Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transgenic tobacco plants expressing the coat protein (CP) gene of tobacco mosaic virus were tested for resistance against infection by five other tobamoviruses sharing 45-82% homology in CP amino acid sequence with the CP of tobacco mosaic virus. The transgenic plants (CP+) showed significant delays in systemic disease development after inoculation with tomato mosaic virus or tobacco mild green mosaic virus compared to the control (CP-) plants, but showed no resistance against infection by ribgrass mosaic virus. On a transgenic local lesion host, the CP+ plants showed greatly reduced numbers of necrotic lesions compared to the CP- plants after inoculation with tomato mosaic virus, pepper mild mottle virus, tobacco mild green mosaic virus, and Odontoglossum ringspot virus but not ribgrass mosaic virus. The implications of these results are discussed in relation to the possible mechanism(s) of CP-mediated protection.
Mol Plant Microbe Interact
PMID:Transgenic tobacco plants expressing a coat protein gene of tobacco mosaic virus are resistant to some other tobamoviruses. 213 Oct 95

About 10 years ago, we implicated immune factors in the pathophysiology of Alzheimer disease (AD), the hypothesis being that AD may be an immunologically derived systemic disease, but clinical effects confined primarily to the brain. We originally hypothesized that an immune basis of the disease may involve faulty immune regulation and autoimmunity. As described here, the activation of immunoregulatory T-lymphocytes with CD8 phenotype may be important in the immunopathogenesis of the disease.
Mol Chem Neuropathol
PMID:Immune-activation model in Alzheimer disease. 887 48

Chromatin, a huge polymer of nucleosomes, has been implicated as an important target of autoantibodies in idiopathic and drug-induced lupus for decades, but the antigenicity of chromatin has only recently been dissected. IgG reactivity with the (H2A-H2B)-DNA complex, a subunit of the nucleosome, is present in the majority of patients with systemic lupus erythematosus, in > 90% of patients with lupus induced by procainamide and in individual patients with lupus induced by a variety of other drugs, but is not seen in people taking these medications who are clinically asymptomatic. Anti-[(H2A-H2B)-DNA] accounted for the bulk of the anti-chromatin activity in drug-induced lupus. The earliest detectable autoantibody in lupus-prone mice recognized similar epitopes in the (H2A-H2B)-DNA subnucleosome complex; as the immune response progressed, native DNA and other constituents of chromatin became antigenic. The importance of chromatin-reactive T cells in the anti-[(H2A-H2B)-DNA] response is suggested by the presence of somatic mutations in antibody VH and VL regions, their predominant IgG isotype and the similarity in kinetics of their production to that of conventional T cell dependent antigens. Together with the serologic data from human lupus-like disease, these results are consistent with chromatin being a common stimulant for both B and T cells. While chromatin-reactive antibodies are closely associated with systemic disease and have recently been implicated in glomerulonephritis in SLE, the absence of renal disease in drug-induced lupus indicates that additional abnormalities are required to manifest the serious pathogenic of anti-[(H2A-H2B)-DNA] antibodies.
Mol Biol Rep 1996
PMID:Autoantibody to the nucleosome subunit (H2A-H2B)-DNA is an early and ubiquitous feature of lupus-like conditions. 911 24

Red pepper, one of the most important vegetable crops in Korea, is severely affected by viral diseases causing 20-50% reduction in product yield. A pepper strain of tobacco mosaic virus (TMV-p) is the most common virus in red pepper. To study the molecular structure of the TMV-p virus, we generated cDNA clones of the viral genome. Partial sequencing of a few cDNA clones revealed that TMV-p shares a 98% identity at the nucleotide level with the Spanish isolate of pepper mild mottle virus (PMMV-s). This suggests that TMV-p should be reclassified as the Korean isolate of PMMV (PMMV-k). The coat protein (CP) gene together with the 3' untranslated region of the PMMV-k virus was obtained by reverse transcriptase-polymerase chain reaction (RT-PCR) using oligomers deduced from the sequence of PMMV-s. The sequence analysis of the CP gene and the 3' untranslated region further confirmed that PMMV-k is highly related to PMMV-s. The CP gene and the 3' untranslated region of PMMV-k were cloned into a plant expression vector and the construct was introduced into tobacco plants. The transgenic plants expressing the PMMV-k CP gene were delayed in developing systemic disease or failed to develop symptoms at all after inoculation with PMMV-k. Delay of symptoms was also observed when the plants were inoculated with TMV-OM which shares a 74% homology with PMMV-k in the amino acid sequence of the CP region. In a local lesion host, the CP expressing plants exhibited a greatly reduced number of necrotic lesions as compared to control plants after inoculation with TMV-OM. Our results show that CP-mediated viral resistance is readily applicable in the case of PMMV-k and can provide resistance to other viruses in the tobamovirus group.
Mol Cells 1997 Jun 30
PMID:Resistance to tobamoviruses in transgenic tobacco plants expressing the coat protein gene of pepper mild mottle virus (Korean isolate). 926 16

The skin represents a site for treatment of cutaneous and systemic disease and is the most accessible somatic tissue for therapeutic gene transfer in humans. Monogenic hereditary skin diseases, such as ichthyosis and epidermolysis bullosa subtypes, and disorders characterized by low levels of polypeptides in the systemic circulation, are current central foci of efforts in cutaneous-gene transfer. Additional efforts center on the treatment of wounds and malignancies. Recent developments in models of gene delivery to the skin underscore key challenges that must be met before successful treatment of human disease by cutaneous gene delivery can be achieved.
Mol Med Today 1997 Dec
PMID:Therapeutic gene delivery to the skin. 944 24

Salmonella infections continue to cause gastrointestinal and systemic disease throughout the world. Salmonella typhimurium DT104 further poses a major health concern due to its acquisition of resistance to multiple antibiotics. The rapid detection of multiresistant S. typhimurium DT104 would facilitate strategies aimed at controlling this pathogen. We developed a specific and sensitive polymerase chain reaction (PCR) assay that amplifies a segment of DNA that is conserved in multiresistant S. typhimurium DT104. To provide further specificity for this PCR-based diagnostic test, we amplified two other gene fragments that are present in S. typhimurium DT104. A multiplex PCR containing primers for targeted sequences resulted in the amplification of predicted size fragments from S. typhimurium DT104 exhibiting the ACSSuT (ampicillin, chloramphenicol, streptomycin, sulphamethoxazole and tetracycline) or ASSuT resistance phenotypes. A minor modification of the multiplex PCR enabled the detection of other related multiresistant Salmonella such as S. typhimurium U302. To augment the detection process, we also designed a fluorogenic PCR assay that can detect the DNA of multiresistant S. typhimurium DT104 in the presence of excess contaminating bacterial DNA. These results provide a method by which multiresistant S. typhimurium DT104, or potentially the next emerging multiresistant Salmonella, can be accurately detected in only 3-4 h.
Mol Cell Probes 1999 Jun
PMID:Detection of multiresistant Salmonella typhimurium DT104 using multiplex and fluorogenic PCR. 1036 47

Sustained systemic dissemination of therapeutic proteins from peripheral sites is an attractive prospect for gene therapy applications. Replication-defective genomic herpes simplex virus type 1 (HSV-1) vectors were evaluated for their ability to express nerve growth factor (NGF) as a model gene product both locally and systemically. Intra-articular inoculation of NGF expression vectors in rabbits resulted in significant increases in joint lavage and blood plasma NGF that persisted for 1 year. A rhesus macaque injected intra-articularly displayed a comparable increase in plasma NGF for at least 6 months, at which time the serum NGF levels of this animal were sufficient to cause differentiation of PC12 cells in culture, but not to increase footpad epidermis innervation. Long-term reporter transgene expression was observed primarily in ligaments, a finding confirmed by direct inoculation of patellar ligament. Patellar ligament inoculation with a NGF vector resulted in elevated levels of circulating NGF similar to those observed following intra-articular vector delivery. These results represent the first demonstration of sustained systemic release of a transgene product using HSV vectors, raising the prospect of new applications for HSV-1 vectors in the treatment of systemic disease.
Mol Ther 2001 Jan
PMID:Herpesvirus-mediated systemic delivery of nerve growth factor. 1116 12

The development of vectors capable of treating systemic diseases is an important goal for gene therapy protocols. In order for a carrier system to preferentially accumulate at sites of systemic disease, such as tumors, sites of inflammation and sites of infection, the carrier must exhibit long circulation lifetimes following intravenous injection. Unfortunately, most gene delivery systems, including viral vectors as well as non-viral vectors, e.g., lipoplexes, polyplexes and lipopolyplexes, are rapidly cleared from the circulation and are preferentially taken up by the 'first-pass' organs such as liver, lung and spleen. Here we review recent literature concerning the ability of non-viral vectors to act as systemic gene therapy agents. The most promising systemic vectors are liposomal systems in which plasmid DNA is encapsulated within a lipid bilayer. The stabilized plasmid-lipid particle (SPLP) system, for example, exhibits circulation half-lives of the order of 6 h following intravenous injection, and preferentially accumulates in distal tumors with gene expression primarily localized to the tumor site.
Curr Opin Mol Ther 2001 Apr
PMID:Long-circulating vectors for the systemic delivery of genes. 1133 28

A significant amount of research has been devoted to the chemical stabilization of synthetic ribozymes, in part, so that applications to systemic disease can be explored. A nuclease-stabilized synthetic hammerhead ribozyme, ANGIOZYME, has been developed which targets the mRNA encoding a vascular endothelial growth factor receptor, Flt-1. Because the stimulation of this receptor may contribute to tumor neovascularization and subsequent tumor growth and metastasis, we have explored the systemic use of ANGIOZYME to down regulate this receptor in a syngeneic model of metastatic cancer. We describe here the application of pharmacokinetic analysis to the selection of a dosing regimen for pharmacodynamic screening in this murine cancer model. These studies demonstrate that the appropriate application of pharmacokinetic analysis is necessary for the optimization of systemic pharmacodynamic studies using synthetic ribozymes.
Curr Issues Mol Biol 2000 Oct
PMID:Ribozyme pharmacokinetic screening for predicting pharmacodynamic dosing regimens. 1147 55

Friedreich Ataxia (FRDA), the most prevalent of the inherited ataxias, is a multi-systemic disease with loss of sensory neurons and life-threatening hypertrophic cardiomyopathy as its most severe manifestations. Reduced levels of the mitochondrial protein frataxin lead to cell-damaging oxidative stress and consequently FRDA is considered as a model for more common neurodegenerative disorders in which reactive radicals and oxidative stress are involved. We have developed a cellular assay system that discriminates between fibroblasts from FRDA patients and unaffected donors on the basis of their sensitivity to pharmacological inhibition of de novo synthesis of glutathione. With this assay we observed that supplementation with selenium effectively improved the viability of FRDA fibroblasts, indicating that basal selenium concentrations are not sufficient to allow an adequate increase in the activity of certain detoxification enzymes (such as GPX). Furthermore, we characterized potential drug candidates and found that idebenone, a mitochondrially localized antioxidant that ameliorates cardiomyopathy in FRDA patients, as well as other lipophilic antioxidants protected FRDA cells from cell death. Our results also demonstrate for the first time that small-molecule GPX mimetics have potential as a novel treatment strategy for Friedreich Ataxia and presumably also for other neurodegenerative diseases with mitochondrial impairment.
Hum Mol Genet 2002 Nov 15
PMID:A cellular model for Friedreich Ataxia reveals small-molecule glutathione peroxidase mimetics as novel treatment strategy. 1241 27


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