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Find video protocols related to scientific articles indexed in Pubmed.
Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies.
Clin. Cancer Res.
PUBLISHED: 09-08-2011
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The clinical success of the first-in-class proteasome inhibitor bortezomib (VELCADE) has validated the proteasome as a therapeutic target for treating human cancers. MLN9708 is an investigational proteasome inhibitor that, compared with bortezomib, has improved pharmacokinetics, pharmacodynamics, and antitumor activity in preclinical studies. Here, we focused on evaluating the in vivo activity of MLN2238 (the biologically active form of MLN9708) in a variety of mouse models of hematologic malignancies, including tumor xenograft models derived from a human lymphoma cell line and primary human lymphoma tissue, and genetically engineered mouse (GEM) models of plasma cell malignancies (PCM).
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Role of AKT kinase in measles virus replication.
J. Virol.
PUBLISHED: 11-25-2009
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Many RNA and DNA viruses activate serine-threonine kinase AKT to increase virus replication. In contrast, measles virus (MV) infection leads to downregulation of AKT. This is thought to be beneficial for the virus because it correlates with immune suppression. To determine whether this is a sacrifice for the virus, we used a recombinant virus and transfected cells expressing constitutively active AKT and evaluated its effect on virus replication. In vitro, overexpression of AKT did not influence virus replication but did affect (cell-type dependent) virus release. In vivo, the recombinant virus did not abrogate inhibition of proliferation of spleen cells from MV-infected cotton rats.
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Sorting signals in the measles virus wild-type glycoproteins differently influence virus spread in polarized epithelia and lymphocytes.
J. Gen. Virol.
PUBLISHED: 07-01-2009
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The spread of virus infection within an organism is partially dictated by the receptor usage of the virus and can be influenced by sorting signals present in the viral glycoproteins expressed in infected cells. In previous studies, we have shown that the haemagglutinin (H) and fusion protein (F) of the measles virus (MV) vaccine strain MV(Edm) harbour tyrosine-dependent sorting signals which influence virus spread in both lymphocytes and epithelial cells to a similar degree. In contrast with the vaccine strain, MV wild-type virus does not use CD46 but CD150/SLAM and a not clearly identified molecule on epithelial cells as receptors. To determine differences in viral spread between vaccine and wild-type virus, we generated recombinant MV expressing glycoproteins of both the wild-type strain WTFb and the corresponding tyrosine mutants. In contrast with observations based on vaccine virus glycoproteins, mutations in wild-type virus H and F differently influenced cell-to-cell fusion and replication in polarized epithelia and lymphocytes. For wild-type H, our data suggest a key role of the cytoplasmic tyrosine signal for virus dissemination in vivo. It seems to be important for efficient virus spread between lymphocytes, while the tyrosine signal in the F protein gains importance in epithelial cells as both signals have to be intact to allow efficient spread of infection within epithelia.
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Hyperalbuminemia associated with hepatocellular carcinoma in a dog.
Vet Clin Pathol
PUBLISHED: 05-15-2009
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A 12-year-old, neutered male, mixed-breed dog was presented to The Ohio State University Veterinary Teaching Hospital with a history of weight loss and weakness. Laboratory abnormalities reported by the referring veterinarian during the past year included increased alkaline phosphatase (ALP) activity, hyperalbuminemia, and nonregenerative anemia. On referral, the dog appeared hydrated and had moderate muscle wasting and hepatomegaly. A large lobular hepatic mass was observed ultrasonographically. Laboratory results included mild to moderate nonregenerative anemia, urine-specific gravity of 1.035, 3+ proteinuria, increased serum activities of alanine aminotransferase (229 U/L, reference interval 10-55 U/L), ALP (813 U/L, reference interval 15-120 U/L), and the steroid-induced isoform of ALP (676 U/L, reference interval 0-6 U/L), marked hyperalbuminemia (5.3 g/dL, reference interval 2.9-4.2 g/dL), and an increased A/G ratio (1.7). Hyperalbuminemia was confirmed by reanalysis on 2 different analyzers and by agarose gel electrophoresis, and colloid osmotic pressure (COP) was markedly increased (42.5 mmHg, reference interval 20-25 mmHg). Cytologic examination of a fine-needle aspirate of the hepatic mass indicated hepatocellular proliferation; histologic examination of an excisional biopsy confirmed hepatocellular carcinoma. Three weeks after surgery, the albumin concentration, A/G ratio, COP, and ALT activity had normalized, but ALP activities remained high. We hypothesized that hyperalbuminemia developed secondary to hepatocellular carcinoma due to increased synthesis of albumin by malignant hepatocytes or due to decreased negative feedback from impaired hepatocellular osmoreceptivity. Hepatocellular carcinoma has been associated with paraneoplastic secretion of other proteins, but hyperalbuminemia has been reported only once in a human patient and has not previously in dogs.
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Cytokine imbalance after measles virus infection has no correlation with immune suppression.
J. Virol.
PUBLISHED: 05-06-2009
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Measles virus infection leads to immune suppression. A potential mechanism is the reduction of interleukin 12 (IL-12) secretion during acute measles, resulting in a TH2 response. Studies in humans have reported conflicting results, detecting either a TH2 or a TH1 response. We have investigated the correlation between a TH2 response and immune suppression in specific-pathogen-free inbred cotton rats which were infected with measles vaccine and wild-type viruses. After infection of bone marrow-derived macrophages with wild-type virus, IL-12 secretion was reduced in contrast to the level for vaccine virus infection. In bronchoalveolar lavage cells, IL-12 secretion was suppressed after infection with both wild-type and vaccine virus on days 2, 4, and 6 and was detectable on days 8 and 10. After stimulation of mediastinal lymph node and spleen cells with UV-inactivated measles virus at various time points after infection, gamma interferon but no IL-4 was found. After stimulation with phorbol myristate acetate-ionomycin, high gamma interferon and low IL-4 levels were detected. To investigate whether the secretion of IL-4 contributes to immune suppression, a recombinant vaccine virus was created which secretes cotton rat IL-4. After infection with this recombinant virus, IL-4 secretion was enhanced. However, neither inhibition of concanavalin A-stimulated spleen cells nor keyhole limpet hemocyanin-specific proliferation of spleen cells was altered after infection with the recombinant virus in comparison to the levels with the parental virus. Our data indicate that measles virus infection leads to a decrease in IL-12 secretion and an increase in IL-4 secretion, but this does not seem to correlate with immune suppression.
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Major histocompatibility complex haplotype determines hsp70-dependent protection against measles virus neurovirulence.
J. Virol.
PUBLISHED: 03-25-2009
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In vitro studies show that hsp70 promotes gene expression for multiple viral families, although there are few reports on the in vivo significance of virus-hsp70 interaction. Previously we showed that hsp70-dependent stimulation of Edmonston measles virus (Ed MeV) transcription caused an increased cytopathic effect and mortality in transgenic hsp70-overexpressing C57BL/6 mice (H-2(b)). The response to MeV infection is influenced by the major histocompatibility complex haplotype; H-2(d) mice are resistant to brain infection due to robust antiviral immune responses, whereas H-2(b) mice are susceptible due to deficiencies in this response. We therefore tested the hypothesis that the outcome of MeV-hsp70 interaction may be dependent upon the host H-2 haplotype. The impact of selective neuronal hsp70 overexpression on Ed MeV brain infection was tested with congenic C57BL/10 H-2(d) neonatal mice. In this context, hsp70 overexpression conferred complete protection against virus-induced mortality, compared to >30% mortality in nontransgenic mice. Selective depletion of T-cell populations showed that transgenic mice exhibit a diminished reliance on T cells for protection. Brain transcript analysis indicated enhanced innate immune activation and signaling through Toll-like receptors 2 and 4 at early times postinfection for transgenic infected mice relative to those for nontransgenic infected mice. Collectively, results suggest that hsp70 can enhance innate antiviral immunity through Toll-like receptor signaling, supporting a protective role for physiological responses that enhance tissue levels of hsp70 (e.g., fever), and that the H-2 haplotype determines the effectiveness of this response.
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Nitric oxide production and nitric oxide synthase type 2 expression by cotton rat (Sigmodon hispidus) macrophages reflect the same pattern as human macrophages.
Dev. Comp. Immunol.
PUBLISHED: 01-18-2009
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Our knowledge of the antibacterial role of nitric oxide (NO) during infection is based on studies of murine macrophages, which secrete large amounts of NO. In contrast, human macrophages produce very little NO and its relevance as an antibacterial mediator during infection of humans is uncertain. We have defined bone marrow-derived macrophages from cotton rats (Sigmodon hispidus). These macrophages display phenotypical and functional characteristics similar to other rodent and human macrophages. The most interesting finding was the low level of NO production which is in contrast to findings for murine macrophages, but consistent with those of humans. In spite of these low levels, inhibition of NO production led to a decrease in killing of bacteria. Cotton rats are highly susceptible to a variety of human pathogens and therefore offer a rodent model of infectious diseases with similar characteristics to humans in terms of NO production.
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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.

How does it work?

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

Video X seems to be unrelated to Abstract Y...

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.