijuana that exerts antiinflammatory effects independent of classical cannabinoid receptors. Recently, 80 clinical trials have investigated the effects of CBD in various diseases from inflammatory bowel disease to graft versus host disease. CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received U.S. Food and Drug Administration approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme. Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell–mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD. EAM was characterized by marked myocardial T-cell infiltration, profound inflammatory response and fibrosis (measured by quantitative real-time polymerase chain reaction, histology and immunohistochemistry analyses) accompanied by marked attenuation of both systolic and diastolic cardiac functions measured with a pressure-volume conductance catheter technique. Chronic treatment with CBD largely attenuated the CD3+ and CD4+ T cell–mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction in mice. In conclusion, CBD may represent a promising novel treatment for managing autoimmune myocarditis and possibly other autoimmune disorders and organ transplantation. PMID:26772776

  8. Supportive Care for Chronic Lymphocytic Leukemia

    MedlinePlus

    ... Chronic Lymphocytic Leukemia Supportive Care for Chronic Lymphocytic Leukemia Supportive care for chronic lymphocytic leukemia (CLL) is ... Treating Hairy Cell Leukemia More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  9. Lymphocyte subsets alteration in patients with argentine hemorrhagic fever.

    PubMed

    Vallejos, D A; Ambrosio, A M; Feuillade, M R; Maiztegui, J I

    1989-02-01

    Peripheral blood lymphocyte subpopulations were studied in 15 patients with Argentine Hemorrhagic Fever (AHF), during the acute period of the disease and in early convalescence. Anti-human Ig antibodies were used to identify B cells and monoclonal antibodies to assess T4 and T8 subsets. During the acute period of the disease, significant alterations were found in B, T4, and T8 lymphocytes (P less than .001), as well as in T4/T8 ratios (P less than .001). These abnormalities disappeared in early convalescence, around 30 days after the clinical onset. Diminished numbers of T4 lymphocytes are interpreted as relevant to the immunodepression that characterizes the acute phase of AHF.

  10. [Laboratory diagnosis of lymphocytic meningitis].

    PubMed

    Marí, José María Navarro; Ruiz, Mercedes Pérez; Anza, Diego Vicente

    2010-01-01

    Lymphocytic meningitis, mainly those with an acute and benign course, are caused by viruses. In our area, the most commonly involved agents are enteroviruses, herpes simplex, varicella zoster and Toscana viruses. Nucleic acids amplification techniques (NAAT) are the methods of choice to diagnose viral meningitis from cerebrospinal fluid (CSF) samples. They are more rapid and sensitive, and indeed, they are not influenced by the viability of the virus in the clinical specimen as traditional methods are. The development of commercial equipments, the degree of automation, and the use of real-time polymerase chain reaction (PCR) systems are the most important premises to choose the molecular method in each laboratory. Recently, commercial kits of real-time PCR are available for the detection of enteroviruses and herpesviruses, which are the most frequently viruses involved in meningitis. Although NAAT from the clinical sample have replaced cell culture for diagnostic purposes, the combination of both methods remain useful. When the detection of the causal agent from the CSF sample is not possible, other specimens (pharyngeal exudates, stools) or serological methods can be used. Serology is the reference method for meningitis caused by West Nile virus and lymphocytic choriomeningitis virus, which are less frequently detected in our area.

  11. Noninvasive Imaging of Myocardial Inflammation in Myocarditis using 68Ga-tagged Mannosylated Human Serum Albumin Positron Emission Tomography

    PubMed Central

    Lee, Seung-Pyo; Im, Hyung-Jun; Kang, Shinae; Chung, Seock-Jin; Cho, Ye Seul; Kang, Hyejeong; Park, Ho Seon; Hwang, Do-Won; Park, Jun-Bean; Paeng, Jin-Chul; Cheon, Gi-Jeong; Lee, Yun-Sang; Jeong, Jae Min; Kim, Yong-Jin

    2017-01-01

    The diagnosis of myocarditis traditionally relies on invasive endomyocardial biopsy but none of the imaging studies so far are specific for infiltration of the inflammatory cells itself. We synthesized 68Ga-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA) by conjugating human serum albumin with mannose, followed by conjugation with NOTA and labeling it with 68Ga. The efficacy of 68Ga-NOTA-MSA positron emission tomography (PET) for imaging myocardial inflammation was tested in a rat myocarditis model. A significant number of mannose receptor-positive inflammatory cells infiltrated the myocardium in both human and rat myocarditis tissue. 68Ga-NOTA-MSA uptake was upregulated in organs of macrophage accumulation, such as liver, spleen, bone marrow and myocardium (0.32 (0.31~0.33) for normal versus 1.02 (0.86~1.06) for myocarditis (median (range), SUV); n=4~6 per group, p-value=0.01). 68Ga-NOTA-MSA uptake in the left ventricle was upregulated in myocarditis compared with normal rats (2.29 (1.42~3.40) for normal versus 4.18 (3.43~6.15) for myocarditis (median (range), average standard uptake value ratio against paraspinal muscle); n=6 per group, p-value<0.01), which was downregulated in rats with cyclosporine-A treated myocarditis (3.69 (2.59~3.86) for myocarditis versus 2.28 (1.76~2.60) for cyclosporine-A treated myocarditis; n=6 per group, p-value<0.01). The specificity of the tracer was verified by administration of excess non-labeled MSA. 68Ga-NOTA-MSA uptake was significantly enhanced earlier in the evolution of myocarditis before any signs of inflammation could be seen on echocardiography. These results demonstrate the potential utility of visualizing infiltration of mannose receptor-positive macrophages with 68Ga-NOTA-MSA PET in the early diagnosis of as well as in the monitoring of treatment response of myocarditis. PMID:28042344

  12. Therapeutic considerations in acute lymphocytic leukemia.

    PubMed Central

    Holland, J. F.

    1978-01-01

    Evidence that the first human neoplasm systematically explored with chemotherapeutic treatments has apparently been cured in a palpable segment of affected patients evokes optimism for other types of cancer. The application of similar effort, similar logic, and quantitative experimental therapeutic approaches to the common cancers augurs well for cancer research and clinical medicine. Images Text-Figure 5 Text-Figure 8 PMID:272122

  13. Panax Notoginseng Saponins Ameliorates Coxsackievirus B3-Induced Myocarditis by Activating the Cystathionine-γ-Lyase/Hydrogen Sulfide Pathway.

    PubMed

    Pan, Lulu; Zhang, Yuanhai; Lu, Jiacheng; Geng, Zhimin; Jia, Lianhong; Rong, Xing; Wang, Zhenquan; Zhao, Qifeng; Wu, Rongzhou; Chu, Maoping; Zhang, Chunxiang

    2015-12-01

    This study is to determine the therapeutic effects of Panax notoginseng saponins (PNSs) on coxsackievirus B3 (CVB3)-induced myocarditis, and whether cystathionine-γ-lyase (CSE)/hydrogen sulfide (H2S) pathway is involved. Mouse model of myocarditis was induced by CVB3 infection, and the mice were subjected to vehicle (saline) or drug treatments (sodium bisulfide (NaHS), propargylglycine (PAG), or PNSs). The results showed that there were inflammatory cell infiltrations, interstitial edemas, and elevated inflammatory cytokines, in CVB3-induced myocarditis. PAG administration increased, whereas NaHS treatment decreased the severity of the myocarditis. PNS treatment dramatically alleviated these myocardial injuries and decreased the viral messenger RNA (mRNA) expression by the enhanced expression of CSE/H2S pathway. Moreover, the therapeutic effects of PNSs on myocarditis were stronger than those of NaHS. Finally, the effect of PNSs on CSE/H2S pathway and cardiac cell protection were verified in cultured cardiac cells. PNSs may be a promising medication for viral myocarditis therapy.

  14. Myocarditis in a traveler returning from the Dominican Republic: an unusual presentation of dengue fever.

    PubMed

    Zea, Diego; Foley, Kimberly; Carey, Jeanne

    2014-07-01

    Myocarditis is an uncommon manifestation of dengue fever. We describe a case of a 69-year-old Hispanic male who presented to an emergency room in New York City 3 days after returning from a trip to the Dominican Republic complaining of a 1-day history of chest pain and fever. His first electrocardiogram showed a new left bundle branch block, and initial cardiac enzymes included troponin of 5 ng/dL, creatine kinase-MB of 9 ng/mL, and myoglobin of 234 ng/mL. Dengue fever antibodies were found to be elevated: immunoglobulin M (IgM) titer was 2.48 (reference range < 0.9), and immunoglobulin G (IgG) titer was 4.26 (reference range < 0.9). The patient was diagnosed with myocarditis caused by dengue fever. He improved after 1 week with conservative management in a telemetry unit and was discharged home.

  15. [A case of eosinophilic myositis presenting with myocarditis and cardiac embolism].

    PubMed

    Madokoro, Yuta; Kato, Hideki; Yuasa, Hiroyuki; Ootaka, Naoya; Mori, Yoshiko; Mitake, Shigehisa

    2015-01-01

    We report the case of a 72-year-old male who presented with the complaints of muscular pain and weakness. The patient showed marked eosinophilia, elevated levels of myogenic enzymes and pathological abnormalities including eosinophil infiltration obtained from the muscle biopsy. Based on these findings, the patient was diagnosed with eosinophilic myositis. During follow-up, left ventricular wall motion abnormalities with transient electrocardiographic abnormalities were identified; these were believed to be concurrent with eosinophilic myocarditis. Further, notable complications included cardiogenic cerebral embolism. Eosinophilic myositis has been found to cause a wide spectrum of complications. Our findings indicate that in cases of suspected eosinophilic myositis, it is crucial to identify myocarditis immediately and to select an anticoagulant therapy to prevent cerebral embolism.

  16. The Role of Protease-Activated Receptors for the Development of Myocarditis: Possible Therapeutic Implications.

    PubMed

    Weithauser, Alice; Witkowski, Marco; Rauch, Ursula

    2016-01-01

    Protease-activated receptors (PARs) are a unique group of four G-protein coupled receptors. They are widely expressed within the cardiovascular system and the heart. PARs are activated via cleavage by serine proteases. In vitro and in vivo studies showed that the activation of PAR1 and PAR2 plays a crucial role in virus induced inflammatory diseases. The receptors enable cells to recognize pathogen-derived changes in the extracellular environment. An infection with Coxsackie-virus B3 (CVB3) can cause myocarditis. Recent studies have been shown that PAR1 signaling enhanced the antiviral innate immune response via interferon β (IFNβ) and thus limited the virus replication and cardiac damage. In contrast, PAR2 signaling decreased the antiviral innate immune response via IFNβ und thus increased the virus replication, which caused severe myocarditis. Along with CVB3 other viruses such as influenza A virus (IAV) and herpes simplex virus (HSV) can induce myocarditis. The role of PAR signaling in IAV infections is contrarily discussed. During HSV infections PARs facilitate the virus infection of the host cell. These studies show that PARs might be interesting drug targets for the treatment of virus infections and inflammatory heart diseases. First studies with PAR agonists, antagonists, and serine protease inhibitors have been conducted in mice. The inhibition of thrombin the main PAR1 activating protease decreased the IFNβ response and increased the virus replication in CVB3-induced myocarditis. This indicates that further studies with direct PAR agonists and antagonists are needed to determine whether PARs are useful drug targets for the therapy of virus-induced heart diseases.

  17. Antimyosin antibody cardiac imaging: Its role in the diagnosis of myocarditis

    SciTech Connect

    Dec, G.W.; Palacios, I.; Yasuda, T.; Fallon, J.T.; Khaw, B.A.; Strauss, H.W.; Haber, E. )

    1990-07-01

    Right ventricular endomyocardial biopsy currently remains the procedure of choice for identifying patients with symptomatic heart failure due to myocarditis from the larger population with idiopathic dilated cardiomyopathy. Despite its specificity, the sensitivity of right ventricular biopsy remains uncertain because of the focal or multifocal nature of the disease. Because myocyte necrosis is an obligate component of myocarditis, the use of indium-111 antimyosin imaging was evaluated in 82 patients with suspected myocarditis. Seventy-four patients had dilated cardiomyopathy of less than 1 year's duration (mean left ventricular ejection fraction 0.30 +/- 0.02); eight patients had normal left ventricular function (mean ejection fraction 0.59 +/- 0.03). Symptoms at presentation included congestive heart failure (92%), chest pain mimicking myocardial infarction (6%) and life-threatening ventricular tachyarrhythmias (2%). All patients underwent planar and single photon emission computed tomographic (SPECT) cardiac imaging after injection of indium-111-labeled antimyosin antibody fragments and right ventricular biopsy within 48 h of imaging. Antimyosin images were interpreted as either abnormal or normal and correlated with biopsy results. On the basis of the right ventricular histologic examination, the sensitivity of antimyosin imaging was 83%, specificity 53% and predictive value of a normal scan 92%. Improvement in left ventricular function occurred within 6 months of treatment in 54% of patients with an abnormal antimyosin scan compared with 18% of those with a normal scan (p less than 0.01). Antimyosin cardiac imaging may be useful for the initial evaluation of patients with dilated and nondilated cardiomyopathy and clinically suspected myocarditis.

  18. Idiopathic giant cell myocarditis--a distinctive clinico-pathological entity.

    PubMed Central

    Davies, M J; Pomerance, A; Teare, R D

    1975-01-01

    Eleven cases of idiopathic giant cell myocarditis are described, The pathological features are unmistakable with serpiginous areas of myocardial necrosis, at the margins of which giant cells can be seen on histological examination. The aetiology of the condition remains obscure but associated pathology suggests that altered immunity may be a factor. The rapid clinical course is, however, highly suggestive of an infective cause though none has been found. Images PMID:1122272

  19. Lymphocyte Redox Imbalance and Reduced Proliferation after a Single Session of High Intensity Interval Exercise.

    PubMed

    Tossige-Gomes, Rosalina; Costa, Karine Beatriz; Ottone, Vinícius de Oliveira; Magalhães, Flávio de Castro; Amorim, Fabiano Trigueiro; Rocha-Vieira, Etel

    2016-01-01

    This study investigated whether an acute session of high-intensity interval training (HIIT) is sufficient to alter lymphocyte function and redox status. Sixteen young healthy men underwent a HIIT session on a cycloergometer, consisting of eight bouts of 1 min at 90-100% of peak power, with 75 seconds of active recovery at 30 W between bouts. Venous blood was collected before, immediately after, and 30 minutes after the HIIT session. In response to Staphylococcus aureus superantigen B (SEB) stimulation, lymphocyte proliferation decreased and the IL-2 concentration increased after the HIIT session. However, the HIIT session had no effect on lymphocyte proliferation or IL-2 response to phytohemagglutinin stimulation. The HIIT session also induced lymphocyte redox imbalance, characterized by an increase in the concentration of thiobarbituric acid reactive substances and a decrease in the activity of the antioxidant enzyme catalase. Lymphocyte viability was not affected by the HIIT session. The frequencies of CD25+ and CD69+ T helper and B lymphocytes in response to superantigen stimulation were lower after exercise, suggesting that superantigen-induced lymphocyte activation was reduced by HIIT. However, HIIT also led to a reduction in the frequency of CD4+ and CD19+ cells, so the frequencies of CD25+ and CD69+ cells within the CD4 and CD19 cell populations were not affected by HIIT. These data indicate that the reduced lymphocyte proliferation observed after HIIT is not due to reduced early lymphocyte activation by superantigen. Our findings show that an acute HIIT session promotes lymphocyte redox imbalance and reduces lymphocyte proliferation in response to superantigenic, but not to mitogenic stimulation. This observation cannot be explained by alteration of the early lymphocyte activation response to superantigen. The manner in which lymphocyte function modulation by an acute HIIT session can affect individual immunity and susceptibility to infection is important

  20. Lymphocyte Redox Imbalance and Reduced Proliferation after a Single Session of High Intensity Interval Exercise

    PubMed Central

    Tossige-Gomes, Rosalina; Costa, Karine Beatriz; Ottone, Vinícius de Oliveira; Magalhães, Flávio de Castro; Amorim, Fabiano Trigueiro; Rocha-Vieira, Etel

    2016-01-01

    This study investigated whether an acute session of high-intensity interval training (HIIT) is sufficient to alter lymphocyte function and redox status. Sixteen young healthy men underwent a HIIT session on a cycloergometer, consisting of eight bouts of 1 min at 90–100% of peak power, with 75 seconds of active recovery at 30 W between bouts. Venous blood was collected before, immediately after, and 30 minutes after the HIIT session. In response to Staphylococcus aureus superantigen B (SEB) stimulation, lymphocyte proliferation decreased and the IL-2 concentration increased after the HIIT session. However, the HIIT session had no effect on lymphocyte proliferation or IL-2 response to phytohemagglutinin stimulation. The HIIT session also induced lymphocyte redox imbalance, characterized by an increase in the concentration of thiobarbituric acid reactive substances and a decrease in the activity of the antioxidant enzyme catalase. Lymphocyte viability was not affected by the HIIT session. The frequencies of CD25+ and CD69+ T helper and B lymphocytes in response to superantigen stimulation were lower after exercise, suggesting that superantigen-induced lymphocyte activation was reduced by HIIT. However, HIIT also led to a reduction in the frequency of CD4+ and CD19+ cells, so the frequencies of CD25+ and CD69+ cells within the CD4 and CD19 cell populations were not affected by HIIT. These data indicate that the reduced lymphocyte proliferation observed after HIIT is not due to reduced early lymphocyte activation by superantigen. Our findings show that an acute HIIT session promotes lymphocyte redox imbalance and reduces lymphocyte proliferation in response to superantigenic, but not to mitogenic stimulation. This observation cannot be explained by alteration of the early lymphocyte activation response to superantigen. The manner in which lymphocyte function modulation by an acute HIIT session can affect individual immunity and susceptibility to infection is important

  1. Low lymphocyte count and cardiovascular diseases.

    PubMed

    Núñez, J; Miñana, G; Bodí, V; Núñez, E; Sanchis, J; Husser, O; Llàcer, A

    2011-01-01

    Inflammation plays a crucial pathophysiological role in the entire continuum of the atherosclerotic process, from its initiation, progression, and plaque destabilization leading ultimately to an acute coronary event. Furthermore, once the clinical event has occurred, inflammation also influences the left ventricular remodelling process. Under the same paradigm, there is evidence that lymphocytes play an important role in the modulation of the inflammatory response at every level of the atherosclerotic process. Low lymphocyte count (LLC) is a common finding during the systemic inflammatory response, and clinical and animal studies suggest that LCC plays a putative role in accelerated atherosclerosis. For instance, there is recent evidence that LLC is associated with worse outcomes in patients with heart failure, chronic ischemic heart disease and acute coronary syndromes. Further indirect evidence supports the pathologic role of LLC related to the fact that 1) lymphopenia--due to a decreased count of lymphocyte T cells--normally occurs as a part of the human ageing process, and 2) increased incidence of cardiovascular events has been reported in conditions where lymphopenia is common, such as renal transplant recipients, human immunodeficiency virus infection, survivors of nuclear disasters and autoimmune diseases. The aim of the present article is to review: a) the pathophysiological mechanisms that have been proposed for the observed association between LLC and cardiovascular diseases (CVD), b) the available evidence regarding the diagnostic and prognostic role attributable to LLC in patients with CVD, and; c) the potential therapeutic implications of these findings.

  2. Myocardial dysfunction in an experimental model of autoimmune myocarditis: role of IFN-gamma.

    PubMed

    Pérez Leirós, C; Goren, N; Sterin-Borda, L; Borda, E S

    1997-01-01

    Experimental autoimmune myocarditis obtained in mice by immunization with heart antigens is characterized by the presence of lymphomononuclear infiltrates in atria and ventricles. Here we show the ability of soluble factors released by immune cells from mice immunized with heart antigens to decrease heart contractility in a similar way to a muscarinic agonist. These effects appear to be mediated by IFN-gamma since all of them could be blocked by an anti-IFN-gamma monoclonal antibody. Moreover, the negative inotropic effect induced by immune cell-conditioned media was blocked by atropine, confirming previous findings that IFN acts as a muscarinic agonist on isolated atria. The role of locally released cytokines and especially of IFN-gamma was also evaluated in infiltrated autoimmune myocarditis hearts; thus, the addition of monoclonal anti-IFN-gamma antibody reversed the decreased contractility characteristics of this model. We conclude that IFN released both systemically and locally by autoreactive T cells may contribute to the impaired cardiac function in this experimental model of autoimmune myocarditis.

  3. Indium-111 antimyosin scintigraphy to assess myocardial damage in patients with suspected myocarditis and cardiac rejection

    SciTech Connect

    Carrio, I.; Berna, L.; Ballester, M.; Estorch, M.; Obrador, D.; Cladellas, M.; Abadal, L.; Ginjaume, M.

    1988-12-01

    Indium-111 antimyosin scans were used to assess myocardial damage in patients with suspected myocarditis and cardiac transplant rejection. The calculation of a myocardium to lung ratio (AM index) to quantify antimyosin uptake was performed. AM index in normal subjects (n = 8) at 48 hr postinjection was 1.46 +/- 0.04. In patients with suspected myocarditis (16 studies in 13 patients), AM index was 2.0 +/- 0.5 (p less than 0.001); suggesting a considerable incidence of ongoing cell damage in this group, despite the small proportion of positive right ventricular endomyocardial biopsy (RVbx) (4/13). In patients studied after cardiac transplantation (37 studies in 17 patients), AM indexes correlated with RVbx. In patients with RVbx proven rejection (n = 14), AM index was 1.87 +/- 0.19 (p less than 0.001). In patients with RVbx showing infiltrates but not myocyte damage (n = 13), AM index was 1.80 +/- 0.27 (p = 0.02). In patients with normal RVbx (n = 10), AM index was 1.56 +/- 0.17 (p = NS versus controls; p = 0.001 versus those with positive RVbx). Calculated AM indexes correlated with graded visual analysis of the scans (r = 0.823; p = 0.001). Antimyosin scans are an appropriate method to assess myocardial damage in patients with suspected myocarditis and cardiac rejection.

  4. Electrocardiographic changes evoked by ajmaline in chronic Chagas' disease with manifest myocarditis.

    PubMed

    Chiale, P A; Przybylski, J; Laiño, R A; Halpern, M S; Sánchez, R A; Gabrieli, A; Elizari, M V; Rosenbaum, M B

    1982-01-01

    Conversion from Chagas' infection to chagasic myocarditis occurs slowly and the earliest signs of myocardial involvement are hard to define. To obtain new information on this difficult clinical problem, ajmaline was administered (1 mg/kg body weight intravenously) to 101 patients with Chagas' infection and to 46 patients without such infection (control group). In 3 patients in the control group left anterior hemiblock alone occurred whereas in the group with Chagas' infection, ajmaline caused the occurrence of right bundle branch block, left anterior hemiblock, or both, in 32 patients (31.6 percent), ventricular extrasystoles in 8 (7.9 percent) and ischemic ST-T changes in 7 (6.9 percent). Ajmaline may thus evoke the most typical electrocardiographic changes of chronic chagasic myocarditis in patients without signs of myocardial involvement or only minor nonspecific signs. A positive ajmaline test, defined in the present context as the occurrence of a fascicular block, ventricular arrhythmias or ischemic ST-T changes, may indicate the existence of localized areas of injured myocardial tissue, not enough to alter the electrocardiogram by itself, but able to give rise to severe abnormalities after exposure to the drug. The test may therefore be used as a nonspecific detector of myocardial damage, and thus may have a much broader scope of clinical application. In chronic Chagas' infection, the ajmaline test is a relatively simple and apparently safe procedure that may serve to unveil the earliest signs of chagasic myocarditis.

  5. The diagnostic value of transthoracic echocardiography for eosinophilic myocarditis: A single center experience from China.

    PubMed

    Xie, Mingxing; Cheng, Tsung O; Fei, Hongwen; Ren, Pingping; He, Yale; Wang, Xinfang; Lu, Qing; Han, Wei; Li, Ke; Li, Ling; Yang, Yali; Chen, Oudi

    2015-12-15

    The aim of this study is to explore the value of transthoracic echocardiography in the diagnosis of eosinophilic myocarditis. The echocardiographic characteristics of nine patients with eosinophilic myocarditis in our hospital between January 2004 and January 2012 were retrospectively reviewed. In our study, four of the nine patients were diagnosed to have small pericardial effusion. The obliteration of the apical cavity was observed in five of the nine patients. There were six patients with both mitral and tricuspid regurgitation, one patient with only mitral regurgitation, and one patient with only tricuspid regurgitation. Transthoracic echocardiography showed that the diameters of the left and right atria were both increased in eight of the nine patients. The diameter of the left ventricle was increased in five patients, and the right ventricular diameter was increased in four patients. The left ventricular ejection fraction was decreased in two of the nine patients. Five of the nine patients had pulmonary hypertension, and one patient had severe pulmonary hypertension. Transthoracic echocardiography is the primary method for the diagnosis of eosinophilic myocarditis and is also useful in follow-up of the disease.

  6. Hypopituitarism due to lymphocytic hypophysitis in a patient with retroperitoneal fibrosis.

    PubMed Central

    Alvarez, A.; Cordido, F.; Sacristán, F.

    1997-01-01

    We present a 78-year-old woman with clinical acute hypopituitarism in whom pathologic findings showed lymphocytic hypophysitis and retroperitoneal fibrosis. Lymphocytic hypophysitis should be included in the differential diagnosis of hypopituitarism at any age. The association with idiopathic retroperitoneal fibrosis suggest an autoimmune origin for this entity. Images Figure 1 Figure 2 PMID:9519190

  7. Simian immunodeficiency virus infection of CD8+ lymphocytes in vivo.

    PubMed Central

    Dean, G A; Reubel, G H; Pedersen, N C

    1996-01-01

    To determine the lymphoid target cells of simian immunodeficiency virus (SIV) in vivo, peripheral blood lymphocytes (PBL) and lymph node lymphocytes (LNL) were positively selected (>97% purity) for surface expression of CD4, CD8, or CD20 and then analyzed for SIV provirus using semiquantitative DNA amplification. We found provirus in CD4+ and CD8+ lymphocytes but none in CD20+ lymphocytes. During acute SIV infection (< or = 214 days postinoculation), the percentage of PBL and LNL CD4+ cells containing proviral DNA ranged from 0.2 to 20% and from 0.2 to 2%, respectively. Proviral burden in the CD8+ population of either PBL or LNL ranged from 0.01 to 0.2%. Virus isolation by cocultivation was positive for both CD4+ and CD8+ purified populations. No difference in proviral burden was observed between PBL and LNL subsets during acute SIV infection. Up to 19.4% of positively selected CD8+ cells also expressed CD4, and thus the provirus may reside within a dual-positive population. This dual-positive population may represent activated lymphocytes that are particularly susceptible to infection and may provide an opportunity for virus entry into the CD8+ CD4- lymphocytes in vivo. PMID:8764081

  8. Necrotizing lymphocytic folliculitis: the early lesion of acne necrotica (varioliformis).

    PubMed

    Kossard, S; Collins, A; McCrossin, I

    1987-05-01

    Skin biopsy specimens from four patients who had recurrent bouts of lesions conforming to the clinical description of acne necrotica were studied. The pathologic findings were dominated by lymphocytic inflammation around centrally placed follicles evolving to follicular necrosis that extended to the perifollicular epidermis and dermis. Early lesions showed the development of multiple individual necrotic keratinocytes within the follicular sheath and adjacent epidermis with lymphocytic exocytosis. Later lesions showed more intense necrosis and scale crust obscuring the central target but were still dominated by a peripheral lymphocytic infiltrate. The early pathologic findings of acne necrotica (varioliformis) are represented by a necrotizing lymphocytic folliculitis and differ from the pattern seen in association with nonspecific excoriations, acute bacterial folliculitis, classic comedogenic acne, or acnitis.

  9. Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2015-11-10

    Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  10. Lymphocytic Choriomeningitis Virus–associated Meningitis, Southern Spain

    PubMed Central

    Navarro-Marí, José-María; Sánchez-Seco, María-Paz; Gegúndez, María-Isabel; Palacios, Gustavo; Savji, Nazir; Lipkin, W. Ian; Fedele, Giovanni; de Ory-Manchón, Fernando

    2012-01-01

    Lymphocytic choriomeningitis virus (LCMV) was detected in 2 patients with acute meningitis in southern Spain within a 3-year period. Although the prevalence of LCMV infection was low (2 [1.3%] of 159 meningitis patients), it represents 2.9% of all pathogens detected. LCMV is a noteworthy agent of neurologic illness in immunocompetent persons. PMID:22515986

  11. What Is Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... About Chronic Lymphocytic Leukemia What Is Chronic Lymphocytic Leukemia? Cancer starts when cells in the body begin ... the lymph nodes, liver, and spleen. What is leukemia? Leukemia is a cancer that starts in the ...

  12. Morphologic and phenotypic characteristics of myocarditis in two pigs infected by foot-and mouth disease virus strains of serotypes O or A

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Myocarditis is often cited as the cause of fatalities associated with foot-and-mouth disease virus (FMDV) infection; however the pathogenesis of FMDV-associated myocarditis has not been described in detail. The current report describes substantial quantities of FMDV in association with a marked mono...

  13. Acute Appendicitis in Patients with Acute Leukemia

    PubMed Central

    Kim, Ki Up; Kim, Jin Kyeung; Won, Jong Ho; Hong, Dae Sik; Park, Hee Sook; Park, Kyeung Kyu

    1993-01-01

    The decision to operate for abdominal pain in patients with leukopenia can be exceedingly difficult. Surgical exploration may be the only effective way to differentiate acute appendicitis from other causes, but it involves considerable risk of infectious complications due to immunesuppression. Leukemic patients, who presented significant RLQ pain, had been indicated for operation, despite having advanced disease or having had received chemotherapy or steroids. Four adult leukemia patients, complicated by acute appendictis, were reviewed. Two patients were in induction chemotherapy, one receiving salvage chemotheapy due to relapse and the other was in conservative treatment. Two patients were acute myelocytic leukemia (AML), one had acute lymphocytic leukemia (ALL), and the other had aleukemic leukemia. All patients underwent appendectomy and recovered without complication. Our experience supports the theory that the surgical management of appendicitis in acute leukemia is the most effective way, in spite of leukopenia. PMID:8268146

  14. Hitch-hiker taken for a ride: an unusual cause of myocarditis, septic shock and adult respiratory distress syndrome

    PubMed Central

    Kushawaha, Anurag; Brown, Mark; Martin, Ismael; Evenhuis, Walther

    2013-01-01

    Rocky Mountain spotted fever (RMSF) is a serious tick-borne illness caused by Rickettsia rickettsii that is endemic in southeastern USA. Although RMSF has been described as causing the classic clinical triad of fever, headache and a characteristic rash, serious and potentially life-threatening manifestations can occur. Cardiopulmonary involvement, although infrequent, may occur with severe cases of RMSF. Rickettsial myocarditis is an uncommon occurrence. We present a case of a previously healthy 26-year-old man, who was hitch-hiking across the southeastern USA, with serologically proven RMSF causing adult respiratory distress syndrome, septic shock and myocarditis manifested by elevated cardiac enzymes and decrease in myocardial function. After treatment with antibiotics, the myocarditis resolved. Therefore, although unusual, clinicians should be aware of possible myocardial involvement in patients with appropriate tick-exposure histories or other clinical signs of RMSF. PMID:23314875

  15. Physiological changes induced in cardiac myocytes by cytotoxic T lymphocytes

    SciTech Connect

    Hassin, D.; Fixler, R.; Shimoni, Y.; Rubinstein, E.; Raz, S.; Gotsman, M.S.; Hasin, Y.

    1987-01-01

    The lethal hit induced by viral specific, sensitized, cytotoxic T lymphocytes (CTL) attacking virus-infected heart cells is important in the pathogenesis of viral myocarditis and reflects the key role of CTL in this immune response. The mechanisms involved are incompletely understood. Studies of the physiological changes induced in mengovirus-infected, cultured, neonatal, rat heart cells by CTL that had been previously sensitized by the same virus are presented. The CTL were obtained from spleens of mengovirus-infected, major histocompatibility complex (MHC) matched adult rats. Cell wall motion was measured by an optical method, action potentials with intracellular microelectrodes, and total exchangeable calcium content by /sup 45/Ca tracer measurements after loading the myocytes with /sup 45/Ca and then exposing them to CTL. After 50 min (mean time) of exposing mengovirus-infected myocytes to the CTL, the mechanical relaxation of the myocyte was slowed, with a subsequent slowing of beating rate and a reduced amplitude of contraction. Impaired relaxation progressed, and prolonged oscillatory contractions lasting up to several seconds appeared, with accompanying oscillations in the prolonged plateau phase of the action potentials. Arrest of the myocyte contractions appeared 98 min (mean time) after exposure to CTL. It is concluded that infection of cultured myocytes with mengovirus predisposes them to attack by mengovirus specific CTL, and that persistent dysfunction of the myocyte is preceded by reversible changes in membrane potential and contraction. This is suggestive of an altered calcium handling by the myocytes possibly resulting in the cytotoxic effect.

  16. Expression of miR-98 in myocarditis and its influence on transcription of the FAS/FASL gene pair.

    PubMed

    Zhang, B Y; Zhao, Z; Jin, Z

    2016-06-03

    Myocarditis is a common cardiovascular disease and frequently occurs in children and teenagers. It is believed to be caused by both endogenous and exogenous factors, among which FAS/FASL gene pair-induced cell apoptosis is a major mechanism of myocardial cell injury. A previous study has detected low expression of microRNA (miR)-98 in myocarditis patients. Therefore, in this study we investigated the functional implications of miR-98 with respect to the disease. We carried out a case-control study including 50 myocarditis patients and 50 healthy individuals. Total RNA was extracted from peripheral blood plasma. Expression levels of miR-98 and the FAS/FASL gene pair were determined by real-time fluorescent quantitative polymerase chain reaction. The interaction between miR-98 and the FAS/FASL pair was visualized by dual-luciferase reporter assay. The expression of the FAS/FASL gene pair was further detected by transfecting with an miR-98 mimic or an miR-98 inhibitor. The content of miR-98 in the peripheral blood of the myocarditis patients was significantly lower than in the healthy individuals. However, the FAS/FASL genes were upregulated by 1.68-fold in the myocarditis patients. miR-98 was shown to interact with the 3'-untranslated region of the FAS/FASL gene pair. The inhibition/facilitation of miR-98 expression in myocardial cells can modulate apoptosis. miR-98 was downregulated in the peripheral blood of myocarditis patients. It may interact with the FAS/FASL gene pair to further modulate cell apoptosis.

  17. Markedly Elevated Cardiac Bio-Markers at Presentation With Normal Ventricular Function: A Novel Clinical Subset of Myocarditis Manifestation

    PubMed Central

    Palla, Amruth R; Sontineni, Siva; Mani, Susan

    2011-01-01

    We present a case of a 19-year-old woman with myocarditis who had significantly elevated cardiac markers at presentation even before any myocardial damage ensued. The patient had complicated clinical course with ventricular arrhythmia and cardiac arrest requiring resuscitation but eventually recovered completely. Though there is limited information available regarding such cases, the significantly elevated initial cardiac markers in the absence of left ventricular decompensation may probably represent a clinical subset of myocarditis and may portend an impending complicated clinical course. Further systematic research is required to define the clinical phenotype and elucidate underlying mechanisms.

  18. Severe Legionnaires' disease with pneumonia and biopsy-confirmed myocarditis most likely caused by Legionella pneumophila serogroup 6.

    PubMed

    Ishimaru, Naoto; Suzuki, Hiromichi; Tokuda, Yasuharu; Takano, Tomoko

    2012-01-01

    We herein describe the successful treatment of a patient with possible Legionella pneumophila serogroup 6 infection complicated by pneumonia and myocarditis. A 32-year-old man presented with a five-day history of cough, dyspnea and chest pain. Chest radiography revealed patchy opacities in both lungs suggestive of bilateral pneumonia, and a urinary antigen test for Legionella pneumophila was positive. After admission, the patient developed congestive heart failure due to pathologically confirmed myocarditis. He was successfully treated with minocycline, macrolide, steroids and noninvasive positive-pressure ventilation (NPPV). He eventually recovered with a normalized cardiac function. L. pneumophila serogroup 6 was isolated from the bathwater in the patient's home.

  19. Use of venoarterial extracorporeal membrane oxygenation in fulminant chagasic myocarditis as a bridge to heart transplant

    PubMed Central

    Durães, André Rodrigues; Figueira, Fernando Augusto Marinho dos Santos; Lafayette, André Rabelo; Martins, Juliana de Castro Solano; Juliano Cavalcante de, Sá

    2015-01-01

    A 17-year-old Brazilian male presented with progressive dyspnea for 15 days, worsening in the last 24 hours, and was admitted in respiratory failure and cardiogenic shock, with multiple organ dysfunctions. Echocardiography showed a left ventricle ejection fraction of 11%, severe diffuse hypokinesia, and a systolic pulmonary artery pressure of 50mmHg, resulting in the need for hemodynamic support with dobutamine (20mcg/kg/min) and noradrenaline (1.7mcg/kg/min). After 48 hours with no clinical or hemodynamic improvement, an extracorporeal membrane oxygenation was implanted. The patient presented with hemodynamic, systemic perfusion and renal and liver function improvements; however, his cardiac function did not recover after 72 hours, and he was transfer to another hospital. Air transport was conducted from Salvador to Recife in Brazil. A heart transplant was performed with rapid recovery of both liver and kidney functions, as well as good graft function. Histopathology of the explanted heart showed chronic active myocarditis and amastigotes of Trypanosoma cruzi. The estimated global prevalence of T. cruzi infections declined from 18 million in 1991, when the first regional control initiative began, to 5.7 million in 2010. Myocarditis is an inflammatory disease due to infectious or non-infectious conditions. Clinical manifestation is variable, ranging from subclinical presentation to refractory heart failure and cardiogenic shock. Several reports suggest that the use of extracorporeal membrane oxygenation in patients presenting with severe refractory myocarditis is a potential bridging therapy to heart transplant when there is no spontaneous recovery of ventricular function. In a 6-month follow-up outpatient consult, the patient presented well and was asymptomatic. PMID:26761479

  20. Use of venoarterial extracorporeal membrane oxygenation in fulminant chagasic myocarditis as a bridge to heart transplant.

    PubMed

    Durães, André Rodrigues; Figueira, Fernando Augusto Marinho dos Santos; Lafayette, André Rabelo; Martins, Juliana de Castro Solano; de Sá, Juliano Cavalcante

    2015-01-01

    A 17-year-old Brazilian male presented with progressive dyspnea for 15 days, worsening in the last 24 hours, and was admitted in respiratory failure and cardiogenic shock, with multiple organ dysfunctions. Echocardiography showed a left ventricle ejection fraction of 11%, severe diffuse hypokinesia, and a systolic pulmonary artery pressure of 50mmHg, resulting in the need for hemodynamic support with dobutamine (20mcg/kg/min) and noradrenaline (1.7mcg/kg/min). After 48 hours with no clinical or hemodynamic improvement, an extracorporeal membrane oxygenation was implanted. The patient presented with hemodynamic, systemic perfusion and renal and liver function improvements; however, his cardiac function did not recover after 72 hours, and he was transfer to another hospital. Air transport was conducted from Salvador to Recife in Brazil. A heart transplant was performed with rapid recovery of both liver and kidney functions, as well as good graft function. Histopathology of the explanted heart showed chronic active myocarditis and amastigotes of Trypanosoma cruzi. The estimated global prevalence of T. cruzi infections declined from 18 million in 1991, when the first regional control initiative began, to 5.7 million in 2010. Myocarditis is an inflammatory disease due to infectious or non-infectious conditions. Clinical manifestation is variable, ranging from subclinical presentation to refractory heart failure and cardiogenic shock. Several reports suggest that the use of extracorporeal membrane oxygenation in patients presenting with severe refractory myocarditis is a potential bridging therapy to heart transplant when there is no spontaneous recovery of ventricular function. In a 6-month follow-up outpatient consult, the patient presented well and was asymptomatic.

  1. Peripheral Veno-Arterial Extracorporeal Membrane Oxygenation as a Bridge to Decision for Pediatric Fulminant Myocarditis.

    PubMed

    Okada, Noritaka; Murayama, Hiroomi; Hasegawa, Hiroki; Kawai, Satoru; Mori, Hiromitsu; Yasuda, Kazushi

    2016-08-01

    It is essential to establish an appropriate initial treatment strategy for pediatric fulminant myocarditis. We reviewed eight cases of pediatric fulminant myocarditis that required extracorporeal membrane oxygenation (ECMO) from 2012 to 2015. The median age was 8 years (range 3 months-13 years), and the median body surface area was 0.89 m(2) (range 0.35-1.34 m(2) ). Peripheral veno-arterial ECMO was initially applied, and we evaluated whether heart decompression was sufficient. If the pump flow was insufficient, central cannulation was performed via median sternotomy (central ECMO). The need for subsequent ventricular assist device (VAD) support was determined 72 h after ECMO initiation. Six patients were bridged to recovery using peripheral ECMO support only (for 3-11 days), whereas two required VAD support. One patient was switched to central ECMO before VAD implantation. Three patients died of multiorgan failure, even though cardiac function recovered in two of those patients. The duration from hospital arrival to ECMO initiation was shorter in the survival (3.3 ± 1.3 h; range 1.6-4.7 h) than in the nonsurvival group (32 ± 28 h; range 0.7-55 h). Peripheral ECMO can be useful as a bridge to decision for pediatric fulminant myocarditis, which is frequently followed by a successful bridge to recovery. It is important to determine whether ECMO support should be initiated before organ dysfunction advances to preserve organ function, which provides a better bridge to subsequent VAD therapy and heart transplant or recovery.

  2. Promising effects of Chinese traditional treatment for child typhoid complicated by myocarditis

    PubMed Central

    Tian, Jing; An, Xinjiang; Fu, Mingyu; Wang, Qingwen

    2016-01-01

    The clinical effects were compared and analyzed of traditional Chinese medicine (TCM) ‘Ling Gui Long Mu soup’ combined with the conventional Western medications in treating child typhoid complicated by myocarditis. From July, 2010 to May, 2014, 54 children suffering from typhoid complicated by myocarditis were enrolled in the present study. The patients were divided into the observation and control groups (n=27 cases per group) according to the random number table. Patients in the observation group were treated with basic Western medicine combined with TCM ‘Ling Gui Long Mu soup’ while patients in the control group were treated only with Western medicine. We analyzed the final curative effects in the two groups. The total effective rate in the observation group was significantly higher than that of the control group and the difference was statistically significant (P<0.05). The improvement rate of the syndrome in the TCM observation group was significantly higher than that in the control group and the difference was statistically significant (P<0.05). Although the C-reactive protein (CRP) and creatinine kinase-MB (CK-MB) levels in the two groups were decreased following the treatment, CRP and CK-MB levels in the observation group were further reduced, and the difference was statistically significant (P<0.05). In conclusion, for child typhoid complicated by myocarditis, TCM ‘Ling Gui Long Mu soup’ significantly improved the clinical efficiency of the treatment and improved the syndrome. Therefore, ‘Ling Gui Long Mu soup’ is useful in clinical practice. PMID:28101150

  3. Phosphoinositide hydrolysis mediated by H1 receptors in autoimmune myocarditis mice

    PubMed Central

    Goren, Nora; Leiros, Claudia Perez; Sterin-Borda, Leonor

    1993-01-01

    Stimulation of phosphoinositide hydrolysis in myocardium from autoimmune myocarditis mice by ThEA and histamine was assayed. Myocardium from autoimmune heart, but not the normal forms, specifically increased phosphoinositide turnover in the presence of histaminergic agonists. This increment was blocked by a specific H1 antagonist mepyramine and to the same extent by the phospholipase C inhibitor NCDC. By using a binding assay H1 histaminergic receptors were detected in autoimmune heart membrane preparations, but this was not observed in normal heart. These data suggest that autoimmune myocardium expressed a functional H1 receptor that could involve a distinctive mechanism operating in the disease. PMID:18475540

  4. Typhoid fever, complicated by myocarditis, in a traveller returning to the UK

    PubMed Central

    Shah, Shreena; Dubrey, Simon William

    2013-01-01

    A 25-year-old male returning traveller presented with sudden onset chest pain. An ECG showed infero-lateral ischaemic changes, with an elevated troponin and inflammatory markers. An echocardiogram showed a normal size left ventricle, dynamic systolic function, structurally normal valves and no regional wall motion abnormality. Angiography revealed normal coronary arteries. A diagnosis of myocarditis was made. Five days later, he developed a significant pyrexia and diarrhoea. Salmonella typhi was isolated from blood cultures. The fever and symptoms resolved after 2 weeks of an intravenous third generation cephalosporin and the patient was discharged. PMID:23417944

  5. Does the Influenza Vaccine Prevent Sequelae Such as Myocarditis from Developing?

    PubMed Central

    Whitney, Ryan; Dazley, Jason; Gilbert, Ryan; Slim, Jihad

    2015-01-01

    Vaccination continues to be a valuable and simple procedure to guard patients from an illness that may prevent them from completing their normal everyday tasks, missing days of work, and even lead to unnecessary sequelae. The following case describes one of the many complications that are seen on a regular basis in any community hospital in different regions of the world. The objective of this publication is to remind the public and practitioner of the urgency to vaccinate each season; thereby, curbing the virus's ability to mutate and preventing unwanted consequences such as bacterial super infection or myocarditis. PMID:26392720

  6. Ga-67 citrate myocardial uptake in a patient with AIDS, toxoplasmosis, and myocarditis

    SciTech Connect

    Memel, D.S.; DeRogatis, A.J.; William, D.C. )

    1991-05-01

    A 38-year-old man with AIDS presented with fever of unknown origin, splenomegaly, anemia, and thrombocytopenia. Admission laboratory data revealed a positive toxoplasmosis titer in the blood. The initial chest x-ray showed small bilateral pleural effusions, a normal cardiac silhouette, no infiltrates, and no interstitial edema. Ga-67 imaging revealed markedly abnormal uptake in the myocardium. A diagnosis of toxoplasmosis myocarditis was made based on laboratory and imaging data. The patient was treated for toxoplasmosis. No myocardial uptake of tracer was demonstrated on a follow-up Ga-67 scan, performed after completion of treatment for toxoplasmosis.

  7. Stressed to death: implication of lymphocyte apoptosis for psychoneuroimmunology.

    PubMed

    Shi, Yufang; Devadas, Satish; Greeneltch, Kristy M; Yin, Deling; Allan Mufson, R; Zhou, Jian-nian

    2003-02-01

    Psychological and physical stressors best exemplify the intercommunication of the immune and the nervous systems. It has been shown that stress significantly impacts leukocyte cellularity and immune responses and alters susceptibility to various diseases. While acute stress has been shown to enhance immune responses, chronic stress often leads to immunosuppression. Among many criteria examined upon exposure to chronic stress, the reduction in lymphocyte mitogenic response and lymphocyte cellularity are commonly assessed. We have reported that chronic restraint stress could induce lymphocyte reduction, an effect dependent on endogenous opioids. Interestingly, the effect of endogenous opioids was found to be exerted through increasing the expression of a cell death receptor, Fas, and an increased sensitivity of lymphocytes to apoptosis. Stress-induced lymphocyte reduction was not affected by adrenalectomy. In this review, based on available literature and our recent data, we will discuss the role of the hypothalamic-pituitary-adrenal axis and endogenous opioids and examine the mechanisms by which chronic stress modulates lymphocyte apoptosis.

  8. Stressed to death: implication of lymphocyte apoptosis for psychoneuroimmunology

    NASA Technical Reports Server (NTRS)

    Shi, Yufang; Devadas, Satish; Greeneltch, Kristy M.; Yin, Deling; Allan Mufson, R.; Zhou, Jian-nian

    2003-01-01

    Psychological and physical stressors best exemplify the intercommunication of the immune and the nervous systems. It has been shown that stress significantly impacts leukocyte cellularity and immune responses and alters susceptibility to various diseases. While acute stress has been shown to enhance immune responses, chronic stress often leads to immunosuppression. Among many criteria examined upon exposure to chronic stress, the reduction in lymphocyte mitogenic response and lymphocyte cellularity are commonly assessed. We have reported that chronic restraint stress could induce lymphocyte reduction, an effect dependent on endogenous opioids. Interestingly, the effect of endogenous opioids was found to be exerted through increasing the expression of a cell death receptor, Fas, and an increased sensitivity of lymphocytes to apoptosis. Stress-induced lymphocyte reduction was not affected by adrenalectomy. In this review, based on available literature and our recent data, we will discuss the role of the hypothalamic-pituitary-adrenal axis and endogenous opioids and examine the mechanisms by which chronic stress modulates lymphocyte apoptosis.

  9. Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2016-10-04

    Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

  10. Human lymphocyte markers defined by antibodies derived from somatic cell hybrids. II. A hybridoma secreting antibody against an antigen expressed by human B and null lymphocytes.

    PubMed

    Beckman, I G; Bradley, J; Brooks, D A; Kupa, A; McNamara, P J; Thomas, M E; Zola, H

    1980-06-01

    A hybridoma (FMC4) has been derived which secretes antibody showing selective reaction with human B lymphocytes, monocytes and some null lymphocytes. Few, if any, T lymphocytes in normal blood are stained, although stimulation of lymphocytes with PHA leads to an increase in the proportion of cells reacting with the hybridoma antibody. The antibody reacts with B and null lymphoblastoid cell lines but not with T cell lines. B chronic lymphocytic leukaemia (CLL) cells but not T-CLLs are stained and null-type acute lymphoblastic leukaemia (ALL) cells but not T-type ALL also react. Normal blood myeloid cells do not react with FMC4 supernatant whilst some myeloid leukaemias do. The expression of the antigen reacting with FMC4 supernatant suggests that FMC4 may secrete an antibody against the human equivalent of the Ia antigen.

  11. Human lymphocyte markers defined by antibodies derived from somatic cell hybrids. II. A hybridoma secreting antibody against an antigen expressed by human B and null lymphocytes.

    PubMed Central

    Beckman, I G; Bradley, J; Brooks, D A; Kupa, A; McNamara, P J; Thomas, M E; Zola, H

    1980-01-01

    A hybridoma (FMC4) has been derived which secretes antibody showing selective reaction with human B lymphocytes, monocytes and some null lymphocytes. Few, if any, T lymphocytes in normal blood are stained, although stimulation of lymphocytes with PHA leads to an increase in the proportion of cells reacting with the hybridoma antibody. The antibody reacts with B and null lymphoblastoid cell lines but not with T cell lines. B chronic lymphocytic leukaemia (CLL) cells but not T-CLLs are stained and null-type acute lymphoblastic leukaemia (ALL) cells but not T-type ALL also react. Normal blood myeloid cells do not react with FMC4 supernatant whilst some myeloid leukaemias do. The expression of the antigen reacting with FMC4 supernatant suggests that FMC4 may secrete an antibody against the human equivalent of the Ia antigen. PMID:6968260

  12. Unusual manifestations of acute Q fever: autoimmune hemolytic anemia and tubulointerstitial nephritis.

    PubMed

    Korkmaz, Serdal; Elaldi, Nazif; Kayatas, Mansur; Sencan, Mehmet; Yildiz, Esin

    2012-05-18

    Q fever is a worldwide zoonotic infection that caused by Coxiella burnetii, a strict intracellular bacterium. It may be manifested by some of the autoimmune events and is classified into acute and chronic forms. The most frequent clinical manifestation of acute form is a self-limited febrile illness which is associated with severe headache, muscle ache, arthralgia and cough. Meningoencephalitis, thyroiditis, pericarditis, myocarditis, mesenteric lymphadenopathy, hemolytic anemia, and nephritis are rare manifestations. Here we present a case of acute Q fever together with Coombs' positive autoimmune hemolytic anemia (AIHA) and tubulointerstitial nephritis treated with chlarithromycin, steroids and hemodialysis. Clinicians should be aware of such rare manifestations of the disease.

  13. What Is the Arrhythmic Substrate in Viral Myocarditis? Insights from Clinical and Animal Studies

    PubMed Central

    Tse, Gary; Yeo, Jie M.; Chan, Yin Wah; Lai, Eric T. H. Lai; Yan, Bryan P.

    2016-01-01

    Sudden cardiac death (SCD) remains an unsolved problem in the twenty-first century. It is often due to rapid onset, ventricular arrhythmias caused by a number of different clinical conditions. A proportion of SCD patients have identifiable diseases such as cardiomyopathies, but for others, the causes are unknown. Viral myocarditis is becoming increasingly recognized as a contributor to unexplained mortality, and is thought to be a major cause of SCD in the first two decades of life. Myocardial inflammation, ion channel dysfunction, electrophysiological, and structural remodeling may play important roles in generating life-threatening arrhythmias. The aim of this review article is to examine the electrophysiology of action potential conduction and repolarization and the mechanisms by which their derangements lead to triggered and reentrant arrhythmogenesis. By synthesizing experimental evidence from pre-clinical and clinical studies, a framework of how host (inflammation), and viral (altered cellular signaling) factors can induce ion electrophysiological and structural remodeling is illustrated. Current pharmacological options are mainly supportive, which may be accompanied by mechanical circulatory support. Heart transplantation is the only curative option in the worst case scenario. Future strategies for the management of viral myocarditis are discussed. PMID:27493633

  14. Inhibition of Drp1 attenuates mitochondrial damage and myocardial injury in Coxsackievirus B3 induced myocarditis.

    PubMed

    Lin, Lin; Zhang, Ming; Yan, Rui; Shan, Hu; Diao, Jiayu; Wei, Jin

    2017-03-11

    Viral myocarditis (VMC) is closely related to apoptosis, oxidative stress, innate immunity, and energy metabolism, which are all linked to mitochondrial dysfunction. A close nexus between mitochondrial dynamics and cardiovascular disease with mitochondrial dysfunction has been deeply researched, but there is still no relevant report in viral myocarditis. In this study, we aimed to explore the role of Dynamin-related protein 1 (Drp1)-linked mitochondrial fission in VMC. Mice were inoculated with the Coxsackievirus B3 (CVB3) and treated with mdivi1 (a Drp1 inhibitor). Protein expression of Drp1 was increased in mitochondria while decreased in cytoplasm and accompanied by excessive mitochondrial fission in VMC mice. In addition, midivi1 treatment attenuate inflammatory cells infiltration in myocardium of the mice, serum Cardiac troponin I (CTnI) and Creatine kinase-MB (CK-MB) level. Mdivi1 also could improved the survival rate of mice and mitochondrial dysfunction reflected as the up-regulated mitochondrial marker enzymatic activities of succinate dehydrogenase (SDH), cytochrome c oxidase (COX) and mitochondrial membrane potential (MMP). At the same time, mdivi1 rescued the body weight loss, myocardial injury and apoptosis of cardiomyocyte. Furthermore, decease in LVEDs and increase in EF and FS were detected by echocardiogram, which indicated the improved myocardial function. Thus, Drp1-linked excessive mitochondrial fission contributed to VMC and midivi1 may be a potential therapeutic approach.

  15. Myocarditis induced by targeted expression of the MCP-1 gene in murine cardiac muscle.

    PubMed Central

    Kolattukudy, P. E.; Quach, T.; Bergese, S.; Breckenridge, S.; Hensley, J.; Altschuld, R.; Gordillo, G.; Klenotic, S.; Orosz, C.; Parker-Thornburg, J.

    1998-01-01

    To explore the possible role of monocyte chemotactic protein (MCP-1) in inflammatory diseases of the heart, we expressed the murine MCP-1(JE) gene under the control of the alpha-cardiac myosin heavy chain promoter to attempt to target MCP-1 expression to the adult heart muscle. The five lines of transgenic mice thus produced showed targeted expression of MCP-1 transcripts and protein in the adult heart muscle and pulmonary vein but not in skeletal muscle. MCP-1 level in the transgenic hearts increased up to 30 to 45 days of age, and leukocyte infiltration into interstitium between cardiomyocytes increased up to 60 to 75 days. The infiltrate was mainly macrophages but not T cells. The presence of MCP-1 in the transgenic hearts did not induce cytokine production indicative of leukocyte activation. Echocardiographic analysis of 1-year-old mice that express MCP-1 in the myocardium and of age-matched controls revealed cardiac hypertrophy and dilation, increases in left ventricular (LV) mass, and systolic and diastolic left ventricular internal diameters. A significant decline in M-mode shortening fraction showed depressed contractile function. Transgenic hearts were 65% heavier, and histological analysis showed moderate myocarditis, edema, and some fibrosis. Thus, MCP-1 expression in the heart muscle may provide a model to investigate myocarditis and cardiomyopathy. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9422528

  16. Requirement for Pathogenic IL-23 Signaling Is Restricted to Initiation of Autoimmune Myocarditis

    PubMed Central

    Wu, Lei; Diny, Nicola L.; Ong, SuFey; Barin, Jobert G.; Hou, Xuezhou; Rose, Noel R.; Talor, Monica V.; Čiháková, Daniela

    2016-01-01

    Using a mouse model of experimental autoimmune myocarditis (EAM), we showed for the first time that IL-23 stimulation of CD4+ T cells is required only briefly at the initiation of GM-CFS-dependent cardiac autoimmunity. IL-23 signal, acting as a switch, turns on pathogenicity of CD4+ T cells, and becomes dispensable once autoreactivity is established. Il23a−/− mice failed to mount an efficient Th17 response to immunization, and were protected from myocarditis. However, remarkably, transient IL-23 stimulation ex vivo fully restored pathogenicity in otherwise nonpathogenic CD4+ T cells raised from Il23a−/− donors. Thus, IL-23 may no longer be necessary to uphold inflammation in established autoimmune diseases. In addition, we demonstrated that IL-23 induced GM-CSF mediates the pathogenicity of CD4+ T cells in EAM. The neutralization of GM-CSF abrogated cardiac inflammation. However, sustained IL-23 signaling is required to maintain IL-17A production in CD4+ T cells. Despite inducing inflammation in Il23a−/− recipients comparable to WT, autoreactive CD4+ T cells downregulated IL-17A production without persistent IL-23 signaling. This divergence on the controls of GM-CSF-dependent pathogenicity on one side and IL-17A production on the other side may contribute to the discrepant efficacies of anti-IL-23 therapy in different autoimmune diseases. PMID:26660726

  17. Remission of CVB3-induced myocarditis with Astragaloside IV treatment requires A20 (TNFAIP3) up-regulation.

    PubMed

    Gui, Jun; Chen, Ruizhen; Xu, Wei; Xiong, Sidong

    2015-04-01

    Viral myocarditis (VMC) most prevalently caused by coxsackievirus B3 (CVB3) infection is characterized by severe cardiac inflammation. Therapeutic options for the disease are still limited. Astragaloside IV (AST-IV), a purified small molecular saponin (C41 H68 O14 , MW 784), is the main active component of Chinese medical herb Astragalus which has been empirically prescribed for the treatment of heart dysfunction for centuries. In this study, we investigated the effect of AST-IV on CVB3-induced myocarditis and explored its possible mechanism involved. The results showed that AST-IV administration alleviated the severity of myocarditis and attenuated cardiac inflammation, which was mediated by inhibition of nuclear factor-kappaB (NF-κB) signalling. Importantly, we further identified that the inhibitory effect of AST-IV on NF-κB signalling was through increasing A20 (TNFAIP3) expression. Moreover, we validated that A20 was critical for the therapeutic efficacy of AST-IV on CVB3-induced myocarditis. Finally, we revealed that AST-IV enhanced A20 expression at post-transcriptional level by stabilization of mRNA. Our findings uncover a previously unknown mechanism for AST-IV in the treatment of VMC because of modulating inflammatory response via increasing A20 expression, which provide a potential target for screening new drugs and are helpful for optimization of the therapeutic strategies for VMC.

  18. Myocarditis in different experimental models infected by Trypanosoma cruzi is correlated with the production of IgG1 isotype.

    PubMed

    Caldas, Ivo Santana; Diniz, Livia de Figueiredo; Guedes, Paulo Marcos da Matta; Nascimento, Álvaro Fernando da Silva do; Galvão, Lúcia Maria da Cunha; Lima, Wanderson Geraldo de; Caldas, Sérgio; Bahia, Maria Terezinha

    2017-03-01

    This study was designed to verify the relationship between IgG antibodies isotypes and myocarditis in Trypanosoma cruzi infection using mice and dogs infected with different T. cruzi strains. The animals were infected with benznidazole-susceptible Berenice-78 and benznidazole-resistant AAS and VL-10 strains. The IgG subtypes were measured in serum samples from dogs (IgG, IgG1, and IgG2) and mice (IgG, IgG1, IgG2a, and IgG2b). The infection of dogs with VL-10 strain induced the highest levels of heart inflammation while intermediate and lower levels were detected with Berenice-78 and AAS strains, respectively. Similar results were found in mice infected with VL-10, but not in those infected with AAS or Berenice-78 strains. The AAS strain induced higher levels of heart inflammation in mice, while Berenice-78 strain was not able to induce it. Correlation analysis between myocarditis and antibody reactivity index revealed very interesting results, mainly for IgG and IgG1, the latter being the most exciting. High IgG1 showed a significant correlation with myocarditis in both experimental models, being more significant in dogs (r=0.94, p<0.0001) than in mice (r=0.58, p=0.047). Overall, our data suggest that IgG1 could be a good marker to demonstrate myocarditis intensity in Chagas disease.

  19. Remission of CVB3-induced myocarditis with Astragaloside IV treatment requires A20 (TNFAIP3) up-regulation

    PubMed Central

    Gui, Jun; Chen, Ruizhen; Xu, Wei; Xiong, Sidong

    2015-01-01

    Viral myocarditis (VMC) most prevalently caused by coxsackievirus B3 (CVB3) infection is characterized by severe cardiac inflammation. Therapeutic options for the disease are still limited. Astragaloside IV (AST-IV), a purified small molecular saponin (C41H68O14, MW 784), is the main active component of Chinese medical herb Astragalus which has been empirically prescribed for the treatment of heart dysfunction for centuries. In this study, we investigated the effect of AST-IV on CVB3-induced myocarditis and explored its possible mechanism involved. The results showed that AST-IV administration alleviated the severity of myocarditis and attenuated cardiac inflammation, which was mediated by inhibition of nuclear factor-kappaB (NF-κB) signalling. Importantly, we further identified that the inhibitory effect of AST-IV on NF-κB signalling was through increasing A20 (TNFAIP3) expression. Moreover, we validated that A20 was critical for the therapeutic efficacy of AST-IV on CVB3-induced myocarditis. Finally, we revealed that AST-IV enhanced A20 expression at post-transcriptional level by stabilization of mRNA. Our findings uncover a previously unknown mechanism for AST-IV in the treatment of VMC because of modulating inflammatory response via increasing A20 expression, which provide a potential target for screening new drugs and are helpful for optimization of the therapeutic strategies for VMC. PMID:25728713

  20. PRODUCTS OF ACTIVATED LYMPHOCYTES

    PubMed Central

    Sorg, Clemens; Bloom, Barry R.

    1973-01-01

    General methods were developed and applied to the biosynthesis and purification of products of activated lymphocytes available in minute quantities. The activity studied here was the migration inhibitory factor (MIF) produced by purified protein derivative (PPD)- or concanavalin A (Con A)-stimulated lymphocytes obtained from one guinea pig or less. The methods selected yielded results in terms of two chemical parameters characteristic of the molecules involved, namely Kd on Sephadex G-75 and isoionic point, pI, on isoelectric focusing. When supernatants were fractionated on G-75 columns, there were several areas even in control supernatants which produced migration inhibition relative to medium controls. However, in PPD- and Con A-stimulated supernatants, at least one peak of MIF activity was found solely in the stimulated cultures, with a Kd of 0.15. A double-labeling technique was used to characterize the proteins of this peak. Control, unstimulated cultures were labeled with [14C]leucine and stimulated cultures were labeled with [3H]leucine. After mixing the supernatants and G-75 filtration, a major "ratiolabeled" broad peak. i.e. one with increased 3H/14C ratio, was found. When a narrow portion of this peak about Kd 0.15, containing most of the MIF activity, was subjected to analytical isoelectric focusing, all of the label was associated with proteins of lower net charge than albumin. A unique ratiolabeled peak was found in PPD- and Con A-stimulated fractions with a pI of approx. 5.3. A micropreparative isoelectric focusing technique was developed and yielded MIF activity in the same region as the major ratiolabeled peak. Further study will be required to ascertain whether the ratiolabeled protein is MIF. By following the Kd, pI, and 3H/14C labeling ratio, at least 14 products of activated lymphocytes, synthesized either de novo or in increased amounts, could be distinguished. PMID:4688317

  1. Lymphocyte function in myasthenia gravis.

    PubMed Central

    Kawanami, S; Kanaide, A; Itoyama, Y; Kuroiwa, Y

    1979-01-01

    Mitogen-induced blastoid transformation of peripheral blood lymphocytes from patients with myasthenia gravis was studied using a microplate culture technique and evaluated with 3H-thymidine incorporation. It was found that both phytohaemagglutinin and pokeweed mitogen responses decreased significantly in patients with myasthenia gravis. In myasthenic crisis, indices of stimulation by phytohaemagglutination became very low. The autologous plasma neither inhibited nor facilitated mitogenic responses of lymphocytes. The decreased mitogen responsiveness of lymphocytes suggests that part of the T lymphocyte function is subnormal in myasthenia. PMID:490180

  2. Lymphocyte 'homing' and chronic inflammation.

    PubMed

    Sakai, Yasuhiro; Kobayashi, Motohiro

    2015-07-01

    Chronic inflammation is a response to prolonged exposure to injurious stimuli that harm and destroy tissues and promote lymphocyte infiltration into inflamed sites. Following progressive accumulation of lymphocytes, the histology of inflamed tissue begins to resemble that of peripheral lymphoid organs, which can be referred to as lymphoid neogenesis or formation of tertiary lymphoid tissues. Lymphocyte recruitment to inflamed tissues is also reminiscent of lymphocyte homing to peripheral lymphoid organs. In the latter, under physiological conditions, homing receptors expressed on lymphocytes adhere to vascular addressin expressed on high endothelial venules (HEVs), initiating a lymphocyte migration process composed of sequential adhesive interactions. Intriguingly, in chronic inflammation, HEV-like vessels are induced de novo, despite the fact that the inflamed site is not originally lymphoid tissue, and these vessels contribute to lymphocyte recruitment in a manner similar to physiological lymphocyte homing. In this review, we first describe physiological lymphocyte homing mechanisms focusing on vascular addressins. We then describe HEV-like vessel-mediated pathogenesis seen in various chronic inflammatory disorders such as Helicobacter pylori gastritis, inflammatory bowel disease (IBD), autoimmune pancreatitis and sclerosing sialadenitis, as well as chronic inflammatory cell neoplasm MALT lymphoma, with reference to our work and that of others.

  3. A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination

    DOE PAGES

    Engler, Renata J. M.; Nelson, Michael R.; Collins Jr., Limone C.; ...

    2015-03-20

    Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV).more » Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. In conclusion, passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a

  4. A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination

    SciTech Connect

    Engler, Renata J. M.; Nelson, Michael R.; Collins Jr., Limone C.; Spooner, Christina; Hemann, Brian A.; Gibbs, Barnett T.; Atwood, J. Edwin; Howard, Robin S.; Chang, Audrey S.; Cruser, Daniel L.; Gates, Daniel G.; Vernalis, Marina N.; Lengkeek, Marguerite S.; McClenathan, Bruce M.; Jaffe, Allan S.; Cooper, Leslie T.; Black, Steve; Carlson, Christopher; Wilson, Christopher; Davis, Robert L.; Horwitz, Marc S.

    2015-03-20

    Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. The study's primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV). Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. In conclusion, passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that

  5. A Prospective Study of the Incidence of Myocarditis/Pericarditis and New Onset Cardiac Symptoms following Smallpox and Influenza Vaccination

    PubMed Central

    Engler, Renata J. M.; Nelson, Michael R.; Collins Jr., Limone C.; Spooner, Christina; Hemann, Brian A.; Gibbs, Barnett T.; Atwood, J. Edwin; Howard, Robin S.; Chang, Audrey S.; Cruser, Daniel L.; Gates, Daniel G.; Vernalis, Marina N.; Lengkeek, Marguerite S.; McClenathan, Bruce M.; Jaffe, Allan S.; Cooper, Leslie T.; Black, Steve; Carlson, Christopher; Wilson, Christopher; Davis, Robert L.

    2015-01-01

    Background Although myocarditis/pericarditis (MP) has been identified as an adverse event following smallpox vaccine (SPX), the prospective incidence of this reaction and new onset cardiac symptoms, including possible subclinical injury, has not been prospectively defined. Purpose The study’s primary objective was to determine the prospective incidence of new onset cardiac symptoms, clinical and possible subclinical MP in temporal association with immunization. Methods New onset cardiac symptoms, clinical MP and cardiac specific troponin T (cTnT) elevations following SPX (above individual baseline values) were measured in a multi-center prospective, active surveillance cohort study of healthy subjects receiving either smallpox vaccine or trivalent influenza vaccine (TIV). Results New onset chest pain, dyspnea, and/or palpitations occurred in 10.6% of SPX-vaccinees and 2.6% of TIV-vaccinees within 30 days of immunization (relative risk (RR) 4.0, 95% CI: 1.7-9.3). Among the 1081 SPX-vaccinees with complete follow-up, 4 Caucasian males were diagnosed with probable myocarditis and 1 female with suspected pericarditis. This indicates a post-SPX incidence rate more than 200-times higher than the pre-SPX background population surveillance rate of myocarditis/pericarditis (RR 214, 95% CI 65-558). Additionally, 31 SPX-vaccinees without specific cardiac symptoms were found to have over 2-fold increases in cTnT (>99th percentile) from baseline (pre-SPX) during the window of risk for clinical myocarditis/pericarditis and meeting a proposed case definition for possible subclinical myocarditis. This rate is 60-times higher than the incidence rate of overt clinical cases. No clinical or possible subclinical myocarditis cases were identified in the TIV-vaccinated group. Conclusions Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post

  6. Lymphocytic Interstitial Pneumonia.

    PubMed

    Panchabhai, Tanmay S; Farver, Carol; Highland, Kristin B

    2016-09-01

    Lymphocytic interstitial pneumonia (LIP) is a rare lung disease on the spectrum of benign pulmonary lymphoproliferative disorders. LIP is frequently associated with connective tissue diseases or infections. Idiopathic LIP is rare; every attempt must be made to diagnose underlying conditions when LIP is diagnosed. Computed tomography of the chest in patients with LIP may reveal ground-glass opacities, centrilobular and subpleural nodules, and randomly distributed thin-walled cysts. Demonstrating polyclonality with immunohistochemistry is the key to differentiating LIP from lymphoma. The 5-year mortality remains between 33% and 50% and is likely to vary based on the underlying disease process.

  7. Anti-lymphocyte antibodies late in the course of pediatric renal transplantation.

    PubMed

    Butani, L; Polinsky, M S; Kaiser, B A; Baluarte, H J

    1999-04-01

    Beyond the immediate post-transplant period, physicians are often reluctant to use anti-lymphocyte preparations to treat episodes of acute renal functional deterioration attributable to acute rejection. This is due to the perception that such episodes are less likely to be reversible, and to concern regarding the potential adverse effects of anti-lymphocyte antibodies, including opportunistic infections, lymphoproliferative disorders, and the development of human anti-mouse antibodies. Records were reviewed for all 365 renal transplants performed in 267 patients at our center from 1971 to 1996. Anti-lymphocyte antibodies were used in an attempt to reverse 6 episodes of corticosteroid-resistant acute rejection in 5 children at a mean interval of 24.5 months following transplantation. The mean serum creatinine at initiation of therapy with the anti-lymphocyte agents was 2.9 mg/dl. Following treatment, the mean serum creatinine decreased to 1.3 mg/dl (P=0.03, Student's t-test). Two patients developed uncomplicated opportunistic infections after completion of anti-lymphocyte therapy; none have developed lymphoproliferative disorders or antibodies to OKT3. We conclude that in the correct clinical setting with corticosteroid-resistant acute rejection, the use of anti-lymphocyte antibodies should not be withheld solely on the basis of length of time since transplantation.

  8. NK-derived IFN-γ/IL-4 triggers the sexually disparate polarization of macrophages in CVB3-induced myocarditis.

    PubMed

    Liu, Li; Yue, Yan; Xiong, Sidong

    2014-11-01

    Coxsackievirus B3 (CVB3) is a common etiology of myocarditis with an increased morbidity and mortality in males. We previously reported that differential polarization of macrophages contributed to sexually dimorphic susceptibility of mice to CVB3-induced myocarditis. However, the underlying kinetics, impetus as well as the molecular mechanism remain unclear. Here, we demonstrated that myocardial macrophages started to polarize at as early as day 5 post CVB3 infection in both genders of BALB/c mice, with M1 phenotype detected in males and M2a phenotype in females, and this trend was further amplified at day 7 when myocarditis reached peak. In addition, we identified that prevailed IFN-γ in males and dominant IL-4 in females were critical myocardial cytokines for the disparate macrophage polarization, which respectively activated JAK1-STAT1 and JAK3-STAT6 pathways. Strikingly, we found that the main source of IFN-γ and IL-4 cytokines in both genders were myocardial infiltrating NK cells, which differentially secreted cytokines in various microenvironments manifested synergistically by sex hormones and CVB3 infection. Consistently, depletion of NK cells significantly impeded the myocardial macrophage polarization in both genders of CVB3-infected mice. Collectively, these data indicated that myocardial NK-derived IFN-γ/IL-4 was critical for the differential polarization of macrophages in CVB3-induced myocarditis via activating JAK1-STAT1 and JAK3-STAT6 pathways respectively. Our study may help understand the mechanism of sexually differential polarization of macrophages and provide clues for the gender bias in CVB3-induced myocarditis.

  9. Protective effect of captopril against clozapine-induced myocarditis in rats: role of oxidative stress, proinflammatory cytokines and DNA damage.

    PubMed

    Abdel-Wahab, Basel A; Metwally, Metwally E; El-khawanki, Mohamed M; Hashim, Alaa M

    2014-06-05

    Clozapine (CLZ) is the most effective therapeutic alternative in the treatment of resistant schizophrenia. However, the cardiotoxicity of CLZ, particularly in young patients, has raised concerns about its safety. Captopril is a well-known angiotensin-converting enzyme inhibitor with antioxidant properties effective in treating hypertension and heart failure. The aim of this study was to investigate the protective effect of captopril against clozapine-induced myocarditis in rats and the possible mechanisms behind this effect. The effect of captopril treatment [5 or 10mg/kg/d, injected intraperitoneally (i.p.) for 21days] on the cardiotoxic effect of coadministered CLZ (25mg/kg/d, i.p.) was assessed. Myocarditis was assessed histopathologically, immunohistochemically and biochemically. Frozen heart specimens were used to determine the amount of lipid peroxides product (MDA), nitric oxide (NO), reduced glutathione (GSH), glutathione peroxidase (GSH-Px) activity, proinflammatory cytokines (TNF-α and IL-10) and DNA degradation product(8-OHdG). Coadministration of captopril with the tested doses of CLZ decreased the histological hallmarks and biochemical markers (CK-MP and LDH) of myocarditis. In addition, captopril attenuated the effects of CLZ on oxidative stress parameters, NO and serum and cardiac 8-OHdG levels. Captopril significantly attenuated the effect of CLZ on all measured parameters in a dose-dependent manner. These results suggested that captopril exerts a protective action against CLZ-induced myocarditis. Multiple mechanisms contribute to this effect, including a decrease in cardiac oxidative stress and proinflammatory cytokines production, modulation of antioxidant status and protection from oxidative DNA damage. Hence, captopril may be effective in reducing the incidence and severity of CLZ-induced myocarditis in humans.

  10. Decreased deformability of lymphocytes in chronic lymphocytic leukemia

    NASA Astrophysics Data System (ADS)

    Zheng, Yi; Wen, Jun; Nguyen, John; Cachia, Mark A.; Wang, Chen; Sun, Yu

    2015-01-01

    This paper reports the first study of stiffness/deformability changes of lymphocytes in chronic lymphocytic leukemia (CLL) patients, demonstrating that at the single cell level, leukemic metastasis progresses are accompanied by biophysical property alterations. A microfluidic device was utilized to electrically measure cell volume and transit time of single lymphocytes from healthy and CLL patients. The results from testing thousands of cells reveal that lymphocytes from CLL patients have higher stiffness (i.e., lower deformability), as compared to lymphocytes in healthy samples, which was also confirmed by AFM indentation tests. This observation is in sharp contrast to the known knowledge on other types of metastatic cells (e.g., breast and lung cancer cells) whose stiffness becomes lower as metastasis progresses.

  11. [Morphometric analysis of lymphocyte nuclei in chronic lymphocytic leukemia].

    PubMed

    Ostapenko, V A; Kruchinskiĭ, N G; Smirnova, L A; Cherednik, A B; Nesterov, V N; Tepliakov, A I

    1994-01-01

    This work is dedicated to the study of use of quantitative analysis of cell nucleus structure for the analysis of peripheral blood lymphocytes in patients with chronic lymphocytic leukaemia. The structure of lymphocytic nuclei of healthy donors was evaluated by means of staining by toluidine blue purified cell suspensions smears. The preparations were analysed on the television measuring system "omnicon" with measurements of the following parameters: square of the nucleus, euchromatin, heterochromatin, and the ratio of heterochromatin and euchromatin squares. Actuarial analysis and nuclei classification of the previously mentioned parameters showed, that in peripheral blood of patients with chronic lymphocytic leukemia a large amount of atypical lymphocytes is present with reduced nucleus sizes. Atypical cells retain the ratio of structural components of chromatine, characteristic to normal cells, which show their low proliferative activity.

  12. Chronic lymphocytic leukaemia

    PubMed Central

    Kipps, Thomas J.; Stevenson, Freda K.; Wu, Catherine J.; Croce, Carlo M.; Packham, Graham; Wierda, William G.; O’Brien, Susan; Gribben, John; Rai, Kanti

    2017-01-01

    Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5+ B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all. Several factors, including the immunoglobulin heavy-chain variable region gene (IGHV) mutational status, genomic changes, patient age and the presence of comorbidities, should be considered when defining the optimal management strategies, which include chemotherapy, chemoimmunotherapy and/or drugs targeting B cell receptor signalling or inhibitors of apoptosis, such as BCL-2. Research on the biology of CLL has profoundly enhanced our ability to identify patients who are at higher risk for disease progression and our capacity to treat patients with drugs that selectively target distinctive phenotypic or physiological features of CLL. How these and other advances have shaped our current understanding and treatment of patients with CLL is the subject of this Primer. PMID:28102226

  13. Activated T lymphocytes in uveitis.

    PubMed Central

    Deschênes, J.; Char, D. H.; Kaleta, S.

    1988-01-01

    Two colour flow cytometry techniques were used to assess the activation stages of peripheral and intraocular T lymphocytes in uveitis. Increased numbers of T lymphocytes bearing the interleukin-2 (IL-2) receptors were found in intraocular fluids or peripheral blood or both of 35/51 patients with uveitis. This increased expression of IL-2 receptors on lymphocytes correlated with increased expression of other early T lymphocyte activation markers, HLA-DR and L-35. Both T helper cells (Leu-3A+) and suppressor cells (Leu 2A+) were activated in vivo. A positive correlation was seen between lymphocyte activation and clinical uveitis activity. In idiopathic uveitis activation of Leu-3A lymphocytes (helper/inducer) was significantly increased, and intraocular activation of the Leu-2A lymphocytes (cytotoxic/suppressor) was significantly decreased. These data show that some patients with idiopathic uveitis have a perturbation of T helper cells. Twenty-two of 31 patients with idiopathic uveitis, not associated with systemic disease, had increased peripheral T lymphocyte activation. This finding indicates that in some inflammations believed to be restricted to the eye an abnormal systemic immune activation exists. PMID:2964862

  14. Obinutuzumab in chronic lymphocytic leukemia.

    PubMed

    Dupuis, Jehan

    2015-09-01

    Obinutuzumab is the second next-generation monoclonal anti-CD20 antibody (after ofatumumab) to enter clinical practice in chronic lymphocytic leukemia. Its superiority in association with chlorambucil as compared with chlorambucil alone has led to its approval as a first-line treatment for chronic lymphocytic leukemia, for patients who are not candidates for a more intensive treatment.

  15. Scaling Aspects of Lymphocyte Trafficking

    PubMed Central

    Perelson, Alan S.; Wiegel, Frederik W.

    2010-01-01

    We consider the long lived pool of B and T cells that recirculate through blood, tissues and the lymphatic system of an animal with body mass M. We derive scaling rules (allometric relations) for: (1) the rate of production of mature lymphocytes; (2) the accumulation of lymphocytes in the tissues; (3) the flux of lymphocytes through the lymphatic system; (4) the number of lymph nodes, (5) the number of lymphocytes per clone within a lymph node, and (6) the total number of lymphocytes within a lymph node. Mass-dependent aspects of immune learning and of the immunological self are shown to be not very significant. Our treatment is somewhat heuristic and aims at a combination of immunological data with recent progress in biological scaling. PMID:19084024

  16. Genetically Engineered Lymphocyte Therapy in Treating Patients With Lymphoma That is Resistant or Refractory to Chemotherapy

    ClinicalTrials.gov

    2015-09-27

    Hematopoietic/Lymphoid Cancer; Adult Acute Lymphoblastic Leukemia in Remission; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma

  17. Molecular Mechanisms of Particle Ration Induced Apoptosis in Lymphocyte

    NASA Astrophysics Data System (ADS)

    Shi, Yufang

    Space radiation, composed of high-energy charged nuclei (HZE particles) and protons, has been previously shown to severely impact immune homeostasis in mice. To determine the molecular mechanisms that mediate acute lymphocyte depletion following exposure to HZE particle radiation mice were exposed to particle radiation beams at Brookhaven National Laboratory. We found that mice given whole body 5 6Fe particle irradiation (1GeV /n) had dose-dependent losses in total lymphocyte numbers in the spleen and thymus (using 200, 100 and 50 cGy), with thymocytes being more sensitive than splenocytes. All phenotypic subsets were reduced in number. In general, T cells and B cells were equally sensitive, while CD8+ T cells were more senstive than CD4+ T cells. In the thymus, immature CD4+CD8+ double-positive thymocytes were exquisitely sensitive to radiation-induced losses, single-positive CD4 or CD8 cells were less sensitive, and the least mature double negative cells were resistant. Irradiation of mice deficient in genes encoding essential apoptosis-inducing proteins revealed that the mechanism of lymphocyte depletion is independent of Fas ligand and TRAIL (TNF-ralated apoptosis-inducing ligand), in contrast to γ-radiation-induced lymphocyte losses which require the Fas-FasL pathway. Using inhibitors in vitro, lymphocyte apoptosis induced by HZE particle radiation was found to be caspase dependent, and not involve nitric oxide or oxygen free radicals.

  18. Severe necrotizing myocarditis caused by serratia marcescens infection in an axolotl (Ambystoma mexicanum).

    PubMed

    Del-Pozo, J; Girling, S; Pizzi, R; Mancinelli, E; Else, R W

    2011-05-01

    This report provides the first account of the pathological changes associated with infection by Serratia marcescens in an adult male axolotl. The infection resulted in septicaemia with severe multifocal necrotizing myocarditis. The latter lesion evolved to cardiac rupture, haemopericardium and death resulting from cardiac tamponade. This animal was exposed to higher than usual temperatures (24-25 °C) 2 weeks before the onset of disease and this may have resulted in immunocompromise and opportunistic bacterial infection. S. marcescens was isolated from the coelomic and pericardial cavity. Both isolates were identical and were resistant to β-lactam antibiotics, but not to aminoglycosides or fluoroquinolones. The production of red prodigiosin pigment by the bacterium suggested an environmental origin. Overall, the clinical and histopathological presentation suggests that S. marcescens should be included in the list of aetiological agents of the 'red-leg'/bacterial dermatosepticaemia syndrome of amphibians.

  19. Autoanti-idiotypes exhibit mimicry of myocyte antigens in virus-induced myocarditis.

    PubMed Central

    Paque, R E; Miller, R

    1991-01-01

    Mice infected with coxsackievirus B develop immunologically mediated inflammatory myocarditis in heart tissue that results in the development of autoantibodies with multiple idiotypes. The specificity and temporal development of autoantibodies produced during coxsackievirus B3 infection were assessed. Antiviral idiotypes and anti-idiotypic antibodies against coxsackievirus B3 idiotypes were detected and quantitated over 21- and 42-day periods, respectively. Both polyclonal and monoclonal anti-idiotypes exhibited greater but nonspecific binding to heart, liver, kidney, and spleen cells from virus-exposed animals and normal tissue. Binding of anti-idiotypes was also demonstrated to myosin and to solubilized heart-associated antigens but not to virus. Western immunoblot analysis revealed that monoclonal and polyclonal anti-idiotypes selectively bound to hypertonic, salt-extracted, solubilized proteins of myocyte extracts of virus-exposed animals. Images PMID:1845881

  20. Inflammatory response to clozapine in the absence of myocarditis: case report

    PubMed Central

    Gee, Siobhan; Shergill, Sukhi S.

    2016-01-01

    Summary A case is presented of a 25-year-old man with treatment-resistant paranoid schizophrenia whose only previous trial of clozapine had been stopped following a suspected clozapine-induced myocarditis. Due to the failure of his psychosis to respond to a number of antipsychotic treatments and augmentation strategies, clozapine was restarted on admission. His rechallenge was marked by intermittent pyrexia, tachycardia and elevated C-reactive protein (CRP), but eosinophilia was absent. Clozapine was started and then stopped twice following extensive investigation and with specialist cardiology consultation. Physical symptoms and CRP elevation resolved shortly after clozapine cessation. We believe this constituted an idiosyncratic systemic inflammatory response to clozapine treatment. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. PMID:27703781

  1. Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in rats

    PubMed Central

    Nakagawa, Pablo; Liu, Yunhe; Liao, Tang-Dong; Chen, Xiaojuan; González, Germán E.; Bobbitt, Kevin R.; Smolarek, Derek; Peterson, Ed L.; Kedl, Ross; Yang, Xiao-Ping; Rhaleb, Nour-Eddine

    2012-01-01

    Myocarditis is commonly associated with cardiotropic infections and has been linked to development of autoimmunity. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a naturally occurring tetrapeptide that prevents inflammation and fibrosis in hypertension and other cardiovascular diseases; however, its effect on autoimmune-mediated cardiac diseases remains unknown. We studied the effects of Ac-SDKP in experimental autoimmune myocarditis (EAM), a model of T cell-mediated autoimmune disease. This study was conducted to test the hypothesis that Ac-SDKP prevents autoimmune myocardial injury by modulating the immune responses. Lewis rats were immunized with porcine cardiac myosin and treated with Ac-SDKP or vehicle. In EAM, Ac-SDKP prevented both systolic and diastolic cardiac dysfunction, remodeling as shown by hypertrophy and fibrosis, and cell-mediated immune responses without affecting myosin-specific autoantibodies or antigen-specific T cell responses. In addition, Ac-SDKP reduced cardiac infiltration by macrophages, dendritic cells, and T cells, pro-inflammatory cytokines [interleukin (IL)-1α, tumor necrosis factor-α, IL-2, IL-17] and chemokines (cytokine-induced neutrophil chemoattractant-1, interferon-γ-induced protein 10), cell adhesion molecules (intercellular adhesion molecule-1, L-selectin), and matrix metalloproteinases (MMP). Ac-SDKP prevents autoimmune cardiac dysfunction and remodeling without reducing the production of autoantibodies or T cell responses to cardiac myosin. The protective effects of Ac-SDKP in autoimmune myocardial injury are most likely mediated by inhibition of 1) innate and adaptive immune cell infiltration and 2) expression of proinflammatory mediators such as cytokines, chemokines, adhesion molecules, and MMPs. PMID:22923621

  2. Meningitis caused by lymphocytic choriomeningitis virus in a patient with leukemia.

    PubMed

    Al-Zein, Naser; Boyce, Thomas G; Correa, Armando G; Rodriguez, Vilmarie

    2008-10-01

    We report a case of 15-year-old girl with T-cell acute lymphoblastic leukemia who had fever, neutropenia, and severe headache while receiving maintenance chemotherapy. Cerebrospinal fluid testing revealed a lymphocytic pleocytosis and no evidence of relapsed leukemia. Meningitis caused by lymphocytic choriomeningitis virus was identified serologically. The patient's course was complicated by hydrocephalus requiring ventriculoperitoneal shunt placement and by an intracranial hemorrhage. Lymphocytic choriomeningitis virus is a rare cause of aseptic meningitis that should be considered in the symptomatic immunocompromised patient with an appropriate exposure history.

  3. Treatment of Chronic Lymphocytic Leukemia by Risk Group

    MedlinePlus

    ... Chronic Lymphocytic Leukemia Typical Treatment of Chronic Lymphocytic Leukemia Treatment options for chronic lymphocytic leukemia (CLL) vary ... Treating Hairy Cell Leukemia More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  4. Drug-induced pulmonary edema and acute respiratory distress syndrome.

    PubMed

    Lee-Chiong, Teofilo; Matthay, Richard A

    2004-03-01

    Noncardiogenic pulmonary edema, and, to a lesser extent, acute respiratory distress syndrome (ARDS), are common clinical manifestations of drug-induced lung diseases. Clinical features and radiographic appearances are generally indistinguishable from other causes of pulmonary edema and ARDS. Typical manifestations include dyspnea, chest discomfort, tachypnea, and hypoxemia. Chest radiographs commonly reveal interstitial and alveolar filling infiltrates. Unlike pulmonary edema that is due to congestive heart failure, cardiomegaly and pulmonary vascular redistribution are generally absent in cases that are drug-related. Rare cases of drug-induced myocarditis with heart failure and pulmonary edema have been described. Results from laboratory evaluation and respiratory function tests are nonspecific.

  5. Lymphocyte abnormalities in ankylosing spondylitis.

    PubMed Central

    Fan, P T; Clements, P J; Yu, D T; Opelz, G; Bluestone, R

    1977-01-01

    Peripheral blood T (SRBC rosette) and B (AgG- and C-receptor) lymphocyte subpopulations and responsiveness to phytohaemagglutinin (PHA) were assayed in 40 patients with ankylosing spondylitis and in 55 normal subjects. There was no significant difference in the lymphocyte concentrations or responsiveness to PHA between the two groups. However, the percentages of T lymphocytes were significantly lower in the patients irrespective of their HLA typing. This was probably due to an increase in the 'null' population since the percentages of both the AgG- and C-receptor cells were normal. PMID:303501

  6. Significance of intraepithelial lymphocytes in appendix.

    PubMed

    Deniz, Kemal; Sökmensüer, Lale Karakoç; Sökmensüer, Cenk; Patiroğlu, Tahir Ercan

    2007-01-01

    The aim of this study was to investigate the importance of the increase in intraepithelial lymphocytes (IELs) in the mucosa of the appendix. One hundred and four retrospective appendectomy specimens were examined to evaluate the IELs. Intraepithelial lymphocytosis was identified in 11.5% (12 cases) of the specimens. Of these 12 cases, 6 cases with intraepithelial lymphocytosis were associated with parasitic infection. No increase in IELs was found in the 36 appendices that were removed in other primary operations. A wide range of immunologic stimuli can raise IELs in the gastrointestinal system. However, in appendectomies with clinical signs of acute appendicitis, an increase in IELs is more likely to be related to parasitic infection. This increase should be considered for the diagnosis of parasitic infections.

  7. T-lymphocyte responsiveness in murine schistosomiasis mansoni is dependent upon the adhesion molecules intercellular adhesion molecule-1, lymphocyte function-associated antigen-1, and very late antigen-4.

    PubMed Central

    Langley, J G; Boros, D L

    1995-01-01

    Granuloma formation in murine schistosomiasis is dependent on CD4+ Th lymphocytes and requires recruitment and accumulation of inflammatory cells at the site of egg deposition. The present study examined the role of three adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1), and very late antigen-4 (VLA-4), that participate in cellular recruitment, interaction, and lymphocyte activation during in vitro activation of acutely and chronically infected spleen and liver granuloma lymphocytes. Blockade of ICAM-1, LFA-1, or VLA-4 by rat monoclonal antibody inhibited spleen and granuloma lymphocyte interleukin-2 (IL-2) and IL-4 production as well as lymphoproliferative responses at similar levels (66 to 87%). The down-modulated cytokine and proliferative responses of chronically infected lymphocytes were inhibited to the same extent as their acutely infected counterparts. Cell sorting analysis demonstrated that acutely and chronically infected splenic and granuloma lymphocytes expressed similar levels of LFA-1, ICAM-1, and VLA-4 and that more ICAM-1 was expressed on infected than on uninfected mouse lymphocytes. By exposure of cells to paired monoclonal antibodies at suboptimal doses, it was determined that whereas all three adhesion molecules may participate, only ICAM-1 and LFA-1 showed synergistic interactions in determining lymphocyte responsiveness. These data suggest that spleen and liver granuloma lymphocytes are equally well armed with functional adhesion receptors. Thus, ICAM-1, LFA-1, and VLA-4 play an important accessory role in inflammatory cytokine production and lymphocyte proliferation, and therefore these adhesion molecules may participate in the initiation and maintenance of the granulomatous inflammation. PMID:7558308

  8. Proteolysis of lymphocytic surface immunoglobulin.

    PubMed Central

    Hough, D W; McIlroy, B M; Stevenson, G T

    1977-01-01

    Limited proteolysis of lymphocytic surface immunoglobulins in guinea-pig, rabbit and man was investigated by immunofluorescence using conjugated antisera specific for immunoglobulin fragments. The cell surface IgM of guinea pig L2C leukaemic lymphocytes and rabbit blood lymphocytes was cleaved in situ at its hinge region by papain. The Fcmicron fragment remained attached to the membrane and could be stained with the appropriate anti-Fc conjugate. The surface IgD and IgM of human chronic lymphocytic leukaemia cells was cleared from the cell surface by papain, as shown by reagents directed against both Fab and Fc region determinants. This could be due either to proteolytic degradation of membrane bound Fc or to initial cleavage of Ig from the membrane at some point other than the hinge region. PMID:321347

  9. A premature low-birth-weight infant with congenital complete atrioventricular block and myocarditis successfully treated by staged pacemaker implantation.

    PubMed

    Fujioka, Tao; Nii, Masaki; Tanaka, Yasuhiko

    2016-06-01

    Congenital complete atrioventricular block is a known lethal condition. Although antenatal diagnosis and the technical advances of pacemaker treatment have reduced its mortality, treatment of premature babies with significant myocardial damage remains a challenge. In this paper, we report the case of a premature low-birth-weight infant with congenital complete atrioventricular block and extremely low ventricular rate, fetal hydrops, and myocarditis who was successfully treated with staged permanent pacemaker implantation.

  10. Chronic Lymphocytic Leukemia

    PubMed Central

    Motta, Marina; Wierda, William G.; Ferrajoli, Alessandra

    2015-01-01

    Patients with purine analogue-refractory chronic lymphocytic leukemia (CLL) have short survival and limited treatment options. Defining the best salvage strategies for this population is challenging, because limited data are available from clinical trials, and because studies have enrolled mixed populations (patients with recurrent and refractory disease or patients with refractory disease and Richter transformation). Moreover, patients with refractory CLL have a high incidence of unfavorable molecular and clinical features, such as high-risk genomic profiles, unmutated immunoglobulin heavy-chain genes, expression of zeta-chain-associated protein kinase 70, and bulky lymphadenopathies. These patients are also severely immunosuppressed because of the underlying disease and the treatments received, and experience a high rate of infectious complications that pose an additional difficulty in selecting treatment. Despite these challenges, in parallel with better characterizations of the biologic features of refractory CLL, the number of available treatment modalities for this population has increased. Several chemoimmunotherapy combinations have been developed, and novel agents with a different mechanism of action are being investigated in clinical trials. Furthermore, allogeneic stem cell transplantation with nonmyeloablative conditioning regimens is a therapeutic strategy that is increasingly offered to patients with refractory CLL. PMID:19536902

  11. Quantifying T Lymphocyte Turnover

    PubMed Central

    De Boer, Rob J.; Perelson, Alan S.

    2013-01-01

    Peripheral T cell populations are maintained by production of naive T cells in the thymus, clonal expansion of activated cells, cellular self-renewal (or homeostatic proliferation), and density dependent cell life spans. A variety of experimental techniques have been employed to quantify the relative contributions of these processes. In modern studies lymphocytes are typically labeled with 5-bromo-2′-deoxyuridine (BrdU), deuterium, or the fluorescent dye carboxy-fluorescein diacetate succinimidyl ester (CFSE), their division history has been studied by monitoring telomere shortening and the dilution of T cell receptor excision circles (TRECs) or the dye CFSE, and clonal expansion has been documented by recording changes in the population densities of antigen specific cells. Proper interpretation of such data in terms of the underlying rates of T cell production, division, and death has proven to be notoriously difficult and involves mathematical modeling. We review the various models that have been developed for each of these techniques, discuss which models seem most appropriate for what type of data, reveal open problems that require better models, and pinpoint how the assumptions underlying a mathematical model may influence the interpretation of data. Elaborating various successful cases where modeling has delivered new insights in T cell population dynamics, this review provides quantitative estimates of several processes involved in the maintenance of naive and memory, CD4+ and CD8+ T cell pools in mice and men. PMID:23313150

  12. Acute pancreatitis: a lesser-known complication of aluminum phosphide poisoning.

    PubMed

    Verma, S K; Ahmad, S; Shirazi, N; Barthwal, S P; Khurana, D; Chugh, M; Gambhir, H S

    2007-12-01

    There have been no case reports on aluminum phosphide-induced pancreatitis in the literature available. In this report, we present the case of a young man who developed acute pancreatitis and probably acute myocarditis following ingestion of aluminum phosphide pellets in the absence of the usual risk factors and after exclusion of other possible causes of pancreatitis. In the absence of re-challenge, we put forth the probable causative association of pancreatitis with aluminum phosphide or phosphine gas, its active pesticidal component.

  13. Dose-dependent protective effect of nicotine in a murine model of viral myocarditis induced by coxsackievirus B3

    PubMed Central

    Li-Sha, Ge; Jing-Lin, Zhao; Guang-Yi, Chen; Li, Liu; De-Pu, Zhou; Yue-Chun, Li

    2015-01-01

    The alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently described as an anti-inflammatory target in various inflammatory diseases. The aim of this study was to investigate the dose-related effects of nicotine, an alpha7 nAChR agonist, in murine model of viral myocarditis. BALB/C mice were infected by an intraperitoneally injection with coxsackievirus B3. Nicotine was administered at doses of 0.1, 0.2 or 0.4 mg/kg three times per day for 7 or 14 consecutive days. The effects of nicotine on survival, myocardial histopathological changes, cardiac function, and cytokine levels were studied. The survival rate on day 14 increased in a dose-dependent fashion and was markedly higher in the 0.2 and 0.4 mg/kg nicotine groups than in the infected untreated group. Treatment with high-dose nicotine reduced the myocardial inflammation and improved the impaired left ventricular function in infected mice. The mRNA expressions and protein levels of TNF-α, IL-1β, IL-6, and IL-17A were significantly downregulated in dose-dependent manners in the nicotine treatment groups compared to the infected untreated group. Nicotine dose-dependently reduced the severity of viral myocarditis through inhibiting the production of proinflammatory cytokines. The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with viral myocarditis. PMID:26507386

  14. Pseudomonas aeruginosa exoenzyme S induces proliferation of human T lymphocytes.

    PubMed Central

    Mody, C H; Buser, D E; Syme, R M; Woods, D E

    1995-01-01

    Pseudomonas aeruginosa is a gram-negative bacterium that is responsible for devastating acute and chronic infections, which include bronchiectasis in cystic fibrosis, nosocomial pneumonia, and infection of burn wounds. Previous studies have demonstrated that these patients have impaired host responses, including cell-mediated immune responses, which are important in anti-Pseudomonas host defense. The P. aeruginosa exoproduct, exoenzyme S, has a number of characteristics which suggest that it might be important in cell-mediated immunity. To determine whether exoenzyme S activates lymphocytes to proliferate, peripheral blood mononuclear cells (PBMC) from normal volunteers were stimulated with purified exoenzyme S, and the lymphocyte response was assessed by measuring [3H]thymidine uptake and by counting the number of cells after various times in culture. Ninety-five percent of healthy adult donors had a lymphocyte response to exoenzyme S. The optimal lymphocyte response occurred on day 7, with 4 x 10(5) PBMC per microtiter well when cells were stimulated with 10 micrograms exoenzyme S per ml. [3H]thymidine uptake correlated with an increase in the number of mononuclear cells, indicating that proliferation occurred. In unseparated PBMC, T cells, and to a lesser extent B cells, proliferated. Purified T cells proliferated, while purified B cells proliferated only after the addition of irradiated T cells. Thus, T lymphocytes are necessary and sufficient for the proliferative response to exoenzyme S. We speculate that exoenzyme S from P. aeruginosa is important in T-lymphocyte-mediated host defense to P. aeruginosa. In strategies to enhance impaired cell-mediated immunity, exoenzyme S should be considered as a potential stimulant. PMID:7537248

  15. Docosahexaenoic Acid Sensitizes Leukemia Lymphocytes to Barasertib and Everolimus by ROS-dependent Mechanism Without Affecting the Level of ROS and Viability of Normal Lymphocytes.

    PubMed

    Zhelev, Zhivko; Ivanova, Donika; Lazarova, Desislava; Aoki, Ichio; Bakalova, Rumiana; Saga, Tsuneo

    2016-04-01

    The aim of the present study was: (i) to investigate the possibility of sensitizing leukemia lymphocytes to anticancer drugs using docosahexaenoic acid (DHA); (ii) to find combinations with synergistic cytotoxic effect on leukemia lymphocytes, without or with only very low cytotoxicity towards normal lymphocytes; (iii) and to clarify the role of reactive oxygen species (ROS) in the induction of apoptosis and cytotoxicity by such combinations. The study covered 15 anticancer drugs, conventional and new-generation. Well-expressed synergistic cytotoxic effects were observed after treatment of leukemia lymphocytes (Jurkat) with DHA in combination with: barasertib, lonafarnib, everolimus, and palbociclib. We selected two synergistic combinations, DHA with everolimus or barasertib, and investigated their effects on viability of normal lymphocytes, as well as on the production of ROS and induction of apoptosis in both cell lines (leukemia and normal). At the selected concentrations, DHA, everolimus and barasertib (applied separately) were cytotoxic towards leukemia lymphocytes, but not normal lymphocytes. In leukemia cells, the cytotoxicity of combinations was accompanied by strong induction of apoptosis and production of ROS. In normal lymphocytes, drugs alone and in combination with DHA did not affect the level of ROS and did not induce apoptosis. To our knowledge, the present study is the first to report synergistic ROS-dependent cytotoxicity between DHA and new-generation anticancer drugs, such as everolimus and barasertib, that is cancer cell-specific (particularly for acute lymphoblastic leukemia cells Jurkat). These combinations are harmless to normal lymphocytes and do not induce abnormal production of ROS in these cells. The data suggest that DHA could be used as a supplementary component in anticancer chemotherapy, allowing therapeutic doses of everolimus and barasertib to be reduced, minimizing their side-effects.

  16. Donor Atorvastatin Treatment in Preventing Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies

    ClinicalTrials.gov

    2017-01-13

    Aggressive Non-Hodgkin Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Aggressive Adult Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia

  17. IL-9 Inhibits Viral Replication in Coxsackievirus B3-Induced Myocarditis

    PubMed Central

    Yu, Miao; Long, Qi; Li, Huan-Huan; Liang, Wei; Liao, Yu-Hua; Yuan, Jing; Cheng, Xiang

    2016-01-01

    Myocardial injuries in viral myocarditis (VMC) are caused by viral infection and related autoimmune disorders. Recent studies suggest that IL-9 mediated both antimicrobial immune and autoimmune responses in addition to allergic diseases. However, the role of IL-9 in viral infection and VMC remains controversial and uncertain. In this study, we infected Balb/c mice with Coxsackievirus B3 (CVB3), and found that IL-9 was enriched in the blood and hearts of VMC mice on days 5 and 7 after virus infection. Most of IL-9 was secreted by CD8+ T cells on day 5 and CD4+ T cells on day 7 in the myocardium. Further, IL-9 knockout exacerbated cardiac damage following CVB3 infection, along with a sharp increase in viral replication and IL-17a expression, as well as a decrease in TGF-β. In contrast, the repletion of IL-9 in Balb/c mice with CVB infection induced the opposite effect. Studies in vitro further revealed that IL-9 directly inhibited viral replication in cardiomyocytes by reducing coxsackie and adenovirus receptor expression, which might be associated with upregulation of TGF-β autocrine effect in these cells. However, IL-9 had no direct effect on apoptosis in cardiomyocytes. Our data indicated that IL-9 played a protective role in disease progression by inhibiting CVB3 replication in the early stages of VMC. PMID:27766098

  18. Unresolved issues in theories of autoimmune disease using myocarditis as a framework.

    PubMed

    Root-Bernstein, Robert; Fairweather, DeLisa

    2015-06-21

    Many theories of autoimmune disease have been proposed since the discovery that the immune system can attack the body. These theories include the hidden or cryptic antigen theory, modified antigen theory, T cell bypass, T cell-B cell mismatch, epitope spread or drift, the bystander effect, molecular mimicry, anti-idiotype theory, antigenic complementarity, and dual-affinity T cell receptors. We critically review these theories and relevant mathematical models as they apply to autoimmune myocarditis. All theories share the common assumption that autoimmune diseases are triggered by environmental factors such as infections or chemical exposure. Most, but not all, theories and mathematical models are unifactorial assuming single-agent causation of disease. Experimental and clinical evidence and mathematical models exist to support some aspects of most theories, but evidence/models that support one theory almost invariably supports other theories as well. More importantly, every theory (and every model) lacks the ability to account for some key autoimmune disease phenomena such as the fundamental roles of innate immunity, sex differences in disease susceptibility, the necessity for adjuvants in experimental animal models, and the often paradoxical effect of exposure timing and dose on disease induction. We argue that a more comprehensive and integrated theory of autoimmunity associated with new mathematical models is needed and suggest specific experimental and clinical tests for each major theory that might help to clarify how they relate to clinical disease and reveal how theories are related.

  19. Toxoplasma gondii Myocarditis after Adult Heart Transplantation: Successful Prophylaxis with Pyrimethamine

    PubMed Central

    Strabelli, Tania Mara V.; Siciliano, Rinaldo Focaccia; Vidal Campos, Silvia; Bianchi Castelli, Jussara; Bacal, Fernando; Bocchi, Edimar A.; Uip, David E.

    2012-01-01

    Toxoplasma gondii primary infection/reactivation after solid organ transplantation is a serious complication, due to the high mortality rate following disseminated disease. We performed a retrospective study of all cases of T. gondii infections in 436 adult patients who had received an orthotopic cardiac transplant at our Institution from May 1968 to January 2011. Six patients (1.3%) developed T. gondii infection/reactivation in the post-operative period. All infections/reactivations occurred before 1996, when no standardized toxoplasmosis prophylactic regimen or co-trimoxazole prophylaxis was used. Starting with the 112th heart transplant, oral pyrimethamine 75 mg/day was used for seronegative transplant recipients whose donors were seropositive or unknown. Two patients (33.3%) presented with disseminated toxoplasmosis infection, and all patients (100%) had myocarditis. Five patients (83.3%) were seronegative before transplant and one patient did not have pre-transplant serology available. Median time for infection onset was 131 days following transplantation. Three patients (50%) died due to toxoplasmosis infection. After 1996, we did not observe any additional cases of T. gondii infection/reactivation. In conclusion, toxoplasmosis in heart allographs was more frequent among seronegative heart recipients, and oral pyrimethamine was highly effective for the prevention of T. gondii infection in this population. PMID:23209479

  20. Coxsackievirus myocarditis: interplay between virus and host in the pathogenesis of heart disease.

    PubMed

    Tam, Patricia E

    2006-01-01

    Coxsackievirus (CVB) infection is a significant cause of myocarditis and dilated cardiomyopathy (DCM). Heart disease may be caused by direct cytopathic effects of the virus, a pathologic immune response to persistent virus, or autoimmunity triggered by the viral infection. CVB interacts with its host at multiple stages during disease development. Signaling through viral receptors may alter the intracellular environment in addition to facilitating virus entry. Viral genetic determinants that encode cardiovirulence have been mapped and may change depending on the nutritional status of the host. Virus persistence is directly associated with pathology, and recent work demonstrates that CVB evolves into a slowly replicating form capable of establishing a low-grade infection in the heart. The innate immune response to CVB has taken on increasing importance because of its role in shaping the development of the adaptive immune response that is responsible for cardiac pathology. Studies of T cell responsiveness and the development of autoimmunity at the molecular level are beginning to clarify the mechanisms through which CVB infection causes inflammatory heart disease.

  1. Unresolved issues in theories of autoimmune disease using myocarditis as a framework

    PubMed Central

    Root-Bernstein, Robert; Fairweather, DeLisa

    2014-01-01

    Many theories of autoimmune disease have been proposed since the discovery that the immune system can attack the body. These theories include the hidden or cryptic antigen theory, modified antigen theory, T cell bypass, T cell-B cell mismatch, epitope spread or drift, the bystander effect, molecular mimicry, anti-idiotype theory, antigenic complementarity, and dual-affinity T cell receptors. We critically review these theories and relevant mathematical models as they apply to autoimmune myocarditis. All theories share the common assumption that autoimmune diseases are triggered by environmental factors such as infections or chemical exposure. Most, but not all, theories and mathematical models are unifactorial assuming single-agent causation of disease. Experimental and clinical evidence and mathematical models exist to support some aspects of most theories, but evidence/models that support one theory almost invariably supports other theories as well. More importantly, every theory (and every model) lacks the ability to account for some key autoimmune disease phenomena such as the fundamental roles of innate immunity, sex differences in disease susceptibility, the necessity for adjuvants in experimental animal models, and the often paradoxical effect of exposure timing and dose on disease induction. We argue that a more comprehensive and integrated theory of autoimmunity associated with new mathematical models is needed and suggest specific experimental and clinical tests for each major theory that might help to clarify how they relate to clinical disease and reveal how theories are related. PMID:25484004

  2. Splenic lymphoma with villous lymphocytes.

    PubMed

    Gupta, Ritu; Naseem, Shano; Sukumaran, Shawgi; Kashyap, Rajesh; Kaur, Sukhpreet; Paul, Lily

    2008-01-01

    Splenic lymphoma with villous lymphocytes (SLVL) is a rare disorder that comprises less than 1% of lymphoid neoplasms. It is the leukemic counterpart of splenic marginal zone lymphoma (SMZL) and is characterized by splenomegaly, often with no lymphadenopathy, moderate lymphocytosis and villous lymphocytes on peripheral blood smear. Here, we report a case of SLVL in a 56-year-old male with very high leukocyte counts, massive splenomegaly and relatively few leukemic cells with subtle villous projections on the surface. This disorder is often confused with other chronic lymphoproliferative disorders, especially chronic lymphocytic leukemia (CLL) and hairy cell leukemia and should be differentiated from them. We are reporting this case to highlight the diagnostic pitfalls associated with this disorder.

  3. Fatty acids and lymphocyte functions.

    PubMed

    Calder, P C; Yaqoob, P; Thies, F; Wallace, F A; Miles, E A

    2002-01-01

    The immune system acts to protect the host against pathogenic invaders. However, components of the immune system can become dysregulated such that their activities are directed against host tissues, so causing damage. Lymphocytes are involved in both the beneficial and detrimental effects of the immune system. Both the level of fat and the types of fatty acid present in the diet can affect lymphocyte functions. The fatty acid composition of lymphocytes, and other immune cells, is altered according to the fatty acid composition of the diet and this alters the capacity of those cells to produce eicosanoids, such as prostaglandin E2, which are involved in immunoregulation. A high fat diet can impair lymphocyte function. Cell culture and animal feeding studies indicate that oleic, linoleic, conjugated linoleic, gamma-linolenic, dihomo-gamma-linolenic, arachidonic, alpha-linolenic, eicosapentaenoic and docosahexaenoic acids can all influence lymphocyte proliferation, the production of cytokines by lymphocytes, and natural killer cell activity. High intakes of some of these fatty acids are necessary to induce these effects. Among these fatty acids the long chain n-3 fatty acids, especially eicosapentaenoic acid, appear to be the most potent when included in the human diet. Although not all studies agree, it appears that fish oil, which contains eicosapentaenoic acid, down regulates the T-helper 1-type response which is associated with chronic inflammatory disease. There is evidence for beneficial effects of fish oil in such diseases; this evidence is strongest for rheumatoid arthritis. Since n-3 fatty acids also antagonise the production of inflammatory eicosanoid mediators from arachidonic acid, there is potential for benefit in asthma and related diseases. Recent evidence indicates that fish oil may be of benefit in some asthmatics but not others.

  4. Platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in patients with rheumatoid arthritis

    PubMed Central

    Peng, You-Fan; Cao, Ling; Zeng, Yan-Hua; Zhang, Zhao-Xia; Chen, Dan; Zhang, Qiong

    2015-01-01

    Objectives It has been well documented that the platelet to lymphocyte ratio (PLR) and the neutrophil to lymphocyte ratio (NLR) are associated with outcomes for patients with gastric cancer, non-small cell lung cancer and acute heart failure. Inflammation may be the hidden factor that explains the correlation between NLP, PLR, and these diseases. However, to date, the data concerning NLR, PLR, and its association with inflammation are lacking in patients with rheumatoid arthritis (RA), thus, our aim to discuss whether NLR and PLR are associated with RA. Methods Patients with RA and healthy individuals were included according to the determined criteria, and laboratory indicators were measured. Results PLR and NLR were significantly higher in RA patients compared with healthy controls (3.20±2.06 vs. 1.56±0.47, P<0.01; 192.85±101.78 vs. 103.49±28.68, P<0.01). When leukocytes, neutrophil percentage, neutrophil, lymphocyte, platelet, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were considered as confounders (crude model), our results indicated that ESR and RF were correlated to RA. Of note, ESR, RF, and PLR were associated with RA after further adjustment based on crude model for PLR and NLR. Receiver operating characteristic (ROC) curves analysis showed that PLR values higher than >115.7 evaluated RA with a sensitivity of 82.5%, a specificity of 74.8% and area under the curve ( AUC ) of 0.847. Conclusions Our results suggest that PLR is associated with RA, and PLR may be an underlying indicator indicating the chronic subclinical inflammation in patients with RA. PMID:28352702

  5. Survival Fraction at 2 Gy and γH2AX Expression Kinetics in Peripheral Blood Lymphocytes From Cancer Patients: Relationship With Acute Radiation-Induced Toxicities

    SciTech Connect

    Pouliliou, Stamatia E.; Dimitriou, Thespis; Giatromanolaki, Alexandra; Papazoglou, Dimitrios; Pappa, Aglaia; Pistevou, Kyriaki

    2015-07-01

    Purpose: Predictive assays for acute radiation toxicities would be clinically relevant in radiation oncology. We prospectively examined the predictive role of the survival fraction at 2 Gy (SF2) and of γH2AX (double-strand break [DSB] DNA marker) expression kinetics in peripheral blood mononuclear cells (PBMCs) from cancer patients before radiation therapy. Methods and Materials: SF2 was measured with Trypan Blue assay in the PBMCs from 89 cancer patients undergoing radiation therapy at 4 hours (SF2{sub [4h]}) and 24 hours (SF2{sub [24h]}) after ex vivo irradiation. Using Western blot analysis and band densitometry, we further assessed the expression of γH2AX in PBMC DNA at 0 hours, 30 minutes, and 4 hours (33 patients) and 0 hour, 4 hours, and 24 hours (56 patients), following ex vivo irradiation with 2 Gy. Appropriate ratios were used to characterize each patient, and these were retrospectively correlated with early radiation therapy toxicity grade. Results: The SF2{sub (4h)} was inversely correlated with the toxicity grade (P=.006). The γH2AX-ratio{sub (30min)} (band density of irradiated/non-irradiated cells at 30 minutes) revealed, similarly, a significant inverse association (P=.0001). The DSB DNA repair rate from 30 minutes to 4 hours, calculated as the relative RγH2AX-ratio (γH2AX-ratio{sub (4h)}/γH2AX-ratio{sub (30min)}) showed a significant direct association with high toxicity grade (P=.01). Conclusions: Our results suggest that SF2 is a significant radiation sensitivity index for patients undergoing radiation therapy. γH2AX Western blot densitometry analysis provided 2 important markers of normal tissue radiation sensitivity. Low γH2AX expression at 30 minutes was linked with high toxicity grade, suggesting that poor γH2AX repair activity within a time frame of 30 minutes after irradiation predicts for poor radiation tolerance. On the other hand, rapid γH2AX content restoration at 4 hours after irradiation, compatible with

  6. Glucose, glycolysis and lymphocyte responses.

    PubMed

    Donnelly, Raymond P; Finlay, David K

    2015-12-01

    Activated lymphocytes engage in robust growth and rapid proliferation. To achieve this, they tend to adopt a form of glucose metabolism termed aerobic glycolysis. This type of metabolism allows for the use of large amounts of glucose to generate energy, but also to support biosynthetic processes. This review article will discuss how aerobic glycolysis supports the biosynthetic demands of activated T cells, B cells and Natural Killer cells, and the emerging concept that glycolysis is integrally linked to the differentiation and function of these lymphocyte populations.

  7. Sustained Dysfunction of Antiviral CD8+ T Lymphocytes after Infection with Hepatitis C Virus

    PubMed Central

    Gruener, Norbert H.; Lechner, Franziska; Jung, Maria-Christina; Diepolder, Helmut; Gerlach, Tilman; Lauer, Georg; Walker, Bruce; Sullivan, John; Phillips, Rodney; Pape, Gerd R.; Klenerman, Paul

    2001-01-01

    Hepatitis C virus (HCV) sets up persistent infection in the majority of those exposed. It is likely that, as with other persistent viral infections, the efficacy of T-lymphocyte responses influences long-term outcome. However, little is known about the functional capacity of HCV-specific T-lymphocyte responses induced after acute infection. We investigated this by using major histocompatibility complex class I-peptide tetrameric complexes (tetramers), which allow direct detection of specific CD8+ T lymphocytes ex vivo, independently of function. Here we show that, early after infection, virus-specific CD8+ T lymphocytes detected with a panel of four such tetramers are abnormal in terms of their synthesis of antiviral cytokines and lytic activity. Furthermore, this phenotype is commonly maintained long term, since large sustained populations of HCV-specific CD8+ T lymphocytes were identified, which consistently had very poor antiviral cytokine responses as measured in vitro. Overall, HCV-specific CD8+ T lymphocytes show reduced synthesis of tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) after stimulation with either mitogens or peptides, compared to responses to Epstein-Barr virus and/or cytomegalovirus. This behavior of antiviral CD8+ T lymphocytes induced after HCV infection may contribute to viral persistence through failure to effectively suppress viral replication. PMID:11356962

  8. Lymphocytic hypophysitis: a rare or underestimated disease?

    PubMed

    Bellastella, Antonio; Bizzarro, Antonio; Coronella, Concetta; Bellastella, Giuseppe; Sinisi, Antonio Agostino; De Bellis, Annamaria

    2003-11-01

    Lymphocytic hypophysitis (LYH) is an uncommon autoimmune disease in which the pituitary gland is infiltrated by lymphocytes, plasma cells and macrophages and its function is usually impaired. It has to be suspected in pregnant women and in women with recent delivery presenting with hyperprolactinemia, headache, visual field alterations and changes of one or more pituitary hormone secretions with secondary impairment of related peripheral target glands, especially when associated with other autoimmune endocrine or non-endocrine disorders. It can also occur less frequently in prepubertal or post-menopausal women and in men. Headache, visual field impairment and more rarely diplopia are due to extrasellar pituitary enlargement with optic chiasma compression and/or to invasion of cavernous sinuses. Among the 'isolated' pituitary hormone deficiencies, ACTH deficit is usually the earliest and most frequent hormonal impairment and in rare cases can induce an acute secondary hyposurrenalism as the first sign of the disease, with high mortality in affected patients. Histopathological findings from pituitary biopsy show lymphoplasmacytic infiltrate with lymphoid aggregates surrounding atropic acini of pituitary cells; immunohistochemical analysis shows numerous mast cells randomly distributed and also localized in the vicinity of capillaries, suggesting a possible influence on capillary permeability and angiogenesis, thus favoring the inflammatory and immunological aggression against pituitary cells. Nuclear magnetic resonance imaging shows uniform sellar floor depression and an extrasellar symmetrical pituitary enlargement, usually displacing the optic chiasma, which shows a rapid homogeneous enhancement after gadolinium also involving the adjacent dura (dural tail). Antipituitary antibodies have been detected in several patients with LYH but their role needs to be clarified. Since a possible spontaneous remission can occur, a careful follow-up is required in subclinical

  9. Flow cytometry of cerebrospinal fluid (CSF) lymphocytes: alterations of blood/CSF ratios of lymphocyte subsets in inflammation disorders of human central nervous system (CNS).

    PubMed

    Kleine, T O; Albrecht, J; Zöfel, P

    1999-03-01

    Flow cytometry was adapted to measure lymphocytes in human cerebrospinal fluid (CSF). The method was sufficiently precise, reproducible and accurate despite low cell counts. In lumbar CSF of controls with 500 to 3500 (10(3)/l) leukocytes, lymphocyte counts correlated with those in corresponding venous blood: blood/CSF ratios of approximately 2000 : 1 were found for total T cells (CD3+) and CD3+ HLA-DR-, CD3+4+, CD3+8+ subsets, ratios were increased for the lymphocyte subsets CD3+ HLA-DR+ < or = CD3+16+56+ < CD16+56+3- < CD8+3- < CD19+; CD8+4+ ratio was half of CD3+ ratio. Data indicate selective barriers (blood-brain and blood-CSF barriers) to blood lymphocyte subsets which favor the transfer of T subsets. Correlation of the subset ratios to the CD3+ ratio indicates distinct barrier properties which changed differently with acute and subacute inflammations and neuroimmunological diseases of central nervous system (CNS) in lumbar or ventricular CSF, but not with simple protein barrier disturbance. HLA DR+ T ratios were higher than HLA DR- T ratios only with controls and some neuroimmunological diseases. Lymphocyte barrier characteristics were related to protein leakage situated at the same barriers, indicating for the lymphocyte subsets selective transfer routes in control subjects and non-selective routes in patients with CNS inflammation where altered ratios revealed a mixture of both routes.

  10. Treating Nodular Lymphocyte Predominant Hodgkin Disease (NLPHD)

    MedlinePlus

    ... for Hodgkin Disease Treating Classic Hodgkin Disease, by Stage Treating Nodular Lymphocyte Predominant Hodgkin Disease (NLPHD) Treating Hodgkin Disease in Children Hodgkin Disease in Pregnancy Hodgkin Disease Treating Hodgkin Disease Treating Nodular Lymphocyte ...

  11. Radionuclide labeled lymphocytes for therapeutic use

    DOEpatents

    Srivastava, Suresh C.; Fawwaz, Rashid A.; Richards, Powell

    1985-01-01

    Lymphocytes labelled with .beta.-emitting radionuclides are therapeutically useful, particularly for lymphoid ablation. They are prepared by incubation of the lymphocytes with the selected radionuclide-oxine complex.

  12. Radionuclide labeled lymphocytes for therapeutic use

    DOEpatents

    Srivastava, S.C.; Fawwaz, R.A.; Richards, P.

    1983-05-03

    Lymphocytes labelled with ..beta..-emitting radionuclides are therapeutically useful, particularly for lymphoid ablation. They are prepared by incubation of the lymphocytes with the selected radionuclide-oxine complex.

  13. What's New in Chronic Lymphocytic Leukemia Research and Treatment?

    MedlinePlus

    ... Lymphocytic Leukemia (CLL) About Chronic Lymphocytic Leukemia What's New in Chronic Lymphocytic Leukemia Research and Treatment? Many ... person's outlook and whether they will need treatment. New drugs for chronic lymphocytic leukemia Dozens of new ...

  14. What Should You Ask Your Doctor about Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... Should You Ask Your Doctor About Chronic Lymphocytic Leukemia? As you cope with cancer and cancer treatment, ... About Chronic Lymphocytic Leukemia? More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  15. Do We Know What Causes Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... Prevention Do We Know What Causes Chronic Lymphocytic Leukemia? The exact cause of most cases of chronic ... Lymphocytic Leukemia Be Prevented? More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  16. What Are the Risk Factors for Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... What Are the Risk Factors for Chronic Lymphocytic Leukemia? A risk factor is something that affects a ... Lymphocytic Leukemia Be Prevented? More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  17. Treatment of chronic lymphocytic leukemia.

    PubMed

    Ferrajoli, Alessandra; O'Brien, Susan M

    2004-04-01

    Treatment options for patients with chronic lymphocytic leukemia have changed over the past two decades. This article reviews the experience accumulated with the use of alkylating agents alone and in combination; purine analogues alone and in combination and monoclonal antibodies such as rituximab, and alemtuzumab alone and in combination. The results obtained with different treatment strategies are summarized, compared, and reviewed.

  18. Rapid exacerbation of lymphocytic infundibuloneurohypophysitis

    PubMed Central

    Shibue, Kimitaka; Fujii, Toshihito; Goto, Hisanori; Yamashita, Yui; Sugimura, Yoshihisa; Tanji, Masahiro; Yasoda, Akihiro; Inagaki, Nobuya

    2017-01-01

    Abstract Rationale: Lymphocytic hypophysitis is a relatively rare autoimmune disease defined by lymphocytic infiltration to the pituitary. Its rarity and wide spectrum of clinical manifestations make clarification of the pathology difficult. Here, we describe a case we examined from the primary diagnosis to final discharge, showing the serial progression of lymphocytic infundibuloneurohypophysitis (LINH) to panhypopituitarism with extrapituitary inflammatory invasion in a short period, and responding favorably to high-dose glucocorticoid treatment. Patient concerns: Polyuria, General fatigue and Nausea/Vomiting. Diagnoses: Central diabetes insipidus (CDI), Lymphocytic infundibuloneurohypophysitis (LINH). Interventions: Desmopressin acetate, High-dose glucocorticoid (GC) treatment. Outcomes: He was prescribed desmopressin acetate and subsequently discharged. A month later, he revisited our hospital with general fatigue and nausea/vomiting. A screening test disclosed hypopituitarism with adrenal insufficiency. MRI revealed expanded contrast enhancement to the peripheral extrapituitary lesion. He received high-dose GC treatment and the affected lesion exhibited marked improvement on MRI, along with the recovery of the anterior pituitary function. Lessons: This case demonstrates the potential for classical LINH to develop into panhypopituitarsim. We consider this is the first documentation of approaching the cause of atypical LINH with progressive clinical course from the pathological viewpoint. PMID:28248860

  19. Lymphocyte receptors for pertussis toxin

    SciTech Connect

    Clark, C.G.; Armstrong, G.D. )

    1990-12-01

    We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, and Jurkat cells. In all three cell systems, the pertussis toxin affinity probe specifically labeled a single protein species with an apparent molecular weight of 70,000 that was not observed when the procedure was performed in the presence of excess unmodified pertussis toxin. A protein comparable in molecular weight to the one detected by the photoaffinity labeling technique was also observed among the species that bound to pertussis toxin-agarose. The results suggest that pertussis toxin may bind to a 70,000-Da receptor in human T lymphocytes.

  20. Mixed lymphocyte culture stimulatory and responding capacity of lymphocytes from patients with lymphoproliferative diseases.

    PubMed Central

    Rühl, H; Vogt, W; Bochert, G; Schmidt, S; Moelle, R; Schaoua, H

    1975-01-01

    Lymphocyte reactivity in vitro was studied in patients with Hodgkin's disease, chronic lymphocytic leukaemia and lymphosarcoma. The responding capacity to phytohaemagglutinin (PHA) was markedly depressed and delayed in all three groups of patients compared with the PHA response observed in lymphocyte cultures from normal individuals. In one-way mixed lymphocyte culture experiments a significant decrease in responding capacity of the patients' lymphocytes to lymphocytes from normal donors could be demonstrated. In contrast, the stimulatory capacity of the patients' lymphocytes was found to be intact, or only slightly reduced. PMID:128426

  1. Diagnostic Contribution of Cardiac Magnetic Resonance in Patients with Acute Coronary Syndrome and Culprit-Free Angiograms

    PubMed Central

    Kawecki, Damian; Morawiec, Beata; Monney, Pierre; Pellaton, Cyril; Wojciechowska, Celina; Jojko, Joanna; Basiak, Marcin; Przywara-Chowaniec, Brygida; Fournier, Stephane; Nowalany-Kozielska, Ewa; Schwitter, Juerg; Muller, Olivier

    2015-01-01

    Background In spite of robust knowledge about underlying ischemic myocardial damage, acute coronary syndromes (ACS) with culprit-free angiograms raise diagnostic concerns. The present study aimed to evaluate the additional value of cardiac magnetic resonance (CMR) over commonly available non-CMR standard tests, for the differentiation of myocardial injury in patients with ACS and non-obstructed coronary arteries. Material/Methods Patients with ACS, elevated hs-TnT, and a culprit-free angiogram were prospectively enrolled into the study between January 2009 and July 2013. After initial evaluation with standard tests (ECG, echocardiography, hs-TnT) and provisional exclusion of acute myocardial infarction (AMI) in coronary angiogram, patients were referred for CMR with the suspicion of myocarditis or Takotsubo cardiomyopathy (TTC). According to the result of CMR, patients were reclassified as having myocarditis, AMI, TTC, or non-injured myocardium as assessed by late gadolinium enhancement. Results Out of 5110 patients admitted with ACS, 75 had normal coronary angiograms and entered the study; 69 of them (92%) were suspected for myocarditis and 6 (8%) for TTC. After CMR, 49 patients were finally diagnosed with myocarditis (65%), 3 with TTC (4%), 7 with AMI (9%), and 16 (21%) with non-injured myocardium. The provisional diagnosis was changed or excluded in 23 patients (31%), with a 9% rate of unrecognized AMI. Conclusions The study results suggest that the evaluation of patients with ACS and culprit-free angiogram should be complemented by a CMR examination, if available, because the initial work-up with non-CMR tests leads to a significant proportion of misdiagnosed AMI. PMID:25604184

  2. Myocardial Chemokine Expression and Intensity of Myocarditis in Chagas Cardiomyopathy Are Controlled by Polymorphisms in CXCL9 and CXCL10

    PubMed Central

    Nogueira, Luciana Gabriel; Santos, Ronaldo Honorato Barros; Ianni, Barbara Maria; Fiorelli, Alfredo Inácio; Mairena, Eliane Conti; Benvenuti, Luiz Alberto; Frade, Amanda; Donadi, Eduardo; Dias, Fabrício; Saba, Bruno; Wang, Hui-Tzu Lin; Fragata, Abilio; Sampaio, Marcelo; Hirata, Mario Hiroyuki; Buck, Paula; Mady, Charles; Bocchi, Edimar Alcides; Stolf, Noedir Antonio; Kalil, Jorge; Cunha-Neto, Edecio

    2012-01-01

    Background Chronic Chagas cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi. Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium. Methods and Results Using confocal immunofluorescence and quantitative PCR, we studied cell surface staining and gene expression of the CXCR3, CCR4, CCR5, CCR7, CCR8 receptors and their chemokine ligands in myocardial samples from end-stage CCC patients. CCR5+, CXCR3+, CCR4+, CCL5+ and CXCL9+ mononuclear cells were observed in CCC myocardium. mRNA expression of the chemokines CCL5, CXCL9, CXCL10, CCL17, CCL19 and their receptors was upregulated in CCC myocardium. CXCL9 mRNA expression directly correlated with the intensity of myocarditis, as well as with mRNA expression of CXCR3, CCR4, CCR5, CCR7, CCR8 and their ligands. We also analyzed single-nucleotide polymorphisms for genes encoding the most highly expressed chemokines and receptors in a cohort of Chagas disease patients. CCC patients with ventricular dysfunction displayed reduced genotypic frequencies of CXCL9 rs10336 CC, CXCL10 rs3921 GG, and increased CCR5 rs1799988CC as compared to those without dysfunction. Significantly, myocardial samples from CCC patients carrying the CXCL9/CXCL10 genotypes associated to a lower risk displayed a 2–6 fold reduction in mRNA expression of CXCL9, CXCL10, and other chemokines and receptors, along with reduced intensity of myocarditis, as compared to those with other CXCL9/CXCL10 genotypes. Conclusions Results may indicate that genotypes associated to reduced risk in closely linked CXCL9 and CXCL10 genes may modulate local expression of the chemokines themselves, and simultaneously affect myocardial expression of other key chemokines as well as intensity of myocarditis. Taken together our results may suggest that

  3. Drug-induced myocarditis after nivolumab treatment in a patient with PDL1- negative squamous cell carcinoma of the lung.

    PubMed

    Semper, H; Muehlberg, F; Schulz-Menger, J; Allewelt, M; Grohé, C

    2016-09-01

    Immunotherapy such as nivolumab is a new promising therapeutic option for advanced stage non small cell lung cancer (NSCLC). Due to the interference with the immune system previously unknown side effects are observed both in clinical studies and experience. Autoimmune phenomena effecting skin, gastrointestinal tract, endocrine glands, kidney and lung have been described. Up to now there is only limited information regarding potential cardiac side effects. We present a case of symptomatic drug induced myocarditis after nine cycles of nivolumab in a patient with efficient anticancer response.

  4. Fludarabine Phosphate, Radiation Therapy, and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2017-03-27

    Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma; T-Cell Large Granular Lymphocyte Leukemia

  5. Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

    ClinicalTrials.gov

    2016-07-18

    B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  6. Protective mechanisms of berberine against experimental autoimmune myocarditis in a rat model.

    PubMed

    Liu, Xuefei; Zhang, Xinghua; Ye, Lin; Yuan, Haitao

    2016-04-01

    Berberine, an alkaloid derivative extracted from numerous plants of the general Berberis and Coptis, has been reported to have immunomodulatory effects against immune-mediated disorders in emerging studies. In this study, the effects of berberine and its underlying molecular mechanisms were investigated from the myosin-induced myocardial injury in rats. Lewis rats were immunized with porcine cardiac myosin to induce experimental autoimmune myocarditis (EAM), treated with berberine and specific JAK inhibitor AG490 as a positive control. Our data showed that both berberine and AG490 significantly reduced the impaired cardiac function and the pathophysiological severity, impeded high levels of anti-cardiac myosin antibody of EAM rats. Th17 and Th1 cells as well as their cytokines IL-17 and IFN-γ were up-regulated in EAM. However, the excessive increase of Th17/Th1 responses was restored by berberine and AG490. We also examined the expression level of phosphorylated proteins of JAK-STAT pathway which has a key role in the Th17 and Th1 lineage commitment. The phosphorylated (p)-STAT1,STAT3 and STAT4 increased significantly in EAM, while berberine notably attenuated their excessive expression. This effect of berberine was equivalent to that of AG490 blockade. Our current study demonstrated that berberine could ameliorate EAM and the underling mechanisms may be due to the fact that berberine differentially modulates the activities of p-STAT1, p-STAT3 and p-STAT4 to suppress Th17 and Th1 cell differentiation.

  7. Toxicological effect of TiO2 nanoparticle-induced myocarditis in mice

    NASA Astrophysics Data System (ADS)

    Hong, Fashui; Wang, Ling; Yu, Xiaohong; Zhou, Yingjun; Hong, Jie; Sheng, Lei

    2015-08-01

    Currently, impacts of exposure to TiO2 nanoparticles (NPs) on the cardiovascular system are not well understood. The aim of this study was to investigate whether TiO2 NPs induce myocarditis and its underlying molecular mechanism in the cardiac inflammation in mice. Mice were exposed to TiO2 NPs for 6 months; biochemical parameters of serum and expression of Th1-related and Th2-related cytokines in the heart were investigated. The results showed that TiO2 NP exposure resulted in cardiac lesions coupling with pulmonary inflammation; increases of aspartate aminotransferase (AST), creatine kinase (CK), C-reaction protein (CRP), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBDH), adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) levels; and a reduction of nitric oxide (NOx) level in the serum. These were associated with increases of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, transforming growth factor-β (TGF-β), creatine kinase, CRP, adhesion molecule-1, and monocyte chemoattractant protein-1, interferon-γ (IFN-γ), signal transducers and activators of transcription (STAT)1, STAT3, or STAT6, GATA-binding domain-3, GATA-binding domain-4, endothelin-1 expression levels, and T-box expressed in T cells expression level that is the master regulator of pro-inflammatory cytokines and transcription factors in the heart. These findings imply that TiO2 NP exposure may increase the occurrence and development of cardiovascular diseases.

  8. A child with influenza A (H1N1)-associated myocarditis rescued by extracorporeal membrane oxygenation.

    PubMed

    Oda, Takeshi; Yasunaga, Hiroshi; Tsutsumi, Yoshimitsu; Shojima, Takahiro; Zaima, Yasuyuki; Nishino, Hiroshi; Ito, Shinichi; Todo, Kageshige

    2010-12-01

    A 6-year-old boy had cold-like symptoms and was diagnosed with influenza A at a clinic. Administration of oseltamivir and azithromycin did not improve the symptoms. He was referred to our hospital and was diagnosed with H1N1 pneumonia. The patient required ventilator support. However, hypoxia and hypercapnia were uncontrollable. To oxygenate and reduce the carbon dioxide concentration, veno-venous extracorporeal membrane oxygenation (ECMO) was applied 24 h after admission. We established outflow via the right internal jugular vein and inflow via the right femoral vein. Six hours later, an electrical storm of ventricular fibrillation occurred, probably due to influenza myocarditis. Chest compression was started immediately. Both cardioversion and medication were ineffective in treating the electrical storm. Therefore, we decided to switch the veno-venous ECMO to veno-arterial ECMO to maintain systemic flow. During chest compression, a 6-mm graft was anastomosed to the left common femoral artery, and an outflow tube was connected to the graft. Consequently, veno-arterial ECMO was established via outflow through the left common femoral artery and inflow through both the right jugular vein and right femoral vein. Veno-arterial ECMO terminated the electrical storm, and cardiac output improved. Veno-arterial ECMO was provided for 107 h, and was then replaced by veno-venous ECMO. Forty-three hours later, veno-venous ECMO was discontinued. The patient was successfully weaned from the mechanical ventilator on the 9th day after admission. Unfortunately, spinal infarction appeared as a complication. The patient was discharged from the hospital on the 86th day, and has now returned to primary school.

  9. Immunoproteomic analysis of antibody in lymphocyte supernatant in patients with typhoid fever in Bangladesh.

    PubMed

    Charles, Richelle C; Liang, Li; Khanam, Farhana; Sayeed, M Abu; Hung, Chris; Leung, Daniel T; Baker, Stephen; Ludwig, Albrecht; Harris, Jason B; Larocque, Regina C; Calderwood, Stephen B; Qadri, Firdausi; Felgner, Philip L; Ryan, Edward T

    2014-03-01

    We have previously shown that an assay based on detection of anti-Salmonella enterica serotype Typhi antibodies in supernatant of lymphocytes harvested from patients presenting with typhoid fever (antibody in lymphocyte supernatant [ALS] assay) can identify 100% of patients with blood culture-confirmed typhoid fever in Bangladesh. In order to define immunodominant proteins within the S. Typhi membrane preparation used as antigen in these prior studies and to identify potential biomarkers unique to S. Typhi bacteremic patients, we probed microarrays containing 2,724 S. Typhi proteins with ALS collected at the time of clinical presentation from 10 Bangladeshis with acute typhoid fever. We identified 62 immunoreactive antigens when evaluating both the IgG and IgA responses. Immune responses to 10 of these antigens discriminated between individuals with acute typhoid infection and healthy control individuals from areas where typhoid infection is endemic, as well as Bangladeshi patients presenting with fever who were subsequently confirmed to have a nontyphoid illness. Using an ALS enzyme-linked immunosorbent assay (ELISA) format and purified antigen, we then confirmed that immune responses against the antigen with the highest immunoreactivity (hemolysin E [HlyE]) correctly identified individuals with acute typhoid or paratyphoid fever in Dhaka, Bangladesh. These observations suggest that purified antigens could be used with ALS and corresponding acute-phase activated B lymphocytes in diagnostic platforms to identify acutely infected patients, even in areas where enteric fever is endemic.

  10. Immunoproteomic Analysis of Antibody in Lymphocyte Supernatant in Patients with Typhoid Fever in Bangladesh

    PubMed Central

    Liang, Li; Khanam, Farhana; Sayeed, M. Abu; Hung, Chris; Leung, Daniel T.; Baker, Stephen; Ludwig, Albrecht; Harris, Jason B.; LaRocque, Regina C.; Calderwood, Stephen B.; Qadri, Firdausi; Felgner, Philip L.; Ryan, Edward T.

    2014-01-01

    We have previously shown that an assay based on detection of anti-Salmonella enterica serotype Typhi antibodies in supernatant of lymphocytes harvested from patients presenting with typhoid fever (antibody in lymphocyte supernatant [ALS] assay) can identify 100% of patients with blood culture-confirmed typhoid fever in Bangladesh. In order to define immunodominant proteins within the S. Typhi membrane preparation used as antigen in these prior studies and to identify potential biomarkers unique to S. Typhi bacteremic patients, we probed microarrays containing 2,724 S. Typhi proteins with ALS collected at the time of clinical presentation from 10 Bangladeshis with acute typhoid fever. We identified 62 immunoreactive antigens when evaluating both the IgG and IgA responses. Immune responses to 10 of these antigens discriminated between individuals with acute typhoid infection and healthy control individuals from areas where typhoid infection is endemic, as well as Bangladeshi patients presenting with fever who were subsequently confirmed to have a nontyphoid illness. Using an ALS enzyme-linked immunosorbent assay (ELISA) format and purified antigen, we then confirmed that immune responses against the antigen with the highest immunoreactivity (hemolysin E [HlyE]) correctly identified individuals with acute typhoid or paratyphoid fever in Dhaka, Bangladesh. These observations suggest that purified antigens could be used with ALS and corresponding acute-phase activated B lymphocytes in diagnostic platforms to identify acutely infected patients, even in areas where enteric fever is endemic. PMID:24371257

  11. [Acute cerebellitis in infectious mononucleosis. One case (author's transl)].

    PubMed

    Dandelot, J B; Samson, M; Augustin, P; Mihout, B; Parain, D

    1979-02-10

    A nineteen year old man present an original clinical case of acute cerebellitis in infectious mononucleosis. Eighteen months after the acute phase of the illness, there persisted a large deficit in the circulating B lymphocytes. A short review of pertinent litterature is presented and current physiopathological hypothesis are discussed. Briefly, delayed immunity and personal predisposition appear to play important etiological roles.

  12. Leptomeningeal disease in chronic lymphocytic leukemia.

    PubMed

    Lange, C P E; Brouwer, R E; Brooimans, R; Vecht, Ch J

    2007-12-01

    Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the western hemisphere, with an annual incidence of 3:100000. Commonly patients are asymptomatic but not rarely disease progression occurs in the setting of lymphadenopathy and extensive leukemic burden. Leptomeningeal involvement in patients with CLL is infrequent, with presenting symptoms of headache (23%), acute or chronic changes in mental status (28%), cranial nerve abnormalities (54%) including optic neuropathy (28%), weakness of lower extremities (23%) and cerebellar signs (18%). In this report, we discuss a CLL patient with leptomeningeal involvement, who presented with neurological symptoms as the first clinical sign, and a diagnosis of leptomeningeal was made based on CSF cytology and flow cytometry. Treatment consisted of radiation therapy and intrathecal chemotherapy with arabinoside-cytosine and systemic chemotherapy. On the basis of this patient-report together with 37 other previously reported cases, the clinical characteristics together with treatment options and outcome of leptomeningeal involvement in CLL are reviewed. Our case together with data from the literature indicate that a timely diagnosis and intensive treatment of leptomeningeal disease of CLL may lead to longstanding and complete resolution of neurological symptoms.

  13. Lymphocytic hypophysitis in a man.

    PubMed

    Guay, A T; Agnello, V; Tronic, B C; Gresham, D G; Freidberg, S R

    1987-03-01

    Fewer than 20 patients with lymphocytic adenohypophysitis have been reported, all of them women, and it usually occurs during pregnancy or the postpartum period. We report the recognition of lymphocytic adenohypophysitis in a man. The patient presented with anterior hypopituitarism and an intrasellar mass on computed tomography. Antipituitary antibodies, found in only one of the previous patients, were not present in this man, although low titer antinuclear antibodies were found. The implications of this latter finding are unclear. The patient's histocompatibility antigen (HLA) types were A2, B8, Bw58, DR1, and DR5. The degree of pituitary failure seemed out of proportion to the size of the mass seen on computed tomographic scan.

  14. Hormonal Regulation of CD4+ T-Cell Responses in Coxsackievirus B3-Induced Myocarditis in Mice

    PubMed Central

    Huber, S. A.; Kupperman, J.; Newell, M. K.

    1999-01-01

    Coxsackievirus B3 infection causes significant cardiac inflammation in male, but not female, B1.Tg.Eα mice. This gender difference in disease susceptibility correlates with selective induction of CD4+ Th1 (gamma interferon-positive) cell responses in animals with testosterone, whereas estradiol promotes preferential CD4+ Th2 (interleukin-4 positive [IL-4+]) cell responses. Differences in immune deviation of CD4+ T cells cannot be explained by variation in B7-1 or B7-2 expression. Infection significantly upregulated both molecules, but no differences were detected between estradiol- and testosterone-treated groups. Significantly increased numbers of activated (CD69+) T cells expressing the γδ T-cell receptor were found in male and testosterone-treated male and female mice. In vivo depletion of γδ+ cells by using monoclonal antibodies inhibited myocarditis and resulted in a shift from a Th1 to Th2 response phenotype. Taken together, our results indicate that testosterone promotes a CD4+ Th1 cell response and myocarditis by promoting increased γδ+ cell activation. PMID:10233928

  15. A Role for Toll-like Receptor 3 Variants in Host Susceptibility to Enteroviral Myocarditis and Dilated Cardiomyopathy*

    PubMed Central

    Gorbea, Carlos; Makar, Kimberly A.; Pauschinger, Matthias; Pratt, Gregory; Bersola, Jeathrina L. F.; Varela, Jacquelin; David, Ryan M.; Banks, Lori; Huang, Chien-Hua; Li, Hua; Schultheiss, Heinz-Peter; Towbin, Jeffrey A.; Vallejo, Jesús G.; Bowles, Neil E.

    2010-01-01

    The innate antiviral response is mediated, at least in part, by Toll-like receptors (TLRs). TLR3 signaling is activated in response to viral infection, and the absence of TLR3 in mice significantly increases mortality after infection with enteroviruses that cause myocarditis and/or dilated cardiomyopathy. We screened TLR3 in patients diagnosed with enteroviral myocarditis/cardiomyopathy and identified a rare variant in one patient as well as a significantly increased occurrence of a common polymorphism compared with controls. Expression of either variant resulted in significantly reduced TLR3-mediated signaling after stimulation with synthetic double-stranded RNA. Furthermore, Coxsackievirus B3 infection of cell lines expressing mutated TLR3 abrogated activation of the type I interferon pathway, leading to increased viral replication. TLR3-mediated type I interferon signaling required cellular autophagy and was suppressed by 3-methyladenine and bafilomycin A1, by inhibitors of lysosomal proteolysis, and by reduced expression of Beclin 1, Atg5, or microtubule-associated protein 1 light chain 3β (MAP1LC3β). However, TLR3-mediated signaling was restored upon exogenous expression of Beclin 1 or a variant MAP1LC3β fusion protein refractory to RNA interference. These data suggest that individuals harboring these variants may have a blunted innate immune response to enteroviral infection, leading to reduced viral clearance and an increased risk of cardiac pathology. PMID:20472559

  16. Modulation of endoplasmic reticulum stress and cardiomyocyte apoptosis by mulberry leaf diet in experimental autoimmune myocarditis rats

    PubMed Central

    Arumugam, Somasundaram; Thandavarayan, Rajarajan A.; Veeraveedu, Punniyakoti T.; Ma, Meilei; Giridharan, Vijayasree V.; Arozal, Wawaimuli; Sari, Flori R.; Sukumaran, Vijayakumar; Lakshmanan, Arunprasath; Soetikno, Vivian; Suzuki, Kenji; Kodama, Makoto; Watanabe, Kenichi

    2012-01-01

    Mulberry is commonly used as silkworm diet and an alternative medicine in Japan and China, has recently reported to contain many antioxidative flavanoid compounds and having the free radical scavenging effects. Antioxidants reduce cardiac oxidative stress and attenuate cardiac dysfunction in animals with pacing-induced congestive heart failure. Hence we investigated the cardioprotective effect of mulberry leaf powder in rats with experimental autoimmune myocarditis. Eight-week-old Lewis rats immunized with cardiac myosin were fed with either normal chow or a diet containing 5% mulberry leaf powder and were examined on day 21. ML significantly decreased oxidative stress, myocyte apoptosis, cellular infiltration, cardiac fibrosis, mast cell density, myocardial levels of sarco/endo-plasmic reticulum Ca2+ ATPase2, p22phox, receptor for advanced glycation end products, phospho-p38 mitogen activated protein kinase, phospho-c-Jun NH2-terminal protein kinase, glucose regulated protein78, caspase12 and osteopontin levels in EAM rats. These results may suggest that mulberry diet can preserve the cardiac function in experimental autoimmune myocarditis by modulating oxidative stress induced MAPK activation and further afford protection against endoplasmic reticulum stress mediated apoptosis. PMID:22448095

  17. Intein-mediated backbone cyclization of VP1 protein enhanced protection of CVB3-induced viral myocarditis

    PubMed Central

    Qi, Xingmei; Xiong, Sidong

    2017-01-01

    CVB3 is a common human pathogen to be highly lethal to newborns and causes viral myocarditis and pancreatitis in adults. However, there is no vaccine available for clinical use. CVB3 capsid protein VP1 is an immunodominant structural protein, containing several B- and T-cell epitopes. However, immunization of mice with VP1 protein is ineffective. Cyclization of peptide is commonly used to improve their in vivo stability and biological activity. Here, we designed and synthesizd cyclic VP1 protein by using engineered split Rma DnaB intein and the cyclization efficiency was 100% in E. coli. As a result, the cyclic VP1 was significantly more stable against irreversible aggregation upon heating and against carboxypeptidase in vitro and the degradation rate was more slowly in vivo. Compared with linear VP1, immunization mice with circular VP1 significantly increased CVB3-specific serum IgG level and augmented CVB3-specific cellular immune responses, consequently afforded better protection against CVB3-induced viral myocarditis. The cyclic VP1 may be a novel candidate protein vaccine for preventing CVB3 infection and similar approaches could be employed to a variety of protein vaccines to enhance their protection effect. PMID:28148910

  18. Clinical Outcomes in Pediatric Patients Hospitalized with Fulminant Myocarditis Requiring Extracorporeal Membrane Oxygenation: A Meta-analysis.

    PubMed

    Xiong, Haolan; Xia, Bingqing; Zhu, Jingyu; Li, Binfei; Huang, Wenqi

    2017-02-01

    We conducted a meta-analysis to provide the survival rates for pediatric patients hospitalized with fulminant myocarditis requiring ECMO. The literature search was conducted using Embase, PubMed, MEDLINE and Elsevier for studies published before April 1, 2016. We focus on survival rates for pediatric patients hospitalized with fulminant myocarditis requiring ECMO, and studies that reported only on adult patients were excluded. Summary of the survival rates was obtained using fixed-effect or random-effect meta-analysis which determined by I (2). Six studies were included in the analysis, encompassing 172 patients. The minimum and maximum reported rates of survival to hospital discharge were 53.8 and 83.3%, respectively. The cumulative rate was 107/172. The calculated Cochran Q value was 3.73, which was not significant for heterogeneity (P = 0.588). The I (2) value was 0%. The pooled estimate rate was 62.9% with a 95% confidence interval of 55.3-69.8%. In pediatric patients with cardiac failure who have failed conventional therapies in FM, venoarterial ECMO should be considered. In total, 62.9% of patients with FM and either cardiogenic shock and/or cardiac arrest survived to hospital discharge with ECMO.

  19. Lymphocytic enteritis in a filly.

    PubMed

    Clark, E S; Morris, D D; Allen, D; Tyler, D E

    1988-11-15

    A yearling Hanoverian filly had intermittent colic for 6 weeks, chylous peritoneal effusion, and a firm mass palpable per rectum. Exploratory laparotomy revealed mesenteric lymphadenopathy, adhesion of the mesenteric root to the duodenum and jejunum, distention of the mesenteric veins and lymphatic vessels, and increased jejunal venous pressure. Lesions in the duodenum, jejunum, and colon included infiltration of lymphocytes and plasma cells in the lamina propria.

  20. Characterisation of a novel pestivirus associated with an outbreak of stillbirths and pre-weaning deaths in pigs due to myocarditis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A syndrome of stillbirths and preweaning losses with myocarditis occurred on 2 Australian pig farms in 2003. While extensive investigations excluded a wide range of know agents, a foetal inoculation study confirmed an infectious agent was present and likely to be viral. This paper describes the iden...

  1. Toxoplasma gondii-Infected Human Myeloid Dendritic Cells Induce T-Lymphocyte Dysfunction and Contact-Dependent Apoptosis

    PubMed Central

    Wei, Shuang; Marches, Florentina; Borvak, Jozef; Zou, Weiping; Channon, Jacqueline; White, Michael; Radke, Jay; Cesbron-Delauw, Marie-France; Curiel, Tyler J.

    2002-01-01

    Dendritic cells ignite adaptive immunity by priming naïve T lymphocytes. Human monocyte-derived dendritic cells (MDDCs) infected with Toxoplasma gondii induce T-lymphocyte gamma interferon production and may thus activate T. gondii-specific immunity. However, we now demonstrate that T. gondii-infected MDDCs are poor at activating T lymphocytes and are unable to induce specific cytotoxic T lymphocytes. On the other hand, MDDCs acquiring nonviable T. gondii antigens directly, or indirectly through captured apoptotic or necrotic cell bodies, induce potent T-lymphocyte activation. T lymphocytes exposed to infected MDDCs are significantly impaired in upregulation of CD69 and CD28, are refractory to activation, and die through contact-dependent apoptosis mediated by an as-yet-unidentified mechanism not requiring Fas, tumor necrosis factor-related apoptosis-inducing ligand, leukocyte function antigen 1, intercellular adhesion molecule 1, tumor necrosis factor alpha, interleukin 10, alpha interferon, gamma interferon, prostaglandins, or reactive nitrogen intermediates. Bystander T lymphocytes that were neither infected nor apoptotic were refractory to activation, suggesting global dysfunction. Immunosuppression and T-lymphocyte unresponsiveness and apoptosis are typical of acute T. gondii infection. Our data suggest that infected dendritic cells contribute to these processes. On the other hand, host cells infected with T. gondii are resistant to multiple inducers of apoptosis. Thus, regulation of host cell and bystander cell apoptosis by viable T. gondii may be significant components of a strategy to evade immunity and enhance intracellular parasite survival. PMID:11895936

  2. [Presence of B cell clones in acute myelomonocytic leukemia].

    PubMed

    Novoa, Viviana; Nuñez, Neri; Cervellini, Mirta; Starosta, Aida; Carballo, Orlando G

    2010-01-01

    The coexistence of acute myeloid leukemia and chronic lymphocytic leukemia in the same patient is rare. The majority of the cases correspond to patients that developed acute leukemia during the evolutionary course of a chronic lymphatic leukemia following treatment with chemotherapy drugs. We report a case of acute myelomonocytic leukemia concurrent with untreated B-cell chronic lymphocytic leukemia in which the use of flow cytometry analysis with a large panel of monoclonal antibodies, allowed the demonstration of different pathological populations and determine immunophenotyping patterns. Published cases of simultaneous chronic lymphocytic leukemia and acute leukemia are reviewed. The use of multiparametric flow cytometry to differentiate the populations demonstrates the utility of this technology in the diagnosis of these hematological malignancies.

  3. 47,XYY karyotype in acute myeloid leukemia.

    PubMed

    Palanduz, S; Aktan, M; Ozturk, S; Tutkan, G; Cefle, K; Pekcelen, Y

    1998-10-01

    A case of acute myelomonocytic leukemia (AMMoL; M4) with a 47,XYY karyotype is reported. This chromosome aneuploidy was found in both bone marrow cells and mitogen-stimulated lymphocytes. The contribution of XYY chromosomal constitution in the pathogenesis of AMMoL is controversial.

  4. The use of decompression to simulate the effect of extravehicular activity on human lymphocyte transformation

    NASA Technical Reports Server (NTRS)

    Meehan, R. T.; Duncan, U.; Neale, L.; Waligora, J.; Taylor, G. R.

    1986-01-01

    Lymphocytes from 35 subjects participating in a chamber study simulating extravehicular activity (EVA) conditions were studied. No significant differences in H3 thymidine uptake between pre chamber and post chamber response to any mitogens autologous plasma, or among circulating mononuclear cells by flow cytometry are observed. The studies could not identify the subjects who developed venous bubbles. Data from eight subjects suggests that acute stress associated with participating in the study augments in vitro lymphocyte proliferation. Results indicate EVA exposure does not greatly influence space-flight induced alterations in immune effector cell function.

  5. Obatoclax, Fludarabine, and Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-09-27

    B-cell Chronic Lymphocytic Leukemia; Leukemia; Prolymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

  6. Oleanolic acid modulates the immune-inflammatory response in mice with experimental autoimmune myocarditis and protects from cardiac injury. Therapeutic implications for the human disease.

    PubMed

    Martín, R; Cordova, C; San Román, J A; Gutierrez, B; Cachofeiro, V; Nieto, M L

    2014-07-01

    Myocarditis and dilated cardiomyopathy (DCM) are inflammatory diseases of the myocardium, for which appropriate treatment remains a major clinical challenge. Oleanolic acid (OA), a natural triterpene widely distributed in food and medicinal plants, possesses a large range of biological effects with beneficial properties for health and disease prevention. Several experimental approaches have shown its cardioprotective actions, and OA has recently been proven effective for treating Th1 cell-mediated inflammatory diseases; however, its effect on inflammatory heart disorders, including myocarditis, has not yet been addressed. Therefore, the present study was undertaken to determine the effectiveness of OA in prevention and treatment of experimental autoimmune myocarditis (EAM). The utility of OA was evaluated in vivo through their administration to cardiac α-myosin (MyHc-α614-629)-immunized BALB/c mice from day 0 or day 21 post-immunization to the end of the experiment, and in vitro through their addition to stimulated-cardiac cells. Prophylactic and therapeutic administration of OA dramatically decreased disease severity: the heart weight/body weight ratio as well as plasma levels of brain natriuretic peptide and myosin-specific autoantibodies production were significantly reduced in OA-treated EAM animals, compared with untreated ones. Histological heart analysis showed that OA-treatment diminished cell infiltration, fibrosis and dystrophic calcifications. OA also decreased proliferation of cardiac fibroblast in vitro and attenuated calcium and collagen deposition induced by relevant cytokines of active myocarditis. Furthermore, in OA-treated EAM mice the number of Treg cells and the production of IL-10 and IL-35 were markedly increased, while proinflammatory and profibrotic cytokines were significantly reduced. We demonstrate that OA ameliorates both developing and established EAM by promoting an antiinflammatory cytokine profile and by interfering with the

  7. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  8. Mechanisms responsible for defective human T-lymphocyte sheep erythrocyte rosette function associated with hepatitis B virus infections.

    PubMed Central

    Chisari, F V; Routenberg, J A; Edgington, T S

    1976-01-01

    The expression of selected lymphocyte surface-membrane markers was evaluated in 37 patients with acute viral hepatitis B, 10 of whom were studied serially through the resolving and convalescent phases of disease. Bone marrow-derived (B) lymphocytes were identified by reference to surface immunoglobulin, whereas normal thymus-derived (T) lymphocytes were assayed by their capacity to form spontaneous nonimmune rosettes with sheep erythrocytes (E rosettes, ER). During the acute and resolving phases of viral hepatitis B, the relative and absolute number of ER-positive lymphocytes was significantly reduced, whereas the number of surface immunoglobulin-positive lymphocytes and the absolute lymphocyte count remained normal. This resulted in the appearance of a third population of cells, deficient in respect to both surface immunoglobulin and ER markers. Such cells accounted for nearly 25% of peripheral blood lymphocytes, approximately 5 x 105ml blood. Depression of the number of ER-positive lymphocytes occurred at least once during the course of disease in every patient studied serially, and was observed in 55 of 67 individual assays of the 37 cases of acute viral hepatitis B. Lymphocytes from some patients reacquired ER function when cultured in fetal calf serum but not in the presence of autologous serum. Such autologous serum was capable of suppressing ER function of lymphocytes from normal donors. The extrinsic suppression of er function by a serum factor (designated as the Rosette Inhibitory Factor), was found to be time dependent, characterized by a 4-h latent period and requiring approximately 18 h for maximum attenuation of ER function. The Serum Rosette Inhibitory Factor was: (a) heat and freeze-thaw stable, (b) nondialyzable, (c) physically separable from hepatitis B surface antigen, (d) not a lymphocytotoxic antibody, and (e) had the buoyant density of a lipoprotein. This extrinsic mechanism was observed in 41.8% of patients with reduced numbers of ER

  9. Human mixed lymphocyte culture using separated lymphocyte populations.

    PubMed Central

    Potter, M R; Moore, M

    1977-01-01

    The ability of human blood lymphocyte populations enriched with T or B cells to act as responder and stimulator populations in the one-way mixed lymphocyte reaction (MLR) was investigated. T- and B-cell-enriched populations were obtained by separation of rosette-forming and non rosette-forming cells and T-cell-enriched populations were also obtained by nylon-fibre column filtration. Using cells prepared by rosette sedimentation, control unseparated and T-cell-enriched populations responded well when stimulated by mitomycin C-treated unseparated cells from a second individual; and stimulation by T- and B-enriched populations generally produced some response, although the magnitude was variable. B-cell-enriched populations gave virtually no response regardless of the composition of the stimulating populations. Nylon-column-enriched T-cell populations responded to stimulation by control unseparated cells but not to T cells purified by the same procedure. T-cell enriched populations prepared by the two methods thus had different activities in the MLR despite containing similar numbers of T cells suggesting that other factors, such as the presence of small numbers of accessory cells, are important in determining the magnitude of the MLR. PMID:139361

  10. Adipose tissue lymphocytes: types and roles.

    PubMed

    Caspar-Bauguil, S; Cousin, B; Bour, S; Casteilla, L; Castiella, L; Penicaud, L; Carpéné, C

    2009-12-01

    Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development.

  11. Effect of hydrodynamics-based delivery of IL-18BP fusion gene on rat experimental autoimmune myocarditis.

    PubMed

    Chang, He; Wang, Yan; Li, Gang; Zhang, Le; Zhang, Guang Wei; Liao, Yan Chun; Hanawa, Haruo; Zou, Jun

    2014-11-01

    Interleukin-18 (IL-18) is a powerful and important cytokine in myocarditis. IL-18-binding protein (IL-18BP), a naturally occurring antagonist of IL-18, is presumed to play a vital regulatory function in IL-18-mediated immune responses. The purpose of this study was to evaluate the alterations of IL-18 and its related protein expressions and the effect of hydrodynamics-based delivery of the IL-18BP gene for treatment of rat experimental autoimmune myocarditis (EAM).Rats were immunized on Day 0 and killed on 2, 3 and 4 weeks to determine IL-18 and its related protein expression and target cells in EAM hearts. On Day 6, rats were injected with a recombinant plasmid encoding IL-18BP-Ig or SP-Ig. On Day 17, rats were detected with echocardiography and then be killed. IL-18BP gene therapy was effective in controlling EAM, as monitored by a decreased ratio of heart weight to body weight, reduced myocarditis areas, reduced expression of atrial natriuretic peptide, brain natriuretic peptide, IL-17, IFN-γ, IL-6 and IL-10. Furthermore, the effect of serum containing IL-18BP on the expression of immune-relevant genes in IL-1α-stimulated NC cells and splenocytes cultured from EAM rats was examined. The results showed that IL-18BP significantly suppressed the expression of IL-17 as well as other proinflammatory genes such as transforming growth factor-β, prostaglandin E2 synthase, cyclooxygenase-2 in IL-1α-stimulated NC cells, and IL-18BP also significantly suppressed the expression of IL-17, IL-17R, IL-21 and IL-17-related transcriptional factor retinoic acid-related orphan nuclear receptor, signal transducer and activator of transcription-3 and Foxp3 in IL-1α-stimulated splenocytes cultured from EAM rats. IL-18 and its related protein played an important role on the development of EAM. IL-18BP effectively prevented progression of EAM by blocking IL-17 and related inflammatory genes expression. This might be a possible mechanism of the amelioration of EAM by IL-18BP

  12. The cloning of T lymphocytes.

    PubMed

    Schwartz, R H

    1982-02-01

    A new era of cellular immunology is clearly at hand. It is now possible, with a little bit of effort, to isolate monoclonal populations of T cells specific for any given antigen. The implications o f this technological advance are enormous in terms of applications to basic research and clinical medicine. In this article the two basic approaches that have been used to clone T lymphocytes are outlined, the pros and cons of each technique discussed and examples are given of recent experiments which have exploited this technology to gain new insights into T-cell specificity.

  13. [Apoptosis in chronic lymphocytic leukemia].

    PubMed

    Giordano, M

    2000-01-01

    Chronic lymphocytic leukemia of B cells (B-CLL) is the most prevalent leukemia in the Occidental Hemisphere. It is characterized by a progressive accumulation of monoclonal CD5+ B lymphocytes, with low amounts of surface Ig. Most B-CLL cells are arrested in the G0 phase of the cell cycle; therefore their accumulation in vivo appears to result from the inhibition of apoptosis which has been attributed to over-expression of the anti-apoptotic protein Bcl-2. When cultured in vitro, spontaneous apoptosis occurs, suggesting the existence in vivo of survival-promoting factors. We here show that non-malignant leukocytes, particularly monocytes and NK cells, are able to inhibit B-CLL cells apoptosis, at least in part, through the release of soluble factors. Neutralizing antibodies directed to interferon-gamma or IL-4 only partially abolish the protecting effects of accessory cells suggesting that they are not the main cytokines involved. Increased apoptosis of B-CLL cells is not associated with modifications in the expression of Bcl-2, Fas or Fas ligand. Considering that B-CLL is associated to autoimmune phenomena and recurrent infections due to hypogammaglobulinemia, it should be interesting to correlate the activation of immune responses with disease progression.

  14. [The clinical practice guidelines of the Sociedad Española de Cardiología on cardiomyopathies and myocarditis].

    PubMed

    Galve Basilio, E; Alfonso Manterola, F; Ballester Rodés, M; Castro Beiras, A; Fernández de Soria Pantoja, R; Penas Lado, M; Sánchez Domínguez, J

    2000-03-01

    Myocardial diseases are a extraordinarily heterogeneous group of processes that only have in common the fact that they involve heart muscle and that they cause a wide spectrum of myocardial dysfunction. The approach of the management and treatment of the cardiomyopathies is a continuous matter of discussion because the vast majority of alternatives in this field have not been based on the best scientific possible evidence and, since except for the case of heart failure associated with dilated cardiomyopathy. The majority of different options have not been studied by means of large (or even small) randomized trials. Nevertheless, this chapter has tried to provide the reader with different approaches on how to deal with important clinical problems in dilated, hypertrophic and restrictive cardiomyopathies, and in myocarditis as well. For this, we have utilized the most relevant information found coupled with our best clinical judgment, although we admit that many of the clinical recommendations can be controversial.

  15. Correlation of left ventricular wall thickness, heart mass, serological parameters and late gadolinium enhancement in cardiovascular magnetic resonance imaging of myocardial inflammation in an experimental animal model of autoimmune myocarditis.

    PubMed

    Kromen, Wolfgang; Korkusuz, Huedayi; Korkusuz, Yuecel; Esters, Philip; Bauer, Ralf W; Huebner, Frank; Lindemayr, Sebastian; Vogl, Thomas J

    2012-12-01

    For a definitive diagnosis of myocarditis, different strategies like analysis of late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR) up to invasive endomyocardial biopsy have been applied. The objective of the study was to investigate inflammatory changes like left ventricular wall thickening and increase of ventricular mass and to quantitatively analyse their correlation with extent and localisation of myocardial damage in CMR and with subsequent changes of serological markers in an animal model of an experimental autoimmune myocarditis (EAM). In the current study, an EAM was induced in 10 male Lewis rats, 10 rats served as control. On day 21, animals were examined with four CMR protocols to assess the extent of LGE in a 12 segment model of the rat heart. Left myocardial wall thickness and mass and histological grade of inflammation were measured to determine localisation and severity of the induced myocarditis. Depending on the CMR sequence, LGE was mostly found in the left anterior (9.6%) and left lateral (8.7%) myocardial wall segments. Wall thickness correlated with the LGE area in CMR imaging and the histopathological severity of myocarditis for the left lateral myocardial wall segment. In a similar way, the heart mass correlated to the extent of LGE for the left lateral segment. We conclude that in our animal model left ventricular wall thickness and mass reflect the severity of myocardial changes in myocarditis and that the EAM rat model is well suited for further investigations of myocarditis.

  16. The Role of Lymphocytes in Radiotherapy-Induced Adverse Late Effects in the Lung

    PubMed Central

    Wirsdörfer, Florian; Jendrossek, Verena

    2016-01-01

    Radiation-induced pneumonitis and fibrosis are dose-limiting side effects of thoracic irradiation. Thoracic irradiation triggers acute and chronic environmental lung changes that are shaped by the damage response of resident cells, by the resulting reaction of the immune system, and by repair processes. Although considerable progress has been made during the last decade in defining involved effector cells and soluble mediators, the network of pathophysiological events and the cellular cross talk linking acute tissue damage to chronic inflammation and fibrosis still require further definition. Infiltration of cells from the innate and adaptive immune systems is a common response of normal tissues to ionizing radiation. Herein, lymphocytes represent a versatile and wide-ranged group of cells of the immune system that can react under specific conditions in various ways and participate in modulating the lung environment by adopting pro-inflammatory, anti-inflammatory, or even pro- or anti-fibrotic phenotypes. The present review provides an overview on published data about the role of lymphocytes in radiation-induced lung disease and related damage-associated pulmonary diseases with a focus on T lymphocytes and B lymphocytes. We also discuss the suspected dual role of specific lymphocyte subsets during the pneumonitic phase and fibrotic phase that is shaped by the environmental conditions as well as the interaction and the intercellular cross talk between cells from the innate and adaptive immune systems and (damaged) resident epithelial cells and stromal cells (e.g., endothelial cells, mesenchymal stem cells, and fibroblasts). Finally, we highlight potential therapeutic targets suited to counteract pathological lymphocyte responses to prevent or treat radiation-induced lung disease. PMID:28018357

  17. The comparison of α-bromo-4-chlorocinnamaldehyde and cinnamaldehyde on coxsackie virus B3-induced myocarditis and their mechanisms.

    PubMed

    Zhang, Ya; Cao, Wei; Xie, Yan-Hua; Yang, Qian; Li, Xiao-Qiang; Liu, Xin-Xin; Wang, Si-Wang

    2012-09-01

    Early experiments showed cinnamaldehyde had obvious therapeutic effect on viral myocarditis, but cinnamaldehyde was unstable in vivo. To overcome this limitation, we used cinnamaldehyde as a lead compound to synthesize α-bromo-4-chlorocinnamaldehyde (BCC). In the present study, we compared the therapeutic effects of BCC with cinnamaldehyde on coxsackie virus B3 (CVB3)-induced viral myocarditis (VMC), as well as investigated the possible mechanism. The antiviral and cytotoxic effects in vitro were evaluated on HeLa cells infected by CVB3 and rat cardiomyocytes respectively. Our results showed that IC50 were 0.78±0.13 μM and 48.16±5.79 μM in BCC and cinnamaldehyde-treated cells. 50% toxic concentration (TC) in BCC-treated cells was 22-fold higher than in the cinnamaldehyde group. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. The results demonstrated that BCC reduced the viral titers and cardiac pathological changes in a dose-dependent manner. Myocardial virus titers were significantly lower in the 50 mg/kg BCC-treated group than in cinnamaldehyde groups. In addition, BCC could significantly inhibit the replication of CVB3 mRNA and the secretion of inflammatory cytokines TNF-α, IL-β and IL-6 in CVB3-infected cardiomyocytes. We further observed that BCC suppressed CVB3-induced NF-κB activation, IκB-α degradation and phosphorylation in a concentration-dependent manner, and reduced Toll like receptor (TLR) 4 protein level in hearts. These results suggest that BCC had a promising therapeutic effect on VMC with a highly significant favorable effects and less toxicity than cinnamaldehyde. Furthermore, the effect of BCC on VMC might be through inhibition of inflammatory signaling.

  18. Activated nuclear transcription factor {kappa}B in patients with myocarditis and dilated cardiomyopathy-relation to inflammation and cardiac function

    SciTech Connect

    Alter, Peter . E-mail: palter@med.uni-marburg.de; Rupp, Heinz; Maisch, Bernhard

    2006-01-06

    Objectives and background: Myocarditis is caused by various agents and autoimmune processes. It is unknown whether viral genome persistence represents inactive remnants of previous infections or whether it is attributed to ongoing adverse processes. The latter also applies to the course of autoimmune myocarditis. One principal candidate for an adverse remodeling is nuclear factor-{kappa}B (NF{kappa}B). Methods: A total of 93 patients with suspected myocarditis/cardiomyopathy was examined. Hemodynamics were assessed by echocardiography as well as right and left heart catheterization. Endomyocardial biopsies were taken from the left ventricle. Biopsies were examined by immunohistochemistry and PCR for viral genomes. Selective immunostaining of activated NF{kappa}B was performed. Results: NF{kappa}B was increased in patients with myocarditis when compared with controls (11.1 {+-} 7.1% vs. 5.0 {+-} 5.3%, P < 0.005) whereas dilated cardiomyopathy showed no significant increase. Patients with myocarditis and preserved left ventricular function exhibited increased activated NF{kappa}B when compared with reduced function (r {sup 2} = 0.72, P < 0.001). In parallel, inverse correlation of NF{kappa}B and left ventricular enddiasstolic volume was found (r {sup 2} = 0.43, P < 0.02). Increased activated NF{kappa}B was found in adenovirus persistence when compared with controls (P = 0.001). Only a trend of increased NF{kappa}B activation was seen in cytomegalovirus persistence. Parvovirus B19 persistence did not affect NF{kappa}B activation. Conclusions: Increased activation of NF{kappa}B is related to inflammatory processes in myocarditis. Since activated NF{kappa}B correlates with left ventricular function, it could be assumed that NF{kappa}B activation occurs at early stages of inflammation. Potentially, NF{kappa}B could inhibit loss of cardiomyocytes by apoptosis and protect from cardiac dilation. Since NF{kappa}B is a crucial key transcription factor of inflammation, its

  19. What Are the Key Statistics for Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... What Are the Key Statistics for Chronic Lymphocytic Leukemia? The American Cancer Society's estimates for leukemia in ... Leukemia Research and Treatment? More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  20. Suppression of mixed lymphocyte reactivity by human chorionic gonadotrophin

    PubMed Central

    Beling, C. G.; Weksler, M. E.

    1974-01-01

    Highly purified human chorionic gonadotrophin inhibits the response of lymphocytes from both male and female subjects to allogeneic cells in mixed lymphocyte culture. Human chorionic gonadotrophin is not cytotoxic for human lymphocytes. PMID:4283122