| the human dnaj protein, htid-1, enhances binding of a multimer of the herpes simplex virus type 1 ul9 protein to oris, an origin of viral dna replication. | we have identified cellular proteins that interact with the herpes simplex virus type 1 (hsv-1) origin-binding protein (ul9 protein) by screening a hela cell complementary dna library by using the yeast two-hybrid system. approximately 7 x 10(5) colonies were screened. five of the 48 positive clones contained cdnas that encoded the p150(glued) component of the dynactin complex, three contained cdnas for the neural f box 42-kda protein (nfb42), which is highly enriched in neural tissue, and three ... | 2002 | 11854491 |
| herpes simplex type 1 infects and establishes latency in the brain and trigeminal ganglia during primary infection of the lip in cotton rats and mice. | the majority of the human population has been infected with herpes simplex virus type 1 (hsv-1). during a typical primary episode, hsv-1 spreads from the oral pharynx to the trigeminal ganglia, where a latent hsv-1 infection is established. cold sores at the mucocutaneous junction of the lip are the typical manifestation of recurrent hsv-1. we investigated whether hsv-1 also infects the brain during the primary infection. we used hsv-1 infected balb/c mice and inbred cotton rats as models. while ... | 2002 | 11855629 |
| differential cytotoxicity and bystander effect of the rabbit cytochrome p450 4b1 enzyme gene by two different prodrugs: implications for pharmacogene therapy. | the time course of cytotoxicity induction and the bystander effect of the rabbit cytochrome p450 4b1 (cyp4b1)/4-ipomeanol (4-im) or 2-aminoanthracene (2-aa) pharmacogene therapy systems were investigated and compared with the herpes simplex virus type 1 thymidine kinase/ganciclovir (hsv-tk/gcv) system. experiments were performed in rat 9l gliosarcoma cells stably expressing cyp4b1 (9l-4b1), hsv-tk (9l-tk), or their egfp (enhanced green fluorescent protein) fusion genes. cyp4b1-mediated activatio ... | 2002 | 11857036 |
| effect of combined cytostatic cyclosporin a and cytolytic suicide gene therapy on the prevention of experimental graft-versus-host disease. | the immunosuppressive drug cyclosporin a (csa) represents the standard preventive treatment of graft-versus-host disease (gvhd), the main complication of allogeneic hematopoietic stem cell transplantation (hsct). however, its efficacy is only partial and many patients develop lethal gvhd despite csa. a strategy of genetic immunosuppression based on conditional elimination of donor t cells expressing the herpes simplex type 1 thymidine kinase (tk) suicide gene was recently developed. in this syst ... | 2002 | 11859423 |
| anti-apoptotic protein kinase of herpes simplex virus. | | 2002 | 11864810 |
| the role of donor cd4(+) t cells in the reconstitution of oral immunity by herpes simplex virus type 1 in severe combined immunodeficiency mice. | severe combined immunodeficiency (scid) mice with ill-developed peyer's patches develop neither antibodies nor protection against lethal herpes simplex virus type 1 (hsv-1) infection by oral immunization. however, scid mice carrying spleen cells from immunocompetent balb/c mice had serum anti--hsv-1 antibody; anti--hsv-1 iga antibody was detected in eye wash samples, and the mice were protected against lethal hsv-1 infection (88% survival rate). western blotting showed that antibodies in scid mi ... | 2002 | 11865391 |
| the role of hsv in the transmission and progression of hiv. | herpes simplex virus (hsv) is a common co-infection in persons infected with human immunodeficiency virus type 1 (hiv-1). chronic perianal ulceration from herpes simplex virus type 2 (hsv-2) was one of the first opportunisitc infections identified among patients with aids. subsequent research has established that the natural history of hsv-2 is altered in co-infected persons as they experience more frequent clinical and subclinical reactivation of hsv than persons infected only with hsv-2. in ad ... | 2001 | 11867018 |
| the association of herpes simplex virus and alzheimer's disease: a potential synthesis of genetic and environmental factors. | the chronic and sporadic nature of alzheimer's disease (ad), in which the majority of presenting cases are over 65 years of age, suggests that compounded injury or long-term exposure to environmental factors is involved in the aetiology, rather than inherited genetic alterations. great hope has been placed on identifying a causative infectious agent that would present the potential for therapeutic or preventative vaccines or drugs. although not the sole causative agent, herpes simplex virus type ... | 2001 | 11867022 |
| il-12 suppresses the expression of ocular immunoinflammatory lesions by effects on angiogenesis. | topical application of plasmid dna encoding il-12 to the cornea of mice prior to ocular infection with herpes simplex virus type 1 (hsv) results in diminished corneal immunoinflammatory lesions. such herpetic stromal keratitis (hsk) reactions in humans represent an important cause of blindness. the effect of il-12 pretreatment acted via inhibitory effects on corneal neovascularization rather than by inhibiting viral replication or the function of cd4(+) t cells that mediate hsk. the antiangiogen ... | 2002 | 11867684 |
| [the mechanism of bystander effect in herpes simplex virus thymidine kinase/ganciclovir-mediated gene therapy]. | to study the mechanism of bystander effect in herpes simplex virus thymidine kinase (hsv-tk)/ganciclovir (gcv)-mediated gene therapy. | 1999 | 11869559 |
| mapping of genes involved in murine herpes simplex virus keratitis: identification of genes and their modifiers. | herpes simplex keratitis (hsk) is an inflammatory response to viral infection and self antigens in the cornea and is a major cause of blindness. using two strains of mice which are susceptible (129/svev) and resistant (c57bl/6) to herpes simplex virus (hsv) strain kos, (129/svev x c57bl/6)f(2) mice were generated and examined for their disease susceptibility in terms of clinical symptoms, ocular disease, and antibody production following corneal scarification with hsv (kos). a genome-wide screen ... | 2002 | 11884574 |
| splicing inhibition at the level of spliceosome assembly in the presence of herpes simplex virus protein icp27. | herpes simplex virus (hsv) immediate-early protein icp27 is a multifunctional regulator of viral and cellular gene expression. it has previously been shown that icp27 directly or indirectly modulates several posttranscriptional processes, such as pre-mrna splicing and polyadenylation. we show here that pre-mrna splicing is inhibited in nuclear extracts prepared from cells in which icp27 has been transiently expressed. our results show that splicing inhibition in icp27 extracts is manifested at e ... | 2002 | 11886277 |
| search for physical interaction between bicp0 of bovine herpesvirus-1 and p53 tumor suppressor protein. | the immediate-early (ie) protein bicp0 of bovine herpesvirus-1 (bhv-1) may have other functions besides transactivation of viral promoters. recently, we observed that bicp0, delivered to cultured cells by a helpervirus-free amplicon system, forms spherical or doughnut-like structures in which the tumor suppressor protein p53 is sequestered. the objective was to determine whether bicp0 and p53 interact physically, we used both yeast and mammalian two-hybrid systems. as a bait plasmid, pva3 which ... | 2002 | 11888693 |
| gene transfer into human prostate adenocarcinoma cells with an adenoviral vector: hyperthermia enhances a double suicide gene expression, cytotoxicity and radiotoxicity. | we have previously developed a recombinant adenovirus containing a fusion gene of escherichia coli cytosine deaminase (cd) and herpes simplex virus type 1 thymidine kinase (hsv-1 tk) controlled by a cytomegalovirus (cmv) enhancer-promoter. this replication-incompetent adenovirus effectively transduced the cd-tk gene into human prostate adenocarcinoma du-145 or pc-3 cells. interestingly, heat shock at 41 degrees c for 4 hours elevated the level of cd-tk by approximately 5- to 20-fold at a multipl ... | 2002 | 11896443 |
| ehv-1 eicp22 protein sequences that mediate its physical interaction with the immediate-early protein are not sufficient to enhance the trans-activation activity of the ie protein. | the early 293 amino acid eicp22 protein (eicp22p) of equine herpesvirus 1 localizes within the nucleus and functions as an accessory regulatory protein (j. virol. 68 (1994) 4329). transient transfection assays indicated that although the eicp22p by itself only minimally trans-activates ehv-1 promoters, the eicp22p functions synergistically with the immediate-early protein (iep) to enhance expression of ehv-1 early genes (j. virol. 71 (1997) 1004). we previously showed that the eicp22 protein enh ... | 2002 | 11900834 |
| mechanisms of replication of alpha- and betaherpesviruses and their pathogenesis. | the diseases caused by herpes simplex virus (hsv) and human cytomegalovirus (cmv) differ and distinct differences in biological properties of these viruses can be noticed at laboratory work. despite of this, the structure of dna and the replication cycle of both viruses shows remarkably common features. analogous proteins encoded by both viruses, act at initiation of viral dna transcription, at viral dna synthesis, at nucleocapsid formation and envelopment. on other hand, considerable difference ... | 2001 | 11901707 |
| the cross-priming apc requires a rel-dependent signal to induce ctl. | induction of ova-specific ctl by cross-priming requires help from cd4 t cells, which use cd154 to signal cd40 on the apc. to further dissect the molecular pathways involved in cross-priming, we examined the role of rel, an nf-kappab family member. c-rel(-/-) mice failed to generate ova-specific ctl by cross-priming, but could induce ctl to hsv-1. using chimeric mice, rel expression was shown to be required by the apc, but not by the t cells. notably, the deficiency in rel could be overcome by tr ... | 2002 | 11907083 |
| replication fidelity of the supf gene integrated in the thymidine kinase locus of herpes simplex virus type 1. | recombinant viruses were constructed to have an escherichia coli replicon containing a mutagenesis marker, the supf gene, integrated within the thymidine kinase locus (tk) of herpes simplex virus type 1. these viruses expressed either wild-type or mutant dna polymerase (pol) and were tested in a mutagenesis assay for the fidelity of their replication of the supf gene. a mutation frequency of approximately 10(-4) was observed for wild-type strain kos-derived recombinants in their replication of t ... | 2002 | 11907200 |
| antiviral activity of ovotransferrin discloses an evolutionary strategy for the defensive activities of lactoferrin. | ovotransferrin (formerly conalbumin) is an iron-binding protein present in birds. it belongs to the transferrin family and shows about 50% sequence homology with mammalian serum transferrin and lactoferrin. this protein has been demonstrated to be capable of delivering iron to cells and of inhibiting bacterial multiplication. however, no antiviral activity has been reported for ovotransferrin, although the antiviral activity of human and bovine lactoferrins against several viruses, including hum ... | 2002 | 11908636 |
| replication-selective herpes simplex virus type 1 mutant therapy of cervical cancer is enhanced by low-dose radiation. | herpes simplex virus type 1 (hsv-1)-based oncolytic treatment is a promising therapeutic approach for malignancy. recombinant strains of hsv-1 containing mutations in the icp 34.5 protein have been shown to replicate preferentially in rapidly proliferating malignant cells, resulting in a direct cytolytic effect. we assessed the efficacy of multimutated hsv-1 strains on human cervical cancer, and then used these viruses in combination with radiation therapy, the standard treatment for cervical ca ... | 2002 | 11916486 |
| highly efficient and specific gene transfer to purkinje cells in vivo using a herpes simplex virus i amplicon. | the transduction of cerebellar neurons in vivo with herpes simplex virus 1 (hsv-1) amplicon carrying the lacz gene has been investigated after injection of the vector in the cerebellar cortex, ventricles, and inferior olive of adult rats. injection into the cerebellar cortex resulted in transduction of purkinje cells near the needle tract and injection into the ventricles yielded no transduced neurons. in contrast, high transduction efficiency was achieved by vector injection into the inferior o ... | 2002 | 11916489 |
| oligodendrocytes from human donors differ in resistance to herpes simplex virus 1 (hsv-1). | primary cultures of human oligodendrocytes (hols) were established from six different donors. differences in resistance to infection with herpes simplex virus 1 (hsv-1) were determined between the primary cultures of hol in tissue culture infective dose 50 (tcid(50)), indirect immunofluoresence (if), and serial electron microscopy (em) studies. virus production at different multiplicities of infection (mois) indicated that differences in hsv-1 replication were statistically significant and moi-d ... | 2002 | 11921206 |
| protective immunity against lethal hsv-1 challenge in mice by nucleic acid-based immunisation with herpes simplex virus type-1 genes specifying glycoproteins gb and gd. | dna-based vaccines were employed to assess protective immunity against herpes simplex virus in experimental infections of hairless (strain skh1) and balb/c mice. mice were vaccinated with plasmids containing the herpes simplex virus type-1 (hsv-1) glycoprotein b (gb) or d (gd) genes under the human cytomegalovirus immediate-early promoter control. vaccines were injected intramuscularly (i.m.) or intraperitoneally (i.p.) as purified dna alone or as formulations supplemented with different non-ion ... | 2002 | 11926742 |
| new anti-hsv therapeutics target the helicase-primase complex. | | 2002 | 11927930 |
| new helicase-primase inhibitors as drug candidates for the treatment of herpes simplex disease. | the vast majority of the world population is infected with at least one member of the human herpesvirus family. herpes simplex virus (hsv) infections are the cause of cold sores and genital herpes as well as life-threatening or sight-impairing disease mainly in immunocompromized patients, pregnant women and newborns. since the milestone development in the late 1970s of acyclovir (zovirax), a nucleosidic inhibitor of the herpes dna polymerase, no new non-nucleosidic anti-herpes drugs have been in ... | 2002 | 11927946 |
| peptide based vaccine design: synthesis and immunological characterization of branched polypeptide conjugates comprising the 276-284 immunodominant epitope of hsv-1 glycoprotein d. | the importance of the length and conjugation site of a protective epitope peptide (276salledpvg284) from glycoprotein d of herpes simplex virus in branched polypeptide conjugates has been investigated. a new set of peptides, with a single attachment site and truncated sequences, was prepared. the immunogenicity of conjugates and the specificity of antibody responses elicited were investigated in balb/c, c57/b1/6 and cba mice. it was found that the covalent coupling of the peptide comprising the ... | 2002 | 11931583 |
| rapid spread of a neurovirulent strain of hsv-1 through the cns of balb/c mice following anterior chamber inoculation. | following uniocular anterior chamber (ac) inoculation of balb/c mice with the kos strain of herpes simplex virus type 1 (hsv-1), virus spreads from the injected eye to the ipsilateral suprachiasmatic nucleus (scn) in the central nervous system (cns) to infect the optic nerve and retina of the contralateral eye, and mice develop retinitis in that eye only. in contrast, after ac inoculation of balb/c mice with the h129 strain of hsv-1, mice develop bilateral retinitis. the pathway(s) by which h129 ... | 2002 | 11935464 |
| herpesvirus (hsv-1, ebv and cmv) infections in atherosclerotic compared with non-atherosclerotic aortic tissue. | the viral nucleic acid of herpes simplex virus type 1 (hsv-1), epstein-barr virus (ebv) and cytomegalovirus (cmv) was studied by polymerase chain reaction (pcr), southern blotting and in situ hybridization (ish) in aortic tissues from 33 autopsies. in 23 cases involving persons who ranged from 23 weeks to 75 years of age at the time of death, the tissue was histologically non-atherosclerotic. of these 23, aortic tissues tested positive for hsv-1 in 13%, for ebv in 13% and for cmv in 4%. in the o ... | 2002 | 11940204 |
| parainfectious encephalomyeloradiculitis associated with herpes simplex virus 1 dna in cerebrospinal fluid. | we describe a patient with acute encephalomyeloradiculitis associated with herpes simplex virus 1 (hsv-1) dna in the cerebrospinal fluid (csf), and we also review 4 similar cases previously reported from japan. a 59-year-old man presented with acute encephalitis and urinary retention. initially, coma and csf pleocytosis improved with acyclovir treatment, but brain stem encephalitis, transverse myelitis, and lumbosacral polyradiculitis subsequently occurred. these conditions responded to corticos ... | 2002 | 11941546 |
| recurrent herpetic whitlow in an immune competent girl without vesicular lesions. | | 2002 | 11954749 |
| potent systemic antitumor activity from an oncolytic herpes simplex virus of syncytial phenotype. | conditionally replicating (oncolytic) viruses, which selectively replicate in tumor cells but not in normal cells, show great promise as antitumor agents for cancer therapy. the principal antitumor activity of these viruses derives from their replication within tumor cells, which results in cell destruction and the production of progeny virions that can spread to adjacent tumor cells. however, one potential limitation of this approach is that viral gene deletions conferring tumor selectivity als ... | 2002 | 11956088 |
| 6-[2-(phosphonomethoxy)alkoxy]pyrimidines with antiviral activity. | 6-hydroxypyrimidines substituted at positions 2 and 4 by hydrogen, methyl, amino, cyclopropylamino, dimethylamino, methylsulfanyl, or hydroxyl group afford by the reaction with diisopropyl 2-(chloroethoxy)methylphosphonate in the presence of nah, cs(2)co(3), or dbu a mixture of n(1)- and o(6)-[2-(diisopropylphosphorylmethoxy)ethyl] isomers which were converted to the free phosphonic acids by treatment with bromotrimethylsilane followed by hydrolysis. analogously, 2,4-diamino-6-hydroxypyrimidine ... | 2002 | 11960502 |
| no evidence of parvovirus b19, chlamydia pneumoniae or human herpes virus infection in temporal artery biopsies in patients with giant cell arteritis. | recent studies have suggested that infective agents may be involved in the pathogenesis of giant cell arteritis (gca), in particular chlamydia pneumoniae and parvovirus b19. we investigated temporal arteries from patients with gca for these infections as well as human herpes viruses using the polymerase chain reaction (pcr). | 2002 | 11961176 |
| immunomodulation as a treatment strategy for genital herpes: review of the evidence. | in this review, we discuss the ongoing development of a new treatment option for genital herpes (gh), the disease caused by herpes simplex virus (hsv) types i and ii. following infection, the virus establishes a latent infection in peripheral neurons, which periodically activates to cause recurrent skin lesions or asymptomatic shedding in the anogenital area. a new class of drugs, the immune response modifiers (irms), modulates the immune system against viral infection. this approach is currentl ... | 2002 | 11962724 |
| neither lat nor open reading frame p mutations increase expression of spliced or intron-containing icp0 transcripts in mouse ganglia latently infected with herpes simplex virus. | latent infections by herpes simplex virus are characterized by repression of productive-cycle gene expression. several hypotheses to explain this repression involve inhibition of expression of the immediate-early gene activator icp0 during latency. to address these hypotheses, we developed quantitative reverse transcriptase-pcr assays that detected spliced and intron-containing icp0 transcripts in mouse ganglia latently infected with wild-type virus. in these ganglia, the numbers of spliced icp0 ... | 2002 | 11967293 |
| crystallization and preliminary diffraction studies of the ectodomain of the envelope glycoprotein d from herpes simplex virus 1 alone and in complex with the ectodomain of the human receptor hvea. | gycoprotein d (gd) is a glycoprotein expressed on the surface of several human and animal alpha herpes viruses. binding of gd to cell-surface receptors has been shown to be necessary for herpes simplex virus 1 and 2 (hsv-1 and hsv-2) cell entry. the gd ectodomain consists of 316 residues and has no sequence homology to any other proteins of known structure. two fragments of the hsv-1 gd ectodomain (gd(22-260): residues 22-260 and gd(285): residues 1-285) have been crystallized in two crystal for ... | 2002 | 11976496 |
| utility of a multiplex pcr assay for detecting herpesvirus dna in clinical samples. | a multiplex pcr was designed to amplify herpes simplex virus types 1 and 2, cytomegalovirus, and varicella-zoster virus dna present in a diverse range of clinical material. the susceptibility of these viruses to in vivo inhibition by at least one antiviral drug was an important consideration in their inclusion in the multiplex detection system. an aliquot of equine herpesvirus was introduced into each specimen prior to extraction and served as an indicator of potential inhibitors of the pcr and ... | 2002 | 11980951 |
| t cell-dependent and -independent pathways to tissue destruction following herpes simplex virus-1 infection. | viral infections can trigger tissue destruction through innate and/or adaptive immune mechanisms. here we show that these pathways can be differentially activated after infection by different strains of the herpes simplex virus-1 (hsv-1) virus. infection of murine corneal tissue by hsv-1 (kos) triggers an autoreactive clone of cd4 cells that is cross-reactive with an hsv-1 epitope to initiate corneal destruction. in contrast, ocular infection by the hsv-1 (re) strain induces murine corneal destr ... | 2002 | 11981829 |
| in vitro reactivation of hiv-1 by stimulation with herpes simplex virus infection. | | 2002 | 11984449 |
| one-step pcr to distinguish b virus from related primate alphaherpesviruses. | by adding betaine to the pcr mixture, we previously established a pcr method to amplify a dna segment of the glycoprotein g gene of b virus (bv) derived from a rhesus macaque. we have found that dna of other bv strains derived from cynomolgus, pigtail, and lion-tailed macaques can also serve as the template in our pcr assay. under the same conditions no product was obtained with dna of simian agent 8 of green monkeys and herpesvirus papio 2 of baboons, or the human herpes simplex viruses types 1 ... | 2002 | 11986284 |
| genital herpes: a hidden epidemic. | | 2002 | 11989464 |
| getting tested for herpes. | | 2002 | 11989473 |
| seroprevalence of herpes simplex virus types 1 and type 2 in the frankfurt am main area, germany. | herpes simplex virus (hsv) types 1 and 2 are widespread human infectious agents that are responsible for persistent and latent infections. hsv type 2 (hsv-2) infection is usually transmitted sexually, while hsv type i (hsv-1) is commonly acquired by saliva contact during childhood. in a retrospective study, sera from more than 4,800 patients were analyzed for hsv type-specific igg antibodies. in people older than 15 years, the seroprevalence of hsv-1 showed no statistically significant discrepan ... | 2002 | 12005327 |
| alteration of ribosomal protein maps in herpes simplex virus type 1 infection. | at present, the effect of herpes simplex virus infection on the entire proteomes of infected cells is very poorly documented. following several studies performed over the past few years, the modifications of a sub-cellular fraction induced by herpes simplex virus type 1 can be documented. these studies were performed in order to characterize the virally-induced modifications of a major component of the translational apparatus, the ribosomes. the very basic nature of most of the ribosomal protein ... | 2002 | 12016002 |
| in vitro activity of polyhydroxycarboxylates against herpesviruses and hiv. | the antiviral activity of 17 polyhydroxycarboxylates derived from phenolic compounds was evaluated against herpesviruses and hiv. when present during virus adsorption several of the polymers exhibited potent activity against herpes simplex virus type 1 (hsv-1), hsv-2, thymidine kinase deficient hsv-1, human cytomegalovirus (hcmv) and hiv-1 and hiv-2 at concentrations that were not toxic to the host cells. a close correlation was found between the 50% inhibitory concentrations of the polyhydroxyc ... | 2001 | 12018678 |
| assessing the contribution of the herpes simplex virus dna polymerase to spontaneous mutations. | the thymidine kinase (tk) mutagenesis assay is often utilized to determine the frequency of herpes simplex virus (hsv) replication-mediated mutations. using this assay, clinical and laboratory hsv-2 isolates were shown to have a 10- to 80-fold higher frequency of spontaneous mutations compared to hsv-1. | 2002 | 12019036 |
| fatal infection of a pet monkey with human herpesvirus. | concerns have been raised about pet monkeys as a potential threat to humans. we report the opposite situation, a danger to pets that arises from humans. similar to herpesvirus b (cercopithecine herpesvirus 1), which endangers humans but not its host species, human herpesvirus 1 can act as a "killer virus" when crossing the species barrier to new world monkeys. | 2002 | 12023925 |
| identification of two nuclear import signals in the alpha-gene product icp22 of herpes simplex virus 1. | the herpes simplex virus 1 (hsv-1) infected cell protein 22 (icp22) is a multifunctional viral regulator that localizes in the nucleus of infected cells. icp22 is required for optimal virus replication in certain cell types and is subject to extensive posttranslational modification. to map the signals in icp22 which mediate its efficient nuclear localization, we investigated the nuclear import of fusion proteins comprising various fragments of icp22 fused to green fluorescent protein (gfp) or be ... | 2002 | 12033795 |
| serological evidence of herpesvirus infection in gibbons. | herpesviruses are not only infectious agents of worldwide distribution in humans, but have also been demonstrated in various non-human primates as well. seventy-eight gibbons were subjected to serological tests by elisa for herpes simplex virus type 1 (hsv-1), herpes simplex virus type 2 (hsv-2), epstein-barr virus (ebv) and cytomegalovirus (cmv). | 2002 | 12038968 |
| s-7 inhibition of herpes simplex virus type 1 infectivity and replication in cultured cells. | the effect of ethyl 2-methylthio-4-methyl-5-pyrimidine, carboxylate (s-7) on the infectivity and replication of herpes simplex virus type 1 in vero cells was studied. s-7, at the highest concentration lacking toxic effect on cells (40 microg/ml), produced, at various inocula, a 40% inhibition of hsv-1 infectivity with respect to the plaque formation detected in control infected cultures. this inhibitory activity was substantiated by studies on progeny production. we cannot conclude that the inhi ... | 1991 | 12041795 |
| herpes simplex virus type 2 ul14 gene product has heat shock protein (hsp)-like functions. | the hsv-2 ul14 gene encodes a 32 kda protein that is a minor component of the viral tegument. the protein relocates other viral proteins such as vp26 and ul33 protein into the nuclei of transiently coexpressing cells (yamauchi et al., 2001). we found that the protein shared some characteristics of heat shock proteins (hsps) or molecular chaperones, such as nuclear translocation upon heat shock, atp deprivation and osmotic shock. interestingly, a significant homology over a stretch of 15 amino ac ... | 2002 | 12045222 |
| in vitro selection of external guide sequences for directing rnase p-mediated inhibition of viral gene expression. | external guide sequences (egss) are small rna molecules that bind to a target mrna, form a complex resembling the structure of a trna, and render the mrna susceptible to hydrolysis by rnase p, a trna processing enzyme. an in vitro selection procedure was used to select egss that direct human rnase p to cleave the mrna encoding thymidine kinase (tk) of herpes simplex virus 1. one of the selected egss, tk17, was at least 35 times more active in directing rnase p in cleaving tk mrna in vitro than t ... | 2002 | 12050148 |
| induction of cd8 t-cell-specific systemic and mucosal immunity against herpes simplex virus with cpg-peptide complexes. | oligodeoxynucleotides (odn) containing unmethylated cpg motifs exert powerful adjuvant activity in vivo and in vitro. administered with antigen they induce a population of antigen-specific cd8+ t cells. in this study we immunized c57bl/6 mice with bioactive cpg odn combined with an immunodominant epitope derived from herpes simplex virus (hsv) glycoprotein b (amino acids 498 to 505; ssiefarl) and analyzed the magnitude and durability of the peptide-specific response. the effectiveness of the cd8 ... | 2002 | 12050369 |
| of the three tegument proteins that package mrna in herpes simplex virions, one (vp22) transports the mrna to uninfected cells for expression prior to viral infection. | an earlier report has shown that herpes simplex virus 1 virions package rna. experiments designed to reveal the identity of the virion proteins capable of binding the rna and to show whether the mrna carried in the newly infected cells was expressed showed the following: (i) (32)p-labeled riboprobe generated by in vitro transcription of the u(s)8.5 orf bound three proteins identified as the products of u(s)11, u(l)47, and u(l)49 (vp22) genes. (ii) viral rna was bound to u(l)47 or u(s)11 proteins ... | 2002 | 12060774 |
| detection and subtyping of herpes simplex virus in clinical samples by lightcycler pcr, enzyme immunoassay and cell culture. | prompt laboratory diagnosis of herpes simplex virus (hsv) infection facilitates patient management and possible initiation of antiviral therapy. in our laboratory, which receives various specimen types for detection of hsv, we use enzyme immunoassay (eia) for rapid detection and culture of this virus. the culture of hsv has traditionally been accepted as the diagnostic 'gold standard'. in this study, we compared the use of real time pcr (lightcycler) for amplification, detection and subtyping of ... | 2002 | 12069697 |
| cell surface major histocompatibility complex class ii proteins are regulated by the products of the gamma(1)34.5 and u(l)41 genes of herpes simplex virus 1. | modulation of host immune responses has emerged as a common strategy employed by herpesviruses both to establish life-long infections and to affect recovery from infection. herpes simplex virus 1 (hsv-1) blocks the major histocompatibility complex (mhc) class i antigen presentation pathway by inhibiting peptide transport into the endoplasmic reticulum. the interaction of viral gene products with the mhc class ii pathway, however, has not been thoroughly investigated, although cd4(+) t cells play ... | 2002 | 12072498 |
| amino acid substitutions in the v domain of nectin-1 (hvec) that impair entry activity for herpes simplex virus types 1 and 2 but not for pseudorabies virus or bovine herpesvirus 1. | the entry of herpes simplex virus (hsv) into cells requires the interaction of viral glycoprotein d (gd) with a cellular gd receptor to trigger the fusion of viral and cellular membranes. nectin-1, a member of the immunoglobulin superfamily, can serve as a gd receptor for hsv types 1 and 2 (hsv-1 and hsv-2, respectively) as well as for the animal herpesviruses porcine pseudorabies virus (prv) and bovine herpesvirus 1 (bhv-1). the hsv-1 gd binding domain of nectin-1 is hypothesized to overlap ami ... | 2002 | 12072525 |
| antiviral activity of plantago major extracts and related compounds in vitro. | plantago major l., a popular traditional chinese medicine, has long been used for treating various diseases varying from cold to viral hepatitis. the aim of present study was to examine the antiviral activity of aqueous extract and pure compounds of p. major. studies were conducted on a series of viruses, namely herpesviruses (hsv-1, hsv-2) and adenoviruses (adv-3, adv-8, adv-11). the antiviral activity of ec50 was defined as the concentration achieved 50% cyto-protection against virus infection ... | 2002 | 12076751 |
| analysis of herpes simplex virus entering into cells of oral origin. | the entry of herpes simplex virus (hsv) into an oral epithelial cell line, primary normal human oral keratinocytes (nhok) and gingival fibroblasts (gf) was examined. infection of these cells by hsv-1 and hsv-2 was blocked by heparin. further examination indicated that heparin reduced viral attachment but not penetration. moreover, neomycin inhibited hsv-1 infection more effectively than hsv-2 infection in gf, but not in nhok. in conclusion, our results elucidated some aspects of the hsv entry pr ... | 2002 | 12076830 |
| novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase. | drug resistance is often a limiting factor in successful chemotherapy. our laboratory has been interested in studying mechanisms of resistance to drugs that are targeted to the thymidylate biosynthesis pathway especially those that target thymidylate synthase (ts) and dihydrofolate reductase (dhfr). we have used leukemia as a model system to study resistance to methotrexate (mtx) and colorectal cancer as the model system to study 5-fluorouracil (5-fu) resistance. in leukemias, we and others have ... | 2002 | 12084458 |
| a prospective study of hormonal contraceptive use and cervical shedding of herpes simplex virus in human immunodeficiency virus type 1-seropositive women. | cross-sectional analyses have demonstrated an association between use of hormonal contraceptives and shedding of herpes simplex virus (hsv). this prospective study evaluated the effect of initiating use of hormonal contraception on cervical hsv detection. two hundred women who were seropositive for hsv-2 and human immunodeficiency virus (hiv) type 1 were examined for cervical mucosal hsv by use of quantitative dna polymerase chain reaction before and after beginning the use of hormonal contracep ... | 2002 | 12085333 |
| use of a fragment of glycoprotein g-2 produced in the baculovirus expression system for detecting herpes simplex virus type 2-specific antibodies. | fragments of glycoprotein g (gg-2(281-594his)), comprising residues 281 to 594 of herpes simplex virus type 2 (hsv-2), glycoprotein g of hsv-1 (gg-1(t26-189his)), and glycoprotein d of hsv-1 (gd-1(1-313)), were expressed in the baculovirus expression system to develop an assay for the detection of hsv-1 and hsv-2 type-specific antibodies. the expression of the gg-1(t26-189his) and gg-2(281-594his) fragments was analyzed by western blotting using monoclonal antibodies lp10 and ap1, respectively. ... | 2002 | 12089274 |
| laboratory diagnosis of central nervous system infections caused by herpesviruses. | herpesviruses may be associated with various types of central nervous system (cns) infections. herpes simplex encephalitis (hse) has to be considered one of the most severe diseases. as effective antiviral drugs are available, rapid and reliable diagnosis has become important. | 2002 | 12091081 |
| herpes consensus pcr test: a useful diagnostic approach to the screening of viral diseases of the central nervous system. | infections of the central nervous system (cns) are a difficult diagnostic problem for both clinicians and microbiologists. various clinical signs, such as encephalitis, myelitis, meningitis, may be associated with herpesviruses. the use of multiplex 'herpes consensus' polymerase chain reaction (hc-pcr) in association with nested pcr (npcr), in addition to classical techniques, made it possible to optimise the management of cerebrospinal fluid (csf) and serum samples from patients affected by the ... | 2002 | 12091084 |
| diagnosis of herpesvirus infections of the central nervous system. | human herpesviruses may cause infections of the central nervous system (cns). the early diagnosis of herpesvirus-associated neurological diseases is of high importance. | 2002 | 12091085 |
| detection of herpes simplex virus type 1 in human ciliary ganglia. | to determine whether herpes simplex virus type 1 (hsv-1) dna is present in the ciliary ganglion (cg). | 2002 | 12091423 |
| salivary defense factors in herpes simplex virus infection. | saliva may contribute to a lowering of the infectious herpes simplex virus (hsv) dose during transmission and consequently abrogate infection or lead to decreased reactivation. to test this hypothesis, we assayed saliva for innate defense factors, immunoglobulin content, and the capacity to interfere with hsv infection. serum or salivary anti-hsv igg levels did not correlate with control of recurrent labial herpes (rlh) and were significantly higher in subjects with rlh compared with asymptomati ... | 2002 | 12097435 |
| ph reduction as a trigger for dissociation of herpes simplex virus type 1 scaffolds. | assembly of the infectious herpes simplex virus type 1 virion is a complex, multistage process that begins with the production of a procapsid, which is formed by the condensation of capsid shell proteins around an internal scaffold fashioned from multiple copies of the scaffolding protein, pre-vp22a. the ability of pre-vp22a to interact with itself is an essential feature of this process. however, this self-interaction must subsequently be reversed to allow the scaffolding proteins to exit from ... | 2002 | 12097553 |
| recombinant full-length human cytomegalovirus protease has lower activity than recombinant processed protease domain in purified enzyme and cell-based assays. | herpesviruses encode a protease that is essential for virus replication. the protease undergoes cleavage to a processed form during capsid maturation. a recombinant 75 kda form of the protease from human cytomegalovirus was purified and compared with the recombinant 29 kda processed form. modification with an active site titrant suggested that most of each recombinant protease preparation was active (66 and 86%, respectively). protease activity was compared using a low-molecular weight peptide s ... | 2002 | 12103430 |
| herpes simplex virus: who should be tested? | | 2002 | 12106507 |
| debate: the argument against. should every std clinic patient be considered for type-specific serological screening for hsv? | while initially attractive, the idea that all individuals attending sexually transmitted disease or genitourinary medicine clinics should be offered type-specific screening for herpes simplex virus may be impractical, and even undesirable, for a number of reasons. these include the lack of a cost-effective and sufficiently specific and sensitive screening test, the absence of an intervention that benefits the health of the individual or reduces the risk of onward transmission and, not least, the ... | 2002 | 12106509 |
| performance and use of hsv type-specific serology test kits. | herpes simplex virus type-specific serology tests based on glycoprotein gg-1 and/or gg-2 are important diagnostic tools to establish aetiology of genital symptoms and identify patients with unrecognized genital herpes. clinicians can now select from three very different food and drug administration-licensed kits. diagnology's pockittrade mark hsv-2 is a point of care test for herpes simplex virus type 2 (hsv-2) antibodies. clinicians can perform this test while the patient waits. focus technolog ... | 2002 | 12106510 |
| debate: the argument against. should all pregnant women be offered type-specific serological screening for hsv infection? | the first goal in minimizing herpes simplex virus (hsv) mortality and morbidity in infants is to reduce the risk of acquisition of new infections during pregnancy, especially in late gestation. antenatal testing does not necessarily predict the risk of transmission to the newborn infant, since this risk is variable. in order to identify newly acquired infection in women who are hsv-seronegative, repeat testing in late pregnancy would need to be offered. in those who are hsv-seropositive, concern ... | 2002 | 12106512 |
| retrograde intrafamilial transmission of primary herpes simplex virus type 1 infection. | | 2002 | 12106627 |
| herpesviruses in brain and alzheimer's disease. | it has been established, using polymerase chain reaction (pcr), that herpes simplex virus type 1 (hsv1) is present in a high proportion of brains of elderly normal subjects and alzheimer's disease (ad) patients. it was subsequently discovered that the virus confers a strong risk of ad when in brain of carriers of the type 4 allele of the apolipoprotein e gene (apoe-epsilon4). this study has now sought, using pcr, the presence of three other herpesviruses in brain: human herpesvirus 6 (hhv6)-type ... | 2002 | 12115887 |
| herpes simplex virus infection. | herpes simplex virus (hsv) infections are among the infections most frequently encountered by humans. two types of hsv infections have been identified-hsv-1, which usually causes orolabial disease, and hsv-2, which is associated more frequently with genital and newborn infections. usually, hsv causes mild and self-limited disease of the mouth and lips or at genital sites. however, on occasion, the disease can be life-threatening. such is the case with neonatal hsv infection and hsv infections of ... | 2002 | 12118847 |
| [genital herpes: epidemiology, transmission, clinic, asymptomatic viral excretion, impact on other sexually transmitted diseases, prevention, and treatment]. | genital herpes is one of the most widespread sexually transmitted diseases in the world. hsv2 predominates (60-80 p. 100), but the prevalence of hsv1 genital herpes is rising (20-40 p. 100). erosive lesions of the genital organs due to hsv infection are a factor favoring hiv contamination and other sexually transmitted diseases. the main factor of transmission is asymptomatic viral excretion. aciclovir, valaciclovir and famciclovir are effective treatment for genital herpes (primary infection, c ... | 2002 | 12122319 |
| [signification and limitations of virology diagnostic tools in herpes facialis, herpes genitalis, herpes gestationis and in neonates at risk]. | cutaneomucous herpes is frequent in humans. laboratory confirmation of clinical diagnosis is important, as there are atypical presentations in genital herpes. | 2002 | 12122321 |
| [cutaneomucosal herpes in immunocompetent pregnant women]. | genital herpes is a common sexually transmitted disease. in pregnant women, the risk of fetal contamination is high, particularly during the per and peripartum period. certain prevention strategies have been changed with the advent of new antiviral agents and treatment protocols at the end of pregnancy remain to be evaluated. based on a review of the literature, we discuss a few of these different questions raised at the french consensus conference on the management of cutaneomucosal herpes in i ... | 2002 | 12122322 |
| [national survey of dermatologists]. | the purpose of this survey was to ascertain current management practices of french dermatologists treating immunocompetent patients with cutaneomucosal herpes (ocular herpes excluded) as a prelude to the french consensus conference on this topic. | 2002 | 12122324 |
| [national survey of gynecologists-obstetricians and general practitioners]. | the purpose of this survey was to ascertain current practices of french gynecologists-obstetricians (go) and general practitioners (gp) treating immunocompetent patients with cutaneomucosal herpes (ocular lesions excluded) as a prelude to the french consensus conference on this topic. | 2002 | 12122325 |
| [natural history of hsv1 and hsv2 infection. asymptomatic viral excretion. mother-infant transmission. indirect transmission]. | recurrent asymptomatic viral shedding accounts for most of the oral, sexual and neonatal transmissions of herpes simplex infections (hsv). in immunocompetent individuals asymptomatic shedding, as determined by culture, occurs during 2-8p.100 of days, and more for persons with hiv infection or if measured by pcr. antiviral therapy dramatically decrease but does not eliminate asymptomatic shedding. the main risk of hsv transmission to the neonate is during vaginal delivery from infected asymptomat ... | 2002 | 12122327 |
| progressive subretinal fibrosis and blindness associated with multifocal granulomatous chorioretinitis: a variant of sympathetic ophthalmia. | to report a case of bilateral progressive subretinal fibrosis and blindness with multifocal granulomatous chorioretinitis occurring after intraocular surgery. we propose that this is a variant of sympathetic ophthalmia. | 2002 | 12153806 |
| ultrastructural localization of the herpes simplex virus type 1 ul31, ul34, and us3 proteins suggests specific roles in primary envelopment and egress of nucleocapsids. | the wild-type ul31, ul34, and us3 proteins localized on nuclear membranes and perinuclear virions; the us3 protein was also on cytoplasmic membranes and extranuclear virions. the ul31 and ul34 proteins were not detected in extracellular virions. us3 deletion caused (i) virion accumulation in nuclear membrane invaginations, (ii) delayed virus production onset, and (iii) reduced peak virus titers. these data support the herpes simplex virus type 1 deenvelopment-reenvelopment model of virion egress ... | 2002 | 12163613 |
| antiviral and cytotoxic activities of some indonesian plants. | ten methanolic extracts from eight indonesian medicinal plants were phytochemically screened and evaluated for antiviral (hsv-1 and poliovirus) and cytotoxic activities on murine and human cancer lines (3ll, l1210, k562, u251, du145, mcf-7). besides melastoma malabathricum (melastomataceae), the indonesian loranthaceae species among which elytranthe tubaeflora, e. maingayi, e. globosa and scurrula ferruginea exhibited attractive antiviral and cytotoxic activities. piper aduncum (piperaceae) was ... | 2002 | 12165336 |
| pronounced cytostatic activity and bystander effect of a novel series of fluorescent tricyclic acyclovir and ganciclovir derivatives in herpes simplex virus thymidine kinase gene-transduced tumor cell lines. | a number of tricyclic acyclovir (acv) and ganciclovir (gcv) derivatives substituted with bulky lipophilic groups have been identified as potent and highly selective cytostatic agents against herpes simplex virus type 1 (hsv-1)-thymidine kinase (tk) gene-transduced human osteosarcoma and murine mammary carcinoma tumor cells. although their affinity for hsv-1 tk was inferior to that of acv or gcv, their cytostatic potency and selectivity was at least as high as observed for the parental acv and gc ... | 2002 | 12170381 |
| positron emission tomography: measurement of transgene expression. | noninvasive and repetitive imaging of transgene expression can play a pivotal role in the development of gene therapy strategies, as it offers investigators a means to determine the effectiveness of their gene transfection protocols. in the last decade, imaging of transgene expression using positron emission tomography (pet) or single-photon emission computed tomography (spect) has received considerable attention and as a result several imaging methods have now been evaluated in animals. as a ty ... | 2002 | 12183112 |
| samarangenin b from limonium sinense suppresses herpes simplex virus type 1 replication in vero cells by regulation of viral macromolecular synthesis. | inhibitory effects of ethanolic extracts from 10 chinese herbs on herpes simplex virus type 1 (hsv-1) replication were investigated. by a bioassay-guided fractionation procedure, samarangenin b (sam b) was isolated from limonium sinense; sam b significantly suppressed hsv-1 multiplication in vero cells without apparent cytotoxicity. time-of-addition experiments suggested that the inhibitory action of sam b on hsv-1 replication was not due to the blocking of virus adsorption. in an attempt to fur ... | 2002 | 12183238 |
| basal-ganglia 'projections' to the prefrontal cortex of the primate. | we used retrograde transneuronal transport of the mcintyre-b strain of herpes simplex virus type 1 to examine the extent and organization of basal-ganglia-thalamocortical projections to five regions of prefrontal cortex in the cebus monkey (cebus apella): medial and lateral area 9 (9m and 9l), dorsal and ventral area 46 (46d and 46v) and lateral area 12 (12l). all of these prefrontal areas were found to be targets of basal-ganglia output that originated in the internal segment of the globus pall ... | 2002 | 12183392 |
| [utilization of hybridization in situ and pcr in situ methods to detect latent infection by the wild strain of hsv-1 and by a mutant with reduced reactivation]. | the aim of the study was to detect the number of latently infected cells with wild type virus and with mutant with reduced reactivation. using pcr in situ method we established, that the number of cells containing genome of these viruses do not differ especially between them. the number of cells with lat expression is significantly reduced in the ganglia infected with mutant with impaired reactivation as we showed using in situ hybridization. based on the observations of other authors, that high ... | 2002 | 12185695 |
| the antiviral efficacy of the murine alpha-1 interferon transgene against ocular herpes simplex virus type 1 requires the presence of cd4(+), alpha/beta t-cell receptor-positive t lymphocytes with the capacity to produce gamma interferon. | alpha/beta interferons (ifn-alpha/betas) are known to antagonize herpes simplex virus type 1 (hsv-1) infection by directly blocking viral replication and promoting additional innate and adaptive, antiviral immune responses. to further define the relationship between the adaptive immune response and ifn-alpha/beta, the protective effect induced following the topical application of plasmid dna containing the murine ifn-alpha 1 transgene onto the corneas of wild-type and t-cell-deficient mice was e ... | 2002 | 12186922 |
| signals that dictate nuclear, nucleolar, and cytoplasmic shuttling of the gamma(1)34.5 protein of herpes simplex virus type 1. | the gamma(1)34.5 protein of herpes simplex virus type 1 (hsv-1) is required for viral neurovirulence in vivo. in infected cells, this viral protein prevents the shutoff of protein synthesis mediated by double-stranded-rna-dependent protein kinase pkr. this is accomplished by recruiting protein phosphatase 1 to dephosphorylate the alpha subunit of translation initiation factor eif-2 (eif-2 alpha). moreover, the gamma(1)34.5 protein is implicated in viral egress and interacts with proliferating ce ... | 2002 | 12186925 |
| ocular infections in patients with atopic dermatitis. | | 2002 | 12189616 |
| improvement of nonviral gene therapy by epstein-barr virus (ebv)-based plasmid vectors. | the nonviral gene transfer technologies include naked dna administration, electrical or particle-mediated transfer of naked dna, and administration of dna-synthetic macromolecule complex vectors. each method has its advantage, such as low immunogenicity, inexpensiveness, ease in handling, etc., but the common disadvantage is that the transfection efficiency has been relatively poor as far as conventional plasmid vectors are involved. to improve the nonviral gene transfer systems, epstein-barr vi ... | 2002 | 12189722 |
| serological evidence of alpha herpesvirus infection in sooty mangabeys. | contact between sooty mangabeys (sms) and a pigtailed macaque prompted the serological screening of sms for evidence of infection with b virus. serological tests detected sm antibodies that reacted with b virus polypeptides. additional testing was performed with sera from sms with no previous contact with macaques. results from these tests indicated that 56% (33/59) of the sms had antibodies that reacted with b virus and sa8. sm antibodies also reacted with herpesvirus papio 2 and to a lesser ex ... | 2002 | 12190852 |
| characterization of herpes simplex virus type 1 thymidine kinase mutants engineered for improved ganciclovir or acyclovir activity. | herpes simplex virus type 1 (hsv-1) thymidine kinase (tk) is currently the most widely used suicide agent for gene therapy of cancer. tumor cells that express hsv-1 thymidine kinase are rendered sensitive to prodrugs due to preferential phosphorylation by this enzyme. although ganciclovir (gcv) is the prodrug of choice for use with tk, this approach is limited in part by the toxicity of this prodrug. from a random mutagenesis library, seven thymidine kinase variants containing multiple amino aci ... | 2002 | 12192082 |
| identification of a herpes b virus-specific glycoprotein d immunodominant epitope recognized by natural and foreign hosts. | the mapping of linear epitopes of b virus (cercopithecine herpesvirus 1 and herpes b virus) glycoprotein d (gd) was accomplished by screening the constructed gd epitope library with serum from b virus-infected macaques. the immunodominant epitope, gd (362-370), was identified within the c-terminal region of b virus gd that was highly conserved among 19 b virus clinical isolates but was not present in either herpes simplex virus (hsv)-1 or hsv-2 gd. a substantial percentage of serum samples from ... | 2002 | 12195371 |
| phase i study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer. | adenovirus-mediated suicide gene therapy may hold promise in the treatment of human cancer. we have developed a novel approach that utilizes a lytic, replication-competent adenovirus (ad5-cd/tkrep) to deliver a cytosine deaminase/herpes simplex virus-1 thymidine kinase fusion gene to tumors. the cytosine deaminase and herpes simplex virus-1 thymidine kinase suicide genes render malignant cells sensitive to specific pharmacological agents and, importantly, sensitize them to radiation. the phase i ... | 2002 | 12208748 |
| intact microtubules support adenovirus and herpes simplex virus infections. | capsids and the enclosed dna of adenoviruses, including the species c viruses adenovirus type 2 (ad2) and ad5, and herpesviruses, such as herpes simplex virus type 1 (hsv-1), are targeted to the nuclei of epithelial, endothelial, fibroblastic, and neuronal cells. cytoplasmic transport of fluorophore-tagged ad2 and immunologically detected hsv-1 capsids required intact microtubules and the microtubule-dependent minus-end-directed motor complex dynein-dynactin. a recent study with epithelial cells ... | 2002 | 12208972 |
| large-scale comparison of experimental adjuvants with herpes simplex virus vaccine reveals a correlation of protection with igg2a and igg2b responses. | the potential of a large number of commercial and experimental adjuvant preparations to enhance the immunogenicity of an hsv-1 glycoprotein subunit vaccine was investigated. evaluation was based on toxicity, hsv-specific antibody production, and protection against lethal challenge. all adjuvants tested increased the titer of antigen specific ig levels when compared to subunit vaccine alone. however, following challenge, a broad range of protective responses were noted. statistically significant ... | 2002 | 12210434 |