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Find video protocols related to scientific articles indexed in Pubmed.
In situ detection of autoreactive CD4 T cells in brain and heart using major histocompatibility complex class II dextramers.
J Vis Exp
PUBLISHED: 08-01-2014
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This report demonstrates the use of major histocompatibility complex (MHC) class II dextramers for detection of autoreactive CD4 T cells in situ in myelin proteolipid protein (PLP) 139-151-induced experimental autoimmune encephalomyelitis (EAE) in SJL mice and cardiac myosin heavy chain-? (Myhc) 334-352-induced experimental autoimmune myocarditis (EAM) in A/J mice. Two sets of cocktails of dextramer reagents were used, where dextramers(+) cells were analyzed by laser scanning confocal microscope (LSCM): EAE, IA(s)/PLP 139-151 dextramers (specific)/anti-CD4 and IA(s)/Theiler's murine encephalomyelitis virus (TMEV) 70-86 dextramers (control)/anti-CD4; and EAM, IA(k)/Myhc 334-352 dextramers/anti-CD4 and IA(k)/bovine ribonuclease (RNase) 43-56 dextramers (control)/anti-CD4. LSCM analysis of brain sections obtained from EAE mice showed the presence of cells positive for CD4 and PLP 139-151 dextramers, but not TMEV 70-86 dextramers suggesting that the staining obtained with PLP 139-151 dextramers was specific. Likewise, heart sections prepared from EAM mice also revealed the presence of Myhc 334-352, but not RNase 43-56-dextramer(+) cells as expected. Further, a comprehensive method has also been devised to quantitatively analyze the frequencies of antigen-specific CD4 T cells in the 'Z' serial images.
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Noninvasive assessment of cardiac abnormalities in experimental autoimmune myocarditis by magnetic resonance microscopy imaging in the mouse.
J Vis Exp
PUBLISHED: 07-08-2014
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Myocarditis is an inflammation of the myocardium, but only -10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-? 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-? 334-352 is shown. EAM and healthy mice were imaged using a 9.4 T (400 MHz) 89 mm vertical core bore scanner equipped with a 4 cm millipede radio-frequency imaging probe and 100 G/cm triple axis gradients. Cardiac images were acquired from anesthetized animals using a gradient-echo-based cine pulse sequence, and the animals were monitored by respiration and pulse oximetry. The analysis revealed an increase in the thickness of the ventricular wall in EAM mice, with a corresponding decrease in the interior diameter of ventricles, when compared with healthy mice. The data suggest that morphological and functional changes in the inflamed hearts can be non-invasively monitored by MRM in live animals. In conclusion, MRM offers an advantage of assessing the progression and regression of myocardial injuries in diseases caused by infectious agents, as well as response to therapies.
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Simvastatin radiosensitizes differentiated and stem-like breast cancer cell lines and is associated with improved local control in inflammatory breast cancer patients treated with postmastectomy radiation.
Stem Cells Transl Med
PUBLISHED: 05-15-2014
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Reported rates of local failure after adjuvant radiation for women with inflammatory breast cancer (IBC) and triple-negative non-IBC are higher than those of women with receptor-expressing non-IBC. These high rates of locoregional recurrence are potentially influenced by the contribution of radioresistant cancer stem cells to these cancers. Statins have been shown to target stem cells and improve disease-free survival among IBC patients. We examined simvastatin radiosensitization of multiple subtypes of breast cancer cell lines in vitro in monolayer and mammosphere-based clonogenic assays and examined the therapeutic benefit of statin use on local control after postmastectomy radiation (PMRT) among IBC patients. We found that simvastatin radiosensitizes mammosphere-initiating cells (MICs) of IBC cell lines (MDA-IBC3, SUM149, SUM190) and of the metaplastic, non-IBC triple-negative receptor cell line (SUM159). However, simvastatin radioprotects MICs of non-IBC cell lines MCF-7 and SKBR3. In a retrospective clinical study of 519 IBC patients treated with PMRT, 53 patients used a statin. On univariate analysis, actuarial 3-year local recurrence-free survival (LRFS) was higher among statin users, and on multivariate analysis, triple negative breast cancer, absence of lymphatic invasion, neoadjuvant pathological tumor response to preoperative chemotherapy, and statin use were independently associated with higher LRFS. In conclusion, patients with IBC and triple-negative non-IBC breast cancer have the highest rates of local failure, and there are no available known radiosensitizers. We report significant improvement in local control after PMRT among statin users with IBC and significant radiosensitization across triple-negative and IBC cell lines of multiple subtypes using simvastatin. These data suggest that simvastatin should be justified as a radiosensitizing agent by a prospective clinical trial.
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SJL mice infected with Acanthamoeba castellanii develop central nervous system autoimmunity through the generation of cross-reactive T cells for myelin antigens.
PLoS ONE
PUBLISHED: 01-01-2014
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We recently reported that Acanthamoeba castellanii (ACA), an opportunistic pathogen of the central nervous system (CNS) possesses mimicry epitopes for proteolipid protein (PLP) 139-151 and myelin basic protein 89-101, and that the epitopes induce experimental autoimmune encephalomyelitis (EAE) in SJL mice reminiscent of the diseases induced with their corresponding cognate peptides. We now demonstrate that mice infected with ACA also show the generation of cross-reactive T cells, predominantly for PLP 139-151, as evaluated by T cell proliferation and IAs/dextramer staining. We verified that PLP 139-151-sensitized lymphocytes generated in infected mice contained a high proportion of T helper 1 cytokine-producing cells, and they can transfer disease to naïve animals. Likewise, the animals first primed with suboptimal dose of PLP 139-151 and later infected with ACA, developed EAE, suggesting that ACA infection can trigger CNS autoimmunity in the presence of preexisting repertoire of autoreactive T cells. Taken together, the data provide novel insights into the pathogenesis of Acanthamoeba infections, and the potential role of infectious agents with mimicry epitopes to self-antigens in the pathogenesis of CNS diseases such as multiple sclerosis.
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Direct staining with major histocompatibility complex class II dextramers permits detection of antigen-specific, autoreactive CD4 T cells in situ.
PLoS ONE
PUBLISHED: 01-01-2014
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We report here the utility of major histocompatibility complex (MHC) class II dextramers for in situ detection of self-reactive CD4 T cells in two target organs, the brain and heart. We optimized the conditions for in situ detection of antigen-specific CD4 T cells using brain sections obtained from SJL mice immunized with myelin proteolipid protein (PLP) 139-151; the sections were costained with IA(s)/PLP 139-151 (specific) or Theiler's murine encephalomyelitis virus (TMEV) 70-86 (control) dextramers and anti-CD4. Analysis of sections by laser scanning confocal microscope revealed detection of cells positive for PLP 139-151 but not for TMEV 70-86 dextramers to be colocalized with CD4-expressing T cells, indicating that the staining was specific to PLP 139-151 dextramers. Further, we devised a method to reliably enumerate the frequencies of antigen-specific T cells by counting the number of dextramer? CD4? T cells in the 'Z' serial images acquired sequentially. We next extended these observations to detect cardiac myosin-specific T cells in autoimmune myocarditis induced in A/J mice by immunizing with cardiac myosin heavy chain-? (Myhc) 334-352. Heart sections prepared from immunized mice were costained with Myhc 334-352 (specific) or bovine ribonuclease 43-56 (control) dextramers together with anti-CD4; the sections showed the infiltrations of Myhc-specific CD4 T cells. The data suggest that MHC class II dextramers are useful tools for enumerating the frequencies of antigen-specific CD4 T cells in situ by direct staining without having to amplify the fluorescent signals, an approach commonly employed with conventional MHC tetramers.
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From medical home to ACO: a physician groups journey.
Healthc Financ Manage
PUBLISHED: 09-21-2013
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The Medical Clinic of North Texas (MCNT) launched a population health initiative in 2010 that has involved working with self-insured companies to manage the health of their employee populations. To achieve the goals of providing high-quality care at a low cost, MCNT uses historical electronic health record and claims data to calculate state-of-health (SOH) scores for a companys individual employees and for the entire employee population. SOH scores reflect risks related to chronic conditions for each patient, thereby providing clinical teams and care coordinators with the information they need to design and execute patient-specific care plans.
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Relevance of Molecular Mimicry in the Mediation of Infectious Myocarditis.
J Cardiovasc Transl Res
PUBLISHED: 08-15-2013
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Heart disease, the leading cause of death in humans, is estimated to affect one in four American adults in some form. One predominant cause of heart failure in young adults is myocarditis, which can lead to the development of dilated cardiomyopathy, a major indication for heart transplantation. Environmental microbes, including viruses, bacteria, and fungi that are otherwise innocuous, have the potential to induce inflammatory heart disease. As the list is growing, it is critical to determine the mechanisms by which microbes can trigger heart autoimmunity and, importantly, to identify their target antigens. This is especially true as microbes showing structural similarities with the cardiac antigens can predispose to heart autoimmunity by generating cross-reactive immune responses. In this review, we discuss the relevance of molecular mimicry in the mediation of infectious myocarditis.
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Mimicry epitope from Ehrlichia canis for interphotoreceptor retinoid-binding protein 201-216 prevents autoimmune uveoretinitis by acting as altered peptide ligand.
J. Neuroimmunol.
PUBLISHED: 05-28-2013
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We report here identification of novel mimicry epitopes for interphotoreceptor retinoid-binding protein (IRBP) 201-216, a candidate ocular antigen that causes experimental autoimmune uveoretinitis (EAU) in A/J mice. One mimicry epitope from Ehrlichia canis (EHC), designated EHC 44-59, induced cross-reactive T cells for IRBP 201-216 capable of producing T helper (Th)1 and Th17 cytokines, but failed to induce EAU in A/J mice. In addition, animals first primed with suboptimal doses of IRBP 201-216 and subsequently immunized with EHC 44-59 did not develop EAU; rather, the mimicry epitope prevented the disease induced by IRBP 201-216. However, alteration in the composition of EHC 44-59 by substituting alanine with valine at position 49, similar to the composition of IRBP 201-216, enabled the mimicry epitope to acquire uveitogenicity. The data provide new insights as to how microbes containing mimicry sequences for retinal antigens can prevent ocular inflammation by acting as naturally occurring altered peptide ligands.
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Autoimmunity in viral myocarditis.
Curr Opin Rheumatol
PUBLISHED: 05-10-2013
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To review how autoimmunity is induced in viral myocarditis.
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Potential of urinary metabolites for diagnosing multiple sclerosis.
ACS Chem. Biol.
PUBLISHED: 02-08-2013
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A definitive diagnostic test for multiple sclerosis (MS) does not exist; instead physicians use a combination of medical history, magnetic resonance imaging, and cerebrospinal fluid analysis (CSF). Significant effort has been employed to identify biomarkers from CSF to facilitate MS diagnosis; however, none of the proposed biomarkers have been successful to date. Urine is a proven source of metabolite biomarkers and has the potential to be a rapid, noninvasive, inexpensive, and efficient diagnostic tool for various human diseases. Nevertheless, urinary metabolites have not been extensively explored as a source of biomarkers for MS. We demonstrate that urinary metabolites have significant promise for monitoring disease-progression, and response to treatment in MS patients. NMR analysis of urine permitted the identification of metabolites that differentiate experimental autoimmune encephalomyelitis (EAE)-mice (prototypic disease model for MS) from healthy and MS drug-treated EAE mice.
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Copper-zinc superoxide dismutase-deficient mice show increased susceptibility to experimental autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein 35-55.
J. Neuroimmunol.
PUBLISHED: 01-05-2013
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In this report, we have addressed the role of copper-zinc superoxide dismutase (SOD1) deficiency in the mediation of central nervous system autoimmunity. We demonstrate that SOD1-deficient C57Bl/6 mice develop more severe autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein (MOG) 35-55, compared with wild type mice. This alteration in the disease phenotype was not due to aberrant expansion of MOG-specific T cells nor their ability to produce inflammatory cytokines; rather lymphocytes generated in SOD1-deficient mice were more prone to spontaneous cell death when compared with their wild type littermate controls. The data point to a role for SOD1 in the maintenance of self-tolerance leading to the suppression of autoimmune responses.
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Identification of a second mimicry epitope from Acanthamoeba castellanii that induces CNS autoimmunity by generating cross-reactive T cells for MBP 89-101 in SJL mice.
Int. Immunol.
PUBLISHED: 11-04-2011
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We had previously reported that Acanthamoeba castellanii (ACA) contains a mimicry epitope for proteolipid protein 139-151 capable of inducing central nervous system (CNS) autoimmunity in SJL/J mice. We now present evidence that ACA also contains a mimicry epitope for myelin basic protein (MBP) 89-101, a derivative from amoebic nicotinamide adenine dinucleotide dehydrogenase subunit 2 (NAD). The epitope, NAD 108-120, contains a discontinuous stretch of six amino acids in the core region (VVFFKNIILIGFL) sharing 46% identity with MBP 89-101 (VHFFKNIVTPRTP; identical residues are underlined). SJL mice immunized with NAD 108-120 develop encephalomyelitis similar to the disease induced by the cognate peptide. We demonstrate that NAD 108-120 induces T cells that cross-react with MBP 89-101; the antigen-sensitized T cells, which produce predominantly T helper (T(h)) 1 and T(h)17 cytokines, transfer disease in naive SJL recipients reminiscent of the disease induced with MBP 89-101. This is the first report to demonstrate that a solitary microbe can induce CNS autoimmunity by generating cross-reactive T cells for multiple myelin antigens.
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The 4 phases of quality maturity.
Healthc Financ Manage
PUBLISHED: 08-27-2011
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Evaluating a hospitals quality performance involves several key considerations: What drives the hospitals quality-of-care scores, and what are the underlying drivers of its outcomes and patient satisfaction? How does the hospitals quality and cost of care compare with those of its peers? Does the organization have a road map for predictable quality improvement? How do quality improvement initiatives affect financial performance? Does the chief quality officer (CQO) have a "seat at the table" in boardroom meetings? Does the strategic plan include quality goals? Does the hospital possess analytical tools to measure and understand quality of care with a holistic view and in financial context?
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Detection of cardiac myosin heavy chain-?-specific CD4 cells by using MHC class II/IA(k) tetramers in A/J mice.
J. Immunol. Methods
PUBLISHED: 06-13-2011
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A/J mice bearing the H-2 allele IA(k) are highly susceptible to autoimmune myocarditis induced with cardiac myosin heavy chain (Myhc)-? 334-352, whereas B10.A mice carrying a similar allele IA(k) are relatively resistant, suggesting that the generation of Myhc-?-reactive T cell repertoires is influenced by genetic background. To enumerate the precursor frequencies of Myhc-?-specific CD4 T cells, we sought to create IA(k) tetramers for Myhc-? 334-352. Tetramers were created using approaches that involve covalent tethering of individual peptide sequences or exogenous loading of peptides into empty IA(k) molecules by peptide-exchange reaction. Using ribonuclease 43-56 tetramers as controls, we demonstrated that by flow cytometry (FC), Myhc-? 334-352 tetramers specifically bind myosin-reactive T cells. CD4 cells isolated from A/J mice immunized with Myhc-? 334-352 were used to optimize conditions for tetramer staining, and neuraminidase treatment prior to tetramer staining permitted the detection of Myhc-?-specific cells ex vivo. The reagents are useful tools for monitoring the frequency of Myhc-?-reactive CD4 cells and to determine their pathogenic potential at a single cell level by FC.
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Detection of autoreactive CD4 T cells using major histocompatibility complex class II dextramers.
BMC Immunol.
PUBLISHED: 04-28-2011
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Tetramers are useful tools to enumerate the frequencies of antigen-specific T cells. However, unlike CD8 T cells, CD4 T cells - especially self-reactive cells - are challenging to detect with major histocompatibility complex (MHC) class II tetramers because of low frequencies and low affinities of their T cell receptors to MHC-peptide complexes. Here, we report the use of fluorescent multimers, designated MHC dextramers that contain a large number of peptide-MHC complexes per reagent.
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Oncogene-induced senescence and its role in tumor suppression.
J Mammary Gland Biol Neoplasia
PUBLISHED: 04-15-2011
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While senescence has been known for some time as an inevitable result of repeated DNA replication, oncogene-induced senescence (OIS) represents a relatively new phenomenon. OIS, like apoptosis, has emerged to represent a putative barrier to tumorigenesis in many tissues, including the breast. Here we discuss signals that initiate OIS, evidence for its role in tumor suppression, and mechanisms for its evasion in tumorigenesis.
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The physician value index: a tool for effective physician integration.
Healthc Financ Manage
PUBLISHED: 03-25-2011
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The physician value index is a metric that can help hospital leaders understand the various levels of physician performance along the care continuum in terms of cost and quality. The metric illustrates physician performance in the context of an overall quality of care composite that incorporates patient satisfaction, care outcomes, patient safety, and hospital financial performance. Hospitals can use the metric to identify and leverage the practices of top-performing physicians to improve overall system financial performance and patient quality of care.
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TCA cycle inactivation in Staphylococcus aureus alters nitric oxide production in RAW 264.7 cells.
Mol. Cell. Biochem.
PUBLISHED: 02-17-2011
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Inactivation of the Staphylococcus aureus tricarboxylic acid (TCA) cycle delays the resolution of cutaneous ulcers in a mouse soft tissue infection model. In this study, it was observed that cutaneous lesions in mice infected with wild-type or isogenic aconitase mutant S. aureus strains contained comparable inflammatory infiltrates, suggesting the delayed resolution was independent of the recruitment of immune cells. These observations led us to hypothesize that staphylococcal metabolism can modulate the host immune response. Using an in vitro model system involving RAW 264.7 cells, the authors observed that cells cultured with S. aureus aconitase mutant strains produced significantly lower amounts of nitric oxide (NO(•)) and an inducible nitric oxide synthase as compared to those cells exposed to wild-type bacteria. Despite the decrease in NO(•) synthesis, the expression of antigen-presentation and costimulatory molecules was similar in cells cultured with wild-type and those cultured with aconitase mutant bacteria. The data suggest that staphylococci can evade innate immune responses and potentially enhance their ability to survive in infected hosts by altering their metabolism. This may also explain the occurrence of TCA cycle mutants in clinical S. aureus isolates.
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miR-27b*, an oxidative stress-responsive microRNA modulates nuclear factor-kB pathway in RAW 264.7 cells.
Mol. Cell. Biochem.
PUBLISHED: 02-17-2011
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Reactive oxygen species (ROS) produced in macrophages is critical for microbial killing, but they also take part in inflammation and antigen presentation functions. MicroRNAs (miRNAs) are endogenous regulators of gene expression, and they can control immune responses. To dissect the complex nature of ROS-mediated effects in macrophages, we sought to characterize miRNAs that are responsive to oxidative stress-induced with hydrogen peroxide (H(2)O(2)) in the mouse macrophage cell line, RAW 264.7. We have identified a set of unique miRNAs that are differentially expressed in response to H(2)O(2). These include miR-27a*, miR-27b*, miR-29b*, miR-24-2*, and miR-21*, all of which were downregulated except for miR-21*. By using luciferase reporter vector containing nuclear factor-kB (NF-kB) response elements, we demonstrate that overexpression of miR-27b* suppresses lipopolysaccharide-induced activation of NF-kB in RAW 264.7 cells. Our data suggest that macrophage functions can be regulated by oxidative stress-responsive miRNAs by modulating the NF-kB pathway.
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Identification of novel mimicry epitopes for cardiac myosin heavy chain-? that induce autoimmune myocarditis in A/J mice.
Cell. Immunol.
PUBLISHED: 02-13-2011
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Myocarditis is one cause of sudden cardiac death in young adolescents, and individuals affected with myocarditis can develop dilated cardiomyopathy, a frequent reason for heart transplantation. Exposure to environmental microbes has been suspected in the initiation of heart autoimmunity, but the direct causal link is lacking. We report here identification of novel mimicry epitopes that bear sequences similar to those in cardiac myosin heavy chain (MYHC)-? 334-352. These epitopes represent Bacillus spp., Magnetospirillum gryphiswaldense, Cryptococcus neoformans and Zea mays. The mimicry peptides induced varying degrees of myocarditis in A/J mice reminiscent of the disease induced with MYHC-? 334-352. We demonstrate that the mimics induce cross-reactive T cell responses for MYHC-? 334-352 as verified by MHC class II IA(k)/tetramer staining and Th-1 and Th-17 cytokines similar to those of MYHC-? 334-352. The data suggest that exposure to environmental microbes which are otherwise innocuous can predispose to heart autoimmunity by molecular mimicry.
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Gender differences in CNS autoimmunity induced by mimicry epitope for PLP 139-151 in SJL mice.
J. Neuroimmunol.
PUBLISHED: 07-05-2010
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Development of multiple sclerosis (MS) is more prevalent in females than in males, but the underlying mechanisms are not clear. Microbial infections have been suspected as triggers of MS and it is not known whether gender differences in reactivity to environmental antigens contribute to the disease pathogenesis. We demonstrated that ACA 83-95, a mimicry epitope from Acanthamoeba castellanii for proteolipid protein (PLP) 139-151, induces clinical signs of encephalomyelitis in both male and female SJL mice. Conversely ACA 83-95-induced effector cells from males fail to induce disease in female mice. Although we found no gender differences in the frequencies of antigen-specific cells including cytokine production, PLP-specific cells induced with ACA 83-95 differed in T cell receptor v? usage from those induced with PLP 139-151. The data suggest that cross-reactive T cell expansion occurs similarly in both males and females, but their disease-inducing ability is influenced by gender.
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Long-term outcomes in patients with isolated supraclavicular nodal recurrence after mastectomy and doxorubicin-based chemotherapy for breast cancer.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 03-02-2010
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To examine the outcome of patients who developed an isolated locoregional recurrence (LRR) involving the supraclavicular fossa (SCV) after initial treatment with modified radical mastectomy and chemotherapy.
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Defining the ATM-mediated barrier to tumorigenesis in somatic mammary cells following ErbB2 activation.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 02-03-2010
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p53, apoptosis, and senescence are frequently activated in preneoplastic lesions and are barriers to progression to malignancy. These barriers have been suggested to result from an ATM-mediated DNA damage response (DDR), which may follow oncogene-induced hyperproliferation and ensuing DNA replication stress. To elucidate the currently untested role of DDR in breast cancer initiation, we examined the effect of oncogene expression in several murine models of breast cancer. We did not observe a detectable DDR in early hyperplastic lesions arising in transgenic mice expressing several different oncogenes. However, DDR signaling was strongly induced in preneoplastic lesions arising from individual mammary cells transduced in vivo by retroviruses expressing either PyMT or ErbB2. Thus, activation of an oncogene after normal tissue development causes a DDR. Furthermore, in this somatic ErbB2 tumor model, ATM, and thus DDR, is required for p53 stabilization, apoptosis, and senescence. In palpable tumors in this model, p53 stabilization and apoptosis are lost, but unexpectedly senescence remains in many tumor cells. Thus, this murine model fully recapitulates early DDR signaling; the eventual suppression of its endpoints in tumorigenesis provides compelling evidence that ErbB2-induced aberrant mammary cell proliferation leads to an ATM-mediated DDR that activates apoptosis and senescence, and at least the former must be overcome to progress to malignancy. This in vivo study also uncovers an unexpected effect of ErbB2 activation previously known for its prosurvival roles, and suggests that protection of the ATM-mediated DDR-p53 signaling pathway may be important in breast cancer prevention.
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The RCAS-TVA system for introduction of oncogenes into selected somatic mammary epithelial cells in vivo.
J Mammary Gland Biol Neoplasia
PUBLISHED: 11-05-2009
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We have reported the use of the RCAS-TVA system to model sporadic tumorigenesis upon oncogenic activation in somatic mammary epithelial cells in the mouse. Here we review the advantages of this approach as compared to conventional mouse models with transgenic oncogene expression. We also in detail describe the RCAS-TVA method for introducing genes into somatic mammary epithelial cells engineered to express the avian receptor tva. This method may be particularly useful in modeling oncogenic activation and subsequent tumorigenesis in distinct breast epithelial cell sub-populations, including progenitor cells.
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An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice.
J. Neuroimmunol.
PUBLISHED: 10-21-2009
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We report here that an epitope (aa, 83-95) derived from Acanthamoeba castellanii (ACA) induces clinical signs of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice reminiscent of the disease induced with myelin proteolipid protein (PLP) 139-151. By using IA(s)/tetramers, we demonstrate that both ACA 83-95 and PLP 139-151 generate antigen-specific cross-reactive CD4 T cells and the T cells secrete identical patterns of cytokines and induce EAE with a similar severity. These results may provide insights into the pathogenesis of multiple sclerosis and ACA-induced granulomatous encephalitis.
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Coxsackievirus B3 infection leads to the generation of cardiac myosin heavy chain-?-reactive CD4 T cells in A/J mice.
Clin. Immunol.
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Enteroviruses like coxsackievirus B3 (CVB3) are common suspects in myocarditis/dilated cardiomyopathy patients. Autoimmunity has been proposed as an underlying mechanism, but direct evidence of its role is lacking. To delineate autoimmune response in CVB3 myocarditis, we used IA(k) dextramers for cardiac myosin heavy chain (Myhc)-? 334-352. We have demonstrated that myocarditis-susceptible A/J mice infected with CVB3 generate Myhc-?-reactive CD4 T cells and such a repertoire was absent in naïve mice as measured by proliferative response to Myhc-? 334-352 and IA(k) dextramer staining. We also detected Myhc-? 334-352 dextramer(+) cells in the hearts of CVB3-infected mice. The autoreactive T cell repertoire derived from infected mice contained a high frequency of interleukin-17-producing cells capable of inducing myocarditis in naïve recipients. The data suggest that CVB3, a bona fide pathogen of cardiovascular system that primarily infects the heart can lead to the secondary generation of autoreactive T cells and contribute to cardiac pathology.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.