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)

Toxoplasma gondii is a ubiquitous parasitic protozoan causing congenital infection and severe encephalitis in the course of the acquired immunodeficiency syndrome. Glycosyl-phosphatidylinositols of T. gondii have been shown to be identical with the low molecular weight antigen which elicits an early immunoglobulin M immune response in humans. A detailed study of the structures of these glycolipid antigens was performed. Radiolabelled glycolipids were extensively analysed by chemical and exoglycosidase treatments in combination with high pH anion-exchange chromatography, gel-filtration and lectin affinity chromatography. In addition, carbohydrate fragments prepared and purified from bulk preparations of unlabelled glycolipids by high performance liquid chromatography were subjected to two-dimensional 1H nuclear magnetic resonance spectroscopy, fast-atom bombardment-mass spectrometry, and methylation linkage analysis in order to elucidate the structure of T. gondii GPIs. The following structures were identified: (ethanolamine-PO4)-Man alpha 1-2Man alpha 1-6(GalNAc beta 1-4)Man alpha 1-4GlcN alpha-inositol-PO4-lipid and the novel structure (ethanolamine-PO4)-Man alpha 1-2Man alpha 1-6(Glc alpha 1-4GalNAc beta 1-4)Man alpha 1-4 GlcN alpha-inositol-PO4-lipid both with and without terminal ethanolamine phosphate. Evidence is provided, that only T. gondii GPIs bearing the unique glucose-N-acetylgalactosamine side branch are immunogenic in humans and that this structure is widely distributed among T. gondii isolates. Monoclonal antibodies have been characterized to recognize structures with different degrees of side-chain modification. We suggest that these reagents in combination with recently devised techniques for insertional mutagenesis in T. gondii should greatly facilitate the cloning of genes essential for GPI side-chain modification.
J Mol Biol 1997 Mar 07
PMID:Molecular structure of the "low molecular weight antigen" of Toxoplasma gondii: a glucose alpha 1-4 N-acetylgalactosamine makes free glycosyl-phosphatidylinositols highly immunogenic. 910 70

During the past decade nitric oxide has emerged as an important mediator of physiological and pathophysiological processes. Elevated nitric oxide bio-synthesis has been associated with nonspecific immune-mediated cellular cytotoxicity and the pathogenesis of chronic, inflammatory autoimmune diseases including rheumatoid arthritis, insulin-dependent diabetes, inflammatory bowel disease, and multiple sclerosis. Recent evidence suggests, however, that nitric oxide is also immunoregulatory and suppresses the function of activated proinflammatory macrophages and T lymphocytes involved in these diseases. This article reviews the role of nitric oxide in the biology of central nervous system glial cells (astrocytes and microglia) as it pertains to the pathogenesis of multiple sclerosis in humans and experimental allergic encephalitis, the animal model of this disease. Although nitric oxide has been clearly implicated as a potential mediator of microglia-dependent primary demyelination, a hallmark of multiple sclerosis, studies with nitric oxide synthase inhibitors in the encephalitis model have been equivocal. These data are critically reviewed in the context of what is know from clinical research on the nitric oxide pathway in multiple sclerosis. Specific recommendations for future preclinical animal model research and clinical research on the nitric oxide pathway in patients are suggested. These studies are necessary to further define the role of nitric oxide in the pathology of multiple sclerosis and to fully explore the potential for nitric oxide synthase inhibitors as novel therapeutics for this disease.
J Mol Med (Berl) 1997 Mar
PMID:The role of nitric oxide in multiple sclerosis. 910 72

Toxoplasma gondii is an important cause of AIDS-related opportunistic infection, manifest as toxoplasmic encephalitis. The clinical treatment of choice is the synergistic combination of antifolate agents, pyrimethamine and sulphadiazine, of which the latter targets the parasite's dihydropteroate synthase (DHPS) activity. Here, we describe the isolation of the gene encoding this activity in T. gondii. The nucleotide sequence contains an open reading frame interrupted by five introns, which encodes a protein of 664 amino acids with an M(r) of 72991. Sequence analysis revealed that, in addition to DHPS, the predicted protein contains a second enzyme function, hydroxymethyldihydropterin pyrophosphokinase (PPPK). This enzyme immediately precedes DHPS in the folate biosynthetic pathway. The bifunctional arrangement of the T. gondii pppk-dhps gene is the same as that observed in the related protozoan parasite, Plasmodium falciparum, and confirms previous biochemical data that these activities were inseparable. Recently, specific mutations within conserved motifs of the DHPS gene of P. falciparum have been identified which give rise to sulphonamide drug resistance. Analysis of seven clinical isolates of T. gondii did not reveal any similar mutations in this limited sample of organisms that had been subjected to drug pressure.
Mol Biochem Parasitol 1997 May
PMID:Isolation and molecular characterization of the bifunctional hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase gene from Toxoplasma gondii. 917 66

The coat protein gene from encephalitis virus infecting Dicentrarhus labrax (DIEV) has been cloned by gene amplification, sequenced and expressed in Escherichia coli. DNA sequencing has revealed an open reading frame of 1017 bases encoding a polypeptide of 338 amino acids. The sequence similarities between the DIEV coat protein gene and the same gene in five encephalitis viruses infected other fish species were over 71.5% at the nucleotide level and over 79.5% at the amino acid level. These results indicate that the nodaviruses that cause encephalopathy and retinopathy in fishes are very closed related. E. coli cells harbouring the plasmid containing the DIEV gene can produce the viral coat protein. An efficient purification scheme using a Sepharore-Ni+2 column is presented. This, gives approx. 10 mg of more than 95% pure protein per gr of E. coli culture.
Biochem Mol Biol Int 1997 Jun
PMID:Cloning, expression and purification of the coat protein of encephalitis virus (DIEV) infecting Dicentrarchus labrax. 923 40

The response of caprine macrophages to exposure to caprine arthritis-encephalitis virus (CAEV) and lipopolysaccharide (LPS) was investigated in female Nubian and Nubian crossbreed of goats. Macrophages were matured in vitro from monocytes isolated from blood of control and CAEV-infected goats and the concentrations of tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) in culture supernatant after exposure of cells to LPS and virus were assayed. Though barely detectable in unstimulated cells, TNF-alpha and IL-6 levels showed peak values of 420 +/- 28 to 530 +/- 32 and 70 +/- 27 to 93 +/- 29, respectively, in supernatants of control goat cells [corrected], remaining high through 24 hrs. post treatment with LPS stimulation. Exposure of these control goat cells [corrected] to virus induced lower secretions (p<0.05) of the cytokines. The peak values occurred between 6 and 12 hrs. post treatment with LPS or virus. Cells prepared from virus-infected goats and treated with the mitogen or virus showed significantly (p<0.05) lower response than those from control goats. The present results suggest a dysregulation, possibly downregulation of the production of both cytokines in macrophages of goats chronically diseased by lentivirus infection.
Cell Mol Biol (Noisy-le-grand) 1997 Nov
PMID:Cytokine production in vitro by macrophages of goats with caprine arthritis-encephalitis. 944 35

Monoclonal antibodies to the Sindbis virus E2 envelope glycoprotein protect mice against lethal encephalitis and mediate viral clearance from neurons. To facilitate structure-function analyses of anti-E2 mAbs, we developed an expression system that can be used for the construction of genetically engineered anti-E2 mAbs. We constructed recombinant Sindbis/immunoglobulin gene chimeric viruses that express heavy and light chains of an anti-E2 monoclonal antibody, R6. We used a PCR-based strategy to clone the entire rearranged heavy and light chain genes from R6 hybridoma cell cDNA into a double subgenomic Sindbis virus vector. The recombinant viruses, SIN/R6L and SIN/R6H, were generated by transfecting BHK-21 cells with in vitro transcribed RNA from Sindbis virus/R6 light chain and Sindbis virus/R6 heavy chain cDNA clones, respectively. Twelve hours after co-infection of BHK cells with SIN/R6L and SIN/R6H, the tissue culture supernatant contained up to 1.4 mg/ml of recombinant R6 IgG. The heavy and light chains of recombinant R6 were associated as judged by co-purification on protein A/G sepharose and co-electrophoresis of non-reduced proteins. The ELISA reactivity to Sindbis virus antigen was similar for recombinant R6 and R6 purified from ascites fluid. Furthermore, the in vivo biologic activity of recombinant R6 was similar to that of R6 purified from ascites; recombinant R6 treatment completely protected Balb/cJ mice from paralysis and death due to infection with neuroadapted Sindbis virus and also resulted in the clearance of infectious virus from the brains of immunodeficient scid mice persistently infected with wild-type Sindbis virus. Thus, the co-infection of BHK cells with SIN/R6L and SIN/R6H leads to the expression, assembly, and secretion of a biologically active recombinant antiviral antibody. Our results suggest that the Sindbis virus vector system is a simple and powerful tool for the production of functional, genetically engineered antibodies.
Mol Immunol
PMID:Expression of a biologically active antiviral antibody using a sindbis virus vector system. 946 26

Astrocyte activation has been postulated to be a major contributor to functional changes in the brain of AIDS patients. We assessed astrocyte activation in the simian immunodeficiency virus (SIV) model. Four groups of macaque brains were examined: uninoculated controls, animals inoculated with virus that did not cause disease, animals inoculated with virus that caused AIDS but did not cause encephalitis, and animals with SIV encephalitis. We examined expression of calbindin-D-28K, a calcium binding protein that is upregulated in astrocytes during excitotoxic events, as well as glial fibrillary acidic protein (GFAP). The presence of calbindin in astrocytes was confirmed by double-labeling using confocal microscopy. Increases in calbindin staining were most apparent in the white matter, but increases in GFAP staining were most apparent in middle layers of the cerebral cortex. Six of the seven animals with SIV encephalitis had calbindin immunoreactive astrocytes in the subcortical white matter, corpus callosum, internal capsule, cerebral peduncle, pontine white matter, and cerebellar white matter. Very rarely, a few, very lightly calbindin-immunoreactive astrocytes were present in the uninoculated control brains. The increase in calbindin expression by astrocytes in SIV encephalitis suggests that these cells are subject to calcium toxicity. In uninoculated control macaques, and in macaques inoculated with virus that did not cause disease, GFAP-immunoreactive astrocytes were present throughout the subcortical white matter and in layer I, but very few were found in layers III-V of the cerebral cortex. Two animals that died of AIDS without encephalitis had somewhat higher numbers of GFAP immunoreactive astrocytes in middle cortical layers. In seven animals that received passaged neurovirulent virus and developed both AIDS and encephalitis, the number of GFAP-immunoreactive astrocytes in middle cortical layers was high, indicating widespread astrocyte activation.
Mol Chem Neuropathol 1998 May
PMID:Neurovirulent simian immunodeficiency virus induces calbindin-D-28K in astrocytes. 977 44

A duplex polymerase chain reaction (PCR) assay for the detection and genotyping of Herpes simplex virus (HSV) 1 and 2 from cerebrospinal fluid (CFS) of infants was developed. The glycoprotein D (gD) gene of HSV was selected as a target for amplification. The assay is highly specific, sensitive and reproducible. Herpes simplex virus detection is performed by agarose gel electrophoresis and Southern blot using a chemiluminescent probe. The probe hybridizes to sequences common to both HSV-1 and 2. A DNA fragment of HSV gD gene was cloned and used as positive control and to determine the specificity and sensitivity of the assay. The PCR assay is user-friendly and unambiguously differentiates in one-step both herpes virus strains. The assay is useful to screen CFS specimens from infants exposed to HSV during birth and at risk of developing encephalitis.
Mol Cell Probes 1999 Aug
PMID:A duplex PCR assay for detection and genotyping of Herpes simplex virus in cerebrospinal fluid. 1044 Dec 4

Oncolytic viral therapy is a promising new method of cancer treatment. Peritoneal dissemination of cancer is a common and fatal clinical condition seen in many malignancies, with few effective therapies available. G207, a multimutated replication-competent herpes simplex virus type-1, effectively treats disseminated peritoneal cancer. This study evaluates viral proliferation and subsequent tumoricidal effects in vitro and in vivo after regional viral delivery. In vitro studies demonstrate that G207 efficiently kills five human gastric cancer cell lines, and that permissiveness to viral replication is correlated with cytotoxicity. In a murine xenograft model of human gastric carcinomatosis, peritoneal delivery of G207 effectively kills tumor and prolongs survival. Data from quantitative PCR characterizes peritoneal clearance of virus after intraperitoneal injection, and identifies G207 replication within tumor cells in vivo, similar to in vitro proliferation. Further analysis of various organs confirms that G207 does not replicate within normal tissue after peritoneal delivery. Wild-type KOS viral replication was also demonstrated in vivo, with significant toxicity secondary to dissemination and encephalitis. In vivo viral proliferation of G207 is restricted to tumor cells, is correlated with in vitro assays, and is an important mechanism of anticancer efficacy.
J Mol Med (Berl) 2000
PMID:Antitumor efficacy of regional oncolytic viral therapy for peritoneally disseminated cancer. 1086 79

Bacteria were isolated from the nasopharynx of BALB/c mice and electroporated with pUR290(NS1)2 containing two copies of tick-borne encephalitis virus (TBEV) strain Sofjin NS1 under the control of the lac promoter. The plasmid persisted in transformants for at least ten passages. The NS1 gene expression was detected in Gram-negative enterobacteria via immunoblotting with monoclonal antibodies against TBEV nonstructural glycoprotein NS1. Recombinant NS1 was detected in bacterial cells and in the culture medium. Intranasal immunization with recombinant bacteria activated production of antibodies against NS1 in serum of BALB/c mice. The humoral immune response to NS1 failed to protect immunized mice from a TBEV challenge.
Mol Biol (Mosk)
PMID:[Expression of the NS1 gene of tick-borne encephalitis virus in gram-negative bacteria from the mouse nasopharynx]. 1123 76


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