bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complete Sequence of a Novel Highly Divergent Simian T-Cell Lymphotropic Virus from Wild-Caught Red-Capped Mangabeys (
Cercocebus torquatus
) from Cameroon: a New Primate T-Lymphotropic Virus Type 3 Subtype
Authors: Meertens Laurent , Mahieux Renaud , Mauclère Philippe , Lewis John , Gessain Antoine 
Published: July 2002

ABSTRACT

Among 65 samples obtained from a primate rescue center located in Cameroon, two female adult red-capped mangabeys (
Cercocebus torquatus
) (CTO-602 and CTO-604), of wild-caught origin, had a peculiar human T-cell lymphotropic virus type 2 (HTLV-2)-like Western blot seroreactivity (p24, RGD21, +/-K55). Analyses of the simian T-cell lymphotropic virus type 3 (STLV-3)/CTO-604 complete proviral sequence (8,919 bp) indicated that this novel strain was highly divergent from HTLV-1 (60% nucleotide similarity), HTLV-2 (62%), or STLV-2 (62%) prototypes. It was, however, related to STLV-3/PH-969 (87%), a divergent STLV strain previously isolated from an Eritrean baboon. The STLV-3/CTO-604 sequence possesses the major open reading frames corresponding to the structural, enzymatic, and regulatory proteins. However, its long terminal repeat is shorter, with only two 21-bp repeats. Furthermore, as demonstrated by reverse transcriptase PCR, this new STLV exhibits significant differences from STLV-3/PH-969 at the mRNA splice junction position level. In all phylogenetic analyses, STLV-3/CTO-604 and STLV-3/PH-969 clustered in a highly supported single clade, indicating an evolutionary lineage independent from primate T-lymphotropic virus type 1 (PTLV-1) and PTLV-2. Nevertheless, the nucleotide divergence between STLV-3/PH-969 and STLV-3/CTO-604 is equivalent to or higher than the divergence observed between the different HTLV-1 or HTLV-2 subtypes. Thus, the STLV-3/CTO-604 strain can be considered the prototype of a second subtype in the PTLV-3 type. The presence of two related viruses in evolutionarily distantly related African monkeys species, living in two opposite ecosystems (rain forest versus desert), reinforces the possible African origin of PTLV and opens new avenues regarding the search for a possible human counterpart of these viruses in individuals exhibiting such HTLV-2-like seroreactivities.
Identification of Amino Acid Residues of gp130 Signal Transducer and gp80 α Receptor Subunit That Are Involved in Ligand Binding and Signaling by Human Herpesvirus 8-Encoded Interleukin-6
Authors: Li Hong , Nicholas John 
Published: July 2002

ABSTRACTHuman herpesvirus 8-encoded interleukin-6 (vIL-6) signals through the gp130 signal transducer but is not dependent on the IL-6 receptor α subunit (IL-6R, gp80) that is required for signaling by endogenous IL-6 proteins; however, IL-6R can enhance vIL-6 activity and can enable signaling through a gp130 variant, gp130.PM5, that is itself unable to support vIL-6 signaling. These findings suggest that the vIL-6-gp130 interactions are qualitatively different from those of human IL-6 (hIL-6) and that vIL-6 signaling may be more promiscuous than that of hIL-6 but that IL-6R may play a role in vIL-6 signaling in vivo. To examine the receptor binding requirements of vIL-6, we have undertaken mutational analyses of regions of gp130 and IL-6R potentially involved in interactions with ligand or in functional complex formation and used these variants in functional, ligand-binding, and receptor dimerization assays. The data presented identify positions within two interstrand loops of the gp130 cytokine-receptor homology domain that are important for vIL-6 signaling and vIL-6-induced receptor dimerization and show that vIL-6, like hIL-6, can form complexes with IL-6R and gp130 but that the roles of putative cytokine-binding residues of IL-6R in ligand-induced functional complex formation are qualitatively different in the case of vIL-6 and hIL-6.
Comprehensive Analysis of CD8+-T-Cell Responses against Hepatitis C Virus Reveals Multiple Unpredicted Specificities
Authors: Lauer Georg M. , Ouchi Kei , Chung Raymond T. , Nguyen Tam N. , Day Cheryl L. , Purkis Deborah R. , Reiser Markus , Kim Arthur Y. , Lucas Michaela , Klenerman Paul , Walker Bruce D. 
Published: July 2002

ABSTRACTThe hepatitis C virus (HCV)-specific CD8+-T-cell response is thought to play a critical role in HCV infection. Studies of these responses have largely relied on the analysis of a small number of previously described or predicted HCV epitopes, mostly restricted by HLA A2. In order to determine the actual breadth and magnitude of CD8+-T-cell responses in the context of diverse HLA class I alleles, we performed a comprehensive analysis of responses to all expressed HCV proteins. By using a panel of 301 overlapping peptides, we analyzed peripheral blood mononuclear cells (PBMC) from a cohort of 14 anti-HCV-positive, HLA A2-positive individuals in an enzyme-linked immunospot assay. Only four subjects had detectable HLA A2-restricted responses in PBMC, and only 3 of 19 predicted A2 epitopes were targeted, all of which were confirmed by tetramer analysis. In contrast, 9 of 14 persons showed responses with more comprehensive analyses, with many responses directed against previously unreported epitopes. These results indicate that circulating HCV-specific CD8+-T-cell responses can be detected in PBMC in the majority of infected persons and that these responses are heterogeneous with no immunodominant epitopes consistently recognized. Since responses to epitopes restricted by single HLA alleles such as HLA A2 do not predict the overall response in an individual, more comprehensive approaches, as shown here, should facilitate definition of the role of the CD8+-T-cell response in HCV infection. Moreover, the low level or absence of responses to many predicted epitopes provides a rationale for immunotherapeutic interventions to broaden cytotoxic-T-lymphocyte recognition.
Increased CCR5 Affinity and Reduced CCR5/CD4 Dependence of a Neurovirulent Primary Human Immunodeficiency Virus Type 1 Isolate
Authors: Gorry Paul R. , Taylor Joann , Holm Geoffrey H. , Mehle Andrew , Morgan Tom , Cayabyab Mark , Farzan Michael , Wang Hui , Bell Jeanne E. , Kunstman Kevin , Moore John P. , Wolinsky Steven M. , Gabuzda Dana 
Published: July 2002

ABSTRACTMost human immunodeficiency virus type 1 (HIV-1) viruses in the brain use CCR5 as the principal coreceptor for entry into a cell. However, additional phenotypic characteristics are necessary for HIV-1 neurotropism. Furthermore, neurotropic strains are not necessarily neurovirulent. To better understand the determinants of HIV-1 neurovirulence, we isolated viruses from brain tissue samples from three AIDS patients with dementia and HIV-1 encephalitis and analyzed their ability to induce syncytia in monocyte-derived macrophages (MDM) and neuronal apoptosis in primary brain cultures. Two R5X4 viruses (MACS1-br and MACS1-spln) were highly fusogenic in MDM and induced neuronal apoptosis. The R5 viruses UK1-br and MACS2-br are both neurotropic. However, only UK1-br induced high levels of fusion in MDM and neuronal apoptosis. Full-length Env clones from UK1-br required lower CCR5 and CD4 levels than Env clones from MACS2-br to function efficiently in cell-to-cell fusion and single-round infection assays. UK1-br Envs also had a greater affinity for CCR5 than MACS2-br Envs in binding assays. Relatively high levels of UK1-br and MACS2-br Envs bound to CCR5 in the absence of soluble CD4. However, these Envs could not mediate CD4-independent infection, and MACS2-br Envs were unable to mediate fusion or infection in cells expressing low levels of CD4. The UK1-br virus was more resistant than MACS2-br to inhibition by the CCR5-targeted inhibitors TAK-779 and Sch-C. UK1-br was more sensitive than MACS2-br to neutralization by monoclonal antibodies (2F5 and immunoglobulin G1b12 [IgG1b12]) and CD4-IgG2. These results predict the presence of HIV-1 variants with increased CCR5 affinity and reduced dependence on CCR5 and CD4 in the brains of some AIDS patients with central nervous system disease and suggest that R5 variants with increased CCR5 affinity may represent a pathogenic viral phenotype contributing to the neurodegenerative manifestations of AIDS.
Differential Effect of Murine Alpha/Beta Interferon Transgenes on Antagonization of Herpes Simplex Virus Type 1 Replication
Authors: Härle Peter , Cull Vanessa , Agbaga Martin-Paul , Silverman Robert , Williams Bryan R. G. , James Cassandra , Carr Daniel J. J. 
Published: July 2002

ABSTRACTAlpha/beta interferons (IFN-α/β) are potent, endogenous antiviral cytokines that suppress the replication of RNA and DNA viruses, including herpes simplex virus type 1 (HSV-1). The present study compared the efficacies of IFN-α/β transgenes, including IFN-α1, -α4, -α5, -α6, -α9, and -β, against HSV-1 infection. L929 cells transfected with the IFN-α/β transgenes produced similar levels of IFN, as measured by bioassay and enzyme-linked immunosorbent assay. In addition, transfected cells were less susceptible to HSV-1 infection than were cells transfected with a plasmid vector control. The murine IFN-β plasmid construct exhibited the greatest reduction, while the murine IFN-α5 transgene showed a modest inhibitory effect in viral titers recovered from the supernatants of transfected, infected L929 cultures. Consistent with this observation, the IFN-β transgene antagonized viral transcript levels, including infected cell protein 27, thymidine kinase, and glycoprotein B, to a greater extent than did the IFN-α transgenes at 6 to 10 h postinfection as determined by real-time PCR. Cells transfected with the IFN-α4, IFN-α9, or IFN-β transgenes showed the greatest reduction in viral protein expression relative to the other transfected cells, which was associated with increased STAT1 expression. The absence of the IFN-responsive protein kinase R (PKR) gene completely abrogated the antiviral induction by all IFN-α/β against HSV-1. In the absence of RNase L, viral yields were increased 10-fold, but the antiviral effect of IFN was either unaffected or enhanced. These results suggest that the predominant IFN-mediated, antiviral pathway during HSV-1 infection taken by IFN-α/β in L929 cells utilizes PKR.
Murine Cytomegalovirus m02 Gene Family Protects against Natural Killer Cell-Mediated Immune Surveillance
Authors: Oliveira Sofia A. , Park Se-Ho , Lee Peter , Bendelac Albert , Shenk Thomas E. 
Published: July 2002

ABSTRACT

The murine cytomegalovirus m02 gene family encodes putative type I membrane glycoproteins named m02 through m16. A subset of these genes were fused to an epitope tag and cloned into an expression vector. In transfected and murine cytomegalovirus-infected cells, m02, m04, m05, m06, m07, m09, m10, and m12 localized to cytoplasmic structures near the nucleus, whereas m08 and m13 localized to a filamentous structure surrounding the nucleus. Substitution mutants lacking the m02 gene (SM
sub
m02) or the entire m02 gene family (SM
sub
m02-16) grew like their wild-type parent in cultured cells. However, whereas SM
sub
m02 was as pathogenic as the wild-type virus, SM
sub
m02-16 was markedly less virulent. SM
sub
m02-16 produced less infectious virus in most organs compared to wild-type virus in BALB/c and C57BL/6J mice, but it replicated to wild-type levels in the organs of immunodeficient γ
c
/Rag2 mice, lacking multiple cell types including natural killer cells, and in C57BL/6J mice depleted of natural killer cells. These results argue that one or more members of the m02 gene family antagonize natural killer cell-mediated immune surveillance.
Redirecting Retroviral Tropism by Insertion of Short, Nondisruptive Peptide Ligands into Envelope
Authors: Gollan Timothy J. , Green Michael R. 
Published: July 2002

ABSTRACT
A potentially powerful approach for in vivo gene delivery is to target retrovirus to specific cells through interactions between cell surface receptors and appropriately modified viral envelope proteins. Previously, relatively large (>100 residues) protein ligands to cell surface receptors have been inserted at or near the N terminus of retroviral envelope proteins. Although viral tropism could be altered, the chimeric envelope proteins lacked full activity, and coexpression of wild-type envelope was required for production of transducing virus. Here we analyze more than 40 derivatives of ecotropic Moloney murine leukemia virus (MLV) envelope, containing insertions of short RGD-containing peptides, which are ligands for integrin receptors. In many cases pseudotyped viruses containing only the chimeric envelope protein could transduce human cells. The precise location, size, and flanking sequences of the ligand affected transduction specificity and efficiency. We conclude that retroviral tropism can be rationally reengineered by insertion of short peptide ligands and without the need to coexpress wild-type envelope.
The Crystal and Molecular Structure of Butorphanol Hydrogen Tartrate
Authors: Jegorov Alexandr , Sobotík Roman , Pakhomova Svetlana , Ondráček Jan , Novotný Jiří , Hušák Michal , Kratochvíl Bohumil 
Published: July 2002

The structure of butorphanol hydrogen tartrate {(9R,13S,14S)-(-)-17-(cyclobutylmethyl)morphinan-3,14-diol (2S,3S)-(-)-hydrogen tartrate} (C21H29NO2 .C4H6O6) was solved by direct methods and refined anisotropically to the R value of 0.029 for 2 069 observed reflections. The title morphine analogue crystallizes in the triclinic space group P1 with lattice parameters a = 7.620(1), b = 9.140(1), c = 9.591(1) Å, α = 105.48(1), β = 112.91(1), γ = 84.29(1)°, Z = 1. The butorphanol B ring possesses the 3E envelope conformation with small 3H2 distortion, C and D rings have a regular chair conformation. The intramolecular N17-H17...O2 hydrogen bond is observed in crystal structure of the title compound. The butorphanol and hydrogen tartrate molecules are joined together by means of O2-H(O2)...O7, O1-H(O1)...O7' and O3-H(O3)...O8" hydrogen bonds to form networks.
Isomorphic Co-Crystallization of Ammonium and Rubidium Bromocarnallites
Authors: Christov Christomir , Balarew Christo , Tepavitcharova Stefka 
Published: July 2002

The solubility isotherm of the system NH4Br.MgBr2.6 H2O - RbBr.MgBr2.6 H2O - H2O has been investigated at 75 °C and formation of a continuous series of mixed crystals is established. The factors determining the values of the distribution coefficients of the components between the crystalline and liquid phases are discussed.
Reactions of 2,4,4,6-Tetraaryl-4H-thiopyrans with Chlorine: An Unusual Reaction Route
Authors: Šebek Pavel , Kroulík Jiří , Sedmera Petr , Havlíček Vladimír , Kuthan Josef 
Published: July 2002

2,4,4,6-Tetraaryl-4H-thiopyrans Ia - Ig react smoothly with carbon disulfide solution of chlorine already at 0 °C yielding the corresponding 3,5-dichloro derivatives IIa - IIg. With longer reaction time and temperature raised to 20 °C, the 4H-thiopyrans Ia - Ie gave exclusively the trichloro derivatives IIIa - IIIe whereas If and Ig underwent a nonselective chlorination leading to multicomponent mixtures of products. Isolation of sulfoxides IVa and IVe from the chlorination of Ia and Ie (upon hydrolysis of the reaction mixture) allowed us to formulate the reaction mechanism for the formation of compounds type III. 1H, 13C NMR, and mass spectra of the prepared compounds are discussed in detail.
Correlates of prepubertal bone mineral density in cystic fibrosis
Authors: Haslam R H M , Borovnicar D J , Stroud D B , Strauss B J G , Bines J E 
Published: July 2002

AIMTo examine early factors in bone mineral accretion in cystic fibrosis (CF).METHODSIn 22 prepubertal children with CF and mild lung disease, the relation between total body bone mineral density (BMD) and measures of body composition, biochemistry, lung function, and physical activity was studied.RESULTSThere was a non-significant mild reduction in mean total body BMD. No relation was found between BMD and anthropometric indices, fat free soft tissue, degree of lung disease, degree of fat malabsorption, dietary energy intake, or level of physical activity. Significant impairments in physical growth were apparent in this population and were found to correlate with degree of lung disease.CONCLUSIONA CF specific factor appears unlikely to be associated with the osteopenia commonly found in CF. Careful attention to general aspects of lifestyle and nutrition is recommended to maximise bone mineral accretion in this population.
Escin/diethylammonium salicylate/heparin combination gels for the topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study
Authors: Wetzel D , Menke W , Dieter R , Smasal V , Giannetti B , Bulitta M 
Published: July 2002

Objectives:To investigate the clinical efficacy and safety of escin-containing gels in the topical treatment of blunt impact injuries.Methods:Competitors in soccer, handball, or karate competitions were enrolled within two hours of sustaining a strain, sprain, or contusion and treated three times with the trial gel within a period of eight hours. Patients were randomised to three parallel groups consisting of two active treatment gels, containing escin (1% or 2%), 5% diethylammonium salicylate, and 5000 IU heparin, or placebo gel. Tenderness produced by pressure was measured at 0 (baseline), 1, 2, 3, 4, 6, and 24 hours after enrolment (within two hours of the injury). Tenderness was defined as the amount of pressure (measured by a calibrated caliper at the centre of the injury) that first produced a pain reaction as reported by the patient.Results:A total of 158 patients were enrolled; 156 were evaluated in the intention to treat analysis. The primary efficacy variable was the area under the curve for tenderness over a six hour period. The gel preparations containing 1% and 2% escin were significantly more effective (a priori ordered hypotheses testing controlling the multiple α = 5% significance level) than placebo (p1= 0.0001 and p2= 0.0002 respectively). The treatment effects were 5.7 kp h/cm2(95% confidence interval (CI) 2.9 to 8.5) and 5.9 kilopond (kp) h/cm2(95% CI 2.9 to 8.8) between 1% escin and placebo and between 2% escin and placebo respectively. These results were supported by secondary efficacy variables. The time to reach the baseline contralateral tenderness value (resolution of pain) at the injured site was shorter in the treatment groups than in the placebo group (p<0.0001). Both active gel preparations produced more rapid pain relief than the placebo gel. No relevant differences were detected between the two active gels. The safety and tolerability of the escin-containing gels were excellent.Conclusions:Escin/diethylammonium salicylate/heparin combination gel preparations are effective and safe for the treatment of blunt impact injuries.
Mortality and cancer incidence among Swedish lumberjacks exposed to phenoxy herbicides: Table 1
Authors: Thörn Åke , Gustavsson Per , Sadigh Jonas , Westerlund-Hännestrand Brita , Hogstedt Christer 
Published: July 2002

OBJECTIVESTo determine mortality and cancer incidence relative to exposure to phenoxy herbicides.METHODSA cohort of Swedish lumberjacks of which 261 were exposed to phenoxy herbicides, and 250 were unexposed, was followed up for mortality from 1954 to 1994, and for cancer incidence from 1958 to 1992. The number of days of exposure to phenoxy herbicides was determined from pay slips. With the county population as a reference, standardised mortality ratios and cancer incidence ratios (SMR and SIR) were calculated.RESULTSMortality and cancer incidence were low with two exceptions; a small but highly exposed group of foremen showed an increased cancer incidence (SIR 274, 95% confidence interval (95% CI) 100 to 596), and over all mortality (SMR 141, 95% CI 68 to 260). Of three cases of non-Hodgkin's lymphoma, two were found among the most exposed workers.CONCLUSIONSThe results provide some support to claims of previous studies that exposure to phenoxy herbicides might be related to non-Hodgkin's lymphoma and to an increased overall cancer risk.
Associations between ambient ozone, hydrocarbons, and childhood wheezy episodes: a prospective observational study in south east London
Authors: Buchdahl Roger , Willems Charlotte Daman , Vander Margaret , Babiker Abdel 
Published: July 2002

OBJECTIVESTo explore the hypothesis that hydrocarbon species and other air pollutants which accumulate at low and high concentrations of ozone are more directly associated with childhood wheezy episodes than ozone.METHODSProspective observational study over 1 year set in the Lewisham district of south east London. The daily attendance rate of children with acute wheeze at the accident and emergency department of Lewisham Hospital was related to local measurements of ozone, hydrocarbon species, nitrogen dioxide (NO2), sulphur dioxide (SO2) and small particulate matter with diameter <10μm (PM10).RESULTSAn inverse relation was found between the air pollutants and ozone. After seasonal and meteorological adjustment a non-linear U shaped trend was found between incidence of wheeze and ozone. The trend was significant in children <2 years of age but not in older children. In the younger age group, after adjustment for season, temperature, wind speed, and respiratory infection, the incidence relative to that at the mean daily ozone concentration of 32.7 μg/m3, was estimated to increase by 65% (95% confidence interval (95% CI) 22% to 122%) at an ozone concentration of 5 μg/m3(1.5 SDs below the mean) and by 63% (95%CI −6% to 184%) at 80 μg/m3(2.5 SDs above the mean). For several hydrocarbons there were significant positive linear relations found, again in children <2 years of age but not older children. For benzene, the incidence increased by 8% (95% CI 2 to 13%) per SD (SD 2.8 μg/m3) increase in benzene concentration. A same day association between incidence and ozone was found to be the most significant but for other pollutants a lag of 2 days gave the most significant associations. No significant association was found for the non-hydrocarbon pollutants including SO2, NO2, and PM10.CONCLUSIONSA U shaped relation was found between ozone and the incidence of wheezy episodes in young children. Certain hydrocarbon pollutants accumulate in the atmosphere when ozone concentrations are low, and are associated with childhood wheezy episodes. However, the U shaped association of ozone on incidence cannot be explained by these other pollutants. The finding supports an earlier finding that incidences of wheeze are at a minimum when ozone concentrations are 30–40 μg/m3.