bluuebunny/crossref_metadata_2025_split huggingface dataset:
Host-Specific Involvement of the HC Protein in the Long-Distance Movement of Potyviruses
Authors: Sáenz Pilar , Salvador Beatriz , Simón-Mateo Carmen , Kasschau Kristin D. , Carrington James C. , García Juan Antonio 
Published: July 2002

ABSTRACTPlum pox virus(PPV) is a member of thePotyvirusgenus that, in nature, infects trees of thePrunusgenus. Although PPV infects systemically several species of theNicotianagenus, such asN. clevelandiiandN. benthamiana, and replicates in the inoculated leaves ofN. tabacum, it is unable to infect systemically the last host. The long-distance movement defect of PPV was corrected in transgenic tobacco plants expressing the 5"-terminal region of the genome of tobacco etch virus (TEV), a potyvirus that infects systemically tobacco. The fact that PPV was unable to move to upper noninoculated leaves in tobacco plants transformed with the same TEV transgene, but with a mutation in the HC protein (HC-Pro)-coding sequences, identifies the multifunctional HC-Pro as the complementing factor, and strongly suggests that a defect in an HC-Pro activity is responsible for the long-distance movement defect of PPV in tobacco. Whereas PPV HC-Pro strongly intensifies the symptoms caused by potato virus X (PVX) in the PPV systemic hostsN. clevelandiiandN. benthamiana, it has no apparent effect on PVX pathogenicity in tobacco, supporting the hypothesis that long-distance movement and pathogenicity enhancement are related activities of the potyviral HC proteins. The movement defect of PPV in tobacco could also be complemented by cucumber mosaic virus in a mixed infection, demonstrating that at least some components of the long-distance machinery of the potyviruses are not strictly virus specific. A general conclusion of this work is that the HC-Pro might be a relevant factor for controlling the host range of the potyviruses.
Human Cytomegalovirus Major Immediate-Early Proteins and Simian Virus 40 Large T Antigen Can Inhibit Apoptosis through Activation of the Phosphatidylinositide 3′-OH Kinase Pathway and the Cellular Kinase Akt
Authors: Yu Yongjun , Alwine James C. 
Published: July 2002

ABSTRACTThe temperature-sensitive cell linets13 is mutated in CCG1, the gene encoding TAFII250, the largest of the TATA-binding protein-associated factors (TAFs) in TFIID. At the nonpermissive temperature, the temperature-sensitive phenotypes are (i) transcription defects, (ii) cell cycle arrest in G1, and (iii) apoptosis. We previously demonstrated that the human cytomegalovirus (HCMV) major immediate-early proteins (MIEPs) can rescue the transcription defects and inhibit apoptosis at the nonpermissive temperature. In the work presented, we show that activation of the cellular kinase Akt alone can inhibit apoptosis ints13 cells grown at the nonpermissive temperature. More significantly, we show that the HCMV MIEPs can activate Akt, resulting in the inhibition of apoptosis. In parallel experiments, we found that simian virus 40 (SV40) large T antigen can mediate the same function. These experiments were done by transfecting the HCMV major immediate-early gene or a cDNA encoding T antigen intots13 cells, and thus neither viral attachment to receptors, viral tegument proteins, nor any other viral protein is required for Akt activation. Akt is activated by the phosphatidylinositide 3′-OH (PI3) kinase pathway. Using a specific inhibitor of PI3 kinase, we show that the ability of the MIEPs and T antigen to activate Akt and inhibit apoptosis is eliminated, suggesting that the viral proteins utilize the PI3 kinase pathway for Akt activation. Transfection of plasmids which express the individual 86-kDa (IEP86; IE2579aa) and 72-kDa (IEP72; IE1491aa) MIEPs indicate that each MIEP could inhibit apoptosis via activation of the PI3 kinase pathway.
Role of N-Linked Glycans in a Human Immunodeficiency Virus Envelope Glycoprotein: Effects on Protein Function and the Neutralizing Antibody Response
Authors: Quiñones-Kochs Miriam I. , Buonocore Linda , Rose John K. 
Published: July 2002

ABSTRACTThe envelope (Env) glycoprotein of human immunodeficiency virus (HIV) contains 24 N-glycosylation sites covering much of the protein surface. It has been proposed that one role of these carbohydrates is to form a shield that protects the virus from immune recognition. Strong evidence for such a role for glycosylation has been reported for simian immunodeficiency virus (SIV) mutants lacking glycans in the V1 region of Env (J. N. Reitter, R. E. Means, and R. C. Desrosiers, Nat. Med. 4:679-684, 1998). Here we used recombinant vesicular stomatitis viruses (VSVs) expressing HIV Env glycosylation mutants to determine if removal of carbohydrates in the V1 and V2 domains affected protein function and the generation of neutralizing antibodies in mice. Mutations that eliminated one to six of the sites for N-linked glycosylation in the V1 and V2 loops were introduced into a gene encoding the HIV type 1 primary isolate 89.6 envelope glycoprotein with its cytoplasmic domain replaced by that of the VSV G glycoprotein. The membrane fusion activities of the mutant proteins were studied in a syncytium induction assay. The transport and processing of the mutant proteins were studied with recombinant VSVs expressing mutant Env G proteins. We found that HIV Env V1 and V2 glycosylation mutants were no better than wild-type envelope at inducing antibodies neutralizing wild-type Env, although an Env mutant lacking glycans appeared somewhat more sensitive to neutralization by antibodies raised to mutant or wild-type Env. These results indicate significant differences between SIV and HIV with regard to the roles of glycans in the V1 and V2 domains.
Immunodominance in Virus-Induced CD8+T-Cell Responses Is Dramatically Modified by DNA Immunization and Is Regulated by Gamma Interferon
Authors: Rodriguez Fernando , Harkins Stephanie , Slifka Mark K. , Whitton J. Lindsay 
Published: July 2002

ABSTRACTThe phenomenon whereby the host immune system responds to only a few of the many possible epitopes in a foreign protein is termed immunodominance. Immunodominance occurs not only during microbial infection but also following vaccination, and clarification of the underlying mechanism may permit the rational design of vaccines which can circumvent immunodominance, thereby inducing responses to all epitopes, dominant and subdominant. Here, we show that immunodominance affects DNA vaccines and that the effects can be avoided by the simple expedient of epitope separation. DNA vaccines encoding isolated dominant and subdominant epitopes induce equivalent responses, confirming a previous demonstration that coexpression of dominant and subdominant epitopes on the same antigen-presenting cell (APC) is central to immunodominance. We conclude that multiepitope DNA vaccines should comprise a cocktail of plasmids, each with its own epitope, to allow maximal epitope dispersal among APCs. In addition, we demonstrate that subdominant responses are actively suppressed by dominant CD8+T-cell responses and that gamma interferon (IFN-γ) is required for this suppression. Furthermore, priming of CD8+T cells to a single dominant epitope results in strong suppression of responses to other normally dominant epitopes in immunocompetent mice, in effect rendering these epitopes subdominant; however, responses to these epitopes are increased 6- to 20-fold in mice lacking IFN-γ. We suggest that, in agreement with our previous observations, IFN-γ secretion by CD8+T cells is highly localized, and we propose that its immunosuppressive effect is focused on the APC with which the dominant CD8+T cell is in contact.
The Crystal and Molecular Structure of sym-fac-(1,4,7-Triazaheptane)-(S)-aspartatocobalt(III) Diperchlorate Dihydrate
Authors: Ondráček Jan , Ondráčková Jana , Maixner Jaroslav , Jursík František 
Published: July 2002

The crystal and molecular structure of s-fac-[Co((S)-Asp)(dien)]ClO4 . HClO4 .2 H2O (dien = 1,4,7-triazaheptane) was solved by the heavy atom method. The position parameters of the non-hydrogen atoms and their anisotropic temperature parameters were refined based on 1 726 observed reflections with a final value of R = 0.073. The substance crystallizes in the orthorhombic system in the space group P212121, Z = 4, a = 8.506(1), b = 17.171(2), c = 13.277(1) Å. The structure involves hydrogen bonds between the O2, O4 and HN2 atoms of aspartic acid and the two molecules of water. The five-membered dien chelate rings take the asymmetric envelope conformations. The five-membered ring of (S)-aspartic acid possesses the symmetric envelope conformation whereas the six-membered ring exhibits the skew boat conformation.
Syntheses and Crystal Structures of Dichlorobis[tetramethyl(phenyl)cyclopentadienyl]titanium(IV) and Chlorobis[tetramethyl(phenyl)cyclopentadienyl]titanium(III)
Authors: Horáček Michal , Polášek Miroslav , Kupfer Volkmar , Thewalt Ulf , Mach Karel 
Published: July 2002

Dichlorobis[η5-tetramethyl(phenyl)cyclopentadienyl]titanium(IV) (1) and chlorobis[η5-tetramethyl- (phenyl)cyclopentadienyl]titanium(III) (2) were prepared by the generally known procedures. The X-ray crystal structures of 1 and 2 showed nearly identical Ti-CE (CE - centroid of the cyclopentadienyl ring) and Ti-Cl distances, the CE-Ti-CE angles and dihedral angles between least-squares planes of the cyclopentadienyl rings to those in [(C5Me5)2TiCl2] and [(C5Me5)2TiCl], respectively. ESR spectra of 2 in 2-methyltetrahydrofuran (MTHF) solutions and glasses revealed that 2 coordinates MTHF to give [(C5Me4Ph)2Ti(Cl)(MTHF)] (2a). The formation of 2a in MTHF solution is completed by lowering temperature to 205 K. A comparison with the known data gives the following order of affinity of [(C5Me4R)2TiCl] towards MTHF: Ph > SiMe3 > H > Me.
Immune function in female elite rowers and non-athletes
Authors: Nieman David C , Nehlsen-Cannarella Sandra L , Fagoaga Omar R , Henson Dru A , Shannon Michael , Hjertman Jannica M E , Schmitt Robert L , Bolton Marc R , Austin Melanie D , Schilling Brian K , Thorpe Richard 
Published: July 2002

Objective—To compare immune function in female rowers and controls in the resting state, and then correlate the results with a two month history of upper respiratory tract infection (URTI).Methods—Subjects included 20 elite female rowers located at the ARCO Olympic Training Centre in Chula Vista, California, and 19 non-athletic female controls. These two groups were compared cross sectionally for immune function and infection rates.Results—Granulocyte/monocyte phagocytosis, oxidative burst activity, and plasma cytokine concentrations (interleukin-6, tumour necrosis factor-α, and interleukin-1 receptor antagonist) did not differ significantly between groups. Phytohaemagglutinin induced lymphocyte proliferative response (adjusted whole blood method) was significantly higher (31% and 36% for optimal and suboptimal concentrations respectively) in rowers than in controls. Natural killer cell activity was substantially higher (1.6-fold for total lytic units) in the female rowers than in controls. Two month health logs disclosed 5.2 (1.2) and 3.3 (1.1) days with URTI symptoms for the rowers and controls respectively (p = 0.268). For all 39 subjects combined, and for the 20 rowers separately, none of the immune parameters correlated significantly with number of days with URTI symptoms.Conclusions—In this cross sectional comparison of elite female rowers and non-athletes, a group difference was found for natural killer cell activity and phytohaemagglutinin induced proliferative response (whole blood technique), but not other measures of immune function. The number of days with URTI symptoms during the spring season did not differ between groups, and variations in blood measures of immunity were unrelated to URTI.
Effects of endurance training on the isocapnic buffering and hypocapnic hyperventilation phases in professional cyclists
Authors: Chicharro José L , Hoyos Jesús , Lucía Alejandro 
Published: July 2002

Objectives—To evaluate the changes produced in both the isocapnic buffering and hypocapnic hyperventilation (HHV) phases of professional cyclists (n = 11) in response to endurance training, and to compare the results with those of amateur cyclists (n = 11).Methods—Each professional cyclist performed three laboratory exercise tests to exhaustion during the active rest (autumn: November), precompetition (winter: January), and competition (spring: May) periods of the sports season. Amateur cyclists only performed one exercise test during the competition period. The isocapnic buffering and HHV ranges were calculated during each test and defined as Vo2and power output (W).Results—No significant differences were found in the isocapnic buffering range in each of the periods of the sports season in professional cyclists. In contrast, there was a significant reduction in the HHV range (expressed in W) during both the competition (p<0.01) and precompetition(p<0.05) periods compared with the rest period. On the other hand, a longer HHV range (p<0.01) was observed in amateur cyclists than in professional cyclists (whether this was expressed in terms of Vo2or W).Conclusions—No change is observed in the isocapnic buffering range of professional cyclists throughout a sports season despite a considerable increase in training loads and a significant reduction in HHV range expressed in terms of power output.
The association football medical research programme: an audit of injuries in professional football
Authors: Hawkins R D , Hulse M A , Wilkinson C , Hodson A , Gibson M 
Published: July 2002

Objectives—To undertake a prospective epidemiological study of the injuries sustained in English professional football over two competitive seasons.Methods—Player injuries were annotated by club medical staff at 91 professional football clubs. A specific injury audit questionnaire was used together with a weekly form that documented each club's current injury status.Results—A total of 6030 injuries were reported over the two seasons with an average of 1.3 injuries per player per season. The mean (SD) number of days absent for each injury was 24.2 (40.2), with 78% of the injuries leading to a minimum of one competitive match being missed. The injury incidence varied throughout the season, with training injuries peaking during July (p<0.05) and match injuries peaking during August (p<0.05). Competition injuries represented 63% of those reported, significantly (p<0.01) more of these injuries occurring towards the end of both halves. Strains (37%) and sprains (19%) were the major injury types, the lower extremity being the site of 87% of the injuries reported. Most injury mechanisms were classified as being non-contact (58%). Re-injuries accounted for 7% of all injuries, 66% of these being classified as either a strain or a sprain. The severity of re-injuries was greater than the initial injury (p<0.01).Conclusions—Professional football players are exposed to a high risk of injury and there is a need to investigate ways of reducing this risk. Areas that warrant attention include the training programmes implemented by clubs during various stages of the season, the factors contributing to the pattern of injuries during matches with respect to time, and the rehabilitation protocols employed by clubs.
Utilisation of erythrocyte 6-thioguanine metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel disease
Authors: Cuffari C , Hunt S , Bayless T 
Published: July 2002

BACKGROUND AND AIMThe immunosuppressive properties of 6-mercaptopurine and its parent compound azathioprine are mediated by their intracellular metabolism into active 6-thioguanine (6-TG) metabolites. Measurement of erythrocyte 6-TG metabolite levels has been proposed as a useful clinical tool for assessing treatment efficacy in patients with inflammatory bowel disease (IBD).AIMThe purpose of the study was to establish a therapeutic index of treatment efficacy based on measurement of erythrocyte 6-TG metabolite levels, and apply it clinically to guide therapy.METHODSHeparinised blood was obtained from 82 adult patients with IBD on long term (more than three months) antimetabolite therapy (63 Crohn's disease; 19 ulcerative colitis). Erythrocyte 6-TG metabolite levels were measured using reverse phase high performance chromatography, and correlated with treatment efficacy. In 22 patients with refractory Crohn's disease despite long term azathioprine therapy, their dosage was increased by 25 mg/day at eight week intervals as needed. Serial erythrocyte 6-TG metabolite levels were measured at each clinic visit and correlated with treatment efficacy.RESULTSClinical remission, as defined by a low disease index score in patients weaned off or on a low alternate day dose (<20 mg on alternate days) of corticosteroid, was achieved in 68% of patients on long term antimetabolite therapy. Treatment efficacy correlated with erythrocyte 6-TG levels greater than 250 pmol/8×108 red blood cells in patients with colonic and fistulising Crohn's disease (p<0.01) but not in patients with ileocolonic disease. Eighteen of 22 patients with incompletely responsive Crohn's disease achieved disease remission by optimising their dose of azathioprine therapy. Median (range) erythrocyte 6-TG metabolite levels increased from 194 (67–688) to 303 (67–737) pmol/8×108 red blood cells (p<0.05). Clinical response associated well with a reduction in corticosteroid requirements. Mean (SEM) white blood cell count decreased from 8.6 (0.9) to 6.9 (0.6) ×103/μl with adjustment in azathioprine dosage. No patient incurred azathioprine induced leucopenia.CONCLUSIONMeasurement of erythrocyte 6-TG metabolite levels is helpful in determining the adequacy of azathioprine dosage and can be used to optimise the dose of antimetabolite therapy to achieve an improved clinical response without inducing leucopenia. Patients who are clinically refractory to azathioprine therapy despite achieving high erythrocyte 6-TG levels (>250) should be considered for adjunct or alternative forms of immunosuppressive therapy or surgery.
Fungal and other spore counts as predictors of admissions for asthma in the Trent region
Authors: Newson R , Strachan D , Corden J , Millington W 
Published: July 2002

OBJECTIVESThe importance of airborne fungal and other spores in provoking asthma attacks is uncertain. Panel studies have generated evidence that suggests a link between outdoor spore counts and severity of asthma. There have been no population based time series studies relating outdoor exposure to spores with incidence of attacks of asthma.METHODSOutcomes were hospital admissions for asthma on 2002 days during 1987–94, for children and adults in the Trent region of England. Predictors were daily counts of 25 spore taxa from volumetric traps in Derby on the same and previous day. Admissions for asthma were adjusted for weekly, seasonal, and longer term trends by log linear autoregressive models. Spore counts on 6 days of asthma epidemics were also examined.RESULTSWhen spore counts for individual taxa were analysed as quantitative variables, two positive and two negative correlations (out of a possible 100) were significant at the 5% level. When spore counts were dichotomised at the 90th percentile, one negative and eight positive correlations (out of 100) were significant at the 5% level. All significantly positive associations related to admissions among children, but none involved the total spore count. However, total spores were above the 90th percentile on four of the six epidemic days (odds ratio (OR) 9.92, 95% confidence interval (95% CI) 1.41 to 109.84), but epidemics occurred on only four of 343 days with high total moulds.CONCLUSIONSThere was some evidence that exceptional rates of admission for asthma tend to occur on days with high total mould spore counts, but no specific taxon was consistently implicated. The predictive power was insufficient to support a public warning system.
Mortality from multiple sclerosis and exposure to residential and occupational solar radiation: a case-control study based on death certificates
Authors: Freedman D Michal , Dosemeci Mustafa , Alavanja Michael C R 
Published: July 2002

OBJECTIVESTo explore whether mortality from multiple sclerosis is negatively associated with exposure to sunlight.METHODSTwo case-control studies based on death certificates were conducted for mortality from multiple sclerosis and non-melanoma skin cancer (as a positive control) to examine associations with residential and occupational exposure to sunlight. Cases were all deaths from multiple sclerosis between 1984 and 1995 in 24 states of the United States. Controls, which were age frequency matched to a series of cases, excluded cancer and certain neurological deaths. The effects of occupational exposure to sunlight were assessed among subjects with usual occupations requiring substantial activity, so as to exclude those whose indoor jobs resulted from disabilities subsequent to the onset of the disease. Multiple logistic regression analyses were applied, with adjustment for age, sex, race, and socioeconomic status.RESULTSUnlike mortality from skin cancer, mortality from multiple sclerosis was negatively associated with residential exposure to sunlight (odds ratio (OR)=0.53 (multiple sclerosis) and OR=1.24 (skin cancer)). Odds ratios for the highest occupational exposure to sunlight were 0.74 (95% confidence interval (95% CI) 0.61 to 0.89) for mortality from multiple sclerosis, compared with 1.21 (1.09 to 1.34) for mortality from non-melanoma skin cancer. The OR was 0.24 for the combined effect of the highest levels of residential and occupational exposure to sunlight on multiple sclerosis, compared with an OR of 1.38 for skin cancer.CONCLUSIONSIn this exploratory study, mortality from multiple sclerosis, unlike mortality from skin cancer, was negatively associated with both residential and occupational exposure to sunlight.
Mortality in chemical workers potentially exposed to 2,4-dichlorophenoxyacetic acid (2,4-D) 1945–94: an update
Authors: Burns C J , Beard K K , Cartmill J B 
Published: July 2002

OBJECTIVETo update and add to a previously identified cohort of employees potentially exposed to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). The putative association between 2,4-D and non-Hodgkin's lymphoma has been debated for more than a decade.METHODSCohort members were male employees of The Dow Chemical Company who manufactured or formulated 2,4-D any time from 1945 to the end of 1994. Their mortality experience was compared with national rates and with more than 40 000 other company employees who worked at the same location.RESULTS330 Deaths were observed among 1517 people compared with 365 expected (standardised mortality ratio (SMR)=0.90, 95% confidence interval (95% CI) 0.81 to 1.01). There were no significantly increased SMRs for any of the causes of death analyzed. When compared with the United States rates, the SMR for non-Hodgkin's lymphoma (NHL) was 1.00 (95% CI 0.21 to 2.92). The internal comparison with other Dow employees showed a non-significant relative risk of 2.63, (95% CI 0.85 to 8.33). Death was attributed to amyotrophic lateral sclerosis (ALS) for three cohort members. Compared with the other company employees, the relative risk was 3.45 (95% CI 1.10 to 11.11). The cases were employed in the manufacture or formulation of 2,4-D at different periods (1947–9, 1950–1, and 1968–86), and for varying durations of time (1.3, 1.8, and 12.5 years).CONCLUSIONThere was no evidence of a causal association between exposure to 2,4-D and mortality due to all causes and total malignant neoplasms. No significant risk due to NHL was found. Although not an initial hypothesis, an increased relative risk of ALS was noted. This finding is unsupported by other animal and human studies.