Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lentiviral vectors have proven to be promising tools for transduction of central nervous system (CNS) cells in vivo and in vitro. In this study, CNS transduction patterns of lentiviral vectors pseudotyped with envelope glycoproteins from Ebola virus, murine leukemia virus (MuLV), lymphocytic choriomeningitis virus (LCMV), or the rabies-related Mokola virus were compared to a vector pseudotyped with the vesicular stomatitis virus glycoprotein (VSV-G). Mokola-, LCMV-, and VSV-G-pseudotyped vectors transduced similar populations, including striatum, thalamus, and white matter. Mokola-pseudotyped vectors were the most efficient of the three. MuLV-pseudotyped lentivirus efficiently transduced striatum and hippocampal dentate gyrus. In contrast, no transduction resulted from injection of Ebola-pseudotyped virus in the CNS. The same pattern was observed in vitro with primary cultured oligodendrocytes. LCMV, MuLV, and Ebola pseudotypes were the most stable. These results demonstrate that targeted transduction in the CNS can be achieved using specific envelope glycoproteins to pseudotype lentiviral vectors, and support the use of Mokola-pseudotyped and MuLV-pseudotyped lentiviral vectors as efficient and stable alternatives to VSV-G-pseudotyped vectors for experiments in the mouse CNS.
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PMID:Targeted transduction patterns in the mouse brain by lentivirus vectors pseudotyped with VSV, Ebola, Mokola, LCMV, or MuLV envelope proteins. 1199 43

Early histologic changes in lesions at vaccine sites were compared in cats, mink, and ferrets. Twenty-four 4-month-old cats, 20 4-month-old mink, and 20 12-month-old ferrets were vaccinated with three rabies virus vaccines, two feline leukemia virus vaccines, alum adjuvant, and saline. Injection sites were excised at selected time points up to 21 days postvaccination. Histologic examination of the tissue revealed significant differences among the cats, mink, and ferrets in the local response to the commercial vaccines. When compared with ferrets and mink, cats had more lymphocytes in response to all three rabies vaccines. Production of fibroblasts, collagen, and macrophages differed among the three killed aluminum-adjuvanted vaccines in cats but did not differ significantly in mink or ferrets. Cats produced fewer binucleate cells than did mink or ferrets in response to the two adjuvanted leukemia virus vaccines. Differences seen in early tissue response of cats to commercial vaccines may be related to the increased predisposition of cats to vaccine-associated sarcomas.
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PMID:Cats differ from mink and ferrets in their response to commercial vaccines: a histologic comparison of early vaccine reactions. 1200 59

The interferon-induced promyelocytic leukaemia (PML) protein localizes both in the nucleoplasm and in matrix-associated multi-protein complexes known as nuclear bodies (NBs). NBs are disorganized in acute promyelocytic leukaemia or during some viral infections, suggesting that PML NBs could be a part of cellular defense mechanism. Rabies virus, a member of the rhabdoviridae family, replicates in the cytoplasm. Rabies phosphoprotein P and four other amino-terminally truncated products (P2, P3, P4, P5) are all translated from P mRNA. P and P2 are located in the cytoplasm, whereas P3, P4 and P5 are found mostly in the nucleus. Infection with rabies virus reorganized PML NBs. PML NBs became larger and appeared as dense aggregates when analysed by confocal or electron microscopy, respectively. The expression of P sequesters PML in the cytoplasm where both proteins colocalize, whereas that of P3 results in an increase in PML body size, as observed in infected cells. The P and P3 interacted directly in vivo and in vitro with PML. The C-terminal domain of P and the PML RING finger seem to be involved in this binding. Moreover, PML-/- primary mouse embryonic fibroblasts expressed viral proteins at a higher level and produced 20 times more virus than wild-type cells, suggesting that the absence of all PML isoforms resulted in an increase in rabies virus replication.
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PMID:Rabies virus P and small P products interact directly with PML and reorganize PML nuclear bodies. 1243 46

Type I diabetes is caused by an autoimmune-mediated elimination of insulin-secreting pancreatic islets. Genetic modification of islets offers a powerful molecular tool for improving our understanding of islet biology. Moreover, efficient genetic engineering of islets could allow for evaluation of new strategies aimed at preventing islet destruction. The present study evaluated the ability of a human immunodeficiency virus (HIV)-based lentiviral vector pseudotyped with various viral envelopes to target human islets ex vivo, with the goal of improving efficiency while minimizing toxicity. Transfer of the enhanced green fluorescent protein reporter gene in human islets was first evaluated with an HIV-based vector pseudotyped with the vesicular stomatitis virus (VSV), murine leukemia virus, Ebola, rabies, Mokola, or lymphocytic choriomeningitis virus (LCMV) envelope glycoprotein to optimize transduction efficiency. Results indicated that LCMV-pseudotyped vector transduced insulin-secreting beta cells with the highest efficiency. Moreover, toxicity associated with transduction of islets was found to be lower with LCMV-pseudotyped vector than with VSV-G-pseudotyped vector, the second most efficient vector for islet transduction. Overall, our study describes an improved methodology for achieving safe and efficient gene transfer into cells of human islets.
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PMID:Transduction of human islets with pseudotyped lentiviral vectors. 1497 93

Antibody titres to selected pathogens (canine adenovirus [CAV-2], feline herpesvirus [FHV], phocine herpesvirus [PHV-1], canine distemper virus, dolphin morbillivirus [DMV], phocine distemper virus [PDV], parainfluenza virus type 3 [PI3], rabies virus, dolphin rhabdovirus [DRV], canine coronavirus, feline coronavirus, feline leukaemia virus, Borrelia burgdorferi and Toxoplasma gondii) were determined in whole blood or serum samples from selected free-ranging terrestrial carnivores and marine mammals, including cougars (Fellis concolor), lynxes (Fellis lynx), American badgers (Taxidea taxus), fishers (Martes pennanti), wolverines (Gulo gulo), wolves (Canis lupus), black bears (Ursus americanus), grizzly bears (Ursus arctos), polar bears (Ursus maritimus), walruses (Odobenus rosmarus) and belugas (Delphinapterus leucas), which had been collected at several locations in Canada between 1984 and 2001. Antibodies to a number of viruses were detected in species in which these infections have not been reported before, for example, antibodies to CAV-2 in walruses, to PDV in black bears, grizzly bears, polar bears, lynxes and wolves, to DMV in grizzly bears, polar bears, walruses and wolves, to PI3 in black bears and fishers, and to DRV in belugas and walruses.
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PMID:Antibodies to selected pathogens in free-ranging terrestrial carnivores and marine mammals in Canada. 1533 5

Lentiviral vectors have proven to be valuable tools for in vitro and in vivo gene delivery because they can transduce dividing and non-dividing cells efficiently, and mediate long-term gene expression. Pseudotyping of lentiviral vectors with envelope proteins other than VSV-G has resulted in enhanced transduction of certain cell types and tissues. In order to improve lentiviral vector-based gene therapy for peripheral neuroectodermal and brain tumors, we compared the efficiency of eight different lentivirus pseudotypes in transducing neuronal and glial tumor cell lines. Here, lentiviral vectors pseudotyped with the envelopes from human foamy virus, rabies, Mokola or amphotropic murine leukemia virus displayed the highest transduction efficiency in neuroblastomas, whereas pseudotyping with the lymphocytic choriomeningitis virus glycoprotein from strain Armstrong 53b resulted in the highest transduction efficiency in gliomas.
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PMID:Transduction of human glial and neuronal tumor cells with different lentivirus vector pseudotypes. 1566 69

Pseudotyping lentiviral vector with other viral surface proteins could be applied for treating genetic anomalies in human skin. In this study, the modification of HIV vector tropism by pseudotyping with the envelope glycoprotein from vesicular stomatitis virus (VSV), the Zaire Ebola (EboZ) virus, murine leukemia virus (MuLV), lymphocytic choriomeningitis virus (LCMV), Rabies or the rabies-related Mokola virus encoding LacZ as a reporter gene was evaluated qualitatively and quantitatively in human skin xenografts. High transgene expression was detected in dermal fibroblasts transduced with VSV-G-, EboZ- or MuLV-pseudotyped HIV vector with tissue irregularities in the dermal compartments following repeated injections of EboZ- or LCMV-pseudotyped vectors. Four weeks after transduction, double-labeling immunofluorescence of beta-galactosidase and involucrin or integrin beta1 demonstrated that VSV-G-, EboZ- or MuLV-pseudotyped HIV vector effectively targeted quiescent epidermal stem cells which underwent terminal differentiation resulting in transgene expression in their progenies. Among the six different pseudotyped HIV-based vectors evaluated, VSV-G-pseudotyped vector was found to be the most efficient viral glycoprotein for cutaneous transduction as demonstrated by the highest level of beta-galactosidase expression and genome copy number evaluated by TaqMan PCR.
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PMID:Gene transfer in human skin with different pseudotyped HIV-based vectors. 1726 32

Lentiviral vectors have proven to be promising tools for transduction of brain cells in vivo and in vitro. In this study, we have examined the central nervous system (CNS) transduction efficiencies and patterns of a self-inactivating simian immunodeficiency virus (SIVmac)-derived lentiviral vector pseudotyped with glycoproteins from the vesicular stomatitis virus (VSV-G), the amphotropic murine leukemia virus (MLV4070Aenv), the lymphocytic choriomeningitis virus (LCMV-GP), the Ross River virus (RRV-GP) and the rabies virus (RV-G). All glycoproteins were efficiently incorporated into SIV virions, allowing efficient transduction of neuronal cell lines as well as of primary dissociated mouse brain cell cultures. After injection of highly concentrated vector stocks into the striatum of adult mice, quantitative analyses revealed high transduction efficiency with VSV-G pseudotypes, while LCMV-GP and RV-G pseudotypes exhibited moderate transduction efficiencies. MLV4070Aenv and RRV-GP pseudotypes, however, showed only weak levels of transduction after stereotactic injection into the brain. Regarding cell tropism in vivo, VSV-G-pseudotyped SIV vectors transduced neuronal as well as glial cells, whereas all other pseudotypes preferentially transduced neuroglial cells. In addition, we analyzed the influence of the central polypurine tract (cPPT) in context of the VSV-G-pseudotyped SIV transfer vector for infection of brain cells. Deletion of the cPPT sequence from the transfer vector decreased the in vivo transduction efficiency by fourfold, and, more importantly, this modification changed the transduction pattern, since these vectors were no longer able to infect neuronal cells in vivo. Vector injection into the brain did elicit a humoral immune response in the injected hemisphere; however, no gross signs of inflammation could be detected. Analysis of the biodistribution of the vector revealed that, besides the injected brain region, no vector-specific sequences could be detected in any of the organs evaluated. These data indicate SIV vectors as efficient gene delivery vehicles for the treatment of neurodegenerative diseases.
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PMID:Simian immunodeficiency virus vector pseudotypes differ in transduction efficiency and target cell specificity in brain. 1761 86

Cross-neutralization between rabies virus (RABV) and two European bat lyssaviruses (EBLV-1 and -2) was analysed using lentiviral pseudotypes as antigen vectors. Glycoprotein (G-protein) cDNA from RABV challenge virus standard-11 (CVS-11) and EBLV-1 and -2 were cloned and co-expressed with human immunodeficiency virus (HIV) or murine leukemia virus (MLV) gag-pol and packageable green fluorescent protein (GFP) or luciferase reporter genes in human cells. The harvested lentiviral (HIV) vector infected over 40% of baby hamster kidney (BHK) target cells, providing high-titre pseudotype stocks. Tests on blinded antibody-positive (n=15) and -negative (n=45) sera, predetermined by the fluorescent antibody virus neutralization (FAVN) test approved by the World Health Organization (WHO) and Office International des Epizooties (OIE), revealed that the CVS-11 pseudotype assay had 100% concordance with FAVN and strongly correlated with neutralization titres (r2=0.89). Cross-neutralization tests using sera from RABV-vaccinated humans and animals on pseudotypes with CVS-11, EBLV-1 and EBLV-2 envelopes showed that the relative neutralization titres correlated broadly with the degree of G-protein diversity. Pseudotypes have three major advantages over live-virus neutralization tests: (i) they can be handled in low-biohazard-level laboratories; (ii) the use of reporter genes such as GFP or beta-galactosidase will allow the assay to be undertaken at low cost in laboratories worldwide; (iii) each assay requires <10 microl serum. This robust microassay will improve our understanding of the protective humoral immunity that current rabies vaccines confer against emerging lyssaviruses, and will be applicable to surveillance studies, thus helping to control the spread of rabies.
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PMID:Investigating antibody neutralization of lyssaviruses using lentiviral pseudotypes: a cross-species comparison. 1875 30

An 18-month-old European shorthair cat was presented with a two week history of progressive decrease in consciousness, ambulatory tetraparesis, moderate ataxia and generalised decreased-to-absent postural reactions. Bilateral facial and nasal hypalgesia, absent menace response and anisocoria were found, and segmental spinal reflexes were normal. Neurological signs progressed to nonambulatory tetraparesis, tremor and spinal hyperalgesia. Histopathological examination revealed a mild-to-moderate lymphoplasmacytic and histiocytic infiltration, predominantly in the dorsal spinal roots, cranial nerves and ganglia in association with marked demyelination and proliferation of Schwann cells. Neurons and axons were preserved. Lesions were multi-focal and varied in severity. A predominantly sensory polyganglioradiculoneuritis was diagnosed. This lesion has not been reported previously in cats. Rabies, herpesviruses, feline infectious peritonitis, feline immunodeficiency virus, Toxoplasma gondii and feline leukaemia virus were excluded as possible aetiologies. Infections by other viruses or an autoimmune disease are discussed.
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PMID:Polyganglioradiculoneuritis in a young cat: clinical and histopathological findings. 1942 74


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