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Sample records for murine myocarditis due

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

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    Shunichi Shibazaki

    2016-01-01

    Full Text Available 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.

  2. Pulmonary Edema and Myocarditis Developing Due to Scorpion Stings

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    Sevdegul Karadas

    2015-11-01

    Full Text Available Although most of the scorpion stings are harmless, deadly species of scorpions may cause multiorgan failure, neurotoxicity, cardiotoxicity, and pulmonary edema. The cases should be observed in the emergency department against the possibility of development of systemic effects. Fatal complications, in particular such as pulmonary edema, and myocarditis should be considered. In this study, a case of myocarditis and pulmonary edema was detected on the patient who had applied to the emergency department due to a scorpion sting is presented.

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

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    Xavier Helluy

    Full Text Available 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.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.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 localization of

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

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    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

  5. Pediatric Death Due to Myocarditis After Exposure to Cannabis

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    Thomas M. Nappe

    2017-03-01

    Full Text Available Since marijuana legalization, pediatric exposures to cannabis have increased. 1 To date, pediatric deaths from cannabis exposure have not been reported. The authors report an 11-month-old male who, following cannabis exposure, presented with central nervous system depression after seizure, and progressed to cardiac arrest and died. Myocarditis was diagnosed post-mortem and cannabis exposure was confirmed. Given the temporal relationship of these two rare occurrences – cannabis exposure and sudden death secondary to myocarditis in an 11-month-old – as well as histological consistency with drug-induced myocarditis without confirmed alternate causes, and prior reported cases of cannabis-associated myocarditis, a possible relationship exists between cannabis exposure in this child and myocarditis leading to death. In areas where marijuana is commercially available or decriminalized, the authors urge clinicians to preventively counsel parents and to include cannabis exposure in the differential diagnosis of patients presenting with myocarditis.

  6. Pharmacokinetics of indium-111-labeled antimyosin monoclonal antibody in murine experimental viral myocarditis

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    Yamada, T.; Matsumori, A.; Watanabe, Y.; Tamaki, N.; Yonekura, Y.; Endo, K.; Konishi, J.; Kawai, C.

    1990-01-01

    The pharmacokinetics of indium-111-labeled antimyosin monoclonal antibody Fab were investigated with use of murine experimental viral myocarditis as a model. The biodistribution of indium-111-labeled antimyosin antibody Fab on days 3, 5, 7, 14, 21 and 28 after encephalomyocarditis virus inoculation demonstrated that myocardial uptake increased significantly on days 5, 7 and 14 (maximum on day 7) in infected versus uninfected mice (p less than 0.001). In vivo kinetics in infected mice on day 7 demonstrated that the heart to blood ratio reached a maximum 48 h after the intravenous administration of indium-111-labeled antimyosin Fab, which was considered to be the optimal time for scintigraphy. The scintigraphic images obtained with indium-111-labeled antimyosin Fab demonstrated positive uptake in the cardiac lesion in infected mice. The pathologic study demonstrated that myocardial uptake correlated well with pathologic grades of myocardial necrosis. High performance liquid chromatography revealed the presence of an antigen-antibody complex in the circulation of infected mice after the injection of indium-111-labeled antimyosin Fab. This antigen bound to indium-111-labeled antimyosin Fab in the circulation might be whole myosin and this complex may decrease myocardial uptake and increase liver uptake. It is concluded that indium-111-labeled antimyosin monoclonal antibody Fab accumulates selectively in damaged heart tissue in mice with acute myocarditis and that indium-111-labeled antimyosin Fab scintigraphy may be a useful method for the visualization of acute myocarditis

  7. Murine model of acute myocarditis and cerebral cortical neuron edema induced by coxsackievirus B4

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    Zhao-Peng Dong

    2018-01-01

    Full Text Available Globally, coxsackievirus B4 (CV-B4 has been continuously isolated and evidence suggests an association with the development of pancreatitis and type I diabetes. In addition, CV-B4 is also associated with myocarditis and severe central nervous system (CNS complications, which remain poorly studied and understood. In the present study, we established an ICR mouse model of CV-B4 infection and examined whether CV-B4 infection resulted in a predisposition to myocarditis and CNS infection. We found high survival in both the treatment and control group, with no significant differences in clinical outcomes observed. However, pathological lesions were evident in both brain and heart tissue of the CV-B4-infected mice. In addition, high viral loads were found in the neural and cardiac tissues as early as 2 d postinfection. Expressions of IFN-γ and IL-6 in sera were significantly higher in CV-B4-infected mice compared to uninfected negative controls, suggesting the involvement of these cytokines in the development of histopathological lesions. Our murine model successfully reproduced the acute myocarditis and cerebral cortical neuron edema induced by CV-B4, and may be useful for the evaluation of vaccine candidates and potential antivirals against CV-B4 infection.

  8. Human cardiac-derived adherent proliferating cells reduce murine acute Coxsackievirus B3-induced myocarditis.

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    Kapka Miteva

    Full Text Available BACKGROUND: Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. We recently isolated and identified novel cardiac-derived cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs. They have similarities with mesenchymal stromal cells, which are known for their anti-apoptotic and immunomodulatory properties. We explored whether CAPs application could be a novel strategy to improve acute Coxsackievirus B3 (CVB3-induced myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the safety of our approach, we first analyzed the expression of the coxsackie- and adenovirus receptor (CAR and the co-receptor CD55 on CAPs, which are both required for effective CVB3 infectivity. We could demonstrate that CAPs only minimally express both receptors, which translates to minimal CVB3 copy numbers, and without viral particle release after CVB3 infection. Co-culture of CAPs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis and viral progeny release. In addition, CAPs reduced CD4 and CD8 T cell proliferation. All CAPs-mediated protective effects were nitric oxide- and interleukin-10-dependent and required interferon-γ. In an acute murine model of CVB3-induced myocarditis, application of CAPs led to a decrease of cardiac apoptosis, cardiac CVB3 viral load and improved left ventricular contractility parameters. This was associated with a decline in cardiac mononuclear cell activity, an increase in T regulatory cells and T cell apoptosis, and an increase in left ventricular interleukin-10 and interferon-γ mRNA expression. CONCLUSIONS: We conclude that CAPs are a unique type of cardiac-derived cells and promising tools to improve acute CVB3-induced myocarditis.

  9. Eosinophilic myocarditis due to Churg-Strauss syndrome with markedly elevated eosinophil cationic protein.

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    Hara, Tomoya; Yamaguchi, Koji; Iwase, Takashi; Kadota, Muneyuki; Bando, Mika; Ogasawara, Kozue; Bando, Sachiko; Ise, Takayuki; Niki, Toshiyuki; Ueda, Yuka; Tomita, Noriko; Taketani, Yoshio; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Sata, Masataka

    2013-01-01

    A 67-year-old woman with asthma visited our hospital with increasing dyspnea and new-onset paresthesia and purpura in her legs. Physical examination showed a wheeze, pretibial edema, and surrounding purpura. Chest X-rays showed cardiac decompensation and an electrocardiogram revealed a new ST-T change. Laboratory data showed leukocytosis, hypereosinophilia (10,450/μL), troponin T(+), elevated BNP, and markedly elevated eosinophil cationic protein (ECP) (> 150 ng/mL). Echocardiography revealed diffuse left ventricular hypokinesis (ejection fraction 30%) with increased wall thickness. Coronary angiography was normal. Cardiac magnetic resonance imaging implied diffuse myocardial edema and subendocardial late gadolinium enhancement. Skin biopsy of purpura showed superfi cial perivascular dermatitis with remarkable eosinophilic infiltrations. No evidence of drug allergies, parasitic infection, or myeloproliferative disorder was detected. Based on these findings, a diagnosis of eosinophilic myocarditis due to Churg-Strauss syndrome was considered. She was administered prednisolone at a dose of 1 mg/kg, cyclophosphamide, and diuretics. Several markers of eosinophilic myocarditis and heart failure gradually improved, including ECP. She was discharged 30 days later with no cardiac event. Eosinophilic myocarditis is characterized by predominantly eosinophilic infi ltration. Eosinophilic granule proteins, such as ECP and major basic protein, play important roles in the pathogenesis of eosinophilic myocarditis. We experienced a rare case of eosinophilic myocarditis due to Churg-Strauss syndrome. Markedly elevated ECP played an important role in the early diagnosis and subsequent reduction in ECP served as a marker of monitoring. In an asthmatic patient with dyspnea, hypereosinophilia, and vasculitis, Churg-Strauss syndrome with eosinophilic myocarditis should be considered.

  10. Complete heart block due to diphtheritic myocarditis in the present era

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    Mithun J Varghese

    2013-01-01

    Full Text Available Diphtheria continues to be reported from many parts of the world. Complete heart block is rare but often fatal complication of diphtheric myocarditis. We report six children with diphtheric myocarditis who presented with complete heart block. Three patients survived, one with persistent complete heart block. Aggressive supportive management including transvenous pacing may result in complete recovery in a significant number of children with diphtheric myocarditis.

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

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

    2017-09-01

    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.

  12. Myocarditis - pediatric

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    ... page: //medlineplus.gov/ency/article/007307.htm Myocarditis - pediatric To use the sharing features on this page, please enable JavaScript. Pediatric myocarditis is inflammation of the heart muscle in ...

  13. CYTOKINE DISBALANCE AT HERPESVIRUS MYOCARDITIS

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    Peremot S. D

    2016-12-01

    , IL-10, INF-γ, TNF-α in blood serum was conducted by the method of solid-phase enzyme-linked immunosorbent assay, population structure of lymphocytes with different antigenic determinants (CD3+, CD4+, CD8+, CD16/56, CD19+, СD95+ was determined by monoclonal antibodies by cytofluorimetric assay. Obtained data processing was conducted with the use of parametric and non-parametric methods of biostatistics by programs EXEL-2003® and Biostatistics 4.03. Results and discussion. The data obtained indicates the disbalance in their system, which above all is characterized by a considerable level increase of pro-inflammatory IL-6 up to 134,09 ± 22,72 pg/ml (control level 11,83 ± 1,64 pg/ml and in relation to moderate growth of levels of IL-2 та TNF-α at subacute myocarditis. Such increase in level of IL-6 can take place due to the change of pro-inflammatory effect to anti-inflammatory in a remote period. In a complex with IL-10 IL-6 limits the secretion of TNF-α. For this reason, its level remains high at chronic herpesvirus myocarditis and exceeds the level of the control group by over 8 times. In addition, there is an increase of levels of anti-inflammatory IL-4, IL-10 cytokines at the chronic form of herpesvirus myocarditis course by 2,9 and 3,1 times respectively. At the same time, the level of IL-10 increased not only in comparison with the level of the control group but also almost 2 times exceeded the proper index at subacute myocarditis. Instead of the predicted INF-γ level rise, its decline was discovered, in patients with subacute course the index value was the lowest. This phenomenon can be the result of mast cells activity and in its turn influences the synthesis of collogen and processes of myocardium remodeling. Analysis of sub-population composition of lymphocytes discovered the increase in number of CD3+CD95+ lymphocytes of peripheral blood at myocarditis, especially in the group of patients with subacute herpesvirus myocarditis with its level

  14. Modern imaging of myocarditis. Possibilities and challenges

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    Baessler, B.; Maintz, D.; Bunck, A.C. [University Hospital of Cologne (Germany). Dept. of Radiology; Koeln Univ. (Germany). Radiology; Schmidt, M. [University Hospital of Cologne (Germany). Dept. of Nuclear Medicine; Luecke, C. [Universitaetsklinikum Leipzig, Herzzentrum Leipzig GmbH (Germany). Diagnostic and Interventional Radiology; Blazek, S. [Universitaetsklinikum Leipzig, Herzzentrum Leipzig GmbH (Germany). Dept. of Internal Medicine/Cardiology; Ou, P. [Universite Paris Diderot (France). Dept. of Cardiovascular Imaging

    2016-10-15

    Myocarditis is known as the chameleon of cardiac diseases. The symptoms and the course of disease vary greatly so that it is often challenging to establish a diagnosis. Early and accurate diagnosis is of utmost importance, since myocarditis is one of the leading causes of sudden cardiac death in young adults and represents an important precursor to dilated cardiomyopathy. Due to the constraints of the routinely used diagnostic approach, including clinical history and examination, laboratory testing, and electrocardiogram, different imaging modalities have emerged over the last decades as contributors to the noninvasive diagnosis of myocarditis. With this interdisciplinary review we would like to present the current state-of-the-art imaging of myocarditis across all available imaging modalities (i.e., echocardiography, cardiac magnetic resonance, cardiac computed tomography, and nuclear medicine). Furthermore, we present novel imaging techniques that might become useful in the near future for easier and more accurate diagnosis of this highly relevant disease.

  15. Vaccine Associated Myocarditis

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    Johnson Francis

    2017-04-01

    Full Text Available Most of the cases of vaccine associated myocarditis have been following small pox vaccination. Reports have also been there after streptococcal pneumonia vaccine and influenza vaccine. In some cases, autoimmune/inflammatory syndrome induced by adjuvants (ASIA used in the vaccine have been implicated. Exclusion of other causes is very important in the diagnostic process, especially that of acute coronary syndrome. Management is similar to that of other etiologies of myocarditis. These rare instances of myocarditis should not preclude one from taking necessary immunization for vaccine preventable diseases.

  16. MRI for myocarditis

    International Nuclear Information System (INIS)

    Gutberlet, M.; Luecke, C.; Krieghoff, C.; Hildebrand, L.; Steiner, J.; Adam, J.; Grotthoff, M.; Lehmkuhl, L.; Lurz, P.; Eitel, I.; Thiele, H.

    2013-01-01

    Cardiovascular magnetic resonance imaging (CMRI) has become the primary tool for the non-invasive assessment in patients with suspected myocarditis, especially after exclusion of acute coronary syndrome (ACS) for the differential diagnosis. Various MRI parameters are available which have different accuracies. Volumetric and functional ventricular assessment and the occurrence of pericardial effusion alone demonstrate only a poor sensitivity and specificity. The calculation of the T2-ratio (edema assessment), the early or global relative myocardial enhancement (gRE) and the late gadolinium enhancement (LGE), which represents irreversibly injured myocardium, are more specific parameters. All MRI parameters demonstrate the best accuracy in infarct-like acute myocarditis, whereas in chronic myocarditis sensitivity and specificity are less accurate. Therefore, a multisequential (at least two out of three parameters are positive) approach is recommended. The assessment of the value of newer, more quantitative MRI sequences, such as T1 and T2-mapping is still under investigation. (orig.) [de

  17. Infectious myocarditis (Clinic, diagnostics, principles of treatment

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    Yu. P. Finogeev

    2016-01-01

    Full Text Available Infective myocarditis can be considered as a case of myocardial damage caused by different infectious agents. Traditionally discusses the questions of diagnostics and treatment infectious myocarditis. The paper has repeatedly stressed the difficulty of clinical diagnosis, and the laboriousness and economic costs of laboratory tests and additional researches. Endomyocardial biopsy findings remain the gold standard for unequivocally establishing the diagnosis. However, it is technically extremely invasive test and can be performed only in specialized cardiology centers. The paper analyzes in detail not only own materials, but also results of researches published in numerous domestic and foreign sources of literature. Publication of «Infectious myocarditis» is necessary due to the fact that patients with a diagnosis of «Myocarditis » account for 11% of all cardiovascular disease in the world. Article is timely and necessary for many professionals, senior students of medical universities.

  18. Ventricular myocarditis coincides with atrial myocarditis in patients

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    Begieneman, Mark P. V.; Emmens, Reindert W.; Rijvers, Liza; Kubat, Bela; Paulus, Walter J.; Vonk, Alexander B. A.; Rozendaal, Lawrence; Biesbroek, P. Stefan; Wouters, Diana; Zeerleder, Sacha; van Ham, Marieke; Heymans, Stephane; van Rossum, Albert C.; Niessen, Hans W. M.; Krijnen, Paul A. J.

    2016-01-01

    Atrial fibrillation (AF) is a common complication in myocarditis. Atrial inflammation has been suggested to play an important role in the pathophysiology of AF. However, little is known about the occurrence of atrial inflammation in myocarditis patients. Here, we analyzed inflammatory cell numbers

  19. Diagnostic approach of myocarditis: strike the golden mean.

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    Hazebroek, M R; Everaerts, K; Heymans, S

    2014-02-01

    Myocarditis is a challenging diagnosis due to the extreme diversity of clinical manifestations. The actual incidence of myocarditis is also difficult to determine as endomyocardial biopsy (EMB), the diagnostic gold standard, is used infrequently. Nevertheless, in up to 30 % of patients with biopsy-proven myocarditis, progression to dilated cardiomyopathy (DCM) can occur and is associated with a poor prognosis. Recent position statements of the European Society of Cardiology (ESC) and the American Heart Association vary widely with regard to indications for performing an EMB in these patients. This makes decision-making, in particular for general practitioners (GPs) and regional hospitals, difficult and unclear. Therefore, we will present a short summary of the ESC Working Group on Myocardial and Pericardial Diseases statement and our suggestions for GPs and regional hospitals for the diagnostic approach in patients with suspected myocarditis.

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

    International Nuclear Information System (INIS)

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

    1984-01-01

    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

  1. Myocardial imaging. Coxsackie myocarditis

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    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.

  2. Myocardial imaging. Coxsackie myocarditis

    International Nuclear Information System (INIS)

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

    1986-01-01

    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

  3. Hypersensitivity myocarditis associated with ephedra use.

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    Zaacks, S M; Klein, L; Tan, C D; Rodriguez, E R; Leikin, J B

    1999-01-01

    Ephedrine has previously been described as a causative factor of vasculitis but myocarditis has not yet been associated with either ephedrine or its plant derivative ephedra. A 39-year-old African American male with hypertension presented to Rush Presbyterian St. Luke's Medical Center with a 1-month history of progressive dyspnea on exertion, orthopnea, and dependent edema. He was taking Ma Huang (Herbalife) 1-3 tablets twice daily for 3 months along with other vitamin supplements, pravastatin, and furosemide. Physical examination revealed a male in mild respiratory distress. The lung fields had rales at both bases without audible wheezes. Internal jugular venous pulsations were 5 cm above the sternal notch. Medical therapy with intravenous furosemide and oral enalapril was initiated upon admission. Cardiac catheterization with coronary angiography revealed normal coronary arteries, a dilated left ventricle, moderate pulmonary hypertension, and a pulmonary capillary wedge pressure of 34 mm Hg. The patient had right ventricular biopsy performed demonstrating mild myocyte hypertrophy and an infiltrate consisting predominantly of lymphocytes with eosinophils present in significantly increased numbers. Treatment for myocarditis was initiated with azothioprine 200 mg daily and prednisone 60 mg per day with a tapering course over 6 months. Anticoagulation with warfarin and diuretics was initiated and angiotensin-converting enzyme inhibition was continued. Hydralazine was added later. One month into therapy, an echocardiogram demonstrated improved left ventricular function with only mild global hypokinesis. A repeat right ventricular biopsy 2 months after the first admission showed no evidence of myocarditis. At 6 months, left ventricular ejection fraction was normal (EFN 50%) and the patient asymptomatic. Ephedra (Ma Huang) is the suspected cause of hypersensitivity myocarditis in this patient due to the temporal course of disease and its propensity to induce vasculitis.

  4. Clinical Presentation of Pediatric Myocarditis in Taiwan

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    Hsiang-Ju Hsiao

    2011-06-01

    Conclusions: Pediatric myocarditis presents primarily with gastrointestinal symptoms in Taiwan. Careful check of heart rhythm may provide a useful objective marker of myocarditis. The predictors of a poor prognosis were gastrointestinal symptoms, hepatomegaly, and hypotension.

  5. Giant Cell Myocarditis: Not Always a Presentation of Cardiogenic Shock

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    Rose Tompkins

    2015-01-01

    Full Text Available Giant cell myocarditis is a rare and often fatal disease. The most obvious presentation often described in the literature is one of rapid hemodynamic deterioration due to cardiogenic shock necessitating urgent consideration of mechanical circulatory support and heart transplantation. We present the case of a 60-year-old man whose initial presentation was consistent with myopericarditis but who went on to develop a rapid decline in left ventricular systolic function without overt hemodynamic compromise or dramatic symptomatology. Giant cell myocarditis was confirmed via endomyocardial biopsy. Combined immunosuppression with corticosteroids and calcineurin inhibitor resulted in resolution of symptoms and sustained recovery of left ventricular function one year later. Our case highlights that giant cell myocarditis does not always present with cardiogenic shock and should be considered in the evaluation of new onset cardiomyopathy of uncertain etiology as a timely diagnosis has distinct clinical implications on management and prognosis.

  6. Myocarditis in auto-immune or auto-inflammatory diseases.

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    Comarmond, Cloé; Cacoub, Patrice

    2017-08-01

    Myocarditis is a major cause of heart disease in young patients and a common precursor of heart failure due to dilated cardiomyopathy. Some auto-immune and/or auto-inflammatory diseases may be accompanied by myocarditis, such as sarcoidosis, Behçet's disease, eosinophilic granulomatosis with polyangiitis, myositis, and systemic lupus erythematosus. However, data concerning myocarditis in such auto-immune and/or auto-inflammatory diseases are sparse. New therapeutic strategies should better target the modulation of the immune system, depending on the phase of the disease and the type of underlying auto-immune and/or auto-inflammatory disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Acute Febrile Illness and Complications Due to Murine Typhus, Texas, USA1,2.

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    Afzal, Zeeshan; Kallumadanda, Sunand; Wang, Feng; Hemmige, Vagish; Musher, Daniel

    2017-08-01

    Murine typhus occurs relatively commonly in southern Texas, as well as in California. We reviewed records of 90 adults and children in whom murine typhus was diagnosed during a 3-year period in 2 hospitals in southern Texas, USA. Most patients lacked notable comorbidities; all were immunocompetent. Initial signs and symptoms included fever (99%), malaise (82%), headache (77%), fatigue (70%), myalgias (68%), and rash (39%). Complications, often severe, in 28% of patients included bronchiolitis, pneumonia, meningitis, septic shock, cholecystitis, pancreatitis, myositis, and rhabdomyolysis; the last 3 are previously unreported in murine typhus. Low serum albumin and elevated procalcitonin, consistent with bacterial sepsis, were observed in >70% of cases. Rash was more common in children; thrombocytopenia, hyponatremia, elevated hepatic transaminases, and complications were more frequent in adults. Murine typhus should be considered as a diagnostic possibility in cases of acute febrile illness in southern and even in more northern US states.

  8. Myocarditis in Paediatric Patients: Unveiling the Progression to Dilated Cardiomyopathy and Heart Failure

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    Inês Teixeira Farinha

    2016-11-01

    Full Text Available Myocarditis is a challenging and potentially life-threatening disease associated with high morbidity in some paediatric patients, due to its ability to present as an acute and fulminant disease and to ultimately progress to dilated cardiomyopathy. It has been described as an inflammatory disease of the myocardium caused by diverse aetiologies. Viral infection is the most frequent cause of myocarditis in developed countries, but bacterial and protozoal infections or drug hypersensitivity may also be causative agents. The prompt diagnosis in paediatric patients is difficult, as the spectrum of clinical manifestation can range from no myocardial dysfunction to sudden cardiac death. Recent studies on myocarditis pathogenesis have revealed a triphasic nature of this disease, which influences the diagnostic and therapeutic strategies to adopt in each patient. Endomyocardial biopsy remains the gold standard for diagnosing myocarditis, and several non-invasive diagnostic tools can be used to support the diagnosis. Intravenous immunoglobulin has become part of routine practice in the treatment of myocarditis in paediatric patients at many centres, but its true effect on the cardiac function has been the target of many studies. The aim of this review is to approach the recently discovered facets of paediatric myocarditis regarding its progression to dilated cardiomyopathy.

  9. Unusual Presentation of Dengue Fever; A child with acute myocarditis

    Directory of Open Access Journals (Sweden)

    Moaz Aslam

    2016-02-01

    Full Text Available Dengue fever (DF is an acute febrile illness that follows a self-limiting course. However, some patients suffer from complications, including myocarditis, due to the involvement of other organs. A child presented at the Aga Khan University Hospital in Karachi, Pakistan, in June 2013 with a high-grade fever, malaise and epigastric pain radiating to the chest. Positive DF antigen and immunoglobulin M assays confirmed the diagnosis of DF. Persistent bradycardia with low blood pressure led to further cardiac investigations which showed a decreased ejection fraction and raised serum cardiac enzymes, indicating myocardial damage. With supportive care and use of inotropes, the spontaneous normalisation of cardiac enzyme levels and ejection fraction was observed. The child was discharged five days after admission. This case highlights the importance of identifying myocarditis in DF patients suffering from cardiac symptoms that are not explained by other potential aetiologies. Awareness, early suspicion and supportive care are essential to ensure favourable outcomes.

  10. Management of acute myocarditis in children

    International Nuclear Information System (INIS)

    Merchant, Q.; Haque, A.; Hasan, B.S.

    2013-01-01

    Myocarditis is defined as the inflammation of the myocardium. It continues to be a significant cause of morbidity and mortality in the paediatric population and is the commonest cause of cardiac failure in a healthy child. Some studies estimate the incidence of myocarditis to be around 1 per 100000. PubMed search was performed using the term myocarditis. The search was limited to age 0-19 years. A total of 50 articles were identified between 1966 to date and reviewed. Myocarditis is a challenging diagnosis to make on clinical grounds and requires high index of suspicion. The cornerstone of treatment remains supportive though therapeutic modalities such as immunosuppressive and intravenous immunoglobulin therapies are being studied extensively. The overall prognosis of the disease is good with survival rates up to 80%. (author)

  11. sup(99m)Tc-pyrophosphate and /sup 201/Tl myocardial scintigrams in a patient with myocarditis

    Energy Technology Data Exchange (ETDEWEB)

    Kondo, M.; Nishimura, T.; Shimoto, Y.; Fuzioka, S.; Kobayashi, K. (Shimada City Hospital, Shizuoka (Japan))

    1981-09-01

    Myocardial necrosis in acute myocarditis was investigated by scintigraphy. sup(99m)Tc-pyrophosphate (PYP) and /sup 201/TI myocardial scintigrams were obtained on a patient with acute myocarditis due to mycoplasma infection. sup(99m)Tc-PYP myocardial scintigrams in the acute stage demonstrated grade 2+ findings, which remained until the chronic stage. /sup 201/TI myocardial scintigrams in the acute stage revealed impaired perfusion restricted to the posterolateral wall, and this decrease continued through the chronic stage. It was concluded that both of sup(99m)Tc-PYP and /sup 201/TI myocardial scintigrams can reveal abnormality of acute myocarditis.

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

    Directory of Open Access Journals (Sweden)

    Alessandro Costagliola

    2016-01-01

    Full Text Available 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.

  13. Myocarditis

    Science.gov (United States)

    ... causes a mild rash, usually in children (fifth disease); and herpes simplex virus. Gastrointestinal infections (echoviruses), mononucleosis (Epstein-Barr virus) and German measles (rubella) also can cause ...

  14. Cardiogenic shock due to citomegalovirus myocarditis: successful clinical treatment Choque cardiogênico devido à miocardite por citomegalovírus: terapêutica clínica com sucesso

    Directory of Open Access Journals (Sweden)

    José Francisco Baumgratz

    2010-06-01

    Full Text Available OBJECTIVE: Cytomegalovirus (CMV systemic disease and myocarditis in healthy persons is infrequently reported in the literature, although in increasing numbers in recent years. The importance of the recognition of the syndrome that usually has an initial picture of a mononucleosis like infection in an otherwise healthy person, is the available therapeutic agent, ganciclovir, that can cure the infectious disease. METHODS: We analyzed the clinical result of pulsotherapy with steroids in a patient with CMV myocarditis after 7 days of etiological treatment, with ganciclovir, intravenous vasodilators, and the conventional treatment for congestive heart failure. RESULTS: The clinical condition of the patient improved accordingly to the better function of the left ventricle, and the ganciclovir was kept for 21 days, most of it in an out patient basis. The patient was dismissed from the hospital, with normal myocardial function. CONCLUSION: Potentially curable forms of myocarditis, like M pneumoniae and CMV, for example, can have an initial disproportionate aggression to the myocardium, by the acute inflammatory reaction, that can by itself make worse the damage to the LV function. In our opinion, the blockade of this process by pulsotherapy with steroids can help in the treatment of these patients. We understand that the different scenario of immunosuppressive treatments for the possible auto immunity of the more chronic forms of the presumably post viral cardiomyopathy has been in dispute in the literature, and has stolen the focus from the truly acute cases.OBJETIVO: Doença sistêmica por citomegalovírus (CMV com miocardite em pessoas saudáveis é raramente referida na literatura, apesar de em maior número em anos recentes. A importância do reconhecimento da síndrome, que usualmente tem um quadro inicial "mononucleosis like" em uma pessoa sadia é a disponibilidade do agente terapêutico ganciclovir, que pode curar a infecção. MÉTODOS: N

  15. Detection of eosinophilic myocarditis using contrast-enhanced magnetic resonance imaging: case report

    International Nuclear Information System (INIS)

    Takahashi, N.; Murakami, Y.; Shimada, T.; Kashima, Y.; Nakamura, K.; Inoue, S.-I.; Sugamori, T.; Katoh, H.; Ishibashi, Y.; Maruyama, R.

    2001-01-01

    Hypereosinophilic syndrome is characterized by idiopathic eosinophilia in the peripheral blood and multiorgan dysfunction secondary to mature eosinophil infiltration. It is essential to diagnose myocardial involvement in the early stage of the disease when active myocarditis due to cardiotoxic substances from eosinophils is still taking place, but clinical tools for the diagnosis of myocardial lesions in patients without overt cardiac dysfunction are not yet available. We present a case of successful detection of myocarditis due to hypereosinophilic syndrome by gadolinium-diethylenetriaminepentaascetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI). (author)

  16. Detection of eosinophilic myocarditis using contrast-enhanced magnetic resonance imaging: case report

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, N.; Murakami, Y.; Shimada, T.; Kashima, Y.; Nakamura, K.; Inoue, S.-I.; Sugamori, T.; Katoh, H.; Ishibashi, Y. [Shimane Medical Univ., The Fourth Dept. of Internal Medicine, Izumo City, Shimane (Japan); Maruyama, R. [Shimane Medical Univ., Dept. of Laboratory Medicine, Izumo City, Shimane (Japan)

    2001-02-01

    Hypereosinophilic syndrome is characterized by idiopathic eosinophilia in the peripheral blood and multiorgan dysfunction secondary to mature eosinophil infiltration. It is essential to diagnose myocardial involvement in the early stage of the disease when active myocarditis due to cardiotoxic substances from eosinophils is still taking place, but clinical tools for the diagnosis of myocardial lesions in patients without overt cardiac dysfunction are not yet available. We present a case of successful detection of myocarditis due to hypereosinophilic syndrome by gadolinium-diethylenetriaminepentaascetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI). (author)

  17. INTEGRAL EVALUATION OF THE CYTOKINE SYSTEM IN VIRAL MYOCARDITIS

    Directory of Open Access Journals (Sweden)

    Peremot S. D.

    2017-10-01

    Full Text Available The need for an individual approach in the choice of means for the prevention of complications in inflammatory processes in cardiomyocytes, the course of which unfolds against a persistent viral infection, dictates the need to determine the general mechanisms for maintaining and progressing of the pathological process and an objective evaluation of immunological changes. The aim of the study was to determine changes in the system of inflammatory mediators in patients with subacute and chronic herpesviral infectious myocarditis on the basis of an integral assessment of the levels of opposing groups of cytokines. Materials & methods. To achieve this goal, we conducted a determination and analysis of changes in the cytokine profile in 87 patients with subacute (from 2 to 6 months and chronic (more than 6 months myocarditis due to an integral assessment of the mediator levels of inflammation of opposing groups in patients with herpesviral myocarditis on treatment in medical institutions of the Kharkov city. The average age of the patients was (27 ± 7.4 years. The control group was attracted to 40 people without clinical manifestations of cardiovascular diseases and in whose anamnesis there were no data on the transferred inflammatory diseases of the myocardium. Both groups of subjects were comparable in age and gender. The main group of subjects was divided into two subgroups. The first was 44 patients with subacute flow, the second - 43 patients with chronic infectious myocarditis. The diagnosis was established in accordance with the recommendations of the Association of Cardiologists of Ukraine and experts of the European Society of Cardiology, according to the formation of definitions of diseases in the International Classification of Diseases (ICD-10 of the tenth revision. The removal of material from patients was carried out according to the rules for the collection of infectious material. The concentration of cytokines: IL-2, IL-4, IL-6, IL

  18. Detection of experimental myocarditis by monoclonal antimyosin antibody, Fab fragment

    Energy Technology Data Exchange (ETDEWEB)

    Rezkalla, S.; Kloner, R.A.; Khaw, B.A.; Haber, E.; Fallon, J.T.; Smith, F.E.; Khatib, R.

    1989-02-01

    The purpose of this study was to determine whether monoclonal antimyosin Fab (antigen binding fragment) was capable of labeling hearts with experimental coxsackievirus myocarditis, and to determine whether Fab could be used for detecting myocardial damage in either early or chronic phases of the disease. Sixty-five, 3-week-old cesarean-derived 1 (CD 1) mice were divided into two groups: group I (noninfected animals) and group II (infected with coxsackievirus B3). Mice from each group were killed on days 7, 17, 30, or 90 of infection. Forty-eight hours before killing, mice were injected with monoclonal I-125 antimyosin, Fab (25 microCi/injection) and radioactivity was counted in the heart. Selected heart sections were also examined by autoradiography. Heart radioactivity, count/m/mg (m +/- SEM) on days 7, 17, 30, and 90 of infection was 10.8 +/- 1.7, 21.3 +/- 1.1, 11.2 +/- 3.4, and 12.4 +/- 1.5 for group I, versus 36.7 +/- 8.0 (p less than 0.01), 50.0 +/- 4.5 (p less than 0.001), 33.4 +/- 16.1 (p = NS), and 40.6 +/- 8.5 (p less than 0.01) for group II, respectively. Autoradiography revealed focal uptake within areas of necrotic myocardium. We conclude that I125 Fab may be useful in detecting myocardial damage in the experimental model of murine myocarditis up to day 90 of infection.

  19. Detection of experimental myocarditis by monoclonal antimyosin antibody, Fab fragment

    International Nuclear Information System (INIS)

    Rezkalla, S.; Kloner, R.A.; Khaw, B.A.; Haber, E.; Fallon, J.T.; Smith, F.E.; Khatib, R.

    1989-01-01

    The purpose of this study was to determine whether monoclonal antimyosin Fab (antigen binding fragment) was capable of labeling hearts with experimental coxsackievirus myocarditis, and to determine whether Fab could be used for detecting myocardial damage in either early or chronic phases of the disease. Sixty-five, 3-week-old cesarean-derived 1 (CD 1) mice were divided into two groups: group I (noninfected animals) and group II (infected with coxsackievirus B3). Mice from each group were killed on days 7, 17, 30, or 90 of infection. Forty-eight hours before killing, mice were injected with monoclonal I-125 antimyosin, Fab (25 microCi/injection) and radioactivity was counted in the heart. Selected heart sections were also examined by autoradiography. Heart radioactivity, count/m/mg (m +/- SEM) on days 7, 17, 30, and 90 of infection was 10.8 +/- 1.7, 21.3 +/- 1.1, 11.2 +/- 3.4, and 12.4 +/- 1.5 for group I, versus 36.7 +/- 8.0 (p less than 0.01), 50.0 +/- 4.5 (p less than 0.001), 33.4 +/- 16.1 (p = NS), and 40.6 +/- 8.5 (p less than 0.01) for group II, respectively. Autoradiography revealed focal uptake within areas of necrotic myocardium. We conclude that I125 Fab may be useful in detecting myocardial damage in the experimental model of murine myocarditis up to day 90 of infection

  20. Gallium-positive Lyme disease myocarditis

    International Nuclear Information System (INIS)

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

    1985-01-01

    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

  1. Substance P Receptor Antagonism: A Potential Novel Treatment Option for Viral-Myocarditis

    Directory of Open Access Journals (Sweden)

    Prema Robinson

    2015-01-01

    Full Text Available Viral-myocarditis is an important cause of heart failure for which no specific treatment is available. We previously showed the neuropeptide substance P (SP is associated with the pathogenesis of murine myocarditis caused by encephalomyocarditis virus (EMCV. The current studies determined if pharmacological inhibition of SP-signaling via its high affinity receptor, NK1R and downstream G-protein, Ras homolog gene family, member-A (RhoA, will be beneficial in viral-myocarditis. Aprepitant (1.2 mg/kg, a SP-receptor antagonist, or fasudil (10 mg/kg, a RhoA inhibitor, or saline control was administered daily to mice orally for 3 days, prior to, or 5 days following, intraperitoneal infection with and without 50 PFU of EMCV, following which disease assessment studies, including echocardiogram and cardiac Doppler were performed in day 14 after infection. Pretreatment and posttreatment with aprepitant significantly reduced mortality, heart and cardiomyocyte size, and cardiac viral RNA levels (P<0.05 all, ANOVA. Only aprepitant pretreatment improved heart functions; it significantly decreased end systolic diameter, improved fractional shortening, and increased peak aortic flow velocity (P<0.05 all, ANOVA. Pre- or posttreatment with fasudil did not significantly impact disease manifestations. These findings indicate that SP contributes to cardiac-remodeling and dysfunction following ECMV infection via its high affinity receptor, but not through the Rho-A pathway. These studies suggest that SP-receptor antagonism may be a novel therapeutic-option for patients with viral-myocarditis.

  2. An expanded dengue syndrome patient with manifestation myocarditis: case report

    Science.gov (United States)

    Arifijanto, M. V.; Luqmana, H. P.; Rusli, M.; Bramantono

    2018-03-01

    Dengue infection may manifest asymptomatic, dengue fever, dengue hemorrhagic fever, dengue shock syndrome. However, atypical manifestations in other organs have been increasingly reported and called expanded dengue syndrome. One of the cardiac complications in dengue is myocarditis. An 18-year-old woman complains of high fever since 3 days, epistaxis, chest pain, dyspnea, and vomiting. Laboratory examination obtained thrombocytopenia, hemoconcentration, NS1, IgG-IgM dengue positive, CKMB and Troponin- I increase. Electrocardiogram result ischemic anterior-posterior. Echocardiography results hyperechogenic on myocardial suspicious a myocarditis. The patient was diagnosed with acute myocarditis and dengue hemorrhagic fever. Condition improved after five days of treatment. Cardiac complications in dengue are now increasingly observed with the most common case is myocarditis. The main mechanism of dengue myocarditis is still unknown though both direct viral infection and immune mediated damage have been suggested to be the cause of myocardial damage. The low incidence of dengue myocarditis is because it’s asymptomatic and diagnosis is easily missed. Almost all cases of dengue myocarditis are self-limiting and severe myocarditis leading to dilated cardiomyopathy is extremely rare. There have been reported a patient with dengue hemorrhagic fever with manifestation myocarditis. Condition improve with supportive management.

  3. A Family History of Dilated Cardiomyopathy Induced by Viral Myocarditis

    Directory of Open Access Journals (Sweden)

    Thomas Cognet

    2012-01-01

    Full Text Available Myocarditis can lead to acute heart failure, cardiogenic shock, or sudden death and later, dilated cardiomyopathy (DCM with chronic heart failure. We report the cases of two DCM induced by acute and past myocarditis in the same family and expressed by its two main complications within few weeks: an hemodynamic presentation as a fulminant myocarditis rapidly leading to cardiac tranplantation and a rythmologic presentation as an electrical storm leading to catheter ablation of ventricular tachycardia. These cases ask the question of the family predisposition to viral myocarditis leading to DCM.

  4. Cardiac Sarcoidosis or Giant Cell Myocarditis? On Treatment Improvement of Fulminant Myocarditis as Demonstrated by Cardiovascular Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Hari Bogabathina

    2012-01-01

    Full Text Available Giant cell myocarditis, but not cardiac sarcoidosis, is known to cause fulminant myocarditis resulting in severe heart failure. However, giant cell myocarditis and cardiac sarcoidosis are pathologically similar, and attempts at pathological differentiation between the two remain difficult. We are presenting a case of fulminant myocarditis that has pathological features suggestive of cardiac sarcoidosis, but clinically mimicking giant cell myocarditis. This patient was treated with cyclosporine and prednisone and recovered well. This case we believe challenges our current understanding of these intertwined conditions. By obtaining a sense of severity of cardiac involvement via delayed hyperenhancement of cardiac magnetic resonance imaging, we were more inclined to treat this patient as giant cell myocarditis with cyclosporine. This resulted in excellent improvement of patient’s cardiac function as shown by delayed hyperenhancement images, early perfusion images, and SSFP videos.

  5. Immunoperoxidase technique in experimental chronic chagasic myocarditis

    OpenAIRE

    M.d. Maria Celina Morales; M.D. José Milei

    1987-01-01

    Chagas'disease has been described as the commonest form of chronic myocarditis. An immunologic pathogenesis has been discribed for this form of the disease. So far, no immunoperoxidase technique has been used for the detection of immunological deposits in chronic experimental Chagas'myocardiopathy. Forty-one Swiss mice, three months old were inoculated intraperitoneally with doses between 10 and 10(5) Tulahuen trypomastigotes. Mice were reinoculated one month after with doses between 10² and ...

  6. Clinical Profile and Outcome of Myocarditis in Children at Dr. Hasan Sadikin General Hospital Bandung from 2008 to 2012

    Directory of Open Access Journals (Sweden)

    Erza Nurtriandari

    2017-03-01

    Full Text Available Background: Diagnosis of myocarditis in children is still challenging due to its inconsistent and wide spectrum of clinical manifestations. There is no specific laboratory test available. This may obscure the true incidence of myocarditis. The purpose of this study was to describe clinical profile and outcome of myocarditis in children. Methods: A descriptive study was performed using 80 medical records of hospitalized pediatrics patients with myocarditis in Dr. Hasan Sadikin General Hospital Bandung from January 2008 to December 2012. The obtained data were age, gender, nutritional status, etiology, chief complaint, physical examination, laboratory findings, other examinations and outcome of the disease. The collected data were analyzed and presented in the form of frequency distribution. Results: The mean age of the patients was 91.46 (45.93 months old, predominantly male. The most etiology was dengue infections (61%. High fever was found as the most common chief complaint (38% and the most common found in physical examinations were tachypnea (65% and hepatomegaly (55%. Electrocardiography (ECG showed the first degree atrioventricular block (AV block (35%, aspartate aminotransferase (AST and creatine kinase myocardial band (CKMB was increased in more than 80% of patients. The majority of patient was improved. Shock was the common complication. Conclusions: Dengue is the most etiology of myocarditis etiology. Tachypnea, hepatomegaly, the first degree AV block in ECG, elevated AST and CKMB were the most common presentations. Most of the patients were improved during treatment.

  7. Inhalant-Abuse Myocarditis Diagnosed by Cardiac Magnetic Resonance.

    Science.gov (United States)

    Dinsfriend, William; Rao, Krishnasree; Matulevicius, Susan

    2016-06-01

    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.

  8. A Case Report of Salmonella muenchen Enteritis Causing Rhabdomyolysis and Myocarditis in a Previously Healthy 26-Year-Old Man.

    Science.gov (United States)

    Chapple, Will; Martell, Jon; Wilson, Joy S; Matsuura, Don T

    2017-04-01

    This case report examines an unusual presentation of a non-typhoidal Salmonella serovar with limited prevalence in the literature. This is the first case report to associate specifically the Salmonella muenchen serovar with rhabdomyolysis and myocarditis. This case report reviews the diagnostic criteria for myocarditis and explores the diagnostic dilemma of troponin elevation in the setting of rhabdomyolysis. It demonstrates that Salmonella muenchen has the ability to present in a broad range of individuals with complications extending beyond classical gastrointestinal symptoms. This report also concludes that diagnosis of the many possible complications from non-typhoidal Salmonella infections can be difficult due to patient comorbidities, variability in the severity of the illnesses, laboratory test limitations, and imaging limitations. When a patient presents with elevated troponins in the setting of rhabdomyolysis a careful workup should be done to evaluate for ischemic causes, myocarditis, or false elevation secondary to rhabdomyolysis.

  9. MRI for myocarditis; MRT bei Myokarditis

    Energy Technology Data Exchange (ETDEWEB)

    Gutberlet, M.; Luecke, C.; Krieghoff, C.; Hildebrand, L.; Steiner, J.; Adam, J.; Grotthoff, M.; Lehmkuhl, L. [Herzzentrum, Universitaet Leipzig, Abteilung fuer Diagnostische und Interventionelle Radiologie, Leipzig (Germany); Lurz, P.; Eitel, I.; Thiele, H. [Herzzentrum, Universitaet Leipzig, Abteilung Kardiologie, Leipzig (Germany)

    2013-01-15

    Cardiovascular magnetic resonance imaging (CMRI) has become the primary tool for the non-invasive assessment in patients with suspected myocarditis, especially after exclusion of acute coronary syndrome (ACS) for the differential diagnosis. Various MRI parameters are available which have different accuracies. Volumetric and functional ventricular assessment and the occurrence of pericardial effusion alone demonstrate only a poor sensitivity and specificity. The calculation of the T2-ratio (edema assessment), the early or global relative myocardial enhancement (gRE) and the late gadolinium enhancement (LGE), which represents irreversibly injured myocardium, are more specific parameters. All MRI parameters demonstrate the best accuracy in infarct-like acute myocarditis, whereas in chronic myocarditis sensitivity and specificity are less accurate. Therefore, a multisequential (at least two out of three parameters are positive) approach is recommended. The assessment of the value of newer, more quantitative MRI sequences, such as T1 and T2-mapping is still under investigation. (orig.) [German] Die kardiale MRT stellt die primaere nichtinvasive bildgebende Modalitaet bei Verdacht auf Myokarditis dar, insbesondere auch nach Ausschluss eines akuten Koronarsyndroms (ACS) zur Differenzialdiagnose. Verschiedene MR-Parameter mit unterschiedlicher Wertigkeit stehen zur Verfuegung. Die Beurteilung der Volumetrie und Ventrikelfunktion weisen ebenso wie der Nachweis eines Perikardergusses alleine nur eine geringe Sensitivitaet und Spezifitaet auf. Die spezifischeren MRT-Inflammationsparameter stellen die T2-Ratio (Oedemnachweis), die fruehe Kontrastmittelanreicherung bzw. das globale relative Enhancement (gRE) und die spaete Kontrastmittelanreicherung, das so genannte Late-Gadolinium-Enhancement (LGE) als Zeichen eines irreversiblen Myokardschadens dar. Alle MR-Parameter zeigen die beste diagnostische Genauigkeit bei einer ''infarktaehnlichen'' akuten

  10. The effect of experimental streptococcus infection in myocarditis on ...

    African Journals Online (AJOL)

    EB

    faecalis induction of myocarditis and its effect on some blood parameters, inflammatory markers and .... LSD. 41. 5. 0.9. Similar characters denote insignificance between groups. *** denote .... detectable in serum, brain and intestine of rat pups.

  11. Saffold virus infection associated with human myocarditis

    DEFF Research Database (Denmark)

    Nielsen, Trine Skov; Nielsen, Alex Yde; Banner, Jytte

    2016-01-01

    BACKGROUND: Saffold virus was described in 2007 as one of the first human viruses within the genus cardioviruses. Cardioviruses may cause severe infections of the myocardium in animals, and several studies have associated saffold virus with human disease. As a result, saffold virus has been...... isolated from different anatomical compartments, including the myocardium, but, until now, it has not been possible to demonstrate the accompanying histopathological signs of inflammation. OBJECTIVES: The aim of the study was to examine if saffold virus is capable of causing invasive infection in the human...... myocardium. STUDY DESIGN: Using real-time PCR, we retrospectively examined formalin-fixed paraffin embedded cardiac tissue specimens from 150 deceased individuals diagnosed with myocarditis at autopsy. The results were compared with histological findings. RESULTS AND CONCLUSIONS: Saffold virus was detected...

  12. Pericardial disease and myocarditis: management guide

    International Nuclear Information System (INIS)

    Marin, Jorge E; Duque, Mauricio; Uribe, William; Medina, Eduardo

    2005-01-01

    Pericardium is a structure that can be primarily affected by a series of different agents and in a secondary way by systemic processes. Its response is not specific and in general it corresponds to an inflammatory process that can be acute, chronic or recurrent. The recognition of these pathologies is of vital significance in the making of a right therapeutic approach. Some basic orientations for the correct classification, diagnosis and therapy of main pericardial syndromes, based on clinical and etiological aspects and para clinical available aids are presented. Likewise, some recommendations for the specific treatment of each one of the main entities usually affecting the pericardium are given. Next, a brief mention of some pathophysiological aspects of acute myocarditis, its main etiologies, and the treatment of the cardiac failure secondary to the disease with its specific differences, is made, and the controversy on its handling with immuno suppressors and the experimental therapy measures are studied in depth

  13. Acute myocarditis mimicking myocardial infarction can misdirect the diagnostic approach

    Directory of Open Access Journals (Sweden)

    Erkan Yildirim

    2016-03-01

    Full Text Available Acute myocarditis is a well-recognized but rare manifestation of mostly viral infections. It can present with various clinical manifestations and may mimic myocardial infarction (MI since patients usually present with chest pain, and the electrocardiographic changes similar to those observed in acute ST-elevation MI. We, herein, present such an extreme case of acute myocarditis characterized by dynamic ST segment elevation with reciprocal changes in the electrocardiogram.

  14. Lyme myocarditis diagnosed by indium-111-antimyosin antibody scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Casans, I.; Villar, A.; Almenar, V.; Blanes, A.

    1989-06-01

    We report a new case of Lyme disease with cardiac manifestations, which has been possible to follow during the long period of 12 years. We have detected the usual ECG abnormalities, and concentric hypertrophic myocardiopathy, by echocardiography. The acute myocarditis was demonstrated by /sup 111/In-antimyosin scintigraphy, which showed global myocardial uptake of the tracer, constituting the first report, to our knowledge, of Lyme myocarditis diagnosed by this method.

  15. Lyme myocarditis diagnosed by indium-111-antimyosin antibody scintigraphy

    International Nuclear Information System (INIS)

    Casans, I.; Villar, A.; Almenar, V.; Blanes, A.

    1989-01-01

    We report a new case of Lyme disease with cardiac manifestations, which has been possible to follow during the long period of 12 years. We have detected the usual ECG abnormalities, and concentric hypertrophic myocardiopathy, by echocardiography. The acute myocarditis was demonstrated by 111 In-antimyosin scintigraphy, which showed global myocardial uptake of the tracer, constituting the first report, to our knowledge, of Lyme myocarditis diagnosed by this method. (orig.)

  16. Parvovirus B19 is a bystander in adult myocarditis.

    Science.gov (United States)

    Koepsell, Scott A; Anderson, Daniel R; Radio, Stanley J

    2012-01-01

    The genomic DNA of parvovirus B19, a small single-stranded DNA virus of the genus Erythrovirus, has been shown to persist in solid tissues of constitutionally healthy, immunocompetent individuals. Despite these data, many case reports and series have linked the presence of parvovirus B19 genomic DNA, detected through nucleic acid amplification testing, with myocarditis and cardiomyopathy. Herein, we use multiple tools to better assess the relationship between parvovirus B19 and myocarditis and cardiomyopathy. Nucleic acid amplification testing, immunohistochemistry, in situ hybridization, and electron microscopy were used to assess the location and activity of parvovirus B19 in cases of myocarditis and in cases with no significant cardiac disease. Nucleic acid amplification testing for parvovirus B19 genomic DNA was positive in 73% of patients with myocarditis/cardiomyopathy and in 26% of patients with no significant disease. In situ hybridization and immunohistochemistry showed that, in cases with amplifiable parvovirus B19 DNA, parvovirus B19 genomic DNA and viral protein production were present in rare mononuclear cells. In a majority of cases of myocarditis and a significant number of otherwise normal hearts, nucleic acid amplification testing detected persistent parvovirus B19 genomic DNA that did not play a significant pathogenic role. The source of parvovirus B19 DNA appeared to be interstitial mononuclear inflammatory cells and not myocardial or endothelial cells. Therefore, nucleic acid amplification testing alone is not diagnostically helpful for determining the etiology of adult myocarditis. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Learning from myocarditis: mimicry, chaos and black holes.

    Science.gov (United States)

    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.

  18. COMPARISON OF CARDIAC BIOMARKERS AND ECHOCARDIOGRAPHY IN DIAGNOSING MYOCARDITIS

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    Nimi Bharathan

    2017-03-01

    Full Text Available BACKGROUND Conventional methods used to diagnose or rule out myocarditis is not useful in detecting cardiac myocyte injury in clinically suspected cases. Endomyocardial biopsy and histopathological examination is not feasible in most government hospitals in India. Sensitive parameters have yet to be found out. The study was conducted to find out whether diagnosis of myocarditis in clinically suspected cases can be done by measurement of serum levels of cardiac troponinI (cTnI and MB isoform of creatine kinase (CK-MB. MATERIALS AND METHODS 19 patients with clinically suspected myocarditis were screened for CK-MB activity and cTnI. Echocardiography, ECG and IgM for leptospirosis were also checked in these patients. RESULTS cTnI was elevated in 10 out of 19 patients with clinically suspected myocarditis. CK-MB was elevated in 7 patients. CONCLUSION Elevation of cTnI level in blood can be taken as an indicator of cardiac muscle cell injury in suspected cases of myocarditis.

  19. Evaluating changes in brain vasculature of murine embryos in utero due to maternal alcohol consumption using optical coherence tomography

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    Raghunathan, Raksha; Wu, Chen; Singh, Manmohan; Liu, Chih-Hao; Miranda, Rajesh C.; Larin, Kirill V.

    2017-04-01

    Fetal Alcohol Syndrome (FAS) refers to the broad spectrum of developmental and behavioral effects caused due to prenatal alcohol exposure (PAE). Wide range of abnormalities vary depending on the amount of alcohol consumed and the period of consumption during gestation. PAE during early stages of pregnancy is very common. However a large number of women continue to consume alcohol even during the second trimester, a critical period for fetal neurogenesis and angiogenesis. Optical coherence tomography (OCT) has shown to be extremely useful in embryonic imaging. Our previous work showed that OCT is capable of quantitative assessment of ventriculomegaly caused by maternal alcohol consumption. Although structural changes and changes in blood flow in the fetal brain after maternal alcohol consumption have been studied, acute vasculature changes are not well documented. Speckle variance OCT (SVOCT), is a functional extension of OCT that has been used to study vasculature development in embryos. We use SVOCT, to detect vasculature changes in the embryonic brain in utero, minutes after maternal alcohol consumption.

  20. Acute Toxic Myocarditis and Pulmonary Oedema Developing from Scorpion Sting

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    Cem Sahin

    2015-03-01

    Full Text Available The majority of scorpion stings are generally seen with a set of simple clinical findings, such as pain, oedema, numbness, and tenderness in the area of the sting. However, occasionally events, such as toxic myocarditis, acute heart failure, acute pulmonary oedema, and Acute Respiratory Distress Syndrome (ARDS, which occur in scorpion sting cases are a significant problem which determine mortality and morbidity. The case presented here was a 38-year-old man who developed acute toxic myocarditis, acute heart failure, and acute pulmonary oedema following a scorpion sting on the 3rd finger of his right hand.

  1. Giant Asian honeybee stings induced acute myocarditis: a case report

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    NP Dinamithra; S Sivansuthan

    2013-01-01

    Hymenopterid stings and subsequent allergic reactions including fatal anaphylaxis are a common indication for emergency department visits worldwide. Less commonly, multiple wasp stings can result in multi-system involvement ranging from intravascular hemolysis, rhabdomyolysis, acute renal failure, cardiac involvement, hepatic dysfunction and occasionally thrombocytopenia and coagulopathy. Here we report one case of multiple Giant Asian honey bee stings induced myocarditis.

  2. Giant Asian honeybee stings induced acute myocarditis: a case report

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    NP Dinamithra

    2013-10-01

    Full Text Available Hymenopterid stings and subsequent allergic reactions including fatal anaphylaxis are a common indication for emergency department visits worldwide. Less commonly, multiple wasp stings can result in multi-system involvement ranging from intravascular hemolysis, rhabdomyolysis, acute renal failure, cardiac involvement, hepatic dysfunction and occasionally thrombocytopenia and coagulopathy. Here we report one case of multiple Giant Asian honey bee stings induced myocarditis.

  3. Juvenile Churg-Strauss Syndrome as an Etiology of Myocarditis and Ischemic Stroke in Adolescents; a Case Report

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    Moradinejad, Mohammad-Hassan; Rezaei, Amir; Ziaee, Vahid

    2011-01-01

    Background Churg-Strauss syndrome (CSS), a systemic vasculitis accompanied by asthma and eosinophilia, almost invariably affects the lung and is frequently associated with cutaneous involvement. It rarely has cardiac involvement. We report an unusual case of CSS with myocardial involvement and stroke. Case Presentation A 16-year old female suffered of allergic asthma for 4 years. She was under treatment with oral prednisolone and seretide inhalation. After CSS diagnosis, she developed paroxysmal atrial tachycardia. Serum levels of Troponin I and Troponin T were increased indicating massive myocardial damage probably due to myocarditis. After 5 months she developed acute hemiparesis without any evidence of ischemic or hemorrhagic event. She was treated with IVIg, intravenous pulses of methylprednisone and cyclophosphamide for each complication. Conclusion Myocarditis and stroke may also complicate CSS which should be taken in consideration for better management. PMID:23056844

  4. Immunoperoxidase technique in experimental chronic chagasic myocarditis

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    M.d. Maria Celina Morales

    1987-04-01

    Full Text Available Chagas'disease has been described as the commonest form of chronic myocarditis. An immunologic pathogenesis has been discribed for this form of the disease. So far, no immunoperoxidase technique has been used for the detection of immunological deposits in chronic experimental Chagas'myocardiopathy. Forty-one Swiss mice, three months old were inoculated intraperitoneally with doses between 10 and 10(5 Tulahuen trypomastigotes. Mice were reinoculated one month after with doses between 10² and 10(5 and sacrificed at 6 (n=21 and 9 months (n=9 after the first inoculation. ECGs were recorded before sacrifice. Immunoperoxidase technique (peroxidase-antiperoxidase method, immunofluorescence (direct and indirect as well as histological studies were performed in myocardiums and skeletal muscles of the surviving animals. The most sensitive methods for detecting chronic chagasic infection were the routine histologic studies (73% and the ECGs 83% and 89% on 6 and 9 mo. post-infected mice, respectively. Myocardial involvement varied from interstitial mild focal lymphocyte infiltrates up to replacement of myocytes by loose connective tissue. Atrial myocardiums (21/23, 91% were more affected than ventricles (9/23, 39%. Typical chagasic nests were rarely found. Skeletal muscle involvement (11/18 and 7/9 varied from mild to extensive lymphocyte and plasmacell infiltrates, and necrotic fibers. The involved antigen were shown in skeletal muscles by the immunoperoxidase technique as diffusely arranged granular intracytoplasmatic deposit for both IgC and total immunoglobulins. The coincidence between this technique and histologic muscle lesions was 11/18 (61(% in 6 mo. and 6/8 (75% at 9 mo. post-infection. In heart, delicate granular deposits of total immunoglobulins were seen diffusely arranged within the ventricular myocytes; coincidence between immunoperoxidase technique anl histologic involvement increased from 36 to 66% in animals sacrifeced 6 and 9 mo. post

  5. Novel Combination of Impella and Extra Corporeal Membrane Oxygenation as a Bridge to Full Recovery in Fulminant Myocarditis

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    Sachin Narain

    2012-01-01

    Full Text Available A 31-year-old male was transferred to our hospital with severe heart failure due to viral myocarditis. He progressed to multiorgan failure requiring intubation and maximal doses of multiple vasopressors. Circulatory support was provided with an Impella device as a bridge to an extracorporeal membrane oxygenation (ECMO system. On full mechanical cardiovascular support, the patient's hemodynamic status improved and ECMO and Impella were explanted after 48 hours. Three days later, he was extubated and continued on to a full recovery. There are no specific therapies for fulminant myocarditis but first-line treatment is supportive care. ECMO is commonly used in patients with severe heart failure. In severe systolic dysfunction, left ventricular decompression is required to reduce myocardial wall stress, decrease myocardial oxygen requirements, and enhance the chances of recovery. The Impella, an active support system, is less invasive than classical decompressive techniques and is associated with lower requirements for blood products with fewer thromboembolic complications. This is the only case reported of the contemporary use of Impella and ECMO as a bridge to full recovery in an adult with myocarditis. It also presents a novel use of the Impella device in decompressing the left ventricle of an adult patient on ECMO.

  6. Four cases of acute chagasic myocarditis in French Guiana.

    Science.gov (United States)

    Carme, B; Aune, I; Nguyen, G; Aznar, C; Beaudet, B

    2001-01-01

    The authors report four cases of acute chagasic myocarditis which had been diagnosed and treated in Cayenne, French Guiana, in the past 6 years. This French territory, which has the highest standard of living in South America, should be considered an area of risk for sporadic Chagas disease with epidemiologic features similar to those of the disease found in dense Amazon forest areas. Appropriate measures must be taken to screen and promptly manage Chagas disease in the French Guiana population.

  7. A CLINICAL CASE OF ACUTE ALLERGIC MYOCARDITIS SIMULATING MYOCARDIAL INFARCTION

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    N. A. Shostak

    2015-01-01

    Full Text Available Objective: to describe a clinical case of evolving acute eosinophilic myocarditis simulating coronary heart disease. Subjects and methods. Patient B. aged 62 years was admitted to Intensive Care Unit Fifteen, N.I. Pirogov First Moscow City Clinical Hospital, by being transferred from Thailand with a referral diagnosis of acute myocardial infarction made on November 1, 2012, with complaints of pressing and aching heart pains. At a Phuket hospital, his electrocardiogram recorded atrial fibrillation; indirect cardiac massage, electric pulse therapy, and mechanical ventilation were performed. After being admitted to the N.I. Pirogov First Moscow City Clinical Hospital, the patient underwent examination: estimation of laboratory indicators over time, electrocardiography (ECG, echocardiography, Holter ECG monitoring, and myocardial scintigraphy. Results. The patient had a history of an allergic reaction as urticaria to the ingestion of fish products. His examination showed practically all diagnostic criteria for allergic myocarditis: hypereosinophilia (the admission level of eosinophils was 9% with their further normalization; the characteristic clinical presentation of myocarditis (pressing retrosternal pain; elevated levels of cardiac specific enzymes (creatinine phosphokinase-MB, lactate dehydrogenase, troponin T; ECG changes – myocardial hypokinesis in the acute period, followed by its pattern normalization. of the pattern. Myocardial scintigraphy (by taking into account the fact that the patient had had a new allergic reaction episode, the investigators decided not to perform coronary angiography revealed decreased radiopharmaceutical accumulation in the lower left ventricular wall in the right coronary arterial bed; perfusion remained in the other myocardial walls. Conclusion. This clinical case reflects the specific features of the course of and difficulties in the diagnosis of acute allergic myocarditis that, in most cases, has no specific

  8. Mononuclear cell secretome protects from experimental autoimmune myocarditis.

    Science.gov (United States)

    Hoetzenecker, Konrad; Zimmermann, Matthias; Hoetzenecker, Wolfram; Schweiger, Thomas; Kollmann, Dagmar; Mildner, Michael; Hegedus, Balazs; Mitterbauer, Andreas; Hacker, Stefan; Birner, Peter; Gabriel, Christian; Gyöngyösi, Mariann; Blyszczuk, Przemyslaw; Eriksson, Urs; Ankersmit, Hendrik Jan

    2015-03-14

    Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Cardiology.

  9. [Cardiac tamponade and myocarditis in Churg-Strauss syndrome].

    Science.gov (United States)

    Baili, L; Aydi, Z; Soussi, G; Ben Dhaou B, B; Zidi, A; Berraies, A; Boussema, F; Kammoun, S; Hamzaoui, A; Kraiem, S; Ben Miled M'rad, K; Rokbani, L

    2014-09-01

    The successive occurrence of pericardial tamponade and myocarditis during a Churg-Strauss syndrome is exceptionally described. We report a patient in whom pericardial tamponade and myocarditis were the presenting manifestation of a Churg-Strauss syndrome. A 58-year-old woman was admitted because of alteration of the clinical status with eosinophilia. One month ago, she was hospitalized for a pericardial tamponade treated by pericardial drainage. Acute myocarditis was diagnosed on chest pain during the second hospitalization. The etiologic inquiry ended in the diagnosis of Churg-Strauss complicated with a double cardiac involvement. A good response of clinical and biological anomalies was obtained after corticosteroid and immunosuppressive treatment. Isolated or multiple involvements of cardiac tunics should lead to make diagnosis of systemic vasculitis. A complete initial assessment and a close observation of the patients followed for Churg-Strauss syndrome is imperative to detect a cardiac achievement and set up an early treatment. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. Associated factors and impact of myocarditis in patients with SLE from LUMINA, a multiethnic US cohort (LV). [corrected].

    Science.gov (United States)

    Apte, M; McGwin, G; Vilá, L M; Kaslow, R A; Alarcón, G S; Reveille, J D

    2008-03-01

    To examine the factors associated with myocarditis and its impact on disease outcomes in SLE patients. SLE patients aged > or = 16 yrs, disease duration NAture vs nurture), a multiethnic US cohort, were studied. Myocarditis was defined as per the category 3 of the pericarditis/myocarditis item of the SLAM-Revised (SLAM-R). Patients with concurrent pericardial involvement were excluded. Patients with myocarditis were compared with those without myocarditis or its sequelae in the preceding year. The association between myocarditis and baseline variables (T(0)) was first examined. The impact of myocarditis on disease activity over time (SLAM-R), damage accrual [SLICC Damage Index (SDI)] at last visit (T(L)) and mortality was evaluated. Fifty-three of the 496 patients studied had myocarditis. African American ethnicity [Odds ratio (OR) = 12.6; 95% CI 1.6, 97.8] and SLAM-R at diagnosis (OR = 1.1, 95% CI 1.0, 1.1) were significantly and independently associated with myocarditis. Myocarditis did not predict disease activity over time, but approached significance as a predictor of SDI at T(L) in multivariable analyses P = 0.051. Kaplan-Meier curves indicated that myocarditis was associated with shorter survival (log-rank = 4.87, P = 0.02), particularly in patients with > or = 5 yrs disease; however, myocarditis was not retained in the Cox proportional hazards regression model. Ethnicity and disease activity at diagnosis were associated with the occurrence of myocarditis in SLE. Myocarditis did not significantly impact on disease activity over time, but impacts some on damage accrual and survival, reflecting overall the more severe disease those patients experience.

  11. Swiss cheese ventricular septal defect with myocarditis - A rare coexistence in a neonate

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    A R Saboo

    2012-01-01

    Full Text Available Myocarditis is defined as acute inflammation of the myocardium, usually following a non-specific flu-like illness, and encompasses a wide range of clinical presentations ranging from mild or subclinical disease to heart failure. We report a 12-day-old healthy full-term neonate who presented with abrupt onset of congestive cardiac failure (CCF following a viral prodrome. Examination revealed persistent sinus tachycardia, lymphocytosis, gross cardiomegaly, nonspecific electrocardiogram changes with echocardiography showing Swiss cheese ventricular septal defect (VSD. VSD alone very rarely presents as early-onset cardiac failure in the absence of other precipitating factors like anemia, sepsis, hypoglycemia etc. Myocarditis, however, can mimic VSD and can present as fulminant cardiac failure in an otherwise healthy newborn. Myocarditis is usually diagnosed based on circumstantial evidence such as a recent viral infection and the sudden onset of cardiac dysfunction while ruling out other diagnostic possibilities. Elevated troponin T level is one of the most crucial noninvasive diagnostic modalities. Several trials have concluded that levels >0.055 ng/ml are statistically significant for diagnosing myocarditis in children. In our case an abrupt onset of cardiac failure following a viral prodrome and markedly elevated cardiac troponin T without sepsis and in the presence of normal coronary anatomy clinched the diagnosis of myocarditis. An early and aggressive treatment for CCF along with regular long-term follow-up plays a key role in the management of myocarditis. Role of high-dose Intravenous immunoglobulin in myocarditis has been studied by many trials with different outcomes. This is the first case report showing coexistence of VSD with myocarditis in a neonate presenting as early-onset acute cardiac failure. The report highlights the importance of screening for myocarditis in all previously normal babies presenting primarily with cardiogenic

  12. Murine iPSC-Derived Macrophages as a Tool for Disease Modeling of Hereditary Pulmonary Alveolar Proteinosis due to Csf2rb Deficiency

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    Adele Mucci

    2016-08-01

    Full Text Available Induced pluripotent stem cells (iPSCs represent an innovative source for the standardized in vitro generation of macrophages (Mφ. We here describe a robust and efficient protocol to obtain mature and functional Mφ from healthy as well as disease-specific murine iPSCs. With regard to morphology, surface phenotype, and function, our iPSC-derived Mφ (iPSC-Mφ closely resemble their counterparts generated in vitro from bone marrow cells. Moreover, when we investigated the feasibility of our differentiation system to serve as a model for rare congenital diseases associated with Mφ malfunction, we were able to faithfully recapitulate the pathognomonic defects in GM-CSF signaling and Mφ function present in hereditary pulmonary alveolar proteinosis (herPAP. Thus, our studies may help to overcome the limitations placed on research into certain rare disease entities by the lack of an adequate supply of disease-specific primary cells, and may aid the development of novel therapeutic approaches for herPAP patients.

  13. Predictors of acute myocarditis in complicated scrub typhus: an endemic province in the Republic of Korea.

    Science.gov (United States)

    Chin, Jung Yeon; Kang, Ki-Woon; Moon, Kyung Min; Kim, Jongwoo; Choi, Yu Jeong

    2018-03-01

    Scrub typhus is known as a self-limited infectious disease. Cardiac complication is uncommon and usually not life-threatening. Until now, few cases of fulminant myocarditis by scrub typhus have been reported. So, we investigated incidence and predictors of acute myocarditis in severe scrub typhus. We retrospectively reviewed 89 patients among 91 scrub typhus confirmed patients who examined an echocardiogram and cardiac biomarkers from 2005 to 2015 in the intensive care unit at our hospital. We excluded two patients who didn't have electrocardiography. Patients were divided into two groups and compared between scrub typhus with (n = 13) and without (n = 76) acute myocarditis. Age, sex, and underlying diseases were similar between the groups. The existence of eschar and duration of general ache and fever were similar between the groups. However, patients with acute myocarditis had more elevated total bilirubin, high incidence of ST elevations and paroxysmal atrial fibrillation (PAF) than those without acute myocarditis. Receiver operating characteristic analysis showed that the PAF was a predictor of myocarditis with a sensitivity of 70% and specificity of 84%. Predictive power of combination of ST-segment elevation and PAF was significantly associated with myocarditis in the multivariate analysis (odds ratio, 1.57; 95% confidence interval [CI], 1.21 to 11.7; p = 0.041) and area under the curve was 0.947 (95% CI, 0.878 to 0.983; p scrub typhus may be more common than previously reported. Patients with high bilirubin and PAF are at increased risk of acute myocarditis with scrub typhus. These patients warrant closer follow-up and echocardiogram would be needed.

  14. A Risk Prediction Model for In-hospital Mortality in Patients with Suspected Myocarditis.

    Science.gov (United States)

    Xu, Duo; Zhao, Ruo-Chi; Gao, Wen-Hui; Cui, Han-Bin

    2017-04-05

    Myocarditis is an inflammatory disease of the myocardium that may lead to cardiac death in some patients. However, little is known about the predictors of in-hospital mortality in patients with suspected myocarditis. Thus, the aim of this study was to identify the independent risk factors for in-hospital mortality in patients with suspected myocarditis by establishing a risk prediction model. A retrospective study was performed to analyze the clinical medical records of 403 consecutive patients with suspected myocarditis who were admitted to Ningbo First Hospital between January 2003 and December 2013. A total of 238 males (59%) and 165 females (41%) were enrolled in this study. We divided the above patients into two subgroups (survival and nonsurvival), according to their clinical in-hospital outcomes. To maximize the effectiveness of the prediction model, we first identified the potential risk factors for in-hospital mortality among patients with suspected myocarditis, based on data pertaining to previously established risk factors and basic patient characteristics. We subsequently established a regression model for predicting in-hospital mortality using univariate and multivariate logistic regression analyses. Finally, we identified the independent risk factors for in-hospital mortality using our risk prediction model. The following prediction model for in-hospital mortality in patients with suspected myocarditis, including creatinine clearance rate (Ccr), age, ventricular tachycardia (VT), New York Heart Association (NYHA) classification, gender and cardiac troponin T (cTnT), was established in the study: P = ea/(1 + ea) (where e is the exponential function, P is the probability of in-hospital death, and a = -7.34 + 2.99 × [Ccr model demonstrated that a Ccr prediction model for in-hospital mortality in patients with suspected myocarditis. In addition, sufficient life support during the early stage of the disease might improve the prognoses of patients with

  15. Fulminant myocarditis mimicking acute coronary syndrome = Miocarditis fulminante, simuladora de síndrome coronario agudo

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    Senior, Juan Manuel

    2014-07-01

    Full Text Available Fulminant myocarditis mimicking acute coronary syndrome We report the case of a 48 year-old man with chest pain and history of coronary and autoimmune diseases, who developed acute heart failure and hemodynamic collapse. We present his clinical evolution and the tests that allowed the diagnosis of fulminant myocarditis secondary to systemic lupus erythematosus. A review of the most important aspects of this disease is also included.

  16. Speckle tracking echocardiography in acute lupus myocarditis: comparison to conventional echocardiography

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    Riëtte Du Toit

    2017-07-01

    Full Text Available Aims: Lupus myocarditis occurs in 5–10% of patients with systemic lupus erythematosus (SLE. No single feature is diagnostic of lupus myocarditis. Speckle tracking echocardiography (STE can detect subclinical left ventricular dysfunction in SLE patients, with limited research on its utility in clinical lupus myocarditis. We report on STE in comparison to conventional echocardiography in patients with clinical lupus myocarditis. Methods and results: A retrospective study was done at a tertiary referral hospital in South Africa. SLE patients with lupus myocarditis were included and compared to healthy controls. Echocardiographic images were reanalyzed, including global longitudinal strain through STE. A poor echocardiographic outcome was defined as final left ventricular ejection fraction (LVEF <40%. 28 SLE patients fulfilled the criteria. Global longitudinal strain correlated with global (LVEF: r = −0.808; P = 0.001 and regional (wall motion score: r = 0.715; P < 0.001 function. In patients presenting with a LVEF ≥50%, global longitudinal strain (P = 0.023, wall motion score (P = 0.005 and diastolic function (P = 0.004 were significantly impaired vs controls. Following treatment, LVEF (35–47% (P = 0.023 and wall motion score (1.88–1.5 (P = 0.017 improved but not global longitudinal strain. Initial LVEF (34%; P = 0.046 and global longitudinal strain (−9.5%; P = 0.095 were lower in patients with a final LVEF <40%. Conclusions: This is the first known report on STE in a series of patients with clinical lupus myocarditis. Global longitudinal strain correlated with regional and global left ventricular function. Global longitudinal strain, wall motion score and diastolic parameters may be more sensitive markers of lupus myocarditis in patients presenting with a preserved LVEF ≥50%. A poor initial LVEF and global longitudinal strain were associated with a persistent LVEF <40%. Echocardiography is a non-invasive tool with diagnostic and

  17. ETIOLOGIC FACTOR IN THE DEVELOPMENT OF MYOCARDITIS IN THE KHARKIV REGION

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    Smelyanskaya MV

    2016-09-01

    Full Text Available Introduction. According to the research conducted in the last decade, there has been growth in the non-coronary disease infarction among all cardiovascular diseases. The prominent place among all non-coronary heart diseases is taken by myocarditis, which predominantly affects young people of working age (30-40 years old. According to the bibliography, the prevalence of myocarditis is 20% of the non-coronary heart lesions and by different authors 5 - 11% of the total amount of diseases of the cardiovascular system. To date, there are no clear criteria of infectious myocarditis. It is widely accepted that myocarditis is natural complication of infectious diseases in which any infectious agent may be the etiological factor. Until recently, Coxsackie virus of group A, B was considered the most cardiotropic. However, the role of enteroviruses has been recently reviewed in favor of persisting viruses and especially family Herpesviridae. Optimization of myocarditis diagnosis using noninvasive tests, will not only reveal the true extent of the disease but may also enable to examine viral myocarditis as a much more common pathology than it seems at present and will increase understanding of the significance of this pathology in the cardiovascular continuum. Material & methods. 87 people diagnosed with infectious myocarditis were examined. Blood and other biological fluids were subject to examination. Patients of the main group have also had their biopsy material, obtained in a result of endomyocardial biopsy, and pericardial fluid, derived as a result of diagnostic and therapeutic puncture under hydro pericarditis, examined. PCR was performed to determine the genomic sequence of enterovirus (HEV, adenovirus (HAdV, human cytomegalovirus (CMV, herpes simplex virus (HSV, Epstein-Barr virus (EBV, human herpes virus 6 (HHV6 and influenza A viruses and B. Results & discussion. Our research confirms the global trend of reducing the role of enteroviruses in

  18. Changes in perfusion and fatty acid metabolism of rat heart with autoimmune myocarditis

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    Tsujimura, Eiichiro; Kusuoka, Hideo; Fukuchi, Kazuki; Hasegawa, Shinji; Yutani, Kenji; Nishimura, Tsunehiko [Osaka Univ., Suita (Japan). Biomedical Research Center; Hori, Masatsugu; Hirono, Satoru; Izumi, Tohru

    2000-10-01

    To elucidate the change in perfusion and aerobic metabolism in myocarditis, tissue counting and dual tracer ex vivo autoradiography with Tl-201 and free fatty acid analog, I-123- or I-125-labeled (p-iodophenyl)-methyl-pentadecanoic acid (BMIPP), were performed in rats with myocarditis induced by immunization with cardiac myosin. Inflammatory damage was classified histologically. At the acute stage (2-4 weeks after the antigen-injection), total heart uptakes of Tl and BMIPP and the ratio (BMIPP/Tl) were significantly reduced in myocarditis rats (N=15) compared with the controls (N=12). Myocardial distribution of Tl and BMIPP was not homogeneous. Relative uptake of Tl and BMIPP (N=9, 128 regions) was gradually decreased with the extent of inflammation, and the regional BMIPP/Tl was smaller than the control. At the subacute stage (7 weeks after the antigen-injection), total Tl uptake in myocarditis rats (N=5) recovered to the control level (N=4), but that of BMIPP was still significantly lower than the control. BMIPP/Tl was still significantly lower in myocarditis. Myocardial distribution of Tl and BMIPP recovered to be more homogeneous. Relative uptake of Tl and BMIPP (N=6, 78 regions) still gradually but significantly decreased with the extent of inflammation. Regional BMIPP/Tl was still depressed in myocarditis. These results indicate that myocardial perfusion and aerobic metabolism were discrepant and heterogeneously suppressed with severe inflammation during the acute stages, but the difference decreases with time. Examination with Tl-201 and BMIPP may provide information about the severity of myocarditis. (author)

  19. Left and right atrial feature tracking in acute myocarditis: A feasibility study

    International Nuclear Information System (INIS)

    Dick, Anastasia; Schmidt, Björn; Michels, Guido; Bunck, Alexander C.; Maintz, David; Baeßler, Bettina

    2017-01-01

    Purpose: The present study aims at evaluating the feasibility and reproducibility of cardiac magnetic resonance (CMR) feature tracking (FT) derived strain and strain rate (SR) parameters of the left and right atrium (LA, RA) in patients with acute myocarditis as well as their potential to detect diastolic dysfunction. In addition, the diagnostic value of LA and RA strain parameters in the setting of acute myocarditis is investigated. Methods: CMR cine data of 30 patients with CMR-positive acute myocarditis were retrospectively analyzed. 25 age- and gender-matched healthy individuals served as a control. Analysis of longitudinal strain and SR of both atria was performed in two long-axis views using a dedicated FT-software. LA and RA deformation was analyzed including reservoir function (total strain [ε s ], peak positive SR [SR s ]), conduit function (passive strain [ε e ], peak early negative SR [SR e ]) and booster pump function (active strain [ε a ], peak late negative SR [SR a ]). Intra- and inter-observer reproducibility was assessed for all strain and SR parameters using Bland-Altman analyses, intra-class correlation coefficients (ICCs) and coefficients of variation (CV). Results: FT analyses of both atria were feasible in all patients and controls. Reproducibility was good for reservoir and conduit function parameters and moderate for booster pump function parameters. Myocarditis patients demonstrated an impaired LA reservoir and conduit function when compared to healthy controls (LA ε s : 32 ± 17 vs. 46 ± 13, p = 0.019; LA SR s : 1.5 ± 0.5 vs. 1.8 ± 0.5, p = 0.117; LA SR e : −1.3 ± 0.5 vs. −1.9 ± 0.5, p < 0.001), while LA booster pump function was preserved. In logistic regression and ROC-analyses, LA SR e proved to be the best independent predictor of acute myocarditis (AUC 0.80), and using LA SR e with a cut-off of −1.6 s −1 resulted in a diagnostic sensitivity of 83% and a specificity of 80%. Changes in RA phasic function parameters

  20. 111indium-antimyosin immunoscintigraphy in suspected myocarditis

    International Nuclear Information System (INIS)

    Krause, T.; Schuemichen, C.; Joseph, A.; Moser, E.; Zeiher, A.

    1991-01-01

    111 Indium-monoclonal antimyosin scans were carried out in 21 patients with suspected myocarditis, confirmed by reduced ejection volume, pericardial effusion and clinical follow up in 12 patients. Coronary heart disease was excluded angiographically in all cases. Quantitative evaluation of myocardial 111 In-antimyosin accumulation 48 hours after injection showed a pathological uptake in 10/12 patients with increased heart/lung ratios (Q 48 >1,58). Ratios were also elevated in 2 patients with cardiomyopathy, 2 suffering from vasculitis and 1 with dermatomyositis. Four patients without proven cardiac disease had normal ratios (Q 48 ≤1,58). Examination after 24 hours was of limited value, depending on the residual blood pool activity. Visual analysis of the scans showed a high interobserver variation despite a positive correlation with quantitative analysis (48 h p.i.: r=0,72; p 111 In-antimyosin scan as a screening method prior to myocardial biopsy. However, scintigraphy cannot definitely elucidate the cause of myocardial damage. Therefore, myocardial biopsy is still recommended after positive antimyosin scans. (orig.) [de

  1. THE ROLE OF HERPESVIRUS IN THE PARADIGM OF INFECTIOUS MYOCARDITIS (REVIEW

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    Peremot S.

    2016-03-01

    Full Text Available According to the research of the last decade, there has been growth in the noncoronary disease infarction, increased their share among the causes temporary or persistent disability, disability and deaths. Among others myocarditis, which constitute 11% of all diseases of the cardiovascular system and is responsible for almost 20% of cases of sudden death in people physically safe. The disease is an inflammatory damage to cardiomyocytes, which is caused by direct action or indirectly through immune mechanisms of infectious agents of bacterial, viral, protozoan nature, as well as chemical and physical factors. The term "myocarditis" was first proposed I F Soberheim in 1837 and in 1900. A. Fiedler described the myocardial injury and justified the very concept of primary myocarditis. It is widely accepted that myocarditis - natural complications of infectious diseases in which etiological factor may be any infectious agent. However, at the present stage bacterial pathogens give way to viral. Those viruses according to numerous studies result in the development of myocarditis and consequently lead to the development of myocardial dysfunction. Until recently, most were considered cardiotropic ECHO viruses, Coxsackie group A, B, causing half of all cases of viral myocarditis. However recently reviewed the role of enteroviruses in favor of persistent virus and particularly the family Herpesviridae. The significance in the etiology of myocarditis herpes simplex virus, human herpes type 6, Epstein - Barr virus, cytomegalovirus. Published data indicate that the development of viral myocarditis patients after serous meningoencephalitis caused by the varicella-zoster virus. Widespread herpesvirus diseases their tropism for endothelial cells and myocardium, the capacity for long-term persistence in the body the opportunity to explain virus inducted inflammatory damage to cardiomyocytes. Increased attention to this issue recently linked with the present stage

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

    International Nuclear Information System (INIS)

    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

  3. Lyme carditis with isolated left bundle branch block and myocarditis successfully treated with oral doxycycline.

    Science.gov (United States)

    Cunha, Burke A; Elyasi, Maekal; Singh, Prince; Jimada, Ismail

    2018-01-01

    Lyme disease may present with a variety of cardiac manifestations ranging from first degree to third degree heart block. Cardiac involvement with Lyme disease may be asymptomatic, or symptomatic. Atrioventrical conduction abnormalities are the most common manifestation of Lyme carditis. Less common, are alternating right bundle branch block (RBBB) and left bundle branch block (LBBB). We present an interesting case of a young male whose main manifestation of Lyme carditis was isolated LBBB. He also had mild Lyme myocarditis. The patient was successfully treated with oral doxycycline, and his isolated LBBB and myocarditis rapidly resolved.

  4. De novo development of eosinophilic myocarditis with left ventricular assist device support as bridge to transplant.

    Science.gov (United States)

    Pereira, Naveen L; Park, Soon J; Daly, Richard C; Kushwaha, Sudhir S; Edwards, William D

    2010-10-01

    The de novo development of myocarditis during left ventricular assist device support for dilated cardiomyopathy has not been previously described. We report a case of severe eosinophilic myocarditis associated with the use of leukotriene-receptor antagonist montelukast that developed during left ventricular assist device support accompanied by intra-device thrombus formation that was hemodynamically tolerated and subsequently discovered in the explanted heart. There may be no visible change in cardiac function as assessed by echocardiography, but the diagnosis should be entertained with the development of peripheral eosinophilia. Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  5. Clozapine-Induced Myocarditis: Is Mandatory Monitoring Warranted for Its Early Recognition?

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    T. A. Munshi

    2014-01-01

    Full Text Available Clozapine is an atypical antipsychotic used for treatment resistant schizophrenia. Its potential to induce agranulocytosis is well known but it can also cause myocarditis. Clozapine is the only antipsychotic known to induce this side effect, typically early in the treatment, and literature is scarce on this condition. We are presenting a case report of a 21-year-old schizophrenic male who developed myocarditis within 3 weeks of starting on clozapine for his treatment resistant psychosis. We then aim to review some of the available literature and raise awareness among physicians as this condition can potentially be fatal if not detected early.

  6. Diagnosis of Acute Global Myocarditis Using Cardiac MRI with Quantitative T1 and T2 Mapping: Case Report and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chul Hwan [Department of Radiology and Research Institute of Radiological Science, Yonsei University Health System, Seoul 135-720 (Korea, Republic of); Choi, Eui-Young [Division of Cardiology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 135-720 (Korea, Republic of); Greiser, Andreas [Healthcare Sector, Siemens AG, Erlangen D-91052 (Germany); Paek, Mun Young [Siemens Ltd., Seoul 120-837 (Korea, Republic of); Hwang, Sung Ho; Kim, Tae Hoon [Department of Radiology and Research Institute of Radiological Science, Yonsei University Health System, Seoul 135-720 (Korea, Republic of)

    2013-07-01

    The diagnosis of myocarditis can be challenging given that symptoms, clinical exam findings, electrocardiogram results, biomarkers, and echocardiogram results are often non-specific. Endocardial biopsy is an established method for diagnosing myocarditis, but carries the risk of complications and false negative results. Cardiac magnetic resonance imaging (MRI) has become the primary non-invasive imaging tool in patients with suspected myocarditis. Myocarditis can be diagnosed by using three tissue markers including edema, hyperemia/capillary leak, and necrosis/fibrosis. The interpretation of cardiac MR findings can be confusing, especially when the myocardium is diffusely involved. Using T1 and T2 maps, the diagnosis of myocarditis can be made even in cases of global myocarditis with the help of quantitative analysis. We herein describe a case of acute global myocarditis which was diagnosed by using quantitative T1 and T2 mapping.

  7. Eosinophilic myocarditis due to Churg-Strauss syndrome mimicking reversible dilated cardiomyopathy.

    Science.gov (United States)

    Chen, Ming-xian; Yu, Bi-lian; Peng, Dao-quan; Zhou, Sheng-hua

    2014-01-01

    A 41-year-old woman with a history of asthma arrived at the emergency room of our hospital with dyspnea. The electrocardiogram showed no specific results. Echocardiography defects revealed an obvious decrease in the left ventricular systolic function and enlargement of the left chamber. We initially considered her condition to be dilated cardiomyopathy. However, she had eosinophilia in the peripheral blood and elevated cardiac enzymes. The coronary angiography showed normal coronary arteries. Single photon emission computed tomography (SPECT) showed infiltrative myocardial disease. She was then diagnosed with eosinophil infiltrations. Combined with peripheral nerve injury and lung involvement, she was diagnosed as having Churg-Strauss syndrome. After initiating prednisone treatment, her eosinophilia and rising cardiac enzymes recovered to normal, and both her echocardiographic abnormalities and symptoms noticeably improved. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Myocarditis Complicated by Complete Atrioventricular Block: Nine Years' Experience in a Medical Center

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    Shao-Ju Chien

    2008-12-01

    Conclusion: The outcome of CAVB complicated with myocarditis is variable. Most of our patients resumed normal heart function. The incidence of persistent CAVB was 22%. VT is a common and serious complication, but it can be effectively treated medically. Persistent low cardiac output after pacemaker implantation and late onset VT should be considered as risk factors of mortality.

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

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    Peter Moritz Becher

    2017-01-01

    Full Text Available 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.

  10. [Bacteremia associated with mycotic aneurysm of the transversal aortic arch and myocarditis caused by Salmonella enteritidis].

    Science.gov (United States)

    Martínez-Martínez, L; Mesa, E; Rodríguez, J E; Sánchez, M P; Ugarte, J; Algora Weber, A; Dámaso, D; Daza, R M; Mendaza, P

    1989-02-01

    A 60-year-old male with diabetes mellitus had Salmonella enteritidis bacteremia associated with mycotic aneurysm of the transverse aortic arc and myocarditis. Antibiotic therapy with ampicillin and chloramphenicol was ineffective despite the fact that the microorganism was sensitive in vitro to those antimicrobials, and the patient had a progressive clinical deterioration which culminated in death.

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

    Directory of Open Access Journals (Sweden)

    Ronny Cohen

    2015-01-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Thomas Sturmberger

    2016-05-01

    Full Text Available 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.

  13. Parvovirus Infection Is Associated With Myocarditis and Myocardial Fibrosis in Young Dogs.

    Science.gov (United States)

    Ford, Jordan; McEndaffer, Laura; Renshaw, Randall; Molesan, Alex; Kelly, Kathleen

    2017-11-01

    Perinatal parvoviral infection causes necrotizing myocarditis in puppies, which results in acute high mortality or progressive cardiac injury. While widespread vaccination has dramatically curtailed the epidemic of canine parvoviral myocarditis, we hypothesized that canine parvovirus 2 (CPV-2) myocardial infection is an underrecognized cause of myocarditis, cardiac damage, and/or repair by fibrosis in young dogs. In this retrospective study, DNA was extracted from formalin-fixed, paraffin-embedded tissues from 40 cases and 41 control dogs under 2 years of age from 2007 to 2015. Cases had a diagnosis of myocardial necrosis, inflammation, or fibrosis, while age-matched controls lacked myocardial lesions. Conventional polymerase chain reaction (PCR) and sequencing targeting the VP1 to VP2 region detected CPV-2 in 12 of 40 cases (30%; 95% confidence interval [CI], 18%-45%) and 2 of 41 controls (5%; 95% CI, 0.1%-16%). Detection of CPV-2 DNA in the myocardium was significantly associated with myocardial lesions ( P = .003). Reverse transcription quantitative PCR amplifying VP2 identified viral messenger RNA in 12 of 12 PCR-positive cases and 2 of 2 controls. PCR results were confirmed by in situ hybridization, which identified parvoviral DNA in cardiomyocytes and occasionally macrophages of juvenile and young adult dogs (median age 61 days). Myocardial CPV-2 was identified in juveniles with minimal myocarditis and CPV-2 enteritis, which may indicate a longer window of cardiac susceptibility to myocarditis than previously reported. CPV-2 was also detected in dogs with severe myocardial fibrosis with in situ hybridization signal localized to cardiomyocytes, suggesting prior myocardial damage by CPV-2. Despite the frequency of vaccination, these findings suggest that CPV-2 remains an important cause of myocardial damage in dogs.

  14. EXPERIENCE IN THE OBSERVATION OF ACUTE AND FULMINANT MYOCARDITIS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    L. V. Bregel

    2017-01-01

    Full Text Available The results of observation of 17 patients aged 2 monthsto 16 years with acute and fulminant myocarditis(FM were analyzed. Patients were observed in the period 2013-2016. Diagnostics used clinical data, laboratory and instrumental studies. Of 17 patients, acute myocarditis was diagnosed in 14 children, fulminant in 3. Therapy included, first of all, measures for the treatment of heart failure – diuretics (furosemide, verospiron, triampur, angiotensin converting enzyme (ACE inhibitors (captopril, beta-blockers, digoxin inotropic agents. Intravenous human immunoglobulin was administered at a dose of 1-2 g/kg/course in 5 of 17 (29.4% patients. When the pathogen was verified, specific antiviral therapy (acyclovir, ganciclovir, cymevene was administered in a standard mode. Immunosuppressive therapy (prednisolone, delagil was prescribed for two of them. Nonsteroidal anti-inflammatory drugs (ibuprofen, diclofenac was obtained in children with acute myocarditis duration of over 2 weeks (13 children prior to 2016. Nonsteroidal antiinflammatory drugs were not administered to hemodynamically unstable patients, regardless of the time period of observation. Overall, 16 out of 17 (94.4% patients recovered with apparent regression of signs of myocarditis on the background of treatment – the symptoms of acute heart failure and cardiogenic shock were treated, and then manifestations of chronic congestive heart failure gradually decreased. 1 (5,6% child with fulminant myocarditis died. After 6 months to 3 years, 14 children were observed. Follow-up within 6 months to 3 years showed that the diameter of the left ventricle normalized in 10 out of 14 (71.4%. Two out of 14 children (14.3% formed postmyocardial dilated cardiomyopathy.

  15. Left and right atrial feature tracking in acute myocarditis: A feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Dick, Anastasia, E-mail: anastasia-dick@web.de [Department of Radiology, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne (Germany); Schmidt, Björn, E-mail: bjoernschmidt1989@gmx.de [Department of Radiology, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne (Germany); Michels, Guido, E-mail: guido.michels@uk-koeln.de [Department III of Internal Medicine, Heart Centre, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne (Germany); Bunck, Alexander C., E-mail: alexander.bunck@uk-koeln.de [Department of Radiology, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne (Germany); Maintz, David, E-mail: david.maintz@uk-koeln.de [Department of Radiology, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne (Germany); Baeßler, Bettina, E-mail: bettina.baessler@uk-koeln.de [Department of Radiology, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne (Germany)

    2017-04-15

    Purpose: The present study aims at evaluating the feasibility and reproducibility of cardiac magnetic resonance (CMR) feature tracking (FT) derived strain and strain rate (SR) parameters of the left and right atrium (LA, RA) in patients with acute myocarditis as well as their potential to detect diastolic dysfunction. In addition, the diagnostic value of LA and RA strain parameters in the setting of acute myocarditis is investigated. Methods: CMR cine data of 30 patients with CMR-positive acute myocarditis were retrospectively analyzed. 25 age- and gender-matched healthy individuals served as a control. Analysis of longitudinal strain and SR of both atria was performed in two long-axis views using a dedicated FT-software. LA and RA deformation was analyzed including reservoir function (total strain [ε{sub s}], peak positive SR [SR{sub s}]), conduit function (passive strain [ε{sub e}], peak early negative SR [SR{sub e}]) and booster pump function (active strain [ε{sub a}], peak late negative SR [SR{sub a}]). Intra- and inter-observer reproducibility was assessed for all strain and SR parameters using Bland-Altman analyses, intra-class correlation coefficients (ICCs) and coefficients of variation (CV). Results: FT analyses of both atria were feasible in all patients and controls. Reproducibility was good for reservoir and conduit function parameters and moderate for booster pump function parameters. Myocarditis patients demonstrated an impaired LA reservoir and conduit function when compared to healthy controls (LA ε{sub s}: 32 ± 17 vs. 46 ± 13, p = 0.019; LA SR{sub s}: 1.5 ± 0.5 vs. 1.8 ± 0.5, p = 0.117; LA SR{sub e}: −1.3 ± 0.5 vs. −1.9 ± 0.5, p < 0.001), while LA booster pump function was preserved. In logistic regression and ROC-analyses, LA SR{sub e} proved to be the best independent predictor of acute myocarditis (AUC 0.80), and using LA SR{sub e} with a cut-off of −1.6 s{sup −1} resulted in a diagnostic sensitivity of 83% and a specificity of

  16. [Comparison analysis of muscle enzymes in children with myocarditis and Duchene/Becker muscular dystrophy].

    Science.gov (United States)

    Zhang, Yali; Wang, Hong; Yu, Xuexin; Xing, Yanlin; Wang, Ce; He, Rong

    2016-09-28

    To compare the changes in muscle enzyme between children with myocarditis and Duchene/Becker muscular dystrophy (DMD/BMD), and to seek the explanations for variation.
 The retrospective analysis for 83 myocarditis children (myocarditis group) and 69 DMD/BMD children (DMD/BMD group), who were collected from Department of Pediatric of Shengjing Hospital affiliated to China Medical University since January 2008 to May 2015, was carried out. At the same time, 24 healthy children from the Department of Pediatric Development served as a control group. The examination indexes included creatine kinase (CK), creatine kinase-isoenzyme MB (CK-MB), creatine kinase isoenzyme MB mass (CK-MB mass), cardiac troponin I (cTnI) and high-sensitive-cTnT (hs-cTnT).
 1) In the myocarditis group, the CK increased from 100 to 1 000 U/L, reached a peak after 5 days, which lasted for a week and then dropped to the normal; the CK-MB reached a peak after 5 to 7 days and dropped to the normal a month later; the CK-MB mass reached a peak on the first day and dropped to the normal after 3 weeks; the cTn reached to a peak after 5 days and dropped to the normal after about 17 days; hs-cTnT reached to a peak on the first day and dropped to the normal after about 19 days. 2) In the DMD/BMD group, the CK increased significantly and 27 cases had a CK value of more than 10 000 U/L. After the treatment for 1 to 2 weeks, their enzyme rose again after a slight drop. In terms of cTnI, 6 cases showed a moderate increase, 5 of them couldn't drop to the normal level until more than 3 weeks later; the hs-cTnT increased in the 45 cases, which lasted for more than 3 weeks in the 31 cases of them and showed a tendency of persisting increase.
 The cTnI and hs-cTnT rise significantly and possess wider observation window than CK and CK-MB mass in myocarditis children, with more sensitive and specific changes. The myocardial damage can occur before myasthenia and keep this trend for a long time in the DMD

  17. Severe human parechovirus type 3 myocarditis and encephalitis in an adolescent with hypogammaglobulinemia

    Directory of Open Access Journals (Sweden)

    Stacey K. Mardekian

    2015-07-01

    Full Text Available Human parechovirus (HPeV belongs to the Picornaviridae family of RNA viruses. HPeV infections can be asymptomatic, lead to mild respiratory and/or gastrointestinal symptoms, or less frequently cause severe diseases such as sepsis, meningitis, encephalitis, and myocarditis. Severe neurological HPeV infections occur most commonly in infants and neonates. There are currently 16 recognized types of HPeV. HPeV type 3 (HPeV3 has been the predominant type associated with severe central nervous system disease in neonates and newborns since its discovery in 1999. Although HPeV-related infections have been reported in adults, symptomatic HPeV3 infections in adolescents and adults are uncommon. A case of severe HPeV3 myocarditis and encephalitis in an adolescent is described.

  18. Role of Electrophysiological Study and Catheter Ablation for Recurrent Ventricular Tachycardia Complicating Myocarditis

    Directory of Open Access Journals (Sweden)

    Emanuele Cecchi

    2012-01-01

    Full Text Available Here we report the case of a 31-year-old man admitted to our hospital with echocardiografic and Cardiac Magnetic Resonance signs of myocarditis complicated by ventricular tachycardia, initially resolved with direct current shock. After the recurrence of ventricular tachycardia the patient was submitted to electrophysiological study revealing a re-entrant circuit at the level of the medium segment of interventricular septum, successfully treated with transcatheter ablation. This case highlights how the presence of recurrent ventricular arrhythmias at the onset of acute myocarditis, suspected or proven, could be associated with a pre-existing arrhythmogenic substrate, therefore these patients should be submitted to electrophysiological study in order to rule out the presence of arrhythmogenic focuses that can be treated with transcatheter ablation.

  19. Churg-Strauss syndrome presenting with eosinophilic myocarditis: a diagnostic challenge.

    Science.gov (United States)

    Correia, Ana Sofia; Gonçalves, Alexandra; Araújo, Vítor; Almeida e Silva, João; Pereira, José Manuel; Rodrigues Pereira, Pedro; Pizarro, Manuel; Silva, João Carlos; Maciel, Maria Júlia

    2013-09-01

    Churg-Strauss syndrome (CSS) is an unusual disease that presents as systemic vasculitis and peripheral eosinophilia in patients with an atopic constitution. Cardiac involvement is unusual and often not prominent on initial presentation, but is an important cause of morbidity and mortality in patients with CSS. We report the case of a young woman with severe acute myocarditis. Coronary arteriography demonstrated extensive focal vasculopathy, consistent with coronary vasculitis, and myocardial biopsy showed eosinophilic myocarditis. This presentation led to an initial diagnosis of CSS in this patient and appropriate therapy resulted in a spectacular remission of disease activity. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  20. Feature-tracking myocardial strain analysis in acute myocarditis. Diagnostic value and association with myocardial oedema

    International Nuclear Information System (INIS)

    Luetkens, Julian A.; Schlesinger-Irsch, Ulrike; Kuetting, Daniel L.; Dabir, Darius; Homsi, Rami; Schmeel, Frederic C.; Sprinkart, Alois M.; Naehle, Claas P.; Schild, Hans H.; Thomas, Daniel; Doerner, Jonas; Fimmers, Rolf

    2017-01-01

    To investigate the diagnostic value of cardiac magnetic resonance (CMR) feature-tracking (FT) myocardial strain analysis in patients with suspected acute myocarditis and its association with myocardial oedema. Forty-eight patients with suspected acute myocarditis and 35 control subjects underwent CMR. FT CMR analysis of systolic longitudinal (LS), circumferential (CS) and radial strain (RS) was performed. Additionally, the protocol allowed for the assessment of T1 and T2 relaxation times. When compared with healthy controls, myocarditis patients demonstrated reduced LS, CS and RS values (LS: -19.5 ± 4.4% vs. -23.6 ± 3.1%, CS: -23.0 ± 5.8% vs. -27.4 ± 3.4%, RS: 28.9 ± 8.5% vs. 32.4 ± 7.4%; P < 0.05, respectively). LS (T1: r = 0.462, P < 0.001; T2: r = 0.436, P < 0.001) and CS (T1: r = 0.429, P < 0.001; T2: r = 0.467, P < 0.001) showed the strongest correlations with T1 and T2 relaxations times. Area under the curve of LS (0.79) was higher compared with those of CS (0.75; P = 0.478) and RS (0.62; P = 0.008). FT CMR myocardial strain analysis might serve as a new tool for assessment of myocardial dysfunction in the diagnostic work-up of patients suspected of having acute myocarditis. Especially, LS and CS show a sufficient diagnostic performance and were most closely correlated with CMR parameters of myocardial oedema. (orig.)

  1. Value of Cine-MRI sequences before and after injection in the diagnosis of acute myocarditis.

    Science.gov (United States)

    Zidi, Asma; Zairi, Ihsen; Mzoughi, Khadija; Zakhama, Lilia; Kamoun, Ikram; Ben Halima, Afef; Ridene, Imen

    2016-11-01

    Cardiovascular magnetic resonance (CMR) has become the examination of choice in case of suspicion of acute myocarditis. Late gadolinium enhancement (LGE) imaging is very important to establish this diagnosis. Cine MRI sequences are useful for the study of the myocardial contractility.   The purpose is to estimate the value of cine MRI sequences before and after injection for the diagnosis of acute myocarditis compared with late gadolinium enhanced sequences. We prospectively included 40 patients having a high suspicion of acute myocarditis and examined using a 1.5 Tesla CMR. Cine MRI sequences before and after injection were performed. The protocol also include  T2-weighted  short- tau-inversion-recovery (STIR T2) fast spin echo MRI and LGE imaging eight minutes after injection with visual adjustment of inversion time. Delayed enhancement was found among 23 patients. Fifteen patients (65 %) presented a spontaneous hyper signal detected visually on Cine MRI sequences before injection and 11 patients (48 %) on STIR T2. The hyper signal on Cine MRI sequences after injection of gadolinium was the same topography that the late raising at 23 patients. In addition, we highlighted a significant difference between this hyper signal before injection and the left ventricle ejection fraction (p=0.022) as well as with the telesystolic volume of the left ventricle (LV) indexed by the body mass (p=0.039). Our study suggests that Cine MRI sequences after injection are of equal performance in the diagnosis of acute myocarditis as the LGE sequences and its contibution is important when we want to shorten the examination or when inversion time isn't optimal.

  2. Feature-tracking myocardial strain analysis in acute myocarditis. Diagnostic value and association with myocardial oedema

    Energy Technology Data Exchange (ETDEWEB)

    Luetkens, Julian A.; Schlesinger-Irsch, Ulrike; Kuetting, Daniel L.; Dabir, Darius; Homsi, Rami; Schmeel, Frederic C.; Sprinkart, Alois M.; Naehle, Claas P.; Schild, Hans H.; Thomas, Daniel [University of Bonn, Department of Radiology, Bonn (Germany); Doerner, Jonas [University Hospital Cologne, Department of Radiology, Cologne (Germany); Fimmers, Rolf [University of Bonn, Department of Medical Biometry, Informatics, and Epidemiology, Bonn (Germany)

    2017-11-15

    To investigate the diagnostic value of cardiac magnetic resonance (CMR) feature-tracking (FT) myocardial strain analysis in patients with suspected acute myocarditis and its association with myocardial oedema. Forty-eight patients with suspected acute myocarditis and 35 control subjects underwent CMR. FT CMR analysis of systolic longitudinal (LS), circumferential (CS) and radial strain (RS) was performed. Additionally, the protocol allowed for the assessment of T1 and T2 relaxation times. When compared with healthy controls, myocarditis patients demonstrated reduced LS, CS and RS values (LS: -19.5 ± 4.4% vs. -23.6 ± 3.1%, CS: -23.0 ± 5.8% vs. -27.4 ± 3.4%, RS: 28.9 ± 8.5% vs. 32.4 ± 7.4%; P < 0.05, respectively). LS (T1: r = 0.462, P < 0.001; T2: r = 0.436, P < 0.001) and CS (T1: r = 0.429, P < 0.001; T2: r = 0.467, P < 0.001) showed the strongest correlations with T1 and T2 relaxations times. Area under the curve of LS (0.79) was higher compared with those of CS (0.75; P = 0.478) and RS (0.62; P = 0.008). FT CMR myocardial strain analysis might serve as a new tool for assessment of myocardial dysfunction in the diagnostic work-up of patients suspected of having acute myocarditis. Especially, LS and CS show a sufficient diagnostic performance and were most closely correlated with CMR parameters of myocardial oedema. (orig.)

  3. The role of extracorporeal life support in acute myocarditis: a bridge to recovery?

    Science.gov (United States)

    Sanders, D Bradford; Sowell, Steven R; Willis, Brigham; Lane, John; Pierce, Christopher; Pophal, Stephen; Arabia, Francisco A; Nigro, John J

    2012-12-01

    Acute myocardial failure associated with myocarditis is highly lethal. Left ventricular assist device support for these patients has been advocated to decompress the left ventricle and facilitate myocardial remodeling and recovery. Concerns exist regarding the ability of venoarterial (VA) extracorporeal life support (ECLS) to decompress the left ventricle and allow effective myocardial recovery. ECLS has several advantages, including availability, rapid deployment, and flexibility, as compared with contemporary ventricular assist devices. The objective of this study was to provide a brief review of acute myocarditis and present our series of patients. After Institutional Review Board approval, we conducted a retrospective data analysis of patients on ECLS experiencing rapidly progressive myocardial failure from a normal baseline. Patients with a history of intrinsic heart disease were excluded. All patients were thought to have myocarditis and had failed medical therapy requiring emergent ECLS support. Five patients demographics are detailed in Table 1. Patients experienced life-threatening intractable dysrhythmias or cardiac arrest and were refractory to medical therapy with severe acidosis and impending multisystem organ failure. All patients were stabilized with VA ECLS, and the left ventricle and atrium were decompressed in four of five patients. A left atrial vent was placed in one patient. Myocardial recovery with successful weaning from ECLS was obtained in four of five patients and to a normal ejection fraction in three of the five. One patient failed ECLS weaning and required biventricular VAD support secondary to severe myocardial necrosis from giant cell myocarditis and was transplanted, one died, all others are alive at follow-up. ECLS is safe and effective to treat acute myocardial failure and may be used to obtain myocardial recovery in certain subsets. We devised a decision algorithm for ECLS deployment in this patient cohort and routinely use ECLS.

  4. Absence of kynurenine 3-monooxygenase reduces mortality of acute viral myocarditis in mice.

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    Kubo, Hisako; Hoshi, Masato; Mouri, Akihiro; Tashita, Chieko; Yamamoto, Yasuko; Nabeshima, Toshitaka; Saito, Kuniaki

    2017-01-01

    Infection of the encephalomyocarditis virus (EMCV) in mice is an established model for viral myocarditis. Previously, we have demonstrated that indoleamine 2,3-dioxygenase (IDO), an L-tryptophan - kynurenine pathway (KP) enzyme, affects acute viral myocarditis. However, the roles of KP metabolites in EMCV infection remain unclear. Kynurenine 3-monooxygenase (KMO) is one of the key regulatory enzymes, which metabolizes kynurenine to 3-hydroxykynurenine in the KP. Therefore, we examined the role of KMO in acute viral infection by comparing between KMO -/- mice and KMO +/+ mice. KMO deficiency resulted in suppressed mortality after EMCV infection. The number of infiltrating cells and F4/80 + cells in KMO -/- mice was suppressed compared with those in KMO +/+ mice. KMO -/- mice showed significantly increased levels of serum KP metabolites, and induction of KMO expression upon EMCV infection was involved in its effect on mortality through EMCV suppression. Furthermore, KMO -/- mice showed significantly suppression of CCL2, CCL3 and CCL4 on day 2 and CXCL1 on day 4 after infection. These results suggest that increased KP metabolites reduced chemokine production, resulting in suppressed mortality upon KMO knockdown in EMCV infection. KP metabolites may thus provide an effective strategy for treating acute viral myocarditis. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  5. A case report and literature review of Churg-Strauss syndrome presenting with myocarditis.

    Science.gov (United States)

    Qiao, Lu; Gao, Dengfeng

    2016-12-01

    Churg-Strauss syndrome (CSS) is a multisystem disorder characterized by asthma, prominent peripheral blood eosinophilia, and vasculitis signs. 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. 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.

  6. Lyme disease presenting with facial palsy and myocarditis mimicking myocardial infarction.

    Science.gov (United States)

    Gilson, Julieta; Khalighi, Koroush; Elmi, Farhad; Krishnamurthy, Mahesh; Talebian, Amirsina; Toor, Rubinder S

    2017-01-01

    A 45-year-old woman presented with a sudden episode of typical chest pain, radiating to her neck. The patient denied premature coronary artery disease in the family. Initial EKG showed normal sinus rhythm with a 1 mm ST-elevation involving lead II and lead aVF and a 1 mm ST-depression in lead V1 with associated T-wave inversion. Initial Troponin I (normal disease. Two days later the patient developed right-sided facial palsy. Diagnosis of Lyme disease was confirmed by ELISA with positive IgM and IgG antibodies. Treatment with intravenous ceftriaxone and oral steroids was started. Eventually resolution of symptoms and, normalization of cardiac markers and EKG changes, were achieved. This is a rare case of Lyme myocarditis associated with markedly elevated Troponin I, normal left ventricle function, and an absence of conduction abnormalities. To the best of our knowledge, Lyme myocarditis mimicking acute coronary syndrome with such high levels of Troponin I and neurologic compromise has not been previously described. Lyme myocarditis may be a challenging diagnosis in endemic areas especially in patients with coronary artery disease risk factors, presenting with typical chest pain, EKG changes and positive cardiac biomarkers. Therefore, it should be considered a differential diagnosis in patients presenting with clinical symptoms suggestive of acute coronary syndrome. Abbreviations AV: Atrioventricular; CK-MB: Creatinine Kinase-MB; EKG: Electrocardiogram; ELISA: Enzyme-Linked Immunosorbent Assay; IgG: Immunoglobulin G; IgM: Immunoglobulin M.

  7. Polymerase chain reaction analysis for viruses in paraffin-embedded myocardium from dogs with dilated cardiomyopathy or myocarditis.

    Science.gov (United States)

    Maxson, T R; Meurs, K M; Lehmkuhl, L B; Magnon, A L; Weisbrode, S E; Atkins, C E

    2001-01-01

    To perform polymerase chain reaction (PCR) analysis on paraffin-embedded myocardium from dogs with dilated cardiomyopathy (DCM) and dogs with myocarditis to screen for canine parvovirus, adenovirus types 1 and 2, and herpesvirus. Myocardial specimens from 18 dogs with an antemortem diagnosis of DCM and 9 dogs with a histopathologic diagnosis of myocarditis were evaluated. Paraffin-embedded myocardial specimens were screened for viral genome by PCR analysis. Positive-control specimens were developed from cell cultures as well as paraffin-embedded tissue specimens from dogs with clinical and histopathologic diagnoses of viral infection with canine parvovirus, adenovirus types 1 and 2, and herpesvirus. The histologic characteristics of all myocardial specimens were classified regarding extent, location, and type of inflammation and fibrosis. Canine adenovirus type 1 was amplified from 1 specimen from a dog with DCM. Canine parvovirus, adenovirus type 2, and herpesvirus were not amplified from any myocardial specimens. Histologic analysis of specimens from dogs with DCM revealed variable amounts of fibrosis; myocardial inflammation was observed in 1 affected dog. Histopathologic analysis of specimens from dogs with myocarditis disclosed variable degrees of inflammation and fibrosis. Viral agents canine parvovirus, adenovirus types 1 and 2, and herpesvirus are not commonly associated with DCM or active myocarditis in dogs. Additional studies evaluating for nucleic acid from viruses that less commonly affect dogs or different types of infectious agents may be warranted to gain insight into the cause of DCM and myocarditis in dogs.

  8. Local experience with extracorporeal membrane oxygenation in children with acute fulminant myocarditis.

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    Botao Ning

    Full Text Available To analyze the clinical effect of extracorporeal membrane oxygenation (ECMO in children with acute fulminant myocarditis, we retrospectively analyzed the data of five children with acute fulminant myocarditis in the intensive care unit (ICU at the Affiliated Children's Hospital, Zhejiang University from February 2009 to November 2012. The study group included two boys and three girls ranging in age from 9 to 13 years (median 10 years. Body weight ranged from 25 to 33 kg (mean 29.6 kg. They underwent extracorporeal membrane oxygenation (ECMO through a venous-arterial ECMO model with an average ECMO supporting time of 89.8 h (40-142 h. Extracorporeal circulation was established in all five children. After treatment with ECMO, the heart rate, blood pressure, and oxygen saturation were greatly improved in the four children who survived. These four children were successfully weaned from ECMO and discharged from hospital machine-free, for a survival rate of 80% (4/5. One child died still dependent on the machine. Cause of death was irrecoverable cardiac function and multiple organ failure. Complications during ECMO included three cases of suture bleeding, one case of acute hemolytic renal failure and suture bleeding, and one case of hyperglycemia. During the follow-up period of 4-50 months, the four surviving children recovered with normal cardiac function and no abnormal functions of other organs. The application of ECMO in acute fulminant myocarditis, even in local centers that experience low incidence of this disease, remains an effective approach. Larger studies to determine optimal timing of placement on ECMO to guide local centers are warranted.

  9. Advances in the Traditional Chinese Medicine-Based Management of Viral Myocarditis.

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    Cao, Yong; Xu, Xia; Zhang, Peiying

    2015-09-01

    Viral myocarditis (VMC) is a common clinical condition; however, no specific treatment has been available from the perspective of modern western medicine, and typically only symptomatic treatment is provided in clinical settings. The traditional Chinese medicine (TCM) has shown certain advantages in treating VMC. Last few years have witnessed certain advances in the TCM-based research on the etiology and pathogenesis of VMC and its clinical management. This article reviews the clinical advances made in the TCM-based management of VMC in the last 5 years.

  10. Ebi3 Prevents Trypanosoma cruzi-Induced Myocarditis by Dampening IFN-γ-Driven Inflammation

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    Tiago Silva Medina

    2017-09-01

    Full Text Available The identification of anti-inflammatory mediators can reveal important targetable molecules capable of counterbalancing Trypanosoma cruzi-induced myocarditis. Composed of Ebi3 and IL-27p28 subunits, IL-27 is produced by myeloid cells and is able to suppress inflammation by inducing IL-10-producing Tr1 cells, thus emerging as a potential candidate to ameliorate cardiac inflammation induced by T. cruzi. Although IL-27 has been extensively characterized as a suppressive cytokine that prevents liver immunopathogenesis after T. cruzi infection, the mechanisms underlying its effects on T. cruzi-induced myocarditis remain largely unknown. Here, wild-type (WT and Ebi3-deficient animals were intraperitoneally infected with trypomastigotes of T. cruzi Y strain and used to evaluate the potential anti-inflammatory properties of Ebi3 during T. cruzi infection. The survival rates of mice were daily recorded, the frequency of inflammatory cells was analyzed by flow cytometry and inflammatory mediators were measured by ELISA, real-time PCR and PCR array. We reported that T. cruzi-induced myocarditis was prevented by Ebi3. Stressors mainly recognized by TLR2 and TLR4 receptors on myeloid cells were essential to trigger IL-27p28 production. In addition, Ebi3 regulated IFN-γ-mediated myocarditis by promoting an anti-inflammatory environment through IL-10, which was most likely produced by Tr1 cells rather than classical regulatory T cells (Tregs, in the heart tissue of T. cruzi-infected animals. Furthermore, in vivo IFN-γ blockade ameliorated the host survival without compromising the parasite control in the bloodstream. In humans, IL-27p28 was correlated with cardiac protection during Chagas disease. Patients with mild clinical forms of the disease produced high levels of IL-27p28, whereas lower levels were found in those with severe forms. In addition, polymorphic sites at Ebi3 gene were associated with severe cardiomyopathy in patients with Chagas disease

  11. Ebi3 Prevents Trypanosoma cruzi-Induced Myocarditis by Dampening IFN-γ-Driven Inflammation

    Science.gov (United States)

    Medina, Tiago Silva; Oliveira, Gabriela Gonçalves; Silva, Maria Cláudia; David, Bruna Araújo; Silva, Grace Kelly; Fonseca, Denise Morais; Sesti-Costa, Renata; Frade, Amanda Farage; Baron, Monique Andrade; Ianni, Barbara; Pereira, Alexandre Costa; Chevillard, Christophe; Cunha-Neto, Edécio; Marin-Neto, José Antonio; Silva, João Santana

    2017-01-01

    The identification of anti-inflammatory mediators can reveal important targetable molecules capable of counterbalancing Trypanosoma cruzi-induced myocarditis. Composed of Ebi3 and IL-27p28 subunits, IL-27 is produced by myeloid cells and is able to suppress inflammation by inducing IL-10-producing Tr1 cells, thus emerging as a potential candidate to ameliorate cardiac inflammation induced by T. cruzi. Although IL-27 has been extensively characterized as a suppressive cytokine that prevents liver immunopathogenesis after T. cruzi infection, the mechanisms underlying its effects on T. cruzi-induced myocarditis remain largely unknown. Here, wild-type (WT) and Ebi3-deficient animals were intraperitoneally infected with trypomastigotes of T. cruzi Y strain and used to evaluate the potential anti-inflammatory properties of Ebi3 during T. cruzi infection. The survival rates of mice were daily recorded, the frequency of inflammatory cells was analyzed by flow cytometry and inflammatory mediators were measured by ELISA, real-time PCR and PCR array. We reported that T. cruzi-induced myocarditis was prevented by Ebi3. Stressors mainly recognized by TLR2 and TLR4 receptors on myeloid cells were essential to trigger IL-27p28 production. In addition, Ebi3 regulated IFN-γ-mediated myocarditis by promoting an anti-inflammatory environment through IL-10, which was most likely produced by Tr1 cells rather than classical regulatory T cells (Tregs), in the heart tissue of T. cruzi-infected animals. Furthermore, in vivo IFN-γ blockade ameliorated the host survival without compromising the parasite control in the bloodstream. In humans, IL-27p28 was correlated with cardiac protection during Chagas disease. Patients with mild clinical forms of the disease produced high levels of IL-27p28, whereas lower levels were found in those with severe forms. In addition, polymorphic sites at Ebi3 gene were associated with severe cardiomyopathy in patients with Chagas disease. Collectively, we

  12. Unusual echocardiographic features seen in a case of giant cell myocarditis.

    Science.gov (United States)

    Kochar, Minisha; López-Candales, Angel; Ramani, Gautam; Rajagopalan, Navin; Edelman, Kathy

    2008-11-01

    The case of an 18-year-old college football player with a recent history of streptococcal pharyngitis who was experiencing progressive disabling dyspnea on exertion with easy fatigability and lack of stamina, and was taken to the hospital after a syncopal episode is described. The patient was initially diagnosed with heart failure and treated accordingly. However, because of a fulminant clinical deterioration, an endomyocardial biopsy was recommended, which showed focal giant cell transformation consistent with giant cell myocarditis. Treatment with methylprednisolone and cyclosporine was promptly initiated. Several apical clots were noted during treatment, but the patient attained full recovery with treatment.

  13. Ga-67 citrate myocardial uptake in a patient with AIDS, toxoplasmosis, and myocarditis

    International Nuclear Information System (INIS)

    Memel, D.S.; DeRogatis, A.J.; William, D.C.

    1991-01-01

    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

  14. Myocarditis with ST elevation and elevated cardiac enzymes misdiagnosed as an ST-elevation myocardial infarction.

    Science.gov (United States)

    Sheldon, Seth H; Crandall, Mark A; Jaffe, Allan S

    2012-12-01

    Acute myocarditis can mimic ST-elevation myocardial infarction (STEMI). Quickly determining the correct diagnosis is critical given the "time is muscle" implication with a STEMI and the potential adverse effects associated with use of fibrinolytic therapy. A 46-year-old man presented to a rural emergency department with chest pain, and an electrocardiogram (ECG) read as showing 0.1 mV of ST-segment elevation in leads III and aVF. His initial cardiac troponin T was 0.44 ng/mL. He received fibrinolytic therapy for presumed STEMI. Cardiac magnetic resonance imaging was later performed and showed epicardial delayed enhancement consistent with myocarditis. Upon further questioning, he acknowledged 3 days of stuttering chest discomfort and a recent upper respiratory infection, as well as similar chest pain in his wife. A systematic evaluation is essential for acute chest pain, including a focused history, identification of cardiac risk factors, and ECG interpretation. A history of recent viral illness, absence of cardiac risk factors, or ECG findings inconsistent with a single anatomic lesion would suggest a potential alternate diagnosis to STEMI. This case emphasizes the importance of a focused history in the initial evaluation of chest pain. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Serum expression of HA and LN in lewis rat models of autoimmune myocarditis

    International Nuclear Information System (INIS)

    Han Li'na; Li Tieling; Zhang Yajing; Yang Tingshu; Ding Yu; Guo Shuli; Zhao Xiaoning

    2011-01-01

    Objective: To study the clinical significance of dynamic changes of serum expressions of hyaluronic acid (HA) and laminin (LN) in Lewis rat models of experimental autoimmune myocarditis (EAM). Methods: Fifty Lewis rat models of experimental autoimmune myocarditis (EAM) were established with injection of recombinant cardiac C protein with complete freund adjuvant into two foot-pads plus intraperitoneal injection of pertussis toxin. At 1w, 2w, 4w, 6w and 8w, 10 models were sacrificed each time;cardiac tissues were examined with HE stain for myocardial inflammatory score and examined with picrosirius red stain for myocardial fibrosis score, also, serum HA and LN expressions were determined with RIA. These examinations were performed in 10 undisturbed animals as controls. Results: The myocardial inflammatory scores of the models at 1w were about the same as those in the controls, but the scores rapidly increased from 2w on to 4w then fell gradually. The myocardial fibrosis scores of the models at 1wk were also not much different from those in controls. The fibrosis scores increased rapidly at 4w and maintained at high level up to 8w. The changes of serum expressions of HA and LN roughly paralleled those of myocardial fibrosis scores i. e. rapidly increased at 4w up to 8w. Conclusion: Serum expressions of HA and LN could faithfully reflect the degree of myocardial fibrosis in rat models of EAM. HA and LN were useful markers of myocardial fibrois and were of prognostic importance. (authors)

  16. Coxsackievirus B3 vaccines: use as an expression vector for prevention of myocarditis.

    Science.gov (United States)

    Henke, Andreas; Jarasch, Nadine; Wutzler, Peter

    2008-12-01

    Coxsackievirus B3 (CVB3), a member of the Picornaviridae family, is considered to be one of the most important infectious agents to cause virus-induced myocarditis. Despite improvements in studying virus pathology, structure and molecular biology, as well as the diagnosis of this disease, there is still no virus-specific drug or vaccine in clinical use. During the last 20 years many investigations have been performed to develop classic and modern immunization techniques against CVB3-induced heart disease. One promising approach among others includes the insertion of coding sequences of cytokines into the viral genome. The application of an IFN-gamma-expressing recombinant coxsackievirus vector is especially efficient against CVB3-induced myocarditis. Beside direct IFN-gamma-mediated antiviral effects, the local and simultaneous expression of IFN-gamma by the virus itself activates the immune system in a strong and long-lasting manner, which protects animals completely against subsequent lethal infections independently of the age of the immunized individual and the route of vaccine administration.

  17. Myocarditis caused by Feline Immunodeficiency Virus in Five Cats with Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Rolim, V Machado; Casagrande, R Assis; Wouters, A Terezinha Barth; Driemeier, D; Pavarini, S Petinatti

    2016-01-01

    Viral infections have been implicated as the cause of cardiomyopathy in several mammalian species. This study describes hypertrophic cardiomyopathy (HCM) and myocarditis associated with feline immunodeficiency virus (FIV) infection in five cats aged between 1 and 4 years. Clinical manifestations included dyspnoea in four animals, one of which also exhibited restlessness. One animal showed only lethargy, anorexia and vomiting. Necropsy examination revealed marked cardiomegaly, marked left ventricular hypertrophy and pallor of the myocardium and epicardium in all animals. Microscopical and immunohistochemical examination showed multifocal infiltration of the myocardium with T lymphocytes and fewer macrophages, neutrophils and plasma cells. An intense immunoreaction for FIV antigen in the cytoplasm and nucleus of lymphocytes and the cytoplasm of some macrophages was observed via immunohistochemistry (IHC). IHC did not reveal the presence of antigen from feline calicivirus, coronavirus, feline leukaemia virus, feline parvovirus, Chlamydia spp. or Toxoplasma gondii. The results demonstrate the occurrence of FIV infection in inflammatory cells in the myocardium of five cats with myocarditis and HCM. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Myocarditis exacerbation in a child undergoing inguinal hernioplasty after viral infection

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    Simić Dušica

    2009-01-01

    Full Text Available Introduction Immunosuppressive effects of general anesthesia and surgery could have unexpected consequences in a child with recent infection. The incidence of myocarditis in childhood is unknown. Case outline During general anesthesia for inguinal hernia repair, a seven-year-old boy suddenly developed heart failure. Clinical presentation included hypotension, pulmonary edema, drop in hemoglobin oxygen saturation, ST segment elevation and premature ventricular contractions. Homodynamic stability and adequate oxygenation were achieved with dopamine and furosemide. Preoperative history, physical examination and complete blood count were unremarkable. Moderate cardiomegaly and pulmonary edema were present on chest radiography. Diminished left ventricular contractility found on echocardiography increased troponin I and CK-MB levels suggested myocardial injury. Increased C-reactive protein with lymphocytosis suggested inflammation as its cause. Parents failed to report rubella 10 days before the operation. A clinical diagnosis of myocarditis as a complication of rubella was based on increased titer of IgM to rubella. With intravenous immunoglobulin, corticosteroids and symptomatic treatment for heart failure, his condition improved and ejection fraction reached 68 % one month after operation. Conclusion In future, we need protocols with instructions for pediatric patients undergoing elective surgery and anesthesia after viral infections.

  19. Molecular screening by polymerase chain reaction detects panleukopenia virus DNA in formalin-fixed hearts from cats with idiopathic cardiomyopathy and myocarditis.

    Science.gov (United States)

    Meurs, K M; Fox, P R; Magnon, A L; Liu, S; Towbin, J A

    2000-01-01

    Viral myocarditis has been suggested as an etiology for cardiomyopathy in several mammalian species. Myocarditis and idiopathic cardiomyopathy have been reported in the domestic cat, although a viral etiology has not been demonstrated. Because of the continuing interest in the potential relationship between viral myocarditis and cardiomyopathy, we evaluated hearts from cats with spontaneous, idiopathic cardiomyopathy for viral genomic material within myocytes by polymerase chain reaction, and for the presence of myocarditis by light microscopy. Thirty-one (31) formalin-fixed hearts from domestic cats who died of idiopathic cardiomyopathy were randomly selected from pathology archives. Seventeen (17) formalin-fixed hearts from healthy cats were similarly selected as normal controls. The polymerase chain reaction (PCR) was used to evaluate myocardial tissue for the presence of viral genome from feline panleukopenia virus, herpes virus, calici virus, and corona virus. Hearts were examined using light microscopy for histologic evidence of myocarditis according to the Dallas criteria. Panleukopenia virus was identified by PCR in 10 of 31 cats with cardiomyopathy but in none of the controls. Neither cardiomyopathic or control cats tested positive by PCR for herpes virus, calici virus, and corona virus. Myocarditis was detected by histologic examination in 18 of 31 cardiomyopathic cats and in none of 17 control cats. Myocarditis and or feline panleukopenia virus genome was detected in felines with idiopathic hypertrophic, dilated, and restrictive cardiomyopathy, suggesting a possible role of viral infection and inflammation in the pathogenesis of cardiomyopathy in this species.

  20. Th2 Regulation of Viral Myocarditis in Mice: Different Roles for TLR3 versus TRIF in Progression to Chronic Disease

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    Eric D. Abston

    2012-01-01

    Full Text Available Viral infections are able to induce autoimmune inflammation in the heart. Here, we investigated the role of virus-activated Toll-like receptor (TLR3 and its adaptor TRIF on the development of autoimmune coxsackievirus B3 (CVB3 myocarditis in mice. Although TLR3- or TRIF-deficient mice developed similarly worse acute CVB3 myocarditis and viral replication compared to control mice, disease was significantly worse in TRIF compared to TLR3-deficient mice. Interestingly, TLR3-deficient mice developed an interleukin (IL-4-dominant T helper (Th2 response during acute CVB3 myocarditis with elevated markers of alternative activation, while TRIF-deficient mice elevated the Th2-associated cytokine IL-33. Treatment of TLR3-deficient mice with recombinant IL-33 improved heart function indicating that elevated IL-33 in the context of a classic Th2-driven response protects against autoimmune heart disease. We show for the first time that TLR3 versus TRIF deficiency results in different Th2 responses that uniquely influence the progression to chronic myocarditis.

  1. 99mTc-Hynic-annexin V imaging to evaluate inflammation and apoptosis in rats with autoimmune myocarditis

    International Nuclear Information System (INIS)

    Tokita, Naoki; Izumi, Tohru; Hasegawa, Shinji; Maruyama, Kaoru; Blankenberg, Francis G.; Tait, Jonathan F.; Strauss, William H.; Nishimura, Tsunehiko

    2003-01-01

    Inflammation and cell death are two important components of myocarditis. We evaluated the distribution of inflammation and apoptotic cell death in rats with autoimmune myocarditis using two radiotracers - technetium-99m Hynic-annexin V ( 99m Tc-annexin) as a marker of apoptotic cell death and carbon-14 deoxyglucose ( 14 C-DG) as a marker of inflammation - in comparison with histologic findings. Three, 7 and 14 weeks after immunization with porcine cardiac myosin (acute, subacute, and chronic phases, respectively) 99m Tc-annexin and 14 C-DG were injected. The uptake in the total heart was determined as the percentage of injected dose per gram (% ID/g) by tissue counting. Dual-tracer autoradiography with 99m Tc-annexin and 14 C-DG was performed. The distribution of each of these agents was compared with the results of hematoxylin and eosin staining to identify areas of inflammation, and TUNEL staining to identify areas of apoptosis. Total cardiac uptake of 99m Tc-annexin in the acute phase of myocarditis was significantly higher than that in normal rats (1.28%±0.30% vs 0.46%±0.01%; P 14 C-DG in the acute phase of myocarditis was significantly higher than that in normal rats (2.78%±0.95% vs 1.02%±0.25%; P 14 C-DG uptake; some also corresponded to areas of high 99m Tc-annexin uptake in the acute phase of myocarditis. 99m Tc-annexin localization was strongly correlated with the number of TUNEL-positive cells (P 14 C-DG showed no relationship with it. There is a marked difference in the distribution of inflammation and apoptotic cell death in the myocardium of animals with immune myocarditis. These changes are mirrored by the localization of 14 C-DG and 99m Tc-annexin. Sites of inflammation and zones of apoptotic cell death change over the course of immune myocarditis. (orig.)

  2. Meningeal hyperaemia and myocarditis in a caged rabbit with encephalitozoonosis: Case report and literature review

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    Davinson Chuka Anyogu

    2017-11-01

    Full Text Available Over the years, encephalitozoonosis in rabbits has raised serious concern owing to the subclinical nature of the infection in most rabbits and the danger of zoonosis in immunocompromised persons. The disease has been diagnosed by clinical signs, histopathological examination and detection of the antibody in serum. The lesions have been described mainly in the brain, kidney and liver of infected rabbits. The present report documented additional lesions seen in a male rabbit presented to the Necropsy Unit of the Department of Veterinary Pathology and Microbiology, University of Nigeria, Nsukka for euthanasia. Following euthanasia, tissue samples from the rabbit were processed and stained with haematoxylin and eosin. The microscopic lesions were comprised of meningeal hyperaemia, myocarditis, chronic nonsuppurative granulomatous hepatitis, and Encephalitozoon cuniculi spores in the brain parenchyma. The study showed the importance of reporting new findings in order to elucidate the pathogenic mechanisms for the disease and to renew attention to its zoonotic potential.

  3. Severe necrotizing myocarditis caused by serratia marcescens infection in an axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    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. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

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    Keiji Okuda

    Full Text Available 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.

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

    Science.gov (United States)

    Okuda, Keiji; Fu, Hai Ying; 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.

  6. Molecular phenotypes of human parvovirus B19 in patients with myocarditis.

    Science.gov (United States)

    Bock, C-Thomas; Düchting, Anja; Utta, Friederike; Brunner, Eva; Sy, Bui Tien; Klingel, Karin; Lang, Florian; Gawaz, Meinrad; Felix, Stephan B; Kandolf, Reinhard

    2014-04-26

    To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy (DCM). Endomyocardial biopsies (EMBs) from 498 B19V-positive patients with myocarditis and DCM were analyzed using molecular methods and functional experiments. EMBs were obtained from the University Hospitals of Greifswald and Tuebingen and additionally from 36 German cardiology centers. Control tissues were obtained at autopsy from 34 victims of accidents, crime or suicide. Identification of mononuclear cell infiltrates in EMBs was performed using immunohistological staining. Anti-B19V-IgM and anti-B19V-IgG were analyzed by enzyme-linked immunosorbent assay (ELISA). B19V viral loads were determined using in-house quantitative real-time polymerase chain reaction (PCR). For B19V-genotyping a new B19V-genotype-specific restriction fragment length polymorphism (RFLP)-PCR was established. B19V-genotyping was verified by direct DNA-sequencing and sequences were aligned using BLAST and BioEdit software. B19V P6-promoter and HHV6-U94-transactivator constructs were generated for cell culture experiments. Transfection experiments were conducted using human endothelial cells 1. Luciferase reporter assays were performed to determine B19V-replication activity. Statistical analysis and graphical representation were calculated using SPSS and Prism5 software. The prevalence of B19V was significantly more likely to be associated with inflammatory cardiomyopathy (iCMP) compared to uninflamed DCM (59.6% vs 35.3%) (P reactivation of B19V-infection by HHV6-coinfection in B19V-associated iCMP. Our findings suggest that B19V-infection of the human heart can be a causative event for the development of an endothelial cell-mediated inflammatory disease and that this is related to both viral load and genotype.

  7. Myositis, Ganglioneuritis, and Myocarditis with Distinct Perifascicular Muscle Atrophy in a 2-Year-Old Male Boxer

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    Paul M. Rossman

    2018-02-01

    Full Text Available A 2-year-old male, intact Boxer was referred for chronic diarrhea, hyporexia, labored breathing, weakness and elevated creatine kinase, and alanine aminotransferase activities. Initial examination and diagnostics revealed a peripheral nervous system neurolocalization, atrial premature complexes, and generalized megaesophagus. Progressive worsening of the dog’s condition was noted after 36 h; the dog developed aspiration pneumonia, was febrile and oxygen dependent. The owners elected humane euthanasia. Immediately postmortem biopsies of the left cranial tibial and triceps muscles and the left peroneal nerve were obtained. Postmortem histology revealed concurrent myositis, myocarditis, endocarditis, and ganglioneuritis. Mixed mononuclear cell infiltrations and a distinct perifascicular pattern of muscle fiber atrophy was present in both muscles. This is a novel case of diffuse inflammatory myopathy with a distinct perifascicular pattern of atrophy in addition to endocarditis, myocarditis, and epicarditis.

  8. Rapid reversal of heart failure in a patient with pheochromocytoma and catecholamine-induced myocarditis/cardiomyopathy

    International Nuclear Information System (INIS)

    Ahmed, I.; Sankaran, R.; Al-Addad, A.

    2002-01-01

    Pheochromocytoma is rare and usually presents as paroxysal or sustained hypertension, nonetheless, it can also cause severe acute pulmonary edema in normotensive individuals. We present a case with pheochromocytoma and severe left ventricular failure caused by catecholamine induced myocarditis/cardiomyopathy. Severe left ventricular failure resolved rapidly and left ventricular systolic function became normal within two weeks of medical treatment. Later, patient underwent elective and uneventful surgical removal of pheochromocytoma. (author)

  9. Pancreatitis and myocarditis followed by pulmonary hemorrhage, a rare presentation of leptospirosis- A case report and literature survey

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    Ranawaka Nuwan

    2013-01-01

    Full Text Available Abstract Background Leptospirosis is a potentially fatal disease which can cause multi-organ dysfunction. It can rarely present as acute pancreatitis. This is the first ever report of leptospirosis presenting with acute pancreatitis and myocarditis followed by diffuse pulmonary hemorrhages to the best of our knowledge. Case presentation A 15-year-old South Asian boy presented with high grade fever, epigastric discomfort and was anicteric on admission. He developed tachycardia, transient hypotension, changes of electro-cardiogram and positive troponin I suggestive of myocarditis. Acute pancreatitis was diagnosed with 12 fold high serum amylase and with the evidence of computerized tomography. Then he developed diffuse pulmonary hemorrhages and later acute renal failure. Leptospirosis was confirmed by positive leptospira IgM, negative IgG and strongly positive Microscopic Agglutination Test. Other possible infective and autoimmune causes were excluded. Patient recovered completely with antibiotics and the supportive care. Conclusion This case illustrates diagnostic difficulties especially in resource poor settings where leptospirosis is common. Additionally it highlights the fact that leptospirosis should be considered in patients presenting with pancreatitis which can be complicated with myocarditis and diffuse pulmonary hemorrhages. We hypothesize that Toll like receptors may play a role in such systemic involvement.

  10. Age-Associated Changes in Estrogen Receptor Ratios Correlate with Increased Female Susceptibility to Coxsackievirus B3-Induced Myocarditis

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    Andreas Koenig

    2017-11-01

    Full Text Available Sexual bias is a hallmark in various diseases. This review evaluates sexual dimorphism in clinical and experimental coxsackievirus B3 (CVB3 myocarditis, and how sex bias in the experimental disease changes with increased age. Coxsackieviruses are major causes of viral myocarditis, an inflammation of the heart muscle, which is more frequent and severe in men than women. Young male mice infected with CVB3 develop heart-specific autoimmunity and severe myocarditis. Females infected during estrus (high estradiol develop T-regulatory cells and when infected during diestrus (low estradiol develop autoimmunity similar to males. During estrus, protection depends on estrogen receptor alpha (ERα, which promotes type I interferon, activation of natural killer/natural killer T cells and suppressor cell responses. Estrogen receptor beta has opposing effects to ERα and supports pro-inflammatory immunity. However, the sexual dimorphism of the disease is significantly ameliorated in aged animals when old females become as susceptible as males. This correlates to a selective loss of the ERα that is required for immunosuppression. Therefore, sex-associated hormones control susceptibility in the virus-mediated disease, but their impact can alter with the age and physiological stage of the individual.

  11. Adult Kawasaki's disease with myocarditis, splenomegaly, and highly elevated serum ferritin levels.

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    Cunha, Burke A; Pherez, Francisco M; Alexiadis, Varvara; Gagos, Marios; Strollo, Stephanie

    2010-01-01

    erythema. We present a case of adult Kawasaki's disease with myocarditis and splenomegaly. The patient's myocarditis rapidly resolved, and he did not develop coronary artery aneurysms. In addition to splenomegaly, this case of adult Kawasaki's disease is remarkable because the patient had highly elevated serum ferritin levels of 944-1303 ng/mL; (normalfever for> or =5 days with conjunctival suffusion, cervical adenopathy, swelling of the dorsum of the hands/feet, thrombocytosis and otherwise unexplained highly elevated ferritin levels. Copyright 2010 Elsevier Inc. All rights reserved.

  12. Effect of adenosine cyclophosphate combined with vitamin C on cellular immune function of children with viral myocarditis

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    Xiu Chang

    2016-06-01

    Full Text Available Objective: To investigate the curative effect of adenosine cyclophosphate combined with vitamin C on children with viral myocarditis andon cellular immune function. Methods: A total of 96 cases of children with viral myocarditis were randomly divided into control group and observation group, 48 cases in each. The control group received routine treatment for viral myocarditis. The observation group received routine treatment for viral myocarditis as well as vitamin C and adenosine cyclophosphate. Results: The total effective rate of observation group 89.59% was higher than that of control group 64.58%, and differences were statistical significant. The electrocardiogram total effective rate of observation group 91.67% was higher than that of control group 68.75%, and differences were statistical significant. After treatment, the level of CD3+ (65.09±10.35%, the level of CD4+ (42.93±6.22%, the level of CD8+ (29.55±4.87% and the level of NK (47.37±8.52% of observation group were higher than the level of CD3+ (51.85±9.33%, the level of CD4+ (35.18±5.73%, the level of CD8+ (24.46±4.03% and the level of NK (35.64±7.72% of control group, and differences were statistical significant. After treatment, myocardial enzyme indexes lactate dehydrogenase (329.65±19.76 U/L, creatine phosphate kinase (126.36±12.92 U/L, hydroxybutyrate dehydrogenase (271.68±14.73 U/L, glutamic oxaloacetic transaminase (31.22±3.76 U/ L and creatine kinase (185.28±13.83 U/L of observation group were lower than lactate dehydrogenase (348.06±20.51 U/L, creatine phosphate kinase (163.19±13.15 U/L, hydroxybutyrate dehydrogenase (305.50±16.42 U/L, glutamic oxaloacetic transaminase (37.87±4.07 U/L and creatine kinase (202.79±15.47 U/L of control group, and differences were statistical significant. After treatment, heart function indexes CI, FS and EF levels of observation group were higher than those of control group, and differences were statistical significant

  13. Functional and morphological parameters with tissue characterization of cardiovascular magnetic imaging in clinically verified ''infarct-like myocarditis''

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    Schwab, Johannes [Paracelsus Medical Univ., General Hospital Nuremberg (Germany). Dept. of Cardiology and Radiology; Rogg, H.J.; Pauschinger, M.; Fessele, K. [Paracelsus Medical Univ., General Hospital Nuremberg (Germany). Dept. of Cardiology; Bareiter, T.; Baer, I. [Paracelsus Medical Univ., General Hospital Nuremberg (Germany). Dept. of Cardiology and Neuroradiology; Loose, R. [Paracelsus Medical Univ., General Hospital Nuremberg (Germany). Dept. of Radiology

    2016-04-15

    Cardiac magnetic resonance (CMR) has increasingly proved to be a valuable diagnostic tool for evaluating patients with suspected myocarditis. The objective of this study was to evaluate the diagnostic value of functional and morphological parameters including tissue characterization in patients with ''infarct-like myocarditis''. 43 patients with clinically verified cases of ''infarct-like myocarditis'' (median time to MRI scanning after admission for acute symptoms 3 days) and 35 control patients matched by age and sex were included in this retrospective case control study. In this study we used a 1.5 T MRI scanner conducting steady-state-free-precession sequences, T2-weighted imaging, T1-weighted imaging before and after contrast administration and late gadolinium enhancement sequences. According to the recommendations for CMR diagnosis of myocarditis (Lake Louise consensus criteria), a scan was positive for acute myocarditis if 2 of 3 CMR criteria were present. 30 % of the patients with ''infarct-like myocarditis'' had a reduced left ventricular ejection fraction, 11 % had an increased LV end-diastolic volume index and 35 % had an increased LV mass index. The sensitivity of wall motion abnormalities was 63 % with a regional distribution in 49 %. In 47 % of cases regional wall motion abnormalities were present in the lateral left ventricular segments. Pericardial effusions were discovered in 65 % of cases with a circular appearance in 21 % and focal manifestation in 44 %. The diagnostic sensitivity, specificity, and accuracy of CMR in patients with ''infarct-like myocarditis'' were 67 %, 100 % and 82 %, respectively. The LGE alone was the most sensitive test parameter with 86 %, providing a specificity of 100 % and accuracy of 92 %. Our study results can be applied to the subgroup of patients with ''infarct-like myocarditis'', where we found that LGE alone was the

  14. Structural and functional characteristics of myocard in patients with different forms of atrial fibrillation

    Directory of Open Access Journals (Sweden)

    L. I. Vasilyeva

    2015-02-01

    Full Text Available Aim. To study structural and functional characteristics of myocard in patients with different forms of atrial fibrillation. Atrial fibrillation is the most prevalent arrhythmia in clinical practice. Atrial fibrillation is a progressive disease: the duration of paroxysms increases over time and paroxysmal atrial fibrillation transforms to persistent, the last one becomes refractory to pharmacological and electrical cardioversion in time and transforms to permanent. So assessment of myocardial remodeling in patients with persistent and permanent atrial fibrillation is very actual. Methods and results. According to the aim of the study 133 patients with persistent atrial fibrillation and 100 patients with permanent atrial fibrillation were included into the study. Echocardiographic parameters of left and right atria function were studied. Conclusion. It was found that patients with persistent and permanent atrial fibrillation are characterized with both left and right atrias remodeling. Remodeling of the atrias is less pronounced in patients with permanent atrial fibrillation in comparison with persistent atrial fibrillation patients and arrhythmia recurrence.

  15. Unresolved issues in theories of autoimmune disease using myocarditis as a framework.

    Science.gov (United States)

    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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Assessment of acute myocarditis by cardiac magnetic resonance imaging: Comparison of qualitative and quantitative analysis methods.

    Science.gov (United States)

    Imbriaco, Massimo; Nappi, Carmela; Puglia, Marta; De Giorgi, Marco; Dell'Aversana, Serena; Cuocolo, Renato; Ponsiglione, Andrea; De Giorgi, Igino; Polito, Maria Vincenza; Klain, Michele; Piscione, Federico; Pace, Leonardo; Cuocolo, Alberto

    2017-10-26

    To compare cardiac magnetic resonance (CMR) qualitative and quantitative analysis methods for the noninvasive assessment of myocardial inflammation in patients with suspected acute myocarditis (AM). A total of 61 patients with suspected AM underwent coronary angiography and CMR. Qualitative analysis was performed applying Lake-Louise Criteria (LLC), followed by quantitative analysis based on the evaluation of edema ratio (ER) and global relative enhancement (RE). Diagnostic performance was assessed for each method by measuring the area under the curves (AUC) of the receiver operating characteristic analyses. The final diagnosis of AM was based on symptoms and signs suggestive of cardiac disease, evidence of myocardial injury as defined by electrocardiogram changes, elevated troponin I, exclusion of coronary artery disease by coronary angiography, and clinical and echocardiographic follow-up at 3 months after admission to the chest pain unit. In all patients, coronary angiography did not show significant coronary artery stenosis. Troponin I levels and creatine kinase were higher in patients with AM compared to those without (both P quantitative (ER 0.89 and global RE 0.80) analyses were also similar. Qualitative and quantitative CMR analysis methods show similar diagnostic accuracy for the diagnosis of AM. These findings suggest that a simplified approach using a shortened CMR protocol including only T2-weighted STIR sequences might be useful to rule out AM in patients with acute coronary syndrome and normal coronary angiography.

  17. Unresolved issues in theories of autoimmune disease using myocarditis as a framework

    Science.gov (United States)

    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

  18. Cardiac Magnetic Resonance Imaging in Myocarditis Reveals Persistent Disease Activity Despite Normalization of Cardiac Enzymes and Inflammatory Parameters at 3-Month Follow-Up.

    Science.gov (United States)

    Berg, Jan; Kottwitz, Jan; Baltensperger, Nora; Kissel, Christine K; Lovrinovic, Marina; Mehra, Tarun; Scherff, Frank; Schmied, Christian; Templin, Christian; Lüscher, Thomas F; Heidecker, Bettina; Manka, Robert

    2017-11-01

    There is a major unmet need to identify high-risk patients in myocarditis. Although decreasing cardiac and inflammatory markers are commonly interpreted as resolving myocarditis, this assumption has not been confirmed as of today. We sought to evaluate whether routine laboratory parameters at diagnosis predict dynamic of late gadolinium enhancement (LGE) as persistent LGE has been shown to be a risk marker in myocarditis. Myocarditis was diagnosed based on clinical presentation, high-sensitivity troponin T, and cardiac magnetic resonance imaging, after exclusion of obstructive coronary artery disease by angiography. Cardiac magnetic resonance imaging was repeated at 3 months. LGE extent was analyzed with the software GT Volume. Change in LGE >20% was considered significant. Investigated cardiac and inflammatory markers included high-sensitivity troponin T, creatine kinase, myoglobin, N-terminal B-type natriuretic peptide, C-reactive protein, and leukocyte count. Twenty-four patients were enrolled. Absolute levels of cardiac enzymes and inflammatory markers at baseline did not predict change in LGE at 3 months. Cardiac and inflammatory markers had normalized in 21 patients (88%). LGE significantly improved in 16 patients (67%); however, it persisted to a lesser degree in 17 of them (71%) and increased in a small percentage (21%) despite normalization of cardiac enzymes. This is the first study reporting that cardiac enzymes and inflammatory parameters do not sufficiently reflect LGE in myocarditis. Although a majority of patients with normalizing laboratory markers experienced improved LGE, in a small percentage LGE worsened. These data suggest that cardiac magnetic resonance imaging might add value to currently existing diagnostic tools for risk assessment in myocarditis. © 2017 American Heart Association, Inc.

  19. Predictive value of cardiac magnetic resonance imaging-derived myocardial strain for poor outcomes in patients with acute myocarditis

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    Lee, Ji Won; Jeong, Yeon Joo; Lee, Gee Won; Lee, Nam Kyung; Lee, Hye Won; Kim, Jin You [Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan (Korea, Republic of); Choi, Bum Sung; Choo, Ki Seok [Pusan National University Yangsan Hospital, Yangsan (Korea, Republic of)

    2017-08-01

    To evaluate the utility of cardiovascular magnetic resonance (CMR)-derived myocardial strain measurement for the prediction of poor outcomes in patients with acute myocarditis We retrospectively analyzed data from 37 patients with acute myocarditis who underwent CMR. Left ventricular (LV) size, LV mass index, ejection fraction and presence of myocardial late gadolinium enhancement (LGE) were analyzed. LV circumferential strain (EccSAX), radial strain (ErrSAX) from mid-ventricular level short-axis cine views and LV longitudinal strain (EllLV), radial strain (ErrLax) measurements from 2-chamber long-axis views were obtained. In total, 31 of 37 patients (83.8%) underwent follow-up echocardiography. The primary outcome was major adverse cardiovascular event (MACE). Incomplete LV functional recovery was a secondary outcome. During an average follow-up of 41 months, 11 of 37 patients (29.7%) experienced MACE. Multivariable Cox proportional hazard regression analysis, which included LV mass index, LV ejection fraction, the presence of LGE, EccSAX, ErrSAX, EllLV, and ErrLax values, indicated that the presence of LGE (hazard ratio, 42.88; p = 0.014), together with ErrLax (hazard ratio, 0.77 per 1%, p = 0.004), was a significant predictor of MACE. Kaplan-Meier analysis demonstrated worse outcomes in patient with LGE and an ErrLax value ≤ 9.48%. Multivariable backward regression analysis revealed that ErrLax values were the only significant predictors of LV functional recovery (hazard ratio, 0.54 per 1%; p = 0.042). CMR-derived ErrLax values can predict poor outcomes, both MACE and incomplete LV functional recovery, in patients with acute myocarditis, while LGE is only a predictor of MACE.

  20. Initial Experience With Simultaneous 18F-FDG PET/MRI in the Evaluation of Cardiac Sarcoidosis and Myocarditis.

    Science.gov (United States)

    Hanneman, Kate; Kadoch, Michael; Guo, Henry H; Jamali, Mehran; Quon, Andrew; Iagaru, Andrei; Herfkens, Robert

    2017-07-01

    The purpose of this study was to compare combined PET/MRI with PET/CT and cardiac MRI in the evaluation of cardiac sarcoidosis and myocarditis. Ten patients (4 men and 6 women; 56.1 ± 9.6 years old) were prospectively enrolled for evaluation of suspected cardiac sarcoidosis or myocarditis. Written informed consent was obtained. Following administration of 9.9 ± 0.9 mCi F-FDG, patients underwent standard cardiac PET/CT followed by combined PET/MRI using a simultaneous 3-T scanner. Cardiac MRI sequences included ECG-triggered cine SSFP, T2-weighted, and late gadolinium-enhanced imaging. Myocardial involvement was assessed with separate analysis of combined PET/MRI, PET/CT, and cardiac MRI data using dedicated postprocessing software. Estimates of radiation dose were derived from the applied doses of F-FDG and CT protocol parameters. Imaging was acquired with a delay from F-FDG injection of 90.2 ± 27.4 minutes for PET/CT and 207.7 ± 40.3 minutes for PET/MRI. Total scan time for PET/MRI was significantly longer than for PET/CT (81.4 ± 14.8 vs 12.0 minutes, P PET/MRI compared with PET/CT (6.9 ± 0.6 vs 8.2 ± 1.1 mSv, P = 0.007). There was no significant difference in the number of positive cases identified between combined PET/MRI (n = 10 [100%]), PET/CT (n = 6 [60%]), and cardiac MRI (n = 8 [80%]), P = 0.091. Simultaneous cardiac PET/MRI is feasible in the evaluation of cardiac sarcoidosis and myocarditis achieving diagnostic image quality.

  1. Mao-to Prolongs the Survival of and Reduces TNF-α Expression in Mice with Viral Myocarditis

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    Zhu Shijie

    2010-01-01

    Full Text Available Goal of this study was to evaluate effects of Mao-to on development of myocarditis induced by encephalomyocarditis (EMC virus in mice. Mice were randomly divided into five groups. Group N included uninfected controls (n = 18, while group A, B and C underwent intraperitoneal injection of EMC virus. Group A was administered oral saline from day 0 to day 4. Group B was administered oral Mao-to (500 mg−1 kg−1 day−1 from day 0 to day 4. Group C was administered Mao-to from day 2 to day 6. Group D was administered Mao-to from day 5 to day 10. Treated mice were followed for survival rates during 2 weeks after infection. Body weight (BW and organ weights including heart (HW, lungs, thymus and spleen were examined on days 4, 6 and 14. Survival rate of group C (36.4% was significantly improved compared with group A, B or D (0% of each, P < 0.05. HW and HW/BW ratio in group C was significantly (P < 0.05 lower than those in group A, B or D. Viral titers of hearts were significantly different among groups A, B and C. Cardiac expression in tumor necrosis factor-α (TNF-α was significantly reduced in group C in comparison with group A, B or D on day 6 by immunohistochemical study. Administration of Mao-to starting on day 2 improves mortality resulting from viral myocarditis in mice with reduced expression of cardiac TNF-α. These findings suggest that timing of Mao-to is crucial for preventing cardiac damage in mice with viral myocarditis.

  2. Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan.

    Science.gov (United States)

    Suzuki, Shigeaki; Ishikawa, Nobuhisa; Konoeda, Fumie; Seki, Nobuhiko; Fukushima, Satoshi; Takahashi, Kikuko; Uhara, Hisashi; Hasegawa, Yoshikazu; Inomata, Shinichiro; Otani, Yasushi; Yokota, Kenji; Hirose, Takashi; Tanaka, Ryo; Suzuki, Norihiro; Matsui, Makoto

    2017-09-12

    To report the clinical features of myasthenia gravis (MG) induced by treatment with immune checkpoint inhibitors using 2-year safety databases based on postmarketing surveys in Japan. We studied 10,277 patients with cancer who had received monotherapy with either nivolumab or ipilimumab between September 2014 and August 2016. As the control group, 105 patients with idiopathic MG were used. There were 12 MG cases (0.12%) among 9,869 patients with cancer who had been treated with nivolumab, but none among 408 patients treated with ipilimumab. These 12 patients included 6 men and 6 women with a mean age of 73.5 ± 6.3 years. MG onset occurred in the early phase after nivolumab treatment and rapidly deteriorated. Nivolumab-related MG (nivoMG) included 4 patients with mild involvement and 8 patients with severe involvement. Bulbar symptoms and myasthenic crisis were observed more frequently in nivoMG than idiopathic MG. Ten patients were positive for anti-acetylcholine receptor antibodies. Serum creatine kinase levels were markedly elevated to an average level of 4,799 IU/L. Among the 12 patients with nivoMG, 4 had myositis and 3 had myocarditis, with 1 of these patients having both. Immunosuppressive therapy was effective. Postintervention status showed that pharmacologic remission or minimal manifestations were obtained in 4 patients; however, 2 patients died. Immune-related adverse events triggered by nivolumab impaired the patients' daily living activity. The prompt and correct recognition of MG following treatment with immune checkpoint inhibitors in patients with cancer is important. © 2017 American Academy of Neurology.

  3. Toxicological effect of TiO2 nanoparticle-induced myocarditis in mice

    Science.gov (United States)

    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.

  4. Ecotropic murine leukemia virus-induced fusion of murine cells

    International Nuclear Information System (INIS)

    Pinter, A.; Chen, T.; Lowy, A.; Cortez, N.G.; Silagi, S.

    1986-01-01

    Extensive fusion occurs upon cocultivation of murine fibroblasts producing ecotropic murine leukemia viruses (MuLVs) with a large variety of murine cell lines in the presence of the polyene antibiotic amphotericin B, the active component of the antifungal agent Fungizone. The resulting polykaryocytes contain nuclei from both infected and uninfected cells, as evidenced by autoradiographic labeling experiments in which one or the other parent cell type was separately labeled with [ 3 H]thymidine and fused with an unlabeled parent. This cell fusion specifically requires the presence of an ecotropic MuLV-producing parent and is not observed for cells producing xenotropic, amphotropic, or dualtropic viruses. Mouse cells infected with nonecotropic viruses retain their sensitivity toward fusion, whereas infection with ecotropic viruses abrogates the fusion of these cells upon cocultivation with other ecotropic MuLV-producing cells. Nonmurine cells lacking the ecotropic gp70 receptor are not fused under similar conditions. Fusion is effectively inhibited by monospecific antisera to gp70, but not by antisera to p15(E), and studies with monoclonal antibodies identify distinct amino- and carboxy-terminal gp70 regions which play a role in the fusion reaction. The enhanced fusion which occurs in the presence of amphotericin B provides a rapid and sensitive assay for the expression of ecotropic MuLVs and should facilitate further mechanistic studies of MuLV-induced fusion of murine cells

  5. Dynamic changes of serum TNF-α and cTnI levels in BALB/c Mouse models of autoimmune myocarditis

    International Nuclear Information System (INIS)

    Han Li'na

    2007-01-01

    Objective: To prepare mouse models of experimental autoimmune myocarditis (EAM) with subcutaneous injection of synthesized peptide (containing heavy chain segment of cardiac myosin) and examine the dynamic changes of cardiac pathology as well as TNF -α, cTnI and autoimmune antibody contents. Methods: BALB/c mice were subcutaneously injected with 0.8 mg of the synthesized peptide to produce the experimental autoimmune myocarditis (EAM) models. The animals were sacrificed 14, 21, 30 and 60d after establishment of the models, heart muscle was examined pathologically to assess the severity of myocarditis and blood were examined for the plasma contents of TNF-α (with RIA) cTnI (with ELISA) and anti-cardiac myosin heavy chain (CMHC) antibody titier (with ELISA). Results: Evidence of myocardial damage appeared on d14 specimens and progressed there after with interstitial infiltration of macrophages and myocardial necrosis. In the 60d specimens, fibrosis was obvious. The plasma TNF-α and cTnI levels were highest in the d30 specimens and declined in the d60 specimens but still remained much higher than normal. Most of the models demonstrated anti-CMHC antibodies in the 21d and 30d specimens. Conclusion: It is feasible to prepare EMC mouse models with subcutaneous injection of synthesized peptide containing heavy chain segment of cardiac myosin and the plasma levels of TNF-α, cTnI in the models are well correlated to the pathologic change of myocarditis. (authors)

  6. Current Translational Research and Murine Models For Duchenne Muscular Dystrophy

    Science.gov (United States)

    Rodrigues, Merryl; Echigoya, Yusuke; Fukada, So-ichiro; Yokota, Toshifumi

    2016-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscle degeneration. Mutations in the DMD gene result in the absence of dystrophin, a protein required for muscle strength and stability. Currently, there is no cure for DMD. Since murine models are relatively easy to genetically manipulate, cost effective, and easily reproducible due to their short generation time, they have helped to elucidate the pathobiology of dystrophin deficiency and to assess therapies for treating DMD. Recently, several murine models have been developed by our group and others to be more representative of the human DMD mutation types and phenotypes. For instance, mdx mice on a DBA/2 genetic background, developed by Fukada et al., have lower regenerative capacity and exhibit very severe phenotype. Cmah-deficient mdx mice display an accelerated disease onset and severe cardiac phenotype due to differences in glycosylation between humans and mice. Other novel murine models include mdx52, which harbors a deletion mutation in exon 52, a hot spot region in humans, and dystrophin/utrophin double-deficient (dko), which displays a severe dystrophic phenotype due the absence of utrophin, a dystrophin homolog. This paper reviews the pathological manifestations and recent therapeutic developments in murine models of DMD such as standard mdx (C57BL/10), mdx on C57BL/6 background (C57BL/6-mdx), mdx52, dystrophin/utrophin double-deficient (dko), mdxβgeo, Dmd-null, humanized DMD (hDMD), mdx on DBA/2 background (DBA/2-mdx), Cmah-mdx, and mdx/mTRKO murine models. PMID:27854202

  7. Cardiac MRI. Estimation of changes in normalized myocardial gadolinium accumulation over time after contrast injection in patients with acute myocarditis and healthy volunteers

    International Nuclear Information System (INIS)

    Breuckmann, F.; Buhr, C.; Maderwald, S.; Bruder, O.; Schlosser, T.; Nassenstein, K.; Erbel, R.; Barkhausen, J.

    2011-01-01

    An increased normalized gadolinium accumulation (NGA) in the myocardium during early washout has been used for the diagnosis of acute myocarditis (AM). Due to the fact that the pharmacokinetics of contrast agents are complex, time-related changes in NGA after contrast injection are likely. Because knowledge about time-related changes of NGA may improve the diagnostic accuracy of MR, our study aimed to estimate the time course of NGA after contrast injection in patients as well as in healthy volunteers. An ECG-triggered inversion recovery SSFP sequence with incrementally increasing inversion times was repetitively acquired over the 15 minutes after injection of 0.2 Gd-DTPA per kg body weight in a 4-chamber view in 15 patients with AM and 20 volunteers. The T 1relaxation times and the longitudinal relaxation rates (R1) of the myocardium and skeletal musculature were calculated for each point in time after contrast injection. The time course of NGA was estimated based on the linear relationship between R 1 and tissue Gd concentration. NGA decreased over time in the form of a negative power function in patients with AM and in healthy controls. NGA in AM tended to be higher than in controls (p > 0.05). NGA rapidly changes after contrast injection, which must be considered when measuring NGA. Although we observed a trend towards higher NGA values in patients with AM with a maximum difference one minute after contrast injection, NGA did not allow us to differentiate patients with AM from healthy volunteers, because the observed differences did not reach a level of significance. (orig.)

  8. Rethinking Molecular Mimicry in Rheumatic Heart Disease andAutoimmune Myocarditis: Laminin, Collagen IV, CAR and B1AR as Initial Targets of Disease

    Directory of Open Access Journals (Sweden)

    Robert eRoot-Bernstein

    2014-08-01

    Full Text Available Rationale: Molecular mimicry theory (MMT suggests that epitope mimicry between pathogens and human proteins can activate autoimmune disease. Group A streptococci (GAS mimics human cardiac myosin in rheumatic heart disease (RHD and coxsackie viruses (CX mimic actin in autoimmune myocarditis (AM. But myosin and actin are immunologically inaccessible and unlikely initial targets. Extracellular cardiac proteins that mimic GAS and CX would be more likely.Objectives: To determine whether extracellular cardiac proteins such as coxsackie and adenovirus receptor (CAR, beta 1 adrenergic receptor (B1AR, CD55/DAF, laminin, and collagen IV mimic GAS, CX and/or cardiac myosin or actin. Methods: BLAST 2.0 and LALIGN searches of the UniProt protein database were employed to identify potential molecular mimics. Quantitative ELISA was used to measure antibody cross-reactivity. Measurements: Similarities were considered to be significant if a sequence contained at least 5 identical amino acids in 10. Antibodies were considered to be cross-reactive if the binding constant had a Kd less than 10-9 M. Main Results: GAS mimics laminin, CAR and myosin. CX mimics actin and collagen IV and B1AR. The similarity search results are mirrored by antibody cross-reactivities. Additionally, antibodies against laminin recognize antibodies against collagen IV; antibodies against actin recognize antibodies against myosin, and antibodies against GAS recognize antibodies against CX. Thus, there is both mimicry of extracellular proteins and antigenic complementarity between GAS-CX in RHD/AM.Conclusions: RHD/AM may be due to combined infections of GAS with CX localize at cardiomyocytes may produce a synergistic, hyperinflammatory response that cross-reacts with laminin, collagen IV, CAR and/or B1AR. Epitope drift shifts the immune response to myosin and actin after cardiomyocytes become damaged.

  9. Activated nuclear transcription factor κB in patients with myocarditis and dilated cardiomyopathy-relation to inflammation and cardiac function

    International Nuclear Information System (INIS)

    Alter, Peter; Rupp, Heinz; Maisch, Bernhard

    2006-01-01

    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-κB (NFκB). 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 NFκB was performed. Results: NFκB was increased in patients with myocarditis when compared with controls (11.1 ± 7.1% vs. 5.0 ± 5.3%, P 2 = 0.72, P 2 = 0.43, P < 0.02). Increased activated NFκB was found in adenovirus persistence when compared with controls (P = 0.001). Only a trend of increased NFκB activation was seen in cytomegalovirus persistence. Parvovirus B19 persistence did not affect NFκB activation. Conclusions: Increased activation of NFκB is related to inflammatory processes in myocarditis. Since activated NFκB correlates with left ventricular function, it could be assumed that NFκB activation occurs at early stages of inflammation. Potentially, NFκB could inhibit loss of cardiomyocytes by apoptosis and protect from cardiac dilation. Since NFκB is a crucial key transcription factor of inflammation, its prognostic and future therapeutic relevance should be addressed

  10. Halofuginone alleviates acute viral myocarditis in suckling BALB/c mice by inhibiting TGF-β1

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xiao-Hua [Department of Emergency, Xi’an Children’s Hospital, Xi' an, 710003, Shanxi (China); Fu, Jia [Department of Infection, Xi’an Children’s Hospital, Xi' an, 710003, Shanxi (China); Sun, Da-Qing, E-mail: daqingsuncd@163.com [Department of Respiration, Xi’an Children’s Hospital, NO. 69 Xijuyuan Lane, Xi' an 710003, Shanxi (China)

    2016-04-29

    Viral myocarditis (VMC) is an inflammation of heart muscle in infants and young adolescents. This study explored the function of halofuginone (HF) in Coxsackievirus B3 (CVB3) -treated suckling mice. HF-treated animal exhibited higher survival rate, lower heart/body weight, and more decreased blood sugar concentration than CVB3 group. HF also reduced the expressions of interleukin(IL)-17 and IL-23 and the numbers of Th17 cells. Moreover, HF downregulated pro-inflammatory cytokine levels and increased anti-inflammatory cytokine levels. The expressions of transforming growth factor(TGF-β1) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) p65/ tumor necrosis factor-α (TNF-α) proteins were decreased by HF as well. Finally, the overexpression of TGF-β1 counteracted the protection effect of HF in CVB3-treated suckling mice. In summary, our study suggests HF increases the survival of CVB3 suckling mice, reduces the Th17 cells and pro-inflammatory cytokine levels, and may through downregulation of the TGF-β1-mediated expression of NF-κB p65/TNF-α pathway proteins. These results offer a potential therapeutic strategy for the treatment of VMC. - Highlights: • Halofuginone (HF) increases the survival of suckling BALB/c mice infected with acute CVB3. • HF reduces the expression of Th17 cell markers (IL-17 and IL-23) and the number of CD4{sup +} IL17{sup +} cells. • Pro-inflammatory cytokines levels associated with myocarditis were reduced by HF in CVB3-treated suckling mice. • HF alleviates VMC via inhibition of TGF-β1-mediated NF-κB p65/TNF-α pathway.

  11. L’infarctus du myocarde du jeune adulte -Analyse rétrospective des cas colligés au CHU de Dakar

    Directory of Open Access Journals (Sweden)

    Nobila Valentin Yameogo

    2010-09-01

    Full Text Available Les données relatives à l’infarctus du myocarde chez le jeune adulte sont rares en Afrique noir. Nous rapportons une série rétrospective de 14 cas d’infarctus du myocarde chez l’adulte jeune noir africain. Pour analyser les caractéristiques épidémiologiques, cliniques, électriques, échographiques, biologiques, thérapeutiques et évolutives de l’infarctus aigu du myocarde chez le jeune adulte nous avons étudié de manière rétrospective les dossiers médicaux d’une série consécutive des patients admis entre Janvier 2003 et Décembre 2008 pour prise en charge d’infarctus aigu du myocarde. Quatre-vingt quatre (84 cas d’infarctus du myocarde ont été pris en charge durant la période d’étude ,14 patients (16,6% avaient un âge inférieur ou égal à 40 ans. L’âge moyen était de 34 +ou-5ans (extrêmes 27ans et 40 ans. Les facteurs de risque cardio-vasculaire étaient dominés par le sexe masculin (n=11, la dyslipidémie (n=7 et le tabagisme par cigarette (n=6. La contraception orale était absente chez le 1/3 des patients. Le délai moyen d’admission était tardif (15 plus ou moins 4 heures. L’IDM était antérieur dans la moitié des cas. L’acide acétylsalicylique, les inhibiteurs de l’enzyme de conversion Les bétabloquants et les statines étaient les médicaments les plus prescrits. La thrombolyse et l’angioplastie étaient respectivement réalisées chez 3 patients et 0 patient. 4 cas d’insuffisance cardiaque, 2 cas de bloc atrio-ventriculaire complet et 1 cas de décès étaient les principales complications. L’infarctus du myocarde concerne également le sujet jeune noir africain. Les facteurs de risque sont essentiellement représentés par le sexe, la dyslipidémie, le tabagisme et la contraception orale.

  12. Characterization of the binding of radioiodinated hybrid recombinant IFN-alpha A/D to murine and human lymphoid cell lines

    International Nuclear Information System (INIS)

    Faltynek, C.R.; Princler, G.L.; Schwabe, M.; Shata, M.T.; Lewis, G.K.; Kamin-Lewis, R.M.

    1990-01-01

    The hybrid recombinant human interferon (IFN) rIFN-alpha A/D was radioiodinated. Specific binding of [125I]rIFN-alpha A/D was observed with both human and murine cell lines. The binding of [125I]rIFN-alpha A/D to human Daudi cells had similar characteristics to the previously described binding of [125I]rIFN-alpha A or -alpha 2. The following lines of evidence demonstrated that [125I]rIFN-alpha A/D bound with high affinity to the same receptor on murine cells as murine IFN-alpha and -beta: (i) the binding of [125I]rIFN-alpha A/D to murine LBRM cells was inhibited to a similar extent by natural murine IFN-alpha, natural murine IFN-beta, and rIFN-A/D; (ii) the Kd (approximately 2 X 10(-10) M) obtained from both competition experiments and saturation binding experiments with [125I]rIFN-alpha A/D was comparable to the previously reported Kd for the binding of natural murine IFN-alpha and -beta to other murine cell lines; (iii) the size of the cross-linked [125I]rIFN-alpha A/D receptor complex formed on murine LBRM cells was similar to the previously reported cross-linked complex formed after binding radioiodinated natural murine IFN-beta to other murine cell lines. Due to the current lack of readily available recombinant murine IFN-alpha or -beta for radiolabeling and the previously demonstrated biological activity of rIFN-alpha A/D on murine cells, [125I]rIFN-alpha A/D should prove to be a useful reagent for further studies of murine IFN receptors

  13. Murine model of long term obstructive jaundice

    Science.gov (United States)

    Aoki, Hiroaki; Aoki, Masayo; Yang, Jing; Katsuta, Eriko; Mukhopadhyay, Partha; Ramanathan, Rajesh; Woelfel, Ingrid A.; Wang, Xuan; Spiegel, Sarah; Zhou, Huiping; Takabe, Kazuaki

    2016-01-01

    Background With the recent emergence of conjugated bile acids as signaling molecules in cancer, a murine model of obstructive jaundice by cholestasis with long-term survival is in need. Here, we investigated the characteristics of 3 murine models of obstructive jaundice. Methods C57BL/6J mice were used for total ligation of the common bile duct (tCL), partial common bile duct ligation (pCL), and ligation of left and median hepatic bile duct with gallbladder removal (LMHL) models. Survival was assessed by Kaplan-Meier method. Fibrotic change was determined by Masson-Trichrome staining and Collagen expression. Results 70% (7/10) of tCL mice died by Day 7, whereas majority 67% (10/15) of pCL mice survived with loss of jaundice. 19% (3/16) of LMHL mice died; however, jaundice continued beyond Day 14, with survival of more than a month. Compensatory enlargement of the right lobe was observed in both pCL and LMHL models. The pCL model demonstrated acute inflammation due to obstructive jaundice 3 days after ligation but jaundice rapidly decreased by Day 7. The LHML group developed portal hypertension as well as severe fibrosis by Day 14 in addition to prolonged jaundice. Conclusion The standard tCL model is too unstable with high mortality for long-term studies. pCL may be an appropriate model for acute inflammation with obstructive jaundice but long term survivors are no longer jaundiced. The LHML model was identified to be the most feasible model to study the effect of long-term obstructive jaundice. PMID:27916350

  14. Therapy with granulocyte colony-stimulating factor in the chronic stage, but not in the acute stage, improves experimental autoimmune myocarditis in rats via nitric oxide.

    Science.gov (United States)

    Shimada, Kana; Okabe, Taka-aki; Mikami, Yu; Hattori, Miki; Fujita, Masatoshi; Kishimoto, Chiharu

    2010-09-01

    We systematically investigated serial efficacy of granulocyte colony-stimulating factor (G-CSF) therapy upon experimental autoimmune myocarditis (EAM) in rats treated with and without the inhibition of nitric oxide (NO) with the analyses of tissue regeneration. G-CSF could mobilize multipotent progenitor cells of bone marrow into the peripheral blood and may improve ventricular function. A rat model of porcine myosin-induced EAM was used. After the immunization of myosin, G-CSF (10 microg/kg/day) or saline was injected intraperitoneally on days 0-21 in experiment 1 and on days 21-42 in experiment 2. Additional myosin-immunized rats were orally given 25 mg/kg/day of N(G)-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase (NOS), in each experiment (each group; n=8-21). Serum cytokines and peripheral blood cell counts were measured in each group. In experiment 1, G-CSF treatment aggravated cardiac pathology associated with increased macrophage inflammatory protein-2 (MIP-2) and interleukin-6 (IL-6) levels and enhanced superoxide production. In experiment 2, G-CSF treatment reduced the severity of myocarditis with increased capillary density and improved left ventricular ejection fraction. In the rats with EAM treated with G-CSF associated with oral L-NAME treatment in experiment 2, the severity of myocarditis was not reduced. Myocardial c-kit(+) cells were demonstrated only in G-CSF-treated group in experiment 2 but not in other groups. G-CSF has differential effects on EAM in rats associated with the modulation of cytokine network. The overwhelming superoxide production by G-CSF administration in the acute stage may worsen the disease. G-CSF therapy improved cardiac function via NO system in a rat model of myocarditis in the chronic stage, but not in the acute stage, possibly through the myocardial regeneration and acceleration of healing process. Copyright 2010 Elsevier Ltd. All rights reserved.

  15. Imported rickettsioses : think of murine typhus

    NARCIS (Netherlands)

    van der Kleij, FGH; Gansevoort, RT; Kreeftenberg, HG

    Murine typhus is a disease still prevalent in many parts of the world. Because the incidence in the US and Europe has declined rapidly, physicians in these continents have become unfamiliar with the clinical picture. Murine typhus is associated with significant morbidity and fatalities do occur,

  16. Due diligence

    International Nuclear Information System (INIS)

    Sanghera, G.S.

    1999-01-01

    The Occupational Health and Safety (OHS) Act requires that every employer shall ensure the health and safety of workers in the workplace. Issues regarding the practices at workplaces and how they should reflect the standards of due diligence were discussed. Due diligence was described as being the need for employers to identify hazards in the workplace and to take active steps to prevent workers from potentially dangerous incidents. The paper discussed various aspects of due diligence including policy, training, procedures, measurement and enforcement. The consequences of contravening the OHS Act were also described

  17. Infarct-like acute myocarditis: relation between electrocardiographic findings and myocardial damage as assessed by cardiac magnetic resonance imaging.

    Science.gov (United States)

    Nucifora, Gaetano; Miani, Daniela; Di Chiara, Antonio; Piccoli, Gianluca; Artico, Jessica; Puppato, Michela; Slavich, Gianaugusto; De Biasio, Marzia; Gasparini, Daniele; Proclemer, Alessandro

    2013-03-01

    Acute myocarditis (AM) may occasionally have an infarct-like presentation. The aim of the present study was to investigate the relation between electrocardiographic (ECG) findings in this group of patients and myocardial damage assessed by cardiac magnetic resonance imaging (MRI) with the late gadolinium enhancement (LGE) technique. Myocardial damage may be associated with ECG changes in infarct-like AM. Forty-one consecutive patients (36 males; mean age, 36 ± 12 years) with diagnosis of AM according to cardiac MRI Lake Louise criteria and infarct-like presentation were included. The relation between site of ST-segment elevation (STE), sum of STE (sumSTE), time to normalization of STE, and development of negative T wave with the extent of LGE (expressed as % of left ventricular mass [%LV LGE]), was evaluated. Most (80%) patients presented with inferolateral STE; mean sumSTE was 5 ± 3 mm. Normalization of STE occurred within 24 hours in 20 (49%) patients. Development of negative T wave occurred in 28 (68%) patients. Cardiac MRI showed LGE in all patients; mean %LV LGE was 9.6 ± 7.2%. Topographic agreement between site of STE and LGE was 68%. At multivariate analysis, sumSTE (β = 0.42, P 24 hours (β = 0.39, P 24 hours, and development of negative T wave) may help to identify patients with larger areas of myocardial damage. © 2012 Wiley Periodicals, Inc.

  18. Clinical Presentation and Outcome in a Contemporary Cohort of Patients with Acute Myocarditis: The Multicenter Lombardy Registry.

    Science.gov (United States)

    Ammirati, Enrico; Cipriani, Manlio; Moro, Claudio; Raineri, Claudia; Pini, Daniela; Sormani, Paola; Mantovani, Riccardo; Varrenti, Marisa; Pedrotti, Patrizia; Conca, Cristina; Mafrici, Antonio; Grosu, Aurelia; Briguglia, Daniele; Guglielmetto, Silvia; Battista Perego, Giovanni; Colombo, Stefania; Caico, Salvatore Ivan; Giannattasio, Cristina; Maestroni, Alberto; Carubelli, Valentina; Metra, Marco; Lombardi, Carlo; Campodonico, Jeness; Agostoni, Piergiuseppe; Peretto, Giovanni; Scelsi, Laura; Turco, Annalisa; Di Tano, Giuseppe; Campana, Carlo; Belloni, Armando; Morandi, Fabrizio; Mortara, Andrea; Cirò, Antonio; Senni, Michele; Gavazzi, Antonello; Frigerio, Maria; Oliva, Fabrizio; Camici, Paolo G

    2018-05-15

    Background -There is controversy regarding outcome of patients with acute myocarditis (AM), and lack of data on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management and long-term outcome of patients with AM based on a retrospective multi-center registry from 19 Italian hospitals. Methods -A total of 684 patients with suspected AM and recent onset of symptoms (70 years and those older than 50 years without coronary angiography were excluded. The final study population comprised 443 patients (median age 34 years, 19.4% female) with AM diagnosed either by endomyocardial biopsy (EMB) or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance (CMR). Results -At presentation, 118 patients (26.6%) had either left ventricular (LV) ejection fraction (EF) presentation and 0% in uncomplicated cases (Log-rank ppresentation had LVEFpresentation. Conclusions -In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with LVEFpresentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent LV systolic dysfunction.

  19. Serotonin transporter gene polymorphism and myocardial infarction: Etude Cas-Témoins de l'Infarctus du Myocarde (ECTIM).

    Science.gov (United States)

    Fumeron, Frédéric; Betoulle, Dina; Nicaud, Viviane; Evans, Alun; Kee, Frank; Ruidavets, Jean-Bernard; Arveiler, Dominique; Luc, Gérald; Cambien, François

    2002-06-25

    Depression is a risk factor for myocardial infarction (MI). Selective serotonin reuptake inhibitors reduce this risk. The site of action is the serotonin transporter (SLC6A4), which is expressed in brain and blood cells. A functional polymorphism in the promoter region of the SLC6A4 gene has been described. This polymorphism may be associated with the risk of MI. The SLC6A4 polymorphism has been investigated by polymerase chain reaction in 671 male patients with MI and in 688 controls from the Etude Cas-Témoins de l'Infarctus du Myocarde (ECTIM) multicentric study. Percentages for LL, LS, and SS genotypes were 35.5%, 45.4%, and 19.1%, respectively, for cases versus 28.1%, 49.1%, and 22.8%, respectively, for controls. S allele frequency was 41.8% and 47.4% for cases and controls, respectively. After adjustment for age and center by using multivariable logistic regression, the odds ratio for MI associated with the LL genotype was 1.40 (95% CI 1.11 to 1.76, P=0.0047). The LL genotype of the SLC6A4 polymorphism is associated with a higher risk of MI. This could be attributable to the effect of the polymorphism on serotonin-mediated platelet activation or smooth muscle cell proliferation or on other risk factors, such as depression or response to stress.

  20. The presence of enterovirus, adenovirus, and parvovirus B19 in myocardial tissue samples from autopsies: an evaluation of their frequencies in deceased individuals with myocarditis and in non-inflamed control hearts.

    Science.gov (United States)

    Nielsen, Trine Skov; Hansen, Jakob; Nielsen, Lars Peter; Baandrup, Ulrik Thorngren; Banner, Jytte

    2014-09-01

    Multiple viruses have been detected in cardiac tissue, but their role in causing myocarditis remains controversial. Viral diagnostics are increasingly used in forensic medicine, but the interpretation of the results can sometimes be challenging. In this study, we examined the prevalence of adenovirus, enterovirus, and parvovirus B19 (PVB) in myocardial autopsy samples from myocarditis related deaths and in non-inflamed control hearts in an effort to clarify their significance as the causes of myocarditis in a forensic material. We collected all autopsy cases diagnosed with myocarditis from 1992 to 2010. Eighty-four suicidal deaths with morphologically normal hearts served as controls. Polymerase chain reaction was used for the detection of the viral genomes (adenovirus, enterovirus, and PVB) in myocardial tissue specimens. The distinction between acute and persistent PVB infection was made by the serological determination of PVB-specific immunoglobulins M and G. PVB was detected in 33 of 112 (29 %) myocarditis cases and 37 of 84 (44 %) control cases. All of the samples were negative for the presence of adenovirus and enterovirus. Serological evidence of an acute PVB infection, determined by the presence of immunoglobulin M, was only present in one case. In the remaining cases, PVB was considered to be a bystander with no or limited association to myocardial inflammation. In this study, adenovirus, enterovirus, and PVB were found to be rare causes of myocarditis. The detection of PVB in myocardial autopsy samples most likely represents a persistent infection with no or limited association with myocardial inflammation. The forensic investigation of myocardial inflammation demands a thorough examination, including special attention to non-viral causes and requires a multidisciplinary approach.

  1. Field and laboratory evidence that Bungowannah virus, a recently recognised pestivirus, is the causative agent of the porcine myocarditis syndrome (PMC).

    Science.gov (United States)

    Finlaison, Deborah S; King, Katherine R; Frost, Melinda J; Kirkland, Peter D

    2009-05-12

    In 2003 an outbreak of sudden deaths occurred in 2-3-week-old piglets on a piggery in New South Wales, Australia. There was a marked increase in the birth of stillborn piglets and preweaning losses associated with a multifocal non-suppurative myocarditis with myonecrosis. The aim of this study was to review existing data and to undertake further investigations of specimens from naturally infected pigs to provide evidence to support the hypothesis that Bungowannah virus, a recently recognised pestivirus, causes the porcine myocarditis syndrome (PMC). Sera collected from gilts and sows from affected and unaffected units were tested for Bungowannah virus antibody by a peroxidase-linked assay and Bungowannah virus RNA by qRT-PCR in selected cases. Stillborn piglets from affected and an unaffected unit were also tested for Bungowannah virus antibody and RNA. Body fluid IgG levels and the incidence of myocardial lesions in these stillborn piglets are summarised. Tissue sections from stillborn piglets with myocarditis/myonecrosis were examined for Bungowannah virus RNA by in situ hybridisation. A clear temporal association between the occurrence of PMC on a unit or module and exposure to Bungowannah virus was identified by serological tests in both breeding aged animals and stillborn pigs. In addition, at the individual animal level on affected units, Bungowannah virus RNA was detected in stillborn piglets in large amounts by qRT-PCR and in association with myocardial lesions by in situ hybridisation. The examination of field material from cases of PMC by serology, qRT-PCR and in situ hybridisation provides strong indirect evidence that Bungowannah virus is the causative agent for PMC.

  2. Filgrastim as a Rescue Therapy for Persistent Neutropenia in a Case of Dengue Hemorrhagic Fever with Acute Respiratory Distress Syndrome and Myocarditis

    Directory of Open Access Journals (Sweden)

    Desh Deepak

    2011-01-01

    Full Text Available Pathogenesis of dengue involves suppression of immune system leading to development of characteristic presentation of haematological picture of thrombocytopenia and leucopenia. Sometimes, this suppression in immune response is responsible for deterioration in clinical status of the patient in spite of all specific and supportive therapy. Certain drugs like steroids are used for rescue therapy in conditions like sepsis. We present a novel use of filgrastim as a rescue therapy in a patient with dengue hemorrhagic fever (DHF with acute respiratory distress syndrome (ARDS, myocarditis, and febrile neutropenia and not responding to standard management.

  3. Re-evaluation of a novel approach for quantitative myocardial oedema detection by analysing tissue inhomogeneity in acute myocarditis using T2-mapping

    International Nuclear Information System (INIS)

    Baessler, Bettina; Treutlein, Melanie; Maintz, David; Bunck, Alexander C.; Schaarschmidt, Frank; Stehning, Christian; Schnackenburg, Bernhard; Michels, Guido

    2017-01-01

    To re-evaluate a recently suggested approach of quantifying myocardial oedema and increased tissue inhomogeneity in myocarditis by T2-mapping. Cardiac magnetic resonance data of 99 patients with myocarditis were retrospectively analysed. Thirthy healthy volunteers served as controls. T2-mapping data were acquired at 1.5 T using a gradient-spin-echo T2-mapping sequence. T2-maps were segmented according to the 16-segments AHA-model. Segmental T2-values, segmental pixel-standard deviation (SD) and the derived parameters maxT2, maxSD and madSD were analysed and compared to the established Lake Louise criteria (LLC). A re-estimation of logistic regression models revealed that all models containing an SD-parameter were superior to any model containing global myocardial T2. Using a combined cut-off of 1.8 ms for madSD + 68 ms for maxT2 resulted in a diagnostic sensitivity of 75% and specificity of 80% and showed a similar diagnostic performance compared to LLC in receiver-operating-curve analyses. Combining madSD, maxT2 and late gadolinium enhancement (LGE) in a model resulted in a superior diagnostic performance compared to LLC (sensitivity 93%, specificity 83%). The results show that the novel T2-mapping-derived parameters exhibit an additional diagnostic value over LGE with the inherent potential to overcome the current limitations of T2-mapping. (orig.)

  4. Re-evaluation of a novel approach for quantitative myocardial oedema detection by analysing tissue inhomogeneity in acute myocarditis using T2-mapping

    Energy Technology Data Exchange (ETDEWEB)

    Baessler, Bettina; Treutlein, Melanie; Maintz, David; Bunck, Alexander C. [University Hospital of Cologne, Department of Radiology, Cologne (Germany); Schaarschmidt, Frank [Leibniz Universitaet Hannover, Institute of Biostatistics, Faculty of Natural Sciences, Hannover (Germany); Stehning, Christian [Philips Research, Hamburg (Germany); Schnackenburg, Bernhard [Philips, Healthcare Germany, Hamburg (Germany); Michels, Guido [University Hospital of Cologne, Department III of Internal Medicine, Heart Centre, Cologne (Germany)

    2017-12-15

    To re-evaluate a recently suggested approach of quantifying myocardial oedema and increased tissue inhomogeneity in myocarditis by T2-mapping. Cardiac magnetic resonance data of 99 patients with myocarditis were retrospectively analysed. Thirthy healthy volunteers served as controls. T2-mapping data were acquired at 1.5 T using a gradient-spin-echo T2-mapping sequence. T2-maps were segmented according to the 16-segments AHA-model. Segmental T2-values, segmental pixel-standard deviation (SD) and the derived parameters maxT2, maxSD and madSD were analysed and compared to the established Lake Louise criteria (LLC). A re-estimation of logistic regression models revealed that all models containing an SD-parameter were superior to any model containing global myocardial T2. Using a combined cut-off of 1.8 ms for madSD + 68 ms for maxT2 resulted in a diagnostic sensitivity of 75% and specificity of 80% and showed a similar diagnostic performance compared to LLC in receiver-operating-curve analyses. Combining madSD, maxT2 and late gadolinium enhancement (LGE) in a model resulted in a superior diagnostic performance compared to LLC (sensitivity 93%, specificity 83%). The results show that the novel T2-mapping-derived parameters exhibit an additional diagnostic value over LGE with the inherent potential to overcome the current limitations of T2-mapping. (orig.)

  5. Epsilon wave on an electronic loop in a case of arrhythmogenic right ventricular dysplasia with myocarditis: an updated definition of the Epsilon wave.

    Science.gov (United States)

    Fontaine, Guy Hugues; Duthoit, Guillaume; Li, Guoliang; Andreoletti, L; Gandjbakhch, Estelle; Frank, Robert

    2017-07-01

    A young man presented with a history of myocarditis with palpitations and dizziness. He had implantation of a loop recorder that showed repetitive short episodes of VT. In addition, there were fragmented potentials immediately following the large and sharp electrograms (EGMs) before as well as after episodes of VT suggesting an Epsilon wave. This signal can be observed in multiple cardiac conditions including coronary artery disease. It was originally recorded on the epicardium as well as on the endocardium. However, in ARVD it can be defined as an electric signal observed after the end of the QRS complex in the right as opposed to the left precordial leads (difference ≥ 25 ms). It can also be an aid to the diagnosis of patients with ARVD who have other signs or symptoms suggesting ARVD including episodes of myocarditis. This potential consists of a slurring at the end of the QRS complex or an independent potential after the return to the isoelectric line. It can be better observed by increasing amplification of the ECG tracing as well as double speed using the Fontaine lead system. Epsilon wave too small to be recorded on the standard ECG can be extracted by Signal Averaging ECG SAECG). Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

  6. The mitochondrial respiratory chain has a critical role in the antiviral process in Coxsackievirus B3-induced myocarditis.

    Science.gov (United States)

    Ebermann, Linda; Wika, Sylwia; Klumpe, Inga; Hammer, Elke; Klingel, Karin; Lassner, Dirk; Völker, Uwe; Erben, Ulrike; Zeichhardt, Heinz; Schultheiss, Heinz-Peter; Dörner, Andrea

    2012-01-01

    Well-established differences in Coxsackievirus B3 (CVB3) elimination in resistant C57BL/6 and permissive A.SW/SnJ mice provide suitable models for studying the significance of the link between mitochondrial respiratory chain (RC), antioxidative stress components and mitochondrion-related apoptosis in the context of myocardial virus elimination. Distinct myocardial CVB3 titer in C57BL/6 (2.5 ± 1.4 × 10(4) plaque-forming units (p.f.u.)/g tissue) and A.SW/SnJ mice (1.4 ± 0.8 × 10(7) p.f.u./g) were associated with differences in the cardiac mitochondrial function 8 days post infection (p.i.). Infected C57BL/6 mouse hearts disclosed increased complex I (CI) and CIII activity, but restricted CII and normal CIV activity of RC. Reduced expression of the antioxidative catalase was accompanied by elevated lipid peroxidation (LPO), indicating oxidative stress. Intrinsic apoptosis was activated demonstrated by elevated levels of Bax, Bcl-2, caspase 3 and DNA degradation. In contrast, all myocardial RC complex activities were restricted in CVB3-infected A.SW/SnJ mice. The antioxidative system provided sufficient protection against oxidative stress shown by an elevated catalase expression and unaltered LPO. Bax and Bcl-2 levels were unchanged in CVB3-infected A.SW/SnJ mice, while caspase 3 was moderately increased but no DNA degradation was detectable. Correlation analyses including data from the two mouse strains revealed that reduced CVB3 titer correlated with increased CI and CIII activity, oxidative stress as well as active apoptosis during acute myocarditis (MC). C57BL/6 mice completely eliminated CVB3 and inflammation and normalized all intracellular parameters, while A.SW/SnJ mice showed permanently restricted CI activity in chronic MC 90 days p.i., at which time the replicating virus was no longer detectable but immunological processes were still active. Consequently, the regulation of energy metabolism appears crucial for an effective virus elimination and may be of

  7. β-Arrestin2 mediates progression of murine primary myelofibrosis.

    Science.gov (United States)

    Rein, Lindsay Am; Wisler, James W; Kim, Jihee; Theriot, Barbara; Huang, LiYin; Price, Trevor; Yang, Haeyoon; Chen, Minyong; Chen, Wei; Sipkins, Dorothy; Fedoriw, Yuri; Walker, Julia Kl; Premont, Richard T; Lefkowitz, Robert J

    2017-12-21

    Primary myelofibrosis is a myeloproliferative neoplasm associated with significant morbidity and mortality, for which effective therapies are lacking. β-Arrestins are multifunctional adaptor proteins involved in developmental signaling pathways. One isoform, β-arrestin2 (βarr2), has been implicated in initiation and progression of chronic myeloid leukemia, another myeloproliferative neoplasm closely related to primary myelofibrosis. Accordingly, we investigated the relationship between βarr2 and primary myelofibrosis. In a murine model of MPLW515L-mutant primary myelofibrosis, mice transplanted with donor βarr2-knockout (βarr2-/-) hematopoietic stem cells infected with MPL-mutant retrovirus did not develop myelofibrosis, whereas controls uniformly succumbed to disease. Although transplanted βarr2-/- cells homed properly to marrow, they did not repopulate long-term due to increased apoptosis and decreased self-renewal of βarr2-/- cells. In order to assess the effect of acute loss of βarr2 in established primary myelofibrosis in vivo, we utilized a tamoxifen-induced Cre-conditional βarr2-knockout mouse. Mice that received Cre (+) donor cells and developed myelofibrosis had significantly improved survival compared with controls. These data indicate that lack of antiapoptotic βarr2 mediates marrow failure of murine hematopoietic stem cells overexpressing MPLW515L. They also indicate that βarr2 is necessary for progression of primary myelofibrosis, suggesting that it may serve as a novel therapeutic target in this disease.

  8. Scanning electron microscopy of the neuropathology of murine cerebral malaria

    Directory of Open Access Journals (Sweden)

    Brenneis Christian

    2006-11-01

    Full Text Available Abstract Background The mechanisms leading to death and functional impairments due to cerebral malaria (CM are yet not fully understood. Most of the knowledge about the pathomechanisms of CM originates from studies in animal models. Though extensive histopathological studies of the murine brain during CM are existing, alterations have not been visualized by scanning electron microscopy (SEM so far. The present study investigates the neuropathological features of murine CM by applying SEM. Methods C57BL/6J mice were infected with Plasmodium berghei ANKA blood stages. When typical symptoms of CM developed perfused brains were processed for SEM or light microscopy, respectively. Results Ultrastructural hallmarks were disruption of vessel walls, parenchymal haemorrhage, leukocyte sequestration to the endothelium, and diapedesis of macrophages and lymphocytes into the Virchow-Robin space. Villous appearance of observed lymphocytes were indicative of activated state. Cerebral oedema was evidenced by enlargement of perivascular spaces. Conclusion The results of the present study corroborate the current understanding of CM pathophysiology, further support the prominent role of the local immune system in the neuropathology of CM and might expose new perspectives for further interventional studies.

  9. Reemergence of Murine Typhus in the US

    Centers for Disease Control (CDC) Podcasts

    2015-04-21

    Dr. Lucas Blanton discusses the Reemergence of Murine Typhus in Galveston Texas in 2013.  Created: 4/21/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/27/2015.

  10. Re-evaluation of a novel approach for quantitative myocardial oedema detection by analysing tissue inhomogeneity in acute myocarditis using T2-mapping.

    Science.gov (United States)

    Baeßler, Bettina; Schaarschmidt, Frank; Treutlein, Melanie; Stehning, Christian; Schnackenburg, Bernhard; Michels, Guido; Maintz, David; Bunck, Alexander C

    2017-12-01

    To re-evaluate a recently suggested approach of quantifying myocardial oedema and increased tissue inhomogeneity in myocarditis by T2-mapping. Cardiac magnetic resonance data of 99 patients with myocarditis were retrospectively analysed. Thirthy healthy volunteers served as controls. T2-mapping data were acquired at 1.5 T using a gradient-spin-echo T2-mapping sequence. T2-maps were segmented according to the 16-segments AHA-model. Segmental T2-values, segmental pixel-standard deviation (SD) and the derived parameters maxT2, maxSD and madSD were analysed and compared to the established Lake Louise criteria (LLC). A re-estimation of logistic regression models revealed that all models containing an SD-parameter were superior to any model containing global myocardial T2. Using a combined cut-off of 1.8 ms for madSD + 68 ms for maxT2 resulted in a diagnostic sensitivity of 75% and specificity of 80% and showed a similar diagnostic performance compared to LLC in receiver-operating-curve analyses. Combining madSD, maxT2 and late gadolinium enhancement (LGE) in a model resulted in a superior diagnostic performance compared to LLC (sensitivity 93%, specificity 83%). The results show that the novel T2-mapping-derived parameters exhibit an additional diagnostic value over LGE with the inherent potential to overcome the current limitations of T2-mapping. • A novel quantitative approach to myocardial oedema imaging in myocarditis was re-evaluated. • The T2-mapping-derived parameters maxT2 and madSD were compared to traditional Lake-Louise criteria. • Using maxT2 and madSD with dedicated cut-offs performs similarly to Lake-Louise criteria. • Adding maxT2 and madSD to LGE results in further increased diagnostic performance. • This novel approach has the potential to overcome the limitations of T2-mapping.

  11. Regulatory T cells protect mice against coxsackievirus-induced myocarditis through the transforming growth factor beta-coxsackie-adenovirus receptor pathway.

    Science.gov (United States)

    Shi, Yu; Fukuoka, Masahiro; Li, Guohua; Liu, Youan; Chen, Manyin; Konviser, Michael; Chen, Xin; Opavsky, Mary Anne; Liu, Peter P

    2010-06-22

    Coxsackievirus B3 infection is an excellent model of human myocarditis and dilated cardiomyopathy. Cardiac injury is caused either by a direct cytopathic effect of the virus or through immune-mediated mechanisms. Regulatory T cells (Tregs) play an important role in the negative modulation of host immune responses and set the threshold of autoimmune activation. This study was designed to test the protective effects of Tregs and to determine the underlying mechanisms. Carboxyfluorescein diacetate succinimidyl ester-labeled Tregs or naïve CD4(+) T cells were injected intravenously once every 2 weeks 3 times into mice. The mice were then challenged with intraperitoneal coxsackievirus B3 immediately after the last cell transfer. Transfer of Tregs showed higher survival rates than transfer of CD4(+) T cells (P=0.0136) but not compared with the PBS injection group (P=0.0589). Interestingly, Tregs also significantly decreased virus titers and inflammatory scores in the heart. Transforming growth factor-beta and phosphorylated AKT were upregulated in Tregs-transferred mice and coxsackie-adenovirus receptor expression was decreased in the heart compared with control groups. Transforming growth factor-beta decreased coxsackie-adenovirus receptor expression and inhibited coxsackievirus B3 infection in HL-1 cells and neonatal cardiac myocytes. Splenocytes collected from Treg-, CD4(+) T-cell-, and PBS-treated mice proliferated equally when stimulated with heat-inactivated virus, whereas in the Treg group, the proliferation rate was reduced significantly when stimulated with noninfected heart tissue homogenate. Adoptive transfer of Tregs protected mice from coxsackievirus B3-induced myocarditis through the transforming growth factor beta-coxsackie-adenovirus receptor pathway and thus suppresses the immune response to cardiac tissue, maintaining the antiviral immune response.

  12. Synchronous advanced pulmonary tuberculosis and acute virus myocarditis mimicked wegener granulomatosis in a 26-year-old man: A case report

    Directory of Open Access Journals (Sweden)

    Pešut Dragica P.

    2016-01-01

    Full Text Available Introduction. Tuberculosis patients are rarely asymptomatic. Acute virus myocarditis presents with a wide range of symptoms, from mild dyspnea or chest pain to cardiogenic shock and death. Case Outline. A 26-year-old Caucasian man non-smoker presented with one-week history of lower extremities’ swelling. The patient’s medical history also revealed a two-day episode of subfebrile temperature with scanty hemoptysis three weeks prior to admission. The episode had not provoked him to seek medical care. Physical examination revealed generalized oedema, and laboratory analysis showed signs of acute renal insufficiency. Enlarged heart and hilar shadows, bilateral massive cavitary pulmonary opacities and pleural effusion were found at chest radiography. Sputum smears were Mycobacteria negative on direct microscopy. Electrocardiogram changes and echocardiography were suggestive of acute myocarditis with dilated cardiomyopathy. IgM titer to adenovirus was positive. Under diuretics, angiotensin-converting-enzyme inhibitor, beta-blocker, antibiotics and bed rest, fast heart compensation and renal function repair were achieved. Radiographic pulmonary changes promptly regressed except for a cavity in the right upper lobe. Bronchial aspirate from the affected lobe was Mycobacteria positive on direct microscopy and culture positive for Mycobacterium tuberculosis. Standard anti-tuberculosis drug regimen led to recovery. Conclusion. In the unusual common existence of two diseases whose presentation initially mimicked Wegener’s granulomatosis, acute dilated cardiomyopathy contributed to pulmonary tuberculosis detection. To prevent diagnostic delay in tuberculosis, further efforts in population education are necessary together with continual medical education. [Projekat Ministarstva nauke Republike Srbije, br. 175095

  13. Signaling pathways regulating murine pancreatic development

    DEFF Research Database (Denmark)

    Serup, Palle

    2012-01-01

    The recent decades have seen a huge expansion in our knowledge about pancreatic development. Numerous lineage-restricted transcription factor genes have been identified and much has been learned about their function. Similarly, numerous signaling pathways important for pancreas development have...... been identified and the specific roles have been investigated by genetic and cell biological methods. The present review presents an overview of the principal signaling pathways involved in regulating murine pancreatic growth, morphogenesis, and cell differentiation....

  14. The Murine Factor H-Related Protein FHR-B Promotes Complement Activation

    Directory of Open Access Journals (Sweden)

    Marcell Cserhalmi

    2017-09-01

    Full Text Available Factor H-related (FHR proteins consist of varying number of complement control protein domains that display various degrees of sequence identity to respective domains of the alternative pathway complement inhibitor factor H (FH. While such FHR proteins are described in several species, only human FHRs were functionally investigated. Their biological role is still poorly understood and in part controversial. Recent studies on some of the human FHRs strongly suggest a role for FHRs in enhancing complement activation via competing with FH for binding to certain ligands and surfaces. The aim of the current study was the functional characterization of a murine FHR, FHR-B. To this end, FHR-B was expressed in recombinant form. Recombinant FHR-B bound to human C3b and was able to compete with human FH for C3b binding. FHR-B supported the assembly of functionally active C3bBb alternative pathway C3 convertase via its interaction with C3b. This activity was confirmed by demonstrating C3 activation in murine serum. In addition, FHR-B bound to murine pentraxin 3 (PTX3, and this interaction resulted in murine C3 fragment deposition due to enhanced complement activation in mouse serum. FHR-B also induced C3 deposition on C-reactive protein, the extracellular matrix (ECM extract Matrigel, and endothelial cell-derived ECM when exposed to mouse serum. Moreover, mouse C3 deposition was strongly enhanced on necrotic Jurkat T cells and the mouse B cell line A20 by FHR-B. FHR-B also induced lysis of sheep erythrocytes when incubated in mouse serum with FHR-B added in excess. Altogether, these data demonstrate that, similar to human FHR-1 and FHR-5, mouse FHR-B modulates complement activity by promoting complement activation via interaction with C3b and via competition with murine FH.

  15. DMPD: The actions of bacterial DNA on murine macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10534106 The actions of bacterial DNA on murine macrophages. Sester DP, Stacey KJ, ... Show The actions of bacterial DNA on murine macrophages. PubmedID 10534106 Title The actions of bacterial DNA on murine macrophage

  16. Faible taux de succes du sevrage tabagique a court et moyen termes au decours d�un infarctus aigu du myocarde dans un service de cardiologie de Dakar au Senegal

    Directory of Open Access Journals (Sweden)

    Alassane Mbaye

    2011-10-01

    Full Text Available e le tabac pendant l�hospitalisation. Apres un suivi de 3 mois, 45% des patients ont repris le tabac, 65% a 6 mois et 85% a 12 mois. CONCLUSION: Le tabagisme est assez frequent chez les patients senegalais presentant un infarctus du myocarde. Le taux de sevrage tabagique a court et moyen termes est faible. Le sevrage tabagique devrait alors constituer un objectif privilegie dans la prevention des maladies cardio-vasculaires.

  17. Bone marrow stromal elements in murine leukemia; Decreased CSF-producing fibroblasts and normal IL-1 expression by macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Ben-Ishay, Z [Laboratory of Experimental Hematology, Department of Anatomy and Embryology, Hebrew University-Hadassah Medical School (Israel); Barak, V [Laboratory of Immunology, Department of Oncology, Hadassah University Hospital (Israel); Shoshan, S [Faculty of Dental Medicine, Connective Tissue Research Laboratory, Hebrew University, Jerusalem (Israel); Prindull, G [Department of Pediatrics, University of Gottingen, Gottingen (Germany, F.R.)

    1990-01-01

    A study of bone marrow stromal elements in murine acute myeloid leukemia (AML) was carried out. Our previous studies had indicated marrow stromal deficiency in murine AML. In the current investigation, separate stromal cells were cultured and the results obtained have shown that, while marrow stromal macrophages are normal in leukemia and express adequate amounts of IL-1, the fibroblasts are markedly reduced. However, if sufficient fibroblasts are pooled in vitro, they produce adequate amounts of CSF. Test of TNF{alpha} in leukemic cells CM, as possible cause of marrow stromal inhibition in leukemia, had not disclosed this cytokine. Further, it was observed that total body lethal irradiation of leukemic mice aggravates the stromal deficiency, confirming results of our previous investigations. It is concluded that bone marrow stromal deficiency in murine AML is due to decreased fibroblasts and, implicity, reduced CSF production. (author).

  18. Murine model of long-term obstructive jaundice.

    Science.gov (United States)

    Aoki, Hiroaki; Aoki, Masayo; Yang, Jing; Katsuta, Eriko; Mukhopadhyay, Partha; Ramanathan, Rajesh; Woelfel, Ingrid A; Wang, Xuan; Spiegel, Sarah; Zhou, Huiping; Takabe, Kazuaki

    2016-11-01

    With the recent emergence of conjugated bile acids as signaling molecules in cancer, a murine model of obstructive jaundice by cholestasis with long-term survival is in need. Here, we investigated the characteristics of three murine models of obstructive jaundice. C57BL/6J mice were used for total ligation of the common bile duct (tCL), partial common bile duct ligation (pCL), and ligation of left and median hepatic bile duct with gallbladder removal (LMHL) models. Survival was assessed by Kaplan-Meier method. Fibrotic change was determined by Masson-Trichrome staining and Collagen expression. Overall, 70% (7 of 10) of tCL mice died by day 7, whereas majority 67% (10 of 15) of pCL mice survived with loss of jaundice. A total of 19% (3 of 16) of LMHL mice died; however, jaundice continued beyond day 14, with survival of more than a month. Compensatory enlargement of the right lobe was observed in both pCL and LMHL models. The pCL model demonstrated acute inflammation due to obstructive jaundice 3 d after ligation but jaundice rapidly decreased by day 7. The LHML group developed portal hypertension and severe fibrosis by day 14 in addition to prolonged jaundice. The standard tCL model is too unstable with high mortality for long-term studies. pCL may be an appropriate model for acute inflammation with obstructive jaundice, but long-term survivors are no longer jaundiced. The LHML model was identified to be the most feasible model to study the effect of long-term obstructive jaundice. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Azithromycin prophylaxis and treatment of murine toxoplasmosis.

    Science.gov (United States)

    Tabbara, Khalid F; Hammouda, Ehab; Tawfik, Abdulkader; Al-Omar, Othman M; Abu El-Asrar, Ahmed M

    2005-03-01

    To evaluate the azithromycin effects alone and in combination with other agents in the prophylaxis and treatment of murine toxoplasmosis. A total of 280 BALB/c mice were included, and 2 x 103 Toxoplasma organisms of the RH strain Toxoplasma gondii strain ATCC50174 were given intraperitoneally to each mouse. In experiment one, 40 animals were given azithromycin 200 milligram/kilogram/daily for 3 days starting the day of inoculation, 40 mice were control. In experiment 2, the treatment was started 48 hours after inoculation and given daily for 3 days: one group received azithromycin 200 milligram/kilogram/day, the second group received pyrimethamine 25 milligram/kilogram/day, and the sulfadiazine 100 milligram/kilogram/day. The third group was control. In experiment 3, 7 groups of animals received one of the following (1) none, (2) azithromycin 200 milligram/kilogram/day, (3) pyrimethamine 25 milligram/kilogram/day and sulfadiazine 100 milligram/kilogram/day, (4) azithromycin and sulfadiazine, (5) azithromycin and pyrimethamine, (6) azithromycin with sulfadiazine and pyrimethamine, (7) sulfadiazine alone. Treatment was initiated 72 hours after inoculation for 3 days. The study was conducted at the Animal Care Facility of King Saud University, Riyadh, Kingdom of Saudi Arabia. Animals that received azithromycin simultaneously with inoculation survived, and all control animals died. All animals died in groups receiving single drug therapy. Animals treated with azithromycin and sulfadiazine showed a survival rate of 40%, sulfadiazine and pyrimethamine 40%, or azithromycin with sulfadiazine and pyrimethamine 95% (p<0.0001). Azithromycin alone was found to be effective in the prophylaxis of murine toxoplasmosis. Combination therapy was effective in the treatment of murine toxoplasmosis.

  20. M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine.

    Science.gov (United States)

    Ye, Ting; Yue, Yan; Fan, Xiangmei; Dong, Chunsheng; Xu, Wei; Xiong, Sidong

    2014-07-31

    Efficient delivery of antigen to mucosal associated lymphoid tissue is a first and critical step for successful induction of mucosal immunity by vaccines. Considering its potential transcytotic capability, M cell has become a more and more attractive target for mucosal vaccines. In this research, we designed an M cell-targeting strategy by which mucosal delivery system chitosan (CS) was endowed with M cell-targeting ability via conjugating with a CPE30 peptide, C terminal 30 amino acids of clostridium perfringens enterotoxin (CPE), and then evaluated its immune-enhancing ability in the context of coxsackievirus B3 (CVB3)-specific mucosal vaccine consisting of CS and a plasmid encoding CVB3 predominant antigen VP1. It had shown that similar to CS-pVP1, M cell-targeting CPE30-CS-pVP1 vaccine appeared a uniform spherical shape with about 300 nm diameter and +22 mV zeta potential, and could efficiently protect DNA from DNase I digestion. Mice were orally immunized with 4 doses of CPE30-CS-pVP1 containing 50 μg pVP1 at 2-week intervals and challenged with CVB3 4 weeks after the last immunization. Compared with CS-pVP1 vaccine, CPE30-CS-pVP1 vaccine had no obvious impact on CVB3-specific serum IgG level and splenic T cell immune responses, but significantly increased specific fecal SIgA level and augmented mucosal T cell immune responses. Consequently, much milder myocarditis and lower viral load were witnessed in CPE30-CS-pVP1 immunized group. The enhanced immunogenicity and immunoprotection were associated with the M cell-targeting ability of CPE30-CS-pVP1 which improved its mucosal uptake and transcytosis. Our findings indicated that CPE30-CS-pVP1 may represent a novel prophylactic vaccine against CVB3-induced myocarditis, and this M cell-targeting strategy indeed could be applied as a promising and universal platform for mucosal vaccine development. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Efficacy of posaconazole in murine experimental sporotrichosis.

    Science.gov (United States)

    Fernández-Silva, Fabiola; Capilla, Javier; Mayayo, Emilio; Guarro, Josep

    2012-05-01

    We developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e., Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, in order to evaluate the efficacy of posaconazole (PSC). The drug was administered at a dose of 2.5 or 5 mg/kg of body weight twice a day by gavage, and one group was treated with amphotericin B (AMB) as a control treatment. Posaconazole, especially at 5 mg/kg, showed good efficacy against all the strains tested, regardless of their MICs, as measured by prolonged survival, tissue burden reduction, and histopathology.

  2. Irradiation Design for an Experimental Murine Model

    International Nuclear Information System (INIS)

    Ballesteros-Zebadua, P.; Moreno-Jimenez, S.; Suarez-Campos, J. E.; Celis, M. A.; Larraga-Gutierrez, J. M.; Garcia-Garduno, O. A.; Rubio-Osornio, M. C.; Custodio-Ramirez, V.; Paz, C.

    2010-01-01

    In radiotherapy and stereotactic radiosurgery, small animal experimental models are frequently used, since there are still a lot of unsolved questions about the biological and biochemical effects of ionizing radiation. This work presents a method for small-animal brain radiotherapy compatible with a dedicated 6MV Linac. This rodent model is focused on the research of the inflammatory effects produced by ionizing radiation in the brain. In this work comparisons between Pencil Beam and Monte Carlo techniques, were used in order to evaluate accuracy of the calculated dose using a commercial planning system. Challenges in this murine model are discussed.

  3. Thrombopoietin inhibits murine mast cell differentiation

    Science.gov (United States)

    Martelli, Fabrizio; Ghinassi, Barbara; Lorenzini, Rodolfo; Vannucchi, Alessandro M; Rana, Rosa Alba; Nishikawa, Mitsuo; Partamian, Sandra; Migliaccio, Giovanni; Migliaccio, Anna Rita

    2009-01-01

    We have recently shown that Mpl, the thrombopoietin receptor, is expressed on murine mast cells and on their precursors and that targeted deletion of the Mpl gene increases mast cell differentiation in mice. Here we report that treatment of mice with thrombopoietin, or addition of this growth factor to bone marrow-derived mast cell cultures, severely hampers the generation of mature cells from their precursors by inducing apoptosis. Analysis of the expression profiling of mast cells obtained in the presence of thrombopoietin suggests that thrombopoietin induces apoptosis of mast cells by reducing expression of the transcription factor Mitf and its target anti-apoptotic gene Bcl2. PMID:18276801

  4. [Virulence of Sporothrix globosa in murine models].

    Science.gov (United States)

    Cruz Choappa, Rodrigo; Pérez Gaete, Salomón; Rodríguez Badilla, Valentina; Vieille Oyarzo, Peggy; Opazo Sanchez, Héctor

    The sporothricosis disease is an infection caused by species included in Sporothrix schenkii complex. Verify the virulence of a strain of S. globosa using two different concentrations of inoculum by intraperitoneally and subcutaneously, into a mouse model. Nonrandomized pilot study, in murine inoculated with a strain of S. globosa (CBS 14.076M) by intraperitoneally and subcutaneously with inoculum concentrations of 0.5 and 4 McFarland. For this purpose 18 rodents CF-1 (ISP, Santiago, Chile) were used. The studied strain did not induce illness or injury on animals, they all survived and neither the tissue culture nor the histopathological analysis showed fungal growth or suggestive infection by organ abnormalities. The S. globosa strain did not present any virulence enough to cause disease at 0.5 and 4.0 McFarland concentration inoculum when inoculated in both intraperitoneally and subcutaneously, in murine models. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. The value of determination of blood cardiac troponin T, IL-8 and TNF-α contents for the diagnosis and prognosis assessment in patients with viral myocarditis

    International Nuclear Information System (INIS)

    Tao Qian; Zhou Xuanyan; Li Enjie

    2006-01-01

    Objective: To investigate the value of determination of blood cardiac troponin T (cTnT), IL-8 and TNF-α contents for the diagnosis and prognosis assessment in patients with viral myocarditis (VMC). Methods: Plasma cTnT (with immuno-infiltration method) and serum IL - 8, TNF ( with ELISA) contents were measured in 86 patients with VMC at different stages ( 1 months, 6 months), and 30 controls. Results: The positive rates of blood cTnT, IL-8 and TNF-α in acute VMC patients were significantly higher than those in patients with history less than 6 months as well as with history more than 6 months and the controls group (P 0.05). The cure rate in patients with positive cTnT was significantly lower than that in patients with negative cTnT both at 1 months and 6 months (P<0.005). Conclusion: Blood cTnT, IL-8 and TNF-α are sensitive and specific predictors for diagnosis and prognosis assessment in patients with VMC. (authors)

  6. Atomic structure of the murine norovirus protruding domain and sCD300lf receptor complex.

    Science.gov (United States)

    Kilic, Turgay; Koromyslova, Anna; Malak, Virginie; Hansman, Grant S

    2018-03-21

    Human noroviruses are the leading cause of acute gastroenteritis in human. Noroviruses also infect animals such as cow, mice, cat, and dog. How noroviruses bind and enter host cells is still incompletely understood. Recently, the type I transmembrane protein CD300lf was recently identified as the murine norovirus receptor, yet it is unclear how the virus capsid and receptor interact at the molecular level. In this study, we determined the X-ray crystal structure of the soluble CD300lf (sCD300lf) and murine norovirus capsid-protruding domain complex at 2.05 Å resolution. We found that the sCD300lf binding site is located on the topside of the protruding domain and involves a network of hydrophilic and hydrophobic interactions. The sCD300lf locked nicely into a complementary cavity on the protruding domain that is additionally coordinated with a positive surface charge on the sCD300lf and a negative surface charge on the protruding domain. Five of six protruding domain residues interacting with sCD300lf were maintained between different murine norovirus strains, suggesting that the sCD300lf was capable of binding to a highly conserved pocket. Moreover, a sequence alignment with other CD300 paralogs showed that the sCD300lf interacting residues were partially conserved in CD300ld, but variable in other CD300 family members, consistent with previously reported infection selectivity. Overall, these data provide insights into how a norovirus engages a protein receptor and will be important for a better understanding of selective recognition and norovirus attachment and entry mechanisms. IMPORTANCE Noroviruses exhibit exquisite host-range specificity due to species-specific interactions between the norovirus capsid protein and host molecules. Given this strict host-range restriction it has been unclear how the viruses are maintained within a species between relatively sporadic epidemics. While much data demonstrates that noroviruses can interact with carbohydrates

  7. Clearance of 131I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody

    International Nuclear Information System (INIS)

    Stewart, J.S.; Sivolapenko, G.B.; Hird, V.; Davies, K.A.; Walport, M.; Ritter, M.A.; Epenetos, A.A.

    1990-01-01

    Five patients treated with intraperitoneal 131I-labeled mouse monoclonal antibody for ovarian cancer also received i.v. exogenous polyclonal human anti-murine immunoglobulin antibody. The pharmacokinetics of 131I-labeled monoclonal antibody in these patients were compared with those of 28 other patients receiving i.p.-radiolabeled monoclonal antibody for the first time without exogenous human anti-murine immunoglobulin, and who had no preexisting endogenous human anti-murine immunoglobulin antibody. Patients receiving i.v. human anti-murine immunoglobulin antibody demonstrated a rapid clearance of 131I-labeled monoclonal antibody from their circulation. The (mean) maximum 131I blood content was 11.4% of the injected activity in patients receiving human anti-murine immunoglobulin antibody compared to 23.3% in patients not given human anti-murine immunoglobulin antibody. Intravenous human anti-murine immunoglobulin antibody decreased the radiation dose to bone marrow (from 131I-labeled monoclonal antibody in the vascular compartment) 4-fold. Following the injection of human anti-murine immunoglobulin antibody, 131I-monoclonal/human anti-murine immunoglobulin antibody immune complexes were rapidly transported to the liver. Antibody dehalogenation in the liver was rapid, with 87% of the injected 131I excreted in 5 days. Despite the efficient hepatic uptake of immune complexes, dehalogenation of monoclonal antibody was so rapid that the radiation dose to liver parenchyma from circulating 131I was decreased 4-fold rather than increased. All patients developed endogenous human anti-murine immunoglobulin antibody 2 to 3 weeks after treatment

  8. A role for smoothened during murine lens and cornea development.

    Directory of Open Access Journals (Sweden)

    Janet J Y Choi

    Full Text Available Various studies suggest that Hedgehog (Hh signalling plays roles in human and zebrafish ocular development. Recent studies (Kerr et al., Invest Ophthalmol Vis Sci. 2012; 53, 3316-30 showed that conditionally activating Hh signals promotes murine lens epithelial cell proliferation and disrupts fibre differentiation. In this study we examined the expression of the Hh pathway and the requirement for the Smoothened gene in murine lens development. Expression of Hh pathway components in developing lens was examined by RT-PCR, immunofluorescence and in situ hybridisation. The requirement of Smo in lens development was determined by conditional loss-of-function mutations, using LeCre and MLR10 Cre transgenic mice. The phenotype of mutant mice was examined by immunofluorescence for various markers of cell cycle, lens and cornea differentiation. Hh pathway components (Ptch1, Smo, Gli2, Gli3 were detected in lens epithelium from E12.5. Gli2 was particularly localised to mitotic nuclei and, at E13.5, Gli3 exhibited a shift from cytosol to nucleus, suggesting distinct roles for these transcription factors. Conditional deletion of Smo, from ∼E12.5 (MLR10 Cre did not affect ocular development, whereas deletion from ∼E9.5 (LeCre resulted in lens and corneal defects from E14.5. Mutant lenses were smaller and showed normal expression of p57Kip2, c-Maf, E-cadherin and Pax6, reduced expression of FoxE3 and Ptch1 and decreased nuclear Hes1. There was normal G1-S phase but decreased G2-M phase transition at E16.5 and epithelial cell death from E14.5-E16.5. Mutant corneas were thicker due to aberrant migration of Nrp2+ cells from the extraocular mesenchyme, resulting in delayed corneal endothelial but normal epithelial differentiation. These results indicate the Hh pathway is required during a discrete period (E9.5-E12.5 in lens development to regulate lens epithelial cell proliferation, survival and FoxE3 expression. Defective corneal development occurs

  9. Baicalein induces cell death in murine T cell lymphoma via inhibition of thioredoxin system.

    Science.gov (United States)

    Patwardhan, Raghavendra S; Pal, Debojyoti; Checker, Rahul; Sharma, Deepak; Sandur, Santosh K

    2017-10-01

    We have earlier demonstrated the radioprotective potential of baicalein using murine splenic lymphocytes. Here, we have studied the effect of baicalein on murine T cell lymphoma EL4 cells and investigated the underlying mechanism of action. We observed that baicalein induced a dose dependent cell death in EL4 cells in vitro and significantly reduced the frequency of cancer stem cells. Previously, we have reported that murine and human T cell lymphoma cells have increased oxidative stress tolerance capacity due to active thioredoxin system. Hence, we monitored the effect of baicalein on thioredoxin system in EL4 cells. Docking studies revealed that baicalein could bind to the active site of thioredoxin reductase. Baicalein treatment led to significant reduction in the activity of thioredoxin reductase and nuclear levels of thioredoxin-1 thereby increasing ASK1 levels and caspase-3 activity. Interestingly, CRISPR-Cas9 based knock-out of ASK1 or over-expression of thioredoxin-1 abolished anti-tumor effects of baicalein in EL4 cells. Further, baicalein administration significantly reduced intra-peritoneal tumor burden of EL4 cells in C57BL/6 mice. Thus, our study describes anti-tumor effects of baicalein in EL4 cells via inhibition of thioredoxin system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Biomechanical Properties of Murine Meniscus Surface via AFM-based Nanoindentation

    Science.gov (United States)

    Li, Qing; Doyran, Basak; Gamer, Laura W.; Lu, X. Lucas; Qin, Ling; Ortiz, Christine; Grodzinsky, Alan J.; Rosen, Vicki; Han, Lin

    2015-01-01

    This study aimed to quantify the biomechanical properties of murine meniscus surface. Atomic force microscopy (AFM)-based nanoindentation was performed on the central region, proximal side of menisci from 6- to 24-week old male C57BL/6 mice using microspherical tips (Rtip ≈ 5 μm) in PBS. A unique, linear correlation between indentation depth, D, and response force, F, was found on menisci from all age groups. This non-Hertzian behavior is likely due to the dominance of tensile resistance by the collagen fibril bundles on meniscus surface that are mostly aligned along the circumferential direction observed on 12-week old menisci. The indentation resistance was calculated as both the effective stiffness, Sind = dF/dD, and the effective modulus, Eind, via the isotropic Hertz model. Values of Sind and Eind were found to depend on indentation rate, suggesting the existence of poro-viscoelasticity. These values do not significantly vary with anatomical sites, lateral versus medial compartments, or mouse age. In addition, Eind of meniscus surface (e.g., 6.1 ± 0.8 MPa for 12 weeks of age, mean ± SEM, n = 13) was found to be significantly higher than those of meniscus surfaces in other species, and of murine articular cartilage surface (1.4 ± 0.1 MPa, n = 6). In summary, these results provided the first direct mechanical knowledge of murine knee meniscus tissues. We expect this understanding to serve as a mechanics-based benchmark for further probing the developmental biology and osteoarthritis symptoms of meniscus in various murine models. PMID:25817332

  11. Anatomy and Histology of the Human and Murine Prostate.

    Science.gov (United States)

    Ittmann, Michael

    2018-05-01

    The human and murine prostate glands have similar functional roles in the generation of seminal fluid to assist in reproduction. There are significant differences in the anatomy and histology of murine and human prostate and knowledge of the normal anatomy and histology of the murine prostate is essential to interpreting changes in genetically engineered mouse models. In this review, the normal anatomy and histology of both human and mouse prostate will be described. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  12. Murine leukemia viruses: objects and organisms.

    Science.gov (United States)

    Rein, Alan

    2011-01-01

    Murine leukemia viruses (MLVs) are among the simplest retroviruses. Prototypical gammaretroviruses encode only the three polyproteins that will be used in the assembly of progeny virus particles. These are the Gag polyprotein, which is the structural protein of a retrovirus particle, the Pol protein, comprising the three retroviral enzymes-protease, which catalyzes the maturation of the particle, reverse transcriptase, which copies the viral RNA into DNA upon infection of a new host cell, and integrase, which inserts the DNA into the chromosomal DNA of the host cell, and the Env polyprotein, which induces the fusion of the viral membrane with that of the new host cell, initiating infection. In general, a productive MLV infection has no obvious effect upon host cells. Although gammaretroviral structure and replication follow the same broad outlines as those of other retroviruses, we point out a number of significant differences between different retroviral genera.

  13. Proliferative capacity of murine hematopoietic stem cells

    International Nuclear Information System (INIS)

    Hellman, S.; Botnick, L.E.; Hannon, E.C.; Vigneulle, R.M.

    1978-01-01

    The present study demonstrates a decrease in self-renewal capacity with serial transfer of murine hematopoietic stem cells. Production of differentiated cell progeny is maintained longer than stem cell self-renewal. In normal animals the capacity for self-renewal is not decreased with increasing donor age. The stem cell compartment in normal animals, both young and old, appears to be proliferatively quiescent. After apparent recovery from the alkylating agent busulfan, the probability of stem cell self-renewal is decreased, there is a permanent defect in the capacity of the bone marrow for serial transplantation, and the stem cells are proliferatively active. These findings support a model of the hematopoietic stem cell compartment as a continuum of cells with decreasing capacities for self-renewal, increasing likelihood for differentiation, and increasing proliferative activity. Cells progress in the continuum in one direction and such progression is not reversible

  14. Formation and maturation of the murine meniscus.

    Science.gov (United States)

    Gamer, Laura W; Xiang, Lin; Rosen, Vicki

    2017-08-01

    Meniscal injuries are commonplace, but current surgical repair procedures do not prevent degenerative joint changes that occur after meniscal injury and often lead to osteoarthritis. Successful tissue regeneration in adults often recapitulates events that occur during embryogenesis, suggesting that understanding the regulatory pathways controlling these early processes may provide clues for developing strategies for tissue repair. While the mouse is now widely used to study joint diseases, detailed knowledge of the basic biology of murine meniscus is not readily available. Here, we examine meniscal morphogenesis in mice from embryonic day 13.5 (E13.5) to 6 months of age using histology, in situ hybridization, and immunohistochemistry. We find that the meniscus is a morphologically distinct structure at E16 when it begins to regionalize. At birth, the meniscus has a distinguishable inner, avascular, round chondrocyte cell region, an outer, vascularized, fibroblast cell region, and a surface superficial zone. Maturation begins at 2 weeks of age when the meniscus expresses type I collagen, type II collagen, type X collagen, and MMP-13 in specific patterns. By 4 weeks of age, small areas of ossification are detected in the anterior meniscal horn, a common feature seen in rodents. Maturation appears complete at 8 weeks of age, when the meniscus resembles the adult structure complete with ossifying tissue that contains bone marrow like areas. Our results provide, the first systematic study of mouse meniscal development and will be a valuable tool for analyzing murine models of knee joint formation and disease. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1683-1689, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  15. Murine colon proteome and characterization of the protein pathways

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    Magdeldin Sameh

    2012-08-01

    Full Text Available Abstract Background Most of the current proteomic researches focus on proteome alteration due to pathological disorders (i.e.: colorectal cancer rather than normal healthy state when mentioning colon. As a result, there are lacks of information regarding normal whole tissue- colon proteome. Results We report here a detailed murine (mouse whole tissue- colon protein reference dataset composed of 1237 confident protein (FDR I and Mw ranged from 3–12 and 4–600 KDa, respectively. Gravy index scoring predicted 19.5% membranous and 80.5% globularly located proteins. GO hierarchies and functional network analysis illustrated proteins function together with their relevance and implication of several candidates in malignancy such as Mitogen- activated protein kinase (Mapk8, 9 in colorectal cancer, Fibroblast growth factor receptor (Fgfr 2, Glutathione S-transferase (Gstp1 in prostate cancer, and Cell division control protein (Cdc42, Ras-related protein (Rac1,2 in pancreatic cancer. Protein abundances calculated with 3 different algorithms (NSAF, PAF and emPAI provide a relative quantification under normal condition as guidance. Conclusions This highly confidence colon proteome catalogue will not only serve as a useful reference for further experiments characterizing differentially expressed proteins induced from diseased conditions, but also will aid in better understanding the ontology and functional absorptive mechanism of the colon as well.

  16. Antinociception induced by rosuvastatin in murine neuropathic pain.

    Science.gov (United States)

    Miranda, Hugo F; Sierralta, Fernando; Aranda, Nicolas; Poblete, Paula; Castillo, Rodrigo L; Noriega, Viviana; Prieto, Juan Carlos

    2018-06-01

    Neuropathic pain, and subsequent hypernociception, can be induced in mice by paclitaxel (PTX) administration and partial sciatic nerve ligation (PSNL). Its pharmacotherapy has been a clinical challenge, due to a lack of effective treatment. In two models of mouse neuropathic pain (PTX and PSNL) the antinociception induced by rosuvastatin and the participation of proinflammatory biomarkers, interleukin (IL)- 1β, TBARS and glutathione were evaluated. A dose-response curve for rosuvastatin ip was obtained on cold plate, hot plate and Von Frey assays. Changes on spinal cord levels of IL-1β, glutathione and lipid peroxidation were measured at 7 and 14days in PTX and PSNL murine models. PTX or PSNL were able to induce in mice peripheral neuropathy with hypernociception, either to 7 and 14days. Rosuvastatin induced a dose dependent antinociception in hot plate, cold plate and Von Frey assays. The increased levels of IL-1β or TBARS induced by pretreatment with PTX or PSNL were reduced by rosuvastatin. The reduction of spinal cord glutathione, by PTX or PSNL, expressed as the ratio GSH/GSSG, were increased significantly in animals pretreated with rosuvastatin. The anti-inflammatory properties of statins could underlie their beneficial effects on neuropathic pain by reduction of proinflammatory biomarkers and activation of glia. The findings of this study suggest a potential usefulness of rosuvastatin in the treatment of neuropathic pain. Copyright © 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  17. Electrocautery effect on intestinal vascularisation in a murine model.

    Science.gov (United States)

    Tremblay, Jean-François; Sideris, Lucas; Leblond, François A; Trépanier, Jean-Sébastien; Badrudin, David; Drolet, Pierre; Mitchell, Andrew; Dubé, Pierre

    2016-09-01

    The use of electrocautery devices is associated with complications such as perforation or fistulisation when used near intestinal structures. This is likely due to its effect on vascularisation of the bowel wall. To test this hypothesis we established a murine model to quantify the effect of electrocautery injury on the intestinal microvascularisation. Sprague-Dawley rats were subjected to five electrocautery injuries on the small bowel in coagulation mode (30 W intensity) and in cut mode (40 W, 80 W and 200 W intensities) for durations of 1, 2 and 5 s. 5 mg/kg of fluorescein was injected intravenously, the injured bowel segments harvested and the rat sacrificed. The segments were analysed to measure the fluorescence of injured bowel compared to adjacent unharmed tissue. A significant decrease in bowel wall microvascularisation occurred with increasing intensity (coag 30 W/cut 40 W versus cut 200 W 1 s: p electrocautery injury (cut 40 W 1/2 s versus 5 s: p electrocautery injury, a significantly greater microvascularisation decrease was observed in jejunum compared to ileum (p electrocautery use. Unsurprisingly, the decrease in microvascularisation is greater with higher intensity and duration of electrocautery and is associated with more perforations in the experimental model. The jejunum seems more vulnerable to electrocautery injury than the ileum. These observations support caution when using electrocautery devices near intestinal structures.

  18. Effect of in vitro and in vivo UV irradiation on the production of ETAF activity by human and murine keratinocytes

    International Nuclear Information System (INIS)

    Ansel, J.C.; Luger, T.A.; Green, I.

    1983-01-01

    Cultured epidermal cells and keratinocytes produce a potent hormone-like factor called epidermal cell-derived thymocyte-activating factor (ETAF). ETAF appears to be similar if not identical to a monocyte-derived lymphokine, known as interleukin 1 (IL-1). These two cytokines are able to amplify a diverse number of proliferative and inflammatory processes. Several recent investigations have suggested that UV-induced immunosuppression may be due in part to the inhibition of IL-1/ETAF production by monocytes and keratinocytes, respectively. We therefore decided to directly study the effects of various doses of in vitro and in vivo UV radiation (UVR) on the production of ETAF by normal murine epidermal cells and a murine (Pam 212) and a human (SCC) keratinocyte cell line. Our results surprisingly demonstrated an increase in both the extracellular and the intracellular ETAF activity of the murine epidermal, Pam 212, and SCC after sublethal amounts of in vitro UVR. Likewise, increased ETAF activity of murine epidermal cells was detected after sublethal doses of in vivo UVR. The UV-induced ETAF activity was cycloheximide-sensitive, suggesting that de novo synthesis of ETAF rather than cell membrane leakage was responsible for the increased ETAF activity. The fact that UV irradiation can increase ETAF activity by keratinocytes could have important local and systemic consequences for the host and may provide an efficient, contaminant-free method for generating ETAF activity for further biochemical and immunologic studies

  19. Nitric oxide synthase 2 is required for conversion of pro-fibrogenic inflammatory CD133(+) progenitors into F4/80(+) macrophages in experimental autoimmune myocarditis.

    Science.gov (United States)

    Blyszczuk, Przemyslaw; Berthonneche, Corrine; Behnke, Silvia; Glönkler, Marcel; Moch, Holger; Pedrazzini, Thierry; Lüscher, Thomas F; Eriksson, Urs; Kania, Gabriela

    2013-02-01

    Experimental autoimmune myocarditis (EAM) model mirrors important mechanisms of inflammatory dilated cardiomyopathy (iDCM). In EAM, inflammatory CD133(+) progenitors are a major cellular source of cardiac myofibroblasts in the post-inflammatory myocardium. We hypothesized that exogenous delivery of macrophage-colony-stimulating factor (M-CSF) can stimulate macrophage lineage differentiation of inflammatory progenitors and, therefore, prevent their naturally occurring myofibroblast fate in EAM. EAM was induced in wild-type (BALB/c) and nitric oxide synthase 2-deficient (Nos2(-/-)) mice and CD133(+) progenitors were isolated from inflamed hearts. In vitro, M-CSF converted inflammatory CD133(+) progenitors into nitric oxide-producing F4/80(+) macrophages and prevented transforming growth factor-β-mediated myofibroblast differentiation. Importantly, only a subset of heart-infiltrating CD133(+) progenitors expresses macrophage-specific antigen F4/80 in EAM. These CD133(+)/F4/80(hi) cells show impaired myofibrogenic potential compared with CD133(+)/F4/80(-) cells. M-CSF treatment of wild-type mice with EAM at the peak of disease markedly increased CD133(+)/F4/80(hi) cells in the myocardium, and CD133(+) progenitors isolated from M-CSF-treated mice failed to differentiate into myofibroblasts. In contrast, M-CSF was not effective in converting CD133(+) progenitors from inflamed hearts of Nos2(-/-) mice into macrophages, and M-CSF treatment did not result in increased CD133(+)/F4/80(hi) cell population in hearts of Nos2(-/-) mice. Accordingly, M-CSF prevented post-inflammatory fibrosis and left ventricular dysfunction in wild-type but not in Nos2(-/-) mice. Active and NOS2-dependent induction of macrophage lineage differentiation abrogates the myofibrogenic potential of heart-infiltrating CD133(+) progenitors. Modulating the in vivo differentiation fate of specific progenitors might become a novel approach for the treatment of inflammatory heart diseases.

  20. Interleukin-6 gene polymorphisms and susceptibility to myocardial infarction: the ECTIM study. Etude Cas-Témoin de l'Infarctus du Myocarde.

    Science.gov (United States)

    Georges, J L; Loukaci, V; Poirier, O; Evans, A; Luc, G; Arveiler, D; Ruidavets, J B; Cambien, F; Tiret, L

    2001-06-01

    There is growing evidence that interleukin (IL) 6 plays an important role in the atherosclerotic process because of its role in mediating immune and inflammatory responses and inducing cell proliferation. The present study examined whether molecular variations at the IL-6 locus are involved in the predisposition to myocardial infarction. The entire coding region, 1,158 bp of the 5' flanking region and 237 bp of the 3' flanking region of the IL-6 gene were screened. We detected three nucleotide substitutions in the 5' region at positions -174 (G/C), -572 (G/C), and -596 (G/A) from the transcription start site, and one insertion/deletion in the 3' region at position +528 after the Stop codon. These polymorphisms were genotyped in the Etude Cas-Témoin de l'Infarctus du Myocarde study comparing male patients (n=640) and age-matched controls (n=719) from Northern Ireland and France. The IL-6/G-174C and IL-6/G-596A polymorphisms were in nearly complete association. Carriers of the IL-6/-174 C allele were more frequent in patients than in controls. The population-adjusted odds ratio for myocardial infarction associated with genotype CC+CG vs. GG was estimated as 1.34. In French patients the number of coronary arteries with greater than 50% stenosis was assessed by angiography. The IL-6/-174 C allele was more frequent in patients with two or fewer stenosed vessels than in patients with three-vessel lesions. These results suggest that genetic variation at the IL-6 locus is associated with susceptibility to myocardial infarction, especially events occurring on less extended lesions. These findings would be compatible with a lower IL-6 secretion associated with the IL-6/-174 C allele, itself or in combination with other promoter polymorphisms, leading to more unstable plaques.

  1. Poly-thymidine oligonucleotides mediate activation of murine glial cells primarily through TLR7, not TLR8.

    Directory of Open Access Journals (Sweden)

    Min Du

    Full Text Available The functional role of murine TLR8 in the inflammatory response of the central nervous system (CNS remains unclear. Murine TLR8 does not appear to respond to human TLR7/8 agonists, due to a five amino acid deletion in the ectodomain. However, recent studies have suggested that murine TLR8 may be stimulated by alternate ligands, which include vaccinia virus DNA, phosphothioate oligodeoxynucleotides (ODNs or the combination of phosphothioate poly-thymidine oligonucleotides (pT-ODNs with TLR7/8 agonists. In the current study, we analyzed the ability of pT-ODNs to induce activation of murine glial cells in the presence or absence of TLR7/8 agonists. We found that TLR7/8 agonists induced the expression of glial cell activation markers and induced the production of multiple proinflammatory cytokines and chemokines in mixed glial cultures. In contrast, pT-ODNs alone induced only low level expression of two cytokines, CCL2 and CXCL10. The combination of pT-ODNs along with TLR7/8 agonists induced a synergistic response with substantially higher levels of proinflammatory cytokines and chemokines compared to CL075. This enhancement was not due to cellular uptake of the agonist, indicating that the pT-ODN enhancement of cytokine responses was due to effects on an intracellular process. Interestingly, this response was also not due to synergistic stimulation of both TLR7 and TLR8, as the loss of TLR7 abolished the activation of glial cells and cytokine production. Thus, pT-ODNs act in synergy with TLR7/8 agonists to induce strong TLR7-dependent cytokine production in glial cells, suggesting that the combination of pT-ODNs with TLR7 agonists may be a useful mechanism to induce pronounced glial activation in the CNS.

  2. Self-gated CINE MRI for combined contrast-enhanced imaging and wall-stiffness measurements of murine aortic atherosclerotic lesions

    NARCIS (Netherlands)

    den Adel, Brigit; van der Graaf, Linda M.; Strijkers, Gustav J.; Lamb, Hildo J.; Poelmann, Robert E.; van der Weerd, Louise

    2013-01-01

    High-resolution contrast-enhanced imaging of the murine atherosclerotic vessel wall is difficult due to unpredictable flow artifacts, motion of the thin artery wall and problems with flow suppression in the presence of a circulating contrast agent. We applied a 2D-FLASH retrospective-gated CINE MRI

  3. Murine Ileocolic Bowel Resection with Primary Anastomosis

    Science.gov (United States)

    Perry, Troy; Borowiec, Anna; Dicken, Bryan; Fedorak, Richard; Madsen, Karen

    2014-01-01

    Intestinal resections are frequently required for treatment of diseases involving the gastrointestinal tract, with Crohn’s disease and colon cancer being two common examples. Despite the frequency of these procedures, a significant knowledge gap remains in describing the inherent effects of intestinal resection on host physiology and disease pathophysiology. This article provides detailed instructions for an ileocolic resection with primary end-to-end anastomosis in mice, as well as essential aspects of peri-operative care to maximize post-operative success. When followed closely, this procedure yields a 95% long-term survival rate, no failure to thrive, and minimizes post-operative complications of bowel obstruction and anastomotic leak. The technical challenges of performing the procedure in mice are a barrier to its wide spread use in research. The skills described in this article can be acquired without previous surgical experience. Once mastered, the murine ileocolic resection procedure will provide a reproducible tool for studying the effects of intestinal resection in models of human disease. PMID:25406841

  4. Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection.

    Directory of Open Access Journals (Sweden)

    Laurent Gillet

    2007-04-01

    Full Text Available Glycosaminoglycans (GAGs commonly participate in herpesvirus entry. They are thought to provide a reversible attachment to cells that promotes subsequent receptor binding. Murine gamma-herpesvirus-68 (MHV-68 infection of fibroblasts and epithelial cells is highly GAG-dependent. This is a function of the viral gp150, in that gp150-deficient mutants are much less GAG-dependent than wild-type. Here we show that the major MHV-68 GAG-binding protein is not gp150 but gp70, a product of ORF4. Surprisingly, ORF4-deficient MHV-68 showed normal cell binding and was more sensitive than wild-type to inhibition by soluble heparin rather than less. Thus, the most obvious viral GAG interaction made little direct contribution to infection. Indeed, a large fraction of the virion gp70 had its GAG-binding domain removed by post-translational cleavage. ORF4 may therefore act mainly to absorb soluble GAGs and prevent them from engaging gp150 prematurely. In contrast to gp70, gp150 bound poorly to GAGs, implying that it provides little in the way of adhesion. We hypothesize that it acts instead as a GAG-sensitive switch that selectively activates MHV-68 entry at cell surfaces.

  5. Analysis of cardiomyocyte movement in the developing murine heart

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Hisayuki [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Yuasa, Shinsuke, E-mail: yuasa@a8.keio.jp [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Tabata, Hidenori [Department of Anatomy, Keio University School of Medicine, Tokyo (Japan); Tohyama, Shugo; Seki, Tomohisa; Egashira, Toru; Hayashiji, Nozomi; Hattori, Fumiyuki; Kusumoto, Dai; Kunitomi, Akira; Takei, Makoto; Kashimura, Shin; Yozu, Gakuto; Shimojima, Masaya; Motoda, Chikaaki; Muraoka, Naoto [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Nakajima, Kazunori [Department of Anatomy, Keio University School of Medicine, Tokyo (Japan); Sakaue-Sawano, Asako; Miyawaki, Atsushi [Life Function and Dynamics, ERATO, JST, 2-1 Hirosawa, Wako-city, Saitama 351-0198 (Japan); Laboratory for Cell Function and Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198 (Japan); Fukuda, Keiichi [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan)

    2015-09-04

    The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cell cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle. - Highlights: • We directly visualized cardiomyocyte movement inside the developing murine heart. • Cell cycle related genes were upregulated in the proliferating cardiomyocytes. • Time-lapse imaging revealed that proliferating murine cardiomyocytes stayed in place. • Murine ventricular cardiomyocytes proliferate on site during development.

  6. Murine Typhus: An Important Consideration for the Nonspecific Febrile Illness

    Directory of Open Access Journals (Sweden)

    Gurjot Basra

    2012-01-01

    Full Text Available Murine typhus is a widely distributed flea-borne infection caused by Rickettsia typhi. Symptoms of murine typhus are nonspecific and mimic a variety of other infectious diseases. We herein report a case of murine typhus in an area where the broad use of DDT in the mid-20th century has now made it a rare disease. The patient described presented with headache, fever, and a faint macular rash. Initial laboratory studies revealed a slight transaminase elevation. Further questioning revealed exposure to opossums, prompting the consideration of murine typhus as a diagnosis. Although typhus group antibodies were not present during the patient’s acute illness, empiric therapy with doxycycline was initiated, and the patient defervesced. One month after convalescence, the patient returned to clinic with serum that contained typhus group antibodies with an IgG titer of 1 : 1024. Murine typhus is an important consideration during the workup of a patient with a nonspecific febrile illness. Exposure to reservoir hosts and the flea vector place humans at risk for this disease. Clinician recognition of this entity is required for diagnosis and effective therapy.

  7. The mechanical fingerprint of murine excisional wounds.

    Science.gov (United States)

    Pensalfini, Marco; Haertel, Eric; Hopf, Raoul; Wietecha, Mateusz; Werner, Sabine; Mazza, Edoardo

    2018-01-01

    A multiscale mechanics approach to the characterization of murine excisional wounds subjected to uniaxial tensile loading is presented. Local strain analysis at a physiological level of tension uncovers the presence of two distinct regions within the wound: i) a very compliant peripheral cushion and ii) a core area undergoing modest deformation. Microstructural visualizations of stretched wound specimens show negligible engagement of the collagen located in the center of a 7-day old wound; fibers remain coiled despite the applied tension, confirming the existence of a mechanically isolated wound core. The compliant cushion located at the wound periphery appears to protect the newly-formed tissue from excessive deformation during the phase of new tissue formation. The early remodeling phase (day 14) is characterized by a restored mechanical connection between far field and wound center. The latter remains less deformable, a characteristic possibly required for cell activities during tissue remodeling. The distribution of fibrillary collagens at these two time points corresponds well to the identified heterogeneity of mechanical properties of the wound region. This novel approach provides new insight into the mechanical properties of wounded skin and will be applicable to the analysis of compound-treated wounds or wounds in genetically modified tissue. Biophysical characterization of healing wounds is crucial to assess the recovery of the skin barrier function and the associated mechanobiological processes. For the first time, we performed highly resolved local deformation analysis to identify mechanical characteristics of the wound and its periphery. Our results reveal the presence of a compliant cushion surrounding a stiffer wound core; we refer to this heterogeneous mechanical behavior as "mechanical fingerprint" of the wound. The mechanical response is shown to progress towards that of the intact skin as healing takes place. Histology and multiphoton microscopy

  8. Preclinical Murine Models for Lung Cancer: Clinical Trial Applications

    Directory of Open Access Journals (Sweden)

    Amelia Kellar

    2015-01-01

    Full Text Available Murine models for the study of lung cancer have historically been the backbone of preliminary preclinical data to support early human clinical trials. However, the availability of multiple experimental systems leads to debate concerning which model, if any, is best suited for a particular therapeutic strategy. It is imperative that these models accurately predict clinical benefit of therapy. This review provides an overview of the current murine models used to study lung cancer and the advantages and limitations of each model, as well as a retrospective evaluation of the uses of each model with respect to accuracy in predicting clinical benefit of therapy. A better understanding of murine models and their uses, as well as their limitations may aid future research concerning the development and implementation of new targeted therapies and chemotherapeutic agents for lung cancer.

  9. Murine Models of Gastric Corpus PreneoplasiaSummary

    Directory of Open Access Journals (Sweden)

    Christine P. Petersen

    2017-01-01

    Full Text Available Intestinal-type gastric adenocarcinoma evolves in a field of pre-existing metaplasia. Over the past 20 years, a number of murine models have been developed to address aspects of the physiology and pathophysiology of metaplasia induction. Although none of these models has achieved true recapitulation of the induction of adenocarcinoma, they have led to important insights into the factors that influence the induction and progression of metaplasia. Here, we review the pathologic definitions relevant to alterations in gastric corpus lineages and classification of metaplasia by specific lineage markers. In addition, we review present murine models of the induction and progression of spasmolytic polypeptide (TFF2–expressing metaplasia, the predominant metaplastic lineage observed in murine models. These models provide a basis for the development of a broader understanding of the physiological and pathophysiological roles of metaplasia in the stomach. Keywords: SPEM, Intestinal Metaplasia, Gastric Cancer, TFF2, Chief Cell, Hyperplasia

  10. Diplopia due to Dacryops

    Directory of Open Access Journals (Sweden)

    Rahmi Duman

    2013-01-01

    Full Text Available Dacryops is a lacrimal ductal cyst. It is known that it can cause globe displacement, motility restriction, and proptosis because of the mass effect. Diplopia due to dacryops has not been reported previously. Here, we present a 57-year-old man with binocular horizontal diplopia that occurred during left direction gaze due to dacryops.

  11. Potent and reversible lentiviral vector restriction in murine induced pluripotent stem cells.

    Science.gov (United States)

    Geis, Franziska K; Galla, Melanie; Hoffmann, Dirk; Kuehle, Johannes; Zychlinski, Daniela; Maetzig, Tobias; Schott, Juliane W; Schwarzer, Adrian; Goffinet, Christine; Goff, Stephen P; Schambach, Axel

    2017-05-31

    Retroviral vectors are derived from wild-type retroviruses, can be used to study retrovirus-host interactions and are effective tools in gene and cell therapy. However, numerous cell types are resistant or less permissive to retrovirus infection due to the presence of active defense mechanisms, or the absence of important cellular host co-factors. In contrast to multipotent stem cells, pluripotent stem cells (PSC) have potential to differentiate into all three germ layers. Much remains to be elucidated in the field of anti-viral immunity in stem cells, especially in PSC. In this study, we report that transduction with HIV-1-based, lentiviral vectors (LV) is impaired in murine PSC. Analyses of early retroviral events in induced pluripotent stem cells (iPSC) revealed that the restriction is independent of envelope choice and does not affect reverse transcription, but perturbs nuclear entry and proviral integration. Proteasomal inhibition by MG132 could not circumvent the restriction. However, prevention of cyclophilin A (CypA) binding to the HIV-1 capsid via use of either a CypA inhibitor (cyclosporine A) or CypA-independent capsid mutants improved transduction. In addition, application of higher vector doses also increased transduction. Our data revealed a CypA mediated restriction in iPSC, which was acquired during reprogramming, associated with pluripotency and relieved upon subsequent differentiation. We showed that murine PSC and iPSC are less susceptible to LV. The block observed in iPSC was CypA-dependent and resulted in reduced nuclear entry of viral DNA and proviral integration. Our study helps to improve transduction of murine pluripotent cells with HIV-1-based vectors and contributes to our understanding of retrovirus-host interactions in PSC.

  12. A rapid murine coma and behavior scale for quantitative assessment of murine cerebral malaria.

    Directory of Open Access Journals (Sweden)

    Ryan W Carroll

    Full Text Available BACKGROUND: Cerebral malaria (CM is a neurological syndrome that includes coma and seizures following malaria parasite infection. The pathophysiology is not fully understood and cannot be accounted for by infection alone: patients still succumb to CM, even if the underlying parasite infection has resolved. To that effect, there is no known adjuvant therapy for CM. Current murine CM (MCM models do not allow for rapid clinical identification of affected animals following infection. An animal model that more closely mimics the clinical features of human CM would be helpful in elucidating potential mechanisms of disease pathogenesis and evaluating new adjuvant therapies. METHODOLOGY/PRINCIPAL FINDINGS: A quantitative, rapid murine coma and behavior scale (RMCBS comprised of 10 parameters was developed to assess MCM manifested in C57BL/6 mice infected with Plasmodium berghei ANKA (PbA. Using this method a single mouse can be completely assessed within 3 minutes. The RMCBS enables the operator to follow the evolution of the clinical syndrome, validated here by correlations with intracerebral hemorrhages. It provides a tool by which subjects can be identified as symptomatic prior to the initiation of trial treatment. CONCLUSIONS/SIGNIFICANCE: Since the RMCBS enables an operator to rapidly follow the course of disease, label a subject as affected or not, and correlate the level of illness with neuropathologic injury, it can ultimately be used to guide the initiation of treatment after the onset of cerebral disease (thus emulating the situation in the field. The RMCBS is a tool by which an adjuvant therapy can be objectively assessed.

  13. Endocarditis due to Lactobacillus jensenii in a Salvin's Amazon parrot (Amazona autumnalis salvini).

    Science.gov (United States)

    Foldenauer, Ulrike; Rusch, Martina; Simova-Curd, Stefka; Nitzl, Dagmar; Hoop, Richard K; Hatt, Jean-Michel

    2009-02-01

    A 30-year-old Salvin's Amazon parrot (Amazona autumnalis salvini) with a history of a lifelong poor diet and inappropriate housing was presented in lateral recumbency to a veterinary teaching hospital for further evaluation. Radiological and ultrasonographic examination revealed a mild proventricular dilatation, mild hepatomegaly, signs of enteritis and airsacculitis. The main laboratory findings included a mild macrocytic hyperchromic anaemia, hypoglobulinaemia, decreased bile acids and increased alkaline phosphatase. In this bird a liver pathology was suspected because of the clinical, laboratory and ultrasonographic findings. The bird was treated with supportive care and metabolic aids. After initial improvement of the clinical signs, the bird's condition deteriorated and it died. Pathological findings revealed an endocarditis and myocarditis due to Lactobacillus jensenii and a bacteraemia. Endocarditis due to Lactobacillus sp. is a rare phenomenon in humans not yet described in animals. It is associated with severe underlying illnesses leading to translocation of otherwise non-pathogenic bacteria in the bloodstream. A similar pattern might be assumed in animals with compromised immunity.

  14. Nanoelectroablation therapy for murine basal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nuccitelli, Richard, E-mail: rich@bioelectromed.com [BioElectroMed Corp., 849 Mitten Rd., Suite 104, Burlingame, CA 94010 (United States); Tran, Kevin; Athos, Brian; Kreis, Mark; Nuccitelli, Pamela [BioElectroMed Corp., 849 Mitten Rd., Suite 104, Burlingame, CA 94010 (United States); Chang, Kris S.; Epstein, Ervin H. [The Children' s Hospital Oakland Research Institute, Oakland, CA 94609 (United States); Tang, Jean Y. [The Children' s Hospital Oakland Research Institute, Oakland, CA 94609 (United States); Stanford University, Stanford, CA 94305 (United States)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Nanoelectroablation is a new, non-thermal therapy that triggers apoptosis in tumors. Black-Right-Pointing-Pointer Low energy, ultrashort, high voltage pulses ablate the tumor with little or no scar. Black-Right-Pointing-Pointer Nanoelectroablation eliminates 99.8% of the BCC but may leave a few remnants behind. Black-Right-Pointing-Pointer Pilot clinical trials on human BCCs are ongoing and leave no remnants in most cases. -- Abstract: When skin tumors are exposed to non-thermal, low energy, nanosecond pulsed electric fields (nsPEF), apoptosis is initiated both in vitro and in vivo. This nanoelectroablation therapy has already been proven effective in treating subdermal murine allograft tumors. We wanted to determine if this therapy would be equally effective in the treatment of autochthonous BCC tumors in Ptch1{sup +/-}K14-Cre-ER p53 fl/fl mice. These tumors are similar to human BCCs in histology and in response to drug therapy . We have treated 27 BCCs across 8 mice with either 300 pulses of 300 ns duration or 2700 pulses of 100 ns duration, all at 30 kV/cm and 5-7 pulses per second. Every nsPEF-treated BCC began to shrink within a day after treatment and their initial mean volume of 36 {+-} 5 (SEM) mm{sup 3} shrunk by 76 {+-} 3% over the ensuing two weeks. After four weeks, they were 99.8% ablated if the size of the treatment electrode matched the tumor size. If the tumor was larger than the 4 mm wide electrode, multiple treatments were needed for complete ablation. Treated tumors were harvested for histological analysis at various times after treatment and exhibited apoptosis markers. Specifically, pyknosis of nuclei was evident as soon as 2 days after nsPEF treatment, and DNA fragmentation as detected via TUNEL staining was also evident post treatment. Nanoelectroablation is effective in triggering apoptosis and remission of radiation-induced BCCs with a single 6 min-long treatment of 2700 pulses.

  15. Panhypopituitarism Due to Hemochromatosis

    OpenAIRE

    Mesut Özkaya; Kadir Gis; Ali Çetinkaya

    2013-01-01

    Hemochromatosis is an iron storage disease. Panhypopituitarism is a clinical condition in which the anterior pituitary hormones are deficient. Herein, we report a rare case of panhypopituitarism due to hemochromatosis. Turk Jem 2013; 17: 125-6

  16. Deference and Due Process

    OpenAIRE

    Vermeule, Cornelius Adrian

    2015-01-01

    In the textbooks, procedural due process is a strictly judicial enterprise; although substantive entitlements are created by legislative and executive action, it is for courts to decide independently what process the Constitution requires. The notion that procedural due process might be committed primarily to the discretion of the agencies themselves is almost entirely absent from the academic literature. The facts on the ground are very different. Thanks to converging strands of caselaw ...

  17. Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes Internalin A for enhanced infectivity in the murine oral infection model

    LENUS (Irish Health Repository)

    Monk, Ian R

    2010-12-13

    Abstract Background Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26), multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlA m*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlA m* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced entry into human

  18. Directed evolution and targeted mutagenesis to murinize listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model

    Directory of Open Access Journals (Sweden)

    Hill Colin

    2010-12-01

    Full Text Available Abstract Background Internalin A (InlA is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells. Results We have created a surface display library of randomly mutated InlA in a non-invasive heterologous host Lactococcus lactis in order to create and screen novel variants of this invasion factor. After sequential passage through a murine cell line (CT-26, multiple clones with enhanced invasion characteristics were identified. Competitive index experiments were conducted in mice using selected mutations introduced into L. monocytogenes EGD-e background. A novel single amino acid change was identified which enhanced virulence by the oral route in the murine model and will form the basis of further engineering approaches. As a control a previously described EGD-InlAm murinized strain was also re-created as part of this study with minor modifications and designated EGD-e InlAm*. The strain was created using a procedure that minimizes the likelihood of secondary mutations and incorporates Listeria-optimized codons encoding the altered amino acids. L. monocytogenes EGD-e InlAm* yielded consistently higher level murine infections by the oral route when compared to EGD-e, but did not display the two-fold increased invasion into a human cell line that was previously described for the EGD-InlAm strain. Conclusions We have used both site-directed mutagenesis and directed evolution to create variants of InlA which may inform future structure-function analyses of this protein. During the course of the study we engineered a murinized strain of L. monocytogenes EGD-e which shows reproducibly higher infectivity in the intragastric murine infection model than the wild type, but does not display enhanced

  19. Injury due to thorotrast

    International Nuclear Information System (INIS)

    Mori, Takesaburo

    1976-01-01

    A synthetic study was performed on some of those to whom Thorotrast had been injected, in Japan. In the epidemiological study of 147 war woundeds to whom Thorotrast had been injected, it was noted that the Thorotrast injection increased the mortality rate and the incidences of malignant hepatic tumor, liver cirrhosis, and hematological diseases. Clinical study of 44 of them showed that the Thorotrast injection resulted in liver and hematopoietic hypofunctions. Analysis of the dissection of the injected area in 118 cases showed malignant hepatic tumor in 63.5%, liver cirrhosis in 14.4% and hematological diseases in 10.2%. The total of the three types of disease was 88.1%. Histological classification showed that of the malignant hepatic tumors due to Thorotrast, hepatobiliary cancer and hemangioendothelioma of the liver were frequent. By the comparison of the absorbed dose in the liver of the malignant hepatic tumors due to Thorotrast with that of the cancers developed in animal experiments, it was noted that the carcinogenic dose was a mean of 2,000 - 3,000 rad by accumulated dose. It was elucidated that carcinogenesis and fibrination were primary in injury due to Thorotrast, i.e., late injury due to Thorotrast, and that the increase in the accumulated dose in rogans and the increase of the local dose due to the gigantic growth of Thorotrast granules in organs greatly influenced carninogenesis and fibrination. (Chiba, N.)

  20. Efficacy of Eosin B as a New Antimalarial Drug in a Murine Model

    Directory of Open Access Journals (Sweden)

    Zahra Zamani

    2012-01-01

    Full Text Available The initial success of any adopted anti-infective strategy to malaria is followed by a descent due to the emergence of resistance to it. The search for new drugs and drug targets is a consistent demand in this disease. Eosin B, a common laboratory dye, is reported to have good antiparasitic properties in vitro. It was studied for its antiparasitic effect in vivo on chloroquine-sensitive Plasmodium berghei murine malaria. Eosin B was administered in 2 different doses by either the oral or parenteral route, once or twice daily to mice infected with Plasmodium berghei. Both the doses of eosin B 400 mg/kg and 800 mg/kg gave better results than the controls which were 40 mg/kg chloroquine and 100 mg/kg of arteether with P<0.005 significance. Percentage suppressive activity by Peter’s test of eosin B was better, though at a higher dose than both the controls. Survival rate of mice receiving the higher dose of eosin B was longer than that of the controls. When administered twice daily, the mice were fully cured after 4 days. Eosin B seems to be a promising drug exhibiting good antimalarial effects in the murine model of the disease.

  1. Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy.

    Directory of Open Access Journals (Sweden)

    Estefanía de Munck

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive motor neuron degenerative disease that has no effective treatment up to date. Drug discovery tasks have been hampered due to the lack of knowledge in its molecular etiology together with the limited animal models for research. Recently, a motor neuron disease animal model has been developed using β-N-methylamino-L-alanine (L-BMAA, a neurotoxic amino acid related to the appearing of ALS. In the present work, the neuroprotective role of VP2.51, a small heterocyclic GSK-3 inhibitor, is analysed in this novel murine model together with the analysis of autophagy. VP2.51 daily administration for two weeks, starting the first day after L-BMAA treatment, leads to total recovery of neurological symptoms and prevents the activation of autophagic processes in rats. These results show that the L-BMAA murine model can be used to test the efficacy of new drugs. In addition, the results confirm the therapeutic potential of GSK-3 inhibitors, and specially VP2.51, for the disease-modifying future treatment of motor neuron disorders like ALS.

  2. Scanning laser optical tomography for in toto imaging of the murine cochlea.

    Directory of Open Access Journals (Sweden)

    Lena Nolte

    Full Text Available The mammalian cochlea is a complex macroscopic structure due to its helical shape and the microscopic arrangements of the individual layers of cells. To improve the outcomes of hearing restoration in deaf patients, it is important to understand the anatomic structure and composition of the cochlea ex vivo. Hitherto, only one histological technique based on confocal laser scanning microscopy and optical clearing has been developed for in toto optical imaging of the murine cochlea. However, with a growing size of the specimen, e.g., human cochlea, this technique reaches its limitations. Here, we demonstrate scanning laser optical tomography (SLOT as a valuable imaging technique to visualize the murine cochlea in toto without any physical slicing. This technique can also be applied in larger specimens up to cm3 such as the human cochlea. Furthermore, immunolabeling allows visualization of inner hair cells (otoferlin or spiral ganglion cells (neurofilament within the whole cochlea. After image reconstruction, the 3D dataset was used for digital segmentation of the labeled region. As a result, quantitative analysis of position, length and curvature of the labeled region was possible. This is of high interest in order to understand the interaction of cochlear implants (CI and cells in more detail.

  3. Transgene stability for three replication competent murine leukemia virus vectors

    DEFF Research Database (Denmark)

    Duch, M.; Carrasco, M.L.; Jespersen, T.

    2004-01-01

    cassette consisting of an internal ribosome entry site followed by the enhanced green fluorescent protein coding sequence inserted in different configurations into murine leukemia virus genomes. In two of the constructs, the insert was located in the upstream part of the U3 region while in the third...

  4. Murine alpha1-adrenoceptor subtypes. I. Radioligand binding studies

    NARCIS (Netherlands)

    Yang, M.; Reese, J.; Cotecchia, S.; Michel, M. C.

    1998-01-01

    Alpha1-adrenoceptors were identified in murine tissues by [3H]prazosin saturation binding studies, with a rank order of cerebral cortex > cerebellum > liver > lung > kidney > heart > spleen, with the spleen not exhibiting detectable expression. Competition binding studies were performed with

  5. Reversal of Liver Fibrosis in Chronic Murine Schistosomiasis ...

    African Journals Online (AJOL)

    NO Al-Harbi, SA Bahashwan, MS Aboonq, MA Ramadan, AA Bahashwan. Abstract. Purpose: To evaluate the safety, pharmacological effect and mechanism of action of an antifibrotic compound, safironil (SAF)/praziquantel (PZQ) combination on reversal of liver fibrogenesis in chronic murine Schistosomiasis mansoni.

  6. Protective antitumor activity induced by a fusion vaccine with murine ...

    African Journals Online (AJOL)

    Targeting angiogenesis is an effective strategy for anticancer therapy. The vascular endothelialcadherin (VE-cad) regulated angiogenesis is a potential target for anti-angiogenesis. Here, we develop a fusion vaccine plasmid DNA pSec-MBD2-VE-cad from VE-cad and murine beta defensin2 (MBD2) to induce immunity for ...

  7. Topical Apigenin Alleviates Cutaneous Inflammation in Murine Models

    Directory of Open Access Journals (Sweden)

    Mao-Qiang Man

    2012-01-01

    Full Text Available Herbal medicines have been used in preventing and treating skin disorders for centuries. It has been demonstrated that systemic administration of chrysanthemum extract exhibits anti-inflammatory properties. However, whether topical applications of apigenin, a constituent of chrysanthemum extract, influence cutaneous inflammation is still unclear. In the present study, we first tested whether topical applications of apigenin alleviate cutaneous inflammation in murine models of acute dermatitis. The murine models of acute allergic contact dermatitis and acute irritant contact dermatitis were established by topical application of oxazolone and phorbol 12-myristate 13-acetate (TPA, respectively. Inflammation was assessed in both dermatitis models by measuring ear thickness. Additionally, the effect of apigenin on stratum corneum function in a murine subacute allergic contact dermatitis model was assessed with an MPA5 physiology monitor. Our results demonstrate that topical applications of apigenin exhibit therapeutic effects in both acute irritant contact dermatitis and allergic contact dermatitis models. Moreover, in comparison with the vehicle treatment, topical apigenin treatment significantly reduced transepidermal water loss, lowered skin surface pH, and increased stratum corneum hydration in a subacute murine allergic contact dermatitis model. Together, these results suggest that topical application of apigenin could provide an alternative regimen for the treatment of dermatitis.

  8. Turnover of T cells in murine gammaherpesvirus 68-infected mice

    DEFF Research Database (Denmark)

    Hamilton-Easton, A M; Christensen, Jan Pravsgaard; Doherty, P C

    1999-01-01

    Respiratory challenge of C57BL/6 mice with murine gammaherpesvirus 68 induces proliferation of T lymphocytes early after infection, as evidenced by incorporation of the DNA precursor bromodeoxyuridine. Using pulse-chase analysis, splenic and peripheral blood activated T lymphocytes were found...

  9. Expression of biologically active murine interleukin-18 in Lactococcus lactis.

    Science.gov (United States)

    Feizollahzadeh, Sadegh; Khanahmad, Hossein; Rahimmanesh, Ilnaz; Ganjalikhani-Hakemi, Mazdak; Andalib, Alireza; Sanei, Mohammad Hossein; Rezaei, Abbas

    2016-11-01

    The food-grade bacterium Lactococcus lactis is increasingly used for heterologous protein expression in therapeutic and industrial applications. The ability of L. lactis to secrete biologically active cytokines may be used for the generation of therapeutic cytokines. Interleukin (IL)-18 enhances the immune response, especially on mucosal surfaces, emphasizing its therapeutic potential. However, it is produced as an inactive precursor and has to be enzymatically cleaved for maturation. We genetically manipulated L. lactis to secrete murine IL-18. The mature murine IL-18 gene was inserted downstream of a nisin promoter in pNZ8149 plasmid and the construct was used to transform L. lactis NZ3900. The transformants were selected on Elliker agar and confirmed by restriction enzyme digestion and sequencing. The expression and secretion of IL-18 protein was verified by SDS-PAGE, western blotting and ELISA. The biological activity of recombinant IL-18 was determined by its ability to induce interferon (IFN)-γ production in L. lactis co-cultured with murine splenic T cells. The amounts of IL-18 in bacterial lysates and supernatants were 3-4 μg mL -1 and 0.6-0.7 ng mL -1 , respectively. The successfully generated L. lactis strain that expressed biologically active murine IL-18 can be used to evaluate the possible therapeutic effects of IL-18 on mucosal surfaces. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. [Effects of Chinese herbal compound for supplementing qi and activating blood circulation on actin, Cx43 expressions and gap junctional intercellular communication functions of myocardial cells in patients with Coxsackie virus B 3 viral myocarditis].

    Science.gov (United States)

    Zhang, Ming-xue; He, Wei; Gu, Ping

    2010-08-01

    To observe the effect of Chinese herbal compound for supplementing qi and activating blood circulation (CHC) on the gap junctional intercellular communication (GJIC) function of myocardial cells in patients with Coxsackie virus B 3 (CVB3) viral myocarditis. Expressions of actin and connexin43 (Cx43) in myocardial cells of patients arranged in three groups (the normal control group, the viral infected group and the CHC treated group) were detected by immunohistochemical method; the fluorescence photobleaching recovery rate of cells was detected by laser scanning confocal microscope. As compared with the viral infected group, the expressions of actin and Cx43 were increased and the GJIC function was improved in the CHC treated group. CHC could antagonize viral injury on skeleton protein, and repair the structure of gap junction channel to improve the GJIC function of myocardial cells after being attacked by CVB3.

  11. Anaphylaxis due to caffeine

    OpenAIRE

    Sugiyama, Kumiya; Cho, Tatsurai; Tatewaki, Masamitsu; Onishi, Shogo; Yokoyama, Tatsuya; Yoshida, Naruo; Fujimatsu, Takayoshi; Hirata, Hirokuni; Fukuda, Takeshi; Fukushima, Yasutsugu

    2015-01-01

    We report a rare case of anaphylaxis due to caffeine intake. A 27-year-old woman suffered her first episode of anaphylaxis and a positive skin prick test suggested that the anaphylaxis was due to an IgE-mediated hypersensitivity reaction to caffeine. She was diagnosed with caffeine allergy and has not had an allergic reaction after avoiding foods and drinks containing caffeine. Although caffeine is known to have antiallergic effects, this case shows that caffeine can be an allergen and cause ...

  12. Characterisation of Neutropenia-Associated Neutrophil Elastase Mutations in a Murine Differentiation Model In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    Michael Wiesmeier

    Full Text Available Severe congenital neutropenia (SCN is characterised by a differentiation block in the bone marrow and low neutrophil numbers in the peripheral blood, which correlates with increased risk of bacterial infections. Several underlying gene defects have been identified in SCN patients. Mutations in the neutrophil elastase (ELANE gene are frequently found in SCN and cyclic neutropenia. Both mislocalization and misfolding of mutant neutrophil elastase protein resulting in ER stress and subsequent induction of the unfolded protein response (UPR have been proposed to be responsible for neutrophil survival and maturation defects. However, the detailed molecular mechanisms still remain unclear, in part due to the lack of appropriate in vitro and in vivo models. Here we used a system of neutrophil differentiation from immortalised progenitor lines by conditional expression of Hoxb8, permitting the generation of mature near-primary neutrophils in vitro and in vivo. NE-deficient Hoxb8 progenitors were reconstituted with murine and human forms of typical NE mutants representative of SCN and cyclic neutropenia, and differentiation of the cells was analysed in vitro and in vivo. ER stress induction by NE mutations could be recapitulated during neutrophil differentiation in all NE mutant-reconstituted Hoxb8 cells. Despite ER stress induction, no change in survival, maturation or function of differentiating cells expressing either murine or human NE mutants was observed. Further analysis of in vivo differentiation of Hoxb8 cells in a murine model of adoptive transfer did not reveal any defects in survival or differentiation in the mouse. Although the Hoxb8 system has been found to be useful for dissection of defects in neutrophil development, our findings indicate that the use of murine systems for analysis of NE-mutation-associated pathogenesis is complicated by differences between humans and mice in the physiology of granulopoiesis, which may go beyond possible

  13. Inhibition of soluble epoxide hydrolase contributes to the anti-inflammatory effect of antimicrobial triclocarban in a murine model

    International Nuclear Information System (INIS)

    Liu Junyan; Qiu Hong; Morisseau, Christophe; Hwang, Sung Hee; Tsai, Hsing-Ju; Ulu, Arzu; Chiamvimonvat, Nipavan; Hammock, Bruce D.

    2011-01-01

    The increasing use of the antimicrobial triclocarban (TCC) in personal care products (PCPs) has resulted in concern regarding environmental pollution. TCC is a potent inhibitor of soluble epoxide hydrolase (sEH). Inhibitors of sEH (sEHIs) are anti-inflammatory, anti-hypertensive and cardio-protective in multiple animal models. However, the in vivo effects anticipated from a sEHI have not been reported for TCC. Here we demonstrated the anti-inflammatory effects in vivo of TCC in a murine model. TCC was employed in a lipopolysaccharide (LPS)-challenged murine model. Systolic blood pressure, plasma levels of several inflammatory cytokines and chemokine, and metabolomic profile of plasma oxylipins were determined. TCC significantly reversed LPS-induced morbid hypotension in a time-dependent manner. TCC significantly repressed the increased release of inflammatory cytokines and chemokine caused by LPS. Furthermore, TCC significantly shifted the oxylipin profile in vivo in a time-dependent manner towards resolution of inflammation as expected from a sEHI. These results demonstrated that at the doses used TCC is anti-inflammatory in the murine model. This study suggests that TCC may provide some benefits in humans in addition to its antimicrobial activities due to its potent inhibition of sEH. It may be a promising starting point for developing new low volume high value applications of TCC. However these biological effects also caution against the general over use of TCC in PCPs. - Graphical abstract: Display Omitted Research Highlights: → Anti-microbial triclocarban (TCC) is anti-inflammatory in a murine model. → TCC significantly shifted the oxylipin profile in vivo as expected from a sEHI. → TCC significantly reversed LPS-induced morbid hypotension in a time-dependent manner. → TCC significantly repressed LPS-induced increased release of inflammatory cytokines.

  14. Directed evolution and targeted mutagenesis to murinize Listeria monocytogenes internalin A for enhanced infectivity in the murine oral infection model.

    LENUS (Irish Health Repository)

    Monk, Ian R

    2010-01-01

    Internalin A (InlA) is a critical virulence factor which mediates the initiation of Listeria monocytogenes infection by the oral route in permissive hosts. The interaction of InlA with the host cell ligand E-cadherin efficiently stimulates L. monocytogenes entry into human enterocytes, but has only a limited interaction with murine cells.

  15. Single Amino Acid Insertion in Loop 4 Confers Amphotropic Murine Leukemia Virus Receptor Function upon Murine Pit1

    DEFF Research Database (Denmark)

    Lundorf, Mikkel D.; Pedersen, Finn Skou; O'Hara, Bryan

    1998-01-01

    Pit1 is the human receptor for gibbon ape leukemia virus (GALV) and feline leukemia virus subgroup B (FeLV-B), while the related human protein Pit2 is a receptor for amphotropic murine leukemia virus (A-MuLV). The A-MuLV-related isolate 10A1 can utilize both Pit1 and Pit2 as receptors. A stretch...

  16. Heart failure due to severe myocardial calcification

    International Nuclear Information System (INIS)

    Takahashi, Shouichi; Maida, Kiyoshi; Yokoyama, Hitoshi; Tanaka, Shigeo

    1993-01-01

    A 28-year-old female who had had irradiation on the chest wall at the age of 5 as a remedy for keloid granulation after burn, recently developed congestive heart failure. Severe tricuspid regurgitation was demonstrated by echocardiography with a certain calcification in the cardiac shadow on chest radiogram. Calcified right ventricle and ventricular septum were noticed operatively, which disturbed ventricular motion and also caused tricuspid valve deformity. These calcified myocardium apparently corresponded with the irradiation field. After tricuspid valve replacement, she regained physical activity satisfactorily without congestive heart failure. Because she had no other known causes of cardiac calcification such as hypercalcemia, myocarditis, myocardial infarction or renal diseases, irradiation on the chest wall could be responsible for the severe myocardial calcification. (author)

  17. Human due diligence.

    Science.gov (United States)

    Harding, David; Rouse, Ted

    2007-04-01

    Most companies do a thorough job of financial due diligence when they acquire other companies. But all too often, deal makers simply ignore or underestimate the significance of people issues in mergers and acquisitions. The consequences are severe. Most obviously, there's a high degree of talent loss after a deal's announcement. To make matters worse, differences in decision-making styles lead to infighting; integration stalls; and productivity declines. The good news is that human due diligence can help companies avoid these problems. Done early enough, it helps acquirers decide whether to embrace or kill a deal and determine the price they are willing to pay. It also lays the groundwork for smooth integration. When acquirers have done their homework, they can uncover capability gaps, points of friction, and differences in decision making. Even more important, they can make the critical "people" decisions-who stays, who goes, who runs the combined business, what to do with the rank and file-at the time the deal is announced or shortly thereafter. Making such decisions within the first 30 days is critical to the success of a deal. Hostile situations clearly make things more difficult, but companies can and must still do a certain amount of human due diligence to reduce the inevitable fallout from the acquisition process and smooth the integration. This article details the steps involved in conducting human due diligence. The approach is structured around answering five basic questions: Who is the cultural acquirer? What kind of organization do you want? Will the two cultures mesh? Who are the people you most want to retain? And how will rank-and-file employees react to the deal? Unless an acquiring company has answered these questions to its satisfaction, the acquisition it is making will be very likely to end badly.

  18. Transcriptome analysis of the ependymal barrier during murine neurocysticercosis

    Directory of Open Access Journals (Sweden)

    Mishra Pramod

    2012-06-01

    Full Text Available Abstract Background Central nervous system (CNS barriers play a pivotal role in the protection and homeostasis of the CNS by enabling the exchange of metabolites while restricting the entry of xenobiotics, blood cells and blood-borne macromolecules. While the blood–brain barrier and blood-cerebrospinal fluid barrier (CSF control the interface between the blood and CNS, the ependyma acts as a barrier between the CSF and parenchyma, and regulates hydrocephalic pressure and metabolic toxicity. Neurocysticercosis (NCC is an infection of the CNS caused by the metacestode (larva of Taenia solium and a major cause of acquired epilepsy worldwide. The common clinical manifestations of NCC are seizures, hydrocephalus and symptoms due to increased intracranial pressure. The majority of the associated pathogenesis is attributed to the immune response against the parasite. The properties of the CNS barriers, including the ependyma, are affected during infection, resulting in disrupted homeostasis and infiltration of leukocytes, which correlates with the pathology and disease symptoms of NCC patients. Results In order to characterize the role of the ependymal barrier in the immunopathogenesis of NCC, we isolated ependymal cells using laser capture microdissection from mice infected or mock-infected with the closely related parasite Mesocestoides corti, and analyzed the genes that were differentially expressed using microarray analysis. The expression of 382 genes was altered. Immune response-related genes were verified by real-time RT-PCR. Ingenuity Pathway Analysis (IPA software was used to analyze the biological significance of the differentially expressed genes, and revealed that genes known to participate in innate immune responses, antigen presentation and leukocyte infiltration were affected along with the genes involved in carbohydrate, lipid and small molecule biochemistry. Further, MHC class II molecules and chemokines, including CCL12, were found

  19. Accumulation of murine amyloid-β mimics early Alzheimer's disease.

    Science.gov (United States)

    Krohn, Markus; Bracke, Alexander; Avchalumov, Yosef; Schumacher, Toni; Hofrichter, Jacqueline; Paarmann, Kristin; Fröhlich, Christina; Lange, Cathleen; Brüning, Thomas; von Bohlen Und Halbach, Oliver; Pahnke, Jens

    2015-08-01

    Amyloidosis mouse models of Alzheimer's disease are generally established by transgenic approaches leading to an overexpression of mutated human genes that are known to be involved in the generation of amyloid-β in Alzheimer's families. Although these models made substantial contributions to the current knowledge about the 'amyloid hypothesis' of Alzheimer's disease, the overproduction of amyloid-β peptides mimics only inherited (familiar) Alzheimer's disease, which accounts for patients with Alzheimer's disease. The inherited form is even regarded a 'rare' disease according to the regulations for funding of the European Union (www.erare.eu). Here, we show that mice that are double-deficient for neprilysin (encoded by Mme), one major amyloid-β-degrading enzyme, and the ABC transporter ABCC1, a major contributor to amyloid-β clearance from the brain, develop various aspects of sporadic Alzheimer's disease mimicking the clinical stage of mild cognitive impairment. Using behavioural tests, electrophysiology and morphological analyses, we compared different ABC transporter-deficient animals and found that alterations are most prominent in neprilysin × ABCC1 double-deficient mice. We show that these mice have a reduced probability to survive, show increased anxiety in new environments, and have a reduced working memory performance. Furthermore, we detected morphological changes in the hippocampus and amygdala, e.g. astrogliosis and reduced numbers of synapses, leading to defective long-term potentiation in functional measurements. Compared to human, murine amyloid-β is poorly aggregating, due to changes in three amino acids at N-terminal positions 5, 10, and 13. Interestingly, our findings account for the action of early occurring amyloid-β species/aggregates, i.e. monomers and small amyloid-β oligomers. Thus, neprilysin × ABCC1 double-deficient mice present a new model for early effects of amyloid-β-related mild cognitive impairment that allows investigations

  20. Premature Coronary Artery Disease due to Homozygous Familial Hypercholesterolemia in a 12-Year-Old Girl

    Directory of Open Access Journals (Sweden)

    Filiz Ekici

    2018-03-01

    Full Text Available Background: Homozygous familial hypercholesterolemia is a rare inherited metabolic disease caused by low-density lipoprotein receptor abnormality. Patients with homozygous familial hypercholesterolemia have an increased risk of cardiovascular complication that usually occurs in the first decade of life. Here, we report a 12-year-old girl with an unpredicted presentation for coronary artery disease and found to have homozygous familial hypercholesterolemia. Case Report: A 12-year-old girl was admitted to our unit with syncope. Chest X-ray showed bilateral diffuse pneumonic consolidation and mild cardiomegaly. We detected stable ST depression by electrocardiography. Echocardiography showed normal systolic functions. Troponin-1 levels were high (66 mcg/dL, upper limit: 0.04 mcg/dL. Influenza A virus DNA was detected by the respiratory viral panel. After her successful treatment for acute pneumonia and myocarditis due to Influenza A virus, her syncope attacks persisted. Marked ST elevation was observed during exercise electrocardiography. Coronary angiography showed severe occlusions in the coronary arteries. High serum levels of total cholesterol (756 mg/dL and low-density lipoprotein-C (556 mg/dL were noticed. She had no tendon xanthomas. Medical histories revealed that her family members were diagnosed with heterozygous familial hypercholesterolemia. A coronary bypass surgery was performed. Statin and ezetimibe treatments were started. We also planned lipid apheresis. Conclusion: Children with homozygous familial hypercholesterolemia may present with symptoms of premature coronary heart disease requiring a routine lipid test and careful anamnesis.

  1. Vitrification by Ultra-fast Cooling at a Low Concentration of Cryoprotectants in a Quartz Microcapillary: A Study Using Murine Embryonic Stem Cells

    Science.gov (United States)

    He, Xiaoming; Park, Eric Y.H.; Fowler, Alex; Yarmush, Martin L.; Toner, Mehmet

    2009-01-01

    Conventional cryopreservation protocols for slow-freezing or vitrification involve cell injury due to ice formation/cell dehydration or toxicity of high cryoprotectant (CPA) concentrations, respectively. In this study, we developed a novel cryopreservation technique to achieve ultra-fast cooling rates using a quartz microcapillary (QMC). The QMC enabled vitrification of murine embryonic stem (ES) cells using an intracellular cryoprotectant concentration in the range used for slowing freezing (1–2 M). The cryoprotectants used included 2 M 1,2-propanediol (PROH, cell membrane permeable) and 0.5 M extracellular trehalose (cell membrane impermeable). More than 70% of the murine ES cells post-vitrification attached with respect to non-frozen control cells, and the proliferation rates of the two groups were similar. Preservation of undifferentiated properties of the pluripotent murine ES cells post vitrification cryopreservation was verified using three different types of assays: the expression of transcription factor Oct-4, the presentation of the membrane surface glycoprotein SSEA-1, and the elevated expression of the intracellular enzyme alkaline phosphatase. These results indicate that vitrification at a low concentration (2 M) of intracellular cryoprotectants is a viable and effective approach for the cryopreservation of murine embryonic stem cells. PMID:18462712

  2. Single-dose-response curves of murine gastrointestinal crypt stem cells

    International Nuclear Information System (INIS)

    Masuda, K.; Withers, H.R.; Mason, K.A.; Chen, K.Y.

    1977-01-01

    Dose-response curves for the reproductive capacity of crypt stem cells of murine colonic, jejunal, and gastric mucosae exposed in situ to multifractionated gamma ray exposures were analyzed and single-dose-survival curves of these cells were constructed. The following conclusions were drawn: (1) The single-dose-response curves bend downward over a dose range of approximately 200 to 1500 rad; (2) cell death seems to be due to nonrepairable damage at doses less than 250 rad for colon, and 220 rad for jejunum; (3) there are 21, 110, and 140 stem cells per crypt of gastric, colonic, and jejunal mucosa, respectively; and (4) jejunal stem cells are the most radiosensitive and gastric mucosal stem cells are the most resistant

  3. The effect of medium composition on interleukin-2 production by murine EL-4 thymoma cells

    Directory of Open Access Journals (Sweden)

    Galesi A. L. L.

    2004-01-01

    Full Text Available Due to the role of interleukin-2 (IL-2 in the mediation of immune response, this cytokine has been used in the treatment of some types of cancer and infectious diseases. However, relatively high levels of this cytokine are required to achieve significant activity. The aim of this work was to study a culture medium composition designed to increase the production of IL-2 by suspended murine EL-4 cells. The cultivations were carried out aiming at producing IL-2 in stirred bioreactors. The effects of concentration of glutamine, phorbol-12-myristate-13-acetate (PMA, concanavalin A (Con A, Pluronic F68, and fetal calf serum (FCS on cell viability and IL-2 production were evaluated. PMA alone was more efficient in IL-2 production than it was in association with Con A. The maximum IL-2 production was around 162 ng/mL with 856 ng/mL PMA and 1.45% (v/v FCS.

  4. A simple quantitative model of macromolecular crowding effects on protein folding: Application to the murine prion protein(121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2013-06-01

    A model of protein folding kinetics is applied to study the effects of macromolecular crowding on protein folding rate and stability. Macromolecular crowding is found to promote a decrease of the entropic cost of folding of proteins that produces an increase of both the stability and the folding rate. The acceleration of the folding rate due to macromolecular crowding is shown to be a topology-dependent effect. The model is applied to the folding dynamics of the murine prion protein (121-231). The differential effect of macromolecular crowding as a function of protein topology suffices to make non-native configurations relatively more accessible.

  5. Technical Due Diligence

    DEFF Research Database (Denmark)

    Jensen, Per Anker; Varano, Mattia

    2011-01-01

    carried out for buyers or sellers involved in real estate transactions. It can also be part of mergers including real estate and other assets or part of facilities management outsourcing. This paper is based on a case study and an interview survey of companies involved in TDD consulting in Denmark......Technical Due Diligence (TDD) as an evaluation of the performance of constructed facilities has become an important new field of practice for consultants. Before the financial crisis started in autumn 2008 it represented the fastest growing activity in some consulting companies. TDD is mostly...... and Italy during 2009. The research identifies the current practice and compares it with the recommended practice in international guidelines. The current practice is very diverse and could in many cases be improved by a more structured approach and stricter adherence to international guidelines. However...

  6. Antibody responses against xenotropic murine leukemia virus-related virus envelope in a murine model.

    Directory of Open Access Journals (Sweden)

    Natalia Makarova

    2011-04-01

    Full Text Available Xenotropic murine leukemia virus-related virus (XMRV was recently discovered to be the first human gammaretrovirus that is associated with chronic fatigue syndrome and prostate cancer (PC. Although a mechanism for XMRV carcinogenesis is yet to be established, this virus belongs to the family of gammaretroviruses well known for their ability to induce cancer in the infected hosts. Since its original identification XMRV has been detected in several independent investigations; however, at this time significant controversy remains regarding reports of XMRV detection/prevalence in other cohorts and cell type/tissue distribution. The potential risk of human infection, coupled with the lack of knowledge about the basic biology of XMRV, warrants further research, including investigation of adaptive immune responses. To study immunogenicity in vivo, we vaccinated mice with a combination of recombinant vectors expressing codon-optimized sequences of XMRV gag and env genes and virus-like particles (VLP that had the size and morphology of live infectious XMRV.Immunization elicited Env-specific binding and neutralizing antibodies (NAb against XMRV in mice. The peak titers for ELISA-binding antibodies and NAb were 1:1024 and 1:464, respectively; however, high ELISA-binding and NAb titers were not sustained and persisted for less than three weeks after immunizations.Vaccine-induced XMRV Env antibody titers were transiently high, but their duration was short. The relatively rapid diminution in antibody levels may in part explain the differing prevalences reported for XMRV in various prostate cancer and chronic fatigue syndrome cohorts. The low level of immunogenicity observed in the present study may be characteristic of a natural XMRV infection in humans.

  7. Three-dimensional alginate spheroid culture system of murine osteosarcoma.

    Science.gov (United States)

    Akeda, Koji; Nishimura, Akinobu; Satonaka, Haruhiko; Shintani, Ken; Kusuzaki, Katsuyuki; Matsumine, Akihiko; Kasai, Yuichi; Masuda, Koichi; Uchida, Atsumasa

    2009-11-01

    Osteosarcoma (OS) is the most common primary malignant tumor of the bone and often forms pulmonary metastases, which are the most important prognostic factor. For further elucidation of the mechanism underlying the progression and metastasis of human OS, a culture system mimicking the microenvironment of the tumor in vivo is needed. We report a novel three-dimensional (3D) alginate spheroid culture system of murine osteosarcoma. Two different metastatic clones, the parental Dunn and its derivative line LM8, which has a higher metastatic potential to the lungs, were encapsulated in alginate beads to develop the 3D culture system. The beads containing murine OS cells were also transplanted into mice to determine their metastatic potential in vivo. In this culture system, murine OS cells encapsulated in alginate beads were able to grow in a 3D structure with cells detaching from the alginate environment. The number of detaching cells was higher in the LM8 cell line than the Dunn cell line. In the in vivo alginate bead transplantation model, the rate of pulmonary metastasis was higher with LM8 cells compared with that of Dunn cells. The cell characteristics and kinetics in this culture system closely reflect the original malignant potential of the cells in vivo.

  8. Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma

    International Nuclear Information System (INIS)

    Seong, Jin Sil; Kim, Sung Hee; Suh, Chang Ok

    2000-01-01

    The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-l, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, 8c1-2, Sax, Bel-XL, Bd-XS, and p21 WAF1/CIP1 . Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gerncitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21 WAF1/CIP1 . Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21 WAF1/CIP1

  9. Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Jin Sil; Kim, Sung Hee; Suh, Chang Ok [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    2000-12-01

    The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-l, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by tumor growth delay assay and by enhancement factor. Apoptotic level was assessed in tissue sections. Expression of regulating molecules was analyzed by western blotting for p53, 8c1-2, Sax, Bel-XL, Bd-XS, and p21{sup WAF1/CIP1}. Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with enhancement factor of 1.6. Induction of apoptosis by a combination of gerncitabine and radiation was shown as only additive level. In analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine was activation of p21 {sup WAF1/CIP1}. Gemcitabine is the first drug showing an enhancement of radioresponse in murine hepatocarcinoma, when combined with radiation. The key element of enhancement is thought to be p21{sup WAF1/CIP1}.

  10. The Role of the MHV Receptor and Related Glycoproteins in Murine Hepatitis Virus Infection of Murine Cell Lines

    Science.gov (United States)

    1995-04-13

    vaccinia virus-T7 RNA polymerase s y stem for e xpression of target genes . Mol . Cell . BioI . 7 : 2538-2544 . Gagneten , S ., Gout , 0 ., Dubois-Dalcq...glycoprotein. These results showed f or the first time that two murine CEA- related genes can be co-expressed in some cell lines from inbred mice...49 Southern Hybridization ................ . ............ 50 Subcloning of PCR Products and Gene Cloning ........ 51 Growth

  11. Salmonella enterica serovar Typhimurium lacking hfq gene confers protective immunity against murine typhoid.

    Directory of Open Access Journals (Sweden)

    Uday Shankar Allam

    Full Text Available Salmonella enterica is an important enteric pathogen and its various serovars are involved in causing both systemic and intestinal diseases in humans and domestic animals. The emergence of multidrug-resistant strains of Salmonella leading to increased morbidity and mortality has further complicated its management. Live attenuated vaccines have been proven superior over killed or subunit vaccines due to their ability to induce protective immunity. Of the various strategies used for the generation of live attenuated vaccine strains, focus has gradually shifted towards manipulation of virulence regulator genes. Hfq is a RNA chaperon which mediates the binding of small RNAs to the mRNA and assists in post-transcriptional gene regulation in bacteria. In this study, we evaluated the efficacy of the Salmonella Typhimurium Δhfq strain as a candidate for live oral vaccine in murine model of typhoid fever. Salmonella hfq deletion mutant is highly attenuated in cell culture and animal model implying a significant role of Hfq in bacterial virulence. Oral immunization with the Salmonella hfq deletion mutant efficiently protects mice against subsequent oral challenge with virulent strain of Salmonella Typhimurium. Moreover, protection was induced upon both multiple as well as single dose of immunizations. The vaccine strain appears to be safe for use in pregnant mice and the protection is mediated by the increase in the number of CD4(+ T lymphocytes upon vaccination. The levels of serum IgG and secretory-IgA in intestinal washes specific to lipopolysaccharide and outer membrane protein were significantly increased upon vaccination. Furthermore, hfq deletion mutant showed enhanced antigen presentation by dendritic cells compared to the wild type strain. Taken together, the studies in murine immunization model suggest that the Salmonella hfq deletion mutant can be a novel live oral vaccine candidate.

  12. Identification of distal silencing elements in the murine interferon-A11 gene promoter.

    Science.gov (United States)

    Roffet, P; Lopez, S; Navarro, S; Bandu, M T; Coulombel, C; Vignal, M; Doly, J; Vodjdani, G

    1996-08-01

    The murine interferon-A11 (Mu IFN-A11) gene is a member of the IFN-A multigenic family. In mouse L929 cells, the weak response of the gene's promoter to viral induction is due to a combination of both a point mutation in the virus responsive element (VRE) and the presence of negatively regulating sequences surrounding the VRE. In the distal part of the promoter, the negatively acting E1E2 sequence was delimited. This sequence displays an inhibitory effect in either orientation or position on the inducibility of a virus-responsive heterologous promoter. It selectively represses VRE-dependent transcription but is not able to reduce the transcriptional activity of a VRE-lacking promoter. In a transient transfection assay, an E1E2-containing DNA competitor was able to derepress the native Mu IFN-A11 promoter. Specific nuclear factors bind to this sequence; thus the binding of trans-regulators participates in the repression of the Mu IFN-A11 gene. The E1E2 sequence contains an IFN regulatory factor (IRF)-binding site. Recombinant IRF2 binds this sequence and anti-IRF2 antibodies supershift a major complex formed with nuclear extracts. The protein composing the complex is 50 kDa in size, indicating the presence of IRF2 or antigenically related proteins in the complex. The Mu IFN-A11 gene is the first example within the murine IFN-A family, in which a distal promoter element has been identified that can negatively modulate the transcriptional response to viral induction.

  13. Disruption of canonical TGFβ-signaling in murine coronary progenitor cells by low level arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Allison, Patrick; Huang, Tianfang; Broka, Derrick; Parker, Patti [Department of Pharmacology and Toxicology College of Pharmacy, Southwest Environmental Health Sciences Center, Steele Children' s Research Center and Bio5 Institute, University of Arizona, Tucson, AZ 85721 (United States); Barnett, Joey V. [Department of Pharmacology, Vanderbilt Medical University, Nashville, TN (United States); Camenisch, Todd D., E-mail: camenisch@pharmacy.arizona.edu [Department of Pharmacology and Toxicology College of Pharmacy, Southwest Environmental Health Sciences Center, Steele Children' s Research Center and Bio5 Institute, University of Arizona, Tucson, AZ 85721 (United States)

    2013-10-01

    Exposure to arsenic results in several types of cancers as well as heart disease. A major contributor to ischemic heart pathologies is coronary artery disease, however the influences by environmental arsenic in this disease process are not known. Similarly, the impact of toxicants on blood vessel formation and function during development has not been studied. During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types including smooth muscle cells which contribute to the coronary vessels. The TGFβ family of ligands and receptors is essential for developmental cardiac epithelial to mesenchymal transition (EMT) and differentiation into coronary smooth muscle cells. In this in vitro study, 18 hour exposure to 1.34 μM arsenite disrupted developmental EMT programming in murine epicardial cells causing a deficit in cardiac mesenchyme. The expression of EMT genes including TGFβ2, TGFβ receptor-3, Snail, and Has-2 are decreased in a dose-dependent manner following exposure to arsenite. TGFβ2 cell signaling is abrogated as detected by decreases in phosphorylated Smad2/3 when cells are exposed to 1.34 μM arsenite. There is also loss of nuclear accumulation pSmad due to arsenite exposure. These observations coincide with a decrease in vimentin positive mesenchymal cells invading three-dimensional collagen gels. However, arsenite does not block TGFβ2 mediated smooth muscle cell differentiation by epicardial cells. Overall these results show that arsenic exposure blocks developmental EMT gene programming in murine coronary progenitor cells by disrupting TGFβ2 signals and Smad activation, and that smooth muscle cell differentiation is refractory to this arsenic toxicity. - Highlights: • Arsenic blocks TGFβ2 induced expression of EMT genes. • Arsenic blocks TGFβ2 triggered Smad2/3 phosphorylation and nuclear translocation. • Arsenic blocks epicardial cell differentiation into cardiac mesenchyme.

  14. Changes in lymphocyte and macrophage subsets due to morphine and ethanol treatment during a retrovirus infection causing murine AIDS

    Energy Technology Data Exchange (ETDEWEB)

    Watson, R.R.; Prabhala, R.H.; Darban, H.R.; Yahya, M.D.; Smith, T.L.

    1988-01-01

    The number of lymphocytes of various subsets were not significantly changed by the ethanol exposure except those showing activation markers which were reduced. The percentage of peripheral blood cells showing markers for macrophage functions and their activation were significantly reduced after binge use of ethanol. Ethanol retarded suppression of cells by retroviral infection. However by 25 weeks of infection there was a 8.6% survival in the ethanol fed mice infected with retrovirus which was much less than virally infected controls. Morphine treatment also increased the percentage of cells with markers for macrophages and activated macrophages in virally infected mice, while suppressing them in uninfected mice. The second and third morphine injection series suppressed lymphocyte T-helper and T-suppressor cells, but not total T cells. However, suppression by morphine was significantly less during retroviral disease than suppression caused by the virus only. At 25 weeks of infection 44.8% of morphine treated, infected mice survived.

  15. [Evaluation of Fusarium spp. pathogenicity in plant and murine models].

    Science.gov (United States)

    Forero-Reyes, Consuelo M; Alvarado-Fernández, Angela M; Ceballos-Rojas, Ana M; González-Carmona, Lady C; Linares-Linares, Melva Y; Castañeda-Salazar, Rubiela; Pulido-Villamarín, Adriana; Góngora-Medina, Manuel E; Cortés-Vecino, Jesús A; Rodríguez-Bocanegra, María X

    The genus Fusarium is widely recognized for its phytopathogenic capacity. However, it has been reported as an opportunistic pathogen in immunocompetent and immunocompromised patients. Thus, it can be considered a microorganism of interest in pathogenicity studies on different hosts. Therefore, this work evaluated the pathogenicity of Fusarium spp. isolates from different origins in plants and animals (murine hosts). Twelve isolates of Fusarium spp. from plants, animal superficial mycoses, and human superficial and systemic mycoses were inoculated in tomato, passion fruit and carnation plants, and in immunocompetent and immunosuppressed BALB/c mice. Pathogenicity tests in plants did not show all the symptoms associated with vascular wilt in the three plant models; however, colonization and necrosis of the vascular bundles, regardless of the species and origin of the isolates, showed the infective potential of Fusarium spp. in different plant species. Moreover, the pathogenicity tests in the murine model revealed behavioral changes. It was noteworthy that only five isolates (different origin and species) caused mortality. Additionally, it was observed that all isolates infected and colonized different organs, regardless of the species and origin of the isolates or host immune status. In contrast, the superficial inoculation test showed no evidence of epidermal injury or colonization. The observed results in plant and murine models suggest the pathogenic potential of Fusarium spp. isolates in different types of hosts. However, further studies on pathogenicity are needed to confirm the multihost capacity of this genus. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Characterization of a Novel Murine Model to Study Zika Virus.

    Science.gov (United States)

    Rossi, Shannan L; Tesh, Robert B; Azar, Sasha R; Muruato, Antonio E; Hanley, Kathryn A; Auguste, Albert J; Langsjoen, Rose M; Paessler, Slobodan; Vasilakis, Nikos; Weaver, Scott C

    2016-06-01

    The mosquito-borne Zika virus (ZIKV) is responsible for an explosive ongoing outbreak of febrile illness across the Americas. ZIKV was previously thought to cause only a mild, flu-like illness, but during the current outbreak, an association with Guillain-Barré syndrome and microcephaly in neonates has been detected. A previous study showed that ZIKV requires murine adaptation to generate reproducible murine disease. In our study, a low-passage Cambodian isolate caused disease and mortality in mice lacking the interferon (IFN) alpha receptor (A129 mice) in an age-dependent manner, but not in similarly aged immunocompetent mice. In A129 mice, viremia peaked at ∼10(7) plaque-forming units/mL by day 2 postinfection (PI) and reached high titers in the spleen by day 1. ZIKV was detected in the brain on day 3 PI and caused signs of neurologic disease, including tremors, by day 6. Robust replication was also noted in the testis. In this model, all mice infected at the youngest age (3 weeks) succumbed to illness by day 7 PI. Older mice (11 weeks) showed signs of illness, viremia, and weight loss but recovered starting on day 8. In addition, AG129 mice, which lack both type I and II IFN responses, supported similar infection kinetics to A129 mice, but with exaggerated disease signs. This characterization of an Asian lineage ZIKV strain in a murine model, and one of the few studies reporting a model of Zika disease and demonstrating age-dependent morbidity and mortality, could provide a platform for testing the efficacy of antivirals and vaccines. © The American Society of Tropical Medicine and Hygiene.

  17. Corn silk induced cyclooxygenase-2 in murine macrophages.

    Science.gov (United States)

    Kim, Kyung A; Shin, Hyun-Hee; Choi, Sang Kyu; Choi, Hye-Seon

    2005-10-01

    Stimulation of murine macrophages with corn silk induced cyclooxygenase (COX)-2 with secretion of PGE2. Expression of COX-2 was inhibited by pyrolidine dithiocarbamate (PDTC), and increased DNA binding by nuclear factor kappa B (NF-kappaB), indicating that COX-2 induction proceeds also via the NF-kappaB signaling pathway. A specific inhibitor of COX-2 decreased the expression level of inducible nitric oxide synthase (iNOS) stimulated by corn silk. PGE2 elevated the expression level of iNOS, probably via EP2 and EP4 receptors on the surface of the macrophages.

  18. Collagen-Induced Arthritis: A model for Murine Autoimmune Arthritis

    OpenAIRE

    Pietrosimone, K. M.; Jin, M.; Poston, B.; Liu, P.

    2015-01-01

    Collagen-induced arthritis (CIA) is a common autoimmune animal model used to study rheumatoid arthritis (RA). The development of CIA involves infiltration of macrophages and neutrophils into the joint, as well as T and B cell responses to type II collagen. In murine CIA, genetically susceptible mice (DBA/1J) are immunized with a type II bovine collagen emulsion in complete Freund’s adjuvant (CFA), and receive a boost of type II bovine collagen in incomplete Freund’s adjuvant (IFA) 21 days aft...

  19. Murine nephrotoxic nephritis as a model of chronic kidney disease

    DEFF Research Database (Denmark)

    Ougaard, M. K.E.; Kvist, P. H.; Jensen, H. E.

    2018-01-01

    Using the nonaccelerated murine nephrotoxic nephritis (NTN) as a model of chronic kidney disease (CKD) could provide an easily inducible model that enables a rapid test of treatments. Originally, the NTN model was developed as an acute model of glomerulonephritis, but in this study we evaluate...... progressive mesangial expansion and significant renal fibrosis within three weeks suggesting CKD development. CD1 and C57BL/6 females showed a similar disease progression, but female mice seemed more susceptible to NTS compared to male mice. The presence of albuminuria, GFR decline, mesangial expansion...

  20. Biological markers as predictors of radiosensitivity in syngeneic murine tumors

    International Nuclear Information System (INIS)

    Chang, Sei Kyung; Shin, Hyun Soo; Seong, Jin Sil; Kim, Sung Hee

    2006-01-01

    We investigated whether a relationship exists between tumor control dose 50 (TCD 50 ) or tumor growth delay (TGD) and radiation induced apoptosis (RIA) in syngeneic murine tumors. Also we investigated the biological markers that can predict radiosensitivity in murine tumor system through analysis of relationship between TCD 50 , TGD, RIA and constitutive expression levels of the genetic products regulating RIA. Syngeneic murine tumors such as ovarian adenocarcinoma, mammary carcinoma, squamous cell carcinoma, fibrosarcoma, hepatocarcinoma were used in this study. C3H/HeJ mice were bred and maintained in our specific pathogen free mouse colony and were 8 ∼ 12 weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for TCD 50 , TGD, and RIA at 8 mm in diameter. The tumors were also analyzed for the constitutive expression levels of p53, p21 WAF1/CIP1 , BAX, Bcl-2, Bcl-x L , Bcl-x S , and p34. Correlation analysis was performed whether the level of RIA were correlated with TCD 50 or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with TCD 50 , TGD, RIA. The level of RIA showed a significant positive correlation (R = 0.922, ρ = 0.026) with TGD, and showed a trend to correlation (R = -0.848), marginally significant correlation with TCD 50 (ρ = 0.070). It indicates that tumors that respond to radiation with high percentage of apoptosis were more radiosensitive. The constitutive expression levels of p21 WAF1/CIP1 and p34 showed a significant correlation either with TCD 50 (R = 0.893, ρ = 0.041 and R = 0.904, ρ = 0.035) or with TGD (R = -0.922, ρ 0.026 and R = -0.890, ρ = 0.043). The tumors with high constitutive expression levels of p21 WAF1/CIP1 or p34 were less radiosensitive than those with low expression. Radiosensitivity may be predicted with the level of RIA in murine tumors. The constitutive expression levels of p21 WAF1/CIP1 or p34 can be used as biological

  1. Anticonvulsive evaluation of THIP in the murine pentylenetetrazole kindling model

    DEFF Research Database (Denmark)

    Simonsen, Charlotte; Boddum, Kim; von Schoubye, Nadia L

    2017-01-01

    . Evaluation of THIP as a potential anticonvulsant has given contradictory results in different animal models and for this reason, we reevaluated the anticonvulsive properties of THIP in the murine pentylenetetrazole (PTZ) kindling model. As loss of δ-GABAA R in the dentate gyrus has been associated...... the observed upregulation of δ-GABAA Rs. Even in the demonstrated presence of functional δ-GABAA Rs, THIP (0.5-4 mg/kg) showed no anticonvulsive effect in the PTZ kindling model using a comprehensive in vivo evaluation of the anticonvulsive properties....

  2. Production of antibodies which recognize opiate receptors on murine leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Carr, D.J.J.; Bost, K.L.; Blalock, J.E.

    1988-01-01

    An antibody has been developed which recognizes opiate receptors on cells of the immune system. This antibody blocks specific binding of the radiolabeled opiate receptor ligand, /sup 3/H-dihydromorphine, to receptors on murine splenocytes. Additionally, the anti-receptor antibody competes with ..beta..-endorphin, meta-enkephalin, and naloxone for the same binding site on the leukocytes. Moreover, the anti-receptor antibody possesses agonist activity similar to ..beta..-endorphin in suppressing cAMP production by lymphocytes. These results suggest the development of an antibody which recognizes classical opiate receptors on cells of the immune system.

  3. Murine cell glycolipids customization by modular expression of glycosyltransferases.

    Science.gov (United States)

    Cid, Emili; Yamamoto, Miyako; Buschbeck, Marcus; Yamamoto, Fumiichiro

    2013-01-01

    Functional analysis of glycolipids has been hampered by their complex nature and combinatorial expression in cells and tissues. We report an efficient and easy method to generate cells with specific glycolipids. In our proof of principle experiments we have demonstrated the customized expression of two relevant glycosphingolipids on murine fibroblasts, stage-specific embryonic antigen 3 (SSEA-3), a marker for stem cells, and Forssman glycolipid, a xenoantigen. Sets of genes encoding glycosyltansferases were transduced by viral infection followed by multi-color cell sorting based on coupled expression of fluorescent proteins.

  4. Studies on murine plasmocytoma treatment with mistletoe lectin I

    International Nuclear Information System (INIS)

    Raabe, F.; Storch, H.

    1987-01-01

    Mistletoe lectin I was tested in vivo and in vitro for its cytotoxic activity against murine plasmacytoma cells P3/X63-Ag8. As a result of this treatment, 30 to 60% of the BALB/c mice developed complete tumor regressions. 83% of the mice treated with mistletoe lectin I were resistant to viable tumor cell challenge after 100 days. The cytotoxic activity in vitro tested by 3 H-thymidine incorporation into P3/X63-Ag8 cells was very high. The rate was markedly reduced at concentrations up to 0.07 ng/ml. (author)

  5. Adrenaline influences the release of interleukin-6 from murine pituicytes

    DEFF Research Database (Denmark)

    Christensen, J D; Hansen, E W; Frederiksen, C

    1999-01-01

    In this study, we examined the effect of adrenaline and interleukin-1beta on interleukin-6 secretion from cultured murine neurohypophyseal cells. Cells were cultured from neurohypophyses of 3- to 5-week-old mice and experiments were performed after 13 days in culture. Interleukin-6 was measured...... in 24-h samples using a sandwich fluoroimmunoassay. Unstimulated cells released 19+/-3 fmol interleukin-6/neurohypophysis/24 h (mean +/- S.E.M., n = 42). Adrenaline and interleukin-1beta increased the release of interleukin-6 from the cells in a concentration-dependent manner. Incubation with adrenaline...

  6. Biological markers as predictors of radiosensitivity in syngeneic murine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Sei Kyung; Shin, Hyun Soo [Bundang CHA General Hospital, Seongnam (Korea, Republic of); Seong, Jin Sil; Kim, Sung Hee [Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2006-06-15

    We investigated whether a relationship exists between tumor control dose 50 (TCD{sub 50}) or tumor growth delay (TGD) and radiation induced apoptosis (RIA) in syngeneic murine tumors. Also we investigated the biological markers that can predict radiosensitivity in murine tumor system through analysis of relationship between TCD{sub 50}, TGD, RIA and constitutive expression levels of the genetic products regulating RIA. Syngeneic murine tumors such as ovarian adenocarcinoma, mammary carcinoma, squamous cell carcinoma, fibrosarcoma, hepatocarcinoma were used in this study. C3H/HeJ mice were bred and maintained in our specific pathogen free mouse colony and were 8 {approx} 12 weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for TCD{sub 50}, TGD, and RIA at 8 mm in diameter. The tumors were also analyzed for the constitutive expression levels of p53, p21{sup WAF1/CIP1}, BAX, Bcl-2, Bcl-x{sub L}, Bcl-x{sub S}, and p34. Correlation analysis was performed whether the level of RIA were correlated with TCD{sub 50} or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with TCD{sub 50}, TGD, RIA. The level of RIA showed a significant positive correlation (R = 0.922, {rho} = 0.026) with TGD, and showed a trend to correlation (R = -0.848), marginally significant correlation with TCD{sub 50} ({rho} = 0.070). It indicates that tumors that respond to radiation with high percentage of apoptosis were more radiosensitive. The constitutive expression levels of p21{sup WAF1/CIP1} and p34 showed a significant correlation either with TCD{sub 50} (R = 0.893, {rho} = 0.041 and R = 0.904, {rho} = 0.035) or with TGD (R = -0.922, {rho} 0.026 and R = -0.890, {rho} = 0.043). The tumors with high constitutive expression levels of p21{sup WAF1/CIP1} or p34 were less radiosensitive than those with low expression. Radiosensitivity may be predicted with the level of RIA in murine tumors. The

  7. Analysis of the capacity to produce IL-3 in murine AIDS

    DEFF Research Database (Denmark)

    Neuenschwander, A U; Marker, O; Thomsen, Allan Randrup

    1994-01-01

    Adult C57BL/6 mice infected with LP-BM5 murine leukaemia virus represent a model of murine AIDS (MAIDS). In this study we have analysed the capacity of CD4+ T cells from infected mice to produce IL-3 following stimulation with ConA for 24-72 h. In contrast to the position with IL-2, the production...

  8. Murine typhus in two travelers returning from Bali, Indonesia: an underdiagnosed disease.

    Science.gov (United States)

    Takeshita, Nozomi; Imoto, Kazuya; Ando, Shuji; Yanagisawa, Kunio; Ohji, Goh; Kato, Yasuyuki; Sakata, Akiko; Hosokawa, Naoto; Kishimoto, Toshio

    2010-01-01

    Two Japanese travelers from Bali were diagnosed with murine typhus in Japan during the same period. Although one had only mild illness, the other experienced liver and kidney dysfunction. Murine typhus may be missed not only in endemic areas around the world, but also in travelers, especially those returning from marine resorts in these areas. © 2010 International Society of Travel Medicine.

  9. Preclinical Validation of 99mTc–Annexin A5–128 in Experimental Autoimmune Myocarditis and Infective Endocarditis: Comparison with 99mTc–HYNIC–Annexin A5

    Directory of Open Access Journals (Sweden)

    Khadija Benali

    2015-01-01

    Full Text Available Hydrazinonicotinamide–annexin A5 (HYNIC-Anx, a 99m technetium (99mTc-labeled agent targeting phosphatidylserine, proved to be sensitive for the detection of apoptosis and thrombosis but is no longer available for clinical use. A mutant of human annexin designed for direct 99mTc labeling (referred to as Anx A5–128 showed improved binding affinity to phosphatidylserine and is expected to be used in humans. We compared both radiotracers with regard to pharmacokinetics and diagnostic ability in animal models. Biodistribution studies were performed in normal rats. Radiolabeled Anx A5–128 and HYNIC-Anx were compared in cardiovascular settings involving phosphatidylserine expression: experimental autoimmune myocarditis and infective endocarditis. Initial blood clearance was faster for Anx A5–128 than for HYNIC-Anx, and tissue biodistribution was similar overall for both tracers. The diagnostic sensitivity of Anx A5–128 was excellent and comparable to that of HYNIC-Anx. Anx A5–128 showed biodistribution and diagnostic ability similar to those of the HYNIC-Anx derivative, supporting its translation to clinical use.

  10. Miocarditis de células gigantes con bloqueo AV completo persistente: respuesta al tratamiento con resincronizador cardiaco Giant cell myocarditis with complete persistent A-V block: treatment response with cardiac resynchronization

    Directory of Open Access Journals (Sweden)

    Julián Aristizábal

    2009-08-01

    Full Text Available La miocarditis de células gigantes es una enfermedad grave y poco frecuente, cuya etiología, posiblemente autoinmune, se caracteriza por la presencia de células gigantes multinucleadas con infiltrado inflamatorio y necrosis extensa en la biopsia endomiocárdica. Es común su asociación con taquicardias ventriculares y con alteraciones de la conducción aurículo-ventricular, lo cual se resuelve algunas veces con tratamiento inmunosupresor. Dada la complejidad del pronóstico de esta entidad, el papel de los dispositivos de resincronización después de la estabilización de la falla cardíaca, no está claro. Aquí se reporta un caso en el cual el implante de uno de estos dispositivos fue parte fundamental de la terapia y recuperación del paciente.Giant cell myocarditis is an infrequent and serious illness, possibly of autoimmune etiology, characterized by the presence of multinucleated giant cells with inflammatory infiltrate and extensive necrosis in the endomyocardial biopsy. Its association with ventricular tachycardia is common and alterations in atrioventricular conduction are frequently solved through immunosuppressive treatment. Given the generally complex prognosis of this entity, the role of the resynchronization devices after the heart failure stabilization, is unclear. We reported a case in which the implant of one of these devices was a fundamental part of the therapy and patient recovery.

  11. Targeted destruction of murine macrophage cells with bioconjugated gold nanorods

    Energy Technology Data Exchange (ETDEWEB)

    Pissuwan, Dakrong [University of Technology Sydney, Institute for Nanoscale Technology (Australia); Valenzuela, Stella M. [University of Technology Sydney, Department of Medical and Molecular Biosciences (Australia)], E-mail: stella.valenzuela@uts.edu.au; Killingsworth, Murray C. [Sydney South West Pathology Service (Australia)], E-mail: murray.killingsworth@swsahs.nsw.gov.au; Xu, Xiaoda; Cortie, Michael B. [University of Technology Sydney, Institute for Nanoscale Technology (Australia)], E-mail: michael.cortie@uts.edu.au

    2007-12-15

    Gold nanorods manifest a readily tunable longitudinal plasmon resonance with light and consequently have potential for use in photothermal therapeutics. Recent work by others has shown how gold nanoshells and rods can be used to target cancer cells, which can then be destroyed using relatively high power laser radiation ({approx}1x10{sup 5} to 1x10{sup 10} W/m{sup 2}). Here we extend this concept to demonstrate how gold nanorods can be modified to bind to target macrophage cells, and show that high intensity laser radiation is not necessary, with even 5x10{sup 2} W/m{sup 2} being sufficient, provided that a total fluence of {approx}30 J/cm{sup 2} is delivered. We used the murine cell line RAW 264.7 and the monoclonal antibody CD11b, raised against murine macrophages, as our model system and a 5 mW solid state diode laser as our energy source. Exposure of the cells labeled with gold nanorods to a laser fluence of 30 J/cm{sup 2} resulted in 81% cell death compared to only 0.9% in the control, non-labeled cells.

  12. Targeted destruction of murine macrophage cells with bioconjugated gold nanorods

    Science.gov (United States)

    Pissuwan, Dakrong; Valenzuela, Stella M.; Killingsworth, Murray C.; Xu, Xiaoda; Cortie, Michael B.

    2007-12-01

    Gold nanorods manifest a readily tunable longitudinal plasmon resonance with light and consequently have potential for use in photothermal therapeutics. Recent work by others has shown how gold nanoshells and rods can be used to target cancer cells, which can then be destroyed using relatively high power laser radiation (˜1×105 to 1×1010 W/m2). Here we extend this concept to demonstrate how gold nanorods can be modified to bind to target macrophage cells, and show that high intensity laser radiation is not necessary, with even 5×102 W/m2 being sufficient, provided that a total fluence of ˜30 J/cm2 is delivered. We used the murine cell line RAW 264.7 and the monoclonal antibody CD11b, raised against murine macrophages, as our model system and a 5 mW solid state diode laser as our energy source. Exposure of the cells labeled with gold nanorods to a laser fluence of 30 J/cm2 resulted in 81% cell death compared to only 0.9% in the control, non-labeled cells.

  13. Targeted destruction of murine macrophage cells with bioconjugated gold nanorods

    International Nuclear Information System (INIS)

    Pissuwan, Dakrong; Valenzuela, Stella M.; Killingsworth, Murray C.; Xu, Xiaoda; Cortie, Michael B.

    2007-01-01

    Gold nanorods manifest a readily tunable longitudinal plasmon resonance with light and consequently have potential for use in photothermal therapeutics. Recent work by others has shown how gold nanoshells and rods can be used to target cancer cells, which can then be destroyed using relatively high power laser radiation (∼1x10 5 to 1x10 10 W/m 2 ). Here we extend this concept to demonstrate how gold nanorods can be modified to bind to target macrophage cells, and show that high intensity laser radiation is not necessary, with even 5x10 2 W/m 2 being sufficient, provided that a total fluence of ∼30 J/cm 2 is delivered. We used the murine cell line RAW 264.7 and the monoclonal antibody CD11b, raised against murine macrophages, as our model system and a 5 mW solid state diode laser as our energy source. Exposure of the cells labeled with gold nanorods to a laser fluence of 30 J/cm 2 resulted in 81% cell death compared to only 0.9% in the control, non-labeled cells

  14. Activation of DNA damage repair pathways by murine polyomavirus

    Energy Technology Data Exchange (ETDEWEB)

    Heiser, Katie; Nicholas, Catherine; Garcea, Robert L., E-mail: Robert.Garcea@Colorado.edu

    2016-10-15

    Nuclear replication of DNA viruses activates DNA damage repair (DDR) pathways, which are thought to detect and inhibit viral replication. However, many DNA viruses also depend on these pathways in order to optimally replicate their genomes. We investigated the relationship between murine polyomavirus (MuPyV) and components of DDR signaling pathways including CHK1, CHK2, H2AX, ATR, and DNAPK. We found that recruitment and retention of DDR proteins at viral replication centers was independent of H2AX, as well as the viral small and middle T-antigens. Additionally, infectious virus production required ATR kinase activity, but was independent of CHK1, CHK2, or DNAPK signaling. ATR inhibition did not reduce the total amount of viral DNA accumulated, but affected the amount of virus produced, indicating a defect in virus assembly. These results suggest that MuPyV may utilize a subset of DDR proteins or non-canonical DDR signaling pathways in order to efficiently replicate and assemble. -- Highlights: •Murine polyomavirus activates and recruits DNA damage repair (DDR) proteins to replication centers. •Large T-antigen mediates recruitment of DDR proteins to viral replication centers. •Inhibition or knockout of CHK1, CHK2, DNA-PK or H2AX do not affect viral titers. •Inhibition of ATR activity reduces viral titers, but not viral DNA accumulation.

  15. Application of murine monoclonal antibodies to the serodiagnosis of tuberculosis

    International Nuclear Information System (INIS)

    Ivanyl, J.; Coates, A.R.M.; Krambovitis, E.

    1982-01-01

    The immune response during infectious diseases leads to a rise in antibody titre to the various different antigenic determinants of the causative organism. The response is further complicated by the fact that it is relatively unusual for one individual to respond to all antigenic components of an organism. Demonstration of the specific immune response of an infected host by serological tests is often hampered by the broad cross-reactivity between several bacterial antigens. The authors report on a serodiagnostic application of murine monoclonal antibodies (MAB), specific for a human pathogen, M. tuberculosis by a technique which is applicable in principle to the serodiagnosis of many other infectious diseases. The serum diagnostic test is based on the competitive inhibition by human sera of the binding of 125 I-labelled murine monoclonal antibodies to M. tuberculosis-coated polyvinyl plates. Five monoclonal antibodies binding to distinct antigenic determinants of the organism were used as structural probes which conferred their stringent combining site specificities to the polyclonal mixture of antibodies from patients' sera. When compared with healthy controls, increased titres of inhibitory antibodies were found in about 70% of patients with active tuberculosis. The diagnostic value of the individual monoclonal antibodies as well as the benefit from the use of multiple specificity probes has been qualified

  16. Murine models of osteosarcoma: A piece of the translational puzzle.

    Science.gov (United States)

    Walia, Mannu K; Castillo-Tandazo, Wilson; Mutsaers, Anthony J; Martin, Thomas John; Walkley, Carl R

    2018-06-01

    Osteosarcoma (OS) is the most common cancer of bone in children and young adults. Despite extensive research efforts, there has been no significant improvement in patient outcome for many years. An improved understanding of the biology of this cancer and how genes frequently mutated contribute to OS may help improve outcomes for patients. While our knowledge of the mutational burden of OS is approaching saturation, our understanding of how these mutations contribute to OS initiation and maintenance is less clear. Murine models of OS have now been demonstrated to be highly valid recapitulations of human OS. These models were originally based on the frequent disruption of p53 and Rb in familial OS syndromes, which are also common mutations in sporadic OS. They have been applied to significantly improve our understanding about the functions of recurrently mutated genes in disease. The murine models can be used as a platform for preclinical testing and identifying new therapeutic targets, in addition to testing the role of additional mutations in vivo. Most recently these models have begun to be used for discovery based approaches and screens, which hold significant promise in furthering our understanding of the genetic and therapeutic sensitivities of OS. In this review, we discuss the mouse models of OS that have been reported in the last 3-5 years and newly identified pathways from these studies. Finally, we discuss the preclinical utilization of the mouse models of OS for identifying and validating actionable targets to improve patient outcome. © 2017 Wiley Periodicals, Inc.

  17. Neurological Disorders in a Murine Model of Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Jean-Marc Chillon

    2014-01-01

    Full Text Available Cardiovascular disease is highly prevalent in patients with chronic renal failure (CRF. However, data on the impact of CRF on the cerebral circulatory system are scarce—despite the fact that stroke is the third most common cause of cardiovascular death in people with CRF. In the present study, we examined the impact of CRF on behavior (anxiety, recognition and ischemic stroke severity in a well-defined murine model of CRF. We did not observe any significant increases between CRF mice and non-CRF mice in terms of anxiety. In contrast, CRF mice showed lower levels of anxiety in some tests. Recognition was not impaired (vs. controls after 6 weeks of CRF but was impaired after 10 weeks of CRF. Chronic renal failure enhances the severity of ischemic stroke, as evaluated by the infarct volume size in CRF mice after 34 weeks of CRF. Furthermore, neurological test results in non-CRF mice tended to improve in the days following ischemic stroke, whereas the results in CRF mice tended to worsen. In conclusion, we showed that a murine model of CRF is suitable for evaluating uremic toxicity and the associated neurological disorders. Our data confirm the role of uremic toxicity in the genesis of neurological abnormalities (other than anxiety.

  18. Differential chemokine responses in the murine brain following lyssavirus infection.

    Science.gov (United States)

    Hicks, D J; Núñez, A; Banyard, A C; Williams, A; Ortiz-Pelaez, A; Fooks, A R; Johnson, N

    2013-11-01

    The hallmark of lyssavirus infection is lethal encephalomyelitis. Previous studies have reported distinct lyssavirus isolate-related differences in severity of cellular recruitment into the encephalon in a murine model of infection following peripheral inoculation with rabies virus (RABV) and European bat lyssavirus (EBLV)-1 and -2. In order to understand the role of chemokines in this process, comparative studies of the chemokine pattern, distribution and production in response to infection with these lyssaviruses were undertaken. Expression of CCL2, CCL5 and CXCL10 was observed throughout the murine brain with a distinct caudal bias in distribution, similar to both inflammatory changes and virus antigen distribution. CCL2 immunolabelling was localized to neuronal and astroglial populations. CCL5 immunolabelling was only detected in the astroglia, while CXCL10 labelling, although present in the astroglia, was more prominent in neurons. Isolate-dependent differences in the amount of chemokine immunolabelling in specific brain regions and chemokine production by neurons in vitro were observed, with a greater expression of CCL5 in vivo and CXCL10 production in vitro after EBLV infection. Additionally, strong positive associations between chemokine immunolabelling and perivascular cuffing and, to a lesser extent, virus antigen score were also observed. These differences in chemokine expression may explain the variation in severity of encephalitic changes observed in animals infected with different lyssavirus isolates. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  19. Development of a murine model of acute radiation encephalopathy

    International Nuclear Information System (INIS)

    Xing Yigang; Tang Yamei; Liu Jun; Sun Ying

    2003-01-01

    Objective: To develop a murine model of acute radiation encephalopathy. Methods: A total of 40 rats were subjected to local γ-irradiation to the brain with the dosage of 7 Gy/d for 6 consecutive days. The amount of food intake, hairs and skin of irradiated field, body weight, general activities, CNS symptoms and signs were examined and recorded after irradiation. On day 3, 7, 14 and 30, the brain tissue was removed to observe histopathologic changes. Results: During the first two days after irradiation, the irradiated rats were agitated, and the amount of food intake decreased from day 2 onwards. No serious skin reaction to irradiation was observed. Survived rats had normal activities without any abnormal nervous signs. Histopathologic changes showed slight neuronal degeneration, smaller cell body, red-colored cytoplasm, disappearance of Nissl body, vacuolation, typical cell shrinkage, chromatin condensation and nuclear divergence. On the 14th and 30th days, hypochromatism, loose and reticular necrotic foci were found in some samples. Conclusion: The murine model of acute radiation encephalopathy is useful and practical in radiobiological studies

  20. [Nuclear matrix organization of the chromocenters in cultured murine fibroblasts].

    Science.gov (United States)

    Sheval', E V; Poliakov, V Iu

    2010-01-01

    In the current work, the structural organization of nuclear matrix of pericentromeric heterochromatin blocks (chromocenters) inside cultured murine fibroblasts was investigated. After 2 M NaCl extraction without DNase I treatment, chromocenters were extremely swelled, and it was impossible to detect them using conventional electron microscopy. Using immunogolding with anti-topoisomerase IIalpha antibody, we demonstrated that residual chromocenters were subdivided into numerous discrete aggregates. After 2 M NaCl extraction with DNase I treatment, the residual chromocenters appeared as a dense meshwork of thin fibers, and using this feature, the residual chromocenters were easily distinguished from the rest of nuclear matrix. After extraction with dextran sulfate and heparin, the chromocenters were decondensed, and chromatin complexes having rosette organization (central core from which numerous DNA fibers radiated) were seen. Probably, the appearance of these rosettes was a consequence of incomplete chromatin extraction. Thus, the nuclear matrix of pericentromeric chromosome regions in cultured murine fibroblasts differs morphologically from the rest of nuclear matrix.

  1. Effects of the murine skull in optoacoustic brain microscopy.

    Science.gov (United States)

    Kneipp, Moritz; Turner, Jake; Estrada, Héctor; Rebling, Johannes; Shoham, Shy; Razansky, Daniel

    2016-01-01

    Despite the great promise behind the recent introduction of optoacoustic technology into the arsenal of small-animal neuroimaging methods, a variety of acoustic and light-related effects introduced by adult murine skull severely compromise the performance of optoacoustics in transcranial imaging. As a result, high-resolution noninvasive optoacoustic microscopy studies are still limited to a thin layer of pial microvasculature, which can be effectively resolved by tight focusing of the excitation light. We examined a range of distortions introduced by an adult murine skull in transcranial optoacoustic imaging under both acoustically- and optically-determined resolution scenarios. It is shown that strong low-pass filtering characteristics of the skull may significantly deteriorate the achievable spatial resolution in deep brain imaging where no light focusing is possible. While only brain vasculature with a diameter larger than 60 µm was effectively resolved via transcranial measurements with acoustic resolution, significant improvements are seen through cranial windows and thinned skull experiments. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Cross-sectional area of the murine aorta linearly increases with increasing core body temperature.

    Science.gov (United States)

    Crouch, A Colleen; Manders, Adam B; Cao, Amos A; Scheven, Ulrich M; Greve, Joan M

    2017-11-06

    The cardiovascular (CV) system plays a vital role in thermoregulation. To date, the response of core vasculature to increasing core temperature has not been adequately studied in vivo. Our objective was to non-invasively quantify the arterial response in murine models due to increases in body temperature, with a focus on core vessels of the torso and investigate whether responses were dependent on sex or age. Male and female, adult and aged mice were anaesthetised and underwent magnetic resonance imaging (MRI). Data were acquired from the circle of Willis (CoW), heart, infrarenal aorta and peripheral arteries at core temperatures of 35, 36, 37 and 38 °C (±0.2 °C). Vessels in the CoW did not change. Ejection fraction decreased and cardiac output (CO) increased with increasing temperature in adult female mice. Cross-sectional area of the aorta increased significantly and linearly with temperature for all groups, but at a diminished rate for aged animals (p temperature are biologically important because they may affect conductive and convective heat transfer. Leveraging non-invasive methodology to quantify sex and age dependent vascular responses due to increasing core temperature could be combined with bioheat modelling in order to improve understanding of thermoregulation.

  3. Murine strain differences and the effects of zinc on cadmium concentrations in tissues after acute cadmium exposure

    Energy Technology Data Exchange (ETDEWEB)

    King, L.M. [ARS USDA, Germplasm and Gamete Physiology Lab., Beltsville, MD (United States); Anderson, M.B. [Dept. of Anatomy, Tulane Univ. School of Medicine, New Orleans, LA (United States); Sikka, S.C. [Dept. of Urology, Tulane Univ. School of Medicine, New Orleans, LA (United States); George, W.J. [Dept. of Pharmacology, Tulane Univ. School of Medicine, New Orleans, LA (United States)

    1998-10-01

    The role of strain differences in cadmium tissue distribution was studied using sensitive (129/J) and resistant (A/J) mice. These murine strains have previously been shown to differ in their susceptibility to cadmium-induced testicular toxicity. Cadmium concentration was measured in testis, epididymis, seminal vesicle, liver, and kidney at 24 h after cadmium chloride exposure (4, 10, and 20 {mu}mol/kg CdCl{sub 2}). The 129/J mice exhibited a significant increase in cadmium concentration in testis, epididymis, and seminal vesicle at all cadmium doses used, compared to A/J mice. However, cadmium concentrations in liver and kidney were not different between the strains, at any dose, indicating that cadmium uptake is similar in these organs at 24 h. These murine strains demonstrate similar hepatic and renal cadmium uptake but significantly different cadmium accumulation in the reproductive organs at 24 h. The mechanism of the protective effect of zinc on cadmium toxicity was studied by assessing the impact of zinc acetate (ZnAc) treatment on cadmium concentrations in 129/J mice after 24 h. Zinc pretreatment (250 {mu}mol/kg ZnAc), given 24 h prior to 20 {mu}mol/kg CdCl{sub 2} administration, significantly decreased the amount of cadmium in the testis, epididymis, and seminal vesicle of 129/J mice, and significantly increased the cadmium content of the liver after 24 h. Cadmium levels in the kidney were unaffected at this time. Zinc pretreatment also prevented the cadmium-induced decrease in testicular sperm concentration and epididymal sperm motility seen in 129/J mice. These findings suggest that the differences in the two murine strains may be attributed partly to the differential accumulation of cadmium in murine gonads. This may be caused by strain differences in the specificity of cadmium transport mechanisms. The protective role of zinc in cadmium-induced testicular toxicity in the sensitive strain may be due to an interference in the cadmium uptake by susceptible

  4. Exposure to low level GSM 935 MHz radiofrequency fields does not induce apoptosis in proliferating or differentiated murine neuroblastoma cells

    International Nuclear Information System (INIS)

    Moquet, J.; Ainsbury, E.; Bouffler, S.; Lloyd, D.

    2008-01-01

    The aim of this study was to investigate whether radiofrequency (RF) fields characteristic of mobile phones at non-thermal levels can induce apoptosis in murine neuroblastoma (N2a) cells in both proliferating and differentiated states. Cells were exposed continuously for 24 h to one of the three 935-MHz RF signals: global system for mobile communication (GSM) basic, GSM talk and a continuous wave, unmodulated signal; all at a specific energy absorption rate of 2 W kg -1 . The measured increase in temperature of the cells due to the RF fields was around 0.06 deg. C. At a number of time points between 0 and 48 h post-exposure, the cells were assessed for apoptosis under a fluorescence microscope using three independent assays: Annexin V, caspase activation and in situ end-labelling. No statistically significant differences in apoptosis levels were observed between the exposed and sham-exposed cells using the three assays at any time point post-exposure. These data suggest that RF exposures, characteristic of GSM mobile phones, do not significantly affect the apoptosis levels in proliferating and differentiated murine neuroblastoma cell line N2a. (authors)

  5. Investigations into the Immunotoxicity and Allergic Potential Induced by Topical Application of N-Butylbenzenesulfonamide (NBBS) in a Murine Model

    Science.gov (United States)

    Marrocco, Antonella; Meade, B. Jean; Long, Carrie M.; Lukomska, Ewa; Marshall, Nikki B.; Anderson, Stacey E.

    2015-01-01

    N-Butylbenzene sulfonamide (NBBS) is a commonly used plasticizer found in numerous products. Due to its extensive use, lack of adequate toxicological data, and suspicion of toxicity based on the presence of structural alerts, it was nominated to the National Toxicology Program for comprehensive toxicological testing. The purpose of this study was to evaluate the potential for hypersensitivity and immune suppression following dermal exposure to NBBS using a murine model. NBBS tested negative in a combined irritancy/local lymph node assay (LLNA), classifying it as nonirritating and nonsensitizing. To estimate the immunosuppressive potential of NBBS, assays that assessed immunotoxicity were performed, including the immumnoglobulin (Ig) M response to T-cell-dependent antigen sheep red blood cells (SRBC), using the plaque-forming cell (PFC) assay and immune cell phenotyping. After a 28-d treatment with NBBS, mice exposed to the lowest concentration (25% NBBS) showed a significant increase in IgM-producing B cells in the spleen. No marked changes were identified in immune cell markers in the lymph node. In contrast to body weight, a significant elevation in kidney and liver weight was observed following dermal exposure to all concentrations of NBBS. These results demonstrate that dermal exposure to NBBS, other than liver and kidney toxicity, did not apparently induce immunotoxicity in a murine model. PMID:26291892

  6. Protective effect of kombucha tea against tertiary butyl hydroperoxide induced cytotoxicity and cell death in murine hepatocytes.

    Science.gov (United States)

    Bhattacharya, Semantee; Manna, Prasenjit; Gachhui, Ratan; Sil, Parames C

    2011-07-01

    Kombucha (KT), a fermented black tea (BT), is known to have many beneficial properties. In the present study, antioxidant property of KT has been investigated against tertiary butyl hydroperoxide (TBHP) induced cytotoxicity using murine hepatocytes. TBHP, a reactive oxygen species inducer, causes oxidative stress resulting in organ pathophysiology. Exposure to TBHP caused a reduction in cell viability, increased membrane leakage and disturbed the intra-cellular antioxidant machineries in hepatocytes. TBHP exposure disrupted mitochondrial membrane potential and induced apoptosis as evidenced by flow cytometric analyses. KT treatment, however, counteracted the changes in mitochondrial membrane potential and prevented apoptotic cell death of the hepatocytes. BT treatment also reverted TBHP induced hepatotoxicity, however KT was found to be more efficient. This may be due to the formation of antioxidant molecules like D-saccharic acid-1,4-lactone (DSL) during fermentation process and are absent in BT. Moreover, the radical scavenging activities of KT were found to be higher than BT. Results of the study showed that KT has the potential to ameliorate TBHP induced oxidative insult and cell death in murine hepatocytes more effectively than BT.

  7. Replacement of Murine Leukemia Virus Readthrough Mechanism by Human Immunodeficiency Virus Frameshift Allows Synthesis of Viral Proteins and Virus Replication

    Science.gov (United States)

    Brunelle, Marie-Noëlle; Brakier-Gingras, Léa; Lemay, Guy

    2003-01-01

    Retroviruses use unusual recoding strategies to synthesize the Gag-Pol polyprotein precursor of viral enzymes. In human immunodeficiency virus, ribosomes translating full-length viral RNA can shift back by 1 nucleotide at a specific site defined by the presence of both a slippery sequence and a downstream stimulatory element made of an extensive secondary structure. This so-called frameshift mechanism could become a target for the development of novel antiviral strategies. A different recoding strategy is used by other retroviruses, such as murine leukemia viruses, to synthesize the Gag-Pol precursor; in this case, a stop codon is suppressed in a readthrough process, again due to the presence of a specific structure adopted by the mRNA. Development of antiframeshift agents will greatly benefit from the availability of a simple animal and virus model. For this purpose, the murine leukemia virus readthrough region was rendered inactive by mutagenesis and the frameshift region of human immunodeficiency virus was inserted to generate a chimeric provirus. This substitution of readthrough by frameshift allows the synthesis of viral proteins, and the chimeric provirus sequence was found to generate infectious viruses. This system could be a most interesting alternative to study ribosomal frameshift in the context of a virus amenable to the use of a simple animal model. PMID:12584361

  8. Rediscovering peritoneal macrophages in a murine endometriosis model.

    Science.gov (United States)

    Yuan, Ming; Li, Dong; An, Min; Li, Qiuju; Zhang, Lu; Wang, Guoyun

    2017-01-01

    What are the features of peritoneal macrophage subgroups and T helper cells in the development of murine endometriosis? During the development of endometriosis in a murine model, large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs) are polarized into M1 and M2 cells, respectively, and the proportions of T helper (Th) 1, Th17 and T regulatory (T reg ) cells are increased. Numerous studies investigating the etiology and pathogenesis of endometriosis have focused on the polarization states of peritoneal macrophages in endometriosis models and patients, but the results are inconclusive. Further studies indicate that peritoneal macrophages are composed of two distinct subsets: LPMs and SPMs, although their roles in endometriosis are unknown. This study involves a prospective and randomized experiment. Fifty C57BL/6 female mice were randomly allocated to five control and five experimental groups (n = 5/group) according to the presence or absence of transplantation. The transplant periods are 0.25, 3, 14, 28 and 42 days. C57BL/6 mice were utilized to establish an endometriosis model by i.p. injection of allogeneic endometrial segments. Dynamic changes of peritoneal macrophage subsets and polarization profiles were evaluated by flow cytometry (FCM). Macrophage morphology and density were assessed by cell counting under a microscope. Dynamic changes of Th1, Th2, Th17 and T reg cells were estimated by FCM. Peritoneal macrophages are composed of two distinct subsets: LPMs and SPMs. The proportion of SPMs increased immediately after peritoneal injection of endometrial tissues, whereas LPMs showed an opposite trend. Peritoneal macrophages differentiated into both M1 and M2 macrophages. The bidirectional polarization of macrophages was caused by the inverse trends of polarization of LPMs and SPMs. Consistently, the proportions of Th1, Th17 and T reg cells were all increased in mice with endometriosis. N/A. In this study, detection was only performed in a

  9. Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Want MY

    2017-03-01

    Full Text Available Muzamil Y Want,1 Mohammad Islammudin,1 Garima Chouhan,1 Hani A Ozbak,2 Hassan A Hemeg,2 Asoke P Chattopadhyay,3 Farhat Afrin2 1Parasite Immunology Laboratory, Department of Biotechnology, Jamia Hamdard, Hamdard University, New Delhi, India; 2Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia; 3Department of Chemistry, University of Kalyani, Kalyani, India Abstract: Visceral leishmaniasis (VL is a fatal, vector-borne disease caused by the intracellular protozoa of the genus Leishmania. Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. Association of artemisinin with liposome is a desirable strategy to circumvent the problem of poor accessibility, thereby improving its efficacy, as demonstrated in a murine model of experimental VL. Nanoliposomal artemisinin (NLA was prepared by thin-film hydration method and optimized using Box–Behnken design with a mean particle diameter of 83±16 nm, polydispersity index of 0.2±0.03, zeta potential of -27.4±5.7 mV, and drug loading of 33.2%±2.1%. Morphological study of these nanoliposomes by microscopy showed a smooth and spherical surface. The mechanism of release of artemisinin from the liposomes followed the Higuchi model in vitro. NLA was free from concomitant signs of toxicity, both ex vivo in murine macrophages and in vivo in healthy BALB/c mice. NLA significantly denigrated the intracellular infection of Leishmania donovani amastigotes and the number of infected macrophages ex vivo with an IC50 of 6.0±1.4 µg/mL and 5.1±0.9 µg/mL, respectively. Following treatment in a murine model of VL, NLA demonstrated superior efficacy compared to artemisinin with a

  10. CD8+ T Cells Contribute to the Development of Coronary Arteritis in the Lactobacillus casei Cell Wall Extract-Induced Murine Model of Kawasaki Disease.

    Science.gov (United States)

    Noval Rivas, Magali; Lee, Youngho; Wakita, Daiko; Chiba, Norika; Dagvadorj, Jargalsaikhan; Shimada, Kenichi; Chen, Shuang; Fishbein, Michael C; Lehman, Thomas J A; Crother, Timothy R; Arditi, Moshe

    2017-02-01

    Kawasaki disease (KD) is the leading cause of acquired heart disease among children in developed countries. Coronary lesions in KD in humans are characterized by an increased presence of infiltrating CD3+ T cells; however, the specific contributions of the different T cell subpopulations in coronary arteritis development remain unknown. Therefore, we sought to investigate the function of CD4+ and CD8+ T cells, Treg cells, and natural killer (NK) T cells in the pathogenesis of KD. We addressed the function of T cell subsets in KD development by using a well-established murine model of Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis. We determined which T cell subsets were required for development of KD vasculitis by using several knockout murine strains and depleting monoclonal antibodies. LCWE-injected mice developed coronary lesions characterized by the presence of inflammatory cell infiltrates. Frequently, this chronic inflammation resulted in complete occlusion of the coronary arteries due to luminal myofibroblast proliferation (LMP) as well as the development of coronary arteritis and aortitis. We found that CD8+ T cells, but not CD4+ T cells, NK T cells, or Treg cells, were required for development of KD vasculitis. The LCWE-induced murine model of KD vasculitis mimics many histologic features of the disease in humans, such as the presence of CD8+ T cells and LMP in coronary artery lesions as well as epicardial coronary arteritis. Moreover, CD8+ T cells functionally contribute to the development of KD vasculitis in this murine model. Therapeutic strategies targeting infiltrating CD8+ T cells might be useful in the management of KD in humans. © 2016, American College of Rheumatology.

  11. Forced recombination of psi-modified murine leukaemia virus-based vectors with murine leukaemia-like and VL30 murine endogenous retroviruses

    DEFF Research Database (Denmark)

    Mikkelsen, J G; Lund, Anders Henrik; Duch, M

    1999-01-01

    Co-encapsidation of retroviral RNAs into virus particles allows for the generation of recombinant proviruses through events of template switching during reverse transcription. By use of a forced recombination system based on recombinational rescue of replication- defective primer binding site-imp....... We note that recombination-based rescue of primer binding site knock-out retroviral vectors may constitute a sensitive assay to register putative genetic interactions involving endogenous retroviral RNAs present in cells of various species.......-impaired Akv-MLV-derived vectors, we here examine putative genetic interactions between vector RNAs and copackaged endogenous retroviral RNAs of the murine leukaemia virus (MLV) and VL30 retroelement families. We show (i) that MLV recombination is not blocked by nonhomology within the 5' untranslated region...... harbouring the supposed RNA dimer-forming cis -elements and (ii) that copackaged retroviral RNAs can recombine despite pronounced sequence dissimilarity at the cross-over site(s) and within parts of the genome involved in RNA dimerization, encapsidation and strand transferring during reverse transcription...

  12. The murine Cd48 gene: allelic polymorphism in the IgV-like region.

    Science.gov (United States)

    Cabrero, J G; Freeman, G J; Reiser, H

    1998-12-01

    The murine CD48 molecule is a member of the immunoglobulin superfamily which regulates the activation of T lymphocytes. prior cloning experiments using mRNA from two different mouse strains had yielded discrepant sequences within the IgV-like domain of murine CD48. To resolve this issue, we have directly sequenced genomic DNA of 10 laboratory strains and two inbred strains of wild origin. The results of our analysis reveal an allelic polymorphism within the IgV-like domain of murine CD48.

  13. Preparation of Murine Submandibular Salivary Gland for Upright Intravital Microscopy.

    Science.gov (United States)

    Ficht, Xenia; Thelen, Flavian; Stolp, Bettina; Stein, Jens V

    2018-05-07

    The submandibular salivary gland (SMG) is one of the three major salivary glands, and is of interest for many different fields of biological research, including cell biology, oncology, dentistry, and immunology. The SMG is an exocrine gland comprised of secretory epithelial cells, myofibroblasts, endothelial cells, nerves, and extracellular matrix. Dynamic cellular processes in the rat and mouse SMG have previously been imaged, mostly using inverted multi-photon microscope systems. Here, we describe a straightforward protocol for the surgical preparation and stabilization of the murine SMG in anesthetized mice for in vivo imaging with upright multi-photon microscope systems. We present representative intravital image sets of endogenous and adoptively transferred fluorescent cells, including the labeling of blood vessels or salivary ducts and second harmonic generation to visualize fibrillar collagen. In sum, our protocol allows for surgical preparation of mouse salivary glands in upright microscopy systems, which are commonly used for intravital imaging in the field of immunology.

  14. Corn silk induces nitric oxide synthase in murine macrophages.

    Science.gov (United States)

    Kim, Kyung A; Choi, Sang Kyu; Choi, Hye Seon

    2004-12-31

    Corn silk has been purified as an anticoagulant previously and the active component is a polysaccharide with a molecular mass of 135 kDa. It activates murine macrophages to induce nitric oxide synthase (NOS) and generate substantial amounts of NO in time and dose-dependent manners. It was detectable first at 15 h after stimulation by corn silk, peaked at 24 h, and undetectable by 48 h. Induction of NOS is inhibited by pyrolidine dithiocarbamate (PDTC) and genistein, an inhibitor of nuclear factor kappa B (NF-kappaB) and tyrosine kinase, respectively, indicating that iNOS stimulated by corn silk is associated with tyrosine kinase and NF-kappaB signaling pathways. IkappaB-alpha degradation was detectible at 10 min, and the level was restored at 120 min after treatment of corn silk. Corn silk induced nuclear translocation of NF-kappaB by phosphorylation and degradation of IkappaB-alpha.

  15. Flow cytometric quantification of radiation responses of murine peritoneal cells

    International Nuclear Information System (INIS)

    Tokita, N.; Raju, M.R.

    1982-01-01

    Methods have been developed to distinguish subpopulations of murine peritoneal cells, and these were applied to the measurement of early changes in peritoneal cells after irradiation. The ratio of the two major subpopulations in the peritoneal fluid, lymphocytes and macrophages, was measured rapidly by means of cell volume distribution analysis as well as by hypotonic propidium iodide (PI) staining. After irradiation, dose and time dependent changes were noted in the cell volume distributions: a rapid loss of peritoneal lymphocytes, and an increase in the mean cell volume of macrophages. The hypotonic PI staining characteristics of the peritoneal cells showed two or three distinctive G 1 peaks. The ratio of the areas of these peaks was also found to be dependent of the radiation dose and the time after irradiation. These results demonstrate that these two parameters may be used to monitor changes induced by irradiation (biological dosimetry), and to sort different peritoneal subpopulations

  16. A novel inexpensive murine model of oral chronic digitalization.

    Science.gov (United States)

    Helber, Izo; Kanashiro, Rosemeire M; Alarcon, Ernesto A; Antonio, Ednei L; Tucci, Paulo J F

    2004-01-01

    A novel inexpensive murine model of oral administration of digitoxin (100 micro g/kg per day) added to routine chow is described. Serum digitoxin levels achieved after oral (n = 5; 116 +/- 14 ng/mL) and subcutaneous (n = 5; 124 +/- 11 ng/mL) administration were similar. A significant increase in the maximal left ventricular pressure rise of treated (n = 9) compared with control (n = 6) rats (dP/dt: 8956 +/- 233 vs 7980 +/- 234 mmHg/s, respectively; P = 0.01) characterized the positive inotropic action of digitoxin. In addition, no differences were observed in treated compared with control rats with regard to the electrocardiogram and systolic and diastolic left ventricular pressures.

  17. The kin17 Protein in Murine Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Anelise C. Ramos

    2015-11-01

    Full Text Available kin17 has been described as a protein involved in the processes of DNA replication initiation, DNA recombination, and DNA repair. kin17 has been studied as a potential molecular marker of breast cancer. This work reports the detection and localization of this protein in the murine melanoma cell line B16F10-Nex2 and in two derived subclones with different metastatic potential, B16-8HR and B16-10CR. Nuclear and chromatin-associated protein fractions were analyzed, and kin17 was detected in all fractions, with an elevated concentration observed in the chromatin-associated fraction of the clone with low metastatic potential, suggesting that the kin17 expression level could be a marker of melanoma.

  18. Haemopedia: An Expression Atlas of Murine Hematopoietic Cells

    Directory of Open Access Journals (Sweden)

    Carolyn A. de Graaf

    2016-09-01

    Full Text Available Hematopoiesis is a multistage process involving the differentiation of stem and progenitor cells into distinct mature cell lineages. Here we present Haemopedia, an atlas of murine gene-expression data containing 54 hematopoietic cell types, covering all the mature lineages in hematopoiesis. We include rare cell populations such as eosinophils, mast cells, basophils, and megakaryocytes, and a broad collection of progenitor and stem cells. We show that lineage branching and maturation during hematopoiesis can be reconstructed using the expression patterns of small sets of genes. We also have identified genes with enriched expression in each of the mature blood cell lineages, many of which show conserved lineage-enriched expression in human hematopoiesis. We have created an online web portal called Haemosphere to make analyses of Haemopedia and other blood cell transcriptional datasets easier. This resource provides simple tools to interrogate gene-expression-based relationships between hematopoietic cell types and genes of interest.

  19. Macropinocytosis is the Entry Mechanism of Amphotropic Murine Leukemia Virus

    DEFF Research Database (Denmark)

    Rasmussen, Izabela; Vilhardt, Frederik

    2015-01-01

    of infection. Understanding how pathogens and toxins exploit or divert endocytosis pathways has advanced our understanding of membrane trafficking pathways, which benefits development of new therapeutical schemes and methods of drug delivery. We show here that Murine Leukemia Virus (A-MLV) pseudotyped......, or NIH-3T3 cells knocked-down for caveolin expression, was unaffected. Conversely, A-MLV infection of NIH-3T3 and HeLa cells was sensitive to amiloride analogues and actin-depolymerizing drugs that interfere with macropinocytosis. Further manipulation of the actin cytoskeleton through conditional...... with the amphotropic (expands the host range to many mammalian cells) envelope protein gains entry into host cells by macropinocytosis. Macropinosomes form as large, fluid-filled vacuoles (up to 10 μm) following collapse of cell surface protrusions and membrane scission. We use drugs or introduction of mutant proteins...

  20. Effects of trichostatins on differentiation of murine erythroleukemia cells

    International Nuclear Information System (INIS)

    Yoshida, M.; Nomura, S.; Beppu, T.

    1987-01-01

    The fungistatic antibiotics trichostatins (TS) A and C were isolated from culture broth of Streptomyces platensis No. 145 and were found to be potent inducers of differentiation in murine erythroleukemia (Friend and RV133) cells at concentrations of 1.5 X 10(-8) M for TSA and 5 X 10(-7) M for TSC. Differentiation induced by TS was cooperatively enhanced by UV irradiation but not by treatment with dimethyl sulfoxide. This enhanced activity was completely inhibited by adding cycloheximide to the culture medium 2 h after exposure to TS, suggesting that TS are dimethyl sulfoxide-type inducers of erythroid differentiation. No inhibitory effect of TS was observed on macromolecular synthesis in cultured cells

  1. First transplantation of isolated murine follicles in alginate.

    Science.gov (United States)

    Vanacker, Julie; Dolmans, Marie-Madeleine; Luyckx, Valérie; Donnez, Jacques; Amorim, Christiani A

    2014-01-01

    Our aim is to develop an artificial ovary allowing survival and growth of isolated follicles and ovarian cells, to restore fertility in women diagnosed with pathologies at high risk of ovarian involvement. For this, alginate beads containing isolated preantral follicles and ovarian cells were autografted to immunocompetent mice. One week after grafting, the beads were invaded by proliferating murine cells (12.1%) and capillaries. The recovery rate of follicles per graft ranged from 0% to 35.5%. Of the analyzed follicles, 77% were Ki67-positive and 81%, TUNEL-negative. Three antral follicles were also identified, evidencing their ability to grow in the matrix. Our results suggest that an artificial ovary is now conceivable, opening new perspectives to restore fertility in women.

  2. Gene expression in IFN-g-activated murine macrophages

    Directory of Open Access Journals (Sweden)

    Pereira C.A.

    2004-01-01

    Full Text Available Macrophages are critical for natural immunity and play a central role in specific acquired immunity. The IFN-gamma activation of macrophages derived from A/J or BALB/c mice yielded two different patterns of antiviral state in murine hepatitis virus 3 infection, which were related to a down-regulation of the main virus receptor. Using cDNA hybridization to evaluate mRNA accumulation in the cells, we were able to identify several genes that are differently up- or down-regulated by IFN-gamma in A/J (267 and 266 genes, respectively, up- and down-regulated or BALB/c (297 and 58 genes, respectively, up- and down-regulated mouse macrophages. Macrophages from mice with different genetic backgrounds behave differently at the molecular level and comparison of the patterns of non-activated and IFN-gamma-activated A/J or BALB/c mouse macrophages revealed, for instance, an up-regulation and a down-regulation of genes coding for biological functions such as enzymatic reactions, nucleic acid synthesis and transport, protein synthesis, transport and metabolism, cytoskeleton arrangement and extracellular matrix, phagocytosis, resistance and susceptibility to infection and tumors, inflammation, and cell differentiation or activation. The present data are reported in order to facilitate future correlation of proteomic/transcriptomic findings as well as of results obtained from a classical approach for the understanding of biological phenomena. The possible implication of the role of some of the gene products relevant to macrophage biology can now be further scrutinized. In this respect, a down-regulation of the main murine hepatitis virus 3 receptor gene was detected only in IFN-gamma-activated macrophages of resistant mice.

  3. Significant reduction of peripheral blood interleukin-35 and CD4+EBI3+ T cells, which are negatively correlated with an increase in the plasma IL-17 and cTnI level, in viral myocarditis patients

    Directory of Open Access Journals (Sweden)

    Han Ouyang

    2017-02-01

    Full Text Available Introduction: Viral myocarditis (VMC has become an increasingly common heart disease that endangers human health. In the present study, the plasma interleukin-35 (IL-35 level and the percentage of CD4 + EBI3 + T cells in VMC patients were detected to investigate the significance of changes in these parameters in the plasma of VMC patients and their association with the disease. Material and methods: ELISA was performed to detect the plasma IL-35 level and the percentage of peripheral blood CD4 + EBI3 + T cells in 40 VMC patients and in 20 healthy individuals. Moreover, the plasma IL-17 levels in the VMC patients and in the healthy individuals were detected using an ELISA, and the cardiac Troponin-I (cTnI levels were detected using a chemiluminescent microparticle immunoassay to compare the differences in the groups. Results : Plasma IL-35 level and the percentage of CD4 + EBI3 + T cells in acute phase VMC patients was lower than that in the healthy control group and the convalescent phase VMC patients. Additionally, the plasma IL-35 level in the VMC patients exhibited a negative correlation with the levels of cTnI and IL-17. The percentage of CD4 + EBI3 + T cells also showed a negative correlation with the levels of cTnI and IL-17. Conclusions : The plasma IL-35 level and the percentage of CD4 + EBI3 + T cells in VMC patients was reduced, and the amount of the decrease was associated with the severity of the disease. These results suggest that IL-35 and CD4 + EBI3 + T might play important roles in the progression of VMC and could be used as indictors of the disease.

  4. Induction of murine embryonic stem cell differentiation by medicinal plant extracts

    Energy Technology Data Exchange (ETDEWEB)

    Reynertson, Kurt A. [Center for Complementary and Integrative Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Charlson, Mary E. [Center for Complementary and Integrative Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu [Center for Complementary and Integrative Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States); Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065 (United States)

    2011-01-01

    Epidemiological evidence indicates that diets high in fruits and vegetables provide a measure of cancer chemoprevention due to phytochemical constituents. Natural products are a rich source of cancer chemotherapy drugs, and primarily target rapidly cycling tumor cells. Increasing evidence indicates that many cancers contain small populations of resistant, stem-like cells that have the capacity to regenerate tumors following chemotherapy and radiation, and have been linked to the initiation of metastases. Our goal is to discover natural product-based clinical or dietary interventions that selectively target cancer stem cells, inducing differentiation. We adapted an alkaline phosphatase (AP) stain to assay plant extracts for the capacity to induce differentiation in embryonic stem (ES) cells. AP is a characteristic marker of undifferentiated ES cells, and this represents a novel approach to screening medicinal plant extracts. Following a survey of approximately 100 fractions obtained from 12 species of ethnomedically utilized plants, we found fractions from 3 species that induced differentiation, decreasing AP and transcript levels of pluripotency markers (Nanog, Oct-4, Rex-1). These fractions affected proliferation of murine ES, and human embryonal, prostate, and breast carcinoma cells in a dose-dependent manner. Several phytochemical constituents were isolated; the antioxidant phytochemicals ellagic acid and gallic acid were shown to affect viability of cultured breast carcinoma cells.

  5. Fungi of the murine gut: episodic variation and proliferation during antibiotic treatment.

    Directory of Open Access Journals (Sweden)

    Serena Dollive

    Full Text Available Antibiotic use in humans has been associated with outgrowth of fungi. Here we used a murine model to investigate the gut microbiome over 76 days of treatment with vancomycin, ampicillin, neomycin, and metronidazole and subsequent recovery. Mouse stool was studied as a surrogate for the microbiota of the lower gastrointestinal tract. The abundance of fungi and bacteria was measured using quantitative PCR, and the proportional composition of the communities quantified using 454/Roche pyrosequencing of rRNA gene tags. Prior to treatment, bacteria outnumbered fungi by >3 orders of magnitude. Upon antibiotic treatment, bacteria dropped in abundance >3 orders of magnitude, so that the predominant 16S sequences detected became transients derived from food. Upon cessation of treatment, bacterial communities mostly returned to their previous numbers and types after 8 weeks, though communities remained detectably different from untreated controls. Fungal communities varied substantially over time, even in the untreated controls. Separate cages within the same treatment group showed radical differences, but mice within a cage generally behaved similarly. Fungi increased ∼40-fold in abundance upon antibiotic treatment but declined back to their original abundance after cessation of treatment. At the last time point, Candida remained more abundant than prior to treatment. These data show that 1 gut fungal populations change radically during normal mouse husbandry, 2 fungi grow out in the gut upon suppression of bacterial communities with antibiotics, and 3 perturbations due to antibiotics persist long term in both the fungal and bacterial microbiota.

  6. The acute exposure effects of inhaled nickel nanoparticles on murine endothelial progenitor cells.

    Science.gov (United States)

    Liberda, Eric N; Cuevas, Azita K; Qu, Qingshan; Chen, Lung Chi

    2014-08-01

    The discovery of endothelial progenitor cells (EPCs) may help to explain observed cardiovascular effects associated with inhaled nickel nanoparticle exposures, such as increases in vascular inflammation, generation of reactive oxygen species, altered vasomotor tone and potentiated atherosclerosis in murine species. Following an acute whole body inhalation exposure to 500 µg/m(3) of nickel nanoparticles for 5 h, bone marrow EPCs from C57BL/6 mice were isolated. EPCs were harvested for their RNA or used in a variety of assays including chemotaxis, tube formation and proliferation. Gene expression was assessed for important receptors involved in EPC mobilization and homing using RT-PCR methods. EPCs, circulating endothelial progenitor cells (CEPCs), circulating endothelial cells (CECs) and endothelial microparticles (EMPs) were quantified on a BD FACSCalibur to examine endothelial damage and repair associated with the exposure. Acute exposure to inhaled nickel nanoparticles significantly increased both bone marrow EPCs as well as their levels in circulation (CEPCs). CECs were significantly elevated indicating that endothelial damage occurred due to the exposure. There was no significant difference in EMPs between the two groups. Tube formation and chemotaxis, but not proliferation, of bone marrow EPCs was impaired in the nickel nanoparticle exposed group. These results coincided with a decrease in the mRNA of receptors involved in EPC mobilization and homing. These data provide new insight into how an acute nickel nanoparticle exposure to half of the current Occupational Safety & Health Administration (OSHA) permissible exposure limit may adversely affect EPCs and exacerbate cardiovascular disease states.

  7. Prospective Isolation of Murine and Human Bone Marrow Mesenchymal Stem Cells Based on Surface Markers

    Directory of Open Access Journals (Sweden)

    Yo Mabuchi

    2013-01-01

    Full Text Available Mesenchymal stem cells (MSCs are currently defined as multipotent stromal cells that undergo sustained in vitro growth and can give rise to cells of multiple mesenchymal lineages, such as adipocytes, chondrocytes, and osteoblasts. The regenerative and immunosuppressive properties of MSCs have led to numerous clinical trials exploring their utility for the treatment of a variety of diseases (e.g., acute graft-versus-host disease, Crohn’s disease, multiple sclerosis, osteoarthritis, and cardiovascular diseases including heart failure and myocardial infarction. On the other hand, conventionally cultured MSCs reflect heterogeneous populations that often contain contaminating cells due to the significant variability in isolation methods and the lack of specific MSC markers. This review article focuses on recent developments in the MSC research field, with a special emphasis on the identification of novel surface markers for the in vivo localization and prospective isolation of murine and human MSCs. Furthermore, we discuss the physiological importance of MSC subtypes in vivo with specific reference to data supporting their contribution to HSC niche homeostasis. The isolation of MSCs using selective markers (combination of PDGFRα and Sca-1 is crucial to address the many unanswered questions pertaining to these cells and has the potential to enhance their therapeutic potential enormously.

  8. Different concentrations of kaempferol distinctly modulate murine embryonic stem cell function.

    Science.gov (United States)

    Correia, Marcelo; Rodrigues, Ana S; Perestrelo, Tânia; Pereira, Sandro L; Ribeiro, Marcelo F; Sousa, Maria I; Ramalho-Santos, João

    2016-01-01

    Kaempferol (3,4',5,7-tetrahydroxyflavone) is a natural flavonoid with several beneficial and protective effects. It has been demonstrated that kaempferol has anticancer properties, particularly due to its effects on proliferation, apoptosis and the cell cycle. However, possible effects on pluripotent embryonic stem cell function have not yet been addressed. Embryonic stem cells have the ability to self-renew and to differentiate into all three germ layers with potential applications in regenerative medicine and in vitro toxicology. We show that exposure of murine embryonic stem cells (mESC) to high concentrations of kaempferol (200 μM) leads to decreased cell numbers, although the resulting smaller cell colonies remain pluripotent. However, lower concentrations of this compound (20 μM) increase the expression of pluripotency markers in mESCs. Mitochondrial membrane potential and mitochondrial mass are not affected, but a dose-dependent increase in apoptosis takes place. Moreover, mESC differentiation is impaired by kaempferol, which was not related to apoptosis induction. Our results show that low concentrations of kaempferol can be beneficial for pluripotency, but inhibit proper differentiation of mESCs. Additionally, high concentrations induce apoptosis and increase mitochondrial reactive oxygen species (ROS). Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Cyclooxygenase-2 inhibition blocks M2 macrophage differentiation and suppresses metastasis in murine breast cancer model.

    Directory of Open Access Journals (Sweden)

    Yi-Rang Na

    Full Text Available Tumor cells are often associated with abundant macrophages that resemble the alternatively activated M2 subset. Tumor-associated macrophages (TAMs inhibit anti-tumor immune responses and promote metastasis. Cyclooxygenase-2 (COX-2 inhibition is known to prevent breast cancer metastasis. This study hypothesized that COX-2 inhibition affects TAM characteristics potentially relevant to tumor cell metastasis. We found that the specific COX-2 inhibitor, etodolac, inhibited human M2 macrophage differentiation, as determined by decreased CD14 and CD163 expressions and increased TNFα production. Several key metastasis-related mediators, such as vascular endothelial growth factor-A, vascular endothelial growth factor-C, and matrix metalloproteinase-9, were inhibited in the presence of etodolac as compared to untreated M2 macrophages. Murine bone marrow derived M2 macrophages also showed enhanced surface MHCII IA/IE and CD80, CD86 expressions together with enhanced TNFα expressions with etodolac treatment during differentiation. Using a BALB/c breast cancer model, we found that etodolac significantly reduced lung metastasis, possibly due to macrophages expressing increased IA/IE and TNFα, but decreased M2 macrophage-related genes expressions (Ym1, TGFβ. In conclusion, COX-2 inhibition caused loss of the M2 macrophage characteristics of TAMs and may assist prevention of breast cancer metastasis.

  10. Essential role of the TFIID subunit TAF4 in murine embryogenesis and embryonic stem cell differentiation.

    Science.gov (United States)

    Langer, Diana; Martianov, Igor; Alpern, Daniel; Rhinn, Muriel; Keime, Céline; Dollé, Pascal; Mengus, Gabrielle; Davidson, Irwin

    2016-03-30

    TAF4 (TATA-binding protein-associated factor 4) and its paralogue TAF4b are components of the TFIID core module. We inactivated the murine Taf4a gene to address Taf4 function during embryogenesis. Here we show that Taf4a(-/-) embryos survive until E9.5 where primary germ layers and many embryonic structures are identified showing Taf4 is dispensable for their specification. In contrast, Taf4 is required for correct patterning of the trunk and anterior structures, ventral morphogenesis and proper heart positioning. Overlapping expression of Taf4a and Taf4b during embryogenesis suggests their redundancy at early stages. In agreement with this, Taf4a(-/-) embryonic stem cells (ESCs) are viable and comprise Taf4b-containing TFIID. Nevertheless, Taf4a(-/-) ESCs do not complete differentiation into glutamatergic neurons and cardiomyocytes in vitro due to impaired preinitiation complex formation at the promoters of critical differentiation genes. We define an essential role of a core TFIID TAF in differentiation events during mammalian embryogenesis.

  11. A Novel Polyaminocarboxylate Compound To Treat Murine Pulmonary Aspergillosis by Interfering with Zinc Metabolism.

    Science.gov (United States)

    Laskaris, Paris; Vicentefranqueira, Rocío; Helynck, Olivier; Jouvion, Grégory; Calera, José Antonio; du Merle, Laurence; Suzenet, Franck; Buron, Frédéric; de Sousa, Rodolphe Alves; Mansuy, Daniel; Cavaillon, Jean-Marc; Latgé, Jean-Paul; Munier-Lehmann, Hélène; Ibrahim-Granet, Oumaima

    2018-06-01

    Aspergillus fumigatus can cause pulmonary aspergillosis in immunocompromised patients and is associated with a high mortality rate due to a lack of reliable treatment options. This opportunistic pathogen requires zinc in order to grow and cause disease. Novel compounds that interfere with fungal zinc metabolism may therefore be of therapeutic interest. We screened chemical libraries containing 59,223 small molecules using a resazurin assay that compared their effects on an A. fumigatus wild-type strain grown under zinc-limiting conditions and on a zinc transporter knockout strain grown under zinc-replete conditions to identify compounds affecting zinc metabolism. After a first screen, 116 molecules were selected whose inhibitory effects on fungal growth were further tested by using luminescence assays and hyphal length measurements to confirm their activity, as well as by toxicity assays on HeLa cells and mice. Six compounds were selected following a rescreening, of which two were pyrazolones, two were porphyrins, and two were polyaminocarboxylates. All three groups showed good in vitro activity, but only one of the polyaminocarboxylates was able to significantly improve the survival of immunosuppressed mice suffering from pulmonary aspergillosis. This two-tier screening approach led us to the identification of a novel small molecule with in vivo fungicidal effects and low murine toxicity that may lead to the development of new treatment options for fungal infections by administration of this compound either as a monotherapy or as part of a combination therapy. Copyright © 2018 American Society for Microbiology.

  12. ALDH2(E487K) mutation increases protein turnover and promotes murine hepatocarcinogenesis.

    Science.gov (United States)

    Jin, Shengfang; Chen, Jiang; Chen, Lizao; Histen, Gavin; Lin, Zhizhong; Gross, Stefan; Hixon, Jeffrey; Chen, Yue; Kung, Charles; Chen, Yiwei; Fu, Yufei; Lu, Yuxuan; Lin, Hui; Cai, Xiujun; Yang, Hua; Cairns, Rob A; Dorsch, Marion; Su, Shinsan M; Biller, Scott; Mak, Tak W; Cang, Yong

    2015-07-21

    Mitochondrial aldehyde dehydrogenase 2 (ALDH2) in the liver removes toxic aldehydes including acetaldehyde, an intermediate of ethanol metabolism. Nearly 40% of East Asians inherit an inactive ALDH2*2 variant, which has a lysine-for-glutamate substitution at position 487 (E487K), and show a characteristic alcohol flush reaction after drinking and a higher risk for gastrointestinal cancers. Here we report the characterization of knockin mice in which the ALDH2(E487K) mutation is inserted into the endogenous murine Aldh2 locus. These mutants recapitulate essentially all human phenotypes including impaired clearance of acetaldehyde, increased sensitivity to acute or chronic alcohol-induced toxicity, and reduced ALDH2 expression due to a dominant-negative effect of the mutation. When treated with a chemical carcinogen, these mutants exhibit increased DNA damage response in hepatocytes, pronounced liver injury, and accelerated development of hepatocellular carcinoma (HCC). Importantly, ALDH2 protein levels are also significantly lower in patient HCC than in peritumor or normal liver tissues. Our results reveal that ALDH2 functions as a tumor suppressor by maintaining genomic stability in the liver, and the common human ALDH2 variant would present a significant risk factor for hepatocarcinogenesis. Our study suggests that the ALDH2*2 allele-alcohol interaction may be an even greater human public health hazard than previously appreciated.

  13. Induction of murine embryonic stem cell differentiation by medicinal plant extracts.

    Science.gov (United States)

    Reynertson, Kurt A; Charlson, Mary E; Gudas, Lorraine J

    2011-01-01

    Epidemiological evidence indicates that diets high in fruits and vegetables provide a measure of cancer chemoprevention due to phytochemical constituents. Natural products are a rich source of cancer chemotherapy drugs, and primarily target rapidly cycling tumor cells. Increasing evidence indicates that many cancers contain small populations of resistant, stem-like cells that have the capacity to regenerate tumors following chemotherapy and radiation, and have been linked to the initiation of metastases. Our goal is to discover natural product-based clinical or dietary interventions that selectively target cancer stem cells, inducing differentiation. We adapted an alkaline phosphatase (AP) stain to assay plant extracts for the capacity to induce differentiation in embryonic stem (ES) cells. AP is a characteristic marker of undifferentiated ES cells, and this represents a novel approach to screening medicinal plant extracts. Following a survey of approximately 100 fractions obtained from 12 species of ethnomedically utilized plants, we found fractions from 3 species that induced differentiation, decreasing AP and transcript levels of pluripotency markers (Nanog, Oct-4, Rex-1). These fractions affected proliferation of murine ES, and human embryonal, prostate, and breast carcinoma cells in a dose-dependent manner. Several phytochemical constituents were isolated; the antioxidant phytochemicals ellagic acid and gallic acid were shown to affect viability of cultured breast carcinoma cells. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. JNK inhibition reduces apoptosis and neovascularization in a murine model of age-related macular degeneration.

    Science.gov (United States)

    Du, Hongjun; Sun, Xufang; Guma, Monica; Luo, Jing; Ouyang, Hong; Zhang, Xiaohui; Zeng, Jing; Quach, John; Nguyen, Duy H; Shaw, Peter X; Karin, Michael; Zhang, Kang

    2013-02-05

    Age-related macular degeneration (AMD) is the leading cause of registered blindness among the elderly and affects over 30 million people worldwide. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in pathogenesis of AMD. In advanced wet AMD, although, most of the severe vision loss is due to bleeding and exudation of choroidal neovascularization (CNV), and it is well known that vascular endothelial growth factor (VEGF) plays a pivotal role in the growth of the abnormal blood vessels. VEGF suppression therapy improves visual acuity in AMD patients. However, there are unresolved issues, including safety and cost. Here we show that mice lacking c-Jun N-terminal kinase 1 (JNK1) exhibit decreased inflammation, reduced CNV, lower levels of choroidal VEGF, and impaired choroidal macrophage recruitment in a murine model of wet AMD (laser-induced CNV). Interestingly, we also detected a substantial reduction in choroidal apoptosis of JNK1-deficient mice. Intravitreal injection of a pan-caspase inhibitor reduced neovascularization in the laser-induced CNV model, suggesting that apoptosis plays a role in laser-induced pathological angiogenesis. Intravitreal injection of a specific JNK inhibitor decreased choroidal VEGF expression and reduced pathological CNV. These results suggest that JNK1 plays a key role in linking oxidative stress, inflammation, macrophage recruitment apoptosis, and VEGF production in wet AMD and pharmacological JNK inhibition offers a unique and alternative avenue for prevention and treatment of AMD.

  15. Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis.

    Science.gov (United States)

    Chen, Wei; Zhang, Xiaobo; Liu, Mimi; Zhang, Jingna; Ye, Ya; Lin, Ying; Luyckx, Jacques; Qu, Jia

    2009-09-01

    The disaccharide trehalose is a key element involved in anhydrobiosis (the capability of surviving almost complete dehydration) in many organisms. Its presence also confers resistance to desiccation and high osmolarity in bacterial and human cells by protecting proteins and membranes from denaturation. The present study used a novel murine dry eye model induced by controlled low-humidity air velocity to determine whether topically applied trehalose could heal ocular surface epithelial disorders caused by ocular surface desiccation. In addition, the efficacy of 87.6 mM trehalose eyedrops was compared with that of 20% serum, the efficacy of which has been well documented. Mice ocular surface epithelial disorders were induced by exposure of murine eyes to continuous controlled low-humidity air velocity in an intelligently controlled environmental system (ICES) for 21 days, which accelerated the tear evaporation. The mice were then randomized into three groups: the control group received PBS (0.01 M) treatment; a second group received 87.6 mM trehalose eyedrops treatment; and the third group received mice serum eyedrops treatment. Each treatment was administered as a 10 microl dose every 6 h for 14 days. The resultant changes in corneal barrier function and histopathologic examination of cornea and conjunctiva were analyzed and the level of apoptosis on the ocular surface was assessed using active caspase-3. After 14 days of treatment, the corneal fluorescein staining area, the ruffling and desquamating cells on the apical corneal epithelium, as well as the apoptotic cells on ocular surface epithelium had significantly reduced in eyes treated with trehalose compared with those treated with serum and PBS. In contrast, after 14 days of treatment, improvements in the thickness of the corneal epithelium, the squamous metaplasia in conjunctival epithelium and the number of goblet cells of the conjunctiva were less marked in eyes treated with trehalose compared with serum

  16. Chimeric anti-tenascin antibody 81C6: Increased tumor localization compared with its murine parent

    International Nuclear Information System (INIS)

    Zalutsky, Michael R.; Archer, Gary E.; Garg, Pradeep K.; Batra, Surinder K.; Bigner, Darell D.

    1996-01-01

    When labeled using the Iodogen method, a chimeric antibody composed of the human IgG 2 constant region and the variable regions of murine anti-tenascin 81C6 exhibited superior uptake in human glioma xenografts compared with its murine parent. In the current study, three paired-label experiments were performed in athymic mice with subcutaneous D-54 MG human glioma xenografts to evaluate further the properties of radioiodinated chimeric 81C6. These studies demonstrated that (a) the enhanced tumor uptake of chimeric 81C6 is specific; (b) when labeling was performed using N-succinimidyl 3-iodobenzoate, chimeric 81C6 again showed preferential accumulation in tumor compared with murine 81C6; and (c) the tumor uptake advantage observed previously with murine 81C6 for N-succinimidyl 3-iodobenzoate compared with Iodogen labeling did not occur with chimeric 81C6

  17. Responses of the Murine Myeloid Colony-Forming Cell to Ansamycin Antibiotics

    Science.gov (United States)

    Horoszewicz, Julius S.; Carter, William A.

    1974-01-01

    The in vitro susceptibility of murine myeloid colony-forming cells to the antiproliferative activities of three ansamycin antibiotics was determined. These cells were found to be 10- to 40-fold more susceptible than the corresponding human ones. PMID:4151701

  18. Diagnosing hypoxia in murine models of rheumatoid arthritis from reflectance multispectral images

    Science.gov (United States)

    Glinton, Sophie; Naylor, Amy J.; Claridge, Ela

    2017-07-01

    Spectra computed from multispectral images of murine models of Rheumatoid Arthritis show a characteristic decrease in reflectance within the 600-800nm region which is indicative of the reduction in blood oxygenation and is consistent with hypoxia.

  19. A fluorescence model of the murine lung for optical detection of pathogenic bacteria

    Science.gov (United States)

    Durkee, Madeleine S.; Cirillo, Jeffrey D.; Maitland, Kristen C.

    2017-07-01

    We present a computer model of intravital excitation and external fluorescence detection in the murine lungs validated with a three-dimensional lung tissue phantom. The model is applied to optical detection of pulmonary tuberculosis infection.

  20. Radiobiological studies on target cell populations in murine bone marrow transplantation recipients.

    NARCIS (Netherlands)

    van Os, Ronald Peter

    1994-01-01

    The experiments presented in this thesis were designed to investigate the role of total body irradiation (TBI) in conditioning murine recipients of syngeneic and allogeneic bone marrow transplantation (BMT). ... Zie: Summary

  1. Acute lethal toxicity following passive immunization for treatment of murine cryptococcosis.

    OpenAIRE

    Savoy, A C; Lupan, D M; Manalo, P B; Roberts, J S; Schlageter, A M; Weinhold, L C; Kozel, T R

    1997-01-01

    Passive immunization with monoclonal antibodies (MAbs) specific for the major capsular polysaccharide of Cryptococcus neoformans alters the course of murine cryptococcosis. During studies of passive immunization for treatment of murine cryptococcosis, we noted the occurrence of an acute, lethal toxicity. Toxicity was characterized by scratching, lethargy, respiratory distress, collapse, and death within 20 to 60 min after injection of antibody. The toxic effect was observed only in mice with ...

  2. Murine scid cells complement ataxia-telangiectasia cells and show a normal port-irradiation response of DNA synthesis

    International Nuclear Information System (INIS)

    Komatsu, K.; Yoshida, M.; Okumura, Y.

    1993-01-01

    The murine severe combined immunodeficient mutation (scid) is characterized by a lack of both B and T cells, due to a deficit in lymphoid variable-(diversity)-joining (V(D)J) rearrangement. Scid cells are highly sensitive to both radiation-induced killing and chromosomal aberrations. Significantly reduced D 0 and n values were demonstrated in scid cells and were similar to ataxia-telangiectasia (AT) cells (a unique human disease conferring whole body radiosensitivity). However, the kinetics of DNA synthesis after irradiation were different between the two cell types. In contrast with the radioresistant DNA synthesis of AT cells, DNA synthesis of scid cells was markedly inhibited after irradiation. The existence of different mutations was also supported by evidence of complementation in somatic cell hybrids between scid cells and AT cells. Results indicate that the radiobiological character of scid is similar to AT but is presumably caused by different mechanisms. (author)

  3. Behavior of a cloned murine interferon alpha/beta receptor expressed in homospecific or heterospecific background.

    Science.gov (United States)

    Uzé, G; Lutfalla, G; Bandu, M T; Proudhon, D; Mogensen, K E

    1992-05-15

    A murine interferon (IFN) alpha/beta receptor was cloned from the IFN-sensitive L1210 cell line on the basis of its homology with the human receptor. A combination of methods that includes the screening of random-primed and oligo(dT)-primed cDNA libraries and polymerase chain reactions with a single-side specificity was used. At the amino acid level, the murine IFN-alpha/beta shows 46% identity with its human counterpart. Both human WISH cells presenting a low sensitivity to mouse IFN and a murine L1210 mutant subline that does not express the receptor have been stably transfected with the murine IFN-alpha/beta receptor. Whereas transfected human cells became sensitive to a limited number of mouse IFN-alpha/beta subtypes, the transfected murine L1210 mutant was found to be fully complemented and became sensitive to all mouse IFN-alpha/beta subtypes tested, including those that were not active on transfected human cells. These results strongly suggest that the receptor described here is implicated in the mediation of the activities of all murine IFN-alpha/beta subtypes.

  4. Handling stress may confound murine gut microbiota studies

    Directory of Open Access Journals (Sweden)

    Cary R. Allen-Blevins

    2017-01-01

    Full Text Available Background Accumulating evidence indicates interactions between human milk composition, particularly sugars (human milk oligosaccharides or HMO, the gut microbiota of human infants, and behavioral effects. Some HMO secreted in human milk are unable to be endogenously digested by the human infant but are able to be metabolized by certain species of gut microbiota, including Bifidobacterium longum subsp. infantis (B. infantis, a species sensitive to host stress (Bailey & Coe, 2004. Exposure to gut bacteria like B. infantisduring critical neurodevelopment windows in early life appears to have behavioral consequences; however, environmental, physical, and social stress during this period can also have behavioral and microbial consequences. While rodent models are a useful method for determining causal relationships between HMO, gut microbiota, and behavior, murine studies of gut microbiota usually employ oral gavage, a technique stressful to the mouse. Our aim was to develop a less-invasive technique for HMO administration to remove the potential confound of gavage stress. Under the hypothesis that stress affects gut microbiota, particularly B. infantis, we predicted the pups receiving a prebiotic solution in a less-invasive manner would have the highest amount of Bifidobacteria in their gut. Methods This study was designed to test two methods, active and passive, of solution administration to mice and the effects on their gut microbiome. Neonatal C57BL/6J mice housed in a specific-pathogen free facility received increasing doses of fructooligosaccharide (FOS solution or deionized, distilled water. Gastrointestinal (GI tracts were collected from five dams, six sires, and 41 pups over four time points. Seven fecal pellets from unhandled pups and two pellets from unhandled dams were also collected. Qualitative real-time polymerase chain reaction (qRT-PCR was used to quantify and compare the amount of Bifidobacterium, Bacteroides, Bacteroidetes, and

  5. Assessment of carbon nanoparticle exposure on murine macrophage function

    Science.gov (United States)

    Suro-Maldonado, Raquel M.

    There is growing concern about the potential cytotoxicity of nanoparticles. Exposure to respirable ultrafine particles (2.5uM) can adversely affect human health and have been implicated with episodes of increased respiratory diseases such as asthma and allergies. Nanoparticles are of particular interest because of their ability to penetrate into the lung and potentially elicit health effects triggering immune responses. Nanoparticles are structures and devises with length scales in the 1 to 100-nanometer range. Black carbon (BC) nanoparticles have been observed to be products of combustion, especially flame combustion and multi-walled carbon nanotubes (MWCNT) have been shown to be found in both indoor and outdoor air. Furthermore, asbestos, which have been known to cause mesothelioma as well as lung cancer, have been shown to be structurally identical to MWCNTs. The aims of these studies were to examine the effects of carbon nanoparticles on murine macrophage function and clearance mechanisms. Macrophages are immune cells that function as the first line of defense against invading pathogens and are likely to be amongst the first cells affected by nanoparticles. Our research focused on two manufactured nanoparticles, MWCNT and BC. The two were tested against murine-derived macrophages in a chronic contact model. We hypothesized that long-term chronic exposure to carbon nanoparticles would decrease macrophages ability to effectively respond to immunological challenge. Production of nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), cell surface macrophage; activation markers, reactive oxygen species formation (ROS), and antigen processing and presentation were examined in response to lipopolysaccharide (LPS) following a 144hr exposure to the particulates. Data demonstrated an increase in TNF-alpha, and NO production; a decrease in phagocytosis and antigen processing and presentation; and a decrease in the expression levels of cell surface macrophage

  6. Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Lingling [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Zhao, Yingmin [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Gu, Xin; Wang, Jijun; Pang, Lei; Zhang, Yanqing; Li, Yaoyao; Jia, Xiaoqin; Wang, Xin [Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Gu, Jian [Department of Hematology, Yangzhou University School of Clinical Medicine, Yangzhou 225001 (China); Yu, Duonan, E-mail: duonan@yahoo.com [Department of Pediatrics, Jingjiang People' s Hospital, Yangzhou University, Jingjiang 214500 (China); Noncoding RNA Center, Yangzhou University, Yangzhou 225001 (China); Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Disease, Yangzhou 225001 (China); Institute of Comparative Medicine, Yangzhou University, Yangzhou 225001 (China); Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis, Yangzhou 225001 (China)

    2016-06-10

    Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment. - Highlights: • LPS alone in culture is required for the proliferation of murine myeloid tumor cells. • Bone marrow stromal cells as a feeder layer is also required for the proliferation of myeloid tumor cells. • However, the growth of myeloid tumor cells is inhibited when LPS and stromal cells are both available in culture. • Thus LPS can either facilitate or attenuate tumor growth through its direct effect or modulation of tumor microenvironment.

  7. Dual effect of LPS on murine myeloid leukemia cells: Pro-proliferation and anti-proliferation

    International Nuclear Information System (INIS)

    Yu, Lingling; Zhao, Yingmin; Gu, Xin; Wang, Jijun; Pang, Lei; Zhang, Yanqing; Li, Yaoyao; Jia, Xiaoqin; Wang, Xin; Gu, Jian; Yu, Duonan

    2016-01-01

    Modification of the bone marrow microenvironment is considered as a promising strategy to control leukemic cell proliferation, diseases progression and relapse after treatment. However, due to the diversity and complexity of the cellular and molecular compartments in the leukemic microenvironment, it is extremely difficult to dissect the role of each individual molecule or cell type in vivo. Here we established an in vitro system to dissect the role of lipopolysaccharide (LPS), stromal cells and endothelial cells in the growth of mouse myeloid tumor cells and B-lymphoma cells. We found that either LPS or bone marrow stromal cells as a feeder layer in culture is required for the proliferation of myeloid tumor cells. Surprisingly, the growth of myeloid leukemic cells on stromal cells is strongly inhibited when coupled with LPS in culture. This opposing effect of LPS, a complete switch from pro-proliferation to antitumor growth is due, at least in part, to the rapidly increased production of interleukin 12, Fas ligand and tissue inhibitor of metalloproteinases-2 from stromal cells stimulated by LPS. These results demonstrate that LPS can either facilitate or attenuate tumor cell proliferation, thus changing the disease course of myeloid leukemias through its direct effect or modulation of the tumor microenvironment. - Highlights: • LPS alone in culture is required for the proliferation of murine myeloid tumor cells. • Bone marrow stromal cells as a feeder layer is also required for the proliferation of myeloid tumor cells. • However, the growth of myeloid tumor cells is inhibited when LPS and stromal cells are both available in culture. • Thus LPS can either facilitate or attenuate tumor growth through its direct effect or modulation of tumor microenvironment.

  8. Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease

    Directory of Open Access Journals (Sweden)

    Muneer G. Hasham

    2017-03-01

    Full Text Available Systemic autoimmune diseases such as systemic lupus erythematosus (SLE and rheumatoid arthritis (RA show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8 agonist Resiquimod. We observe a cardiac phenotype reminiscent of autoimmune-mediated dilated cardiomyopathy, and identify auto-antibodies as major contributors to cardiac tissue damage. Resiquimod-induced heart disease is a highly relevant mouse model for mechanistic and therapeutic studies aiming to protect the heart during autoimmunity.

  9. Hemorrhagic Tamponade as Initial Manifestation of Systemic Lupus with Subsequent Refractory and Progressive Lupus Myocarditis Resulting in Cardiomyopathy and Mitral Regurgitation

    Directory of Open Access Journals (Sweden)

    Nicole Marijanovich

    2018-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a heterogeneous autoimmune disease with a wide range of clinical and serological manifestations. Cardiac disease among patients with SLE is common and can involve the pericardium, myocardium, valves, conduction system, and coronary arteries. We are reporting a case of SLE in a young woman that is unique is unique in that initial symptoms consisted of pericarditis and hemorrhagic tamponade which remained progressive and resistant to aggressive immunosuppressive treatment and led to severe cardiomyopathy (ejection fraction of 25% and severe (+4 mitral regurgitation. Her immunosuppressive treatment included hydroxychloroquine, high-dose steroids, intravenous immunoglobulins, azathioprine, and mycophenolate mofetil. Her disease progression was felt to be due to underlying uncontrolled SLE because the complement levels remained persistently low throughout the entire course and PET Myocardial Perfusion and Viability study showed stable persistent active inflammation. Eventually, she was treated with cyclophosphamide which led to improvement in ejection fraction to 55% with only mild mitral regurgitation.

  10. DMPD: Toll-like receptor 9 in murine lupus: more friend than foe! [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18241699 Toll-like receptor 9 in murine lupus: more friend than foe! Yu P, Musette ...us: more friend than foe! PubmedID 18241699 Title Toll-like receptor 9 in murine lupus...P, Peng SL. Immunobiology. 2008;213(2):151-7. Epub 2007 Sep 21. (.png) (.svg) (.html) (.csml) Show Toll-like receptor 9 in murine lup

  11. Murine Models of Heart Failure With Preserved Ejection Fraction

    Directory of Open Access Journals (Sweden)

    Maria Valero-Muñoz, PhD

    2017-12-01

    Full Text Available Heart failure with preserved ejection fraction (HFpEF is characterized by signs and symptoms of heart failure in the presence of a normal left ventricular ejection fraction. Despite accounting for up to 50% of all clinical presentations of heart failure, the mechanisms implicated in HFpEF are poorly understood, thus precluding effective therapy. The pathophysiological heterogeneity in the HFpEF phenotype also contributes to this disease and likely to the absence of evidence-based therapies. Limited access to human samples and imperfect animal models that completely recapitulate the human HFpEF phenotype have impeded our understanding of the mechanistic underpinnings that exist in this disease. Aging and comorbidities such as atrial fibrillation, hypertension, diabetes and obesity, pulmonary hypertension, and renal dysfunction are highly associated with HFpEF, yet the relationship and contribution between them remains ill-defined. This review discusses some of the distinctive clinical features of HFpEF in association with these comorbidities and highlights the advantages and disadvantage of commonly used murine models used to study the HFpEF phenotype.

  12. A murine model of targeted infusion for intracranial tumors.

    Science.gov (United States)

    Kim, Minhyung; Barone, Tara A; Fedtsova, Natalia; Gleiberman, Anatoli; Wilfong, Chandler D; Alosi, Julie A; Plunkett, Robert J; Gudkov, Andrei; Skitzki, Joseph J

    2016-01-01

    Historically, intra-arterial (IA) drug administration for malignant brain tumors including glioblastoma multiforme (GBM) was performed as an attempt to improve drug delivery. With the advent of percutaneous neuorovascular techniques and modern microcatheters, intracranial drug delivery is readily feasible; however, the question remains whether IA administration is safe and more effective compared to other delivery modalities such as intravenous (IV) or oral administrations. Preclinical large animal models allow for comparisons between treatment routes and to test novel agents, but can be expensive and difficult to generate large numbers and rapid results. Accordingly, we developed a murine model of IA drug delivery for GBM that is reproducible with clear readouts of tumor response and neurotoxicities. Herein, we describe a novel mouse model of IA drug delivery accessing the internal carotid artery to treat ipsilateral implanted GBM tumors that is consistent and reproducible with minimal experience. The intent of establishing this unique platform is to efficiently interrogate targeted anti-tumor agents that may be designed to take advantage of a directed, regional therapy approach for brain tumors.

  13. Murine leukemia virus (MLV replication monitored with fluorescent proteins

    Directory of Open Access Journals (Sweden)

    Bittner Alexandra

    2004-12-01

    Full Text Available Abstract Background Cancer gene therapy will benefit from vectors that are able to replicate in tumor tissue and cause a bystander effect. Replication-competent murine leukemia virus (MLV has been described to have potential as cancer therapeutics, however, MLV infection does not cause a cytopathic effect in the infected cell and viral replication can only be studied by immunostaining or measurement of reverse transcriptase activity. Results We inserted the coding sequences for green fluorescent protein (GFP into the proline-rich region (PRR of the ecotropic envelope protein (Env and were able to fluorescently label MLV. This allowed us to directly monitor viral replication and attachment to target cells by flow cytometry. We used this method to study viral replication of recombinant MLVs and split viral genomes, which were generated by replacement of the MLV env gene with the red fluorescent protein (RFP and separately cloning GFP-Env into a retroviral vector. Co-transfection of both plasmids into target cells resulted in the generation of semi-replicative vectors, and the two color labeling allowed to determine the distribution of the individual genomes in the target cells and was indicative for the occurrence of recombination events. Conclusions Fluorescently labeled MLVs are excellent tools for the study of factors that influence viral replication and can be used to optimize MLV-based replication-competent viruses or vectors for gene therapy.

  14. Collagen-Induced Arthritis: A model for Murine Autoimmune Arthritis.

    Science.gov (United States)

    Pietrosimone, K M; Jin, M; Poston, B; Liu, P

    2015-10-20

    Collagen-induced arthritis (CIA) is a common autoimmune animal model used to study rheumatoid arthritis (RA). The development of CIA involves infiltration of macrophages and neutrophils into the joint, as well as T and B cell responses to type II collagen. In murine CIA, genetically susceptible mice (DBA/1J) are immunized with a type II bovine collagen emulsion in complete Freund's adjuvant (CFA), and receive a boost of type II bovine collagen in incomplete Freund's adjuvant (IFA) 21 days after the first injection. These mice typically develop disease 26 to 35 days after the initial injection. C57BL/6J mice are resistant to arthritis induced by type II bovine collagen, but can develop arthritis when immunized with type II chicken collagen in CFA, and receive a boost of type II chicken collagen in IFA 21 days after the first injection. The concentration of heat-killed Mycobacterium tuberculosis H37RA (MT) in CFA also differs for each strain. DBA/1J mice develop arthritis with 1 mg/ml MT, while C57BL/6J mice require and 3-4 mg/ml MT in order to develop arthritis. CIA develops slowly in C57BL/6J mice and cases of arthritis are mild when compared to DBA/1J mice. This protocol describes immunization of DBA/1J mice with type II bovine collagen and the immunization of C57BL/6J mice with type II chicken collagen.

  15. An in vitro model of murine middle ear epithelium.

    Science.gov (United States)

    Mulay, Apoorva; Akram, Khondoker M; Williams, Debbie; Armes, Hannah; Russell, Catherine; Hood, Derek; Armstrong, Stuart; Stewart, James P; Brown, Steve D M; Bingle, Lynne; Bingle, Colin D

    2016-11-01

    Otitis media (OM), or middle ear inflammation, is the most common paediatric disease and leads to significant morbidity. Although understanding of underlying disease mechanisms is hampered by complex pathophysiology it is clear that epithelial abnormalities underpin the disease. There is currently a lack of a well-characterised in vitro model of the middle ear (ME) epithelium that replicates the complex cellular composition of the middle ear. Here, we report the development of a novel in vitro model of mouse middle ear epithelial cells (mMECs) at an air-liquid interface (ALI) that recapitulates the characteristics of the native murine ME epithelium. We demonstrate that mMECs undergo differentiation into the varied cell populations seen within the native middle ear. Proteomic analysis confirmed that the cultures secrete a multitude of innate defence proteins from their apical surface. We showed that the mMECs supported the growth of the otopathogen, nontypeable Haemophilus influenzae (NTHi), suggesting that the model can be successfully utilised to study host-pathogen interactions in the middle ear. Overall, our mMEC culture system can help to better understand the cell biology of the middle ear and improve our understanding of the pathophysiology of OM. The model also has the potential to serve as a platform for validation of treatments designed to reverse aspects of epithelial remodelling that underpin OM development. © 2016. Published by The Company of Biologists Ltd.

  16. Hamster and Murine Models of Severe Destructive Lyme Arthritis

    Science.gov (United States)

    Munson, Erik; Nardelli, Dean T.; Du Chateau, Brian K.; Callister, Steven M.; Schell, Ronald F.

    2012-01-01

    Arthritis is a frequent complication of infection in humans with Borrelia burgdorferi. Weeks to months following the onset of Lyme borreliosis, a histopathological reaction characteristic of synovitis including bone, joint, muscle, or tendon pain may occur. A subpopulation of patients may progress to a chronic, debilitating arthritis months to years after infection which has been classified as severe destructive Lyme arthritis. This arthritis involves focal bone erosion and destruction of articular cartilage. Hamsters and mice are animal models that have been utilized to study articular manifestations of Lyme borreliosis. Infection of immunocompetent LSH hamsters or C3H mice results in a transient synovitis. However, severe destructive Lyme arthritis can be induced by infecting irradiated hamsters or mice and immunocompetent Borrelia-vaccinated hamsters, mice, and interferon-gamma- (IFN-γ-) deficient mice with viable B. burgdorferi. The hamster model of severe destructive Lyme arthritis facilitates easy assessment of Lyme borreliosis vaccine preparations for deleterious effects while murine models of severe destructive Lyme arthritis allow for investigation of mechanisms of immunopathology. PMID:22461836

  17. Mechanism of immunotoxicological effects of tributyltin chloride on murine thymocytes.

    Science.gov (United States)

    Sharma, Neelima; Kumar, Anoop

    2014-04-01

    Tributyltin-chloride, a well-known organotin compound, is a widespread environmental toxicant. The immunotoxic effects of tributyltin-chloride on mammalian system and its mechanism is still unclear. This study is designed to explore the mode of action of tributyltin-induced apoptosis and other parallel apoptotic pathways in murine thymocytes. The earliest response in oxidative stress followed by mitochondrial membrane depolarization and caspase-3 activation has been observed. Pre-treatment with N-acetyl cysteine and buthionine sulfoximine effectively inhibited the tributyltin-induced apoptotic DNA and elevated the sub G1 population, respectively. Caspase inhibitors pretreatment prevent tributyltin-induced apoptosis. Western blot and flow cytometry indicate no translocation of apoptosis-inducing factor and endonuclease G in the nuclear fraction from mitochondria. Intracellular Ca(2+) levels are significantly raised by tributyltin chloride. These results clearly demonstrate caspase-dependent apoptotic pathway and support the role of oxidative stress, mitochondrial membrane depolarization, caspase-3 activation, and calcium during tributyltin-chloride (TBTC)-induced thymic apoptosis.

  18. Genomic rearrangement in radiation-induced murine myeloid leukemia

    International Nuclear Information System (INIS)

    Ishihara, Hiroshi

    1994-01-01

    After whole body irradiation of 3Gy X ray to C3H/He male mice, acute myeloid leukemia is induced at an incidence of 20 to 30% within 2 years. We have studied the mechanism of occurrence of this radiation-induced murine myeloid leukemia. Detection and isolation of genomic structural aberration which may be accumulated accompanied with leukemogenesis are helpful in analyzing the complicated molecular process from radiation damage to leukemogenesis. So, our research work was done in three phases. First, structures of previously characterized oncogenes and cytokine-related genes were analyzed, and abnormal structures of fms(protooncogene encoding M-CSF receptor gene)-related and myc-related genes were found in several leukemia cells. Additionally, genomic structural aberration of IL-3 gene was observed in some leukemia cells, so that construction of genomic libraries and cloning of the abnormal IL-3 genomic DNAs were performed to characterize the structure. Secondly, because the breakage of chromosome 2 that is frequently observed in myeloid leukemia locates in proximal position of IL-1 gene cluster in some cases, the copy number of IL-1 gene was determined and the gene was cloned. Lastly, the abnormal genome of leukemia cell was cloned by in-gel competence reassociation method. We discussed these findings and evaluated the analysis of the molecular process of leukemogenesis using these cloned genomic fragments. (author)

  19. Effect of SPG (Sonifilan) immunotherapy and PDT on murine tumor

    International Nuclear Information System (INIS)

    Korbelik, M.; Krosl, G.; Dougherty, G.J.; Chaplin, D.J.

    1992-01-01

    PhotoDynamic Therapy of solid tumors is unique in eliciting a strong host immune response unparalleled in other cancer therapies. This immune response is manifested as an acute inflammatory reaction, and can be readily seen as redness and edema around the treated area. Destruction of typical solid tumor cannot be accomplished solely by direct phototoxic action. This was shown to be the case even with drugs more potent in this direct killing effect than Photofrin, the photosensitizer presently used in clinical PDT. Limiting factors seem to be regional insufficiencies in supply of molecular oxygen, needed for generation of phototoxic species. They can be ascribed to the existence of chronically and acute hypoxic tumor regions, oxygen consumption by the photodynamic process, and vascular shutdown induced during PDT. The remaining tumor mass is eradicated by an indirect effect, necrosis induced by destruction of tumor vasculature. Since most events in PDT treated tumor that lead to vascular collapse are, in fact, typical inflammatory manifestations, it was suggested that PDT-induced acute inflammatory reaction actually leads to vascular damage. In a related report characteristics are shown of cellular inflammatory infiltrate in PDT-treated murine tumor. This work examines the effect of combining PDT with immunotherapy, in an attempt to investigate a possibility of amplification of immune reaction to PDT and its direction towards more pervasive destruction of treated tumors. (authors). 6 refs

  20. Reduction in DNA repair capacity following differentiation of murine proadipocytes

    International Nuclear Information System (INIS)

    Tofilon, P.J.; Meyn, R.E.

    1988-01-01

    It has been suggested that terminally differentiated mammalian cells have a decreased DNA repair capacity, compared with proliferating stem cells. To investigate this hypothesis, we have examined γ-ray-induced DNA strand breaks and their repair in the murine proadipocyte stem cell line 3T3-T. By exposure to human plasma, 3T3-T cells can be induced to undergo nonterminal and then terminal differentiation. DNA strand breaks were evaluated using the technique of alkaline elution. No difference was detected among stem, nonterminally differentiated, and terminally differentiated cells in the initial levels of radiation-induced DNA strand breaks. Each of the strand break dose responses increased as a linear function of γ-ray dose. The strand breaks induced by 4 Gy rejoined following biphasic kinetics for each cell type. At each time point examined after irradiation, however, the percentage of strand breaks that had not rejoined in terminally differentiated cells was three to six times greater than in stem cells. The rate of strand break rejoining in nonterminally differentiated cells was of an intermediate value between that of the stem and of the terminally differentiated cells. These results indicate that, at least for 3T3-T cells, differentiated cells have a reduced capacity for DNA repair

  1. Enterocin CRL35 inhibits Listeria monocytogenes in a murine model.

    Science.gov (United States)

    Salvucci, Emiliano; Saavedra, Lucila; Hebert, Elvira Maria; Haro, Cecilia; Sesma, Fernando

    2012-01-01

    Listeria monocytogenes is a foodborne pathogen causative of opportunistic infections. Listeriosis is associated with severe infections in pregnant women causing abortion or neonatal listeriosis. An alternative to antibiotics are safe novel bacteriocins peptides such as enterocin CRL35 with strong antilisterial activity produced by Enterococcus mundtii CRL35. In the present paper, our goal is to study the effectiveness of this peptide and the producer strain in a murine model of pregnancy-associated listeriosis. A single dose of 5×10(9) colony-forming unit of L. monocytogenes FBUNT (Faculty of Biochemistry-University of Tucumán) resulted in translocation of pathogen to liver and spleen of BALB/c pregnant mice. The maximum level of Listeria was observed on day 3 postinfection. Interestingly, the intragastric administration of enterocin CRL35 significantly reduced the translocation of the pathogen to vital organs. On the other hand, the preadministration of E. mundtii CRL35 slightly inhibited this translocation. Listeria infection caused a significant increase in polymorphonuclear leukocytes at day 3 postinfection compared to the noninfected group. This value was reduced after the administration of enterocin CRL35. No significant changes were observed in either white blood cells or lymphocytes counts. Based on the data presented in the present work enterocin CRL35 would be a promising alternative for the prevention of Listeria infections.

  2. Effects of spaceflight on the muscles of the murine shoulder.

    Science.gov (United States)

    Shen, Hua; Lim, Chanteak; Schwartz, Andrea G; Andreev-Andrievskiy, Alexander; Deymier, Alix C; Thomopoulos, Stavros

    2017-12-01

    Mechanical loading is necessary for the development and maintenance of the musculoskeletal system. Removal of loading via microgravity, paralysis, or bed rest leads to rapid loss of muscle mass and function; however, the molecular mechanisms that lead to these changes are largely unknown, particularly for the spaceflight (SF) microgravity environment. Furthermore, few studies have explored these effects on the shoulder, a dynamically stabilized joint with a large range of motion; therefore, we examined the effects of microgravity on mouse shoulder muscles for the 15-d Space Transportation System (STS)-131, 13-d STS-135, and 30-d Bion-M1 missions. Mice from STS missions were euthanized within 4 h after landing, whereas mice from the Bion-M1 mission were euthanized within 14 h after landing. The motion-generating deltoid muscle was more sensitive to microgravity than the joint-stabilizing rotator cuff muscles. Mice from the STS-131 mission exhibited reduced myogenic ( Myf5 and -6 ) and adipogenic ( Pparg , Cebpa , and Lep ) gene expression, whereas either no change or an increased expression of these genes was observed in mice from the Bion-M1 mission. In summary, muscle responses to microgravity were muscle-type specific, short-duration SF caused dramatic molecular changes to shoulder muscles and responses to reloading upon landing were rapid.-Shen, H., Lim, C., Schwartz, A. G., Andreev-Andrievskiy, A., Deymier, A. C., Thomopoulos, S. Effects of spaceflight on the muscles of the murine shoulder. © FASEB.

  3. Megakaryocytes compensate for Kit insufficiency in murine arthritis.

    Science.gov (United States)

    Cunin, Pierre; Penke, Loka R; Thon, Jonathan N; Monach, Paul A; Jones, Tatiana; Chang, Margaret H; Chen, Mary M; Melki, Imene; Lacroix, Steve; Iwakura, Yoichiro; Ware, Jerry; Gurish, Michael F; Italiano, Joseph E; Boilard, Eric; Nigrovic, Peter A

    2017-05-01

    The growth factor receptor Kit is involved in hematopoietic and nonhematopoietic development. Mice bearing Kit defects lack mast cells; however, strains bearing different Kit alleles exhibit diverse phenotypes. Herein, we investigated factors underlying differential sensitivity to IgG-mediated arthritis in 2 mast cell-deficient murine lines: KitWsh/Wsh, which develops robust arthritis, and KitW/Wv, which does not. Reciprocal bone marrow transplantation between KitW/Wv and KitWsh/Wsh mice revealed that arthritis resistance reflects a hematopoietic defect in addition to mast cell deficiency. In KitW/Wv mice, restoration of susceptibility to IgG-mediated arthritis was neutrophil independent but required IL-1 and the platelet/megakaryocyte markers NF-E2 and glycoprotein VI. In KitW/Wv mice, platelets were present in numbers similar to those in WT animals and functionally intact, and transfer of WT platelets did not restore arthritis susceptibility. These data implicated a platelet-independent role for the megakaryocyte, a Kit-dependent lineage that is selectively deficient in KitW/Wv mice. Megakaryocytes secreted IL-1 directly and as a component of circulating microparticles, which activated synovial fibroblasts in an IL-1-dependent manner. Transfer of WT but not IL-1-deficient megakaryocytes restored arthritis susceptibility to KitW/Wv mice. These findings identify functional redundancy among Kit-dependent hematopoietic lineages and establish an unanticipated capacity of megakaryocytes to mediate IL-1-driven systemic inflammatory disease.

  4. Chromosomal mechanisms in murine radiation acute myeloid leukemogenesis

    International Nuclear Information System (INIS)

    Bouffler, S.D.; Breckon, G.; Cox, R.

    1996-01-01

    Chromosome 2 abnormalities, particularly interstitial deletions, characterize murine radiation-induced acute myeloid leukaemias (AMLs). Here, G-band analyses in CBA/H mice of early (1-6 month) post 3 Gy X-radiation events in bone marrow cells in vivo and karyotype evolution in one unusual AML are presented. The early event analysis showed that all irradiated animals carry chromosome 2 abnormalities, that chromosome 2 abnormalities are more frequent than expected and that interstitial deletions are more common in chromosome 2 than in the remainder of the genome. On presentation AML case N122 carried a t(2; 11) terminal translocation which, with passaging, evolved into a del2(C3F3). Therefore two pathways in leukaemogenesis might exist, one deletion-driven, the other terminal tranlocation-driven involving interstitial genes and terminal genes respectively of chromosome 2. As all irradiated individuals carried chromosome 2 abnormalities, the formation of these aberrations does not determine individual leukaemogenic sensitivity as only 20-25% of animals would be expected to develop AML. Similar lines of argument suggest that chromosome 2 abnormalities are necessary but not sufficient for radiation leukaemogenesis in CBA/H nor are they rate limiting in leukaemogenesis. (Author)

  5. Retino-hypothalamic regulation of light-induced murine sleep

    Directory of Open Access Journals (Sweden)

    Fanuel eMuindi

    2014-08-01

    Full Text Available The temporal organization of sleep is regulated by an interaction between the circadian clock and homeostatic processes. Light indirectly modulates sleep through its ability to phase shift and entrain the circadian clock. Light can also exert a direct, circadian-independent effect on sleep. For example, acute exposure to light promotes sleep in nocturnal animals and wake in diurnal animals. The mechanisms whereby light directly influences sleep and arousal are not well understood. In this review, we discuss the direct effect of light on sleep at the level of the retina and hypothalamus in rodents. We review murine data from recent publications showing the roles of rod-, cone- and melanopsin-based photoreception on the initiation and maintenance of light-induced sleep. We also present hypotheses about hypothalamic mechanisms that have been advanced to explain the acute control of sleep by light. Specifically, we review recent studies assessing the roles of the ventrolateral preoptic area and the suprachiasmatic nucleus. We also discuss how light might differentially promote sleep and arousal in nocturnal and diurnal animals respectively. Lastly, we suggest new avenues for research on this topic which is still in its early stages.

  6. Tofacitinib Ameliorates Murine Lupus and Its Associated Vascular Dysfunction.

    Science.gov (United States)

    Furumoto, Yasuko; Smith, Carolyne K; Blanco, Luz; Zhao, Wenpu; Brooks, Stephen R; Thacker, Seth G; Abdalrahman, Zarzour; Sciumè, Giuseppe; Tsai, Wanxia L; Trier, Anna M; Nunez, Leti; Mast, Laurel; Hoffmann, Victoria; Remaley, Alan T; O'Shea, John J; Kaplan, Mariana J; Gadina, Massimo

    2017-01-01

    Dysregulation of innate and adaptive immune responses contributes to the pathogenesis of systemic lupus erythematosus (SLE) and its associated premature vascular damage. No drug to date targets both systemic inflammatory disease and the cardiovascular complications of SLE. Tofacitinib is a JAK inhibitor that blocks signaling downstream of multiple cytokines implicated in lupus pathogenesis. While clinical trials have shown that tofacitinib exhibits significant clinical efficacy in various autoimmune diseases, its role in SLE and the associated vascular pathology remains to be characterized. MRL/lpr lupus-prone mice were administered tofacitinib or vehicle by gavage for 6 weeks (therapeutic arm) or 8 weeks (preventive arm). Nephritis, skin inflammation, serum levels of autoantibodies and cytokines, mononuclear cell phenotype and gene expression, neutrophil extracellular traps (NETs) release, endothelium-dependent vasorelaxation, and endothelial differentiation were compared in treated and untreated mice. Treatment with tofacitinib led to significant improvement in measures of disease activity, including nephritis, skin inflammation, and autoantibody production. In addition, tofacitinib treatment reduced serum levels of proinflammatory cytokines and interferon responses in splenocytes and kidney tissue. Tofacitinib also modulated the formation of NETs and significantly increased endothelium-dependent vasorelaxation and endothelial differentiation. The drug was effective in both preventive and therapeutic strategies. Tofacitinib modulates the innate and adaptive immune responses, ameliorates murine lupus, and improves vascular function. These results indicate that JAK inhibitors have the potential to be beneficial in SLE and its associated vascular damage. © 2016, American College of Rheumatology.

  7. Combination effect of cisplatin and radiation in murine solid tumors

    International Nuclear Information System (INIS)

    Egawa, Shin; Lee, Kan-ei; Ishibashi, Akira; Komiyama, Hiroki; Umezawa, Iwao.

    1986-01-01

    The combination effect of cisplatin and radiation was studied using the two different murine systems of sarcoma 180 and Ehrlich solid tumors. In sarcoma 180 solid tumor the minimal effective doses (MED) of cisplatin and radiation were 19.5 mg/kg and 10375 rad respectively whereas these doses did not show any effective antitumor activity practically. Administration of cisplatin with a doses of 9 mg/kg given 24 hours before radiation (1000 rad), however, showed synergistic antitumor activity. In Ehrlich solid tumor the MED of cisplatin and radiation were 13.8 mg/kg and 2892 rad respectively. Treatment with cisplatin, 3, 6 or 9 mg/kg, given 24 hours before radiation (1000 rad) showed also synergistic antitumor activity also. Sodium thiosulfate (STS) rescue was effective in reducing toxicity of cisplatin on combined use of the drug with radiation. Cell kinetics of sarcoma 180 solid tumor in vivo after the combined treatment was analyzed by computer aided flowcytometry. Accumulation of cells in the radiosensitive G 2 + M phase was observed 18 to 42 hours after a single intraperitoneal administration of 9 mg/kg of cisplatin. It is strongly suggested that this synchronization is one of the mechanisms of the synergism in the combination therapy. (author)

  8. High salt intake does not exacerbate murine autoimmune thyroiditis

    Science.gov (United States)

    Kolypetri, P; Randell, E; Van Vliet, B N; Carayanniotis, G

    2014-01-01

    Recent studies have shown that high salt (HS) intake exacerbates experimental autoimmune encephalomyelitis and have raised the possibility that a HS diet may comprise a risk factor for autoimmune diseases in general. In this report, we have examined whether a HS diet regimen could exacerbate murine autoimmune thyroiditis, including spontaneous autoimmune thyroiditis (SAT) in non-obese diabetic (NOD.H2h4) mice, experimental autoimmune thyroiditis (EAT) in C57BL/6J mice challenged with thyroglobulin (Tg) and EAT in CBA/J mice challenged with the Tg peptide (2549–2560). The physiological impact of HS intake was confirmed by enhanced water consumption and suppressed aldosterone levels in all strains. However, the HS treatment failed to significantly affect the incidence and severity of SAT or EAT or Tg-specific immunoglobulin (Ig)G levels, relative to control mice maintained on a normal salt diet. In three experimental models, these data demonstrate that HS intake does not exacerbate autoimmune thyroiditis, indicating that a HS diet is not a risk factor for all autoimmune diseases. PMID:24528002

  9. An in vitro model of murine middle ear epithelium

    Directory of Open Access Journals (Sweden)

    Apoorva Mulay

    2016-11-01

    Full Text Available Otitis media (OM, or middle ear inflammation, is the most common paediatric disease and leads to significant morbidity. Although understanding of underlying disease mechanisms is hampered by complex pathophysiology it is clear that epithelial abnormalities underpin the disease. There is currently a lack of a well-characterised in vitro model of the middle ear (ME epithelium that replicates the complex cellular composition of the middle ear. Here, we report the development of a novel in vitro model of mouse middle ear epithelial cells (mMECs at an air–liquid interface (ALI that recapitulates the characteristics of the native murine ME epithelium. We demonstrate that mMECs undergo differentiation into the varied cell populations seen within the native middle ear. Proteomic analysis confirmed that the cultures secrete a multitude of innate defence proteins from their apical surface. We showed that the mMECs supported the growth of the otopathogen, nontypeable Haemophilus influenzae (NTHi, suggesting that the model can be successfully utilised to study host–pathogen interactions in the middle ear. Overall, our mMEC culture system can help to better understand the cell biology of the middle ear and improve our understanding of the pathophysiology of OM. The model also has the potential to serve as a platform for validation of treatments designed to reverse aspects of epithelial remodelling that underpin OM development.

  10. Snake venoms components with antitumor activity in murine melanoma cells

    International Nuclear Information System (INIS)

    Queiroz, Rodrigo Guimaraes

    2012-01-01

    Despite the constant advances in the treatment of cancer, this disease remains one of the main causes of mortality worldwide. So, the development of new treatment modalities is imperative. Snake venom causes a variety of biological effects because they constitute a complex mixture of substances as disintegrins, proteases (serine and metalo), phospholipases A2, L-amino acid oxidases and others. The goal of the present work is to evaluate a anti-tumor activity of some snake venoms fractions. There are several studies of components derived from snake venoms with this kind of activity. After fractionation of snake venoms of the families Viperidae and Elapidae, the fractions were assayed towards murine melanoma cell line B16-F10 and fibroblasts L929. The results showed that the fractions of venom of the snake Notechis ater niger had higher specificity and potential antitumor activity on B16-F10 cell line than the other studied venoms. Since the components of this venom are not explored yet coupled with the potential activity showed in this work, we decided to choose this venom to develop further studies. The cytotoxic fractions were evaluated to identify and characterize the components that showed antitumoral activity. Western blot assays and zymography suggests that these proteins do not belong to the class of metallo and serine proteinases. (author)

  11. Melatonin modulates adiponectin expression on murine colitis with sleep deprivation.

    Science.gov (United States)

    Kim, Tae Kyun; Park, Young Sook; Baik, Haing-Woon; Jun, Jin Hyun; Kim, Eun Kyung; Sull, Jae Woong; Sung, Ho Joong; Choi, Jin Woo; Chung, Sook Hee; Gye, Myung Chan; Lim, Ju Yeon; Kim, Jun Bong; Kim, Seong Hwan

    2016-09-07

    To determine adiponectin expression in colonic tissue of murine colitis and systemic cytokine expression after melatonin treatments and sleep deprivation. The following five groups of C57BL/6 mice were used in this study: (1) group I, control; (2) group II, 2% DSS induced colitis for 7 d; (3) group III, 2% DSS induced colitis and melatonin treatment; (4) group IV, 2% DSS induced colitis with sleep deprivation (SD) using specially designed and modified multiple platform water baths; and (5) group V, 2% DSS induced colitis with SD and melatonin treatment. Melatonin (10 mg/kg) or saline was intraperitoneally injected daily to mice for 4 d. The body weight was monitored daily. The degree of colitis was evaluated histologically after sacrificing the mice. Immunohistochemical staining and Western blot analysis was performed using anti-adiponectin antibody. After sampling by intracardiac punctures, levels of serum cytokines were measured by ELISA. Sleep deprivation in water bath exacerbated DSS induced colitis and worsened weight loss. Melatonin injection not only alleviated the severity of mucosal injury, but also helped survival during stressful condition. The expression level of adiponectin in mucosa was decreased in colitis, with the lowest level observed in colitis combined with sleep deprivation. Melatonin injection significantly (P sleep deprivation.

  12. Concepts for treatment of micrometastases developed in murine systems

    International Nuclear Information System (INIS)

    Schabel, F.M. Jr.

    1976-01-01

    Current knowledge of tumor cell population growth kinetics indicates that the growth fraction (viable tumor cells undergoing active cell replication) is inversely related to population size. Tumor cells in micrometastases should, therefore, be more sensitive to anticancer drugs active against anabolizing cells than are tumor cells in the larger, grossly apparent primary tumor from which they were derived. This indicates the probability that micrometastases will be effectively responsive to more drugs than is the primary and clinically apparent tumor from which they came. Studies with at least four metastatic and uniformly fatal murine solid tumors (lung, breast, colon, and melanoma) have demonstrated significantly improved cure rates with drug treatment following surgical removal of the grossly apparent primary tumor than can be obtained with either surgery or drug treatment when used alone. Further, both disease staging and drug dosage have been shown to influence cure rates of combined-modality treatment. With several mouse tumors, a significantly smaller number of viable tumor cells can establish lethal tumors in the presence of radiation-inactivated tumor cells than in their absence. This suggests that small numbers of residual viable tumor cells in radiation-treated tumor sites may be a greater threat to clinical cure than smaller tumor cell populations remaining in situ after surgery

  13. Serial passaging of Candida albicans in systemic murine infection suggests that the wild type strain SC5314 is well adapted to the murine kidney.

    Directory of Open Access Journals (Sweden)

    Anja Lüttich

    Full Text Available The opportunistic fungal pathogen Candida albicans has a remarkable ability to adapt to unfavorable environments by different mechanisms, including microevolution. For example, a previous study has shown that passaging through the murine spleen can cause new phenotypic characteristics. Since the murine kidney is the main target organ in murine Candida sepsis and infection of the spleen differs from the kidney in several aspects, we tested whether C. albicans SC5314 could evolve to further adapt to infection and persistence within the kidney. Therefore, we performed a long-term serial passage experiment through the murine kidney of using a low infectious dose. We found that the overall virulence of the commonly used wild type strain SC5314 did not change after eight passages and that the isolated pools showed only very moderate changes of phenotypic traits on the population level. Nevertheless, the last passage showed a higher phenotypic variability and a few individual strains exhibited phenotypic alterations suggesting that microevolution has occurred. However, the majority of the tested single strains were phenotypically indistinguishable from SC5314. Thus, our findings indicate that characteristics of SC5314 which are important to establish and maintain kidney infection over a prolonged time are already well developed.

  14. Differential activation of murine herpesvirus 68- and Kaposi's sarcoma-associated herpesvirus-encoded ORF74 G protein-coupled receptors by human and murine chemokines

    NARCIS (Netherlands)

    Verzijl, D.; Fitzsimons, C.P.; Van Dijk, M.; Stewart, J.P.; Timmerman, H.; Smit, M.J.; Leurs, R.

    2004-01-01

    Infection of mice with murine gammaherpesvirus 68 (MHV-68) is a well-characterized small animal model for the study of gammaherpesvirus infection. MHV-68 belongs to the same herpesvirus family as herpesvirus saimiri (HVS) of New World squirrel monkeys and human herpesvirus 8 (HHV-8) (also referred

  15. Polymorphisms of the P-selectin gene and risk of myocardial infarction in men and women in the ECTIM extension study. Etude cas-temoin de l'infarctus myocarde.

    Science.gov (United States)

    Kee, F; Morrison, C; Evans, A E; McCrum, E; McMaster, D; Dallongeville, J; Nicaud, V; Poirier, O; Cambien, F

    2000-11-01

    Studies in animal models and humans implicate cell adhesion molecules in atherogenesis but their role in mediating the risk of myocardial infarction is unclear. The ECTIM (étude cas-temoin de l'infarctus myocarde) extension study was established to determine whether a previously implicated polymorphism of the P-selectin gene was associated with myocardial infarction risk in men and women in Belfast and Glasgow. PATIENTS AND STUDY SETTING: 696 cases with a recent myocardial infarction and 561 age matched controls (both male and female) were recruited into a case-control study in MONICA project areas of Belfast and Glasgow. Demographic and lifestyle information was collected by interview administered questionnaire, and each subject was examined and provided a blood sample for DNA extraction. The polymerase chain reaction (PCR) was used to amplify regions encompassing the P-selectin Thr-->Pro (A/C) polymorphism at position 715. Genotype odds ratios for myocardial infarction were estimated by logistic regression adjusted for population, age, and sex. There was no significant association between conventional risk factors (such as hypercholesterolaemia, increased body mass index, or raised blood pressure) and either the rare or the common Pro(715) allele of the P-selectin gene in controls. Overall, comparing Pro(715)/Pro(715) and Pro(715)/Thr(715) with Thr(715)/Thr(715), with adjustment for centre, age, and sex, the odds ratio was 0.78 (95% confidence interval 0.60 to 1.00) (p = 0.054), indicating a "protective" effect of the less common Pro(715) allele. There was no significant heterogeneity in odds ratios between men and women either in this sample or when combined with the original ECTIM subjects. In a large population based study in two regions of the UK, we have been able to corroborate the earlier ECTIM findings of a lower frequency of the Thr/Pro(715) polymorphism in subjects with myocardial infarction. An apparently "protective effect" of similar magnitude also

  16. New polymorphisms of the angiotensin II type 1 receptor gene and their associations with myocardial infarction and blood pressure: the ECTIM study. Etude Cas-Témoin de l'Infarctus du Myocarde.

    Science.gov (United States)

    Poirier, O; Georges, J L; Ricard, S; Arveiler, D; Ruidavets, J B; Luc, G; Evans, A; Cambien, F; Tiret, L

    1998-10-01

    In an earlier report, we suggested that a polymorphism located in the 3' untranslated region of the angiotensin II type 1 receptor gene (AT1R+1166 A/C) might interact with the angiotensin I converting enzyme (ACE) insertion/deletion (I/D) polymorphism to increase the risk of myocardial infarction. Since the AT1R+1166 A/C polymorphism does not appear to be functional, we postulated that it might be in linkage disequilibrium with an unidentified functional variant which would affect the regulation of the gene in response to angiotensin II. The present study was conducted to identify new polymorphisms of the AT1R gene that might be responsible for this interaction. The first four exons, which are untranslated, and 2.2 kb in the 5' flanking region of the AT1R gene were explored by polymerase chain reaction/single-strand conformation polymorphism. Seven polymorphisms were detected in the 5' region at positions -1424, -810, -713, -521, -214, -213 and -153 upstream from the start of transcription. The genotypes of the -810, -713, -214, -213 and -153 polymorphisms were completely concordant. One substitution was detected at the 55th nucleotide of exon 4. These polymorphisms, together with the +1166 A/C polymorphism and a previously described T/C substitution at the 573th nucleotide of exon 5, were genotyped in the Etude Cas-Témoin de l'Infarctus du Myocarde (ECTIM) study, a multicentre study comparing 651 patients who had survived a myocardial infarction and 728 controls from Belfast (United Kingdom) and Lille, Strasbourg and Toulouse (France). The newly identified polymorphisms were not in linkage disequilibrium with the +1166 A/C polymorphism and therefore could not explain the interaction observed with ACE I/D. None of the polymorphisms was associated with blood pressure levels in control subjects. In the four populations, the A allele of the -810 polymorphism was associated with a lower risk of myocardial infarction (population-adjusted odds ratio of 0.80, confidence

  17. [Dehydration due to "mouth broken"].

    Science.gov (United States)

    Meijler, D P M; van Mossevelde, P W J; van Beek, R H T

    2012-09-01

    Two children were admitted to a medical centre due to dehydration after an oral injury and the extraction of a tooth. One child complained of "mouth broken". Dehydration is the most common water-electrolyte imbalance in children. Babies and young children are prone to dehydration due to their relatively large body surface area, the high percentage extracellular fluid, and the limited ability of the kidneys to conserve water. After the removal ofa tooth, after an oral trauma or in case of oral discomfort, a child is at greater risk of dehydration by reduced fluid and food intake due to oral pain and/or discomfort and anxiety to drink. In those cases, extra attention needs to be devoted to the intake of fluids.

  18. Teacher Dismissal and Due Process.

    Science.gov (United States)

    Leichner, Edward C.; Blackstone, Sidney

    1977-01-01

    This article addresses due process requirements in the nonrenewal and dismissal of tenured and nontenured teachers. The Georgia Fair Dismissal Law is used as a basis for discussing the grounds for teacher dismissal. Dismissal grounds discussed are 1) incompetency; 2) insubordination; 3) willful neglect of duties; 4) immorality; 5) inciting,…

  19. Due Process Hearing Case Study

    Science.gov (United States)

    Bateman, David F.

    2009-01-01

    William is 9 years of age, residing with his parent within the boundaries of an unnamed district ("the District"). As a student with autism he is eligible for special education programming and services. There was one issue presented for this due process hearing: What was the appropriate program and placement for him for the 2008-2009 school year?…

  20. Non-contact respiration monitoring for in-vivo murine micro computed tomography: characterization and imaging applications

    International Nuclear Information System (INIS)

    Burk, Laurel M; Lee, Yueh Z; Wait, J Matthew; Lu Jianping; Zhou, Otto Z

    2012-01-01

    A cone beam micro-CT has previously been utilized along with a pressure-tracking respiration sensor to acquire prospectively gated images of both wild-type mice and various adult murine disease models. While the pressure applied to the abdomen of the subject by this sensor is small and is generally without physiological effect, certain disease models of interest, as well as very young animals, are prone to atelectasis with added pressure, or they generate too weak a respiration signal with this method to achieve optimal prospective gating. In this work we present a new fibre-optic displacement sensor which monitors respiratory motion of a subject without requiring physical contact. The sensor outputs an analogue signal which can be used for prospective respiration gating in micro-CT imaging. The device was characterized and compared against a pneumatic air chamber pressure sensor for the imaging of adult wild-type mice. The resulting images were found to be of similar quality with respect to physiological motion blur; the quality of the respiration signal trace obtained using the non-contact sensor was comparable to that of the pressure sensor and was superior for gating purposes due to its better signal-to-noise ratio. The non-contact sensor was then used to acquire in-vivo micro-CT images of a murine model for congenital diaphragmatic hernia and of 11-day-old mouse pups. In both cases, quality CT images were successfully acquired using this new respiration sensor. Despite the presence of beam hardening artefacts arising from the presence of a fibre-optic cable in the imaging field, we believe this new technique for respiration monitoring and gating presents an opportunity for in-vivo imaging of disease models which were previously considered too delicate for established animal handling methods. (paper)

  1. Currently available murine Leydig cell lines can be applied to study early steps of steroidogenesis but not testosterone synthesis

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    Roger T. Engeli

    2018-02-01

    Full Text Available Androgen biosynthesis in males occurs to a large extent in testicular Leydig cells. This study focused on the evaluation of three murine Leydig cell lines as potential screening tool to test xenobiotics interfering with gonadal androgen synthesis. The final step of testosterone (T production in Leydig cells is catalyzed by the enzyme 17β-hydroxysteroid dehydrogenase 3 (17β-hsd3. The endogenous 17β-hsd3 mRNA expression and Δ4-androstene-3,17-dione (AD to T conversion were determined in the murine cell lines MA-10, BLTK1 and TM3. Additionally, effects of 8-Br-cAMP and forskolin stimulation on steroidogenesis and T production were analyzed. Steroids were quantified in supernatants of cells using liquid chromatography–tandem mass spectrometry. Unstimulated cells incubated with AD produced only very low T but substantial amounts of the inactive androsterone. Stimulated cells produced low amounts of T, moderate amounts of AD, but high amounts of progesterone. Gene expression analyses revealed barely detectable 17β-hsd3 levels, absence of 17β-hsd5 (Akr1c6, but substantial 17β-hsd1 expression in all three cell lines. Thus, MA-10, BLTK1 and TM3 cells are not suitable to study the expression and activity of the gonadal T synthesizing enzyme 17β-hsd3. The low T production reported in stimulated MA-10 cells are likely a result of the expression of 17β-hsd1. This study substantiates that the investigated Leydig cell lines MA-10, BLTK1, and TM3 are not suitable to study gonadal androgen biosynthesis due to altered steroidogenic pathways. Furthermore, this study emphasizes the necessity of mass spectrometry-based steroid quantification in experiments using steroidogenic cells such as Leydig cells.

  2. Intravenous immunoglobulin prevents murine antibody-mediated acute lung injury at the level of neutrophil reactive oxygen species (ROS production.

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    John W Semple

    Full Text Available Transfusion-related acute lung injury (TRALI is a leading cause of transfusion-associated mortality that can occur with any type of transfusion and is thought to be primarily due to donor antibodies activating pulmonary neutrophils in recipients. Recently, a large prospective case controlled clinical study of cardiac surgery patients demonstrated that despite implementation of male donors, a high incidence of TRALI still occurred and suggested a need for additional interventions in susceptible patient populations. To examine if intravenous immunoglobulin (IVIg may be effective, a murine model of antibody-mediated acute lung injury that approximates human TRALI was examined. When BALB/c mice were injected with the anti-major histocompatibility complex class I antibody 34-1-2s, mild shock (reduced rectal temperature and respiratory distress (dyspnea were observed and pre-treatment of the mice with 2 g/kg IVIg completely prevented these symptoms. To determine IVIg's usefulness to affect severe lung damage, SCID mice, previously shown to be hypersensitive to 34-1-2s were used. SCID mice treated with 34-1-2s underwent severe shock, lung damage (increased wet/dry ratios and 40% mortality within 2 hours. Treatment with 2 g/kg IVIg 18 hours before 34-1-2s administration completely protected the mice from all adverse events. Treatment with IVIg after symptoms began also reduced lung damage and mortality. While the prophylactic IVIg administration did not affect 34-1-2s-induced pulmonary neutrophil accumulation, bone marrow-derived neutrophils from the IVIg-treated mice displayed no spontaneous ROS production nor could they be stimulated in vitro with fMLP or 34-1-2s. These results suggest that IVIg prevents murine antibody-mediated acute lung injury at the level of neutrophil ROS production and thus, alleviating tissue damage.

  3. Hyper-radiation sensitivity of murine scid mutation and mapping of the human homologue HYRC1 gene

    International Nuclear Information System (INIS)

    Komatsu, Kenshi; Ohta, Tohru; Niikawa, Norio; Okumura, Yutaka; Kubota, Nobuo.

    1994-01-01

    The murine severe combined immunodeficient mutation (scid) is characterized by a lack of both B and T cells, due to a defect in lymphoid variable-(diversity)-joining(V(D)J) rearrangement. Scid cells are highly sensitive to both radiation-induced killing and chromosomal aberrations. Present experiments also demonstrated the high sensitivity of scid cells to killing, because of a deficient repair of double strand breaks(DSB). Scid cells can repair only 60% of radiation-induced DSB for 3 hours, while normal cells repair 85% of the DSB. Significantly reduced Do and n values were obtained from survival curves of scid cells and were similar to ataxia-telangiectasia(AT) cells (a unique human disease conferring whole body radiosensitivity). However, the kinetics of DNA synthesis after irradiation were different between the two cell types. In contrast with the radioresistant DNA synthesis of AT cells, DNA synthesis of scid cells was markedly inhibited after irradiation. The existence of different mutations was also supported by evidence of complementation in somatic cell hybrids between scid cells and AT cells. Using these hybrid cells, fragments of human chromosome 8 were introduced into scid cells HPRT mutant via X-irradiation and somatic cell fusion. The resulting hybrid clones contained human DNA fragment(s) which complemented the hyper-radiosensitivity of the scid cells. Alu-PCR products from these hybrids were used for chromosome painting using the technique of chromosome in situ suppression hybridization, allowing assignment of the human HYRC1 (hyper-radiosensitivity of murine scid mutation, complementing 1) gene, a candidate for a V(D)J recombinant gene, to human chromosome 8q11. (author)

  4. Innate and adaptive immune response to chronic pulmonary infection of hyphae of Aspergillus fumigatus in a new murine model.

    Science.gov (United States)

    Wang, Fengyuan; Zhang, Caiyun; Jiang, Yuan; Kou, Caixia; Kong, Qingtao; Long, Nanbiao; Lu, Ling; Sang, Hong

    2017-10-01

    The pathogenesis of chronic pulmonary aspergillosis (CPA) has seldom been studied due partly to a lack of animal models. Since hypha is the main morphology colonizing the airway in CPA, it's critical to study the immune reaction to chronic pulmonary infection of hyphae of Aspergillus fumigatus, which also has seldom been studied in vivo before. We established a novel murine model of chronic pulmonary infection of hyphae by challenging immunocompetent mice with tightly-structured hyphae balls intratracheally, and described the ensuing immunoreaction to hyphae and conidia, and the pathogenesis of CPA. Our experiment proved that the hyphae balls could induce a chronic pulmonary infection for 28 days with a considerable recrudescence at day 28 post-infection. Lungs infected with hyphae balls were remarkable for the many neutrophils and macrophages that flooded into airway lumens, with peribronchiolar infiltration of leukocytes. There was a transient increase of Th2 cells and Th17 cells at day 7 post-infection in the lung tissue. In contrast, lungs infected with conidia showed no peribronchiolar infiltration of leukocytes, but an influx of a great number of macrophages, and a much less number of neutrophils in the lumen. Besides, conidia activated the co-response of Th1, Th2 and Th17 cells with an increase of Treg cells in the lung tissue (quite different from most previous studies). We established a new murine model of chronic infection of hyphae to mimic the formation of CPA, and provide a new marker for different immune responses to hyphae and conidia.

  5. Chest radiographic findings of tsutsugamushi disease and murine typhus in Chunchon

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Heung Chul; Han, Tae Giun; Jang, Won Ho; Hwang, Woo Chul; Park, Man Soo; Lee, Myoung Gu; Kim, Yoon Won [School of Medicine, Hallym University, Chuncheon (Korea, Republic of); Park, Choong Ki [College of Medicine, Hanyang University, Guri (Korea, Republic of)

    1995-06-15

    To evaluate the chest radiographic findings of rickettsial disease including murine typhus and tsutsugamushi disease in Chunchon. Chest radiographic films of 81 cases diagnosed as rickettsial disease(55 cases of tsutsugamushi disease, 26 cases of murine typhus) by immunofluorescence test were retrospectively analyzed. Main serotypes of Rickettsia tsutsugamushi were Gilliam and Karp. Incidence rate of tsutsugamushi disease was 2.1 times greater than that of murine typhus. Chest radiographs were abnormal in 63.6% of tsutsugamushi disease, and in 30.8% of murine typhus. Radiographic findings were Kerly's B line, reticulonodular densities, hilar enlargement, pleural effusion, and splenomegaly in both entities, but pulmonary consolidation was only found in tsutsugamushi disease. The patients with the abnormal radiographic findings were statistically well correlated with cardiomegaly ({rho} < 0.01) and azygos engorgement ({rho} < 0.05), as compared to the patients with normal radiographic findings. Radiographic findings of both murine typhus and tsutsugamushi disease were interstitial pattern. But the chest radiographs in patients with tsutsugamushi disease showed more severe pattern with higher rate of abnormality.

  6. Enhanced detection and study of murine norovirus-1 using a more efficient microglial cell line

    Directory of Open Access Journals (Sweden)

    Lu Yuanan

    2009-11-01

    Full Text Available Abstract Background Human Noroviruses are the predominant cause of non-bacterial gastroenteritis worldwide. To facilitate prevention and control, a norovirus isolated from mice can provide a model to understand human noroviruses. To establish optimal viral infectivity conditions for murine noroviruses, several cell lines of hematopoietic lineage, including murine BV-2, RAW 264.7, and TIB, as well as human CHME-5, were tested comparatively for their sensitivity to murine norovirus-1. Results Except for CHME-5, all three murine-derived cell lines were susceptible to MNV infection. Viral infection of these cells was confirmed by RT-PCR. Using both viral plaque and replication assays, BV-2 and RAW 264.7 cells were determined to have comparable sensitivities to MNV-1 infection. Comparisons of cell growth characteristics, general laboratory handling and potential in-field applications suggest the use of BV-2 to be more advantageous. Conclusion Results obtained from these studies demonstrate that an immortalized microglial cell line can support MNV-1 replication and provides a more efficient method to detect and study murine noroviruses, facilitating future investigations using MNV-1 as a model to study, detect, and control Human Norovirus.

  7. Chest radiographic findings of tsutsugamushi disease and murine typhus in Chunchon

    International Nuclear Information System (INIS)

    Kim, Heung Chul; Han, Tae Giun; Jang, Won Ho; Hwang, Woo Chul; Park, Man Soo; Lee, Myoung Gu; Kim, Yoon Won; Park, Choong Ki

    1995-01-01

    To evaluate the chest radiographic findings of rickettsial disease including murine typhus and tsutsugamushi disease in Chunchon. Chest radiographic films of 81 cases diagnosed as rickettsial disease(55 cases of tsutsugamushi disease, 26 cases of murine typhus) by immunofluorescence test were retrospectively analyzed. Main serotypes of Rickettsia tsutsugamushi were Gilliam and Karp. Incidence rate of tsutsugamushi disease was 2.1 times greater than that of murine typhus. Chest radiographs were abnormal in 63.6% of tsutsugamushi disease, and in 30.8% of murine typhus. Radiographic findings were Kerly's B line, reticulonodular densities, hilar enlargement, pleural effusion, and splenomegaly in both entities, but pulmonary consolidation was only found in tsutsugamushi disease. The patients with the abnormal radiographic findings were statistically well correlated with cardiomegaly (ρ < 0.01) and azygos engorgement (ρ < 0.05), as compared to the patients with normal radiographic findings. Radiographic findings of both murine typhus and tsutsugamushi disease were interstitial pattern. But the chest radiographs in patients with tsutsugamushi disease showed more severe pattern with higher rate of abnormality

  8. Chest radiographic findings of tsutsugamushi disease and murine typhus in Chunchon

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Heung Chul; Han, Tae Giun; Jang, Won Ho; Hwang, Woo Chul; Park, Man Soo; Lee, Myoung Gu; Kim, Yoon Won [School of Medicine, Hallym University, Chuncheon (Korea, Republic of); Park, Choong Ki [College of Medicine, Hanyang University, Guri (Korea, Republic of)

    1995-06-15

    To evaluate the chest radiographic findings of rickettsial disease including murine typhus and tsutsugamushi disease in Chunchon. Chest radiographic films of 81 cases diagnosed as rickettsial disease(55 cases of tsutsugamushi disease, 26 cases of murine typhus) by immunofluorescence test were retrospectively analyzed. Main serotypes of Rickettsia tsutsugamushi were Gilliam and Karp. Incidence rate of tsutsugamushi disease was 2.1 times greater than that of murine typhus. Chest radiographs were abnormal in 63.6% of tsutsugamushi disease, and in 30.8% of murine typhus. Radiographic findings were Kerly's B line, reticulonodular densities, hilar enlargement, pleural effusion, and splenomegaly in both entities, but pulmonary consolidation was only found in tsutsugamushi disease. The patients with the abnormal radiographic findings were statistically well correlated with cardiomegaly ({rho} < 0.01) and azygos engorgement ({rho} < 0.05), as compared to the patients with normal radiographic findings. Radiographic findings of both murine typhus and tsutsugamushi disease were interstitial pattern. But the chest radiographs in patients with tsutsugamushi disease showed more severe pattern with higher rate of abnormality.

  9. Temporal Regulation of fim Genes in Uropathogenic Escherichia coli during Infection of the Murine Urinary Tract

    Directory of Open Access Journals (Sweden)

    William R. Schwan

    2017-01-01

    Full Text Available Uropathogenic Escherichia coli (UPEC adhere to cells in the human urinary tract via type 1 pili that undergo phase variation where a 314-bp fimS DNA element flips between Phase-ON and Phase-OFF orientations through two site-specific recombinases, FimB and FimE. Three fim-lux operon transcriptional fusions were created and moved into the clinical UPEC isolate NU149 to determine their temporal regulation in UPEC growing in the urinary tract. Within murine urinary tracts, the UPEC strains demonstrated elevated transcription of fimA and fimB early in the infection, but lower transcription by the fifth day in murine kidneys. In contrast, fimE transcription was much lower than either fimA or fimB early, increased markedly at 24 h after inoculation, and then dropped five days after inoculation. Positioning of fimS was primarily in the Phase-ON position over the time span in UPEC infected bladders, whereas in UPEC infected murine kidneys the Phase-OFF orientation was favored by the fifth day after inoculation. Hemagglutination titers with guinea pig erythrocytes remained constant in UPEC growing in infected murine bladders but fell substantially in UPEC infected kidneys over time. Our results show temporal in vivo regulation of fim gene expression in different environmental niches when UPEC infects the murine urinary tract.

  10. Intrapulmonary Versus Nasal Transduction of Murine Airways With GP64-pseudotyped Viral Vectors

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    Mayumi Oakland

    2013-01-01

    Full Text Available Persistent viral vector-mediated transgene expression in the airways requires delivery to cells with progenitor capacity and avoidance of immune responses. Previously, we observed that GP64-pseudotyped feline immunodeficiency virus (FIV-mediated gene transfer was more efficient in the nasal airways than the large airways of the murine lung. We hypothesized that in vivo gene transfer was limited by immunological and physiological barriers in the murine intrapulmonary airways. Here, we systematically investigate multiple potential barriers to lentiviral gene transfer in the airways of mice. We show that GP64-FIV vector transduced primary cultures of well-differentiated murine nasal epithelia with greater efficiency than primary cultures of murine tracheal epithelia. We further demonstrate that neutrophils, type I interferon (IFN responses, as well as T and B lymphocytes are not the major factors limiting the transduction of murine conducting airways. In addition, we observed better transduction of GP64-pseudotyped vesicular stomatitis virus (VSV in the nasal epithelia compared with the intrapulmonary airways in mice. VSVG glycoprotein pseudotyped VSV transduced intrapulmonary epithelia with similar efficiency as nasal epithelia. Our results suggest that the differential transduction efficiency of nasal versus intrapulmonary airways by FIV vector is not a result of immunological barriers or surface area, but rather differential expression of cellular factors specific for FIV vector transduction.

  11. Trans-10, cis 12-Conjugated Linoleic Acid-Induced Milk Fat Depression Is Associated with Inhibition of PPARγ Signaling and Inflammation in Murine Mammary Tissue

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    Anil K. G. Kadegowda

    2013-01-01

    Full Text Available Exogenous trans-10, cis-12-CLA (CLA reduces lipid synthesis in murine adipose and mammary (MG tissues. However, genomewide alterations in MG and liver (LIV associated with dietary CLA during lactation remain unknown. We fed mice (n=5/diet control or control + trans-10, cis-12-CLA (37 mg/day between d 6 and d 10 postpartum. The 35,302 annotated murine exonic evidence-based oligo (MEEBO microarray and quantitative RT-PCR were used for transcript profiling. Milk fat concentration was 44% lower on d 10 versus d 6 due to CLA. The CLA diet resulted in differential expression of 1,496 genes. Bioinformatics analyses underscored that a major effect of CLA on MG encompassed alterations in cellular signaling pathways and phospholipid species biosynthesis. Dietary CLA induced genes related to ER stress (Xbp1, apoptosis (Bcl2, and inflammation (Orm1, Saa2, and Cp. It also induced marked inhibition of PPARγ signaling, including downregulation of Pparg and Srebf1 and several lipogenic target genes (Scd, Fasn, and Gpam. In LIV, CLA induced hepatic steatosis probably through perturbations in the mitochondrial functions and induction of ER stress. Overall, results from this study underscored the role of PPARγ signaling on mammary lipogenic target regulation. The proinflammatory effect due to CLA could be related to inhibition of PPARγ signaling.

  12. Critical transition in tissue homeostasis accompanies murine lung senescence.

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    Carla L Calvi

    Full Text Available BACKGROUND: Respiratory dysfunction is a major contributor to morbidity and mortality in aged populations. The susceptibility to pulmonary insults is attributed to "low pulmonary reserve", ostensibly reflecting a combination of age-related musculoskeletal, immunologic and intrinsic pulmonary dysfunction. METHODS/PRINCIPAL FINDINGS: Using a murine model of the aging lung, senescent DBA/2 mice, we correlated a longitudinal survey of airspace size and injury measures with a transcriptome from the aging lung at 2, 4, 8, 12, 16 and 20 months of age. Morphometric analysis demonstrated a nonlinear pattern of airspace caliber enlargement with a critical transition occurring between 8 and 12 months of age marked by an initial increase in oxidative stress, cell death and elastase activation which is soon followed by inflammatory cell infiltration, immune complex deposition and the onset of airspace enlargement. The temporally correlative transcriptome showed exuberant induction of immunoglobulin genes coincident with airspace enlargement. Immunohistochemistry, ELISA analysis and flow cytometry demonstrated increased immunoglobulin deposition in the lung associated with a contemporaneous increase in activated B-cells expressing high levels of TLR4 (toll receptor 4 and CD86 and macrophages during midlife. These midlife changes culminate in progressive airspace enlargement during late life stages. CONCLUSION/SIGNIFICANCE: Our findings establish that a tissue-specific aging program is evident during a presenescent interval which involves early oxidative stress, cell death and elastase activation, followed by B lymphocyte and macrophage expansion/activation. This sequence heralds the progression to overt airspace enlargement in the aged lung. These signature events, during middle age, indicate that early stages of the aging immune system may have important correlates in the maintenance of tissue morphology. We further show that time-course analyses of aging

  13. Ribosomopathy-like properties of murine and human cancers.

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    Sucheta Kulkarni

    Full Text Available Ribosomopathies comprise a heterogeneous group of hematologic and developmental disorders, often characterized by bone marrow failure, skeletal and other developmental abnormalities and cancer predisposition. They are associated with mutations and/or haplo-insufficiencies of ribosomal proteins (RPs and inefficient ribosomal RNA (rRNA processing. The resulting ribosomal stress induces the canonical p19ARF/Mdm2/p53 tumor suppressor pathway leading to proliferative arrest and/or apoptosis. It has been proposed that this pathway is then inactivated during subsequent neoplastic evolution. We show here that two murine models of hepatoblastoma (HB and hepatocellular carcinoma (HCC unexpectedly possess features that mimic the ribosomopathies. These include loss of the normal stoichiometry of RP transcripts and proteins and the accumulation of unprocessed rRNA precursors. Silencing of p19ARF, cytoplasmic sequestration of p53, binding to and inactivation of Mdm2 by free RPs, and up-regulation of the pro-survival protein Bcl-2 may further cooperate to drive tumor growth and survival. Consistent with this notion, re-instatement of constitutive p19ARF expression in the HB model completely suppressed tumorigenesis. In >2000 cases of human HCC, colorectal, breast, and prostate cancer, RP transcript deregulation was a frequent finding. In HCC and breast cancer, the severity of this dysregulation was associated with inferior survival. In HCC, the presence of RP gene mutations, some of which were identical to those previously reported in ribosomopathies, were similarly negatively correlated with long-term survival. Taken together, our results indicate that many if not all cancers possess ribosomopathy-like features that may affect their biological behaviors.

  14. Helicobacter pylori impairs murine dendritic cell responses to infection.

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    Ya-Hui Wang

    Full Text Available BACKGROUND: Helicobacter pylori, a human pathogen associated with chronic gastritis, peptic ulcer and gastric malignancies, is generally viewed as an extracellular microorganism. Here, we show that H. pylori replicates in murine bone marrow derived-dendritic cells (BMDCs within autophagosomes. METHODOLOGY/PRINCIPAL FINDINGS: A 10-fold increase of CFU is found between 2 h and 6 h p.i. in H. pylori-infected BMDCs. Autophagy is induced around the bacterium and participates at late time points of infection for the clearance of intracellular H. pylori. As a consequence of infection, LC3, LAMP1 and MHC class II molecules are retained within the H. pylori-containing vacuoles and export of MHC class II molecules to cell surface is blocked. However, formalin-fixed H. pylori still maintain this inhibitory activity in BMDC derived from wild type mice, but not in from either TLR4 or TLR2-deficient mice, suggesting the involvement of H. pylori-LPS in this process. TNF-alpha, IL-6 and IL-10 expression was also modulated upon infection showing a TLR2-specific dependent IL-10 secretion. No IL-12 was detected favoring the hypothesis of a down modulation of DC functions during H. pylori infection. Furthermore, antigen-specific T cells proliferation was also impaired upon infection. CONCLUSIONS/SIGNIFICANCE: H. pylori can infect and replicate in BMDCs and thereby affects DC-mediated immune responses. The implication of this new finding is discussed for the biological life cycle of H. pylori in the host.

  15. Induction and regulation of murine emphysema by elastin peptides.

    Science.gov (United States)

    Sellami, Mehdi; Meghraoui-Kheddar, Aïda; Terryn, Christine; Fichel, Caroline; Bouland, Nicole; Diebold, Marie-Daniele; Guenounou, Moncef; Héry-Huynh, Stéphanie; Le Naour, Richard

    2016-01-01

    Emphysema is the major component of chronic obstructive pulmonary disease (COPD). During emphysema, elastin breakdown in the lung tissue originates from the release of large amounts of elastase by inflammatory cells. Elevated levels of elastin-derived peptides (EP) reflect massive pulmonary elastin breakdown in COPD patients. Only the EP containing the GXXPG conformational motif with a type VIII β-turn are elastin receptor ligands inducing biological activities. In addition, the COOH-terminal glycine residue of the GXXPG motif seems a prerequisite to the biological activity. In this study, we endotracheally instilled C57BL/6J mice with GXXPG EP and/or COOH-terminal glycine deleted-EP whose sequences were designed by molecular dynamics and docking simulations. We investigated their effect on all criteria associated with the progression of murine emphysema. Bronchoalveolar lavages were recovered to analyze cell profiles by flow cytometry and lungs were prepared to allow morphological and histological analysis by immunostaining and confocal microscopy. We observed that exposure of mice to EP elicited hallmark features of emphysema with inflammatory cell accumulation associated with increased matrix metalloproteinases and desmosine expression and of remodeling of parenchymal tissue. We also identified an inactive COOH-terminal glycine deleted-EP that retains its binding-activity to EBP and that is able to inhibit the in vitro and in vivo activities of emphysema-inducing EP. This study demonstrates that EP are key actors in the development of emphysema and that they represent pharmacological targets for an alternative treatment of emphysema based on the identification of EP analogous antagonists by molecular modeling studies. Copyright © 2016 the American Physiological Society.

  16. Inactivation of murine norovirus by chemical biocides on stainless steel

    Science.gov (United States)

    2009-01-01

    Background Human norovirus (NoV) causes more than 80% of nonbacterial gastroenteritis in Europe and the United States. NoV transmission via contaminated surfaces may be significant for the spread of viruses. Therefore, measures for prevention and control, such as surface disinfection, are necessary to interrupt the dissemination of human NoV. Murine norovirus (MNV) as a surrogate for human NoV was used to study the efficacy of active ingredients of chemical disinfectants for virus inactivation on inanimate surfaces. Methods The inactivating properties of different chemical biocides were tested in a quantitative carrier test with stainless steel discs without mechanical action. Vacuum-dried MNV was exposed to different concentrations of alcohols, peracetic acid (PAA) or glutaraldehyde (GDA) for 5 minutes exposure time. Detection of residual virus was determined by endpoint-titration on RAW 264.7 cells. Results PAA [1000 ppm], GDA [2500 ppm], ethanol [50% (v/v)] and 1-propanol [30% (v/v)] were able to inactivate MNV under clean conditions (0.03% BSA) on the carriers by ≥ 4 log10 within 5 minutes exposure time, whereas 2-propanol showed a reduced effectiveness even at 60% (v/v). Furthermore, there were no significant differences in virus reduction whatever interfering substances were used. When testing with ethanol, 1- and 2-propanol, results under clean conditions were nearly the same as in the presence of dirty conditions (0.3% BSA plus 0.3% erythrocytes). Conclusion Products based upon PAA, GDA, ethanol and 1-propanol should be used for NoV inactivation on inanimate surfaces. Our data provide valuable information for the development of strategies to control NoV transmission via surfaces. PMID:19583832

  17. Inactivation of murine norovirus by chemical biocides on stainless steel

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    Steinmann Jörg

    2009-07-01

    Full Text Available Abstract Background Human norovirus (NoV causes more than 80% of nonbacterial gastroenteritis in Europe and the United States. NoV transmission via contaminated surfaces may be significant for the spread of viruses. Therefore, measures for prevention and control, such as surface disinfection, are necessary to interrupt the dissemination of human NoV. Murine norovirus (MNV as a surrogate for human NoV was used to study the efficacy of active ingredients of chemical disinfectants for virus inactivation on inanimate surfaces. Methods The inactivating properties of different chemical biocides were tested in a quantitative carrier test with stainless steel discs without mechanical action. Vacuum-dried MNV was exposed to different concentrations of alcohols, peracetic acid (PAA or glutaraldehyde (GDA for 5 minutes exposure time. Detection of residual virus was determined by endpoint-titration on RAW 264.7 cells. Results PAA [1000 ppm], GDA [2500 ppm], ethanol [50% (v/v] and 1-propanol [30% (v/v] were able to inactivate MNV under clean conditions (0.03% BSA on the carriers by ≥ 4 log10 within 5 minutes exposure time, whereas 2-propanol showed a reduced effectiveness even at 60% (v/v. Furthermore, there were no significant differences in virus reduction whatever interfering substances were used. When testing with ethanol, 1- and 2-propanol, results under clean conditions were nearly the same as in the presence of dirty conditions (0.3% BSA plus 0.3% erythrocytes. Conclusion Products based upon PAA, GDA, ethanol and 1-propanol should be used for NoV inactivation on inanimate surfaces. Our data provide valuable information for the development of strategies to control NoV transmission via surfaces.

  18. Effect of bleaching agent extracts on murine macrophages.

    Science.gov (United States)

    Fernandes, Aletéia M M; Vilela, Polyana G F; Valera, Marcia C; Bolay, Carola; Hiller, Karl Anton; Schweikl, Helmut; Schmalz, Gottfried

    2018-05-01

    The aim of this study was to evaluate the cytotoxicity and the influence of bleaching agents on immunologically cell surface antigens of murine macrophages in vitro. RAW 264.7 cells were exposed to bleaching gel extracts (40% hydrogen peroxide or 20% carbamide peroxide) and different H 2 O 2 concentrations after 1 and 24-h exposure periods and 1-h exposure and 23-h recovery. Tests were performed with and without N-acetyl cysteine (NAC) and buthionine sulfoximine (BSO). Cell viability was determined by MTT assay. The expression of surface markers CD14, CD40, and CD54 with and without LPS stimulation was detected by flow cytometry, while the production of TNF-α was measured by ELISA. Statistical analysis was performed using the Mann-Whitney U test (α = 0.05). Extracts of bleaching agents were cytotoxic for cells after a 1-h exposure; cells could not recover after 24 h. This effect can be mitigated by the antioxidant NAC and increased by BSO, an inhibitor of glutathione (GSH) synthesis. LPS stimulated expression of all surface markers and TNF-α production. Exposure to bleaching agent extracts and H 2 O 2 leads to a reduction of TNF-α, CD14, and CD40 expression, while the expression of CD54 was upregulated at non-cytotoxic concentrations. Whereas NAC reduced this effect, it was increased in the presence of BSO. Extracts of bleaching agents were irreversibly cytotoxic to macrophages after a 1-h exposure. Only the expression of CD54 was upregulated. The reactions are mediated by the non-enzymatic antioxidant GSH. The addition of an antioxidant can downregulate unfavorable effects of dental bleaching.

  19. In vitro assessment of curcumin against murine neuroblastoma cells.

    Science.gov (United States)

    Vanisree, Arambakkam Janardhanam; Ramanan, Ramya

    2007-04-01

    Neuroblastoma (NB) is a well-known malignant disease in infants, which comprises 10% of childhood malignancies. Despite recent advances in understanding the neuro-oncology, NB still accounts for more death in childhood than any other cancer. Research in childhood tumors should not only be focused on the malignant signatures of cancer cells but also novel drug prototypes using phytochemicals. The present study was aimed to determine the role of curcumin against murine neuroblastoma cell line (N2a). The in vitro assessment of curcumin against was made in N2a cell line in a dose-dependent manner (group I (control) and group II - IX (10 microM-80 microM). The efficacy of the drug was evaluated by estimating the levels of protein bound carbohydrates, glycoprotein, genomic DNA, total RNA levels, and inhibition of MMP-9 were studied. The gap junctional communication in the cells was also assessed. The levels of protein bound carbohydrates, DNA, RNA levels, glycoprotein were found to be altered on drug supplementation in NB cells. Inhibition of MMP-9 in curcumin-supplemented N2a cells was revealed by zymographic analysis. Assessment of Lucifer yellow dye uptake in curcumin-supplemented N2a cells showed the up-regulation of GJIC. These observations suggest that the curcumin, the active principle of curcuma longa, could be developed into an effective chemo preventive and chemotherapeutic agent. This selected concentration range needs further studies at molecular level, for conforming its role and its action against uncontrolled proliferation of NB.

  20. Murine model for congenital CMV infection and hearing impairment

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    Tao Liu

    2011-02-01

    Full Text Available Abstract Background Congenital cytomegalovirus (CMV infection is the leading cause of sensorineural hearing loss (SNHL, and SNHL is the most frequent sequela of congenital CMV infection. But the pathogenic mechanism remains unknown, and there is no ideal CMV intrauterine infection animal model to study the mechanisms by which SNHL develops. Methods We established the congenital murine cytomegalovirus (MCMV infection model by directly injecting the virus into the placenta on day 12.5 of gestation. Then, we observed the development and the MCMV congenital infection rate of the fetuses on the day they were born. Furthermore, we detected the auditory functions, the conditions of the MCMV infection, and the histological change of the inner ears of 28-day-old and 70-day-old offspring. Results Both the fetal loss rate and the teratism rate of offspring whose placentas were inoculated with MCMV increased, and their body length, head circumference, and weight decreased. The hearing level of offspring both decreased at both 28- and 70-days post birth; the 70-day-old mice developed lower hearing levels than did the 28-day old mice. No significant inflammatory changes in the cochleae of the mice were observed. MCMV DNA signals were mainly detected in the spiral ganglion neurons and the endolymph area, but not in the perilymph area. The number of neurons decreased, and their ultrastructures changed. Moreover, with age, the number of neurons dramatically decreased, and the ultrastructural lesions of neurons became much more severe. Conclusions The results suggest that the direct injection of MCMV into the placenta may efficiently cause fetal infection and disturb the intrauterine development of the fetus, and placental inoculation itself has no obvious adverse effects on offspring. The reduction in the number of spiral ganglion neurons and the ultrastructural lesions of the neurons may be the major cause of congenital CMV infection-induced progressive SNHL.

  1. Murine macrophage heparanase: inhibition and comparison with metastatic tumor cells

    International Nuclear Information System (INIS)

    Savion, N.; Disatnik, M.H.; Nevo, Z.

    1987-01-01

    Circulating macrophages and metastatic tumor cells can penetrate the vascular endothelium and migrate from the circulatory system to extravascular compartments. Both activated murine macrophages and different metastatic tumor cells attach, invade, and penetrate confluent vascular endothelial cell monolayer in vitro, by degrading heparan sulfate proteoglycans in the subendothelial extracellular matrix. The sensitivity of the enzymes from the various sources degrading the heparan sulfate proteoglycan was challenged and compared by a series of inhibitors. Activated macrophages demonstrate a heparanase with an endoglycosidase activity that cleaves from the [ 35 S]O 4 - -labeled heparan sulfate proteoglycans of the extracellular matrix 10 kDa glycosaminoglycan fragments. The degradation of [ 35 S]O 4 - -labeled extracellular matrix proteoglycans by the macrophages' heparanase is significantly inhibited in the presence of heparan sulfate (10μg/ml), arteparon (10μg/ml), and heparin at a concentration of 3 μg/ml. Degradation of this heparan sulfate proteoglycan is a two-step sequential process involving protease activity followed by heparanase activity. B16-BL6 metastatic melanoma cell heparanase, which is also a cell-associated enzyme, was inhibited by heparin to the same extent as the macrophage haparanase. On the other hand, heparanase of the highly metastatic variant (ESb) of a methylcholanthrene-induced T lymphoma, which is an extracellular enzyme released by the cells to the incubation medium, was more sensitive to heparin and arteparon than the macrophages' heparanase. These results may indicate the potential use of heparin or other glycosaminoglycans as specific and differential inhibitors for the formation in certain cases of blood-borne tumor metastasis

  2. Radiobiologic effect of intermittent radiation exposure in murine tumors

    International Nuclear Information System (INIS)

    Sugie, Chikao; Shibamoto, Yuta; Ito, Masato; Ogino, Hiroyuki; Miyamoto, Akihiko; Fukaya, Nobuyuki; Niimi, Hiroshige; Hashizume, Takuya

    2006-01-01

    Purpose: In stereotactic irradiation using a linear accelerator, the effect of radiation may be reduced during intermittent exposures owing to recovery from sublethal damage in tumor cells. After our previous in vitro study suggesting this phenomenon, we investigated the issue in murine tumors. Methods and Materials: We used EMT6 and SCCVII tumors approximately 1 cm in diameter growing in the hind legs of syngeneic mice. Three schedules of intermittent radiation were investigated. First, 2 fractions of 10 Gy were given at an interval of 15-360 min to investigate the pattern of recovery from sublethal damage. Second, 5 fractions of 4 Gy were given with interfraction intervals of 2.5-15 min each. Third, 10 fractions of 2 Gy were given with interfraction intervals of 1-7 min each. Doses of 15-20 Gy were also given without interruption to estimate the dose-modifying factors. Tumors were excised 20 h later, and tumor cell survival was determined by an in vivo-in vitro assay. Results: In the 2-fraction experiment, the increase in cell survival with elongation of the interval was much less than that observed in our previous in vitro study. In the 5- and 10-fraction experiments, no significant increase in cell survival was observed after the intermittent exposures. Moreover, cell survival decreased at most points of the 5-fraction experiments by interruption of radiation in both EMT6 and SCCVII tumors. In the 10-fraction experiment, cell survival also decreased when the interruption was 3 or 7 min in EMT6 tumors. Conclusion: The results of the present in vivo studies were different from those of our in vitro studies in which cell survival increased significantly when a few minutes or longer intervals were posed between fractions. This suggests that recovery from sublethal damage in vivo may be counterbalanced by other phenomena such as reoxygenation that sensitizes tumor cells to subsequent irradiation

  3. Nuclear localization of Annexin A7 during murine brain development

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    Noegel Angelika A

    2005-04-01

    Full Text Available Abstract Background Annexin A7 is a member of the annexin protein family, which is characterized by its ability to interact with phospholipids in the presence of Ca2+-ions and which is thought to function in Ca2+-homeostasis. Results from mutant mice showed altered Ca2+-wave propagation in astrocytes. As the appearance and distribution of Annexin A7 during brain development has not been investigated so far, we focused on the distribution of Annexin A7 protein during mouse embryogenesis in the developing central nervous system and in the adult mouse brain. Results Annexin A7 is expressed in cells of the developing brain where a change in its subcellular localization from cytoplasm to nucleus was observed. In the adult CNS, the subcellular distribution of Annexin A7 depends on the cell type. By immunohistochemistry analysis Annexin A7 was detected in the cytosol of undifferentiated cells at embryonic days E5–E8. At E11–E15 the protein is still present in the cytosol of cells predominantly located in the ventricular germinative zone surrounding the lateral ventricle. Later on, at embryonic day E16, Annexin A7 in cells of the intermediate and marginal zone of the neopallium translocates to the nucleus. Neuronal cells of all areas in the adult brain present Annexin A7 in the nucleus, whereas glial fibrillary acidic protein (GFAP-positive astrocytes exhibit both, a cytoplasmic and nuclear staining. The presence of nuclear Annexin A7 was confirmed by extraction of the nucleoplasm from isolated nuclei obtained from neuronal and astroglial cell lines. Conclusion We have demonstrated a translocation of Annexin A7 to nuclei of cells in early murine brain development and the presence of Annexin A7 in nuclei of neuronal cells in the adult animal. The role of Annexin A7 in nuclei of differentiating and mature neuronal cells remains elusive.

  4. Development of a murine model of blunt hepatic trauma.

    Science.gov (United States)

    Nemzek-Hamlin, Jean A; Hwang, Haejin; Hampel, Joseph A; Yu, Bi; Raghavendran, Krishnan

    2013-10-01

    Despite the prevalence of blunt hepatic trauma in humans, there are few rodent models of blunt trauma that can be used to study the associated inflammatory responses. We present a mouse model of blunt hepatic trauma that was created by using a cortical contusion device. Male mice were anesthetized with ketamine-xylazine-buprenorphine and placed in left lateral recumbency. A position of 2 mm ventral to the posterior axillary line and 5 mm caudal to the costal margin on the right side was targeted for impact. An impact velocity of 6 m/s and a piston depth of 12 mm produced a consistent pattern of hepatic injury with low mortality. All mice that recovered from anesthesia survived without complication for the length of the study. Mice were euthanized at various time points (n = 5 per group) until 7 d after injury for gross examination and collection of blood and peritoneal lavage fluids. Some mice were reanesthetized for serial monitoring of hepatic lesions via MRI. At 2 h after trauma, mice consistently displayed laceration, hematoma, and discoloration of the right lateral and caudate liver lobes, with intraabdominal hemorrhage but no other gross injuries. Blood and peritoneal lavage fluid were collected from all mice for cytokine analysis. At 2 h after trauma, there were significant increases in plasma IL10 as well as peritoneal lavage fluid IL6 and CXCL1/KC; however, these levels decreased within 24 h. At 7 d after trauma, the mice had regained body weight, and the hepatic lesions, which initially had increased in size during the first 48 h, had returned to their original size. In summary, this technique produced a reliable, low mortality, murine model that recreates features of blunt abdominal liver injury in human subjects with similar acute inflammatory response.

  5. Ureaplasma parvum causes hyperammonemia in a pharmacologically immunocompromised murine model.

    Science.gov (United States)

    Wang, X; Greenwood-Quaintance, K E; Karau, M J; Block, D R; Mandrekar, J N; Cunningham, S A; Mallea, J M; Patel, R

    2017-03-01

    A relationship between hyperammonemia and Ureaplasma infection has been shown in lung transplant recipients. We have demonstrated that Ureaplasma urealyticum causes hyperammonemia in a novel immunocompromised murine model. Herein, we determined whether Ureaplasma parvum can do the same. Male C3H mice were given mycophenolate mofetil, tacrolimus, and prednisone for 7 days, and then challenged with U. parvum intratracheally (IT) and/or intraperitoneally (IP), while continuing immunosuppression over 6 days. Plasma ammonia concentrations were determined and compared using Wilcoxon rank-sum tests. Plasma ammonia concentrations of immunosuppressed mice challenged IT/IP with spent broth (median, 188 μmol/L; range, 102-340 μmol/L) were similar to those of normal (median, 226 μmol/L; range, 154-284 μmol/L, p > 0.05), uninfected immunosuppressed (median, 231 μmol/L; range, 122-340 μmol/L, p > 0.05), and U. parvum IT/IP challenged immunocompetent (median, 226 μmol/L; range, 130-330 μmol/L, p > 0.05) mice. Immunosuppressed mice challenged with U. parvum IT/IP (median 343 μmol/L; range 136-1,000 μmol/L) or IP (median 307 μmol/L; range 132-692 μmol/L) had higher plasma ammonia concentrations than those challenged IT/IP with spent broth (p < 0.001). U. parvum can cause hyperammonemia in pharmacologically immunocompromised mice.

  6. Discrete innervation of murine taste buds by peripheral taste neurons.

    Science.gov (United States)

    Zaidi, Faisal N; Whitehead, Mark C

    2006-08-09

    The peripheral taste system likely maintains a specific relationship between ganglion cells that signal a particular taste quality and taste bud cells responsive to that quality. We have explored a measure of the receptoneural relationship in the mouse. By injecting single fungiform taste buds with lipophilic retrograde neuroanatomical markers, the number of labeled geniculate ganglion cells innervating single buds on the tongue were identified. We found that three to five ganglion cells innervate a single bud. Injecting neighboring buds with different color markers showed that the buds are primarily innervated by separate populations of geniculate cells (i.e., multiply labeled ganglion cells are rare). In other words, each taste bud is innervated by a population of neurons that only connects with that bud. Palate bud injections revealed a similar, relatively exclusive receptoneural relationship. Injecting buds in different regions of the tongue did not reveal a topographic representation of buds in the geniculate ganglion, despite a stereotyped patterned arrangement of fungiform buds as rows and columns on the tongue. However, ganglion cells innervating the tongue and palate were differentially concentrated in lateral and rostral regions of the ganglion, respectively. The principal finding that small groups of ganglion cells send sensory fibers that converge selectively on a single bud is a new-found measure of specific matching between the two principal cellular elements of the mouse peripheral taste system. Repetition of the experiments in the hamster showed a more divergent innervation of buds in this species. The results indicate that whatever taste quality is signaled by a murine geniculate ganglion neuron, that signal reflects the activity of cells in a single taste bud.

  7. Enhancers Are Major Targets for Murine Leukemia Virus Vector Integration

    Science.gov (United States)

    De Ravin, Suk See; Su, Ling; Theobald, Narda; Choi, Uimook; Macpherson, Janet L.; Poidinger, Michael; Symonds, Geoff; Pond, Susan M.; Ferris, Andrea L.; Hughes, Stephen H.

    2014-01-01

    ABSTRACT Retroviral vectors have been used in successful gene therapies. However, in some patients, insertional mutagenesis led to leukemia or myelodysplasia. Both the strong promoter/enhancer elements in the long terminal repeats (LTRs) of murine leukemia virus (MLV)-based vectors and the vector-specific integration site preferences played an important role in these adverse clinical events. MLV integration is known to prefer regions in or near transcription start sites (TSS). Recently, BET family proteins were shown to be the major cellular proteins responsible for targeting MLV integration. Although MLV integration sites are significantly enriched at TSS, only a small fraction of the MLV integration sites (integration map of more than one million integration sites from CD34+ hematopoietic stem cells transduced with a clinically relevant MLV-based vector. The integration sites form ∼60,000 tight clusters. These clusters comprise ∼1.9% of the genome. The vast majority (87%) of the integration sites are located within histone H3K4me1 islands, a hallmark of enhancers. The majority of these clusters also have H3K27ac histone modifications, which mark active enhancers. The enhancers of some oncogenes, including LMO2, are highly preferred targets for integration without in vivo selection. IMPORTANCE We show that active enhancer regions are the major targets for MLV integration; this means that MLV preferentially integrates in regions that are favorable for viral gene expression in a variety of cell types. The results provide insights for MLV integration target site selection and also explain the high risk of insertional mutagenesis that is associated with gene therapy trials using MLV vectors. PMID:24501411

  8. Autoerotic death due to electrocution

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    Piotr Arkuszewski

    2014-08-01

    Full Text Available Autoerotic death is a very rare case in forensic medicine. It is usually caused by asphyxia, but other reasons are also possible. Herein we present a case of autoerotic death due to electrocution caused by a self-made electrical device. The device was constructed to increase sexual feelings through stimulation of the scrotal area.

  9. Dose due to 40K

    International Nuclear Information System (INIS)

    Escareno J, E.; Vega C, H. R.

    2011-10-01

    The dose due to 40 K has been estimated. Potassium is one of the most abundant elements in nature, being approximately 2% of the Earth's crust. Potassium has three isotopes 39 K, 40 K and 41 K, two are stable while 40 K is radioactive with a half life of 1.2x10 9 years; there is 0.0117% 40 K-to-K ratio. Potassium plays an important role in plants, animals and humans growth and reproduction. Due to the fact that K is an essential element for humans, 40 K is the most abundant radioisotope in human body. In order to keep good health conditions K must be intake at daily basis trough food and beverages, however when K in ingested above the requirements produce adverse health effects in persons with renal, cardiac and hypertension problems or suffering diabetes. In 89.3% 40 K decays to 40 C through β-decay, in 10.3% decays through electronic capture and emitting 1.46 MeV γ-ray. K is abundant in soil, construction materials, sand thus γ-rays produced during 40 K decay contribute to external dose. For K in the body practically all 40 K decaying energy is absorbed by the body; thus 40 K contributes to total dose in humans and it is important to evaluate its contribution. In this work a set of 40 K sources were prepared using different amounts of KCl salt, a γ-ray spectrometer with a NaI(Tl) was characterized to standardized the sources in order to evaluate the dose due to 40 K. Using thermoluminescent dosemeters the dose due to 40 K was measured and related to the amount of 40 K γ-ray activity. (Author)

  10. Classifying murine glomerulonephritis using optical coherence tomography and optical coherence elastography.

    Science.gov (United States)

    Liu, Chih-Hao; Du, Yong; Singh, Manmohan; Wu, Chen; Han, Zhaolong; Li, Jiasong; Chang, Anthony; Mohan, Chandra; Larin, Kirill V

    2016-08-01

    Acute glomerulonephritis caused by antiglomerular basement membrane marked by high mortality. The primary reason for this is delayed diagnosis via blood examination, urine analysis, tissue biopsy, or ultrasound and X-ray computed tomography imaging. Blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution, with reduced sensitivity. Optical coherence tomography is a noninvasive and high-resolution imaging technique that provides superior spatial resolution (micrometer scale) as compared to ultrasound and CT. Changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signals, such as optical attenuation and speckle variance. Furthermore, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, OCT has been utilized to quantify the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, its classification accuracy is clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improves from 76% to 95%. These results show that OCT combined with OCE can be a powerful tool for identifying and classifying nephritis. Therefore, the OCT/OCE method could potentially be used as a minimally invasive tool for longitudinal studies during the progression and therapy of glomerulonephritis as well as complement and, perhaps, substitute highly invasive tissue biopsies. Elastic-wave propagation in mouse healthy and nephritic kidneys. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Dosage effect of a Phex mutation in a murine model of X-linked hypophosphatemia

    Science.gov (United States)

    Ichikawa, Shoji; Gray, Amie K.; Bikorimana, Emmanuel; Econs, Michael J.

    2013-01-01

    X-linked hypophosphatemia (XLH) is caused by mutations in the PHEX gene, which increase circulating levels of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Since XLH is a dominant disease, one mutant allele is sufficient for manifestation of the disease. However, dosage effect of a PHEX mutation in XLH is not completely understood. To examine the effect of Phex genotypes, we compared serum biochemistries and skeletal measures between all five possible genotypes of a new murine model of XLH (PhexK496X or PhexJrt). Compared to sex-matched littermate controls, all Phex mutant mice had hypophosphatemia, mild hypocalcemia, and increased parathyroid hormone and alkaline phosphatase levels. Furthermore, mutant mice had markedly elevated serum Fgf23 levels due to increased Fgf23 expression and reduced cleavage of Fgf23. Although females with a homozygous Phex mutation were slightly more hypocalcemic and hypophosphatemic than heterozygous females, the two groups had comparable intact Fgf23 levels. Similarly, there was no difference in intact Fgf23 or phosphorus concentrations between hemizygous males and heterozygous females. Compared to heterozygous females, homozygous counterparts were significantly smaller and had shorter femurs with reduced bone mineral density, suggesting the existence of dosage effect in the skeletal phenotype of XLH. However, overall phenotypic trends in regards to mineral ion homeostasis were mostly unaffected by the presence of one or two mutant Phex allele(s). The lack of gene dosage effect on circulating Fgf23 (and thus, phosphorus) levels suggests that a Phex mutation may create the lower set point for extracellular phosphate concentrations. PMID:23700148

  12. Virucidal efficacy of treatment with photodynamically activated curcumin on murine norovirus bio-accumulated in oysters.

    Science.gov (United States)

    Wu, Juan; Hou, Wei; Cao, Binbin; Zuo, Tao; Xue, Changhu; Leung, Albert Wingnang; Xu, Chuanshan; Tang, Qing-Juan

    2015-09-01

    Norovirus (NoV) is one of the most important seafood- and water-borne viruses, and is a major cause of acute gastroenteritis outbreaks. In the present study we investigated the effect of curcumin as a sensitizer to photodynamic treatment both in buffer and in oysters against murine norovirus 1 (MNV-1), a surrogate of NoV. MNV-1 cultured in buffer and MNV-1 bio-accumulated in oysters were irradiated with a novel LED light source with a wavelength of 470nm and an energy of 3.6J/cm(2). Inactivation of MNV-1 was investigated by plaque assays. After virus was extracted from the gut of oysters treated over a range of curcumin concentrations, the ultrastructural morphology of the virus was observed using electron microscopy, and the integrity of viral nucleic acids and stability of viral capsid proteins were also determined. Results showed that the infectivity of MNV-1 was significantly inhibited by 1-3logPFU/ml, with significant damage to viral nucleic acids in a curcumin dose-dependent manner after photodynamic activation. Virus morphology was altered after the photodynamic treatment with curcumin, presumably due to the change of the viral capsid protein structures. The data suggest that treatment of oysters with photodynamic activation of curcumin is a potentially efficacious and cost-effective method to inactivate food-borne NoV. Further studies are necessary to evaluate the toxicology of this approach in detail and perform sensory evaluation of the treated product. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Functional imaging of murine hearts using accelerated self-gated UTE cine MRI.

    Science.gov (United States)

    Motaal, Abdallah G; Noorman, Nils; de Graaf, Wolter L; Hoerr, Verena; Florack, Luc M J; Nicolay, Klaas; Strijkers, Gustav J

    2015-01-01

    We introduce a fast protocol for ultra-short echo time (UTE) Cine magnetic resonance imaging (MRI) of the beating murine heart. The sequence involves a self-gated UTE with golden-angle radial acquisition and compressed sensing reconstruction. The self-gated acquisition is performed asynchronously with the heartbeat, resulting in a randomly undersampled kt-space that facilitates compressed sensing reconstruction. The sequence was tested in 4 healthy rats and 4 rats with chronic myocardial infarction, approximately 2 months after surgery. As a control, a non-accelerated self-gated multi-slice FLASH sequence with an echo time (TE) of 2.76 ms, 4.5 signal averages, a matrix of 192 × 192, and an acquisition time of 2 min 34 s per slice was used to obtain Cine MRI with 15 frames per heartbeat. Non-accelerated UTE MRI was performed with TE = 0.29 ms, a reconstruction matrix of 192 × 192, and an acquisition time of 3 min 47 s per slice for 3.5 averages. Accelerated imaging with 2×, 4× and 5× undersampled kt-space data was performed with 1 min, 30 and 15 s acquisitions, respectively. UTE Cine images up to 5× undersampled kt-space data could be successfully reconstructed using a compressed sensing algorithm. In contrast to the FLASH Cine images, flow artifacts in the UTE images were nearly absent due to the short echo time, simplifying segmentation of the left ventricular (LV) lumen. LV functional parameters derived from the control and the accelerated Cine movies were statistically identical.

  14. Expansion of murine gammaherpesvirus latently infected B cells requires T follicular help.

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    Christopher M Collins

    2014-05-01

    Full Text Available X linked lymphoproliferative disease (XLP is an inherited immunodeficiency resulting from mutations in the gene encoding the slam associated protein (SAP. One of the defining characteristics of XLP is extreme susceptibility to infection with Epstein-Barr virus (EBV, a gammaherpesvirus belonging to the genus Lymphocryptovirus, often resulting in fatal infectious mononucleosis (FIM. However, infection of SAP deficient mice with the related Murine gammaherpesvirus 68 (MHV68, a gammaherpesvirus in the genus Rhadinovirus, does not recapitulate XLP. Here we show that MHV68 inefficiently establishes latency in B cells in SAP deficient mice due to insufficient CD4 T cell help during the germinal center response. Although MHV68 infected B cells can be found in SAP-deficient mice, significantly fewer of these cells had a germinal center phenotype compared to SAP-sufficient mice. Furthermore, we show that infected germinal center B cells in SAP-deficient mice fail to proliferate. This failure to proliferate resulted in significantly lower viral loads, and likely accounts for the inability of MHV68 to induce a FIM-like syndrome. Finally, inhibiting differentiation of T follicular helper (TFH cells in SAP-sufficient C57Bl/6 mice resulted in decreased B cell latency, and the magnitude of the TFH response directly correlated with the level of infection in B cells. This requirement for CD4 T cell help during the germinal center reaction by MHV68 is in contrast with EBV, which is thought to be capable of bypassing this requirement by expressing viral proteins that mimic signals provided by TFH cells. In conclusion, the outcome of MHV68 infection in mice in the setting of loss of SAP function is distinct from that observed in SAP-deficient patients infected with EBV, and may identify a fundamental difference between the strategies employed by the rhadinoviruses and lymphocryptoviruses to expand B cell latency during the early phase of infection.

  15. An Anacardiaceae preparation reduces the expression of inflammation-related genes in murine macrophages.

    Science.gov (United States)

    Leiro, J; García, D; Arranz, J A; Delgado, R; Sanmartín, M L; Orallo, F

    2004-08-01

    This study investigated the effects of an aqueous extract of the stem bark of Mangifera indica L. (Anacardiaceae; Vimang), which contains a defined mixture of components including polyphenols (principally mangiferin, MA), triterpenes, phytosteroids, fatty acids and microelements, on expression of inflammation mediators in inflammatory murine macrophages after stimulation in vitro with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). In vitro treatment with Vimang at 4 microg/ml reduced levels of NOS-2 mRNA and NOS-2, while treatment at 40 microg/ml also reduced levels of COX-2 mRNA, COX-2, and prostaglandin E2 (PGE2). Results suggested that MA is involved in these effects. In vitro treatment with Vimang at 40 microg/ml also inhibited mRNA levels of the proinflammatory cytokines interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha) and colony-stimulating factor (GM-CSF), but did not affect mRNA levels of IL-6 or tumor growth factor-beta (TGF-beta). Extracellular release of TNF-alpha by inflammatory macrophages was inhibited by in vitro treatment with Vimang at the same concentrations that showed inhibition of TNF-alpha mRNA levels. The inhibition of TNF-alpha production appears to be at least partially attributable to MA. Vimang at 4 microg/ml decreased mRNA levels of nuclear factor-kappaB (NF-kappaB) but did not affect expression of the NF-kappaB inhibitor (IkappaB). These data indicate that the potent anti-inflammatory effects of Vimang are due to selective modulation of the expression of inflammation-related genes, leading to attenuation of macrophage activation.

  16. Protein-RNA linkage and posttranslational modifications of feline calicivirus and murine norovirus VPg proteins

    Directory of Open Access Journals (Sweden)

    Allan Olspert

    2016-06-01

    Full Text Available Members of the Caliciviridae family of positive sense RNA viruses cause a wide range of diseases in both humans and animals. The detailed characterization of the calicivirus life cycle had been hampered due to the lack of robust cell culture systems and experimental tools for many of the members of the family. However, a number of caliciviruses replicate efficiently in cell culture and have robust reverse genetics systems available, most notably feline calicivirus (FCV and murine norovirus (MNV. These are therefore widely used as representative members with which to examine the mechanistic details of calicivirus genome translation and replication. The replication of the calicivirus RNA genome occurs via a double-stranded RNA intermediate that is then used as a template for the production of new positive sense viral RNA, which is covalently linked to the virus-encoded protein VPg. The covalent linkage to VPg occurs during genome replication via the nucleotidylylation activity of the viral RNA-dependent RNA polymerase. Using FCV and MNV, we used mass spectrometry-based approach to identify the specific amino acid linked to the 5′ end of the viral nucleic acid. We observed that both VPg proteins are covalently linked to guanosine diphosphate (GDP moieties via tyrosine positions 24 and 26 for FCV and MNV respectively. These data fit with previous observations indicating that mutations introduced into these specific amino acids are deleterious for viral replication and fail to produce infectious virus. In addition, we also detected serine phosphorylation sites within the FCV VPg protein with positions 80 and 107 found consistently phosphorylated on VPg-linked viral RNA isolated from infected cells. This work provides the first direct experimental characterization of the linkage of infectious calicivirus viral RNA to the VPg protein and highlights that post-translational modifications of VPg may also occur during the viral life cycle.

  17. Influence of maternal gestational treatment with mycobacterial antigens on postnatal immunity in an experimental murine model.

    Directory of Open Access Journals (Sweden)

    Muhammad Jubayer Rahman

    Full Text Available BACKGROUND: It has been proposed that the immune system could be primed as early as during the fetal life and this might have an impact on postnatal vaccination. Therefore, we addressed in murine models whether gestational treatment with mycobacterial antigens could induce better immune responses in the postnatal life. METHODS/FINDINGS: BALB/c mice were treated subcutaneously (s.c. at the second week of gestation with antigen (Ag85A or heparin-binding hemagglutinin (HBHA in the absence of adjuvant. Following birth, offspring mice were immunized intranasally (i.n. with the same antigens formulated with the adjuvant cholera toxin (CT at week 1 and week 4. One week after the last immunization, we assessed antigen-specific recall interferon gamma (IFN-gamma responses by in vitro restimulation of lung-derived lymphocytes. Protection against infection was assessed by challenge with high dose Mycobacterium bovis Bacille Calmette-Guérin (BCG given i.n. We found that recall IFN-gamma responses were higher in the offspring born to the treated mother compared to the untreated-mother. More importantly, we observed that the offspring born to the treated mother controlled infection better than the offspring born to the untreated mother. Since the gestational treatment was done in absence of adjuvant, essentially there was no antibody production observed in the pregnant mice and therefore no influence of maternal antibodies was expected. We hypothesized that the effect of maternal treatment with antigen on the offspring occurred due to antigen transportation through placenta. To trace the antigens, we conjugated fluorescent nanocrystals with Ag85A (Qdot-ITK-Ag85A. After inoculation in the pregnant mice, Qdot-ITK-Ag85A conjugates were detected in the liver, spleen of pregnant females and in all the fetuses and placentas examined. CONCLUSION: The fetal immune system could be primed in utero by mycobacterial antigens transported through the placenta.

  18. Apoptosis induction and attenuation of inflammatory gene expression in murine macrophages via multitherapeutic nanomembranes

    International Nuclear Information System (INIS)

    Pierstorff, Erik; Krucoff, Max; Ho, Dean

    2008-01-01

    The realization of optimized therapeutic delivery is impaired by the challenge of localized drug activity and by the dangers of systemic cytotoxicity which often contribute to patient treatment complications. Here we demonstrate the block copolymer-mediated deposition and release of multiple therapeutics which include an LXRα/β agonist 3-((4-methoxyphenyl)amino)-4-phenyl-1-(phenylmethyl)-1H-pyrrole-2,5-dione (LXRa) and doxorubicin hydrochloride (Dox) at the air-water interface via Langmuir-Blodgett deposition, as well as copolymer-mediated potent drug elution toward the Raw 264.7 murine macrophage cell line. The resultant copolymer-therapeutic hybrid serves as a localized platform that can be functionalized with virtually any drug due to the integrated hydrophilic and hydrophobic components of the polymer structure. In addition, the sequestering function of the copolymer to anchor the drugs to implant surfaces can enhance delivery specificity when compared to systemic drug administration. Confirmation of drug functionality was confirmed via suppression of the interleukin 6 (Il-6) and tumor necrosis factor alpha (TNFα) inflammatory cytokines (LXRa), as well as DNA fragmentation analysis (Dox). Furthermore, the fragmentation assays and gene expression analysis demonstrated the innate biocompatibility of the copolymeric material at the gene expression level via the confirmed absence of material-induced apoptosis and a lack of inflammatory gene expression. This modality enables layer-by-layer control of agonist and chemotherapeutic functionalization at the nanoscale for the localization of drug dosage, while simultaneously utilizing the copolymer platform as an anchoring mechanism for drug sequestering, all with an innate material thickness of 4 nm per layer, which is orders of magnitude thinner than existing commercial technologies. Furthermore, these studies comprehensively confirmed the potential translational applicability of copolymeric nanomaterials as

  19. Comparative Virucidal Efficacy of Seven Disinfectants Against Murine Norovirus and Feline Calicivirus, Surrogates of Human Norovirus.

    Science.gov (United States)

    Zonta, William; Mauroy, Axel; Farnir, Frederic; Thiry, Etienne

    2016-03-01

    Human noroviruses (HuNoV) are the leading cause of acute non-bacterial gastroenteritis in humans and can be transmitted either by person-to-person contact or by consumption of contaminated food. A knowledge of an efficient disinfection for both hands and food-contact surfaces is helpful for the food sector and provides precious information for public health. The aim of this study was to evaluate the effect of seven disinfectants belonging to different groups of biocides (alcohol, halogen, oxidizing agents, quaternary ammonium compounds, aldehyde and biguanide) on infectious viral titre and on genomic copy number. Due to the absence of a cell culture system for HuNoV, two HuNoV surrogates, such as murine norovirus and feline calicivirus, were used and the tests were performed in suspension, on gloves and on stainless steel discs. When, as criteria of efficacy, a log reduction >3 of the infectious viral titre on both surrogates and in the three tests is used, the most efficacious disinfectants in this study appear to be biocidal products B, C and D, representing the halogens, the oxidizing agents group and a mix of QAC, alcohol and aldehyde, respectively. In addition, these three disinfectants also elicited a significant effect on genomic copy number for both surrogate viruses and in all three tests. The results of this study demonstrate that a halogen compound, oxidizing agents and a mix of QAC, alcohol and aldehyde are advisable for HuNoV disinfection of either potentially contaminated surfaces or materials in contact with foodstuffs.

  20. Murine liver damage caused by exposure to nano-titanium dioxide

    International Nuclear Information System (INIS)

    Hong, Jie; Zhang, Yu-Qing

    2016-01-01

    Due to its unique physiochemical properties, nano-titanium dioxide (nano-TiO_2) is widely used in all aspects of people’s daily lives, bringing it into increasing contact with humans. Thus, this material’s security issues for humans have become a heavily researched subject. Nano-TiO_2 can enter the body through the mouth, skin, respiratory tract or in other ways, after which it enters the blood circulation and is deposited in the liver, changing biochemical indicators and causing liver inflammation. Meanwhile, the light sensitivity of these nanoparticles allows them to become media-generating reactive oxygen species (ROS), causing an imbalance between oxidation and anti-oxidation that leads to oxidative stress and liver damage. Nano-TiO_2 can be transported into cells via phagocytosis, where the nanoparticles bind to the mitochondrial membrane, resulting in the disintegration of the membrane and the electron transport chain within the mitochondria. Thus, more ROS are produced. Nano-TiO_2 can also enter the nucleus, where it can directly embed into or indirectly affect DNA, thereby causing DNA breakage or affecting gene expression. These effects include increased mRNA and protein expression levels of inflammation-related factors and decreased mRNA and protein expression levels of IκB and IL-2, resulting in inflammation. Long-term inflammation of the liver causes HSC cell activation, and extracellular matrix (ECM) deposition is promoted by multiple signalling pathways, resulting in liver fibrosis. In this paper, the latest progress on murine liver injury induced by environmental TiO_2 is systematically described. The toxicity of nano-TiO_2 also depends on size, exposure time, surface properties, dosage, administration route, and its surface modification. Therefore, its toxic effects in humans should be studied in greater depth. This paper also provides useful reference information regarding the safe use of nano-TiO_2 in the future. (topical review)

  1. Proteolytically modified human beta 2-microglobulin augments the specific cytotoxic activity in murine mixed lymphocyte culture

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Claësson, M H

    1987-01-01

    the endogenous production of interleukin 2 in the MLC culture; monoclonal antibody which reacts with both the native beta 2-m and M-beta 2-m molecule blocks the augmentation of cytotoxic T lymphocyte production induced by M-beta 2-m; murine as well as human MLC responder cells can proteolytically modify native......A proteolytically modified form of beta 2-microglobulin (beta 2-m) present in the serum of patients suffering from autoimmune, immunodeficient diseases and cancer has been reported in the literature. In the present study we show that human beta 2-m as well as the proteolytically modified human form...... (M-beta 2-m) bind to murine lymphocytes expressing H-2 class I antigens; M-beta 2-m, when added at day 0 and 1 of culture in nanomolar concentrations to a one-way murine allogeneic mixed lymphocyte culture (MLC) augments the generation of specific cytotoxic T lymphocytes; M-beta 2-m increases...

  2. Local IL-23 expression in murine vaginal candidiasis and its relationship with infection and immune status.

    Science.gov (United States)

    Wu, Yan; Tan, Zhijian; Liu, Zhixiang; Xia, Dechao; Li, Jiawen

    2006-01-01

    To investigate the expression of vaginal IL-23 and its role in experimental murine vaginal candidiasis and its relationship with infection and immune status, immuno-competent (group A) and immuno-suppressed (group B) murine models of vaginal candidiasis were established in estrogen-treated mice. Non-estrogen-treated mice were used as controls (group C). The level of IL-23 p19 mRNA in murine vaginal tissue was determined by RT-PCR. Significantly increased levels of IL-23p19mRNA were observed on the 4th, the 7th and 14th day after inoculation in immuno-competent group when compared with that in control group (Pvaginal candidiasis and has a protective function during infection. Low vaginal IL-23 level may correlate with the increased susceptibility to Candida albicans in immuno-suppressed group.

  3. Characterization of an immunodominant cancer-specific O-glycopeptide epitope in murine podoplanin (OTS8)

    DEFF Research Database (Denmark)

    Steentoft, Catharina; Schjoldager, Katrine T; Cló, Emiliano

    2010-01-01

    antibody 237, developed to a spontaneous murine fibrosarcoma, was shown to be directed to murine podoplanin (OTS8) with truncated Tn O-glycans. Our understanding of such cancer-specific auto-antibodies to truncated glycoforms of glycoproteins is limited. Here we have investigated immunogenicity...... of a chemoenzymatically produced Tn-glycopeptide derived from the putative murine podoplanin O-glycopeptide epitope. We found that the Tn O-glycopeptide was highly immunogenic in mice and produced a Tn-glycoform specific response with no reactivity against unglycosylated peptides or the O-glycopeptide with extended O......-glycan (STn and T glycoforms). The immunodominant epitope was strictly dependent on the peptide sequence, required Tn at a specific single Thr residue (Thr(77)), and antibodies to the epitope were not found in naive mice. We further tested a Tn O-glycopeptide library derived from human podoplanin...

  4. Murine models of H. pylori-induced gastritis and gastric adenocarcinoma.

    Science.gov (United States)

    Krueger, Sabine; Roessner, Albert; Kuester, Doerthe

    2011-10-15

    Laboratory mice have become one of the best animal species for mechanistic studies in gastrointestinal research. Their abundant genetic information, the way of causing carcinogenesis easily by transgenic and gene knockout techniques, limited effort in time and costs, and their practicability provide advantages over other animal models. Meanwhile, several murine practical models have been established for the investigation of the initiation, expansion, and progression of gastritis and gastric carcinoma, for assessing the effects of bacterial, genetic and environmental factors, and for evaluating therapeutic and preventive strategies in gastric diseases. This article gives a review of murine models of gastritis and gastric cancer, placing emphasis on the models associated with Helicobacter pylori infection and techniques used in our laboratory. We discuss matters of murine gastric anatomy, as well as techniques of infection, tissue preparation, and histology. Copyright © 2011 Elsevier GmbH. All rights reserved.

  5. Depressive disorder due to craniopharyngioma.

    Science.gov (United States)

    Spence, S A; Taylor, D G; Hirsch, S R

    1995-01-01

    Secondary causes of depression are legion, and must always be considered in patients presenting with features atypical of primary idiopathic depressive disorder. The case described is that of a middle-aged woman presenting initially with a major depressive disorder who was subsequently found to have a craniopharyngioma, leading to a revised diagnosis of mood disorder due to the tumour. Some features of the presentation might have led to earlier diagnosis had their localizing significance been recognized. Diencephalic lesions should always be considered in patients presenting with the hypersomnic-hyperphagic variant of depressive disorder. Images Figure 1 PMID:8544149

  6. Maculopathy due to drug inhalation.

    Science.gov (United States)

    Asensio-Sánchez, V M; Gonzalez-Buendia, L; Marcos-Fernández, M

    2014-08-01

    A case of maculopathy due to "poppers" is described. Poppers is a drug composed of various forms of alkyl nitrite. A 39 year-old man, who had been using poppers for years, was seen in the clinic with phosphenes, reduced visual acuity and central scotoma. The SD-OCT in the right eye showed disruption at the level of the IS/OS junction line. The SD-OCT scan in the left eye showed an outer rectangular retinal hole and an outer retinal cyst. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  7. Anaphylaxis Due to Head Injury

    Directory of Open Access Journals (Sweden)

    Bruner, Heather C.

    2015-05-01

    Full Text Available Both anaphylaxis and head injury are often seen in the emergency department, but they are rarely seen in combination. We present a case of a 30-year-old woman who presented with anaphylaxis with urticaria and angioedema following a minor head injury. The patient responded well to intramuscular epinephrine without further complications or airway compromise. Prior case reports have reported angioedema from hereditary angioedema during dental procedures and maxillofacial surgery, but there have not been any cases of first-time angioedema or anaphylaxis due to head injury. [West J Emerg Med. 2015;16(3:435–437.

  8. Anaphylaxis due to head injury.

    Science.gov (United States)

    Bruner, Heather C; Bruner, David I

    2015-05-01

    Both anaphylaxis and head injury are often seen in the emergency department, but they are rarely seen in combination. We present a case of a 30-year-old woman who presented with anaphylaxis with urticaria and angioedema following a minor head injury. The patient responded well to intramuscular epinephrine without further complications or airway compromise. Prior case reports have reported angioedema from hereditary angioedema during dental procedures and maxillofacial surgery, but there have not been any cases of first-time angioedema or anaphylaxis due to head injury.

  9. PIF1 disruption or NBS1 hypomorphism does not affect chromosome healing or fusion resulting from double-strand breaks near telomeres in murine embryonic stem cells.

    Science.gov (United States)

    Reynolds, Gloria E; Gao, Qing; Miller, Douglas; Snow, Bryan E; Harrington, Lea A; Murnane, John P

    2011-11-10

    Telomerase serves to maintain telomeric repeat sequences at the ends of chromosomes. However, telomerase can also add telomeric repeat sequences at DNA double-strand breaks (DSBs), a process called chromosome healing. Here, we employed a method of inducing DSBs near telomeres to query the role of two proteins, PIF1 and NBS1, in chromosome healing in mammalian cells. PIF1 was investigated because the PIF1 homolog in Saccharomyces cerevisiae inhibits chromosome healing, as shown by a 1000-fold increase in chromosome in PIF1-deficient cells. NBS1 was investigated because the functional homolog of NBS1 in S. cerevisiae, Xrs2, is part of the Mre11/Rad50/Xrs2 complex that is required for chromosome healing due to its role in the processing of DSBs and recruitment of telomerase. We found that disruption of mPif1 had no detectable effect on the frequency of chromosome healing at DSBs near telomeres in murine embryonic stem cells. Moreover, the Nbs1(ΔB) hypomorph, which is defective in the processing of DSBs, also had no detectable effect on the frequency of chromosome healing, DNA degradation, or gross chromosome rearrangements (GCRs) that result from telomeric DSBs. Although we cannot rule out small changes in chromosome healing using this system, it is clear from our results that knockout of PIF1 or the Nbs1(ΔB) hypomorph does not result in large differences in chromosome healing in murine cells. These results represent the first genetic assessment of the role of these proteins in chromosome healing in mammals, and suggest that murine cells have evolved mechanisms to ensure the functional redundancy of Pif1 or Nbs1 in the regulation of chromosome healing. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Adherence of murine lymphocytes to high endothelial venules in vitro and its radiation effect

    Energy Technology Data Exchange (ETDEWEB)

    Lixin, Liu; Zijun, Mao; Zhiwei, Yin [Suzhou Medical Coll., JS (China). Dept. of Pathophysiology

    1991-02-01

    Using the assay of specific adhesion of lymphocytes to high endothelial venules (HEV) on cryostat sections of mesenteric lymph nodes (MLN), the effects of different doses (0, 1, 2, 4, 8 Gy) of {sup 60}Co {gamma}-ray irradiation of murine MLN lymphocytes in vitro on adhesion to normal HEV was observed. The results showed that in the irradiated murine MLN lymphocytes the ability to adhere to HEV of normal MLN was reduced. Statistical significance was revealed at 2, 4, 8 Gy irradiations. This results suggests that irradiation can inhibit the specific recognition and adhesion of lymphocytes to HEV to a certain extent.

  11. Tick-Borne Transmission of Murine Gammaherpesvirus 68

    Directory of Open Access Journals (Sweden)

    Valeria Hajnická

    2017-10-01

    Full Text Available Herpesviruses are a large group of DNA viruses infecting mainly vertebrates. Murine gammaherpesvirus 68 (MHV68 is often used as a model in studies of the pathogenesis of clinically important human gammaherpesviruses such as Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. This rodent virus appears to be geographically widespread; however, its natural transmission cycle is unknown. Following detection of MHV68 in field-collected ticks, including isolation of the virus from tick salivary glands and ovaries, we investigated whether MHV68 is a tick-borne virus. Uninfected Ixodes ricinus ticks were shown to acquire the virus by feeding on experimentally infected laboratory mice. The virus survived tick molting, and the molted ticks transmitted the virus to uninfected laboratory mice on which they subsequently fed. MHV68 was isolated from the tick salivary glands, consistent with transmission via tick saliva. The virus survived in ticks without loss of infectivity for at least 120 days, and subsequently was transmitted vertically from one tick generation to the next, surviving more than 500 days. Furthermore, the F1 generation (derived from F0 infected females transmitted MHV68 to uninfected mice on which they fed, with MHV68 M3 gene transcripts detected in blood, lung, and spleen tissue of mice on which F1 nymphs and F1 adults engorged. These experimental data fulfill the transmission criteria that define an arthropod-borne virus (arbovirus, the largest biological group of viruses. Currently, African swine fever virus (ASFV is the only DNA virus recognized as an arbovirus. Like ASFV, MHV68 showed evidence of pathogenesis in ticks. Previous studies have reported MHV68 in free-living ticks and in mammals commonly infested with I. ricinus, and neutralizing antibodies to MHV68 have been detected in large mammals (e.g., deer including humans. Further studies are needed to determine if these reports are the result of tick-borne transmission

  12. Botulinum Toxin Confers Radioprotection in Murine Salivary Glands

    Energy Technology Data Exchange (ETDEWEB)

    Zeidan, Youssef H., E-mail: zeidan@miami.edu [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Xiao, Nan; Cao, Hongbin [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Kong, Christina [Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California (United States); Department of Pathology, Stanford University School of Medicine, Stanford, California (United States); Le, Quynh-Thu; Sirjani, Davud [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States)

    2016-04-01

    Purpose: Xerostomia is a common radiation sequela, which has a negative impact on the quality of life of patients with head and neck cancer. Current treatment strategies offer only partial relief. Botulinum toxins (BTX) have been successfully used in treating a variety of radiation sequelae such as cystitis, proctitis, fibrosis, and facial pain. The purpose of this study was to evaluate the effect of BTX on radiation-induced salivary gland damage. Methods and Materials: We used a previously established model for murine salivary gland irradiation (IR). The submandibular glands (SMGs) of C5BL/6 mice (n=6/group) were injected with saline or BTX 72 hours before receiving 15 Gy of focal irradiation. Saliva flow was measured 3, 7, and 28 days after treatment. The SMGs were collected for immunohistochemistry, confocal microscopy, and Western blotting. A cytokine array consisting of 40 different mouse cytokines was used to evaluate cytokine profiles after radiation treatment. Results: Irradiated mice showed a 50% reduction in saliva flow after 3 days, whereas mice preinjected with BTX had 25% reduction in saliva flow (P<.05). Cell death detected by TUNEL staining was similar in SMG sections of both groups. However, neutrophil infiltrate, detected by myeloperoxidase staining, was 3-fold lower for the BTX treated mice. A cytokine array showed a 2-fold upregulation of LPS-induced chemokine (LIX/CXCL5) 3 days after IR. BTX pretreatment reduced LIX levels by 40%. At 4 weeks after IR, the saline (control) group showed a 40% reduction in basal SMG weight, compared with 20% in the BTX group. Histologically, BTX-pretreated glands showed relative preservation of acinar structures after radiation. Conclusions: These data suggest that BTX pretreatment ameliorates radiation-induced saliva dysfunction. Moreover, we demonstrate a novel role for CXCL5 in the acute phase of salivary gland damage after radiation. These results carry important clinical implications for the treatment of

  13. DYSTOCIA DUE TO SOFT TISSUE

    Science.gov (United States)

    DeCarle, Donald W.

    1954-01-01

    In dystocia caused by abnormal conditions of the soft parts, the etiologic changes may be either in the genital tissues or in adjacent soft structures. Broadly, the conditions causing the difficulty may be grouped as follows: (1) anomalies or congenital modifications; (2) tumors; (3) modifications due to age, accident or surgical operations; (4) modification of the expulsive forces; (5) abnormalities of the products of conception. Often in such circumstances cesarean section is necessary. Sometimes when tumor is present it can be removed before it interferes with delivery, but decision to excise the growth must be guided by such factors as the location of the lesion and the stage of gestation. This would determine to what extent the maintenance of pregnancy would be jeopardized by surgical intervention before term. PMID:13190430

  14. Single fatherhood due to cancer.

    Science.gov (United States)

    Yopp, Justin M; Rosenstein, Donald L

    2012-12-01

    Cancer is a leading cause of widowed fatherhood in the USA. Fathers whose spouses have died from cancer constitute a potentially vulnerable population as they adjust to their role as sole or primary caregiver while managing their own grief and that of their children. The importance of addressing the psychological needs of widowed fathers is underscored by data showing that father's coping and emotional availability are closely tied to their bereaved children's mental health. Surprisingly, scant attention has been given to the phenomenon of widowed fatherhood with virtually no clinical resources or research studies devoted to fathers who have lost their wives to cancer. This commentary highlights key challenges facing this underserved population of widowers and calls for development of research agendas and clinical interventions for single fathers due to cancer. Copyright © 2011 John Wiley & Sons, Ltd.

  15. Occupational injuries due to violence.

    Science.gov (United States)

    Hales, T; Seligman, P J; Newman, S C; Timbrook, C L

    1988-06-01

    Each year in the United States, an estimated 800 to 1,400 people are murdered at work, and an unknown number of nonfatal injuries due to workplace violence occur. Based on Ohio's workers' compensation claims from 1983 through 1985, police officers, gasoline service station employees, employees of the real estate industry, and hotel/motel employees were found to be at the highest risk for occupational violent crime (OVC) injury and death. Grocery store employees, specifically those working in convenience food stores, and employees of the real estate industry had the most reported rapes. Four previously unidentified industries at increased risk of employee victimization were described. Identification of industries and occupations at high risk for crime victimization provides the opportunity to focus preventive strategies to promote employee safety and security in the workplace.

  16. APPENDICULAR INVAGINATION DUE TO ENDOMETRIOSIS

    Directory of Open Access Journals (Sweden)

    Vasja Kruh

    2003-12-01

    Full Text Available Background. Invagination of the vermiform appendix is a very rare occurrence. We summarize epidemiologic and etiologic factors, types of classification, symtomatology, diagnostic features and treatment.Patients and treatment. The authors present 49-years old female with long-standing abdominal pains, who came in our hospital due to acute exacerbation with sever abdominal pain. Because of progressive symptoms and sensitivity in the right-lower abdominal quadrant a diagnostic laparoscopy was performed. An anomaly of cecum and the absence of appendix vermiformis have forced us to proceed with laparotomy in McBurnay point. After cecotomy an invaginated gangrenous appendix was found. The histological examination revealed endometriosis.Conclusions. By presenting this extremely rare pathology we also want to emphasize the important role of diagnostic laparoscopy in front of acute abdomen.

  17. Eosinophilic myocarditis during treatment with olanzapine

    DEFF Research Database (Denmark)

    Vang, Torkel; Rosenzweig, Mary; Bruhn, Christina Hedegaard

    2016-01-01

    -mortem toxicological examination demonstrated presence of olanzapine, morphine, venlafaxine and oxazepam. Syringes indicating substance abuse were found in his home. Case 2 was a 36-year-old Caucasian man diagnosed with schizophrenia was found dead unexpectedly. There was no history of substance abuse. Current...

  18. Acute fulminant myocarditis complicated by complete atrioventricular ...

    African Journals Online (AJOL)

    room (ER) of a tertiary care hospital with a 5-day history of high-grade, ... catheter was inserted into the right ventricle at midseptal level (pacing .... system; BiPAP = Bilevel positive airway pressure; CVL = central venous line; IJV = internal ...

  19. Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease.

    Directory of Open Access Journals (Sweden)

    Eniko Nagy

    Full Text Available Studies in transgenic murine models have provided insight into the complexity underlying inflammatory bowel disease (IBD, a disease hypothesized to result from an injurious immune response against intestinal microbiota. We recently developed a mouse model of IBD that phenotypically and histologically resembles human childhood-onset ulcerative colitis (UC, using mice that are genetically modified to be deficient in the cytokines TNF and IL-10 ("T/I" mice. Here we report the effects of early life onset of colon inflammation on growth and reproductive performance of T/I mice. T/I dams with colitis often failed to get pregnant or had small litters with pups that failed to thrive. Production was optimized by breeding double homozygous mutant T/I males to females homozygous mutant for TNF deficiency and heterozygous for deficiency of IL-10 ("T/I-het" dams that were not susceptible to spontaneous colon inflammation. When born to healthy (T/I-het dams, T/I pups initially gained weight similarly to wild type (WT pups and to their non-colitis-susceptible T/I-het littermates. However, their growth curves diverged between 8 and 13 weeks, when most T/I mice had developed moderate to severe colitis. The observed growth failure in T/I mice occurred despite a significant increase in their food consumption and in the absence of protein loss in the stool. This was not due to TNF-induced anorexia or altered food consumption due to elevated leptin levels. Metabolic studies demonstrated increased consumption of oxygen and water and increased production of heat and CO2 in T/I mice compared to their T/I-het littermates, without differences in motor activity. Based on the clinical similarities of this early life onset model of IBD in T/I mice to human IBD, these results suggest that mechanisms previously hypothesized to explain growth failure in children with IBD require re-evaluation. The T/I mouse model may be useful for further investigation of such mechanisms and

  20. [Nephropathy due to Puumala hantavirus].

    Science.gov (United States)

    Dandolo, A; Prajs, N; Lizop, M

    2014-12-01

    Hemorrhagic fever with renal syndrome (HFRS) is due to an infection by the virus of the Hantavirus genus. Rodent hosts of Hantavirus are present in restricted areas in France; consequently, there are ecological niches and microepidemics of human Hantavirus infections. A HFRS case was diagnosed in the Paris region. The 11-year-old child had an acute debut fever-persistent despite antipyretic medication-asthenia, headache, abdominal pain, myalgia, thrombocytopenia, as well as renal failure with proteinuria. The diagnosis was made with a relevant clinical history and the specific serology of Puumala hantavirus. Therefore, a kidney biopsy was not necessary. What was interesting was the diagnostic approach because of the difference between the place and time of contamination and where the child became ill and developed the symptoms. The child was infected by Puumala hantavirus in Les Ardennes, a high-risk area, but became ill in the Paris region, an area with no prevalence. We review Hantavirus infections in France and its differential diagnosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. Structural Basis for Species Selectivity in the HIV-1 gp120-CD4 Interaction: Restoring Affinity to gp120 in Murine CD4 Mimetic Peptides

    Directory of Open Access Journals (Sweden)

    Kristin Kassler

    2011-01-01

    Full Text Available The first step of HIV-1 infection involves interaction between the viral glycoprotein gp120 and the human cellular receptor CD4. Inhibition of the gp120-CD4 interaction represents an attractive strategy to block HIV-1 infection. In an attempt to explore the known lack of affinity of murine CD4 to gp120, we have investigated peptides presenting the putative gp120-binding site of murine CD4 (mCD4. Molecular modeling indicates that mCD4 protein cannot bind gp120 due to steric clashes, while the larger conformational flexibility of mCD4 peptides allows an interaction. This finding is confirmed by experimental binding assays, which also evidenced specificity of the peptide-gp120 interaction. Molecular dynamics simulations indicate that the mCD4-peptide stably interacts with gp120 via an intermolecular β-sheet, while an important salt-bridge formed by a C-terminal lysine is lost. Fixation of the C-terminus by introducing a disulfide bridge between the N- and C-termini of the peptide significantly enhanced the affinity to gp120.

  2. In Vivo Efficacy of Plazomicin Alone or in Combination with Meropenem or Tigecycline against Enterobacteriaceae Isolates Exhibiting Various Resistance Mechanisms in an Immunocompetent Murine Septicemia Model.

    Science.gov (United States)

    Abdelraouf, Kamilia; Kim, Aryun; Krause, Kevin M; Nicolau, David P

    2018-06-04

    Background : Plazomicin is a next-generation aminoglycoside with potent in vitro activity against multidrug- and carbapenem-resistant Enterobacteriaceae. The objective of this study was to assess the efficacy of plazomicin exposure, alone and in combination with meropenem or tigecycline, against Enterobacteriaceae in the immunocompetent murine septicemia model. Methods : ICR mice were inoculated intraperitoneally with bacterial suspensions. Eight Enterobacteriaceae isolates with wide ranges of plazomicin, meropenem and tigecycline MICs were utilized. Treatment mice were administered plazomicin, meropenem or tigecycline human-equivalent doses alone or in combinations of plazomicin/meropenem and plazomicin/tigecycline. Treatments were initiated 1h post-infection and continued for 24h. Efficacy was assessed by survival through 96h. Results : Compared with controls, plazomicin monotherapy produced significant improvement in survival for all isolates (P32 and 2 mg/L, respectively), combination therapies showed significant reduction in mortality compared with any monotherapy (P<0.05). Conclusion : Plazomicin monotherapy resulted in improved survival in the immunocompetent murine septicemia model, notably for isolates with plazomicin MIC ≤4 mg/L. As evidenced by our current data, co-administration of meropenem or tigecycline could potentially lead to further improvement in survival. These data support a role for plazomicin in the management of septicemia due to Enterobacteriaceae with plazomicin MIC ≤4 mg/L, including carbapenem-resistant isolates. Copyright © 2018 American Society for Microbiology.

  3. Phage-display libraries of murine and human antibody Fab fragments

    DEFF Research Database (Denmark)

    Engberg, J; Andersen, P S; Nielsen, L K

    1996-01-01

    We provide efficient and detailed procedures for construction, expression, and screening of comprehensive libraries of murine or human antibody Fab fragments displayed on the surface of filamentous phage. In addition, protocols for producing and using ultra-electrocompetent cells, for producing Fab...

  4. Coagulation and inflammation in scrub typhus and murine typhusu-a prospective comparative study from Laos

    NARCIS (Netherlands)

    Paris, D. H.; Chansamouth, V.; Nawtaisong, P.; Löwenberg, E. C.; Phetsouvanh, R.; Blacksell, S. D.; Lee, S. J.; Dondorp, A. M.; van der Poll, T.; Newton, P. N.; Levi, M. [=Marcel M.; Day, N. P. J.

    2012-01-01

    Scrub typhus (caused by Orientia tsutsugamushi) and murine typhus (caused by Rickettsia typhi) cause up to 28% of febrile episodes in Thailand and Laos. The current understanding of coagulation and inflammation in the pathogenesis of these clinically very similar vasculotropic diseases is limited.

  5. A murine ESC-like state facilitates transgenesis and homologous recombination in human pluripotent stem cells

    NARCIS (Netherlands)

    C. Buecker (Christa); H.H. Chen; J.M. Polo (Jose); L. Daheron (Laurence); L. Bu (Lei); T.S. Barakat (Tahsin Stefan); P. Okwieka (Patricia); A. Porter (Andrew); J.H. Gribnau (Joost); K. Hochedlinger (Konrad); N. Geijsen (Niels)

    2010-01-01

    textabstractMurine pluripotent stem cells can exist in two functionally distinct states, LIF-dependent embryonic stem cells (ESCs) and bFGF-dependent epiblast stem cells (EpiSCs). However, human pluripotent cells so far seemed to assume only an epiblast-like state. Here we demonstrate that human

  6. Functional imaging of murine hearts using accelerated self-gated UTE cine MRI

    NARCIS (Netherlands)

    Motaal, Abdallah G.; Noorman, Nils; de Graaf, Wolter L.; Hoerr, Verena; Florack, Luc M. J.; Nicolay, Klaas; Strijkers, Gustav J.

    2015-01-01

    We introduce a fast protocol for ultra-short echo time (UTE) Cine magnetic resonance imaging (MRI) of the beating murine heart. The sequence involves a self-gated UTE with golden-angle radial acquisition and compressed sensing reconstruction. The self-gated acquisition is performed asynchronously

  7. P2X7 receptor activation induces cell death and microparticle release in murine erythroleukemia cells.

    NARCIS (Netherlands)

    Constantinescu, P.; Wang, B.; Kovacevic, K.; Jalilian, I.; Bosman, G.J.C.G.M.; Wiley, J.S.; Sluyter, R.

    2010-01-01

    Extracellular ATP induces cation fluxes in and impairs the growth of murine erythroleukemia (MEL) cells in a manner characteristic of the purinergic P2X7 receptor, however the presence of P2X7 in these cells is unknown. This study investigated whether MEL cells express functional P2X7. RT-PCR,

  8. Characterization of murine melanocortin receptors mediating adipocyte lipolysis and examination of signalling pathways involved

    DEFF Research Database (Denmark)

    Møller, Cathrine Laustrup; Raun, Kirsten; Jacobsen, Marianne Lambert

    2011-01-01

    hormone (a-MSH) generated from proopiomelanocortin (POMC), as well as synthetic MSH analogues to stimulate lipolysis in murine 3T3-L1 adipocytes it is shown that MC2R and MC5R are lipolytic mediators in differentiated 3T3-L1 adipocytes. Involvement of cAMP, phosphorylated extracellular signal...

  9. Characterization, expression and complex formation of the murine Fanconi anaemia gene product Fancg.

    Science.gov (United States)

    van de Vrugt, Henri J; Koomen, Mireille; Berns, Mariska A D; de Vries, Yne; Rooimans, Martin A; van der Weel, Laura; Blom, Eric; de Groot, Jan; Schepers, Rik J; Stone, Stacie; Hoatlin, Maureen E; Cheng, Ngan Ching; Joenje, Hans; Arwert, Fré

    2002-03-01

    Fanconi anaemia (FA) is an autosomal recessive chromosomal instability disorder. Six distinct FA disease genes have been identified, the products of which function in an integrated pathway that is thought to support a nuclear caretaker function. Comparison of FA gene characteristics in different species may help to unravel the molecular function of the FA pathway. We have cloned the murine homologue of the Fanconi anaemia complementation group G gene, FANCG/XRCC9. The murine Fancg protein shows an 83% similarity to the human protein sequence, and has a predicted molecular weight of 68.5 kDa. Expression of mouse Fancg in human FA-G lymphoblasts fully corrects their cross-linker hypersensitivity. At mRNA and protein levels we detected the co-expression of Fancg and Fanca in murine tissues. In addition, mouse Fancg and Fanca proteins co-purify by immunoprecipitation. Upon transfection into Fanca-deficient mouse embryonic fibroblasts EGFP-Fancg chimeric protein was detectable in the nucleus. We identified a murine cDNA, Fancg, which cross-complements the cellular defect of human FA-G cells and thus represents a true homologue of human FANCG. Spleen, thymus and testis showed the highest Fancg expression levels. Although Fancg and Fanca are able to form a complex, this interaction is not required for Fancg to accumulate in the nuclear compartment.

  10. Effect of fucoidan on B16 murine melanoma cell melanin formation ...

    African Journals Online (AJOL)

    Background:Fucoidan is a complex sulfated polysaccharide extracted from brown seaweed and has a wide variety of biological activities. It not only inhibits cancer cell growth but also inhibits tyrosinase in vitro. Therefore, it is of interest to investigate the effect of fucoidan on B16 murine melanoma cells as the findings may ...

  11. GPBAR1/TGR5 mediates bile acid-induced cytokine expression in murine Kupffer cells.

    Directory of Open Access Journals (Sweden)

    Guiyu Lou

    Full Text Available GPBAR1/TGR5 is a novel plasma membrane-bound G protein-coupled bile acid (BA receptor. BAs are known to induce the expression of inflammatory cytokines in the liver with unknown mechanism. Here we show that without other external stimuli, TGR5 activation alone induced the expression of interleukin 1β (IL-1β and tumor necrosis factor-α (TNF-α in murine macrophage cell line RAW264.7 or murine Kupffer cells. The TGR5-mediated increase of pro-inflammatory cytokine expression was suppressed by JNK inhibition. Moreover, the induced pro-inflammatory cytokine expression in mouse liver by 1% cholic acid (CA diet was blunted in JNK-/- mice. TGR5 activation by its ligands enhanced the phosphorylation levels, DNA-binding and trans-activities of c-Jun and ATF2 transcription factors. Finally, the induced pro-inflammatory cytokine expression in Kupffer cells by TGR5 activation correlated with the suppression of Cholesterol 7α-hydroxylase (Cyp7a1 expression in murine hepatocytes. These results suggest that TGR5 mediates the BA-induced pro-inflammatory cytokine production in murine Kupffer cells through JNK-dependent pathway. This novel role of TGR5 may correlate to the suppression of Cyp7a1 expression in hepatocytes and contribute to the delicate BA feedback regulation.

  12. In vitro activation of murine DRG neurons by CGRP-mediated mucosal mast cell degranulation

    NARCIS (Netherlands)

    De Jonge, F; De Laet, A; Van Nassauw, L; Miller, HRP; van Bogaert, PP; Timmermans, JP; Kroese, ABA

    Upregulation of CGRP-immunoreactive (IR) primary afferent nerve fibers accompanied by mastocytosis is characteristic for the Schistosoma mansoni-infected murine ileum. These mucosal mast cells (MMC) and CGRP-IR fibers, which originate from dorsal root (DRG) and nodose ganglia, are found in close

  13. Molecular and functional characterization of Kv7 K+ channel in murine gastrointestinal smooth muscles

    DEFF Research Database (Denmark)

    Jepps, Thomas Andrew; Greenwood, Iain A; Moffatt, James D

    2009-01-01

    that K(v)7.x especially K(v)7.4 and K(v)7.5 are expressed in different regions of the murine gastrointestinal tract and blockers of K(v)7 channels augment inherent contractile activity. Drugs that selectively block K(v)7.4/7.5 might be promising therapeutics for the treatment of motility disorders...

  14. Adipocytes enhance murine pancreatic cancer growth via a hepatocyte growth factor (HGF)-mediated mechanism.

    Science.gov (United States)

    Ziegler, Kathryn M; Considine, Robert V; True, Eben; Swartz-Basile, Deborah A; Pitt, Henry A; Zyromski, Nicholas J

    2016-04-01

    Obesity accelerates the development and progression of pancreatic cancer, though the mechanisms underlying this association are unclear. Adipocytes are biologically active, producing factors such as hepatocyte growth factor (HGF) that may influence tumor progression. We therefore sought to test the hypothesis that adipocyte-secreted factors including HGF accelerate pancreatic cancer cell proliferation. Murine pancreatic cancer cells (Pan02 and TGP-47) were grown in a) conditioned medium (CM) from murine F442A preadipocytes, b) HGF-knockdown preadipocyte CM, c) recombinant murine HGF at increasing doses, and d) CM plus HGF-receptor (c-met) inhibitor. Cell proliferation was measured using the MTT assay. ANOVA and t-test were applied; p TGP-47 cell proliferation relative to control (59 ± 12% and 34 ± 12%, p TGP-47 cells remained unchanged. Recombinant HGF dose-dependently increased Pan02, but not TGP-47, proliferation (p TGP-47 cells. These experiments demonstrate that adipocyte-derived factors accelerate murine pancreatic cancer proliferation. In the case of Pan02 cells, HGF is responsible, in part, for this proliferation. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  15. Gastrointestinal expression and partial cDNA cloning of murine Muc2

    NARCIS (Netherlands)

    van Klinken, B. J.; Einerhand, A. W.; Duits, L. A.; Makkink, M. K.; Tytgat, K. M.; Renes, I. B.; Verburg, M.; Büller, H. A.; Dekker, J.

    1999-01-01

    To help us investigate the role of mucin in the protection of the colonic epithelium in the mouse, we aimed to identify the murine colonic mucin (MCM) and its encoding gene. We isolated MCM, raised an anti-MCM antiserum, and studied the biosynthesis of MCM in the gastrointestinal tract. Isolated MCM

  16. Erythropoietin treatment alleviates ultrastructural myelin changes induced by murine cerebral malaria

    DEFF Research Database (Denmark)

    Hempel, Casper; Hyttel, Poul; Staalsø, Trine

    2012-01-01

    the effects of EPO treatment in this context. METHODS: The study consisted of two groups of Plasmodium berghei-infected mice and two groups of uninfected controls that were either treated with EPO or placebo (n = 4 mice/group). In the terminal phase of murine CM the brains were removed and processed...

  17. Development of an ex vivo BrdU labeling procedure for the murine LLNA

    Science.gov (United States)

    The murine local lymph node assay (LLNA) is widely used to identify chemicals that may cause allergic contact dermatitis. Exposure to a dermal sensitizer results in proliferation of local lymph node T cells, which has traditionally been measured by in vivo incorporation of [3H]m...

  18. Modeling of Chronic Myeloid Leukemia : An Overview of In Vivo Murine and Human Xenograft Models

    NARCIS (Netherlands)

    Sontakke, Pallavi; Jaques, Jenny; Vellenga, Edo; Schuringa, Jan Jacob

    2016-01-01

    Over the past years, a wide variety of in vivo mouse models have been generated in order to unravel the molecular pathology of Chronic Myeloid Leukemia (CML) and to develop and improve therapeutic approaches. These models range from (conditional) transgenic models, knock-in models, and murine bone

  19. Murine muscular dystrophy caused by a mutation in the laminin alpha 2 (Lama2) gene

    DEFF Research Database (Denmark)

    Xu, H; Wu, X R; Wewer, U M

    1994-01-01

    The classic murine muscular dystrophy strain, dy, was first described almost 40 years ago. We have identified the molecular basis of an allele of dy, called dy2J, by detecting a mutation in the laminin alpha 2 chain gene--the first identified mutation in laminin-2. The G to A mutation in a splice...

  20. Dual Role of Host Par2 in a Murine Model of Spontaneous Metastatic B16 Melanoma

    Czech Academy of Sciences Publication Activity Database

    Olejár, Tomáš; Větvička, D.; Zadinová, M.; Poučková, P.; Kukal, J.; Ježek, Petr; Matěj, R.

    2014-01-01

    Roč. 34, č. 7 (2014), s. 3511-3515 ISSN 0250-7005 R&D Projects: GA ČR(CZ) GAP302/10/0346 Institutional support: RVO:67985823 Keywords : PAR2 * melanoma * metastasis * murine model Subject RIV: EA - Cell Biology Impact factor: 1.826, year: 2014

  1. The murine retinoblastoma homolog maps to chromosome 14 near Es-10

    NARCIS (Netherlands)

    Stone, J.C.; Crosby, J.J.; Kozak, C.A.; Schievella, A.R.; Bernards, R.A.; Nadeau, J.H.

    1989-01-01

    Restriction fragment length variants have been exploited to map genetically Rb-1, the murine homolog of the human retinoblastoma gene. Rb-1 localized to mouse chromosome 14 on the basis of results from analysis of somatic cell hybrids. In an interspecific backcross involving Mus spretus, Rb-1 and

  2. Porcine humoral immune responses to multiple injections of murine monoclonal antibodies

    DEFF Research Database (Denmark)

    Lohse, Louise; Nielsen, Jens; Kamstrup, Søren

    2005-01-01

    In humans and cattle, multiple injections of murine monoclonal antibodies (m-mAbs) induce anti-mouse antibody responses. The objectives of the present. study were to investigate whether a similar response could be seen when pigs were subjected to m-mAb therapy, and to study the kinetics of such a...

  3. Coinfection with Borrelia burgdorferi sensu stricto and Borrelia garinii alters the course of murine Lyme borreliosis

    NARCIS (Netherlands)

    Hovius, Joppe W. R.; Li, Xin; Ramamoorthi, Nandhini; van Dam, Alje P.; Barthold, Stephen W.; van der Poll, Tom; Speelman, Peter; Fikrig, Erol

    2007-01-01

    Ixodes ricinus ticks and mice can be infected with both Borrelia burgdorferi sensu stricto and Borrelia garinii. The effect of coinfection with these two Borrelia species on the development of murine Lyme borreliosis is unknown. Therefore, we investigated whether coinfection with the

  4. Major differences between human atopic dermatitis and murine models as determined by global transcriptomic profiling

    DEFF Research Database (Denmark)

    Ewald, David Adrian; Noda, Shinji; Oliva, Margeaux

    2017-01-01

    , and a comparison of these models with the human AD transcriptomic fingerprint is lacking. We sought to evaluate the transcriptomic profiles of six common murine models and determine how they relate to human AD skin. Transcriptomic profiling was performed using microarrays and qRT-PCR on biopsies from NC/Nga, flaky...

  5. Limited role of murine ATM in oncogene-induced senescence and p53-dependent tumor suppression.

    Directory of Open Access Journals (Sweden)

    Alejo Efeyan

    Full Text Available Recent studies in human fibroblasts have provided a new general paradigm of tumor suppression according to which oncogenic signaling produces DNA damage and this, in turn, results in ATM/p53-dependent cellular senescence. Here, we have tested this model in a variety of murine experimental systems. Overexpression of oncogenic Ras in murine fibroblasts efficiently induced senescence but this occurred in the absence of detectable DNA damage signaling, thus suggesting a fundamental difference between human and murine cells. Moreover, lung adenomas initiated by endogenous levels of oncogenic K-Ras presented abundant senescent cells, but undetectable DNA damage signaling. Accordingly, K-Ras-driven adenomas were also senescent in Atm-null mice, and the tumorigenic progression of these lesions was only modestly accelerated by Atm-deficiency. Finally, we have examined chemically-induced fibrosarcomas, which possess a persistently activated DNA damage response and are highly sensitive to the activity of p53. We found that the absence of Atm favored genomic instability in the resulting tumors, but did not affect the persistent DNA damage response and did not impair p53-dependent tumor suppression. All together, we conclude that oncogene-induced senescence in mice may occur in the absence of a detectable DNA damage response. Regarding murine Atm, our data suggest that it plays a minor role in oncogene-induced senescence or in p53-dependent tumor suppression, being its tumor suppressive activity probably limited to the maintenance of genomic stability.

  6. Gender and dose dependent ovalbumin induced hypersensitivity responses in murine model of food allergy

    Science.gov (United States)

    While federal regulations mandate the labeling of major food allergens, allowable food allergen thresholds have yet to be determined. Therefore the aim of this project was to identify the lowest egg allergen ovalbumin (OVA) dose causing hypersensitization using a validated murine model. Mice were or...

  7. Novel Application of Micro-Computerized Tomography for Morphologic Characterization of the Murine Penis.

    Science.gov (United States)

    O'Neill, Marisol; Huang, Gene O; Lamb, Dolores J

    2017-12-01

    The murine penis model has enriched our understanding of anomalous penile development. The morphologic characterization of the murine penis using conventional serial sectioning methods is labor intensive and prone to errors. To develop a novel application of micro-computerized tomography (micro-CT) with iodine staining for rapid, non-destructive morphologic study of murine penis structure. Penises were dissected from 10 adult wild-type mice and imaged using micro-CT with iodine staining. Images were acquired at 5-μm spatial resolution on a Bruker SkyScan 1272 micro-CT system. After images were acquired, the specimens were washed of any remaining iodine and embedded in paraffin for conventional histologic examination. Histologic and micro-CT measurements for all specimens were made by 2 independent observers. Measurements of penile structures were made on virtual micro-CT sections and histologic slides. The Lin concordance correlation coefficient demonstrated almost perfect strength of agreement for interobserver variability for histologic section (0.9995, 95% CI = 0.9990-0.9997) and micro-CT section (0.9982, 95% CI = 0.9963-0.9991) measurements. Bland-Altman analysis for agreement between the 2 modalities of measurement demonstrated mean differences of -0.029, 0.022, and -0.068 mm for male urogenital mating protuberance, baculum, and penile glans length, respectively. There did not appear to be a bias for overestimation or underestimation of measured lengths and limits of agreement were narrow. The enhanced ability offered by micro-CT to phenotype the murine penis has the potential to improve translational studies examining the molecular pathways contributing to anomalous penile development. The present study describes the first reported use of micro-CT with iodine staining for imaging the murine penis. Producing repeated histologic sections of identical orientation was limited by inherent imperfections in mounting and tissue sectioning, but this was

  8. Molecular cloning and expression of the human homologue of the murine gene encoding myeloid leukemia-inhibitory factor

    International Nuclear Information System (INIS)

    Gough, N.M.; Gearing, D.P.; King, J.A.; Willson, T.A.; Hilton, D.J.; Nicola, N.A.; Metcalf, D.

    1988-01-01

    A human homologue of the recently cloned murine leukemia-inhibitory factor (LIF) gene was isolated from a genomic library by using the marine cDNA as a hybridization probe. The nucleotide sequence of the human gene indicated that human LIF has 78% amino acid sequence identity with murine LIF, with no insertions or deletions, and that the region of the human gene encoding the mature protein has one intervening sequence. After oligonucleotide-mediated mutagenesis, the mature protein-coding region of the LIF gene was introduced into the yeast expression vector YEpsec1. Yeast cells transformed with the resulting recombinant could be induced with galactose to produce high levels of a factor that induced the differentiation of murine M1 leukemic cells in a manner analogous to murine LIF. This factor competed with 125 I-labeled native murine LIF for binding to specific cellular receptors on murine cells, compatible with a high degree of structural similarity between the murine and human factors

  9. Dose-effect relationship of apoptosis induced by fission-neutron in murine thymocytes

    International Nuclear Information System (INIS)

    Yuan Bin; Li Liang; Xue Wencheng; Sun Jianmin; Wang Baoqin

    2000-01-01

    Objective: To investigate the effectiveness of high LET fission-neutron to induce apoptosis in murine thymocytes and to compare it with that of low LET 60 Co γ-ray. Methods: Apoptosis induction was studied qualitatively by light and transmission electron microscopy and DNA gel electrophoresis,also quantitatively by flow cytometry(FCM) and diphenylamine (DPA)methods. Results: DNA ladders of murine thymocytes were detectable, the typical apoptosis of thymocytes could be observed morphologically by means of light and electron microscopy at 6 h after fission-neutron irradiation with doses ranging from 0.5 to 5.0 Gy, meanwhile the percentages of apoptosis increased with increasing doses. After exposure to γ-rays with doses ranging from 1.0 to 30 Gy, the experimental results were similar to those from neutron radiation. The incidence of apoptosis peaked at about 20 Gy, the percentages did not increase further when doses increased. Conclusion: Apoptosis of murine thymocytes can be induced when mice are exposed to either fission-neutron (0.5-5.0 Gy) or to γ-ray (1-30 Gy). Although the relationship between apoptosis and radiation doses is similar, the percentage of apoptosis induced by neutron irradiation is higher than that induced by γ-irradiation. The RBE values of fission-neutron for inducing apoptosis murine thymocytes are 2.09 (by FCM method) and 2.37 (by DPA method), respectively. These results also suggest that fission-neutron-induced murine immune tissue is more severe than that induced by γ-rays at several hours post-irradiation and this might be the basis for heavy damage to immune tissues induced by fission-neutron-irradiation in later period

  10. The Effects of Inhaled Nickel Nanoparticles on Murine Endothelial Progenitor Cells

    Science.gov (United States)

    Liberda, Eric N.

    Introduction. Particulate air pollution, specifically nickel found on or in particulate matter, has been associated with an increased risk of mortality in human population studies and can cause increases in vascular inflammation, generate reactive oxygen species, alter vasomotor tone, and potentiate atherosclerosis in murine exposures. With the discovery of endothelial progenitor cells (EPCs), a door has been opened which may explain these observed cardiovascular effects associated with inhaled air particles and nickel exposure. In order to further quantify the effects of inhaled nickel nanoparticles and attempt to elucidate how the observed findings from other studies may occur, several whole body inhalation exposure experiments to nickel nanoparticles were performed. Methods. Following whole body exposure to approximately 500mug/m3 of nickel nanoparticles for 5 hrs, bone marrow EPCs from C57BL/6 mice were isolated. EPCs were harvested for their RNA or used in a variety of assays including chemotaxis, tube formation, and proliferation. Gene expression was assessed for important receptors involved in EPC mobilization and homing using RT-PCR methods. EPCs, circulating endothelial progenitor cells, circulating endothelial cells (CECs), and endothelial microparticles (EMPs) were quantified on a BD FACSCalibur to examine endothelial damage and repair associated with the inhalation exposure. Plasma proteins were assessed using the 2D DIGE proteomic approach and commercially available ELISAs. Results and Conclusions. Exposure to inhaled nickel nanoparticles significantly increased both bone marrow EPCs as well as their levels in circulation. CECs were significantly upregulated suggesting that endothelial damage occurred due to the exposure. There was no significant difference in EMPs between the two groups. Tube formation and chemotaxis, but not proliferation, of bone marrow EPCs was impaired in the nickel nanoparticle exposed group. This decrease in EPC function

  11. Involvement of Nitric Oxide on Bothropoides insularis Venom Biological Effects on Murine Macrophages In Vitro.

    Directory of Open Access Journals (Sweden)

    Ramon R P P B de Menezes

    Full Text Available Viperidae venom has several local and systemic effects, such as pain, edema, inflammation, kidney failure and coagulopathy. Additionally, bothropic venom and its isolated components directly interfere on cellular metabolism, causing alterations such as cell death and proliferation. Inflammatory cells are particularly involved in pathological envenomation mechanisms due to their capacity of releasing many mediators, such as nitric oxide (NO. NO has many effects on cell viability and it is associated to the development of inflammation and tissue damage caused by Bothrops and Bothropoides venom. Bothropoides insularis is a snake found only in Queimada Grande Island, which has markedly toxic venom. Thus, the aim of this work was to evaluate the biological effects of Bothropoides insularis venom (BiV on RAW 264.7 cells and assess NO involvement. The venom was submitted to colorimetric assays to identify the presence of some enzymatic components. We observed that BiV induced H2O2 production and showed proteolytic and phospholipasic activities. RAW 264.7 murine macrophages were incubated with different concentrations of BiV and then cell viability was assessed by MTT reduction assay after 2, 6, 12 and 24 hours of incubation. A time- and concentration-dependent effect was observed, with a tendency to cell proliferation at lower BiV concentrations and cell death at higher concentrations. The cytotoxic effect was confirmed after lactate dehydrogenase (LDH measurement in the supernatant from the experimental groups. Flow cytometry analyses revealed that necrosis is the main cell death pathway caused by BiV. Also, BiV induced NO release. The inhibition of both proliferative and cytotoxic effects with L-NAME were demonstrated, indicating that NO is important for these effects. Finally, BiV induced an increase in iNOS expression. Altogether, these results demonstrate that B. insularis venom have proliferative and cytotoxic effects on macrophages, with

  12. Interactions of Francisella tularensis with Alveolar Type II Epithelial Cells and the Murine Respiratory Epithelium.

    Directory of Open Access Journals (Sweden)

    Matthew Faron

    Full Text Available Francisella tularensis is classified as a Tier 1 select agent by the CDC due to its low infectious dose and the possibility that the organism can be used as a bioweapon. The low dose of infection suggests that Francisella is unusually efficient at evading host defenses. Although ~50 cfu are necessary to cause human respiratory infection, the early interactions of virulent Francisella with the lung environment are not well understood. To provide additional insights into these interactions during early Francisella infection of mice, we performed TEM analysis on mouse lungs infected with F. tularensis strains Schu S4, LVS and the O-antigen mutant Schu S4 waaY::TrgTn. For all three strains, the majority of the bacteria that we could detect were observed within alveolar type II epithelial cells at 16 hours post infection. Although there were no detectable differences in the amount of bacteria within an infected cell between the three strains, there was a significant increase in the amount of cellular debris observed in the air spaces of the lungs in the Schu S4 waaY::TrgTn mutant compared to either the Schu S4 or LVS strain. We also studied the interactions of Francisella strains with human AT-II cells in vitro by characterizing the ability of these three strains to invade and replicate within these cells. Gentamicin assay and confocal microscopy both confirmed that F. tularensis Schu S4 replicated robustly within these cells while F. tularensis LVS displayed significantly lower levels of growth over 24 hours, although the strain was able to enter these cells at about the same level as Schu S4 (1 organism per cell, as determined by confocal imaging. The Schu S4 waaY::TrgTn mutant that we have previously described as attenuated for growth in macrophages and mouse virulence displayed interesting properties as well. This mutant induced significant airway inflammation (cell debris and had an attenuated growth phenotype in the human AT-II cells. These

  13. Dietary manipulation and social isolation alter disease progression in a murine model of coronary heart disease.

    Directory of Open Access Journals (Sweden)

    Yumiko Nakagawa-Toyama

    Full Text Available BACKGROUND: Mice with a deficiency in the HDL receptor SR-BI and low expression of a modified apolipoprotein E gene (SR-BI KO/ApoeR61(h/h called 'HypoE' when fed an atherogenic, 'Paigen' diet develop occlusive, atherosclerotic coronary arterial disease (CHD, myocardial infarctions (MI, and heart dysfunction and die prematurely (50% mortality ~40 days after initiation of this diet. Because few murine models share with HypoE mice these cardinal, human-like, features of CHD, HypoE mice represent a novel, small animal, diet-inducible and genetically tractable model for CHD. To better describe the properties of this model, we have explored the effects of varying the composition and timing of administration of atherogenic diets, as well as social isolation vs. group housing, on these animals. METHODOLOGY/PRINCIPAL FINDINGS: HypoE mice were maintained on a standard lab chow diet (control until two months of age. Subsequently they received one of three atherogenic diets (Paigen, Paigen without cholate, Western or control diet for varying times and were housed in groups or singly, and we determined the plasma cholesterol levels, extent of cardiomegaly and/or survival. The rate of disease progression could be reduced by lowering the severity of the atherogenic diet and accelerated by social isolation. Disease could be induced by Paigen diets either containing or free of cholate. We also established conditions under which CHD could be initiated by an atherogenic diet and then subsequently, by replacing this diet with standard lab chow, hypercholesterolemia could be reduced and progression to early death prevented. CONCLUSIONS/SIGNIFICANCE: HypoE mice provide a powerful, surgery-free, diet-'titratable' small animal model that can be used to study the onset of recovery from occlusive, atherosclerotic CHD and heart failure due to MI. HypoE mice can be used for the analysis of the effects of environment (diet, social isolation on a variety of features of

  14. Low-Dose Gene Therapy for Murine PKU Using Episomal Naked DNA Vectors Expressing PAH from Its Endogenous Liver Promoter

    Directory of Open Access Journals (Sweden)

    Hiu Man Grisch-Chan

    2017-06-01

    Full Text Available Limited duration of transgene expression, insertional mutagenesis, and size limitations for transgene cassettes pose challenges and risk factors for many gene therapy vectors. Here, we report on physiological expression of liver phenylalanine hydroxylase (PAH by delivery of naked DNA/minicircle (MC-based vectors for correction of homozygous enu2 mice, a model of human phenylketonuria (PKU. Because MC vectors lack a defined size limit, we constructed a MC vector expressing a codon-optimized murine Pah cDNA that includes a truncated intron and is under the transcriptional control of a 3.6-kb native Pah promoter/enhancer sequence. This vector, delivered via hydrodynamic injection, yielded therapeutic liver PAH activity and sustained correction of blood phenylalanine comparable to viral or synthetic liver promoters. Therapeutic efficacy was seen with vector copy numbers of 95% loss of vector genomes and PAH activity in liver, demonstrating that MC vectors had not integrated into the liver genome. In conclusion, MC vectors, which do not have a defined size-limitation, offer a favorable safety profile for hepatic gene therapy due to their non-integration in combination with native promoters.

  15. Biophysical and morphological effects of nanodiamond/nanoplatinum solution (DPV576) on metastatic murine breast cancer cells in vitro

    International Nuclear Information System (INIS)

    Ghoneum, Alia; Zhu, Huanqi; Woo, JungReem; Zabinyakov, Nikita; Sharma, Shivani; Gimzewski, James K

    2014-01-01

    Nanoparticles have recently gained increased attention as drug delivery systems for the treatment of cancer due to their minute size and unique chemical properties. However, very few studies have tested the biophysical changes associated with nanoparticles on metastatic cancer cells at the cellular and sub-cellular scales. Here, we investigated the mechanical and morphological properties of cancer cells by measuring the changes in cell Young’s Modulus using AFM, filopodial retraction (FR) by time lapse optical light microscopy imaging and filopodial disorganization by high resolution AFM imaging of cells upon treatment with nanoparticles. In the current study, nanomechanical changes in live murine metastatic breast cancer cells (4T1) post exposure to a nanodiamond/nanoplatinum mixture dispersed in aqueous solution (DPV576), were monitored. Results showed a decrease in Young’s modulus at two hours post treatment with DPV576 in a dose dependent manner. Partial FR at 20 min and complete FR at 40 min were observed. Moreover, analysis of the retraction distance (in microns) measured over time (minutes), showed that a DPV576 concentration of 15%v/v yielded the highest FR rate. In addition, DPV576 treated cells showed early signs of filopodial disorganization and disintegration. This study demonstrates the changes in cell stiffness and tracks early structural alterations of metastatic breast cancer cells post treatment with DPV576, which may have important implications in the role of nanodiamond/nanoplatinum based cancer cell therapy and sensitization to chemotherapy drugs. (paper)

  16. Salmonella enterica serovar Enteritidis enterocolitis during late stages of gestation induces an adverse pregnancy outcome in the murine model.

    Directory of Open Access Journals (Sweden)

    Mariángeles Noto Llana

    Full Text Available Foodborne diseases caused by Salmonella enterica serovar Enteritidis (S. Enteritidis are a significant health problem. Pregnancy, state of immunological tolerance, is a predisposing condition for the development of infections with intracellular pathogens. Salmonella species can cause pregnancy complications such as chorioamnionitis, transplacental fetal infection, pre term labor, abortions, neonatal and maternal septicemia. However, the specific mechanisms by which Salmonella infections trigger these alterations are not clear. In the present work, using a self-limiting enterocolitis murine model, we show that the ingestion of a low dose of S. Enteritidis at late stages of pregnancy (day 15 of gestation is sufficient to induce massive maternal infection. We found that Salmonella infection leads to 40% of pre term delivery, 33% of abortion and fetal growth restriction. Placental dysfunction during S. Enteritidis enterocolitis was confirmed through cellular infiltration and hypoxia markers (MPO activity and COX-1 and COX-2 expression, respectively. Apoptosis in placental tissue due to Salmonella infection was also evident at day 18 of gestation when investigated by morphometric procedure, DNA fragmentation and Fas/FasL expression. Also, the expression of IFN-γ, TNF-α, IL-17 and IL-10 was up regulated in response to Salmonella not only in placenta, but also in amniotic fluid and maternal serum. Altogether, our results demonstrate that S. Enteritidis enterocolitis during late stages of gestation causes detrimental effect on pregnancy outcome.

  17. Melatonin promotes the in vitro development of pronuclear embryos and increases the efficiency of blastocyst implantation in murine.

    Science.gov (United States)

    Wang, Feng; Tian, XiuZhi; Zhang, Lu; Tan, DunXian; Reiter, Russel J; Liu, GuoShi

    2013-10-01

    When a defect occurs in the in vitro development of a pronuclear embryo, the interruption of the subsequent implantation limits the success of assisted conception. This common problem remains to be solved. In this study, we observed that melatonin at its physiological concentration (10(-7)  m) significantly promoted the in vitro development of murine pronuclear embryos. This was indicated by the increased blastocyst rate, hatching blastocyst rate, and blastocyst cell number with melatonin treatment. In addition, when these blastocysts were implanted into female recipient mice, the pregnancy rates (95.0% versus control 67.8%), litter sizes (4.1 pups/litter versus control 2.7 pups/litter), and postnatal survival rates of offspring (96.84% versus control 81.24%) were significantly improved compared with their non-melatonin-treated counterparts. Mechanistic studies revealed that melatonin treatment upregulates gene expression of the antioxidant enzyme, superoxide dismutase (SOD), and the anti-apoptotic factor bcl-2 while downregulating the expression of pro-apoptotic genes p53 and caspase-3. Due to these changes, melatonin treatment reduces ROS production and cellular apoptosis during in vitro embryo development and improves the quality of blastocysts. The implantation of blastocysts with higher quality leads to more healthy offspring and increased pup survival. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Inflammation-mediated memory dysfunction and effects of a ketogenic diet in a murine model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Do Young Kim

    Full Text Available A prominent clinical symptom in multiple sclerosis (MS, a progressive disorder of the central nervous system (CNS due to heightened neuro-inflammation, is learning and memory dysfunction. Here, we investigated the effects of a ketogenic diet (KD on memory impairment and CNS-inflammation in a murine model of experimental autoimmune encephalomyelitis (EAE, using electrophysiological, behavioral, biochemical and in vivo imaging approaches. Behavioral spatial learning deficits were associated with motor disability in EAE mice, and were observed concurrently with brain inflammation. The KD improved motor disability in the EAE model, as well as CA1 hippocampal synaptic plasticity (long-term potentiation and spatial learning and memory (assessed with the Morris Water Maze. Moreover, hippocampal atrophy and periventricular lesions in EAE mice were reversed in KD-treated EAE mice. Finally, we found that the increased expression of inflammatory cytokines and chemokines, as well as the production of reactive oxygen species (ROS, in our EAE model were both suppressed by the KD. Collectively, our findings indicate that brain inflammation in EAE mice is associated with impaired spatial learning and memory function, and that KD treatment can exert protective effects, likely via attenuation of the robust immune response and increased oxidative stress seen in these animals.

  19. Differences in sensitivity of murine spermatogonia and somatic cells in vivo to sister-chromatid exchange induction by nitrosoureas.

    Science.gov (United States)

    Morales-Ramírez, P; Cruz-Vallejo, V; Rodríguez-Reyes, R

    2001-07-01

    Previously published data indicate that spermatogonia (SPG) are less sensitive to a sister-chromatid exchange (SCE) induction for different mutagens. In an earlier study, we have observed that bromodeoxyuridine (BrdU) substituted murine SPG are less sensitive to SCE induction by gamma ray in cells, than bone marrow (BM) and salivary gland (SG) cells in vivo. This was interpreted to mean that SPG are more efficient in DNA repair or are less prone to SCE induction. That the lower induction of SCE could be due to a reduced accessibility of mutagens to the SPG by virtue of a physiological barrier, was discarded by using gamma radiation. The aim of the present study was to establish whether or not there are differences in SCE induction by nitrosoureas among SPG, SG and BM cells with BrdU substituted or unsubstituted DNA. It was observed that SCE induction by methylnitrosourea (MNU) or by ethylnitrosourea (ENU) in SPG was, respectively, five and two times lower than in SG, and ten and three times lower than in BM. In SPG after BrdU incorporation, there was no increase in efficiency of SCE induction; in fact, there was even a slight decrease by exposure to MNU or ENU. BM and SG cells showed an increased efficiency in SCE induction after BrdU incorporation. This implies that SPG are also less sensitive to SCE induction by nitrosoureas, which cause a different kind of damage from previously assayed mutagens.

  20. Augmentation of arginase 1 expression by exposure to air pollution exacerbates the airways hyperresponsiveness in murine models of asthma

    Directory of Open Access Journals (Sweden)

    Amatullah Hajera

    2011-02-01

    Full Text Available Abstract Background Arginase overexpression contributes to airways hyperresponsiveness (AHR in asthma. Arginase expression is further augmented in cigarette smoking asthmatics, suggesting that it may be upregulated by environmental pollution. Thus, we hypothesize that arginase contributes to the exacerbation of respiratory symptoms following exposure to air pollution, and that pharmacologic inhibition of arginase would abrogate the pollution-induced AHR. Methods To investigate the role of arginase in the air pollution-induced exacerbation of airways responsiveness, we employed two murine models of allergic airways inflammation. Mice were sensitized to ovalbumin (OVA and challenged with nebulized PBS (OVA/PBS or OVA (OVA/OVA for three consecutive days (sub-acute model or 12 weeks (chronic model, which exhibit inflammatory cell influx and remodeling/AHR, respectively. Twenty-four hours after the final challenge, mice were exposed to concentrated ambient fine particles plus ozone (CAP+O3, or HEPA-filtered air (FA, for 4 hours. After the CAP+O3 exposures, mice underwent tracheal cannulation and were treated with an aerosolized arginase inhibitor (S-boronoethyl-L-cysteine; BEC or vehicle, immediately before determination of respiratory function and methacholine-responsiveness using the flexiVent®. Lungs were then collected for comparison of arginase activity, protein expression, and immunohistochemical localization. Results Compared to FA, arginase activity was significantly augmented in the lungs of CAP+O3-exposed OVA/OVA mice in both the sub-acute and chronic models. Western blotting and immunohistochemical staining revealed that the increased activity was due to arginase 1 expression in the area surrounding the airways in both models. Arginase inhibition significantly reduced the CAP+O3-induced increase in AHR in both models. Conclusions This study demonstrates that arginase is upregulated following environmental exposures in murine models of

  1. Ascorbyl stearate and ionizing radiation potentiate apoptosis through intracellular thiols and oxidative stress in murine T lymphoma cells.

    Science.gov (United States)

    Mane, Shirish D; Kamatham, Akhilender Naidu

    2018-02-01

    Ascorbyl stearate (Asc-s) is a derivative of ascorbic acid with better anti-tumour efficacy compared to its parent compound ascorbic acid. In this study, we have examined radio-sensitizing effect of Asc-s in murine T cell lymphoma (EL4) cells at 4 Gy. Asc-s and radiation treatment reduced cell proliferation, induced apoptosis in a dose dependent manner by arresting the cells at S/G2-M phase of cell cycle. It also decreased the frequency of cancer stem cells per se, with significantly higher decrease in combination with radiation treatment./Further, Asc-s and radiation treatment increased the level of reactive oxygen species (ROS), drop in mitochondrial membrane potential (MMP) and increased caspase-3 activity resulting in apoptosis of EL4 cells. Further it also significantly decreased GSH/GSSG ratio due to binding of Asc-s with thiols. The increase in oxidative stress induced by Asc-s and radiation treatment was abrogated by thiol antioxidants in EL4 cells. Interestingly, this redox modulation triggered significant increase in protein glutathionylation in a time dependent manner. Asc-s treatment resulted in glutathionylation of IKK, p50-NF-kB and mutated p53, thereby inhibiting cancer progression during oxidative stress. Asc-s quenches GSH ensuing Asc-s + GSH adduct thereby further modulating GSH/GSSG ratio as evident from HPLC and docking studies. The anti-tumour effect of Asc-s along with radiation was studied by injecting EL4 cells in synegenicC57/BL6 male mice. Intraperitoneal injection of Asc-s followed by radiation exposure at 4 Gy to the tumour bearing mice resulted in radio-sensitization which is evident from significant regression of tumour as evident from tumour burden index. The survival study supports the data that Asc-s pre-treatment enhances radio-sensitization in murine lymphoma. Our data, suggest that Asc-s and ionizing radiation induced cell cycle arrest and apoptosis by perturbing redox balance through irreversible complexes of thiols with Asc

  2. Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies.

    LENUS (Irish Health Repository)

    El-Khuffash, Afif

    2014-09-01

    We evaluated the clinical effectiveness of variable courses of paracetamol on patent ductus arteriosus (PDA) closure and examined its effect on the in vitro term and preterm murine ductus arteriosus (DA).

  3. JST Thesaurus Headwords and Synonyms: murine leukemia virus [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term murine leukemia virus 名詞 一般 * * *... * マウス白血病ウイルス マウスハッケツビョウウイルス マウスハッケツビョーウイルス Thesaurus2015 200906060491156251 C LS07 UNKNOWN_2 murine leukemia virus

  4. JST Thesaurus Headwords and Synonyms: murine hepatitis virus [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term murine hepatitis virus 名詞 一般 * * * * マウス肝炎...ウイルス マウスカンエンウイルス マウスカンエンウイルス Thesaurus2015 200906024862381907 C LS07 UNKNOWN_2 murine hepatitis virus

  5. Selective host range restriction of goat cells for recombinant murine leukemia virus and feline leukemia virus type A.

    OpenAIRE

    Fischinger, P J; Thiel, H J; Blevins, C S; Dunlop, N M

    1981-01-01

    We isolated a strain of normal goat fibroblasts which was uniquely selective in that it allowed the replication of xenotropic murine leukemia virus but not polytropic recombinant murine leukemia virus. In addition, feline leukemia virus type A replication was severely diminished in these goat cells, whereas feline leukemia virus type B and feline endogenous RD114-CCC viruses replicated efficiently. No other known cells exhibit this pattern of virus growth restriction. These goat cells allow t...

  6. Effect of different forms of adenylate cyclase toxin of Bordetella pertussis on protection afforded by an acellular pertussis vaccine in a murine model.

    Science.gov (United States)

    Cheung, Gordon Y C; Xing, Dorothy; Prior, Sandra; Corbel, Michael J; Parton, Roger; Coote, John G

    2006-12-01

    Four recombinant forms of the cell-invasive adenylate cyclase toxin (CyaA) of Bordetella pertussis were compared for the ability to enhance protection against B. pertussis in mice when coadministered with an acellular pertussis vaccine (ACV). The four forms were as follows: fully functional CyaA, a CyaA form lacking adenylate cyclase enzymatic activity (CyaA*), and the nonacylated forms of these toxins, i.e., proCyaA and proCyaA*, respectively. None of these forms alone conferred significant (P > 0.05) protection against B. pertussis in a murine intranasal challenge model. Mice immunized with ACV alone showed significant (P protection was only significant (P protection provided by CyaA* was due to an augmentation of both Th1 and Th2 immune responses to B. pertussis antigens.

  7. Three-dimensional in vivo imaging of the murine liver: a micro-computed tomography-based anatomical study.

    Directory of Open Access Journals (Sweden)

    Teresa Fiebig

    Full Text Available Various murine models are currently used to study acute and chronic pathological processes of the liver, and the efficacy of novel therapeutic regimens. The increasing availability of high-resolution small animal imaging modalities presents researchers with the opportunity to precisely identify and describe pathological processes of the liver. To meet the demands, the objective of this study was to provide a three-dimensional illustration of the macroscopic anatomical location of the murine liver lobes and hepatic vessels using small animal imaging modalities. We analysed micro-CT images of the murine liver by integrating additional information from the published literature to develop comprehensive illustrations of the macroscopic anatomical features of the murine liver and hepatic vasculature. As a result, we provide updated three-dimensional illustrations of the macroscopic anatomy of the murine liver and hepatic vessels using micro-CT. The information presented here provides researchers working in the field of experimental liver disease with a comprehensive, easily accessable overview of the macroscopic anatomy of the murine liver.

  8. A murine model of graft-versus-host disease induced by allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Hu Jiangwei; Jin Jiangang; Ning Hongmei; Yu Liquan; Feng Kai; Chen Hu; Wang Lisha

    2007-01-01

    Objective: To establish the model of graft-versus-host disease (GVHD) in mice with allogeneic bone marrow transplantation. Methods: Bone marrow cells were combined with spleen cells of male donor C57BL/6 mice according to different proportions, then were transfused into female postradiation recipient BALB/c mice. General state, life span and histopathology of the recipient mice and detected chimera were observed. Results and Conclusion:The recipient mice groups which accepted above 5 x 10 6 donor spleen cells developed acute GVHD after different peroids of time. The GVHD model in mice after allo-BMT was successfully established. The transfusion of 5 x 10 6 -5 x 10 7 spleen cells may be adequate to establish the murine model of GVHD for the prevention and treatment of GVHD. The number of murine spleen cells can be chosen according to the experimental requirement. (authors)

  9. NetH2pan: A Computational Tool to Guide MHC peptide prediction on Murine Tumors

    DEFF Research Database (Denmark)

    DeVette, Christa I; Andreatta, Massimo; Bardet, Wilfried

    2018-01-01

    With the advancement of personalized cancer immunotherapies, new tools are needed to identify tumor antigens and evaluate T-cell responses in model systems, specifically those that exhibit clinically relevant tumor progression. Key transgenic mouse models of breast cancer are generated and mainta......With the advancement of personalized cancer immunotherapies, new tools are needed to identify tumor antigens and evaluate T-cell responses in model systems, specifically those that exhibit clinically relevant tumor progression. Key transgenic mouse models of breast cancer are generated...... for evaluating antigen specificity in the murine FVB strain. Our study provides the first detailed molecular and immunoproteomic characterization of the FVB H-2q MHC Class I alleles, including >8500 unique peptide ligands, a multi-allele murine MHC peptide prediction tool, and in vivo validation of these data...

  10. Murine protein H is comprised of 20 repeating units, 61 amino acids in length

    DEFF Research Database (Denmark)

    Kristensen, Torsten; Tack, B F

    1986-01-01

    A cDNA library constructed from size-selected (greater than 28 S) poly(A)+ RNA isolated from the livers of C57B10. WR mice was screened by using a 249-base-pair (bp) cDNA fragment encoding 83 amino acid residues of human protein H as a probe. Of 120,000 transformants screened, 30 hybridized......, 448 bp of 3'-untranslated sequence, and a polyadenylylated tail of undetermined length. Murine pre-protein H was deduced to consist of an 18-amino acid signal peptide and 1216 residues of H-protein sequence. Murine H was composed of 20 repetitive units, each about 61 amino acid residues in length...

  11. Absence of hypoxanthine:guanine phosphoribosyltransferase activity in murine Dunn osteosarcoma

    International Nuclear Information System (INIS)

    Abelson, H.T.; Gorka, C.

    1983-01-01

    The transplantable murine Dunn osteosarcoma has no detectable hypoxanthine:guanine phosphoribosyltransferase (EC 2.4.2.8) activity. This was established from the tumors directly and from tissue culture cell lines derived from the tumor using a variety of assays: e.g., no [3H]hypoxanthine uptake into tumor or tissue culture cells, no conversion of [3H]hypoxanthine to [3H]IMP by cell extracts from tumors or tissue culture cells, no growth of tissue culture cells in hypoxanthine:aminopterin:thymidine medium, and normal growth of these cells in 10 microM 6-mercaptopurine. Ten human osteosarcomas have been assayed, and two have no apparent hypoxanthine:guanine phosphoribosyltransferase enzyme activity. After high-dose methotrexate treatment in vivo, murine tumors could be selectively killed and normal tissues could be spared by using a rescue regimen of hypoxanthine-thymidine-allopurinol

  12. Role of P2X7 on steroid synthesis in murine luteal cells

    Directory of Open Access Journals (Sweden)

    Chunping Zhang

    2016-03-01

    Full Text Available The extracellular adenosine triphosphate (ATP regulates different cellular functions through activating purinergic receptors as a signalling molecule or neurotransmitter. P2X7 is highly expressed in murine small luteal cells. In this study, murine luteal cells were cultured in vitro and treated with P2X7 agonists – ATP and 2′(3′-O-(4-benzoyl-benzoyl-adenosine 50-triphosphate (BzATP and with P2X7 antagonist – brilliant blue G (BBG. We found that ATP and BzATP increased the production of progesterone and had no influence on the production of estradiol. BBG reversed the effect of BzATP and ATP. Further studies demonstrated that ATP and BzATP promoted the expression of CYP11A. These results revealed that P2X7 receptor activation is involved in the steroid synthesis in corpus luteum.

  13. Finanční due diligence

    OpenAIRE

    Slonka, Tomáš

    2015-01-01

    Thesis on financial due diligence focuses on the use of due diligence in practice. The aim of this work is to determine the risk for the investor and the calculation of the target company with and without conducting due diligence, thus finding out the added value of due diligence.

  14. 5 CFR 732.301 - Due process.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Due process. 732.301 Section 732.301...) NATIONAL SECURITY POSITIONS Due Process and Reporting § 732.301 Due process. When an agency makes an... any determination. (b) Comply with all applicable administrative due process requirements, as provided...

  15. Isolation and characterisation of Ebolavirus-specific recombinant antibody fragments from murine and shark immune libraries.

    Science.gov (United States)

    Goodchild, Sarah A; Dooley, Helen; Schoepp, Randal J; Flajnik, Martin; Lonsdale, Stephen G

    2011-09-01

    Members of the genus Ebolavirus cause fulminating outbreaks of disease in human and non-human primate populations with a mortality rate up to 90%. To facilitate rapid detection of these pathogens in clinical and environmental samples, robust reagents capable of providing sensitive and specific detection are required. In this work recombinant antibody libraries were generated from murine (single chain variable domain fragment; scFv) and nurse shark, Ginglymostoma cirratum (IgNAR V) hosts immunised with Zaire ebolavirus. This provides the first recorded IgNAR V response against a particulate antigen in the nurse shark. Both murine scFv and shark IgNAR V libraries were panned by phage display technology to identify useful antibodies for the generation of immunological detection reagents. Two murine scFv were shown to have specificity to the Zaire ebolavirus viral matrix protein VP40. Two isolated IgNAR V were shown to bind to the viral nucleoprotein (NP) and to capture viable Zaire ebolavirus with a high degree of sensitivity. Assays developed with IgNAR V cross-reacted to Reston ebolavirus, Sudan ebolavirus and Bundibugyo ebolavirus. Despite this broad reactivity, neither of IgNAR V showed reactivity to Côte d'Ivoire ebolavirus. IgNAR V was substantially more resistant to irreversible thermal denaturation than murine scFv and monoclonal IgG in a comparative test. The demonstrable robustness of the IgNAR V domains may offer enhanced utility as immunological detection reagents in fieldable biosensor applications for use in tropical or subtropical countries where outbreaks of Ebolavirus haemorrhagic fever occur. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  16. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs

    OpenAIRE

    Mathew, Biji; Jacobson, Jeffrey R.; Berdyshev, Evgeny; Huang, Yong; Sun, Xiaoguang; Zhao, Yutong; Gerhold, Lynnette M.; Siegler, Jessica; Evenoski, Carrie; Wang, Ting; Zhou, Tong; Zaidi, Rafe; Moreno-Vinasco, Liliana; Bittman, Robert; Chen, Chin Tu

    2011-01-01

    Clinically significant radiation-induced lung injury (RILI) is a common toxicity in patients administered thoracic radiotherapy. Although the molecular etiology is poorly understood, we previously characterized a murine model of RILI in which alterations in lung barrier integrity surfaced as a potentially important pathobiological event and genome-wide lung gene mRNA levels identified dysregulation of sphingolipid metabolic pathway genes. We hypothesized that sphingolipid signaling components...

  17. Homocysteine enhances MMP-9 production in murine macrophages via ERK and Akt signaling pathways

    International Nuclear Information System (INIS)

    Lee, Seung Jin; Lee, Yi Sle; Seo, Kyo Won; Bae, Jin Ung; Kim, Gyu Hee; Park, So Youn; Kim, Chi Dae

    2012-01-01

    Homocysteine (Hcy) at elevated levels is an independent risk factor of cardiovascular diseases, including atherosclerosis. In the present study, we investigated the effect of Hcy on the production of matrix metalloproteinases (MMP) in murine macrophages. Among the MMP known to regulate the activities of collagenase and gelatinase, Hcy exclusively increased the gelatinolytic activity of MMP-9 in J774A.1 cells as well as in mouse peritoneal macrophages. Furthermore, this activity was found to be correlated with Western blot findings in J774A.1 cells, which showed that MMP-9 expression was concentration- and time-dependently increased by Hcy. Inhibition of the ERK and Akt pathways led to a significant decrease in Hcy-induced MMP-9 expression, and combined treatment with inhibitors of the ERK and Akt pathways showed an additive effects. Activity assays for ERK and Akt showed that Hcy increased the phosphorylation of both, but these phosphorylation were not affected by inhibitors of the Akt and ERK pathways. In line with these findings, the molecular inhibition of ERK and Akt using siRNA did not affect the Hcy-induced phosphorylation of Akt and ERK, respectively. Taken together, these findings suggest that Hcy enhances MMP-9 production in murine macrophages by separately activating the ERK and Akt signaling pathways. -- Highlights: ► Homocysteine (Hcy) induced MMP-9 production in murine macrophages. ► Hcy induced MMP-9 production through ERK and Akt signaling pathways. ► ERK and Akt signaling pathways were activated by Hcy in murine macrophages. ► ERK and Akt pathways were additively act on Hcy-induced MMP-9 production. ► Hcy enhances MMP-9 production in macrophages via activation of ERK and Akt signaling pathways in an independent manner.

  18. The pharmacokinetics and metabolism of lumiracoxib in chimeric humanized and murinized FRG mice.

    Science.gov (United States)

    Dickie, A P; Wilson, C E; Schreiter, K; Wehr, R; Wilson, E M; Bial, J; Scheer, N; Wilson, I D; Riley, R J

    2017-07-01

    The pharmacokinetics and metabolism of lumiracoxib were studied, after administration of single 10mg/kg oral doses to chimeric liver-humanized and murinized FRG mice. In the chimeric humanized mice, lumiracoxib reached peak observed concentrations in the blood of 1.10±0.08μg/mL at 0.25-0.5h post-dose with an AUC inf of 1.74±0.52μgh/mL and an effective half-life for the drug of 1.42±0.72h (n=3). In the case of the murinized animals peak observed concentrations in the blood were determined as 1.15±0.08μg/mL at 0.25h post-dose with an AUC inf of 1.94±0.22μgh/mL and an effective half-life of 1.28±0.02h (n=3). Analysis of blood indicated only the presence of unchanged lumiracoxib. Metabolic profiling of urine, bile and faecal extracts revealed a complex pattern of metabolites for both humanized and murinized animals with, in addition to unchanged parent drug, a variety of hydroxylated and conjugated metabolites detected. The profiles obtained in humanized mice were different compared to murinized animals with e.g., a higher proportion of the dose detected in the form of acyl glucuronide metabolites and much reduced amounts of taurine conjugates. Comparison of the metabolic profiles obtained from the present study with previously published data from C57bl/6J mice and humans, revealed a greater though not complete match between chimeric humanized mice and humans, such that the liver-humanized FRG model may represent a useful approach to assessing the biotransformation of such compounds in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Sequential Expression of the Neuropeptides Substance P and Somatostatin in Granulomas Associated with Murine Cysticercosis

    OpenAIRE

    Robinson, Prema; White, A. Clinton; Lewis, Dorothy E.; Thornby, John; David, Elliott; Weinstock, Joel

    2002-01-01

    Neurocysticercosis, a parasitic infection of the human central nervous system caused by Taenia solium, is a leading cause of seizures. Seizures associated with neurocysticercosis are caused mainly by the host inflammatory responses to dying parasites in the brain parenchyma. We previously demonstrated sequential expression of Th1 cytokines in early-stage granulomas, followed by expression of Th2 cytokines in later-stage granulomas in murine cysticercosis. However, the mechanism leading to thi...

  20. Targeted detection of murine colonic dysplasia in vivo with flexible multispectral scanning fiber endoscopy

    Science.gov (United States)

    Joshi, Bishnu P.; Miller, Sharon J.; Lee, Cameron; Gustad, Adam; Seibel, Eric J.; Wang, Thomas D.

    2012-02-01

    We demonstrate a multi-spectral scanning fiber endoscope (SFE) that collects fluorescence images in vivo from three target peptides that bind specifically to murine colonic adenomas. This ultrathin endoscope was demonstrated in a genetically engineered mouse model of spontaneous colorectal adenomas based on somatic Apc (adenomatous polyposis coli) gene inactivation. The SFE delivers excitation at 440, 532, 635 nm with human patients by simultaneously visualizing multiple over expressed molecular targets unique to dysplasia.

  1. Murine Double Minute 2 SNP T309G Polymorphism and Urinary Tract Cancer Risk

    OpenAIRE

    Ding, Hui; Dai, Yu; Ning, Zhongyun; Fan, Ning; Wang, Zhiping; Li, Pei; Zhang, Liyuan; Tao, Yan; Wang, Hanzhang

    2016-01-01

    Abstract Urinary tract cancer is a common cause of cancer-related death. The etiology and pathogenesis of urinary tract cancer remain unclear, with genetic and epigenetic factors playing an important role. Studies of the polymorphism of murine double minute 2 (MDM2) have shown inconclusive trends in the risk of urinary tract cancer. To clarify this inconsistency, we conducted updated meta-analyses to evaluate the role of MDM2 T309G polymorphism in urinary tract cancer susceptibility. Data sou...

  2. Interleukin-2 treatment potentiates induction of oral tolerance in a murine model of autoimmunity.

    OpenAIRE

    Rizzo, L V; Miller-Rivero, N E; Chan, C C; Wiggert, B; Nussenblatt, R B; Caspi, R R

    1994-01-01

    The present study addresses the feasibility of potentiating oral tolerance by immunomanipulation, using the murine model of experimental autoimmune uveoretinitis (EAU) induced by immunization with the retinal antigen interphotoreceptor retinoid binding protein (IRBP). Three feedings of 0.2 mg IRBP every other day before immunization did not protect against EAU, whereas a similar regimen of five doses was protective. However, supplementing the nonprotective 3x regimen with as little as one inj...

  3. Homocysteine enhances MMP-9 production in murine macrophages via ERK and Akt signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Jin; Lee, Yi Sle; Seo, Kyo Won; Bae, Jin Ung; Kim, Gyu Hee; Park, So Youn; Kim, Chi Dae, E-mail: chidkim@pusan.ac.kr

    2012-04-01

    Homocysteine (Hcy) at elevated levels is an independent risk factor of cardiovascular diseases, including atherosclerosis. In the present study, we investigated the effect of Hcy on the production of matrix metalloproteinases (MMP) in murine macrophages. Among the MMP known to regulate the activities of collagenase and gelatinase, Hcy exclusively increased the gelatinolytic activity of MMP-9 in J774A.1 cells as well as in mouse peritoneal macrophages. Furthermore, this activity was found to be correlated with Western blot findings in J774A.1 cells, which showed that MMP-9 expression was concentration- and time-dependently increased by Hcy. Inhibition of the ERK and Akt pathways led to a significant decrease in Hcy-induced MMP-9 expression, and combined treatment with inhibitors of the ERK and Akt pathways showed an additive effects. Activity assays for ERK and Akt showed that Hcy increased the phosphorylation of both, but these phosphorylation were not affected by inhibitors of the Akt and ERK pathways. In line with these findings, the molecular inhibition of ERK and Akt using siRNA did not affect the Hcy-induced phosphorylation of Akt and ERK, respectively. Taken together, these findings suggest that Hcy enhances MMP-9 production in murine macrophages by separately activating the ERK and Akt signaling pathways. -- Highlights: ► Homocysteine (Hcy) induced MMP-9 production in murine macrophages. ► Hcy induced MMP-9 production through ERK and Akt signaling pathways. ► ERK and Akt signaling pathways were activated by Hcy in murine macrophages. ► ERK and Akt pathways were additively act on Hcy-induced MMP-9 production. ► Hcy enhances MMP-9 production in macrophages via activation of ERK and Akt signaling pathways in an independent manner.

  4. CD44 antibodies and immune thrombocytopenia in the amelioration of murine inflammatory arthritis.

    Directory of Open Access Journals (Sweden)

    Patrick J Mott

    Full Text Available Antibodies to CD44 have been used to successfully ameliorate murine models of autoimmune disease. The most often studied disease model has been murine inflammatory arthritis, where a clear mechanism for the efficacy of CD44 antibodies has not been established. We have recently shown in a murine passive-model of the autoimmune disease immune thrombocytopenia (ITP that some CD44 antibodies themselves can induce thrombocytopenia in mice, and the CD44 antibody causing the most severe thrombocytopenia (IM7, also is known to be highly effective in ameliorating murine models of arthritis. Recent work in the K/BxN serum-induced model of arthritis demonstrated that antibody-induced thrombocytopenia reduced arthritis, causing us to question whether CD44 antibodies might primarily ameliorate arthritis through their thrombocytopenic effect. We evaluated IM7, IRAWB14.4, 5035-41.1D, KM201, KM114, and KM81, and found that while all could induce thrombocytopenia, the degree of protection against serum-induced arthritis was not closely related to the length or severity of the thrombocytopenia. CD44 antibody treatment was also able to reverse established inflammation, while thrombocytopenia induced by an anti-platelet antibody targeting the GPIIbIIIa platelet antigen, could not mediate this effect. While CD44 antibody-induced thrombocytopenia may contribute to some of its therapeutic effect against the initiation of arthritis, for established disease there are likely other mechanisms contributing to its efficacy. Humans are not known to express CD44 on platelets, and are therefore unlikely to develop thrombocytopenia after CD44 antibody treatment. An understanding of the relationship between arthritis, thrombocytopenia, and CD44 antibody treatment remains critical for continued development of CD44 antibody therapeutics.

  5. Noncanonical microRNAs and endogenous siRNAs in lytic infection of murine gammaherpesvirus.

    Directory of Open Access Journals (Sweden)

    Jing Xia

    Full Text Available MicroRNA (miRNA and endogenous small interfering RNA (endo-siRNA are two essential classes of small noncoding RNAs (sncRNAs in eukaryotes. The class of miRNA is diverse and there exist noncanonical miRNAs that bypass the canonical miRNA biogenesis pathway. In order to identify noncanonical miRNAs and endo-siRNAs responding to virus infection and study their potential function, we sequenced small-RNA species from cells lytically infected with murine gammaherpesvirus 68 (MHV68. In addition to three novel canonical miRNAs in mouse, two antisense miRNAs in virus and 25 novel noncanonical miRNAs, including miRNAs derived from transfer RNAs, small nucleolar RNAs and introns, in the host were identified. These noncanonical miRNAs exhibited features distinct from that of canonical miRNAs in lengths of hairpins, base pairings and first nucleotide preference. Many of the novel miRNAs are conserved in mammals. Besides several known murine endo-siRNAs detected by the sequencing profiling, a novel locus in the mouse genome was identified to produce endo-siRNAs. This novel endo-siRNA locus is comprised of two tandem inverted B4 short interspersed nuclear elements (SINEs. Unexpectedly, the SINE-derived endo-siRNAs were found in a variety of sequencing data and virus-infected cells. Moreover, a murine miRNA was up-regulated more than 35 fold in infected than in mock-treated cells. The putative targets of the viral and the up-regulated murine miRNAs were potentially involved in processes of gene transcription and protein phosphorylation, and localized to membranes, suggesting their potential role in manipulating the host basal immune system during lytic infection. Our results extended the number of noncanonical miRNAs in mammals and shed new light on their potential functions of lytic infection of MHV68.

  6. Efficacy and immunological actions of FAHF-2 in a murine model of multiple food allergies.

    Science.gov (United States)

    Srivastava, Kamal D; Bardina, Ludmilla; Sampson, Hugh A; Li, Xiu-Min

    2012-05-01

    Food Allergy Herbal Formula-2 (FAHF-2) prevents anaphylaxis in a murine model of peanut allergy. Multiple food allergies (MFA) are common and associated with a higher risk of anaphylaxis. No well-characterized murine model of sensitization to multiple food allergens exists, and no satisfactory therapy for MFA is currently available. To determine the effect of FAHF-2 in a murine model of MFA. C3H/HeJ mice were orally sensitized to peanut, codfish, and egg concurrently. Oral FAHF-2 treatment commenced 1 day after completing sensitization and continued daily for 7 weeks. Mice were subsequently orally challenged with each allergen. Antibodies in sera from mice simultaneously sensitized with peanut, codfish, and egg recognized major allergens of all 3 foods, demonstrating sensitization to multiple unrelated food allergens (MFA mice). Sham-treated MFA mice exhibited anaphylactic symptoms accompanied by elevation of plasma histamine and hypothermia. In contrast, FAHF-2-treated MFA mice showed no anaphylactic symptoms, normal body temperature, and histamine levels after challenge with each allergen. Protection was accompanied by reduction in allergen-specific immunoglobulin E levels. Allergen-stimulated Th2 cytokine interleukin-4 and interleukin-13 production levels decreased, whereas the Th1 cytokine interferon-γ levels were elevated in cultured splenocytes and mesenteric lymph node cells in FAHF-2-treated mice. We established the first murine model of MFA. FAHF-2 prevents peanut, egg, and fish-induced anaphylactic reactions in this model, suggesting that FAHF-2 may have potential for treating human MFA. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells

    Czech Academy of Sciences Publication Activity Database

    Zjablovskaja, Polina; Daněk, Petr; Kardošová, Miroslava; Alberich-Jorda, Meritxell

    č. 132 (2018), č. článku e57033. ISSN 1940-087X R&D Projects: GA ČR GA15-03796S Institutional support: RVO:68378050 Keywords : 32D/G-CSF-R cells * murine myeloid precursor cells * liquid culture * differentiation * neutrophils * proliferation * cytokines * IL-3 * G-CSF Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.232, year: 2016

  8. Bacterial Clearance and Cytokine Profiles in a Murine Model of Postsurgical Nosocomial Pneumonia

    OpenAIRE

    Manderscheid, Patricia A.; Bodkin, Ryan P.; Davidson, Bruce A.; Jensen, Erik; Russo, Thomas A.; Knight, Paul R.

    2004-01-01

    The development of a nosocomial pneumonia is facilitated by alterations in host innate pulmonary antibacterial defenses following surgical trauma, which can result in decreased pulmonary bacterial clearance and increased morbidity and mortality. In a murine model of postoperative nosocomial infection, surgical stress (laparotomy) decreased Escherichia coli clearance from the lungs of animals that underwent surgery. Consistent with previous studies, (i) pulmonary levels of tumor necrosis facto...

  9. Puerarin Facilitates T-Tubule Development of Murine Embryonic Stem Cell-Derived Cardiomyocytes

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    Lu Wang

    2014-07-01

    Full Text Available Aims: The embryonic stem cell-derived cardiomyocytes (ES-CM is one of the promising cell sources for repopulation of damaged myocardium. However, ES-CMs present immature structure, which impairs their integration with host tissue and functional regeneration. This study used murine ES-CMs as an in vitro model of cardiomyogenesis to elucidate the effect of puerarin, the main compound found in the traditional Chinese medicine the herb Radix puerariae, on t-tubule development of murine ES-CMs. Methods: Electron microscope was employed to examine the ultrastructure. The investigation of transverse-tubules (t-tubules was performed by Di-8-ANEPPS staining. Quantitative real-time PCR was utilized to study the transcript level of genes related to t-tubule development. Results: We found that long-term application of puerarin throughout cardiac differentiation improved myofibril array and sarcomeres formation, and significantly facilitated t-tubules development of ES-CMs. The transcript levels of caveolin-3, amphiphysin-2 and junctophinlin-2, which are crucial for the formation and development of t-tubules, were significantly upregulated by puerarin treatment. Furthermore, puerarin repressed the expression of miR-22, which targets to caveolin-3. Conclusion: Our data showed that puerarin facilitates t-tubule development of murine ES-CMs. This might be related to the repression of miR-22 by puerarin and upregulation of Cav3, Bin1 and JP2 transcripts.

  10. Establishment of a method of murine obestatin RIA and its primary application

    International Nuclear Information System (INIS)

    Yan Guangtao Lin Ji; Hao Xiuhua; Xue Hui; Den Zihui; Di Dongdong

    2009-01-01

    Objective: To develop a method of murine obestatin RIA and study the role obestatin played in traumatic stress responses. Methods: New Zealand white rabbits were immunized with synthetic murine obestatin to obtain anti-serum, while chloramines-T method was used to iodinate obestatin antigen and a method of RIA for obestatin was established. A mouse sepsis model made with cecal ligation and puncture was established. Serum obestatin levels in the sacrificed models were determined with this method of RIA at 3h, 6h, 9h after the cecum puncture respectively (5 animals each time) as well as in 5 animals after sham operation. Results: Both the shape of standard curve and metrical results of the obestatin RIA were satisfactory. Serum obstatin levels at 6h after injury were significantly higher than those in animals with sham operation out the levels at 3h and 9h were not much different from those in sham operation animals. Meanwhile, the levels at 6h after injury expressed a trend to be significantly higher than that at 3h or 9h after injury. Conclusion: The established method for murine obestatin RIA is highly sensitive, simple and reliable, and it can be used to detect samples from rats and mice. Obestatin may be a traumatic stress factor participating in the modulation of homeostasis after sepsis. (authors)

  11. Generation of a conditional knockout of murine glucocerebrosidase: utility for the study of Gaucher disease.

    Science.gov (United States)

    Sinclair, Graham B; Jevon, Gareth; Colobong, Karen E; Randall, Derrick R; Choy, Francis Y M; Clarke, Lorne A

    2007-02-01

    Gaucher disease is a disorder of sphingolipid metabolism resulting from an inherited deficiency of the lysosomal hydrolase glucocerebrosidase. Affected individuals present with a spectrum of clinical symptoms ranging from hepatosplenomegaly, haematological abnormalities, and bone pain in type 1 disease, to severe neurodegeneration and premature death in types 2 and 3 disease. Although the basic biochemical defect is well characterized, there remains a poor understanding of the underlying pathophysiology of disease. In vitro studies suggest that macrophage glucocerebroside storage leads to tissue dysfunction through complex mechanisms involving altered intracellular calcium homeostasis and apoptosis. In order to study the pathogenic roles of these complex interactions, a viable animal model for Gaucher disease is needed. The complexity of this single gene disorder has been emphasized by the varied results of previous murine Gaucher models, ranging from perinatal lethality to phenotypically and biochemically asymptomatic animals. Recognizing the need to modulate the biochemical phenotype in mice to produce a relevant model, we have created a murine strain with key exons of the glucocerebrosidase gene flanked by loxP sites. We show that expression of Cre-recombinase in cells of hematopoietic and endothelial origin results in deficiency of glucocerebrosidase in the liver, spleen, bone marrow, and peripheral white cells. Glucocerebroside storage in this model leads to progressive splenomegaly with Gaucher cell infiltration and modest storage in the liver by 26 weeks of age. These results indicate the utility of this loxP GBA targeted murine strain for understanding the complex pathophysiology of Gaucher disease.

  12. Differential gene expression in the murine gastric fundus lacking interstitial cells of Cajal

    Directory of Open Access Journals (Sweden)

    Ward Sean M

    2003-06-01

    Full Text Available Abstract Background The muscle layers of murine gastric fundus have no interstitial cells of Cajal at the level of the myenteric plexus and only possess intramuscular interstitial cells and this tissue does not generate electric slow waves. The absence of intramuscular interstitial cells in W/WV mutants provides a unique opportunity to study the molecular changes that are associated with the loss of these intercalating cells. Method The gene expression profile of the gastric fundus of wild type and W/WV mice was assayed by murine microarray analysis displaying a total of 8734 elements. Queried genes from the microarray analysis were confirmed by semi-quantitative reverse transcription-polymerase chain reaction. Results Twenty-one genes were differentially expressed in wild type and W/WV mice. Eleven transcripts had 2.0–2.5 fold higher mRNA expression in W/WV gastric fundus when compared to wild type tissues. Ten transcripts had 2.1–3.9 fold lower expression in W/WV mutants in comparison with wild type animals. None of these genes have ever been implicated in any bowel motility function. Conclusions These data provides evidence that several important genes have significantly changed in the murine fundus of W/WV mutants that lack intramuscular interstitial cells of Cajal and have reduced enteric motor neurotransmission.

  13. Cytoplasmic superoxide dismutase and catalase activity and resistance to radiation lethality in murine tumor cells

    International Nuclear Information System (INIS)

    Davy, C.A.; Tesfay, Z.; Jones, J.; Rosenberg, R.C.; McCarthy, C.; Rosenberg, S.O.

    1986-01-01

    Reduced species of molecular oxygen are produced by the interaction of ionizing radiation with aqueous solutions containing molecular oxygen. The enzymes catalase and superoxide dismutase (SOD) are thought to function in vivo as scavengers of metabolically produced peroxide and superoxide respectively. SOD has been shown to protect against the lethal effects of ionizing radiation in vitro and in vivo. The authors have investigated the relationship between the cytosolic SOD catalase content and the sensitivity to radiation lethality of a number of murine cell lines (402AX, EL-4, MB-2T3, MB-4, MEL, P-815, SAI, SP-2, and SV-3T3). K/sub i/(CN - ) for murine Cu-Zn-SOD was determined to be 6.8 x 10 -6 M. No cytosolic Mn-SOD activity was found in any of the cell lines studied. No correlation was found between the cytosolic Cu-Zn-SOD or cytosolic catalase activity and the resistance to radiation lethality or the murine cell lines studied

  14. Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition.

    Science.gov (United States)

    Baglietto-Vargas, David; Kitazawa, Masashi; Le, Elaine J; Estrada-Hernandez, Tatiana; Rodriguez-Ortiz, Carlos J; Medeiros, Rodrigo; Green, Kim N; LaFerla, Frank M

    2014-02-01

    Recent studies on tauopathy animal models suggest that the concomitant expression of the endogenous murine tau delays the pathological accumulation of human tau, and interferes with the disease progression. To elucidate the role of endogenous murine tau in a model with both plaques and tangles, we developed a novel transgenic mouse model by crossing 3xTg-AD with mtauKO mice (referred to as 3xTg-AD/mtauKO mice). Therefore, this new model allows us to determine the pathological consequences of the murine tau. Here, we show that 3xTg-AD/mtauKO mice have lower tau loads in both soluble and insoluble fractions, and lower tau hyperphosphorylation level in the soluble fraction relative to 3xTg-AD mice. In the 3xTg-AD model endogenous mouse tau is hyperphosphorylated and significantly co-aggregates with human tau. Despite the deletion of the endogenous tau gene in 3xTg-AD/mtauKO mice, cognitive dysfunction was equivalent to 3xTg-AD mice, as there was no additional impairment on a spatial memory task, and thus despite increased tau phosphorylation, accumulation and NFTs in 3xTg-AD mice no further effects on cognition are seen. These findings provide better understanding about the role of endogenous tau to Alzheimer's disease (AD) pathology and for developing new AD models. © 2013.

  15. Development and characterization of antiserum to murine granulocyte-macrophage colony-stimulating factor

    International Nuclear Information System (INIS)

    Mochizuki, D.Y.; Eisenman, J.R.; Conlon, P.J.; Park, L.S.; Urdal, D.L.

    1986-01-01

    The expression in yeast of a cDNA clone encoding murine granulocyte-macrophage colony-stimulating factor (GM-CSF) has made possible the purification of large quantities of this recombinant protein. Rabbits immunized with pure recombinant GM-CSF generated antibodies that were shown to be specific for both recombinant GM-CSF and GM-CSF isolated from natural sources. Other lymphokines, including IL 1β, IL 2, IL 3, and recombinant human GM-CSF did not react with the antiserum. The antiserum together with recombinant GM-CSF that had been radiolabeled with 125 I to high specific activity, formed the foundation for a rapid, sensitive, and quantitative radioimmunoassay specific for murine GM-CSF. Furthermore, the antiserum was found to inhibit the biologic activities of GM-CSF as measured in both a bone marrow proliferation assay and a colony assay, and thus should prove to be a useful reagent for dissecting the complex growth factor activities involved in murine hematopoiesis

  16. Trp53 activity is repressed in radio-adapted cultured murine limb bud cells

    International Nuclear Information System (INIS)

    Vares, Guillaume; Wang, Bing; Tanaka, Kaoru; Shang, Yi; Fujita, Kazuko; Hayata, Isamu; Nenoi, Mitsuru

    2011-01-01

    Understanding the effects of ionizing radiation (IR) at low dose in fetal models is of great importance, because the fetus is considered to be at the most radiosensitive stage of the development and prenatal radiation might influence subsequent development. We previously demonstrated the existence of an adaptive response (AR) in murine fetuses after pre-exposure to low doses of X-rays. Trp53-dependent apoptosis was suggested to be responsible for the teratogenic effects of IR; decreased apoptosis was observed in adapted animals. In this study, in order to investigate the role of Trp53 in AR, we developed a new model of irradiated micromass culture of fetal limb bud cells, which replicated proliferation, differentiation and response to IR in murine embryos. Murine fetuses were exposed to whole-body priming irradiation of 0.3 Gy or 0.5 Gy at embryonic day 11 (E11). Limb bud cells (collected from digital ray areas exhibiting radiation-induced apoptosis) were cultured and exposed to a challenging dose of 4 Gy at E12 equivalent. The levels of Trp53 protein and its phosphorylated form at Ser18 were investigated. Our results suggested that the induction of AR in mouse embryos was correlated with a repression of Trp53 activity. (author)

  17. Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene

    Energy Technology Data Exchange (ETDEWEB)

    Kyle, J.W.; Vogler, C.; Hoffmann, J.W.; Sly, W.S. (St. Louis Univ. School of Medicine, MO (USA)); Birkenmeier, E.H.; Gwynn, B. (Jackson Laboratory, Bar Harbor, ME (USA))

    1990-05-01

    The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{sup mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.

  18. L1-mediated retrotransposition of murine B1 and B2 SINEs recapitulated in cultured cells.

    Science.gov (United States)

    Dewannieux, Marie; Heidmann, Thierry

    2005-06-03

    SINEs are short interspersed nucleotide elements with transpositional activity, present at a high copy number (up to a million) in mammalian genomes. They are 80-400 bp long, non-coding sequences which derive either from the 7SL RNA (e.g. human Alus, murine B1s) or tRNA (e.g. murine B2s) polymerase III-driven genes. We have previously demonstrated that Alus very efficiently divert the enzymatic machinery of the autonomous L1 LINE (long interspersed nucleotide element) retrotransposons to transpose at a high rate. Here we show, using an ex vivo assay for transposition, that both B1 and B2 SINEs can be mobilized by murine LINEs, with the hallmarks of a bona fide retrotransposition process, including target site duplications of varying lengths and integrations into A-rich sequences. Despite different phylogenetic origins, transposition of the tRNA-derived B2 sequences is as efficient as that of the human Alus, whereas that of B1s is 20-100-fold lower despite a similar high copy number of these elements in the mouse genome. We provide evidence, via an appropriate nucleotide substitution within the B1 sequence in a domain essential for its intracellular targeting, that the current B1 SINEs are not optimal for transposition, a feature most probably selected for the host sake in the course of evolution.

  19. Effect of small dose of radiation on induction of apoptosis in murine tumors

    International Nuclear Information System (INIS)

    Seong, Jin Sil; Pyo, Hong Ryull; Chung, Eun Ji; Kim, Sung Hee; Suh, Chang Ok

    1999-01-01

    To investigate the presence of adaptive response by low dose radiation in murine tumors in relation to radiation induced apoptosis as well as related mechanism. Syngeneic murine tumors, OCa-1 and HCa-l, were given 0.05 Gy pretreatment followed by therapeutic dose of 25 Gy radiation. Induction of apoptosis was analyzed for each treatment group. Regulating molecules of apoptosis. p53, Bcl-2, Sax, Bel-X, were also analyzed by Western blotting. In 0.05 Gy pretreatment group of OCa-l, 25 Gy-induced apoptosis per 1000 cell