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influence of ph, salinity, and organic matter on the adsorption of enteric viruses to estuarine sediment.this study was designed to determine the degree of adsorption of enteric viruses to marine sediment and factors controlling this association. adsorption and elution characteristics of several enteroviruses and one rotavirus to estuarine sediments were studied under varying conditions of ph, salinity, and presence of soluble organics. greater than 99% of the added poliovirus type 1 (lsc), coxsackievirus type b3 (nancy), echovirus type 7 (wallace), and rotavirus (sa-11) adsorbed to sediment. echov ...197939508
virus-induced diabetes mellitus: infection of mice with variants of encephalomyocarditis virus, coxsackievirus b4, and reovirus type 3. 1979227239
effect of antiviral lipids, heat, and freezing on the activity of viruses in human milk.semliki forest virus (sfv), herpes simplex virus type 1 (hsv-1), coxsackievirus b4, and cytomegalovirus (cmv) were added to human milk, which was then subjected to treatments that approximated those required for the decontamination or storage of milk. boiling was the only treatment that eliminated these viruses from the milk. pasteurization (at 62.5 c for 30 min) did destroy cmv, but the other viruses could still be detected. all of the viruses except hsv-1 were detectable after the contaminated ...1979227969
a study of infections and illnesses in a day nursery based on inclusion-bearing cells in the urine and infectious agent in faeces, urine and nasal secretion.during an epidemic-free period of nearly 2 years infections and illnesses were followed in a group of small children (2-3 1/2 years) in a day nursery. the incidence of illness was fairly low, 6.3 per child and year. the viral infections were followed by means of the inclusion reaction in the urine and isolation of virus, and the bacterial by culture of nasal secretion. in 60% of the cases the viral infection was accompanied by illness. in 57 cases of illness there were 27 (47%) with merely virus ...1979231298
control of in vitro and in vivo spread of coxsackievirus b4 infection by sensitized spleen cells and antibody. 1978308084
identification of candidate sequences that determine virulence in coxsackievirus b4.we have previously shown that a major determinant of virulence for coxsackievirus b4 mapped to the 5' end of the viral genome. comparison of the corresponding cdna sequences of a virulent and a non-virulent virus has allowed the identification of candidate determinants of virulence in the 5' untranslated region and the capsid proteins vp1, vp2 and vp4. thirteen nucleotide substitutions were observed in a region spanning 3298 nucleotides. four mutations were detected in the non-coding region. of ...19921320798
coxsackievirus b4 infection alters thymic, splenic, and peripheral lymphocyte repertoire preceding onset of hyperglycemia in mice.diabetogenic coxsackievirus b4 infection may trigger autoimmune islet loss in diabetes-susceptible mice, resulting in hyperglycemia in nearly 90% of the animals at 6-8 weeks postinfection (p.i.). to ascertain whether changes in lymphocyte repertoire following infection could predispose these animals to diabetes, alterations in their thymic, splenic, and peripheral lymphocytes were analyzed. additionally, lymphocyte changes were correlated with the virus load in these tissues and with lymphocyte ...19921334127
androstenediol regulates systemic resistance against lethal infections in mice.we previously reported that subcutaneous injection of dhea (5-androsten-3 beta-ol-17-one, dehydroepiandrosterone) protected mice from lethal infection. this included both a lethal herpes virus type 2 encephalitis and a lethal systemic coxsackievirus b4 (cb4) infection. androstenediol (5-androsten-3 beta-17 beta-diol, aed), a metabolic product of dhea is up to 100 x more effective in regulating systemic resistance against lethal infection with cb 4 than its precursor dhea. compared to dhea, treat ...19921456887
coxsackievirus b4-induced development of antibodies to 64,000-mr islet autoantigen and hyperglycemia in mice.diabetogenic coxsackievirus b4 infection produces a diabetes syndrome in susceptible mice resembling insulin-dependent diabetes mellitus. we reported a two- to threefold increased expression of a 64,000-mr (64 k) islet autoantigen in the infected mice preceding the development of hyperglycemia, suggesting a possible role of the virus in autoimmunity. to assess if the virus could be a trigger of autoimmunity, 64 k autoantibody development was correlated with hyperglycemia and virus replication in ...19911660313
immunodeficiency as primary phenotype of diabetes mutation db. studies with coxsackievirus b4.restriction of food intake (r) in the c57bl/ksj db/db diabetic mutant mouse prevents phenotypic expression of diabetes, whereas ad libitum feeding (al) results in spontaneous diabetes. previous results showed that coxsackievirus b4 (cb4)-infected genetically identical db/db mice with and without diabetes could be distinguished by the levels of cb4-neutralizing antibody and virus-specific antibodies as determined by enzyme-linked immunosorbent assay and the numbers of splenic antibody-forming cel ...19902161367
detection of conserved and nonconserved epitopes on coxsackievirus b4: frequency of antigenic change.a sensitive microneutralization assay was used to detect antigenic variants of coxsackievirus b4. analysis of 47 clinical isolates with 16 monoclonal neutralizing antibodies revealed highly conserved, moderately conserved, and poorly conserved epitopes. upon passage of coxsackievirus b4 in tissue culture, certain epitopes disappeared and others appeared in the apparent absence of selective pressure. changes in epitopes often exceeded a frequency of 10(-2). despite considerable variation in indiv ...19852413617
protection against acute lethal viral infections with the native steroid dehydroepiandrosterone (dhea).a significant protective effect of a native adrenal steroid, dehydroepiandrosterone (dhea), was demonstrated in studies of two lethal viral infection models in mice: systemic coxsackievirus b4 and herpes simplex type 2 encephalitis. the steroid was active either by long-term feeding or by a single subcutaneous injection. a closely related steroid, etiocholanolone, was not protective in these models. histopathological analysis, leukocyte counts, and numbers of spleen antibody forming cells in the ...19882974468
membrane-bound virions of coxsackievirus b4: cellular localization, analysis of the genomic rna, genome-linked protein, and effect on host macromolecular synthesis.hela cells infected with several group b coxsackieviruses contain, in addition to standard virions, a population of virus-specific ribonucleoprotein particles which we (5) designated membrane-bound virions (mbv). mbvs differ from standard virions in buoyant density, yield, appearance, protein composition and infectivity. here we present several new features of mbvs of coxsackievirus b4. the mbvs are lighter (rho about 1.30) and are localized in rough membranes, intermixed with virions. they cont ...19852985028
an outbreak of coxsackievirus b infection followed by one case of diabetes mellitus.during the fall of 1979, 22/250 swedish un soldiers serving in egypt were hospitalized with fever and gastroenteritis associated with aseptic meningitis. one of the 22 developed insulin dependent diabetes mellitus (iddm) 10 weeks following the infection. the majority of the 22 patients showed significant titer rise for coxsackievirus b by plaque reduction neutralization test. the serology results indicate that coxsackievirus b4 most likely caused the outbreak. all 22 were also tested for islet c ...19852986280
mobilization of cutaneous immunity for systemic protection against infections.this laboratory reported that a single subcutaneous (sc) injection of the natural steroid hormone dehydroepiandrosterone (dhea) resulted in significant protection against a lethal herpes virus type 2 encephalitis or a systemic coxsackievirus b4 infection. our previous results have shown that sc injection of dhea resulted in upregulation of the specific host immune response resulting in protection against a lethal infection. this hormone did not have any direct antiviral effects in vitro. further ...19921318664
coxsackievirus b4 infection of sympathetic ganglia in squirrel monkeys.lumbar sympathetic ganglionitis was found by light microscopy in 2 of 17 (12%) squirrel monkeys (saimiri sciureus) experimentally infected with coxsackievirus b4. this finding shows that viruses can cause ganglionitis which, in turn, must cause autonomic nervous system dysfunction. such viral ganglionitis may explain some diseases, including cardiovascular ones, of poorly understood or unknown etiology which present with manifestations of dysfunction of the sympathetic nervous system.19852992318
neutralization kinetic analysis of echovirus 30 and coxsackievirus b4 strains revealed little antigenic variation amongst the echovirus strains.an antigenic analysis was made of echovirus 30 and coxsackievirus b4 isolates by determining neutralization rate constants in neutralization kinetic tests. the seven echovirus 30 isolates included the prototype strain and six others isolated in melbourne, australia, between 1959 and 1982. little antigenic heterogeneity was observed in contrast to the evidence of antigenic variation recorded in similar tests on seven coxsackievirus b4 isolates. these isolates also included the prototype strain, a ...19852994613
focal ventricular thinning caused by indomethacin in the late phase of coxsackievirus b4 murine myocarditis.indomethacin has been shown to increase virus titers and to worsen cardiac injury in the acute phase of coxsackievirus b4 murine myocarditis. the authors evaluated the effects of indomethacin on the histopathologic changes in a later phase of this disease after virus clearance. two-day old cd1 mice were infected with coxsackievirus b4. ten days later, surviving animals were randomized to receive indomethacin or saline intraperitoneally for 10 days. they were then euthanatized, and their hearts w ...19921311498
fatal coxsackievirus b4 infection in a neonate.we reported a fatal coxsackievirus b4 infection in a neonate. the csf wbc was elevated, with polymorphonuclear leukocytes predominating initially and lymphocytes predominating later in the illness. autopsy findings included inflammation of the heart and liver. coxsackievirus b4 was isolated from the heart and quantitated as 10(3) 50% tissue culture infectious doses (tcid50) per gram of myocardium.19852996154
coxsackievirus b4 myocarditis in mice: valvular changes in virus-infected and control animals.suckling, weanling, and adult ham/icr and swiss-webster mice were inoculated intraperitoneally with the tc631 and dowell strains of coxsackievirus b4. vero cell-inoculated and uninoculated control mice were also studied under code. an intense, necrotizing myopericarditis was produced in suckling mice; it was less severe in weanlings. myocarditis did not occur when coxsackievirus b4 was inoculated into adult mice. progressive sclerosis and thickening of all valves in both strains of mice were obs ...1978649986
persistent infection of rat insulinoma cells with coxsackie b4 virus. brief report.plaque purified coxsackie b4 virus (cb4) caused a persistent infection of rat insulinoma (rin) cells which lasted for the 70 day observation period. infectious virus was produced and no cytopathic effect was observed. indirect immunofluorescence and infectious center assays demonstrated that a majority of rin cells were infected. defective interfering particles were not demonstrated. despite persistent infection, insulin synthesis by rin cells was not altered.19863002301
monoclonal antibody to coxsackievirus b4 reacts with myocardium. 19863003209
isolation of a virus from the pancreas of a child with diabetic ketoacidosis.a healthy 10-year-old boy was admitted to the hospital in diabetic ketoacidosis within three days of onset of symptoms of a flu-like illness. he died seven days later and post-mortem examination showed lymphocytic infiltration of the islets of langerhans and necrosis of beta cells. inoculation of mouse, monkey and human cell cultures with homogenates from the patient's pancreas led to isolation of a virus. serologic studies revealed a rise in the titer of neutralizing antibody to this virus from ...1979219345
humoral immune response in hereditary and overt diabetes mellitus.the inbred diabetic mutant mouse, c57bl/ksj db +/db + (db +/db +), spontaneously develops diabetes mellitus when allowed food ad libitum. however, restriction of food intake prevents the expression of this genetic predisposition for diabetes. this experimental design has been used previously to demonstrate a deficient neutralizing antibody response to coxsackievirus b4 (cb4) in mutants with the genetic predisposition only. these observations demonstrate that in the genetically predisposed diabet ...19863016167
isolation of apparently wild strains of poliovirus type 1 from sewage in the ottawa area.in the first 4 months of 1974, 140 gauze pad samples of sewage collected in the ottawa area were analysed by the bs-c-1 cell system for the presence of viruses pathogenic for humans. viruses were isolated from 111 (79%) of the samples. of the 72 (65%) isolates identified by serology and electron microscopic examination, 56 (78%) were reoviruses and 16 (22%), enteroviruses. the enterovirus isolates included one coxsackievirus b4, one vaccine strain of poliovirus type 3, nine vaccine strains of po ...1977188533
relative resistance to chlorine of poliovirus and coxsackievirus isolates from environmental sources and drinking water.several poliovirus and coxsackievirus isolates from environmental sources were compared with laboratory strains to determine their rate of inactivation by chlorine. all viruses were tested for up to 1,000 min in the presence of an initial free residual chlorine level of ca. 0.4 mg/liter. coxsackievirus b5 (cb-5) isolates were found to be more resistant to chlorine than coxsackievirus b4 (cb-4), followed by poliovirus 1, 2, and 3 in order of decreasing resistance to chlorine. environmental isolat ...19852988441
coxsackievirus b4 heterogeneity: effect of passage on neutralization and mortality.we have compared two cb4 isolates for virulence, tissue tropism, and antigenic drift using monoclonal antibodies. both isolates replicated in c57b1/6 and balb/c mice. the human isolate edwards, recovered from a fatal case of encephalohepatomyocarditis, produced lethal infection in adult animals. lethal infections were associated with high viral titers in visceral organs but not with the presence of specific neutralizing epitopes. virulence seemed stable upon passage, and also the avirulent jvb i ...19862881467
purification and characterization of a strain of coxsackievirus b4 of human origin that induces diabetes in mice.a diabetogenic strain of coxsackievirus b4 of human origin has been purified to study its biochemistry and diabetogenicity. tissue culture cells infected with the virus contain two distinct types of particles--virions and membrane-bound virions (mbv). mbvs are lighter (p = 1.29) than virions (p = 1.34), and they contain relatively more protein than rna. virons contain four capsid proteins, vpi-4, of various molecular weights: vp1, 37,500; vp2, 36,000; vp3, 26,000; and vp4, 5,500. mbvs contain th ...19882846770
polioviruses, coxsackieviruses, and echoviruses comparison of the genomes by rna hybridization.hybridization of single-stranded rna from virions of human enteroviruses with denatured double-stranded rna from infected cells indicates that a minimum of about 5% of the genome is shared by these viruses. polynucleotide sequence relationships, furthermore, are consistent with the biologic classification into polioviruses, coxsackieviruses groups a and b, and echoviruses. in general, about 30 to 50% of the nucleotide sequences are shared by different serotypes of virus within each of these majo ...19734351457
role of coxsackievirus b4 in the pathogenesis of acute glomerulonephritis.coxsackievirus b(4) was isolated from the throat, nose, blood, stools and urine of a 9-year-old boy with acute glomerulonephritis and a pneumonitis. neutralization test showed a greater than fourfold rise in the antibody titre to coxsackievirus b(4). the antistreptolysin o titre was elevated, but the complement component was within the normal range. the importance of the coxsackievirus b(4) in the pathogenesis of acute glomerulonephritis is clearly indicated; however, further investigations are ...19734750301
pathologic findings in the pancreas of mice infected with coxsackievirus b4. 19714932531
effect of coxsackievirus b4 infection in mice on expression of 64,000-mr autoantigen and glucose sensitivity of islets before development of hyperglycemia.diabetogenic strains of coxsackievirus b4 (cb4) produce a diabetes syndrome in susceptible mice that resembles insulin-dependent diabetes mellitus. to assess the possible role of autoimmunity, the expression of a 64,000-mr islet antigen in sjl/j and cd1 mice infected with a diabetogenic strain of cb4 was monitored in early and late infection. additionally, virus-induced abnormalities in glucose metabolism were correlated with several changes in purified islets to assess beta-cell physiology. ove ...19882843410
insulin mrna content in pancreatic beta cells of coxsackievirus b4-induced diabetic mice.molecular hybridization was used to measure poly(a)-containing mrna and insulin mrna, and to evaluate viral persistence, in pancreatic beta cells of coxsackievirus b4-induced diabetic mice. cellular rna was hybridized with [3h]poly(u) to measure poly(a)-containing total mrna, 32p-labeled preproinsulin i and ii probes to measure insulin mrna, and a 32p-labeled virus-specific probe to evaluate persistence. the infected mice (80-90%) showed subnormal blood glucose at 72 h postinfection and were hyp ...19882833417
pancreatic d-cell disorder in coxsackievirus b4-induced diabetic mice.pancreatic d-cell disorder was analyzed in coxsackievirus b4-induced diabetic mice employing molecular hybridization with a radiolabelled probe to quantitate somatostatin mrna, and specific immunoprecipitation to measure somatostatin synthesis and its release. many infected mice showed blood glucose lower than noninfected control animals at 72 h postinfection and 85% became hyperglycemic at 6-8 weeks postinfection. pancreatic somatostatin decreased by 24% and 43% at 72 h and 6 weeks postinfectio ...19892575548
detection of enteroviruses using cdna and synthetic oligonucleotide probes.this study compares the detection of enterovirus rna by cdna probes prepared from both the 5' and 3' end of the genome of coxsackie a21 and b4 with the use of synthetic oligonucleotides prepared from short but highly conserved sequences in the 5' end non-coding region of the picornavirus genome. the cdna probes detected enteroviruses with a variable level of sensitivity which presumably depended on the degree of genomic homology with the detecting probes. generally probes from coxsackievirus a21 ...19892550504
neutralization epitope diversity of coxsackievirus b4 isolates detected by monoclonal antibodies.only recently have we begun to fully realize the diversity of virions within a single human isolate of the group b coxsackieviruses. these intratypic (strain) differences may be one of the important factors influencing pathogenesis, e.g., myocarditis vs. pancreatitis. yet, until the virion strains within a type can be well differentiated, a thorough analysis of the pathogenic potential of each is not possible. we compared two human isolates, jvb and edwards, and 15 isolates derived from these tw ...19862428930
pathogenicity of newly isolated coxsackievirus b4 for mouse pancreas.coxsackievirus b4 fresh isolates from patients with upper respiratory illness and aseptic meningitis were studied for their pathogenicity in the pancreas of sjl/j mice. out of 12 virus isolates, 7 induced hypoglycaemia in mice 2 to 4 days after virus inoculation. all 3 isolates from faeces of patients induced hypoglycaemia in contrast to 3 viruses isolated from the cerebrospinal fluid which did not. six isolates from throat swabs were either pathogenic (4 isolates) or non-pathogenic (2 isolates) ...19846151359
autoantigen (64000-mr) expression in coxsackievirus b4-induced experimental diabetes. 19902199165
evaluation of virus neutralization antibody levels in diabetic mutant mice.experiments were designed to determine whether genetic predisposition to diabetes or overt diabetes in the identical genotype had an effect on the level of neutralization antibodies to coxsackievirus b4 (cb4). quantitation of neutralization antibody (nt) levels against cb4 was performed using both the 50% endpoint procedure and the multivariate wilcoxon rank sum test. the results of these experiments demonstrate that the use of the multivariate procedure for the analysis of neutralization antibo ...19902166746
virus infection of endothelial cells.endothelial injury is important in the pathogenesis of thrombosis, atherosclerosis, disseminated intravascular coagulation, and vasculitis. the ability of several common human viruses to infect cultures of endothelial cells obtained from human umbilical veins or bovine thoracic aorta was demonstrated. indicators of infection included cytopathology, viral growth curves, and antigen detection by immunofluorescence. herpes simplex virus type 1, adenovirus type 7, measles virus, and parainfluenza vi ...19816260874
a neutralizing monoclonal antibody against coxsackievirus b4 cross-reacts with contractile muscle proteins.a panel of coxsackievirus b4 (cvb4) neutralizing monoclonal antibodies (mabs) were tested against a panel of normal mouse tissues. one mab, 356-1, reacted specifically with murine heart tissue. immunohistochemical studies revealed an a band pattern of staining of the heart. examination of sequential differential extracts of heart by western immunoblotting showed that 356-1 predominantly reacted with the murine cardiac myosin heavy chain. a rather weak cross-reaction was found with actin. these o ...19902161486
evidence suggesting that virulence maps to the p1 region of the coxsackievirus b4 genome.a chimeric virus containing the p1 region of a virulent variant of coxsackievirus b4 and the p2 and p3 regions of a nonvirulent strain was constructed from cdna clones. the chimeric virus induced pancreatitis with concurrent hypoglycemia similar to that observed in mice infected with the virulent variant.19902159563
experimental coxsackievirus b4 valvulitis in squirrel monkeys. 19826282621
a mouse model of transmural myocardial necrosis due to coxsackievirus b4: observations over 12 months.the course of coxsackievirus b4 necrotizing myocarditis was studied over a 12-month period in 712 icr swiss mice inoculated at less than 48 h of age. affected animals were sacrificed at intervals until 1 year. microscopically, focal myocardial necrosis, which was often transmural in extent with mixed inflammatory exudate, and subsequent fibrous replacement were induced in 75% of the examined animals. the left ventricle (63 of 69 subjects, 91.3%), interventricular septum (39 of 69 subjects, 56.5% ...19826292132
chorioretinitis induced by coxsackievirus b4 infection. 19902154107
alterations in coxsackievirus b4 heart muscle disease in icr swiss mice by anti-thymocyte serum.coxsackievirus b4 (cb4) infection in infant icr swiss mice induces synchronous peaks in both virus titres and pathologic changes in the heart. among surviving mice, transmural necrosis is followed by fibrosis and ventricular aneurysm. rabbit antimouse thymocyte serum (ats) was given before cb4 infection to determine the effects of thymus-dependent functions upon the course of disease. the mortality in ats-treated mice was 75.9% (65 of 83 mice died) compared to 21.3% (16 of 75 mice died) in norma ...19836296300
seroepidemiological evidence of widespread enteroviral infection in anambra state, nigeria.serum samples from 339 apparently healthy subjects, 298 adult blood donors and 41 infants aged 21 months and below, were screened for neutralising activity against poliovirus 1 and coxsackieviruses a7 and b4. among the adult serum samples 85% showed high activity (greater than or equal to 320) against poliovirus 1 while frequencies of similar activities were 65% and 64% for coxsackieviruses a7 and b4 respectively. about 60% showed multiple activity against all three viruses; 15% against both cox ...19901966236
molecular cloning of a heart antigen that cross-reacts with a neutralizing antibody to coxsackievirus b4.a panel of coxsackievirus b4 (cvb4) neutralizing monoclonal antibodies was tested against a panel of normal mouse tissues. one mab, 356-1, reacted specifically with murine heart tissue. examination of the reactivity of 356-1 with cvb4 polypeptides using western immunoblotting revealed that 356-1 binds to the vp-1 capsid protein. immunohistochemical studies revealed an a band pattern of staining of the heart by this antibody. western immunoblotting of sequential differential extracts of heart sho ...19911717274
antiretroviral activity, biochemistry, and pharmacokinetics of 3'-azido-2',3'-dideoxy-5-methylcytidine.3'-azido-2',3'-dideoxy-5-methylcytidine (cs-92, azddmec) is an antiviral nucleoside analogue structurally related to 3'-azido-3'-deoxythymidine (azt). cs-92 is a potent and selective inhibitor of hiv-1 reverse transcriptase and hiv-1 replication in human lymphocytes and macrophages. the ec50 for cs-92 in hiv-1-infected human pbm cells was 0.09 microm. in hiv-1-infected human macrophages, the ec50 was 0.006 microm. this compound was also effective against human immunodeficiency virus type 2 in ly ...19901706574
enhancement of coxsackievirus b4 virulence by indomethacin.the safety of nonsteroidal anti-inflammatory agents in viral infections was assessed in a mouse model of coxsackievirus b4 neonatal myocarditis. two-day-old mice were infected intraperitoneally with 10(4) tcid50 coxsackievirus b4 and then randomized to receive indomethacin or saline for 7 days. a number of them were killed on designated days. mortality, viral titers, antibody, and interferon levels plus histopathologic changes in the heart were compared. among treated animals, mortality was grea ...19901695914
mapping of a neutralizing antigenic site of coxsackievirus b4 by construction of an antigen chimera.a neutralizing antigenic site of coxsackievirus b4 (cvb4) was identified by construction of an antigen chimera between coxsackievirus b3 (cvb3) and cvb4. this chimera, designated cvb3/4, was constructed by inserting five amino acids of the putative bc loop of the structural protein vp1 of cvb4 into the corresponding loop of cvb3 by site-directed mutagenesis of infectious recombinant cvb3 cdna. the chimeric cdna was capable of inducing an infectious cycle upon transfection of permissive host cell ...19911645779
a point mutation in the vp4 coding sequence of coxsackievirus b4 influences virulence.in analyzing the molecular determinants of virulence of coxsackievirus b4, chimeric viruses were constructed from avirulent and virulent viruses. the vcb424 recombinant contained a single nucleotide substitution on an avirulent genetic background, resulting in replacement of ser-16 of vp4 with arg-16. mice infected with vcb424 displayed an intermediate phenotype.19957474153
coxsackievirus b4 infection of the mouse pancreas: acute and persistent infection.the course of infection of a pancreas-adapted isolate of coxsackievirus b4 was followed over a 10 month period in a murine model. following intraperitoneal inoculation a typical acute infection was seen in nine of 10 inbred mouse strains. virus rapidly infected the exocrine pancreas, titres peaking 3 to 4 days post-infection (p.i.). lesions were almost exclusively confined to pancreatic acinar cells and varied in severity among the inbred strains. virus shed into the blood-stream was not cell-as ...19921607860
coxsackievirus b4 infection of the mouse pancreas: the role of natural killer cells in the control of virus replication and resistance to infection.the role of natural killer (nk) cells in the early immune response to a pancreatropic isolate of coxsackievirus b4 (cvb4) was investigated in a murine model of pancreatitis. endogenous (background) nk cell activity in fresh spleen effector cells from eight mouse strains was compared with virus-augmented nk cell activity 4 days post-infection (p.i.). a significant virus-induced increase (p less than or equal to 0.003) in nk cell activity was seen in seven of eight infected mouse strains, when vir ...19921607859
functional alterations in pancreatic beta cells as a factor in virus-induced hyperglycemia in mice.alterations in the functional capacity of pancreatic beta cells appear to contribute to coxsackievirus b4-induced, long-term hyperglycemia in mice. mice infected with prototype b4 or its diabetogenic e2 variant were monitored for abnormalities in sugar metabolism (by the glucose tolerance test), for total protein and insulin synthesis in intact beta cells, for alterations in beta cell proteins, and for virus replication. the infected mice were hypoglycemic at 72 h postinfection and hyperglycemic ...19852995390
experimental coxsackievirus b4 meningitis. 19852997389
pathogenesis of virus-induced diabetes in mice.male cd-1 mice were challenged with a diabetogenic strain (e2) of coxsackievirus b4 (cvb4). at 7 weeks, 6 months, and 1 year after inoculation, mean histopathologic scores, postprandial blood glucose levels, and serum levels of antibody to islet cells were significantly elevated and mean fasting serum insulin levels significantly reduced in infected mice versus uninfected controls (p < .001 for each). at 7 weeks after infection, viral rna, but not protein or infectious virus, was demonstrated in ...19957751687
genetic predisposition to diabetes mellitus is associated with impaired humoral immunity to coxsackievirus b4.experiments were performed to determine whether genetic predisposition to diabetes mellitus (dm) or clinical dm or both exert an influence on the production of neutralization antibodies to coxsackievirus b4 (cb4). the homozygous diabetic mutant mouse db+/db+, on the inbred c57bl/ksj genetic background, develops a diabetes-like disease when maintained on ad libitum diet but restriction of excess food intake prevents overt disease. the doubly heterozygote db+/+m or the homozygote +m/+m misty coat ...19863013555
the complete nucleotide sequence of coxsackievirus b4 and its comparison to other members of the picornaviridae.the genome of the prototype stain of coxsackievirus b4 (j.v.b. benschoten) has been cloned in escherichia coli and its complete nucleotide sequence determined. excluding the poly(a) tract, the rna genome is 7395 nucleotides in length and appears to encode a single polyprotein of 2183 amino acids. the predicted amino acid sequence of the polyprotein shows close homology (88%) to that of the previously sequenced coxsackievirus b3 and to certain regions of the polyproteins of the polioviruses and h ...19873037008
anti-idiotypic antibodies to monoclonal antibodies that neutralize coxsackievirus b4 do not recognize viral receptors.we have made anti-idiotypic antibodies in rabbits against three mouse monoclonal neutralizing antibodies with specificities for independent epitopes on coxsackievirus b4. each of these anti-idiotypic antibodies was found to react specifically with the immunizing monoclonal antibody in radioimmunoassays and did not react with the other monoclonal antibodies. in addition, the anti-idiotypic antibodies specifically inhibited the function (i.e., virus neutralization) of the immunizing antibody. thes ...19863962185
inhibition of enterovirus cytopathic effects by 2-(alpha-hydroxybenzyl)-benzimidazole.bablanian, rostom (the rockefeller university, new york, n.y.), hans j. eggers, and igor tamm. inhibition of enterovirus cytopathic effects by 2-(alpha-hydroxybenzyl)-benzimidazole. j. bacteriol. 91:1289-1294. 1966.-2-(alpha-hydroxybenzyl)-benzimidazole (hbb), a specific inhibitor of enterovirus multiplication, markedly delayed the development of cytopathological changes induced by echovirus 12 or coxsackievirus b4 in monkey kidney cells, but did not prevent the ultimate degeneration of infected ...19664956333
aseptic meningitis, montreal, 1969: a clinical and laboratory study.during the summer and fall of 1969 an outbreak of aseptic meningitis occurred in montreal and its environs. forty-four patients were admitted to the infectious disease ward of the montreal children's hospital in august, september and october. half of the patients were in the age group 6 to 10 years. the ratio of males to females was two to one. patients showed the typical signs and symptoms of aseptic meningitis, namely fever, vomiting, headache, neck stiffness and pleocytosis of the cerebrospin ...19715101641
influence of diabetes mellitus heredity on susceptibility to coxsackievirus b4.using the criteria of virus susceptibility as defined by the 50 percent lethal dose response and the percent cumulative mortality response it was shown that the diabetic mutation db, located on chromosome 4, exerted a particular influence on the host response to cb4 challenge. neither the yellow obese mutation ay on chromosome 2 nor the misty coat color mutation located one centimorgan from the db mutation had the same effect on cb4 response. the obese diabetic mutation ob located on chromosome ...19846089704
complete nucleotide sequence of a beta-cell tropic variant of coxsackievirus b4.a mouse pancreas-adapted variant of coxsackievirus b4 (p-cb4) has been shown to replicate in, and cause an excessive release of insulin from, pancreatic beta cells cultured in vitro. the prototype cb4 strain (jvb benschoten), from which the adapted variant was derived, although able to replicate in cultured islets does not cause a similar release of insulin from the beta cells. the pancreas-adapted virus has also been shown to cause host cell protein synthesis shut-off in beta cells and to inhib ...19948046427
coxsackievirus b4: in vitro genetic markers and cardiovirulence. brief report.the relationship of cardiovirulence in mice (ham/icr, swiss nd-4) of four coxsackievirus b4 strains to previously described in vitro markers (t, d, ds, deae-d, g, ps) has been determined. a relationship between plaque size and acardiovirulence was demonstrated in the ham/icr coxsackievirus b4 mouse system.19846089708
elimination of some enteroviruses in the excrements of experimentally infected rats (rattus norvegicus) and gulls (larus ridibundus).young rats of both sexes, weight 150-170 g, the first laboratory progeny of captured wild parent pairs, were used throughout this experiment. rats in two experimental groups comprising a total of 34 animals were infected orally with type 2 poliovirus vaccine strain given in each group at doses of 500, 5000 or 50,000 tcd50. in the first experiment, the presence of poliovirus in rat excrements was detectable irregularly till day 13, in the second experiment till day 2 after infection. small quanti ...19846092458
heterogeneity of a human isolate of coxsackie b4: biological differences.evidence is presented to demonstrate existence of virion heterogeneity within the human isolate, edwards, of coxsackievirus b4 (cb4-edw). three virion types (e1, e2 and e3) were cloned by repeated plaque purification of cb4-edw and then all were compared relative to their effects on the pancreas of mice during acute infection. seventy-two hours post-infection blood glucose, plasma amylase and insulin levels were monitored in mice of the swr/j strain (previously classified susceptible to other di ...19836193205
viruses in sewage as an indicator of their presence in the community.the results of a three year study of the viruses isolated from sewage by means of five tissue culture types are reported. the enteroviruses identified demonstrated a seasonal pattern which was similar to that of clinical isolates. echoviruses and coxsackieviruses displayed a changing pattern of dominant serotypes in both sewage and clinical isolates; echovirus 6, 19, 3 and coxsackievirus b4, b5, a9 successively became the most common serotypes. the poliovirus in sewage was all vaccine-like in ch ...19816257783
coxsackievirus b4 infection of spinal sympathetic ganglion. 19816263670
host factors in coxsackievirus b4-induced pancreopathy.the diabetogenic potential of the human isolate, coxsackievirus b4 (cb4) (edwards) was studied in three inbred mice strains, swr/j, dba/2, and c57bl/6. the mice were infected with this agent and evaluated for mortality, pancreatic histopathology, and glucose tolerance. results showed that the mortality induced by cb4 in these inbred strains differed considerably. there was no evidence of a correlation between virus-induced mortality and virus-induced pancreopathy. although cb4 (edwards) was most ...19826279960
coxsackievirus b4 nephritis in the squirrel monkey.seventeen squirrel monkeys (saimiri sciureus) were experimentally infected with coxsackievirus b4, and the kidneys, as well as other organs, were studied for pathological changes induced by the virus. seven (41%) of these monkeys developed renal lesions--interstitial and glomerular. the coxsackievirus was identified in 4 of these 7 monkeys (by isolation from the renal tissue in 2, by immunofluorescence staining of viral antigen in 1, and by electron microscopic finding of viral particles in 1). ...19826295434
a nucleotide sequence comparison of coxsackievirus b4 isolates from aquatic samples and clinical specimens.ten coxsackievirus b4 (cvb4) strains isolated from clinical and environmental sources in northern ireland in 1985-7, were compared at the nucleotide sequence level. dideoxynucleotide sequencing of a polymerase chain reaction (pcr) amplified fragment, spanning the vp1/p2a genomic region, classified the isolates into two distinct groups or genotypes as defined by rico-hesse and colleagues for poliovirus type 1. isolates within each group shared approximately 99% sequence identity at the nucleotide ...19938386098
structure-activity relationships of new antiviral compounds.in preliminary experiments, the compound 2-amino-5-(2-sulfamoylphenyl)-1,3,4-thiadiazole (g413) was shown to possess high activity against dna viruses (herpes simplex viruses 1 and 2 and adenovirus 17) and rna viruses (poliovirus 1, echovirus 2, and coxsackievirus b4). experiments on the replicative cycle of poliovirus 1 and production of infectious rna viruses demonstrate that this compound probably prevents assembly of virus particles by acting on structural proteins. in the present experiment ...19826297385
antibody capture radioimmunoassay (macria) for coxsackievirus b4 and b5-specific igm.an antibody capture radioimmunoassay was established for the detection of coxsackievirus b4 and b5-specific igm. a significant feature of the assay was the use of an unrefined coxsackievirus b (cbv) antigen. the antigen was prepared by freeze thawing, ultrasonication and low speed centrifugation of infected vero cells with no purification or concentration of the antigen being performed. results of sera tested were expressed as a serum ratio (sr) by comparison with a low positive control serum. t ...19836306097
the effects of pre-existing coxsackievirus b4 myocardial disease on the expression of coxsackievirus b3 myocarditis.to assess the expression of coxsackievirus b3 (cb3) myocarditis in mice with pre-existing cb4 myocardial disease.19938394194
coxsackievirus b4 hepatitis in monkeys.hepatitis was produced by coxsackievirus b4, an agent highly infectious to man, in 3 of 9 experimentally infected squirrel monkeys. although the virus could not be isolated from the livers of these monkeys, viral antigen was found in the liver cells of one monkey with severe hepatitis by direct immunofluorescent antibody staining, and a virus crystal was found in the kidney of this monkey by electron microscopy. these and previous studies strongly suggest that the coxsackievirus can exist in the ...19836310015
genetic mapping of the determinants of plaque morphology of coxsackievirus b4.the genetic determinants of plaque size of two variants of coxsackie-virus b4, cb4-p and cb4-v, were identified using a panel of recombinant, chimeric viruses. when grown in monkey kidney cells, cb4-v yielded large plaques with an average size of 1.0 cm while cb4-p yielded small plaques with an average size of 0.4 cm. two genetic domains, the 5' untranslated region and the vp4 gene sequence, independently influenced plaque size. recombinant viruses containing the cb4-p genetic background with po ...19958572942
coxsackievirus b4: in vitro genetic markers and virulence.the relationship of virulence to mice of the coxsackievirus b4 prototype jbv strain and selected mutants to several in vitro genetic markers has been examined. markers studied include the t, d, ds, deae-d, and guanidine resistance (g), markers and a plaque size marker, here designated ps. the jvb strain was found to have the characteristics t-, d-, ds+, deae-d+, g-, ps+ and to be virulent when inoculated by the intraperitoneal route into suckling cd-1 mice (log titer/ld50 = 6.4/6.0). one natural ...19836312933
rhabdomyolysis in diabetic ketoacidosis.a 2-year-old boy became ill with diabetic ketoacidosis complicated by severe rhabdomyolysis. he completely recovered from the rhabdomyolysis, but has persistent insulin-dependent diabetes mellitus (iddm). serological studies showed that the patient's serum contained high titers of coxsackievirus b4 antibody, suggesting that the development of rhabdomyolysis and iddm may have been related to this infection. a review of the records of 133 patients admitted with onset of iddm disclosed one addition ...19816782859
picornavirus 2a proteinase-mediated stimulation of internal initiation of translation is dependent on enzymatic activity and the cleavage products of cellular proteins.poliovirus and human rhinovirus 2a proteinases are known to stimulate translation initiation on the cognate viral internal ribosome entry segments (ireses). the molecular mechanism of this translational transactivation was investigated in vitro using dicistronic mrnas containing picornaviral ireses as the intercistronic spacer and purified human rhinovirus type 2 and coxsackievirus b4 2a proteinases. the stimulation achieved on the hrv2 ires in the presence of the cognate 2a proteinase at 1 micr ...19957491779
characterization of the n-terminal part of the neutralizing antigenic site i of coxsackievirus b4 by mutation analysis of antigen chimeras.coxsackievirus b3 (cvb3) as a potential rna virus vector for the presentation of foreign antigenic epitopes was further characterized. insertion mutagenesis of infectious cvb3 cdna yielded viable antigen chimeras containing variant bc loops of vp1 of coxsackievirus b4 (cvb4). analysis of three antigen chimeras allowed the mapping of the n-terminal part of the neutralizing antigenic site 1 (n-ag1) of cvb4 which is located in the bc loop of the structural protein vp1. a significant neutralization ...19947531922
analysis of sewage effluent for human immunodeficiency virus (hiv) using infectivity assay and reverse transcriptase polymerase chain reaction.environmental survival of human immunodeficiency virus type 1 (hiv-1) is an important public health concern. survival of hiv in waste water is of particular interest to those who work at treatment facilities and to the general public who have contact with rivers or ocean water receiving treated sewage effluent. other researchers have reported that hiv can be detected in waste water. their studies, however, detected homologous nucleic acid sequences but did not attempt to determine infectivity. t ...19957585358
complete heart block and cardiogenic shock with coxsackievirus b4 myocarditis requiring permanent pacing and intra-aortic balloon counterpulsation. 19957663597
protein kinase in nondiabetogenic coxsackievirus b4.alkali-dissociated, purified preparations of prototype coxsackievirus b4 release a protein kinase that catalyzes the incorporation of gamma-phosphate from 32p-labeled atp into three virus capsid proteins (vp1, vp3, vp4), several additional proteins of the particle, and exogenous acceptor proteins. using protamine sulfate as an acceptor protein, we detected nearly 20-fold more enzyme activity in membrane-bound virions (mbv) than in virions of the virus. the activity in the mbv is cyclic nucleotid ...19863018140
selection of coxsackievirus b4 variants with monoclonal antibodies results in attenuation.inoculation of suckling mice with coxsackievirus b4 (cb4) results in the death of a majority of the animals. in this study we selected antigenic variants of cb4 in the presence of neutralizing monoclonal antibodies and tested them to see whether they were attenuated. antigenic variants selected with a single antibody showed little or no attenuation by producing a high mortality (60 to 100%). a double variant selected with two antibodies showed considerable attenuation by causing only 25% mortali ...19873029310
expression of coxsackievirus b4 proteins vp0 and 2c in escherichia coli and generation of virus protein recognizing antisera.coxsackievirus b4 (cbv-4) capsid protein vp0 and non-structural 2c protein were expressed and purified using a glutathione-s-transferase (gst) fusion protein expression system. we used a full-size cbv-4 cdna as a template to amplify the genes by polymerase chain reaction (pcr). the genes were cloned into expression vector pgex-2t and expressed as a fusion protein with gst. the gst-fusion proteins (gst-2c and gst-vp0) were purified in denatured and native forms and used to generate antibodies in ...19979504760
sequence homology of the diabetes-associated autoantigen glutamate decarboxylase with coxsackie b4-2c protein and heat shock protein 60 mediates no molecular mimicry of autoantibodies.molecular mimicry between viral antigens and host proteins was often suggested to be involved in induction of autoimmune diseases. in type 1 diabetes where pancreatic beta cells are destroyed by autoimmune phenomena, a linear sequence homology between a major autoantigen, glutamate decarboxylase (gad), and the 2c protein of coxsackie b4 was identified. in addition, a sequence homology between gad and the mycobacterial heat shock protein 60 was described and the suggestions were made that molecul ...19947913951
the effect of subsequent myocardial damage on the expression of coxsackievirus b4 myocarditis and the development of ventricular aneurysms.coxsackievirus b (cb) 4 causes transmural myocarditis in suckling mice with ensuing development of focal ventricular thinning or aneurysms. we studied whether subsequent infection with another cardiotropic virus influences the expression of cb4 disease. cb4 infection was established in 2-day-old cd1 mice by intraperitoneal (ip) inoculation. three weeks later, surviving animals were randomized to receive cb3 or saline ip. they were then killed over a 45-day period. cb4 neutralizing antibody (na) ...19947988609
pericardioscopy and epicardial biopsy--new diagnostic tools in pericardial and perimyocardial disease.pericardioscopy is a new diagnostic tool for macroscopic visualization of alterations in both the epicardium and pericardium. we report on 35 patients with pericardial effusion due to inflammatory perimyocardial disease. after puncture of the pericardial effusion, an 8f sheath was introduced over a guidewire under x-ray control. the pericardial pressures were measured; the fluid was removed by aspiration and exchanged with 100 ml of body-warm saline until the pericardial fluid was clear. to visu ...19947995273
exposure to enteroviruses and hepatitis a virus among divers in environmental waters in france, first biological and serological survey of a controlled cohort.an epidemiological study of hepatitis a and enteroviruses was conducted in a military diving training school, by evaluating the viral contamination of water using an ultrafiltration concentration technique, and assessing seroconversion and the presence of virus in stool specimens obtained from 109 divers and 48 controls. three of 29 water specimens were positive for enterovirus by cell culture and 9 by molecular hybridization. there was little or no risk of virus infection during the training co ...19947995363
detection of igm antibodies against coxsackie b viruses by a western blot technique.we report the application of a modified western blot (wb) micromethod basically relying on a diffusion-blotting technique (modi-blot) combined with an immunological detection system using monoclonal antibodies and a biotinavidin amplification step for the detection of igm antibodies against coxsackieviruses b1 (cbv1), cbv2 and cbv4. fifty-one adult patients with clinical signs of coxsackievirus b infection (e.g. myocarditis and meningitis) were investigated. the test revealed a total of 31 (60%) ...19938105643
genomic and phylogenetic characterization of coxsackievirus b2 prototype strain ohio-1.the human picornavirus coxsackievirus b2 (cvb2) is often linked to several infections, from mild respiratory diseases to more severe illnesses such as myocarditis. in this study, we report the complete genome sequence of cvb2 prototype strain ohio-1. the genome sequence was determined from reverse transcribed viral rna, amplified with long distance pcr and used for non-radioactive sequencing. the full length pcr amplicons were used for in vitro transcription and the obtained crna was lipofected ...199910082394
the 5'-untranslated regions of picornavirus rnas contain independent functional domains essential for rna replication and translation.the role of the 5'-untranslated region (5'utr) in the replication of enteroviruses has been studied by using a series of poliovirus type 3 (pv3) replicons containing the chloramphenicol acetyltransferase reporter gene in which the 5'utr was replaced by the 5'utr of either coxsackievirus b4 or human rhinovirus 14 or composite 5'utrs derived from sequences of pv3, human rhinovirus 14, coxsackievirus b4, or encephalomyocarditis virus. the results indicate that efficient replication of an enteroviru ...19948207812
win 54954 treatment of mice infected with a diabetogenic strain of group b coxsackievirus.the therapeutic efficacy of an experimental antiviral agent, win 54954, was evaluated in a mouse model in which infection by coxsackievirus b4 (cvb4) strain e2 was followed by diabetes mellitus. male cd1 mice (age, 5 weeks) were inoculated with 10(4) pfu of cvb4. win 54954 was administered orally via gavage tube in a dose of either 5 or 50 mg/kg of body weight per day. treatment was initiated on the day of inoculation and was continued for 10 days. control animals received the xanthan gum carrie ...19938215268
protein-free culture of vero cells: a substrate for replication of human pathogenic viruses.a protein-free chemically defined medium designated pfek-1 was developed for culture of vero cells on polyvinyl formal (pvf) culture surface without serum or other macromolecular supplements. vero cells proliferated in pfek-1 medium on pvf surface to a similar extent as cells in serum-supplemented medium without previous adaptation from serum-containing conditions. the protein-free culture infected with coxsackievirus b4, herpes simplex virus types 1 and 2, measles virus and poliovirus types 1, ...19938220316
coxsackievirus b4 myocarditis in an orangutan.a 37-year-old female orangutan died at the zoological garden. autopsy examination demonstrated severe coxsackievirus b4 myocarditis immunohistochemically as a cause of the death. apoptosis of the cardiac muscle cells was observed using the tdt-mediated dutp-biotin nick endo labeling method and was considered to play a role in the myocarditis. congestion of the liver and both lungs due to cardiac failure was also observed. coxsackievirus infection is found frequently in the okinawan human populat ...199910490214
relation between t-cell responses to glutamate decarboxylase and coxsackievirus b4 in patients with insulin-dependent diabetes mellitus.the role of enteroviruses has been implicated in the etiology of insulin-dependent diabetes mellitus (iddm). a possible connection between glutamate decarboxylase (gad) autoimmunity and enterovirus infections in iddm has been suggested to be based on a homology region between gad and the non-structural protein 2c of coxsackievirus b4 (cvb4).199910588452
persistence of coxsackievirus b4 infection in rhabdomyosarcoma cells for 30 months. brief report.a persistent infection of rhabdomyosarcoma (rd) cells by coxsackie b4 virus (cbv-4) was established. the persistently infected rd (pird) cells have been maintained for over 130 passages (30 months) and have released virus continuously without cellular destruction. the production of infectious virus declined three times during the study. after the first decline (third week post infection) a viral variant with a littered cytopathic effect (cpe) and a marked delayed replication cycle on green monke ...199910603178
coxsackievirus b4 alters pancreatic glutamate decarboxylase expression in mice soon after infection.the 64,000-m(r) (64k) islet autoantigen, which is considered to be a target protein of beta cell destruction in insulin-dependent diabetes mellitus (iddm), has recently been identified as the enzyme glutamic acid decarboxylase (gad). we reported a two- to three-fold increased expression of the antigen in islets of diabetes-susceptible mice following infection with a diabetogenic strain of coxsackievirus b4 (cb4) at 72-h postinfection (p.i.), a time point of active virus replication in the islets ...19938240659
molecular epidemiology of coxsackievirus b4 and disclosure of the correct vp1/2a(pro) cleavage site: evidence for high genomic diversity and long-term endemicity of distinct genotypes.genetic diversity among 107 coxsackievirus b4 field isolates has been studied. these isolates included clinical and environmental isolates originating from finland, the netherlands and france, and also from several other countries, including the usa. three genomic regions were used for phylogenetic analyses: the vp1/2a junction, the entire vp1 and the vp4/vp2 region. alignment of the deduced amino acid sequence in the vp1/2a junction revealed extensive sequence variation at the previously propos ...200010675418
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