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gene expression during reactivation of herpes simplex virus type 1 from latency in the peripheral nervous system is different from that during lytic infection of tissue cultures.herpes simplex virus (hsv) replicates in peripheral tissues and forms latent infections in neurons of the peripheral nervous system. it can be reactivated from latency by various stimuli to cause recurrent disease. during lytic infection in tissue culture cells, there is a well-described temporal pattern of (i) immediate-early, (ii) early, and (iii) late gene expression. however, latency is characterized by little if any expression of genes of the lytic cycle of infection. during reactivation, t ...19979188595
expression of interleukin-10 mrna in herpes simplex virus-infected keratinocytes in vivo and in vitro. 19979191326
development of an hsv-based vector for the treatment of parkinson's disease.the restricted pattern of neurodegeneration seen in parkinson's disease, and the identification of trophic factors that prevent toxin-induced degeneration of dopaminergic neurons, has spurred research into potential gene therapy for this disease. herpes simplex virus (hsv-1) is a neurotrophic virus which naturally establishes latency in neurons. hsv-based vectors have been demonstrated to transfer and transiently express transgenes in neurons in brain in vivo. recent experiment have shown that d ...19979126159
cytokines released by human peripheral blood mononuclear cells inhibit the production of early and late cytomegalovirus proteins.cytomegalovirus-infected human fibroblasts are susceptible to lysis by natural killer cells and cytotoxic t cells. the purpose of this study was to determine whether non-lytic mechanisms might also contribute to the control of cytomegalovirus infection. the appearance of cytomegalovirus proteins in infected fibroblasts was determined by flow cytometry. infected fibroblasts incubated with peripheral blood mononuclear cells for 3 days expressed less early and late proteins than fibroblasts incubat ...19979194039
fulminant hepatitis during herpes simplex virus infection in apparently immunocompetent adults: report of two cases and review of the literature.two apparently immunocompetent adult patients developed acute fulminant hepatitis during presumptive primary herpes simplex virus type 1 (hsv-1) infection without any visible mucocutaneous lesions. hsv hepatitis was not suspected in the case of patient 1, who died without treatment. patient 2 was empirically treated with acyclovir because of the triad of high fever, leukopenia, and markedly elevated levels of aminotransferases, and this patient survived. most immunocompetent patients with fulmin ...19979195081
the herpes simplex virus type 1 latency-associated transcript gene regulates the establishment of latency.herpes simplex virus type 1 establishes latent infections in sensory neurons. during latency only one locus, the latency-associated transcript (lat), is abundantly transcribed. several lines of evidence suggest that this locus is required for the efficient reactivation from latency in experimental models. however, it is not yet clear whether this is a direct effect on the reactivation process per se or, as we have suggested, an indirect effect resulting from a decreased efficiency of establishme ...19979188615
the ul20 gene product of pseudorabies virus functions in virus egress.the ul20 open reading frame is positionally conserved in different alphaherpesvirus genomes and is predicted to encode an integral membrane protein. a previously described ul20- mutant of herpes simplex virus type 1 (hsv-1) exhibited a defect in egress correlating with retention of virions in the perinuclear space (j. d. baines, p. l. ward, g. campadelli-fiume, and b. roizman, j. virol. 65:6414-6424, 1991). to analyze ul20 function in a related but different herpesvirus, we constructed a ul20- p ...19979188641
human t-cell lymphotropic virus tax and epstein-barr virus dna in peripheral blood of multiple sclerosis patients during acute attack.a study was performed to determine whether persistent or latent viruses are reactivated during the acute attack in relapsing remitting multiple sclerosis (ms).19979174643
antiviral activity of galangin isolated from the aerial parts of helichrysum aureonitens.the in vitro antiviral activity of galangin (3,5,7-trihydroxyflavone), the major antimicrobial compound isolated from the shoots of helichrysum aureonitens, was investigated against herpes simplex virus type 1 (hsv-1), coxsackie b virus type 1 (cox b1), adenovirus type 31 (ad31) and reovirus. at concentrations ranging from 12-47 micrograms/ml galangin showed significant antiviral activity against hsv-1 and coxb1, limited activity against reovirus, and no antiviral activity against ad31.19979174978
intracellular thiol redox status affects rat cytomegalovirus infection of vascular cells.there is increasing evidence for cytomegalovirus (cmv) induced vascular pathology during acute infection in the immunocompromised host. inflammation is involved in such processes, which is frequently associated with increased levels of oxidative mediators and reduced anti-oxidant protection. a relation between viral infection and oxidative stress has been recognized for human immunodeficiency virus and herpes simplex virus-1 infections, but little is known in this respect for cmv infections. we ...19979175256
formation of herpes simplex virus type 1 replication compartments by transfection: requirements and localization to nuclear domain 10.during infection, the seven essential herpes simplex virus type 1 (hsv-1) replication proteins are found in globular nuclear structures called replication compartments. replication compartments form adjacent to nd10, nuclear matrix-bound domains which are present in most cell types but whose function is unknown (g. g. maul, i. m. ishov, and r. d. everett, virology 217:67-75, 1996). we now demonstrate that replication compartments can be formed by cotransfecting vero cells with constructs express ...19979032376
herpes simplex virus virulence: the functions of the gamma (1)34.5 gene. 19979179780
evaluation of retinal toxicity and efficacy of anti-cytomegalovirus and anti-herpes simplex virus antiviral phosphorothioate oligonucleotides isis 2922 and isis 4015.retinal toxicity of isis 2922 and isis 4015, phosphorothioate oligonucleotides complementary to human cytomegalovirus (cmv) and herpes simplex virus (hsv) rna, were evaluated. the intravitreal concentration of isis 2922 found not to cause permanent toxic changes in the rabbit retina was 10 microm and in the pig retina, 5 microm. the 3 microm concentration was associated with a transient inflammatory response, and 1 microm caused no retinal toxicity or inflammation. isis 4015 showed very mild tox ...19979180168
treatment of experimental subcutaneous human melanoma with a replication-restricted herpes simplex virus mutant.modified, non-neurovirulent herpes simplex viruses (hsv) have shown promise for the treatment of brain tumors, including intracranial melanoma. in this report, we show that hsv-1716, an hsv-1 mutant lacking both copies of the gene coding-infected cell protein 34.5 (icp 34.5), can effectively treat experimental subcutaneous human melanoma in mice. in vitro, hsv-1716 replicated in all 26 human melanoma cell lines tested, efficiently lysing the cells. therapeutic infection of subcutaneous human mel ...19979182825
antiherpetic and anticoagulant properties of carrageenans from the red seaweed gigartina skottsbergii and their cyclized derivatives: correlation between structure and biological activity.the antiviral activity against herpes simplex virus types 1 and 2 of kappa/l-, partially cyclized mu/v-, and lambda-carrageenans isolated from the red seaweed gigartina skottsbergii and their cyclized derivatives was analyzed. lambda-carrageenans and the partially cyclized mu/v-carrageenan were the most potent inhibitors of herpes viruses (including acyclovir-resistant variants and clinical isolates), with ic50 values lower than 1 microgram ml-1 against both serotypes and selectivity indices hig ...19979184941
construction and characterization of a replication-defective herpes simplex virus 2 icp8 mutant strain and its use in immunization studies in a guinea pig model of genital disease.a replication-defective mutant of herpes simplex virus 2 (hsv-2) was engineered by replacing the icp8 gene of hsv-2 strain 186 with an icp8-lacz fusion gene from the herpes simplex virus 1 (hsv-1) hd-2 mutant strain. the resulting virus, hsv-2 5blacz, is defective for growth in vero cells but is capable of growth in a cell line that expresses hsv-1 icp8. in vero cells, the mutant virus is defective for dna synthesis but is able to express many viral proteins at levels similar to those of wild-ty ...19979185583
suppression of apoptotic dna fragmentation in herpes simplex virus type 1-infected cells.hep-2 cells underwent apoptosis when the cells were incubated in medium containing sorbitol. infection with herpes simplex virus type 1 (hsv-1) prior to the sorbitol treatment suppressed this apoptosis completely, indicating that hsv-1 carries an antiapoptosis gene. in addition, hsv-1 multiplication was restricted in these apoptotic hep-2 cells.19979032402
persistence of ribosomal protein synthesis after infection of hela cells by herpes simplex virus type 1.because synthesis of rrna persists late during herpes simplex type 1 infection and because s6 phosphorylation is always correlated with efficient translation of ribosomal protein mrna, we tested the hypothesis that ribosomal protein synthesis and ribosome biogenesis could persist after infection. at different times after infection, proteins were labelled with 35s for 1 h before harvesting and ribosomes were purified. measurement of radioactivity incorporated into individual ribosomal proteins se ...19979018067
biochemical analyses of mutations in the hsv-1 helicase-primase that alter atp hydrolysis, dna unwinding, and coupling between hydrolysis and unwinding.herpes simplex virus type 1 encodes a heterotrimeric helicase-primase composed of the products of the ul5, ul52, and ul8 genes. ul5 possesses six motifs conserved among superfamily 1 of helicase proteins. substitutions of conserved residues in each motif abolishes dna replication in vivo (zhu, l., and weller, s. k. (1992) j. virol. 66, 469-479). purified ul5.52 harboring a gly to ala change in motif v retains primase and helicase activities in vitro but exhibits a higher km for single-stranded d ...19979020191
naturally occurring herpes simplex encephalitis in a domestic rabbit (oryctolagus cuniculus).an approximately 1-year-old domestic rabbit showed severe neurologic signs with circling and turning somersaults. histologically, a nonsuppurative meningoencephalitis with neuronal cell necrosis and numerous intranuclear inclusion bodies in neurons and glial cells was found. electron microscopic examination revealed herpesvirus particles in affected cells. a human herpes simplex virus was identified by means of immunocytochemistry and in situ hybridization as the causal agent and was further cla ...19979150545
the herpes simplex virus immediate-early protein icp0 affects transcription from the viral genome and infected-cell survival in the absence of icp4 and icp27.icp4, icp0, and icp27 are the immediate-early (ie) regulatory proteins of herpes simplex virus that have the greatest effect on viral gene expression and growth. comparative analysis of viral mutants defective in various subsets of these ie genes should help elucidate how these proteins affect cellular and viral processes. this study focuses on the mutant d97, which is defective for the genes encoding icp4, icp0, and icp27 and expresses the bacterial beta-galactosidase (beta-gal) gene from the i ...19979151855
localization of latency-associated transcripts in the uterovaginal plexus of herpes simplex virus type 1 and 2 latently infected mice.the vagina and medulla of the adrenal gland of mice vaginally infected with herpes simplex virus (hsv) types 1 and 2 were examined in the latent stage of infection (5 to 51 weeks post-infection). rna in situ hybridization with hsv-1 and -2 latency-associated transcript (lat) rna probes resulted in positively stained neuronal cell nuclei in the uterovaginal plexus, but not in the medulla of the adrenal gland. these organs were chosen because hsv antigens can be detected not only in the vaginal ep ...19979152429
differential effects of hsv-1 and hcmv infection on adhesion molecule expression on human corneal keratocytes.previous studies have shown that keratoplasty buttons obtained at surgery from patients with herpes simplex virus-1 (hsv-1) keratitis have elevated localized expression of the adhesion molecule icam-1, which plays a critical role in the initiation and amplification of an immune response. we performed studies to determine whether changes in expression of icam-1 and hla class i are direct effects of productive infection of human corneal fibroblasts with hsv-1.19979154389
herpes simplex virus-1 plasmid vectors for gene transfer into neurons. 19978993693
structure of the herpes simplex virus capsid: peptide a862-h880 of the major capsid protein is displayed on the rim of the capsomer protrusions.the herpes simplex virus-1 (hsv-1) capsid shell has 162 capsomers arranged on a t = 16 icosahedral lattice. the major capsid protein, vp5 mw = 149,075) is the structural component of the capsomers. vp5 is an unusually large viral capsid protein and has been shown to consist of multiple domains. to study the conformation of vp5 as it is folded into capsid promoters, we identified the sequence recognized by a vp5-specific monoclonal antibody and localized the epitope on the capsid surface by cryoe ...19979123829
replacement of the herpes simplex virus type 1 vmw175 dna binding domain with its varicella-zoster virus counterpart results in a protein with novel regulatory properties that can support virus growth.the alphaherpesviruses encode major immediate early transactivator proteins that are essential for the expression of later classes of viral genes. we have previously shown that the extensive sequence similarity between the herpes simplex virus type 1 (hsv-1) and varicella-zoster virus (vzv) members of the family (proteins vmw175 and vzv140k) extends to function, since a virus which expresses vzv140k in place of vmw175 is able to grow, albeit at reduced efficiency. we have also shown that the dna ...19979010302
in vitro selection of variants of herpes simplex virus type 1 which differ in cytopathic changes.to analyze the mechanisms for in vitro emergence of the syncytial variants of herpes simplex virus type 1 (hsv-1), several cell lines were infected with a mixture of equal amounts of two hsv-1 variants, one syncytial and the other non-syncytial, and changes in their relative abundance were monitored during passage. with a combination of two variants of the miyama strain of hsv-1, the syncytial variant became dominant during passage in vero, rk-13 and fl cells. on the other hand, the ratios of th ...19979130231
herpetic urethritis in male patients in ibadan.in a study of 151 male patients attending a sexually transmitted disease clinic, 40 (26.4%) had non-gonococcal urethritis. herpes simplex virus was isolated in tissue culture of hep-2 cell line from 10 of the patients with non-gonococcal urethritis, and identified by complement fixation and indirect immunofluorescent anti body tests. of the isolates, 30% were herpes simplex virus type 1 (hsv-1), while 70% were herpes simplex virus types (hsv-2).19979133820
proinflammatory functions of il-2 in herpes simplex virus corneal infection.herpes simplex virus type 1 infection of corneas can lead to blinding inflammation in the corneal stroma, which is referred to clinically as herpes stromal keratitis. in our mouse model of this prevalent human disease, a heavy polymorphonuclear neutrophil (pmn) infiltration of the infected cornea leads to progressive tissue destruction. this inflammatory process can be abrogated by in vivo depletion of cd4 t lymphocytes and by neutralization of the cytokines il-2 and ifn-gamma. the goal of this ...19979013970
clear detection and typing of herpes simplex virus types 1 and 2 by an indirect elisa assay: comparison with three different combined methods--capture elisa, restriction enzymes, and polymerase chain reaction.the severity and recurrences of herpes simplex virus (hsv) infection depend on the type of the infectious agent (hsv-1 or hsv-2), which induces the necessity of a nonambiguous detecting typing. the commonly used capture elisa technique has to be often supported by dna analysis to confirm the detection and the typing of hsv viruses in exposed patients. in this report, we describe a rapid and cheap indirect elisa method using anti-hsv monospecific polyclonal antibodies prepared in the laboratory. ...19979138103
protection and therapy of experimental herpesvirus infections in mice with immunomodulating propionibacterium avidum kp-40 and/or acyclovir.protection and therapy of nmri mice with experimental herpes virus (hsv-1) encephalitis were investigated using heat-killed, lyophilized propionibacterium avidum kp-40 (pa) and/or the herpes-specific antiviral substance acyclovir (acl) as immunomodifier. poly i:c as a potent macrophage activator was used as a reference compound for pa. survival of experimental hsv-1 infections during 18 days following the inoculation of viruses was used for the evaluation of the effects of immunotherapy. the app ...19979084118
antigenic structure of soluble herpes simplex virus (hsv) glycoprotein d correlates with inhibition of hsv infection.soluble forms of herpes simplex virus (hsv) glycoprotein d (gd) block viral penetration. likewise, most hsv strains are sensitive to gd-mediated interference by cells expressing gd. the mechanism of both forms of gd-mediated inhibition is thought to be at the receptor level. we analyzed the ability of different forms of soluble, truncated gd (gdt) to inhibit infection by different strains of hsv-1 and hsv-2. strains that were resistant to gd-mediated interference were also resistant to inhibitio ...19979060653
a continuous spectrophotometric assay for aspartate transcarbamylase and atpases.a new continuous coupled uv-spectrophotometric assay is described for two phosphate-releasing enzymes, aspartate transcarbamylase and atpase of herpes simplex virus (hsv). phosphate release is coupled to the phosphorolysis of the nucleoside analog 7-methylinosine (m7ino) catalyzed by purine nucleoside phosphorylase. when this reaction is monitored at 291 nm, the coupled assay can readily detect 10 nmol pi released/min. our method offers advantages over a recently reported continuous assay devise ...19979056187
intercellular trafficking and protein delivery by a herpesvirus structural protein.we show that the hsv-1 structural protein vp22 has the remarkable property of intercellular transport, which is so efficient that following expression in a subpopulation the protein spreads to every cell in a monolayer, where it concentrates in the nucleus and binds chromatin. vp22 movement was observed both after delivery of dna by transfection or microinjection and during virus infection. moreover, we demonstrate that vp22 trafficking occurs via a nonclassical golgi-independent mechanism. sens ...19979008163
association of herpes simplex virus regulatory protein icp22 with transcriptional complexes containing eap, icp4, rna polymerase ii, and viral dna requires posttranslational modification by the u(l)13 proteinkinase.the expression of herpes simplex virus 1 gamma (late) genes requires functional alpha proteins (gamma1 genes) and the onset of viral dna synthesis (gamma2 genes). we report that late in infection after the onset of viral dna synthesis, cell nuclei exhibit defined structures which contain two viral regulatory proteins (infected cell proteins 4 and 22) required for gamma gene expression, rna polymerase ii, a host nucleolar protein (eap or l22) known to be associated with ribosomes and to bind smal ...19978995634
identification of sympathetic preganglionic neurons controlling the small intestine in hamsters using a recombinant herpes simplex virus type-1.sympathetic preganglionic neurons (spns) may be organized topographically within the spinal cord for selective control of visceral organs. we used a recombinant herpes simplex virus type-1 (rhsv-1) to identify spns innervating the small intestine in hamsters. these spns were distributed bilaterally in the cord from the fifth thoracic spinal segment to the second lumbar segment, but predominantly in thoracic segments 5-10. they had morphology similar to that of renal and adrenal spns infected wit ...19979125409
gene therapeutic strategies for neuroprotection: implications for parkinson's disease.gene transfer methodologies are being explored as strategies to restore and preserve neuronal function in parkinson's disease. this technology represents a new therapeutic modality, holding promise for continuous and localized delivery, of neuroprotective molecules. two primary approaches for gene transfer have emerged: in vivo and ex vivo. recent advances in the construction and characterization of gene transfer vectors have generated more efficient vehicles to deliver and express candidate the ...19979126153
herpes simplex virus type 1 glycoprotein k is not essential for infectious virus production in actively replicating cells but is required for efficient envelopment and translocation of infectious virions from the cytoplasm to the extracellular space.we characterized the glycoprotein k (gk)-null herpes simplex virus type 1 [hsv-1] (kos) delta gk and compared it to the gk-null virus hsv-1 f-gkbeta (l. hutchinson et al., j. virol. 69:5401-5413, 1995). delta gk and f-gkbeta mutant viruses produced small plaques on vero cell monolayers at 48 h postinfection. f-gkbeta caused extensive fusion of 143tk cells that was sensitive to melittin, a specific inhibitor of gk-induced cell fusion, while delta gk virus did not fuse 143tk cells. a recombinant p ...19979188566
dentate output channels: motor and cognitive components. 19979193166
structure-activity relationships of 2'-deoxy-2',2'-difluoro-l-erythro-pentofuranosyl nucleosides.following the recent discoveries that some l-nucleosides are more or equal potent than their d-counterparts, we synthesized 2'-deoxy-2',2'-difluoro-l-erythro-pentofuranosyl nucleosides as potential antiviral agents. the target compounds were synthesized via the key intermediates 7a or 7b from l-gulono gamma-lactone. compound 2 was oxidatively cleaved and coupled with ethyl bromodifluoroacetate in the presence of activated zinc under reformatsky conditions to obtain a diasteomeric mixture of 4(r) ...19979357530
growth hormone improves immune function and survival in burned mice infected with herpes simplex virus type 1.recombinant human growth hormone (rhgh) is often used clinically for the treatment of burned patients to promote wound healing and to improve protein metabolism. recently, the immunomodulatory activity of gh has been described, but it remains unclear whether immune abnormalities associated with burn are improved by rhgh administration. to determine the immunoregulatory activities of rhgh in thermal injury, the survival of burned mice infected with herpes simplex virus type 1 (hsv-1), along with ...19979202664
low rate shedding of hsv-1 dna, but not of infectious virus from human donor corneae into culture media.fluid samples derived from 451 organ cultured corneae were tested for the presence of hsv-1 dna after electroseparation and amplification for fragments of the glycoprotein d- and thymidine kinase-encoding genes. of the culture media, 134 were processed immediately after withdrawal (group 1); 100 were stored at ambient temperature for 6 to 60 weeks (group 2); 90 were stored at -8 degrees c for 4 to 9 weeks (group 3); and 127 were stored at -20 degrees c for 2 to 30 weeks (group 4). the degradatio ...19979210043
synthesis and cellular uptake of 2'-substituted analogues of (e)-5-(2-[125i]iodovinyl)-2'-deoxyuridine in tumor cells transduced with the herpes simplex type-1 thymidine kinase gene. evaluation as probes for monitoring gene therapy.a useful synthetic methodology was developed to synthesize and radiolabel a series of (e)-5-(2-[125i]iodovinyl)uracil nucleoside substrates for herpes simplex virus type-1 thymidine kinase (hsv-1 tk). (e)-5-(2-[125i]iodovinyl)-2'-deoxyuridine ([125i]ivdu, 10), (e)-5-(2-[125i]iodovinyl)-2'-fluoro-2'-deoxyuridine ([125i]ivfru, 11), (e)-5-(2-[125i]iodovinyl)-2'-fluoro-2'-deoxyarabinouridine ([125i]ivfau, 12), and (e)-5-(2-[125i]iodovinyl)arabinouridine ([125i]ivau, 13) were synthesized in 63-83% ra ...19979216837
active site cavity of herpesvirus proteases revealed by the crystal structure of herpes simplex virus protease/inhibitor complex.human herpes simplex virus type 1 (hsv-1) and type 2 (hsv-2) are responsible for herpes labialis (cold sores) and genital herpes, respectively. they encode a serine protease that is required for viral replication, and represent a viable target for therapeutic intervention. here, we report the crystal structures of hsv-1 and hsv-2 proteases, the latter in the presence and absence of the covalently bound transition state analog inhibitor diisopropyl phosphate (dip). the hsv-1 and hsv-2 protease st ...19979369473
glycoprotein d of herpes simplex virus (hsv) binds directly to hvem, a member of the tumor necrosis factor receptor superfamily and a mediator of hsv entry.glycoprotein d (gd) is a structural component of the herpes simplex virus (hsv) envelope which is essential for virus entry into host cells. chinese hamster ovary (cho-k1) cells are one of the few cell types which are nonpermissive for the entry of many hsv strains. however, when these cells are transformed with the gene for the herpesvirus entry mediator (hvem), the resulting cells, cho-hvem12, are permissive for many hsv strains, such as hsv-1(kos). by virtue of its four cysteine-rich pseudore ...19979223502
efficacy of a recombinant glycoprotein d subunit vaccine on the development of primary and recurrent ocular infection with herpes simplex virus type 1 in mice.the protective efficacy of a glycoprotein d subunit vaccine (gd2 sb as4) was evaluated in a mouse model of human recurrent herpetic stromal keratitis (hsk). when administered before primary infection, gd2 sb as4 protected mice against corneal pathology, mortality, and latency resulting from ocular viral challenge with herpes simplex virus type 1 (hsv-1) mckrae strain. in addition, gd2 sb as4 significantly decreased postreactivation corneal disease. a control vaccine, gd2 alum, protected against ...19979237697
[central nervous system infection due to herpes simplex virus in aids].infections of the central nervous system by herpes simplex viruses (herpes simplex type 1 and herpes simplex type 2) are uncommon in acquired immune deficiency syndrome and are often clinically and pathologically atypical. we have collected 11 cases of herpes simplex encephalomyelitis in aids patients reported in the literature. only 3 of these cases presented with a typical, necrotizing, limbic encephalitis. other clinicopathological patterns included ventriculitis, rhombencephalitis and myelit ...19979382607
us9, a stable lysine-less herpes simplex virus 1 protein, is ubiquitinated before packaging into virions and associates with proteasomes.the us9 gene of herpes simplex virus 1 encodes a virion tegument protein with a predicted mr of 10,000. earlier studies have shown that the gene is not essential for viral replication in cells in culture. we report that (i) us9 forms in denaturing polyacrylamide gels multiple overlapping bands ranging in mr from 12,000 to 25,000; (ii) the protein recovered from infected cells or purified virions reacts with anti-ubiquitin antibodies; (iii) autoradiographic images of us9 protein immunoprecipitate ...19979391137
mhc-ii but not mhc-i responses are required for vaccine-induced protection against ocular challenge with hsv-1.to determine the importance of major histocompatibility complex (mhc) class-i versus mhc class-ii immune responses in protecting naive versus vaccinated mice against an ocular hsv-1 challenge.19979395776
a new antiherpetic agent, ah-1763 iia, produced by streptomyces cyaneus strain no. 1763.a new antiherpetic agent, ah-1763 iia, was isolated from the culture broth of strain no. 1763 identified as streptomyces cyaneus. it was purified through column chromatographies of diaion hp-10 and silica gel. the structure was determined to be 11-hydroxy-5-methyl-2-(2-hydroxy-1-methylpropyl)-4h-anthraceno [1,2-b]pyran-4,7,12-trione by several spectroscopic experiments, that is a new antibiotic belonging to pluramycin-group.19979402987
use of ebv-based vector/hvj-liposome complex vector for targeted gene therapy of ebv-associated neoplasms.targeted suicide gene therapy for epstein-barr virus (ebv)-associated neoplasms was attempted by using ebv-based plasmid vectors coupled with hemagglutinating virus of japan (hvj)-liposome in vitro. expression of ebv nuclear antigen (ebna)1 is a common feature of the neoplasms associated with ebv. when various leukemic cell lines were transduced with a vector carrying a marker gene and ebv replication origin of plasmid (orip), the marker gene product was exclusively detected in cells expressing ...19979405242
spread of hsv-1 to the suprachiasmatic nuclei and retina in t cell depleted balb/c mice.following uniocular anterior chamber inoculation of the kos strain of hsv-1 in euthymic balb/c mice, virus spreads from the injected eye to the brain, and from the brain to the optic nerve and retina of the uninjected eye by day 7 post inoculation (p.i.), but the optic nerve and retina of the injected eye are not infected with virus. infection of the optic nerve and retina of the injected eye is observed only in athymic mice or in mice depleted of both cd4+ and cd8+ t cells. to determine the rol ...19979413273
epstein-barr virus nuclear protein lp stimulates ebna-2 acidic domain-mediated transcriptional activation.epstein-barr virus (ebv) nuclear proteins ebna-lp and ebna-2 are the first two proteins expressed in latent infection of primary b lymphocytes. ebna-2 is essential for lymphocyte transformation, and ebna-lp is at least critical. while ebna-2 activates specific viral and cellular promoters, ebna-lp's role has been obscure. we now show that ebna-lp stimulates ebna-2 activation of the lmp1 promoter and of the lmp1/lmp2b bidirectional transcriptional regulatory element. ebna-lp alone has only a nega ...19979261383
utilization of the herpes simplex virus type 1 latency-associated regulatory region to drive stable reporter gene expression in the nervous system.the ability of herpes simplex virus type 1 (hsv-1) to establish a lifelong, transcriptionally active, latent infection in neurons has led to much interest in developing hsv-based vectors for gene delivery to the nervous system. a prerequisite of such vectors is that they should be capable of directing long-term transgene expression in latently infected neurons. the continued transcription of hsv-1 latency-associated transcripts (lats) during neuronal latency suggests that regulatory sequences wh ...19979060683
detection of herpes simplex dna in semen and menstrual blood of individuals attending an infertility clinic.to determine a possible link between herpes simplex virus 1 (hsv) and infertility.19979094812
purification of herpes simplex virus type 1 by density gradient centrifugation and estimation of the sedimentation coefficient of the virion.purification of herpes simplex virus type 1 (hsv-1) is often performed by centrifugation in gradients of various materials. a major problem with such procedures is a gradual decrease in the infectivity of the virus, probably due to the influence of the gradient material. in the present work we have compared nycodenz gradients with ficoll gradients for hsv-1 purification. both gradient materials have low osmolarities. the purity of the preparations recovered from the two gradients was similar, as ...19979137520
a novel multiply-mutated hsv-1 strain for the treatment of human brain tumors.a promising approach for the therapeutic treatment of brain tumors utilizes replication-competent, neuroattenuated herpes simplex virus-1 (hsv-1) mutants. this approach requires mutation of hsv-1 to eliminate killing of normal, nondividing cells of the brain (e.g., neurons). we have generated a hsv-1 double-mutant, designated 3616ub, by interrupting the uracil dna glycosylase (ung) gene in a previously studied icp34.5 mutant, r3616. the hsv-1-encoded ung gene is required for efficient hsv-1 repl ...19979095405
mixed vaginal infections of balb/c mice with low virulent herpes simplex type 1 strains result in restoration of virulence properties: vaginitis/vulvitis and neuroinvasiveness.vaginal infections of balb/c ann mice with herpes simplex virus type 1 (hsv-1) were studied. mice were inoculated with virulent strains ang path and 17 syn+ or low-virulent recombinant strains 27/iii and 17-syn3 that differ from parental strains in their glycoprotein b (gb) gene sequences. when low-virulent strains were inoculated separately, no vaginitis/vulvitis was produced despite replication in the vagina. in contrast, after coinfection of mice with the two low-virulent strains, vaginitis/v ...19979138293
overexpression of a heterologous thymidine kinase delays apoptosis induced by factor deprivation and inhibitors of deoxynucleotide metabolism.perturbing deoxyribonucleoside triphosphate (dntp) metabolism with inhibitors of the de novo synthesis of dntp causes apoptosis in the interleukin-3 (il-3)-dependent pre-b cell line baf3. under these conditions apoptosis is prevented when deoxyribonucleosides for dntp synthesis are supplied in the culture medium. on the other hand, removal of il-3 from cultures of baf3 cells resulted in down-regulation of thymidine kinase activity, rapid imbalance in dntp levels, and apoptosis. in this study we ...19979099710
infection and replication of herpes simplex virus type 1 in an organotypic epithelial culture system.we have used the organotypic culture system as a model to study the initial infectious process and spread of herpes simplex virus type 1 (hsv-1) in fully stratified and differentiated human epithelial tissue. the growth kinetics of hsv-1 were determined in organotypic tissues of human epidermal or ectocervical origin. concurrently, we followed the spread of hsv-1 by immunostaining thin sections of infected organotypic tissue. after hsv-1 was applied to the top cornified epithelial layer, virus p ...19979143279
the product of orf o located within the domain of herpes simplex virus 1 genome transcribed during latent infection binds to and inhibits in vitro binding of infected cell protein 4 to its cognate dna site.the partially overlapping orf p and orf o are located within the domains of the herpes simplex virus 1 genome transcribed during latency. earlier studies have shown that orf p is repressed by infected cell protein 4 (icp4), the major viral regulatory protein, binding to its cognate site at the transcription initiation site of orf p. the orf p protein binds to p32, a component of the asf/sf2 alternate splicing factors; in cells infected with a recombinant virus in which orf p was derepressed ther ...19979294219
the virion host shutoff function of herpes simplex virus type 1 plays a role in corneal invasion and functions independently of the cell cycle.a significant restriction was demonstrated in the ability of herpes simplex virus type 1 virion host shutoff (vhs) mutant viruses to invade the corneal epithelium. viral replication and invasion was confined to the areas of the cornea which were scarified prior to infection. differences between wild-type and vhs mutant replication in corneas in vivo were 100- to 1000-fold at all timepoints postinfection. smaller but still significant growth restrictions were observed in cultured corneal cells. t ...19979143299
in vitro inactivation of herpes simplex virus by a biological response modifier, psk.herpes simplex virus (hsv) causes herpes genitalis, primary gingivostomatitis and recurrent herpes labialis. in order to elucidate in vivo mechanisms by which psk, a biological response modifier, exerts a protective effect against hsv infection, we used an in vitro system to study whether psk inactivated infectivity of hsv-type 1 (hsv-1) and hsv-type 2 (hsv-2) isolated from patients with herpes genitalis in addition to a laboratory-cultured strain of hsv type 1 (hsv-1-gc+). it was found that hsv ...19979298752
cutaneously applied acyclovir acts systemically in the treatment of herpetic infection in the hairless mouse.using the skh-1 hairless mouse (hm) we have addressed the issue as to whether topically applied acyclovir (acv) may mediate some of its antiviral actions by a systemic effect. when topically applied in a formulation consisting of polyvinyl alcohol (25% w/v):dmso:cremophor el:linoleic acid (63:16:16:5, v/v/v/v), acv penetrated hairless mouse skin in a concentration-dependent manner and dose-dependently reduced cutaneous herpes simplex virus 1 (hsv-1) kos infection. topically applied acv also effe ...19979298755
use of defective herpes-derived plasmid vectors. 19979108524
gene transfer into enteric neurons of the rat small intestine in organ culture using a replication defective recombinant herpes simplex virus type 1 (hsv1) vector, but not recombinant adenovirus vectors.we have designed a system in which to test gene transfer into gut neurons consisting of an organ culture of neonatal rat small intestine. the tissue was exposed to herpes simplex- and adenovirus-derived vectors: (1) a temperature-sensitive herpes simplex virus-1 (hsv1) vector (tsk-beta gal) containing the lacz gene encoding beta-galactosidase (beta-gal), under the transcriptional control of the hsv1 immediate-early 3 (ie3) promoter; (2) rad35, an e1-/e3- replication-deficient adenovirus expressi ...19979176519
structure of the viral tap-inhibitor icp47 induced by membrane association.herpes simplex virus type i protein icp47 (ie12) turns off antigen presentation by specifically binding to and blocking the major histocompatibility complex- (mhc-) encoded transporter associated with antigen processing (tap). due to the lack of translocated peptides inside the endoplasmic reticulum, mhc class i molecules fail to assemble and therefore mhc-peptide complexes do not reach the cell surface for immune recognition by cytotoxic t-lymphocytes. here we investigated the structure of icp4 ...19979109681
chlamydia pneumoniae, cytomegalovirus, and herpes simplex virus in atherosclerosis of the carotid artery.chlamydia pneumoniae and the herpes viruses cytomegalovirus (cmv) and herpes simplex virus type 1 (hsv-1) have been associated with human atherosclerosis in seroepidemiological and separate histopathological studies. we investigated the concurrent presence of these microorganisms in patients undergoing carotid endarterectomy.19979337182
cerebrospinal fluid viral antibodies in obsessive-compulsive disorder in an indian population.immunoglobulin g viral antibodies for herpes simplex virus type 1, varicella zoster virus, cytomegalovirus, measles, and mumps were studied in 76 subjects with obsessive-compulsive disorder and compared with a control population. there was a significantly higher titer for herpes simplex virus type 1 antibodies. sera: cerebrospinal fluid ratios were suggestive of intrathecal synthesis.19979099415
comparative analyses of the latency-associated transcript promoters from herpes simplex virus type 1 strains h129, +gc and kos-63.we have analyzed the activity of a specific portion of the latency-associated transcript (lat) promoter of three strains of herpes simplex virus type 1 (hsv-1) in neuronal and non-neuronal cell types. restriction fragments containing the lat promoter sequences and the 5'-end of the lats were isolated from hsv-1 strains h129, +gc and kos-63, sequenced and cloned into a chloramphenicol transferase (cat) plasmid vector. these vectors were separately assayed for cat production in human (sknsh) and m ...19979255939
taming the sinister side of bmt: dr. jekyll and mr. hyde. 19979256268
prophylactic efficacy of traditional herbal medicines against recurrent herpes simplex virus type 1 infection from latently infected ganglia in mice.traditional herbal medicines with anti-herpes simplex virus type 1 (hsv-1) activity in vivo were examined for their prophylactic effects on recurrent hsv-1 infection in mice. mice were intradermally infected with hsv-1 in the pinna and recurrent hsv-1 disease was induced by ultraviolet irradiation. herbal extracts arrested the progression of recurrent hsv-1 disease, reduced the incidence of severe erythema and/or vesicles in the pinna, and/or shortened the period of severe recurrent lesions comp ...19979049811
evaluation of a novel lipid prodrug for intraocular drug delivery: effect of acyclovir diphosphate dimyristoylglycerol in a rabbit model with herpes simplex virus-1 retinitis.acyclovir diphosphate dimyristoylglycerol is a lipid prodrug of acyclovir that forms liposomes and provides substantial activity against herpes simplex virus, acyclovir-resistant strains of herpes simplex virus, and human cytomegalovirus. we therefore tested this promising new drug in a rabbit model of herpes simplex retinitis.19979051844
treatment of herpes simplex gingivostomatitis with aciclovir in children: a randomised double blind placebo controlled study.to examine the efficacy of aciclovir suspension for treating herpetic gingivostomatitis in young children.19979224082
viral regulation of cd95 expression and apoptosis in t lymphocytes.t lymphocyte apoptosis has been observed in vivo in association with viral infections. one mechanism known to mediate t cell apoptosis is the cd95 (fas/apo-1) ag apoptotic pathway. cd95 is a cell surface protein that is expressed on activated t cells and is capable of relaying an intracellular apoptotic signal upon binding with cd95 ligand. cd95-dependent apoptosis has been shown to be involved in the homeostatic control of peripheral t cell numbers; however, the functional significance of the c ...19979233613
herpes simplex virus type 1 induces apoptosis in peripheral blood t lymphocytes.apoptosis in peripheral blood t lymphocytes induced by herpes simplex virus type 1 (hsv-1) was investigated by use of dna content analysis and the terminal deoxytransferase-mediated dutp nick end-labeling method. the hypodiploid fraction in the cell cycle and dna fragmentation were both increased in hsv-1-infected t lymphocytes compared with that in mock-infected t lymphocytes on stimulation with phytohemagglutinin (pha). there was no difference in the hypodiploid fraction and dna fragmentation ...19979129090
design, synthesis, and antiviral evaluation of 2-chloro-5,6-dihalo-1-beta-d-ribofuranosylbenzimidazoles as potential agents for human cytomegalovirus infections.2-chloro-5,6-difluorobenzimidazole (8) was prepared from 4,5-difluoro-2-nitroaniline (5) via successive reduction, cyclization, and diazotization reactions. 2-chloro-5,6-dibromobenzimidazole (10) was obtained by a direct bromination of 2-chlorobenzimidazole (9) with bromine-water. 2-chloro-5,6-diiodobenzimidazole (15) was synthesized by a stepwise transformation of the nitro functions of 2-chloro-5,6-dinitrobenzimidazole (11) into iodo groups via diazotization reactions. ribosylation of 8, 10, a ...19979057868
use of herpes simplex virus thymidine kinase to improve the antiviral activity of zidovudine.many antiviral drugs must be metabolized to their active form by cellular enzymes. their antiviral activity may therefore be limited by an inefficient metabolism, leading to low intracellular concentration of the active form or to the accumulation of toxic intermediate metabolites. gene transfer might be used to overcome such limitations by transducing a gene able to increase intracellular drug metabolism. to prove such a concept, we chose the well-studied paradigm of zidovudine (azt) metabolism ...19979281520
genital herpes: epidemiology and pathophysiology. update and new perspectives.genital herpes simplex virus (hsv) is a sexually transmitted disease (std) which affects millions of people worldwide and is mainly due to hsv type 2. seroprevalence rates as high as 60-90% have been reported in developing countries. in developed countries, 20% of the general population is hsv2 seropositive. recent epidemiological surveys employing type-specific antibody assays show that the prevalence of hsv-2 infections is rising at an alarming rate. also, the epidemiology is changing with an ...19979538399
expression of natural and synthetic genes encoding herpes simplex virus 1 protease in escherichia coli and purification of the protein.an attractive target for anti-herpes chemotherapy is the herpes simplex virus 1 (hsv-1) protease encoded by the ul26 gene. studies with hsv-1 strains that harbour mutations in the protease gene have demonstrated that the protease is essential for dna packaging and virus maturation. the ul26 translation product is 635 amino acids long and undergoes autoproteolytic processing between residues ala247/ser248 and ala610/ser611. the n-terminal processing product (amino acids 1-247) contains the protea ...19979288912
in vitro and in vivo effects of polyhexamethylene biguanide against herpes simplex virus infection.the differential diagnosis of acanthamoeba keratitis frequently includes herpes simplex viral keratitis. previous in vitro studies with chlorhexidine, a drug with antiacanthamoebic action, have suggested concomitant antiviral activity against herpes simplex virus. we tested another related antiacanthamoebic compound, polyhexamethylene biguanide (phmb), to determine its activity against herpes simplex virus (hsv) in vitro and herpes simplex viral keratitis in vivo.19979294689
the nucleotidylylation of herpes simplex virus 1 regulatory protein alpha22 by human casein kinase ii.the products of the alpha genes of herpes simplex virus 1, the infected cells proteins (icp) 0, 4, 22, and 27 perform regulatory functions, are nucleotidylylated, and share the signaling or recognition sequence (rr(a/t)(p/s)r) that correctly predicted the nucleotidylylation of viral proteins encoded by ul21, ul31, ul49, and ul47 genes expressed later in infection. extracts from uninfected hela cells or casein kinase ii purified from sea star nucleotidylylated the icp22 moiety of a glutathione s- ...19979312161
herpes simplex virus type 1 (hsv-1) strain hszp host shutoff gene: nucleotide sequence and comparison with hsv-1 strains differing in early shutoff of host protein synthesis.the ul41 gene of the hszp strain of herpes simplex virus type 1 (hsv-1) defective with respect to the early shutoff of host protein synthesis was sequenced and compared with the corresponding hsv-1 strain kos and 17 gene sequences. in comparison with strain 17, nine mutations (base changes) were hszp specific, five kos specific and four were common for both strains. nine mutations caused codon changes. three of these mapped to the nonconserved regions and the others to the conserved regions of t ...19979421879
gene therapy for inherited retinal degeneration. 19979422936
herpes simplex keratitis after photorefractive keratectomy. 19979427197
ascending myelitis in association with herpes simplex virus. a case report.a 50 year old man developed ascending necrotizing myelitis without any associated disease. after admission due to gait disturbance, the symptoms progressed rapidly and quickly. neurological disturbance had progressed to an incomplete paraplesia below c 4 level; incontinence and drowsiness developed. herpes simplex viral myelitis was suspected through virological tests, which showed higher specific hsv antibody values of hsv-1 igg of 640-fold in serum. myelin basic protein (mbp) in the cerebrospi ...19979436377
intracerebral recombinant hsv-1 vector does not reactivate latent hsv-1.herpes simplex virus type-1 (hsv-1) has been used for gene delivery in the nervous system for the treatment of brain tumors and other neurological diseases. in most protocols, recombinant viruses containing the gene of interest are directly injected into the brain. since many people harbor latent wild-type hsv-1 virus in sensory ganglia and other regions of the nervous system, there is a potential risk that the injected recombinant virus may reactivate the latent wild-type virus to cause severe ...19979472553
a novel method to assay herpes simplex virus neutralizing antibodies using bhkicp6lacz-5 (elvis) cells.a novel method for determining neutralizing serum antibody titers to herpes simplex virus type 2 (hsv-2) was developed based on reduction of infectivity in bhkicp6lacz-5 (elvis) cells; baby hamster kidney (bhk) cells that have been genetically engineered to contain the escherichia coli lacz gene under the control of an inducible herpes simplex virus type 1 (hsv-1) promoter. the test has a semiautomated, colorimetric readout resulting in rapid, objective readings of infectivity reduction. extent ...19979473152
plasmovirus: replication cycle of a novel nonviral/viral vector for gene transfer.we recently described a novel nonviral/viral vector for gene transfer, the plasmovirus (noguiez-hellin p, robert-le meur m, laune s, et al. c r acad sci paris, sciences de la vie. 1996;319:45-50; noguiez-hellin p, robert-le meur m, salzmann j-l, et al. proc natl acad sci usa. 1996;93:4175-4180). plasmoviruses are plasmids capable of expressing all the viral genes required for generating infectious particles and packaging a defective genome containing a transgene. transfected as plasmids, plasmov ...19979345600
acyclic nucleoside phosphonates in the chemotherapy of dna virus and retrovirus infections.the acyclic nucleoside phosphonates [hpmpc (cidofovir), pmea (adefovir) and pmpa] have proved to the effective in vitro (cell culture systems) and in vivo (animal models, clinical studies) against a wide variety of dna virus and retrovirus infections: i.e., hpmpc against herpesvirus (herpes simplex virus type 1 and 2, varicella-zoster virus, cytomegalovirus, epstein-barr virus, human herpesvirus types 6, 7, and 18), polyoma-, papilloma-, adeno-, and poxvirus (vaccinia virus, molluscum contagiosu ...19979675635
production of interferon-alpha/beta by murine dendritic cell lines stimulated by virus and bacteria.the interferon-alpha and -beta (ifn-alpha/beta) producing ability of the two murine dendritic cell (dc) lines d2sc/1 and fsdc was studied. the d2sc/1 cells produced ifn-alpha and -beta when stimulated by herpes simplex virus (hsv), sendai virus (sv) or by the bacteria escherichia coli or staphylococcus aureus cowan i. precultivating (priming) d2sc/1 cells with recombinant ifn-beta or a combination of ifn-beta and granulocyte-macrophage colony-stimulating factor increased production of ifn-alpha/ ...19979315110
alterations in catalytic activity and virus maturation produced by mutation of the conserved histidine residues of herpes simplex virus type 1 protease.mutant herpes simplex virus type 1 (hsv-1) viruses were constructed to characterize the roles of the conserved histidine residues (h61 and h148) of hsv-1 protease in the regulation of catalytic activity and virus maturation. viruses containing mutations at h61 (h61v-v711, h61y-v715, and h61a-v730) were unable to grow on vero cells. these mutant viruses could process neither pra to n0 nor icp-35cd to icp-35ef. transmission electron microscopy studies of h61a-v730-infected vero cells indicated tha ...19979343215
mutational analysis of the herpes simplex virus type 1 icp0 c3hc4 zinc ring finger reveals a requirement for icp0 in the expression of the essential alpha27 gene.the herpes simplex virus type 1 (hsv-1) immediate-early (ie) protein icp0 has been implicated in the regulation of viral gene expression and the reactivation of latent hsv-1. evidence demonstrates that icp0 is an activator of viral gene expression yet does not distinguish between a direct or indirect role in this process. to further our understanding of the function of icp0 in the context of the virus life cycle, site-directed mutagenesis of the consensus c3hc4 zinc finger domain was performed, ...19979343218
epitope mapping and functional characterization of monoclonal antibodies specific for herpes simplex virus type i dna polymerase.three monoclonal antibodies (mabs 1051a, 1051b and 1051c) were raised against a surface region (residues 597-686) of the herpes simplex virus type 1 (hsv-1) dna polymerase (hsv pol), and their epitopes were mapped. the mabs reacted serotype specifically with the native and denatured hsv pol, as shown by western blot analysis, immunoprecipitation and immunofluorescence microscopy, indicating their usefulness for biochemical studies and clinical diagnosis of hsv-1 infections, mab 1051c, displaying ...19979268769
herpes simplex virus genome replication and transcription during induced reactivation in the rabbit eye.pcr analysis of herpes simplex virus (hsv) genome replication and productive-cycle transcription was used to examine the role of the cornea in the latency-associated transcript (lat)-mediated reactivation of hsv type 1 (hsv-1) in the rabbit eye model. the reduced relative reactivation frequency of 17 delta pst (a lat- virus) compared to those of wild-type and lat+ rescuants correlated with reduced levels of viral dna and transcription in the cornea following epinephrine induction. the timing of ...19979261434
nitric oxide production induced by herpes simplex virus type 1 does not alter the course of the infection in human monocytic cells.undifferentiated u937 cells were not susceptible to herpes simplex virus type 1 (hsv-1) infection, but after differentiation with phorbol 12-myristate 13-acetate an increase in the permissivity to the virus was observed accompanied by the production of significant levels of viral particles. high levels of nitric oxide (no) were produced in differentiated u937 cells infected with hsv-1. this production was comparable to that observed after addition of the no donor glycerine trinitrate. the levels ...19979266997
infected cell protein 22 of herpes simplex virus 1 regulates the expression of virion host shutoff gene u(l)41.the u(l)41 protein of herpes simplex virus 1 (hsv-1) is packaged into virions, and in newly infected cells the protein mediates indiscriminate degradation of mrna, which causes a shutoff of protein synthesis. we report that in cells infected with mutant virus in which either alpha22/u(s)1.5 or u(l)13 had been deleted: (i) the shutoff of protein synthesis and the degradation of mrna did not take place or were greatly reduced, and consistent with these observations (ii) cells infected with mutant ...19979268153
antiviral efficacies of famciclovir, valaciclovir, and brivudin in disseminated herpes simplex virus type 1 infection in mice.the animal model of necrotic hepatitis caused by hsv-1 infection in juvenile mice was used to compare the efficacies of the oral antiherpes agents famciclovir (fcv), valaciclovir (vacv) and brivudin (bvdu). the experimental infection allows the measurement of viral replication in the liver by macroscopic lesions and the evaluation of mortality from encephalitis. mice intravenously inoculated with a highly virulent clinical hsv-1 isolate were orally treated by gavage over a period of 3 days start ...19979268766
bystander effects of different enzyme-prodrug systems for cancer gene therapy depend on different pathways for intercellular transfer of toxic metabolites, a factor that will govern clinical choice of appropriate regimes.transfer of suicide genes into tumor cells renders them sensitive to cytotoxic effects of specific prodrugs. we show here that both the herpes simplex virus thymidine kinase/ganciclovir (tk/gcv) and thymidine phophorylase/5'-deoxy-5-fluorouridine (tp/dfur) suicide gene systems can induce cell death in tumor cells. additionally in mixed cultures of cells with and without the suicide gene, death occurred in both cell types, indicative of a bystander effect. we demonstrate, in human and rodent cell ...19979358032
effect of il-4 and il-12 liposomal formulations on the induction of immune response to bovine herpesvirus type-1 glycoprotein d.activation of different t-helper (th) responses following immunisation has profound and specific influences on the development of the immune response and on the ability of a vaccine to confer protection. since cytokines are capable of influencing the stimulation of distinct t-cell responses, their encapsulation in vaccines should modulate antigen-specific immune responses. unfortunately, the use of cytokines in vivo is hampered by their rapid clearance and inactivation. one possible solution to ...19979364679
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