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[effect of thymosin on interferon production and antiviral resistance in mice].the 5th and 6th fractions of thymosin, a hormone of the thymus gland, stimulated interferon production both in vivo (experiments in white and cba mice) and in vitro in cba mouse splenocytes when different interferon inducers were used (phage dsrna, poly(g): poly(c), ndv, and mitogens). the highest stimulating effect in vivo was observed with interferon induction 6-8 hours after thymosin administration. an increase in production of both alpha/beta and gamma interferons under the influence of thym ...19852581368
double-stranded rna-dependent protein kinase and 2-5a system are both activated in interferon-treated, encephalomyocarditis virus-infected hela cells.activation of the interferon-inducible, double-stranded rna-dependent protein kinase was monitored in monolayer cultures of control and interferon-treated hela cells infected with encephalomyocarditis virus. the extent of phosphorylation in the intact cell of the alpha-subunit of eucaryotic protein synthesis initiation factor eif2 by the kinase was determined for the first time in this type of system, using a two-dimensional immunoblot technique. virus protein synthesis and the kinetics of activ ...19852582150
rapid development of renal lesions in diabetic dba mice infected with the d-variant of encephalomyocarditis virus (emc-d).marked hyperglycaemia and renal lesions developed rapidly in dba mice infected with 10 plaque-forming units of the d-variant of encephalomyocarditis virus (emc-d). renal alterations were demonstrated in the glomeruli, tubular epithelium and small vessels 2 months after infection. glomerular changes were characterized by mesangial thickening due to an increase of basement membrane-like material in the mesangial matrix. nodular glomerular lesions were commonly observed 3 months after infection, wh ...19892765387
characteristics of lymphocytes cultured from murine viral myocarditis specimens: a preliminary and technical report.long-term culture of lymphocytes from myocardial biopsy specimens has been reported. to test the usefulness of this technique in experimental models of murine myocarditis, the culture and characterization of lymphocytes from mice infected with encephalomyocarditis virus or coxsackievirus b3 were studied. lymphocytes were successfully cultured from three hearts of encephalomyocarditis virus-infected mice in interleukin 2-containing culture. after approximately 10 days, lymphocytes migrated out of ...19892768726
enhanced in vivo therapeutic response to interferon in mice with an in vitro interferon-resistant b-cell lymphoma.a stable subline of 38c13 b-cell lymphoma (sir-1) resistant to the antiproliferative effects of alpha-interferon (ifn) was isolated. in addition to defects in antiproliferative effects of ifn, sir-1 is defective in ifn-mediated antiviral activity against both encephalomyocarditis virus and vesicularstomatitis virus. it is also defective in the induction of 2'-5'-oligoadenylate synthetase mrna and enzyme activity, enhancement of h-2 antigen expression, and transient induction and subsequent repre ...19892787203
prodromal immune manifestations in emc-m virus induced diabetes: islet bound and circulating antibodies, and changes in lymphocyte subsets.the thymus-dependence of the encephalomyocarditis (emc-m) virus induced diabetes has been demonstrated in comparative studies of normal and immunodeficient mice. since the lymphocytic infiltration in the islets of langerhans is modest during the virus infection, we have looked for possible indications of humoral immune mechanisms. using fluorescence microscopy the presence of immunoglobulins in the islets could be shown 3 days after emc-m-virus inoculation, gradually disappearing about day 14. t ...19872820645
pathogenesis and preventive and therapeutic trials in an animal model of dilated cardiomyopathy induced by a virus.an animal model of dilated cardiomyopathy following encephalomyocarditis (emc) virus has been developed. virus was isolated from mouse hearts and viral antigens were detected in the myocardium until the second week of infection, but neither was found thereafter. differences were found among different strains of mice in the frequency of occurrence and severity of myocarditis, and even in the character of the pathologic lesions. thus, genetic factors may play an important role in the pathogenesis. ...19872822976
possible mechanisms in the pathogenesis of virus-induced diabetes mellitus.insulin-dependent diabetes mellitus results from destruction of pancreatic beta cells. viruses and autoimmunity have been implicated as possible causes of beta cell destruction in genetically predisposed individuals. the evidence for viruses comes largely from experiments in animals, but several studies in humans point to viruses as triggers in the pathogenesis of diabetes in some cases. in animal models, at least 4 different possible mechanisms for virus-induced diabetes have been proposed. the ...19872824113
impaired cytokine response in male icr swiss mice after infection with d variant of encephalomyocarditis virus.the basis for the resistance of the female and the susceptibility of the male icr swiss mouse to the diabetogenicity of the d variant of encephalomyocarditis virus (emcv-d) is unknown. this pattern of disease resistance and susceptibility can be reversed if females are treated with testosterone and males are treated with estrogen before virus infection. as a possible explanation for this sex difference in disease development, differences in early antiviral host responses were explored. cellular ...19872824259
factors affecting the infection of the d variant of encephalomyocarditis virus in the b cells of c57bl/6j mice.the d variant of encephalomyocarditis virus is capable of infecting most inbred strains of mice. however, only certain strains are susceptible to the diabetogenic effect of this virus. in order to understand why some inbred strains do not become diabetic, the pathogenesis of infection was studied in diabetes-resistant c57bl/6j mice. it was the purpose of the investigation to ascertain whether specific host defense factors might play a crucial role in the mechanism of resistance. to determine whe ...19872824265
site-specific mutations at a picornavirus vp3/vp1 cleavage site disrupt in vitro processing and assembly of capsid precursors.most proteolytic cleavages within the picornavirus polyproteins are carried out by viral protease 3c. for encephalomyocarditis virus, the protease 3c-catalyzed processing occurs between gln-gly or gln-ser amino acid pairs which are flanked by proline residues, but the sequence-specific constraints on recognition and cleavage by the enzyme are not completely understood. to examine alternative cleavage site sequences, we constructed a cdna plasmid which expresses the viral l-p1-2a capsid precursor ...19872824807
encephalomyocarditis virus-induced diabetes mellitus in mice: model of viral pathogenesis.encephalomyocarditis (emc) virus induction of diabetes mellitus in mice has proven to be an excellent experimental model for the pathogenesis of viral disease. in sjl and dba/2 mice, diabetes results exclusively from the infection and damage of beta cells by the virus. in addition, in balb/cby mice subclinical beta cell damage caused by the virus is followed by autoimmune beta cell destruction, which results in hyperglycemia. studies of two closely related plaque variants (emc-d and emc-b) selec ...19872825321
on the interrelationship between virus concentration and pathological changes of pancreas in mice induced by emc-virus. 19872826531
an apparent deletion of an oligonucleotide detected by rna fingerprint in the nondiabetogenic b variant of encephalomyocarditis virus is caused by a point mutation.the diabetogenic d variant of encephalomyocarditis virus (emc-d) was previously shown to be different from the nondiabetogenic b variant of encephalomyocarditis virus (emc-b) by a single spot in an oligonucleotide fingerprint after rnase t1 digestion of their genomic rnas. an oligoribonucleotide was missing from emc-b but was present in emc-d. the oligoribonucleotide specific to emc-d was isolated from a two-dimensional polyacrylamide gel and sequenced as 5'-acaaucucacuuuuccaacaacag-3'. molecula ...19882826821
selective inhibition of proteins synthesized from different mrna species in reticulocyte lysates containing l-pyrroline-5-carboxylic acid.l-pyrroline-5-carboxylic acid is a naturally occurring nonprotein amino acid present in human plasma that changes concentrations with diet. l-pyrroline-5-carboxylic acid inhibited net synthesis of globin in untreated reticulocyte lysates in a dose dependent manner. this inhibition was greater than that observed with equimolar gssg or nadp+ and was prevented by a nadph generating system. l-pyrroline-5-carboxylic acid also inhibited net synthesis of proteins from brome mosaic and alfalfa mosaic vi ...19882827672
inactivation of 12 viruses by heating steps applied during manufacture of a hepatitis b vaccine.the efficacy of two heating cycles (90 sec at 103 degrees c and 10 hr at 65 degrees c) used during manufacture of a plasma-derived hepatitis-b vaccine was validated for the inactivation of 12 virus families. a period of 15 min warming up to 65 degrees c had already completely inactivated representatives of nine virus families, ie, poxvirus (vaccinia), picornavirus (encephalomyocarditis virus), togavirus (sindbis virus), coronavirus (mouse hepatitis virus), orthomyxovirus (influenza virus), rhabd ...19872828525
prophylaxis and therapy of virulent encephalomyocarditis virus infection in mice by monoclonal antibodies. brief report.two encephalomyocarditis virus (emcv) neutralizing monoclonal antibodies (mas), recognizing different determinants on emcv, were both able to protect mice prophylactically and therapeutically against a lethal dose of emcv.19882829795
sequence homology between encephalomyocarditis virus protein vpi and histidyl-trna synthetase supports a hypothesis of molecular mimicry in polymyositis.the amino acid sequence of histidyl-trna synthetase, the jo-i antigen of polymyositis, has been compared with that of the polyprotein of encephalomyocarditis virus (emcv), an agent shown recently to produce polymyositis symptoms in mice. it is shown that there is significant sequence homology between a region of the synthetase formerly identified by us as a possible epitope and a region on the coat protein vpi of emcv. the viral protein also shows significant sequence homology with several muscl ...19882830474
asbestos-mediated transfection of mammalian cell cultures.the capacity of asbestos to mediate transfection was tested in a rapid and relatively simple system: picornavirus rnas and mammalian cells in vitro. thirteen asbestos samples, including amosite, anthophyllite, chrysotile, and crocidolite, 4 picornaviruses (poliovirus 1 and 2, echovirus 7, and encephalomyocarditis virus), and 4 cell lines (cli, chimpanzee liver; kb, human carcinoma; eta, monkey kidney; nih 3t3, mouse embryo) were tested. the results showed that all asbestos samples mediated trans ...19882832359
virus vaccine and passive immunization for the prevention of viral myocarditis in mice.the effect of an inactivated virus vaccine and passive immunization was studied in an animal model of viral myocarditis. encephalomyocarditis (emc) virus was inactivated by 1:4000 formalin. four-week-old cd-1 mice were injected subcutaneously and after 7 days intravenously with 0.1 ml vaccine. seven days after the second vaccine, live emc virus was inoculated intraperitoneally. none of ten mice with vaccine treatment died or showed myocardial lesions after challenge with emc virus, whereas all t ...19872832629
amino acid differences in capsid protein, vp1, between diabetogenic and nondiabetogenic variants of encephalomyocarditis virus.the genes for the major capsid protein, vp1(1d), of both diabetogenic d variant (emc-d) and nondiabetogenic b variant (emc-b) of encephalomyocarditis virus were cloned by using two synthetic primers which are common to both emc-d and emc-b. the cloned genes were mapped for major restriction enzyme sites including acci, bamhi, ecori, hincii, kpni, pvuii, ssti, taqi, and xbai. among those nine restriction enzyme sites, only the taqi site distinguished emc-d genome from the counterpart of emc-b gen ...19882833013
[4,5-s-rnai in virus-specific polyribosomes from ascitic krebs 2 carcinoma cells infected with encephalomyocarditis virus].polyribosomes of krebs 2 ascite carcinoma cells non-infected and infected with encephalomyocarditis (emc) virus contain a heterogeneous population of low molecular weight small rnas. analysis of the rnas by polyacrylamide gel electrophoresis did not reveal any qualitative differences in the small rna sets within the composition of polyribosomes from virus-infected and non-infected cells. however, the content of one of the small rnas was markedly elevated in polyribosomes from virus-infected cell ...19872833938
[an inhibitor of translation in cellular mrna containing the 100s structure from krebs ii ascites carcinoma cells infected with encephalomyocarditis virus].as shown previously, the bulk of cellular mrna in krebs ii ascite carcinoma cells infected with encephalomyocarditis virus during active virus-specific synthesis is bound to ribosomes within the 100s structure which is inactive in protein synthesis. in order to elucidate the reasons for the translation repression of cellular mrna within the 100s structure, a fraction of loosely bound proteins which are liberated by treatment of the 100s structure with 0.5 m kcl an which contain sum translation f ...19882833939
identification of antigenic differences between the diabetogenic and non-diabetogenic variants of encephalomyocarditis virus using monoclonal antibodies.the m variant of encephalomyocarditis (emc) virus consists of two biologically distinct variants: one, diabetogenic d variant (emc-d) and the other, non-diabetogenic b variant (emc-b). these two variants cannot be distinguished by hyperimmune sera. monoclonal antibodies were generated against emc-d or emc-b to identify antigenic differences between these two variants. fourteen independent hybrid cell lines, selected from seven separate fusions of mouse myeloma cells to spleen cells isolated from ...19882836552
synthesis, antiviral activity, and conformational characterization of mouse-human alpha-interferon hybrids.reciprocal hybrids were constructed between human and mouse interferons (ifns), and their antiviral activity was examined on different target cells and compared to the activity of the parental molecules. in addition, we used a number of predictive algorithms on a data base of the available alpha-interferon sequences to propose a working model for the overall conformation of the alpha-interferon molecule that is consistent with the structural predictions. remarkable conservation within the predic ...19882837469
quinazolyl benzophenothiazines as potential antiviral agents.the reaction of anthranilic acid with excess of benzoylchloride in the presence of pyridine yielded 2-phenyl(3h) 4-oxo-3,1-benzoxazine(i). interaction of (i) with 2-aminoethanol afforded 2-phenyl-3-hydroxy-ethyl(3h) 4-oxo-quinazoline (ii). the condensation of (ii) with beta-naphthol in the presence of conc. h2so4 gave 1-(2'-phenyl-3'-ethyl-4'-oxo-quinazolyl) beta-naphthol (iii). the reaction of (iii) with primary aromatic amines in the presence of anhydrous zinc-chloride afforded 1-(2'-phenyl-3' ...19882837789
detection of antibody to encephalomyocarditis virus in mummified or stillborn pigs.fetal sera or thoracic fluids of the abnormal fetuses from different swine farms were tested for the presence of antibody to encephalomyocarditis (emc) virus. sera of swine fetuses infected experimentally with emc virus were also tested. high antibody titers ranging 1:128-4096 were detected in both field and experimental samples. detection of the positive antibody was associated with clinical herd history of increased mummification, stillbirth and neonatal death. the results suggest that emc vir ...19882839129
histopathology of balb/c mice infected with the d variant of encephalomyocarditis virus.balb/c mice infected with 10(5) pfu of the d variant of encephalomyocarditis virus were examined histopathologically during the subacute stage of infection. main pathologic changes were observed in the brain, heart (massive myocardial necrosis with subsequent organization (i.e., replacement of necrotic myocardium by connective tissue) and congestion and dilatation of the right ventricle) and pancreas (moderate degranulation of beta-cells resulting in elevation of blood glucose level). the brain ...19882839220
a segment of the 5' nontranslated region of encephalomyocarditis virus rna directs internal entry of ribosomes during in vitro translation.picornavirus rnas are uncapped messengers and have unusually long 5' nontranslated regions (5'ntrs) which contain many noninitiating aug triplets. the translational efficiency of different picornavirus rnas varies between different cell-free extracts and even in the same extract, such as micrococcal nuclease-treated rabbit reticulocyte lysates. the effect of the poliovirus 5'ntr on in vitro translation was compared with that of the 5'ntr of encephalomyocarditis virus by the use of synthetic mrna ...19882839690
studies on the role of the 2'-5'-oligoadenylate synthetase-rnase l pathway in beta interferon-mediated inhibition of encephalomyocarditis virus replication.interferons inhibit the replication of vesicular stomatitis virus (vsv), but not of encephalomyocarditis virus (emcv), in mouse jlsv-11 cells. we report the isolation of clonal derivatives from this cell line in which the replication of both viruses is impaired by interferons. these clones were selected from the parental line by virtue of their rescue by interferon treatment from the cytopathic effects of emcv infection. in one such clone, rk8, the replication of vsv and emcv and the production ...19882841470
relationship of p220 cleavage during picornavirus infection to 2a proteinase sequencing.infection of hela cells by poliovirus results in an abrupt inhibition of host cell protein synthesis. it is thought that the mechanism of this inhibition involves proteolytic cleavage of the p220 component of the cap-binding protein complex, thereby causing functional inactivation of the cap-binding protein complex and preventing capped (cellular) mrnas from binding ribosomes. current data suggest that the viral proteinase 2a indirectly induces p220 cleavage via alteration or activation of a sec ...19882845133
comparison of the nucleotide sequences of diabetogenic and nondiabetogenic encephalomyocarditis virus.the nucleotide sequences of a diabetogenic variant of encephalomyocarditis (emc) virus (d variant, ifp- phenotype) and a nondiabetogenic variant of emc virus (b variant, ifp+ phenotype) have been compared. these variants differ at eight sites. the poly(c) tract of emc-b is three bases shorter than that of emc-d. of the seven sites at which nucleotide substitutions were confirmed using rna templates, four resulted in amino acid changes in three different proteins, the leader peptide, 1b (vp2), an ...19882845665
reduced tumorigenicity of rodent tumour cells and tumour explants following infection with wild type and mutant herpes simplex virus, bovine mammillitis virus and encephalomyocarditis virus.the tumorigenicity of neoplastic hamster and mouse cell lines and tumour explants was reduced by infection with herpes simplex virus (hsv-1), a thymidine-kinaseless mutant of herpes simplex virus, namely 'mdk', encephalomyocarditis virus (emc) and bovine mammillitis virus (bmv). there was an approximate relationship between duration of virus infection in vitro and reduction in incidence and/or rate of tumour development. the rate of tumour development was also reduced by 'site inoculation' of vi ...19882846027
the natural history of encephalomyocarditis virus-induced myositis and myocarditis in mice. viral persistence demonstrated by in situ hybridization.picornaviruses can initiate chronic inflammation that persists after the virus can no longer be cultured from inflamed tissues. in an attempt to understand this transition we have sought evidence for viral persistence by methods that detect viral genome independent of whether or not whole competent virus is present. in mice infected with a myotropic variant of encephalomyocarditis virus, emc-221a, virus can be cultured in high yield at 1 wk and in low yield at 2 wk from skeletal muscle, heart, a ...19882846742
mode of action of a new type of udp-glucose analog against herpesvirus replication.the mode of action of a new type of udp-glucose analog against herpes simplex virus type 1 (hsv-1) replication was examined. the analog showed good selectivity and potent activity. at 10 micrograms/ml, p-536 inhibited the formation of infectious hsv-1 by more than 90%, whereas at 100 micrograms/ml it had no cytotoxic effects, as evidenced by phase-contrast microscopy. p-536 showed a wide spectrum of action and was active against hsv-1, adenovirus type 5, vaccinia virus, poliovirus type 1, enceph ...19882847650
[an enzyme hydrolyzing the covalent bond between rna and vpg of picornaviruses. substrates and methods of analysis of activity].some new substrates--rna-vpg, rna-peptide and a small fragment of rna peptide--labelled at the peptide component with [125i]bolton-hunter reagent have been proposed for use in the isolation and characterization of the enzyme hydrolyzing the phosphodiester bond between the vpg protein and encephalomyocarditis virus rna. a novel procedure for the analysis of the specific enzyme activity is based on thin-layer chromatography of hydrolytic products on silicagel or polyethylenimine cellulose. the mol ...19882847820
effects of cyclosporine on encephalomyocarditis virus infection in mice. 19882848238
[experimental viral-bacterial infections. ii. development and course of mixed emc virus and staphylococcus aureus infection in mice]. 19882850413
encephalomyocarditis virus infection in pigs. 19882850788
application of immunoassay of encephalomyocarditis virus in cell culture with enzyme-labeled virus-specific monoclonal antibodies for rapid detection of virus, neutralizing antibodies, and interferon.encephalomyocarditis virus (emcv)-specific monoclonal antibody um 21.1 labeled with horseradish peroxidase was used to detect emcv in l-cell monolayers. this direct enzyme immunoassay of emcv, performed in wells of 96-well plates, could be applied for various purposes, such as early detection of virus multiplication, determination of 50% tissue culture infective doses, and rapid titration of interferon and emcv-neutralizing antibodies. multiplication of emcv is indicated by a rapid increase of t ...19882852674
[viral infections in medicine. 4. viral myocarditis and cardiomyopathy]. 19882854544
structure/function studies on recombinant human gamma interferon.structure/function relationships for human gamma interferon (ifn-gamma) were investigated using recombinant dna-derived homologues produced in e. coli. the various biological effects examined were antiviral, growth inhibitory and 2-5a synthetase activities, as well as receptor binding characteristics. specific structural changes led to ifn-gamma homologues with defined alterations in biological activities. amino acid residue changes at the hydrophobic core of the molecule resulted in two homolog ...19882855574
derivatives of benzo(c)fluorene. vi. antiviral and interferon-inducing activities of three benzo(c)fluorenone derivatives in mice.the antiviral effect of 3 derivatives of benzo(c)fluorenone against encephalomyocarditis (emc) and vaccinia viruses in mice was compared with that of tilorone hydrochloride (thcl). all 3 derivatives were effective against either virus following single-dose oral application as well as after 4-times repeated subcutaneous (s.c.) treatment, but following oral administration only the vufb 14162 derivative exerted an antiviral effect corresponding to that of thcl. after s.c. application, however, vufb ...19852859757
glucocorticoid-mediated establishment of an antiviral state coincident with other glucocorticoid-induced biochemical activities in l929 cells.incubation of l929 cells with three different glucocorticoids, hydrocortisone, dexamethasone and triamcinolone acetonide, rendered the cells unable to support plaque formation by several unrelated dna and rna viruses. the establishment of this antiviral state by dexamethasone coincided with an inhibition of cell growth and induction of glutamine synthetase activity. these steroid-mediated activities occurred only in cultures of l929 cells and not in cultures of rabbit skin or rat glioma cells.19852864388
induction of beta 2-interferon by tumor necrosis factor: a homeostatic mechanism in the control of cell proliferation.earlier studies showed that tumor necrosis factor (tnf) exerts a mitogenic effect in human diploid fibroblasts. here we demonstrate that purified e. coli-derived recombinant human tnf inhibits encephalomyocarditis virus replication in "aged" human fibroblasts. addition of neutralizing antibodies to human beta interferon (ifn-beta) blocked the antiviral action of tnf, indicating that this action is mediated by the generation of ifn-beta. we also show that antiserum to ifn-beta enhanced the mitoge ...19862871942
immunomodulation by bordetella pertussis: antiviral effects.treatment of mice by intraperitoneal inoculation of pertussis vaccine or lipopolysaccharide extracted from b. pertussis will effect resistance to rabies virus, encephalomyocarditis virus, semliki forest virus, and herpes simplex virus. our previous observations indicated that treatment of c3h/hen (+/nu) and bdf1 mice with pertussis vaccine injected i.p. five days prior to a mouse adenovirus lethal dose i.p. challenge elicited resistance to clinical disease and death. susceptibility returned to a ...19852872109
immunologic identification of lymphocyte subsets in experimental murine myocarditis with encephalomyocarditis virus. different kinetics of lymphocyte subsets between the heart and the peripheral blood, and significance of thy 1.2+ (pan t) and lyt 1+, 23+ (immature t) subsets in the development of myocarditis.to clarify the immune mechanism in myocarditis, immunofluorescence techniques with laser flow cytometry were used to examine serial changes in lymphocyte subsets in the heart, spleen, and peripheral blood of dba/2 and balb/c mice inoculated with encephalomyocarditis virus (experiment i). b cells were identified by staining with fluorescein isothiocyanate-labelled rabbit anti-mouse immunoglobulin. t-cell subsets were identified with rat anti-thy 1.2, and nonpolymorphic lyt 1 and lyt 2 monoclonal ...19872889539
tuftsin a natural peptide with antiviral activity--structural basis of its action.the influence of tuftsin--the natural phagocytosis stimulating tetrapeptide and its elongated analogues--on the mortality of encephalomyocarditis virus-infected nmri mice was investigated. it seems that amino acids elongation in the parent peptide chain does not result in significant increase of antiviral activity of the compounds tested.19882897777
the mouse immune interferon receptor gene is located on chromosome 10.when mouse l cells are incubated with 32p-labeled recombinant murine immune interferon ( [32p]mu-ifn-gamma) and subsequently cross-linked with disuccinimidyl suberate, a major complex with an apparent molecular mass of 95,000-125,000 daltons can be visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. the complex was not formed when the binding was performed in the presence of excess unlabeled mu-ifn-gamma or when chinese hamster ovary cells were used. this complex therefore r ...19872952646
the effect of serum deprivation on the initiation of protein synthesis in mouse neuroblastoma cells.growth of mouse neuroblastoma cells becomes stationary when cultured in serum-free medium. within 60 h, the protein-synthesizing capacity of the cells declines to 25% as compared to that of exponentially growing cells. the transitional activity of the crude ribosomal salt washes from serum-deprived and control cells was compared in in vitro protein-synthesizing ph 5 systems. it appears that the ribosomal salt wash from serum-deprived cells has significantly (70%) lost its ability to support the ...19852981551
respective role of each of the purine n-6 amino groups of 5'-o-triphosphoryladenylyl(2'----5')adenylyl(2----5')adenosine in binding to and activation of rnase l.we have synthesized a series of 2-5a (ppp5'-a2'p5'a2'p5'a) analogs in which each adenosine residue has been sequentially replaced by inosine: viz., ppp5'i2'p5'a2'p5'a, ppp5'a2'p5'i2'p5'a, and ppp5'a2'p5'a2'p5'i. these transformations enabled us to delineate the role of each of the three purine n-6 amino groups of 2-5a in determining oligonucleotide binding to and activation of the 2-5a-dependent endoribonuclease, rnase l. with the rnase l activity of both mouse l cells and human daudi lymphoblas ...19852981855
the reversion of temperature-sensitive mutants of encephalomyocarditis virus upon serial passage in three continuous cell lines.several temperature-sensitive mutants of encephalomyocarditis virus were serially passed numerous times in hela, l929 and bhk-21 cells. the reversion of most of the mutants occurred most rapidly in bhk-21 cells and least rapidly in hela cells.19852981972
treatment of viral myocarditis with ribavirin in an animal preparation.the therapeutic effects of ribavirin, a broad-spectrum, antiviral agent, on experimental myocarditis caused by encephalomyocarditis (emc) virus were investigated. four-week-old dba/2 mice were inoculated with 10 plaque-forming units (pfu) of emc virus. ribavirin in a dose of 100 (group 1, n = 20), 200 (group 2, n = 10), or 400 mg/kg/day (group 3, n = 10) was administered subcutaneously on days 0 to 12 after virus inoculation, and animals were observed for 12 days. control animals were injected w ...19852982522
clinical findings in acute viral myocarditis. with special attention to experimental and immunological evidence.according to analysis of 40,000 autopsies, the incidence of myocarditis is approximately 3.5%, the diagnosis of which had not been established in the majority prior to death. the clinical characteristics of myocarditis encompass a wide spectrum from an asymptomatic course to sudden cardiac death. symptoms and findings of congestive heart failure or an inflammatory virus disease may be present. there is usually evidence of nonspecific clinical, radiologic, electrocardiographic, echocardiographic ...19852984098
encephalomyocarditis virus and diabetes mellitus: studies on virus mutants in susceptible and non-susceptible mice.the so-called m-variant (especially subtype d) of encephalomyocarditis virus (emcv) induces a diabetes-like syndrome in certain mouse strains which may serve as a model of insulin-dependent diabetes mellitus (iddm) in man. the development and course of diabetes was influenced by a number of virus and host factors, among these being virus strain, virus dose, mouse strain, age, sex, and the host's immunological status. in a d-variant stock of emcv, we found a virus plaque variant (pv 2) diabetogen ...19852984315
sequence analysis of hepatitis a virus cdna coding for capsid proteins and rna polymerase.we report here the nucleotide sequence corresponding to two large regions of the hepatitis a virus (hav) genome. these comprise a sequence of 3274 bases corresponding to the 5' end of the genome, which includes the putative capsid protein region of this picornavirus, and 1590 bases corresponding to the 3' end of the genome, terminating in a 15-base poly(a) tract. these sequences revealed that hav had the characteristic genomic organization of picornaviruses: an open reading frame beginning appro ...19852984684
biochemical changes induced by coxsackie b4 virus in short-term culture of mouse pancreatic islets.isolated mouse pancreatic islets were infected in vitro with two strains of coxsackie b4 virus--a tissue culture-adapted strain and a mouse pancreas-adapted strain. within 48 h of infection changes had occurred in the biochemical activities of islets infected with the mouse pancreas-adapted strain of virus. basal insulin release was increased two-fold in these islets, while glucose-induced insulin secretion remained unchanged. insulin biosynthesis was greatly reduced at a stimulatory concentrati ...19852985140
shutoff of host translation by encephalomyocarditis virus infection does not involve cleavage of the eucaryotic initiation factor 4f polypeptide that accompanies poliovirus infection.studies were conducted to determine whether encephalomyocarditis virus infection causes proteolytic cleavage of any of the polypeptides which comprise eucaryotic initiation factor 4f. since no such alterations in the components of the initiation factor were detected, these observations confirmed that the mechanisms whereby encephalomyocarditis virus and poliovirus shut off host translation are different.19852985829
[natural interferon inducers: double-stranded rna of killer plasmids of saccharomyces cerevisiae].methods for isolation and purification of yeast double spiral rna (dsrna) are described. the most simple method includes reprecipitation of dsrna in solutions of lithium chloride and its interphase distribution in the system of chloroform: isoamilic alcohol: water. preparations with the content (w/w) of dsrna from 30 to 90 per cent were obtained. they possess a high interferon-inducing activity and an antiviral effect on the experimental infection caused by the virus of mouse encephalomyocarditi ...19852986543
immunologic behavior of lymphocytes in experimental viral myocarditis: significance of t lymphocytes in the severity of myocarditis and silent myocarditis in balb/c-nu/nu mice.to clarify the immune mechanism in myocarditis, we examined by immunofluorescence techniques the serial changes in percentages of t and b lymphocytes in the heart, spleen, and peripheral blood of dba/2 mice inoculated with encephalomyocarditis (emc) virus (experiment i). b cells were demonstrated by staining with fluorescein isothiocyanate (fitc)-labeled rabbit antimouse immunoglobulin (ig). t cells were demonstrated with rat anti-thy1.2 monoclonal antibody plus fitc-labeled antimouse ig. there ...19852986878
is insulin-dependent diabetes mellitus caused by coxsackievirus b infection? a review of the epidemiologic evidence.the evidence that coxsackievirus b plays a causal role in the etiology of insulin-dependent diabetes mellitus (iddm) is reviewed. this hypothesis is biologically plausible; one variant of another picornavirus, encephalomyocarditis virus, causes diabetes in genetically susceptible mice, but prior infection with another, serologically indistinguishable variant prevents this. the seasonal distributions of infection due to coxsackievirus b and of iddm are similar. case reports document coxsackieviru ...19852988099
a practical cytopathic effect/dye-uptake interferon assay for routine use in the clinical laboratory.the clinical value of interferon (ifn) level determinations has been demonstrated, but a practical assay procedure for routine use in the diagnostic laboratory has not been available. the authors examined the susceptibility of five cell lines (wish, hep-2, vero, a549, and wi-26va4) to vesicular stomatitis virus (vsv) and encephalomyocarditis virus (emcv), and compared the response of these cells to the inhibitory activity of ifn-alpha and ifn-gamma for the respective viral cytopathic effect (cpe ...19852988328
alterations in immunological reactivity in encephalomyocarditis virus-induced murine diabetes. i. defective primary igm plaque forming cell responses to sheep erythrocytes: correction by islet cell transplantation.increasing data suggest a possible viral aetiology of juvenile onset, insulin-dependent diabetes mellitus. the m variant of the encephalomyocarditis (emc) virus infects murine pancreatic beta cells and causes a diabetes like syndrome in susceptible strains of mice. abnormalities in immunological function have been documented in patients with diabetes mellitus and in spontaneous, streptozotocin-induced and alloxan-induced diabetes in animals. the present study documents a significant impairment o ...19852988831
in vivo antiviral activity of recombinant murine gamma interferon.recombinant murine gamma interferon (gamma-ifn) was tested for its antiviral activity in vivo. ifn preparations purified to greater than 95% purity were administered to cd-1 mice infected with lethal doses of encephalomyocarditis (emc) virus. an initial treatment with rmuifn-gamma administered 4 h prior to infection with virus, followed by daily treatment for 3 consecutive days significantly protected mice against emc virus as evidenced by animal survival after 3-4 weeks post-viral infection. va ...19852989389
establishment of cell lines persistently infected with foot-and-mouth disease virus.cell lines persistently infected with foot-and-mouth disease virus (fmdv) have been established by growth of bhk-21 (c-13) or ibrs-2 (c-26) that survived standard cytolytic infections with fmdv. they maintain cytoplasmic fmdv rna sequences, as shown by dot blot hybridization tests, using cloned fmdv cdna as probes. cell line c1-bhk-rc1 was derived by infection of cloned bhk-21 c1 cells and plaque-purified fmdv c-s8 c1. indirect immunofluorescence assays indicated the presence of fmdv antigens. i ...19852990100
[preparation of 1-substituted 4-dialkylaminoalkylamino-3-methyl-1h -pyrazole(3,4-b)quinolines with an antiviral effect]. 19852990741
cell cycle position and expression of encephalomyocarditis virus in mouse embryo fibroblasts.infection of mouse embryo fibroblasts in g1 or s phase with encephalomyocarditis virus gave different kinetics of viral rna synthesis. in s phase cells, rna synthesis was faster and reached higher levels than in g1 cells. virus-specified proteins were fewer in g1 cells than in s cells during the early stage of the infection and c.p.e. in g1 cells appeared about 4 h later than in s cells. addition of a cellular factor with ability to affect cell conformation had an inhibitory effect on viral rna ...19852991426
immunology of viral diabetes. 19852992061
[preparation of 4-phenoxy and 4-phenylthio derivatives of 1h-pyrazolo[3,4-b]-quinoline with an antiviral effect]. 19852992819
virus-induced diabetes mellitus. no evidence for immune mechanisms in the destruction of beta-cells by the d-variant of encephalomyocarditis virus.a possible contribution of the immune system to the pathogenesis of virus-induced diabetes mellitus was investigated using the d-variant of encephalomyocarditis (emc-d) virus. studies on the f1 and backcross progeny of susceptible and resistant strains of mice gave no suggestion of a linkage between susceptibility and the major histocompatibility locus. immuno-suppression by antilymphocyte serum did not prevent the induction of emc-d-induced diabetes. athymic nude mice infected with emc-d virus ...19852993085
analysis of the secondary structure of the poly(c) tract in foot-and-mouth disease virus rnas.sodium bisulphite modification of foot-and-mouth disease virus (fmdv) rna in solution indicates that the majority of the poly(c) tract in the rna is single-stranded in concordance with previous results with encephalomyocarditis virus rna. the reaction kinetics are biphasic; 60% of the cytidylic acid in the poly(c) tract reacts like synthetic poly(c), and the remainder with the kinetics of the cytidylic acid in the rest of the rna. the reactivity of the poly(c) tract with poly(i) indicates that i ...19852993483
natural antiviral activity of mouse macrophages against encephalomyocarditis virus.resident mouse peritoneal cells (pc) express a significant antiviral activity against encephalomyocarditis virus (emcv) in vitro, as judged by decreased virus yield from infected mouse embryo fibroblasts (mef). this natural antiviral activity of pc was not due either to enhanced lysis of virus-infected cells, as these were protected from lysis rather than destructed by pc, or to interferon (ifn) production, as no direct correlation between ifn and anti-emcv activity was found. among pc, macropha ...19852994562
genetic control of multisystem autoimmune disease in encephalomyocarditis virus infected balb/ccum and balb/cbyj mice. 19852994955
genetic influences on the immunologic pathogenesis of encephalomyocarditis (emc) virus-induced diabetes mellitus.dba/2 and balb/cby mice were infected with approximately 30 plaque-forming units of the m-variant of encephalomyocarditis (emc-m) virus. seven days after inoculation the majority of the animals of both strains were hyperglycemic. a significant correlation between increased concentrations of virus in the pancreas and hyperglycemia was found among individual dba/2 animals, but not among balb/cby mice. t-lymphocyte depletion of dba/2 mice before infection failed to alter the incidence or severity o ...19852995182
the regulation of translation in reovirus-infected cells.the regulation of translation in reovirus-infected cells has been investigated by double-infection experiments. different cell lines were able to translate uncapped encephalomyocarditis (emc) virus mrna and capped vesicular stomatitis virus (vsv) mrnas both early and late during reovirus infection. these results are not fully in agreement with a previously suggested model in which, in the early phase of reovirus infection, only capped mrnas are translated, whereas in the late phase the cells are ...19852995553
interferon sensitivity of fibroblast cell cultures derived from patients with neoplasms of the head and neck.interferon (ifn) is a protein with antiviral activity that has been shown to inhibit the growth of many different types of cells. we have measured the ifn sensitivity of nine cell cultures isolated from patients with squamous cell carcinoma and one with malignant melanoma of the head and neck. normal-appearing fibroblast cultures isolated from these tissues appear quite sensitive to the antiviral effects of ifn. when the encephalomyocarditis virus yield reduction assay is used, these diploid cel ...19852995901
perspectives on the role of viruses in insulin-dependent diabetes.insulin-dependent diabetes mellitus (iddm) results from the destruction of pancreatic beta cells. viruses have been suggested as one of the possible causes. the evidence for viruses comes largely from experiments in animals, but several studies in humans also point to viruses as a trigger of this disease in some cases. encephalomyocarditis (emc) virus, mengovirus (2t), and coxsackie b4 virus infect and destroy pancreatic beta cells when inoculated into mice. this results in hypoinsulinemia and h ...19852996865
interferon production and sensitivity of rabbit corneal epithelial and stromal cells.the induction of interferon and the ability of interferon to induce the antiviral state were studied using rabbit corneal epithelial and stromal cells which were cultured for fewer than five passages. interferon titers in the range of 7000 units/ml were induced in epithelial cell cultures and 76,000 units/ml in stromal cell cultures treated with uv-inactivated bluetongue virus. the interferon induced was stable to ph 2.0 treatment and heating to 56 degrees c for 16 hr. infection of epithelial an ...19852997072
huifn-gamma antiviral activity correlates with immunological reactivity in a double-monoclonal antibody radiometric assay.several lines of evidence have been obtained that correlate biological activity with reactivity in an immunoradiometric assay (irma) employing two different monoclonal antibodies. antiviral activity and immunological reactivity decreased in parallel when freeze-dried human gamma-interferon (huifn-gamma) was heated for prolonged periods of time at elevated temperatures. likewise, aqueous preparations of huifn-gamma inactivated by acid ph or heat responded similarly in the biological assay and irm ...19852997336
a comparative study on the translation of cardiovirus rnas in rabbit reticulocyte lysates.in rabbit reticulocyte lysates the rnas of encephalomyocarditis (emc) virus, mengovirus, and mous-elberfeld (me) virus directed the synthesis of similar sets of products. moreover, the viral protease synthesized from any one of the three viral rnas could cause cleavage of the viral capsid precursor proteins synthesized from any of the three rnas. however, the three rnas differed in their dependence on trna supplementation (to the lysates) for effective translation. in the absence of trna supplem ...19852998057
diabetogenic potential of coxsackie b viruses in nature.thirty-seven clinical isolates of coxsackievirus (cv) serotypes b-1, b-3, b-4, and b-5 were inoculated into male sjl mice. twelve strains resulted in minor abnormalities of glucose metabolism in one or more of six infected mice (tables 1 and 2). sequential infection of male sjl mice with cvb-3, cvb-4, and cvb-5 resulted in abnormal glucose metabolism in 25 percent of the mice (fig. 1). the glucose index of the abnormal animals was similar to that produced by sequential infection with reovirus an ...19852998300
virus-induced murine diabetes. enhancement by immunosuppression.adult, male icr swiss mice are susceptible to the diabetogenic effects of the d-variant of encephalomyocarditis virus (emc-d) in contrast to adult c3h/hej male mice, which are relatively resistant. to date, experimental evidence suggests that the immune system plays a role in the pathogenesis of this infection. we have investigated the potential involvement of the immune system in the pathogenesis of emc-d-induced diabetes using cyclosporin-a (cya), a potent immunosuppressive drug. the data show ...19852998910
a murine model of insulin-dependent diabetes mellitus resulting from the cumulative effects of the nondiabetogenic strain of encephalomyocarditis virus and a single low dose of streptozocin.the induction of insulin-dependent diabetes in outbred male and female mice was examined using a combination of the usually nondiabetogenic b-variant of encephalomyocarditis (emc-b) virus and single low doses of streptozocin (stz). neither emc-b virus nor low doses of stz were overtly diabetogenic when administered alone; however, when these two insults occurred 1 day apart, diabetes resulted in male but not in female mice. the induction of diabetes was dependent on the time interval between the ...19852998912
[mathematical planning of an experiment for assessing the combined action of new interferon inducers]. 19853000087
[synthesis of virus-specific and cellular proteins in the presence of bonafton].inhibition of the synthesis of virus-specific proteins of influenza a/wsn/33 virus in the cells of chick embryo fibroblasts and in continuous cells of dog embryonal kidney was discovered as was a negligible inhibition of the synthesis of cell proteins in the presence of an original synthetic antivirus drug bonaphthon. experiments were made to attain selective inhibition of individual virus-specific proteins of influenza virus in these cultures. in model experiments in vitro in a cell-free protei ...19853000819
immunoradiometric assay of a recombinant human alpha-2 interferon (sch 30500).a sensitive immunoradiometric assay for recombinant alpha-2 interferon (ifn-alpha 2; sch 30500) was developed by using the monoclonal antibody nk2. a polystyrene bead with polyclonal sheep anti-human ifn-alpha (hu ifn-alpha) antibody adsorbed to it formed the solid phase of the assay. the monoclonal antibody, labeled with 125i, reacted with the ifn-alpha 2 which bound to the polyclonal antibody on the bead. the assay was sensitive, capable of measuring less than 5 iu/ml, and it was precise. coef ...19853001133
[preparation of 4-(hydroxyanilino)- and 4-(alkoxyanilino) derivatives of 1,3-dimethyl-1h-pyrazolo[3,4-b]quinoline with a potential antiviral effect]. 19853002640
mouse peritoneal cells confer an antiviral state on mouse cell monolayers: role of interferon.vesicular stomatitis virus and encephalomyocarditis virus do not multiply in the majority of peritoneal macrophages freshly explanted from 4- to 8-week-old male or female mice. however, when peritoneal macrophages were cultivated in vitro for 3 to 5 days, these cells became permissive for both viruses. the loss of antiviral state in "aged" macrophages paralleled a significant decrease in the intracellular levels of (2'-5')oligo-adenylate synthetase activity. although biologically active interfer ...19863003378
guanidine-selected mutants of poliovirus: mapping of point mutations to polypeptide 2c.sequence analysis of the genomic rna of interstrain guanidine-resistant and antibody-resistant variant recombinants of poliovirus type 1 mapped the resistance of mutants capable of growth in 2.0 mm guanidine hydrochloride to a region located 3' of nucleotide 4444. this region of the viral genome specifies the nonstructural protein 2c. the sequence of genomic rna encoding 2c from six independently isolated mutants resistant to 2.0 mm guanidine was determined. all six isolates contained a mutation ...19863003395
a detailed kinetic analysis of the in vitro synthesis and processing of encephalomyocarditis virus products.translation of encephalomyocarditis virus rna in rabbit reticulocyte lysates has been used to analyse the pathway of proteolytic processing of the primary translation products. a minimum of two distinct proteases is required to account for the results: one for the excision of the capsid precursor protein, a1, from the nascent polyprotein, and the other for all other cleavages including cleavage at the f/c junction. the excision of a1 is an extremely rapid reaction which occurs as soon as the cle ...19863004023
[pathogenesis of virus-induced diabetes (a review of the literature)]. 19853004041
[leukocyte interferon reaction in patients with primary immunodeficiencies].the capacity of leukocytes from children with primary immunodeficiency to produce alpha- and gamma-interferons in vitro was studied. interferon response of leukocytes in most of the patients examined was found to be practically unchanged. the immunostimulating therapy in some cases exerted a regulating effect on leukocyte capacity for interferon production. it is assumed that the interferon-producing function of t lymphocytes may be preserved in patients suffering from primary immunodeficiency.19853006358
effects of prednisolone on acute viral myocarditis in mice.the effect of prednisolone on viral myocarditis was studied in balb/c mice with encephalomyocarditis virus myocarditis. prednisolone was injected intramuscularly, 10 mg/kg once a day, on days 4 to 13 (experiment 1) and on days 8 to 17 (experiment 2). the control mice in each experiment received injections of distilled water. in experiment 1, myocardial virus titers were maximal but neutralizing antibodies were rarely present on day 4, and viral titers were still elevated and antibody titers were ...19863007597
mural thrombi in mice with acute viral myocarditis.in an investigation of the relationship between mural thrombosis and congestive heart failure (chf) in acute viral myocarditis, inbred balb/c mice were inoculated intraperitoneally with the m variant of encephalomyocarditis (emc) virus and sacrificed on days 7 (n = 33), 10 (n = 35) and 14 (n = 39). myocarditis was found in 105 of 107 sacrificed mice (98.1%). myocardial necrosis with cellular infiltration was evident after day 7 and was extensive in the ventricles and atria. in the 105 mice with ...19853007795
[experimental viral-bacterial infections. i. elaboration of the model of mixed infection with emc virus and staphylococcus aureus in mice]. 19853007896
the interaction of recombinant huifn-gamma 1 and recombinant huifn-alpha 2 on the 2-5a system in two distinct cell types. 19853008171
encephalomyocarditis virus infection and pig disease in queensland. 19853008693
[characteristics of an enzyme hydrolyzing the covalent bond between rna and protein vpg of the encephalomyocarditis virus].the enzyme termed by us as uridilylpolynucleotide-(5'p----o)-tyrosine phosphodiesterase (y-pupn pde) was isolated from mouse ascites krebs ii cells by ion-exchange and affinity chromatography. the enzyme was found to specifically split the natural covalent bond between vpg and emc or polio viral rnas. the enzyme is completely inactivated at 55 degrees c and partially by edta. the enzyme preparation isolated by the above-mentioned procedure is not homogeneous and contains inhibiting admixture(s). ...19863008862
effect of inapparent murine hepatitis virus infections on macrophages and host resistance.inapparent infections of mice with murine hepatitis virus (mhv) altered host resistance to experimental infection with a second virus, encephalomyocarditis virus (emc), reduced the protective effects of exogenously administered interferon against emc infections, and it altered macrophage ectoenzyme phenotypes in two macrophage populations. resident peritoneal macrophages from mice experimentally infected with one of two strains of mhv also demonstrated altered ectoenzyme phenotypes. these data d ...19863009672
interferon production in l929 cells under impaired translational conditions: comparison of rates of interferon, actin, newcastle disease and encephalomyocarditis viruses mrnas initiation of protein synthesis.the pattern of interferon (ifn) production in virus-infected cells has been compared with the rate of bulk cellular protein synthesis, on one hand, and with the synthesis of representative cell and virus proteins such as actin, the gamma and the np proteins of encephalomyocarditis (emc) and newcastle disease (ndv) viruses, on the other hand. this was investigated under conditions of impaired protein synthesis such as i) high osmolarity media, ii) a virus-induced shut-off, and iii) in cells expos ...19863010904
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