bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intradermal doxorubicin reduces ganglionic reactivation of latent herpes simplex virus in mice after pretreatment with hypertonic saline
Authors: Sekizawa Tsuyoshi , Openshaw Harry , Itoyama Yasuto 
Published: April 2003

AbstractRecurrent lesions from herpes simplex virus (HSV) occur after reactivation of latent HSV in neurons of sensory ganglion, axonal transport of reactivated virus, and HSV replication on the skin. A potential treatment strategy is to inject epithelial sites of frequent recurrences with anti‐viral or cytotoxic agents that are taken up by nerve terminals and transported by axoplasmic flow to latently infected ganglionic neurons. Doxorubicin is transported by nerves and destroys the corresponding nerve cell bodies, but earlier attempts in HSV animal models required intraneural injection to eliminate HSV infection and this treatment destroyed the nerve and large portions of the ganglion. The present study used intradermal doxorubicin in latently infected mice that had been inoculated with HSV by the lip route and passively immunized at the time of inoculation. As found previously, doxorubicin injection in the lip 2 or more months after HSV inoculation did not eliminate HSV latency as evaluated by recovery of virus from trigeminal ganglionic explants. However, when hypertonic saline was injected in the same site 24 hr prior to doxorubicin, there was a 55% reduction of positive ganglionic explant cultures. Edema from the hypertonic saline may increase access of doxorubicin to nerve terminals. This technique with hypertonic saline, which has also been used to enhance virulence of HSV skin innoculation, may have general application of increasing axoplasmic transport of drugs or biologicals. Skin toxicity may preclude doxorubicin use for HSV recurrences in patients; however, the results of this study support the concept of anti‐HSV treatment via retrograde axoplasmic transport. J. Med. Virol. 70: 263–266, 2003. © 2003 Wiley‐Liss, Inc.
Evaluation of active human herpesvirus 6 infection by reverse transcription‐PCR
Authors: Yoshikawa Tetsushi , Akimoto Shiho , Nishimura Naoko , Ozaki Takao , Ihira Masaru , Ohashi Masahiro , Morooka Masashi , Suga Sadao , Asano Yoshizo , Takemoto Masaya , Nishiyama Yukihiro 
Published: April 2003

AbstractMonitoring of active human herpesvirus 6 (HHV‐6) infection is important for distinguishing between reactivation and latency of the virus. The reverse transcription polymerase chain reaction (RT‐PCR) may be a useful tool in order to distinguish active and latent HHV‐6 infection. An RT‐PCR assay detecting 4 different HHV‐6 gene transcripts was established. Samples of peripheral blood mononuclear cells (PBMCs) were collected from patients with exanthem subitum and used to evaluate the reliability of the assay. After confirming the reliability of the assay, RT‐PCR was used to determine whether HHV‐6 reactivation occurs in children with hypercytokinemia. Three gene transcripts (U31, U39, and U94) were detected in 90–100% of the PBMC samples collected from febrile period of exanthem subitum patients, from which HHV‐6 was isolated. The two gene transcripts encoding the late proteins U31 and U39, however, were not detected in samples collected during the convalescent period that contained no infectious virus. The putative latency associated gene transcript, U94, was detected in 2 (10%) of the 20 convalescent samples, and another immediate early gene transcript, U90, was also detected in 3 (15%) of the 20 convalescent samples. The frequency of HHV‐6 reactivation in patients with hypercytokinemia, suggesting monocyte/macrophage activation, was studied. Only 9 of 17 patients diagnosed with Kawasaki disease and 1 patient diagnosed with juvenile rheumatoid arthritis were positive for HHV‐6 DNA in their PBMCs samples. Neither the U31 gene nor the U94 gene transcript was detected in any of the 10 samples. An RT‐PCR assay screening for both immediate early and late genes may be useful for monitoring active HHV‐6 infection. No HHV‐6 reactivation was found in patients with hypercytokinemia using the RT‐PCR assay. J. Med. Virol. 70: 267–272, 2003. © 2003 Wiley‐Liss, Inc.
Lymphocytic choriomeningitis virus infection in a province of Spain: Analysis of sera from the general population and wild rodents
Authors: Lledó Lourdes , Gegúndez María Isabel , Saz José Vicente , Bahamontes Noemí , Beltrán María 
Published: April 2003

AbstractLymphocytic choriomeningitis virus (LCMV) is a rodent‐borne virus belonging to the family Arenaviridae, genus Arenavirus, which causes a wide spectrum of human disease. However, data on LCMV infection in Spain is scant. To investigate whether this virus causes infection in Spain, 400 serum samples from the general population (191 males, 209 females) and 100 from wild rodents were studied by immunofluorescence assay (IFA) using L‐929 cells infected with LCMV. The study was performed in the “Community of Madrid,” a region with both rural and urban areas in different ecological settings. Of the 400 human serum samples tested, antibodies against LCMV were detected in 7 (1.7%). No statistical differences in prevalence were found with respect to either age or rural or urban residence, but differences were seen with respect to sex. Nine (9%) of the rodent serum samples were positive. These results confirm the occurrence of LCMV infections in Man and rodents in Spain. J. Med. Virol. 70: 273–275, 2003. © 2003 Wiley‐Liss, Inc.
Cellular and humoral immune responses to measles in immune adults re‐immunized with measles vaccine
Authors: Wong‐Chew Rosa Maria , Beeler Judy A. , Audet Susette , Santos José Ignacio 
Published: April 2003

AbstractThe objective of this study was to characterize the kinetics of the cellular and humoral immune responses elicited by measles vaccine given to previously immune adults. The cellular and humoral immune responses to measles were measured in seven healthy adults, before vaccination and at 1, 2, 3, and 4 weeks and 3 months after vaccination, using measles‐specific T‐cell proliferation and plaque reduction neutralization assays. All study subjects had detectable measles antibodies, but only six (85%) showed protective titers, defined as >1:120, before immunization. However measles‐specific T‐cell proliferation was not detectable before vaccination in any of the subjects. The six subjects with protective titers showed a positive stimulation index (SI) of >3.0 within the first 4 weeks after vaccination, an SI of 5 at the 4th week, and an SI of 3 at 3 months after vaccination. The subject with a low antibody titer (1:99) before vaccination developed a high SI at 3 months after vaccination. This subject was the only participant whose neutralizing antibody titers increased more than 4‐fold by 3 months after vaccination. No significant increases in geometric mean titers were detected in the other six subjects during the follow‐up period. These data suggest that high measles antibody titers interfere with the humoral response in subjects who receive a booster immunization, whereas the cellular response is boosted at least transiently, after revaccination. J. Med. Virol. 70: 276–280, 2003. © 2003 Wiley‐Liss, Inc.
Seroprevalence of human metapneumovirus in Japan
Authors: Ebihara Takashi , Endo Rika , Kikuta Hideaki , Ishiguro Nobuhisa , Yoshioka Mikio , Ma Xiaoming , Kobayashi Kunihiko 
Published: April 2003

AbstractA new human pneumovirus, provisionally designated human metapneumovirus, was discovered by Dutch researchers. We examined 142 serum samples from the general population aged from 1 month to 35 years in Japan for human metapneumovirus antibody by indirect immunofluorescence assays using human metapneumovirus‐infected monkey kidney cells. The overall prevalence of human metapneumovirus infection was 72.5%. The seropositive rate was lowest in the age group of 6 months to 1 year and gradually increased with age. All of the children had been exposed to human metapneumovirus by the age of 10 years. The results show that human metapneumovirus is circulating in the Japanese population and is a ubiquitous virus acquired early in life. J. Med. Virol. 70: 281–283, 2003. © 2003 Wiley‐Liss, Inc.
Identification of a new genotype H wild‐type mumps virus strain and its molecular relatedness to other virulent and attenuated strains
Authors: Amexis Georgios , Rubin Steven , Chatterjee Nando , Carbone Kathryn , Chumakov Kostantin 
Published: April 2003

AbstractA single clinical isolate of mumps virus designated 88‐1961 was obtained from a patient hospitalized with a clinical history of upper respiratory tract infection, parotitis, severe headache, fever and lymphadenopathy. We have sequenced the full‐length genome of 88‐1961 and compared it against all available full‐length sequences of mumps virus. Based upon its nucleotide sequence of the SH gene 88‐1961 was identified as a genotype H mumps strain. The overall extent of nucleotide and amino acid differences between each individual gene and protein of 88‐1961 and the full‐length mumps samples showed that the missense to silent ratios were unevenly distributed. Upon evaluation of the consensus sequence of 88‐1961, four positions were found to be clearly heterogeneous at the nucleotide level (NP 315C/T, NP 318C/T, F 271A/C, and HN 855C/T). Sequence analysis revealed that the amino acid sequences for the NP, M, and the L protein were the most conserved, whereas the SH protein exhibited the highest variability among the compared mumps genotypes A, B, and G. No identifying molecular patterns in the non‐coding (intergenic) or coding regions of 88‐1961 were found when we compared it against relatively virulent (Urabe AM9 B, Glouc1/UK96, 87‐1004 and 87‐1005) and non‐virulent mumps strains (Jeryl Lynn and all Urabe Am9 A substrains). J. Med. Virol. 70: 284–286, 2003. © 2003 Wiley‐Liss, Inc.
Hemagglutinin‐neuraminidase sequence and phylogenetic analyses of mumps virus isolates from a vaccinated population in Singapore
Authors: Lim C.S. , Chan K.P. , Goh K.T. , Chow Vincent T.K. 
Published: April 2003

AbstractDuring 1999–2000, a sustained mumps outbreak in the highly vaccinated population in Singapore was attributed to vaccine failure associated with the Rubini vaccine strain. To explain this phenomenon, the complete nucleotide and amino acid sequences of the hemagglutinin‐neuraminidase (HN) gene of eight mumps virus isolates from patients with parotitis in Singapore were determined and compared with those of known vaccine strains. Phylogenetic trees constructed on the basis of HN nucleotide and amino acid sequences showed that the Singapore mumps virus isolates were more closely related to the Urabe strain and belonged to a different cluster from the Rubini and Jeryl‐Lynn strains. The Rubini vaccine showed only ∼93% nucleotide and ∼96% amino acid sequence similarity to Urabe and Singapore isolates. Compared with the vaccine strains, six of the eight isolates lacked the extracellular glycosylation site at residues 400–402. Other significant amino acid disparities (e.g., at residue 354) may also affect the antigenic properties of the HN protein. These findings suggest that the evolution and adaptation of the currently circulating mumps virus strains in the community has led to the emergence of genetically distinct viral strains. The low vaccine efficacy of the Rubini strain represents a major reason for the recent mumps resurgence and failure of mumps immunization in Singapore. J. Med. Virol. 70: 287–292, 2003. © 2003 Wiley‐Liss, Inc.
VP1 pseudocapsids, but not a glutathione‐S‐transferase VP1 fusion protein, prevent polyomavirus infection in a T‐cell immune deficient experimental mouse model
Authors: Vlastos Andrea , Andreasson Kalle , Tegerstedt Karin , Holländerová Dana , Heidari Shirin , Forstová Jitka , Ramqvist Torbjörn , Dalianis Tina 
Published: April 2003

AbstractThe ability to vaccinate against polyomavirus infection in a T‐cell deficient as well as a normal immune context was studied using polyomavirus major capsid protein (VP1) pseudocapsids (VP1‐ps) or a glutathione‐S‐transferase‐VP1 (GST‐VP1) fusion protein. VP1‐ps (1 or 10 μg) were administered subcutaneously, alone or together with Freund's complete and incomplete adjuvant, to CD4−/−8−/− T‐cell deficient or normal C57Bl/6 mice on four occasions. Alternatively, CD4−/−8−/− and normal mice were inoculated with either GST‐VP1 or Py‐VP1‐ps (5 μg). Following immunisation, antibody titres were tested by ELISA to VP1‐ps or GST‐VP1 or by haemagglutination inhibition (HAI). Mice were then infected with polyomavirus. Three weeks post‐infection, the mice were killed and examined for the presence of polyomavirus DNA by PCR. Viral DNA was not detected in CD4−/−8−/− mice immunised with either VP1‐ps alone or in combination with Freund's complete and incomplete adjuvant, or in any of the normal mice immunised with VP1‐ps or GST‐VP1. However, viral DNA was detected in 2/5 of the CD4−/−8−/− mice immunised with GST‐VP1 and in non‐immunised controls. Greater antibody titres were observed to VP1‐ps than to GST‐VP1 in CD4−/−8−/− mice after VP1‐ps compared to GST‐VP1 immunisation and antibody responses were better in normal than in immune‐deficient mice. Only immunisation with VP1‐ps resulted in haemagglutination inhibition. Complete protection against polyomavirus infection in the T‐cell deficient context was obtained with VP1‐ps, but not with GST‐VP1, immunisation using the present vaccination protocol. J. Med. Virol. 70: 293–300, 2003. © 2003 Wiley‐Liss, Inc.
Immune responses to the nonglycosylated ectodomain of respiratory syncytial virus attachment glycoprotein mediate pulmonary eosinophilia in inbred strains of mice with different MHC haplotypes
Authors: Hancock Gerald E. , Tebbey Paul W. , Scheuer Catherine A. , Pryharski Karin S. , Heers Kristen M. , LaPierre Natisha A. 
Published: April 2003

AbstractDevelopment of subunit vaccines against respiratory syncytial virus (RSV) for naive human infants is hindered by concerns that immunization with the fusion or attachment (G) proteins will elicit polarized Type 2 T cell responses and cause immunopotentiation upon subsequent natural infection. We investigated the regions of G protein responsible for inducing a Type 2 T cell phenotype in inbred mice of different MHC haplotype toward development of vaccines with improved safety. As demonstrated by IL‐5‐dependent pulmonary eosinophilia after challenge and serum anti‐G protein IgG1 to IgG2 ratios, highly purified native G protein sensitized all strains for a Type 2 T cell phenotype. Stimulation of G protein‐primed splenocytes with synthetic overlapping peptides indicated that the nonglycosylated ectodomain was primarily responsible. Respectively the recall responses of BALB/c (H2d), C57BL/6 (H‐2b), SJL (H‐2s), and C3H/HeJ (H‐2k) mice were directed against epitopes within peptides spanning amino acids 184–198 (pep184–198), 168–181 (pep168–181) or 171–185 (pep171–185), 176–190 (pep176–190), and 104–118 (pep104–118) or 159–173 (pep159–173). Injection of pep184–198conjugated to KLH (pep184–198‐KLH) primed H2d[BALB/c, B6.C‐H2d/bBy], but not H‐2b[C57Bl/6, C.B10‐H2b/LiMcd] mice for pulmonary eosinophilia. Sensitization with a peptide‐KLH conjugate encompassing amino acids 149–200 (pep149–200‐KLH) further confirmed that Type 2 T cell responses in BALB/c, C57BL/6 and SJL, but not C3H/HeJ mice were induced by the nonglycosylated ectodomain of G protein. These data are important for design of safe and efficacious subunit and attenuated vaccines for RSV. J. Med. Virol. 70: 301–308, 2003. © 2003 Wiley‐Liss, Inc.
Moderate local and systemic respiratory syncytial virus‐specific T‐cell responses upon mild or subclinical RSV infection
Authors: de Waal L. , Koopman L.P. , van Benten I.J. , Brandenburg A.H. , Mulder P.G.H. , de Swart R.L. , Fokkens W.J. , Neijens H.J. , Osterhaus A.D.M.E. 
Published: April 2003

AbstractRespiratory syncytial virus (RSV) infections are a major cause of severe respiratory disease in infants. It has been shown that there is an increased frequency of childhood wheezing in ex‐bronchiolitic preteen children. This was postulated to be mediated by a vigorous virus‐specific Th2 response influencing the further development of the immune system. Little is known about the possible role of the immune response to clinically mild RSV infections in this respect. We have studied the RSV‐specific cellular immune response in infants with a laboratory‐confirmed RSV upper respiratory tract infection (URTI; n = 13, mean age 12 months, range 2–22 months) in comparison with infants with non‐RSV mediated URTI (n = 9, mean age 9.3 months, range 4–18 months) or infants with severe RSV bronchiolitis (n = 11, mean age 2.3 months, range 1–6 months). RSV‐specific cytokine‐producing cells were enumerated using the ELISPOT method in peripheral blood mononuclear cells and nasal brush T‐cells, collected during the acute and convalescent phase of the infection. Mixed Th1 (IFN‐γ) and Th2 (IL‐4 and IL‐13) responses were detected in all three groups. Frequencies of RSV‐specific T‐cells were lower in both URTI groups than in the RSV bronchiolitis group, and not significantly different between the RSV URTI and the non‐RSV URTI group. The absence of vigorous virus‐specific Th2 responses upon mild RSV infection does not support the hypothesis that these infections influence the development of the immune system and that they predispose for the development of atopic disease. J. Med. Virol. 70: 309–318, 2003. © 2003 Wiley‐Liss, Inc.
Detection of rhinovirus RNA in middle turbinate of patients with common colds by in situ hybridization
Authors: Pitkäranta Anne , Puhakka Tuomo , Mäkelä Mika J. , Ruuskanen Olli , Carpen Olli , Vaheri Antti 
Published: April 2003

AbstractHuman rhinovirus 14 RNA was determined by in situ hybridization from middle turbinate biopsies in 32 patients with diagnosed common colds and in five control individuals. Twenty‐two (69%) biopsies from common colds patients but none of the five control biopsies showed reactivity for human rhinovirus 14 antisense probe. The signal was detected both in the respiratory epithelium and in mucosal inflammatory cells. In situ hybridization of the middle turbinate tissue yielded more positive results than RT‐PCR (47%) or virus culture (34%) assayed from nasopharyngeal aspirates, but no statistical significant differences were observed (P = 0.265, P = 0.425, respectively). The results indicated that in situ hybridization procedure was slightly more sensitive than PCR assays and classical culture for the detection of human rhinovirus infection of upper respiratory tract. However, in situ hybridization procedure appeared to be an interesting methodology to investigate the physiopathology of respiratory tract infection by rhinoviruses. J. Med. Virol. 70: 319–323, 2003. © 2003 Wiley‐Liss, Inc.
Distribution of human group a rotavirus VP7 and VP4 types circulating in Seoul, Korea between 1998 and 2000
Authors: Song Mi‐Ok , Kim Ki‐Jung , Chung Sang‐In , Lim Inseok , Kang Shien‐Young , An Chang‐Nam , Kim Wonyong 
Published: April 2003

AbstractThree hundred forty‐eight fecal specimens collected from young children with acute diarrhea in Seoul, Korea between January 1998 and February 2000 were examined for G and P types. Of these, 205 samples (59%) were confirmed as group A rotavirus by ELISA for the detection of VP6 antigen. Confirmed rotavirus isolates were characterized using G serotyping ELISA and RT‐PCR methodologies for G and P genotyping of the outer capsid proteins VP7 and VP4, respectively. Serotyping of the outer capsid protein, VP7, revealed G4 as the dominant circulating serotype (41%) followed by G1 (28%) and quite a high incidence of mixed infection (14%). Genotyping of the VP4 protein was carried out on 55 of the rotavirus isolates with the dominant type being P[8] (46%). Of interest were a number of unusual G and P type combinations detected in Korea for the first time, especially the P[4] genotype associated with non‐G2 serotypes. There were also a number of P[6] isolates identified including one G2P[6] isolate. J. Med. Virol. 70: 324–328, 2003. © 2003 Wiley‐Liss, Inc.
Live varicella vaccine polarizes the mucosal adjuvant action of cholera toxin or its B subunit on specific Th1‐type helper T cells with a single nasal coadministration in mice
Authors: Sasaki Keiko , Kato Michio , Takahashi Tsuyoshi , Ochi Sadayuki , Ichinose Yoshio , Shiraki Kimiyasu , Asano Yoshizo , Iwanaga Masaaki , Tsuji Takao 
Published: April 2003

AbstractThis study was undertaken to determine whether the specific Th1‐ or Th2‐cell response to varicella‐zoster virus was induced predominantly by a mucosal adjuvant, cholera toxin, in mice. A commercially available live varicella vaccine (Oka strain) and cholera toxin or its B subunit were administered simultaneously via the nasal route. Delayed‐type hypersensitivity to the Oka vaccine was induced, but the systemic neutralizing antibody response was low. The delayed‐type hypersensitivity evoked after a single administration was relatively higher than that on administration three times. When spleen cells from mice immunized once with the vaccine and cholera toxin or its B subunit were restimulated with the live vaccine in vitro, there was greater thymidine uptake and production of interleukin‐ 2 (IL‐2) than controls, but only a low level of IL‐4 production. The production of IL‐2 induced by the B subunit of cholera toxin was less than that by cholera toxin and a mutant of Escherichia coli enterotoxin on co‐immunization with the vaccine in mice. Cholera toxin and its B subunit have been reported to induce predominantly a specific Th2‐type T‐cell response to various antigens. However, the Oka vaccine is an antigen that polarizes the activation of specific Th1/Th2‐type T cells by cholera toxin or its B subunit to the Th1‐type side. Cholera toxin and its B subunit are thus useful mucosal adjuvants for inducing cellular immunity to the Oka vaccine similar to Escherichia coli enterotoxin. J. Med. Virol. 70: 329–335, 2003. © 2003 Wiley‐Liss, Inc.
Adenosine triphosphate induces proliferation of human neural stem cells: Role of calcium and p70 ribosomal protein S6 kinase
Authors: Ryu Jae K. , Choi Hyun B. , Hatori Kozo , Heisel Rochelle L. , Pelech Steven L. , McLarnon James G. , Kim Seung U. 
Published: April 2003

AbstractHuman neural stem cells (NSCs) grown in culture responded to extracellularly applied adenosine triphosphate (ATP), and the rate of proliferation increased as shown by immunocytochemical and RT‐PCR analysis. Activation of P2 purinoceptors by ATP is coupled to the release of intracellular calcium ([Ca2+]i) from thapsigargin‐sensitive intracellular stores. ATP‐induced proliferation was blocked by thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+‐ATPase. Neither EGTA, a calcium chelator, nor caffeine had any effect on ATP‐induced [Ca2+]i increases. Multiblot kinase analysis, by which activation of 24 different kinases could be determined, showed that application of ATP to NSCs predominantly activated p70 ribosomal protein S6 kinase (p70 S6 kinase). As well, rapamycin, a p70 S6 kinase inhibitor, blocked the ATP‐mediated proliferative response in NSCs. After outlining a role for p70 S6 kinase in ATP‐mediated NSC proliferation, we examined the possibility that phosphatidylinositol 3‐kinase (PI3‐kinase) acts upstream of p70 S6 kinase. The application of wortmannin, a PI3‐kinase inhibitor, decreased both ATP‐mediated p70 S6 kinase activation and NSC proliferation. From these results, we conclude that ATP application to NSCs induces release of Ca2+ from intracellular Ca2+ stores and that this increase in intracellular Ca2+ in turn promotes NSC proliferation. The increase in NSC proliferation observed following ATP application can also be mediated by PI3‐kinase‐dependent p70 S6 kinase activation. © 2003 Wiley‐Liss, Inc.