bluuebunny/crossref_metadata_2025_split huggingface dataset:
Requirement of a 12-Base-Pair TATT-Containing Sequence and Viral Lytic DNA Replication in Activation of the Kaposi's Sarcoma-Associated Herpesvirus K8.1 Late Promoter
Authors: Tang Shuang , Yamanegi Koji , Zheng Zhi-Ming 
Published: February 2004

ABSTRACT

Kaposi's sarcoma-associated herpesvirus (KSHV) K8.1 late promoter consists of a minimal 24-bp sequence, with a TATA-like, 12-bp promoter core, AATATTAAAGGG, and is active on a reporter only in butyrate-induced KSHV-infected cells. The activity of the K8.1 promoter can be enhanced (>15-fold) by the KSHV left-end lytic origin of DNA replication (oriLyt-L) sequence while providing inefficient replication of plasmid DNA and is inhibited by viral DNA replication inhibitors, suggesting that activation of the K8.1 promoter on the reporter is involved in KSHV lytic DNA replication largely by
trans
.
Bovine Papillomavirus Replicative Helicase E1 Is a Target of the Ubiquitin Ligase APC
Authors: Mechali Francisca , Hsu Chiung-Yueh , Castro Anna , Lorca Thierry , Bonne-Andrea Catherine 
Published: February 2004

ABSTRACT
The papillomavirus E1 replicative helicase is essential for replication and maintenance of extrachromosomal viral genomes in infected cells. We previously found that the bovine papillomavirus E1 protein is a substrate of the ubiquitin-dependent proteolytic pathway. Here we show that E1 is targeted for degradation by the anaphase-promoting complex (APC). Inhibition of APC activity by the specific inhibitor Emi1 or point mutations in the D-box and KEN-box motifs of E1 stabilize the protein and increase viral DNA replication in both a cell-free system and in living cells. These findings involve APC as the ubiquitin ligase that controls E1 levels to maintain a constant low copy number of the viral genome during latent infection.
Roles of the E6 and E7 Proteins in the Life Cycle of Low-Risk Human Papillomavirus Type 11
Authors: Oh Stephen T. , Longworth Michelle S. , Laimins Laimonis A. 
Published: February 2004

ABSTRACT
Many important functions have been attributed to the high-risk human papillomavirus (HPV) E6 and E7 proteins, including binding and degradation of p53 as well as interacting with Rb proteins. In contrast, the physiological roles of the low-risk E6 and E7 proteins remain unclear. Previous studies demonstrated that the high-risk E6 and E7 proteins also play roles in the productive life cycle by facilitating the maintenance of viral episomes (J. T. Thomas, W. G. Hubert, M. N. Ruesch, and L. A. Laimins, Proc. Natl. Acad. Sci. USA 96:8449-8454, 1999). In order to determine whether low-risk E6 or E7 is similarly necessary for the stable maintenance of episomes, HPV type 11 (HPV-11) genomes that contained translation termination mutations in E6 or E7 were constructed. Upon transfection into normal human keratinocytes, genomes in which E6 function was abolished were unable to be maintained episomally. Transfection of genomes containing substitution mutations in amino acids conserved in high- and low-risk HPV types suggested that multiple protein domains are involved in this process. Examination of cells transfected with HPV-11 genomes in which E7 function was inhibited were found to exhibit a more complex phenotype. At the second passage following transfection, mutant genomes were maintained as episomes but at significantly reduced levels than in cells transfected with the wild-type HPV-11 genome. Upon further passage in culture, however, the episomal forms of these E7 mutant genomes quickly disappeared. These findings identify important new functions for the low-risk E6 and E7 proteins in the episomal maintenance of low-risk HPV-11 genomes and suggest that they may act in a manner similar to that observed for the high-risk proteins.
Binding of the 2F5 Monoclonal Antibody to Native and Fusion-Intermediate Forms of Human Immunodeficiency Virus Type 1 gp41: Implications for Fusion-Inducing Conformational Changes
Authors: de Rosny Eve , Vassell Russell , Jiang Shibo , Kunert Renate , Weiss Carol D. 
Published: February 2004

ABSTRACT
We investigated how the broadly neutralizing monoclonal antibody 2F5 affects the human immunodeficiency virus type 1 envelope glycoprotein as it undergoes receptor-induced conformational changes and show that 2F5 binds both native and fusion-intermediate conformations, suggesting inhibition of a late step in virus entry. We also demonstrate conformational changes in the C heptad of gp41.
Role of Indoleamine-2,3-Dioxygenase in Alpha/Beta and Gamma Interferon-Mediated Antiviral Effects against Herpes Simplex Virus Infections
Authors: Adams O. , Besken K. , Oberdörfer C. , MacKenzie C. R. , Takikawa O. , Däubener W. 
Published: February 2004

ABSTRACTGamma interferon (IFN-γ)-mediated indoleamine-2,3-dioxygenase (IDO) activity in human astrocytoma cells and in native astrocytes was found to be responsible for the inhibition of herpes simplex virus replication. The effect is abolished in the presence of excess amounts ofl-tryptophan. Both IFN-α and IFN-β restricted herpes simplex virus replication in both cell types, but (in contrast to the results seen with IFN-γ) the addition of an excess amount ofl-tryptophan did not inhibit the induced antiviral effect.
Identification of Peptides That Inhibit the DNA Binding,trans-Activator, and DNA Replication Functions of the Human Papillomavirus Type 11 E2 Protein
Authors: Deng Su-Jun , Pearce Kenneth H. , Dixon Eric P. , Hartley Kelly A. , Stanley Thomas B. , Lobe David C. , Garvey Edward P. , Kost Thomas A. , Petty Regina L. , Rocque Warren J. , Alexander Kenneth A. , Underwood Mark R. 
Published: February 2004

ABSTRACTPeptide antagonists of the human papillomavirus type 11 (HPV-11) E2-DNA association were identified using a filamentous bacteriophage random peptide library. Synthetic peptides antagonized the E2-DNA interaction, effectively blocked E2-mediated transcriptional activation of a reporter gene in cell culture, and inhibited E1-E2-mediated HPV-11 DNA replication in vitro. These peptides may prove to be useful tools for characterizing E2 function and for exploring the effectiveness of E2-inhibitor-based treatments for HPV-associated diseases.
Jaagsiekte Sheep Retrovirus Envelope Efficiently Pseudotypes Human Immunodeficiency Virus Type 1-Based Lentiviral Vectors
Authors: Liu Shan-Lu , Halbert Christine L. , Miller A. Dusty 
Published: February 2004

ABSTRACT
Jaagsiekte sheep retrovirus (JSRV) infects lung epithelial cells in sheep, and oncoretroviral vectors bearing JSRV Env can mediate transduction of human cells, suggesting that such vectors might be useful for lung-directed gene therapy. Here we show that JSRV Env can also efficiently pseudotype a human immunodeficiency virus type 1-based lentiviral vector, a more suitable vector for transduction of slowly dividing lung epithelial cells. We created several chimeric Env proteins that, unlike the parental Env, do not transform rodent fibroblasts but are still capable of pseudotyping lentiviral and oncoretroviral vectors.
Contribution of Disulfide Bridging to Epitope Expression of the Dengue Type 2 Virus Envelope Glycoprotein
Authors: Roehrig John T. , Volpe Katharine E. , Squires Jennifer , Hunt Ann R. , Davis Brent S. , Chang Gwong-Jen J. 
Published: February 2004

ABSTRACT

The individual contributions of each of the six conserved disulfide (SS) bonds in the dengue 2 virus envelope (E) glycoprotein (strain 16681) to epitope expression was determined by measuring the reactivities of a panel of well-defined monoclonal antibodies (MAbs) with LLC-MK
2
cells that had been transiently transformed with plasmid vectors expressing E proteins that were mutant in their SS bonds. Three domain I (DI) epitopes (C1, C3, and C4) were affected by elimination of any SS bond and were essentially the only epitopes affected by elimination of the amino-proximal SS1 formed between Cys 3 and Cys 30. The remaining DI epitope (C2) was sensitive to only SS3-bond (Cys 74-Cys 105) and SS6-bond (Cys 302-Cys 333) elimination. Of the four DII epitopes examined, reactivities of three anti-epitope MAbs (A1, A2, and A5) were reduced by elimination of SS2 (Cys 61-Cys 121), SS3, SS4 (Cys 94-Cys 116), SS5 (Cys 185-Cys 285), or SS6. The other DII epitope examined (A3) was sensitive only to SS2- and SS3-bond elimination. The three DIII epitopes tested (B2, B3, and B4) were most sensitive to elimination of SS6. The flavivirus group epitope (A1) was less sensitive to elimination of SS3 and SS6. This result may indicate that the region proximal to the E-protein fusion motif (amino acids 98 to 110) may have important linear components. If this observation can be confirmed, peptide mimics from this region of E protein might be able to interfere with flavivirus replication.
Reactivity of p-Substituted Benzaldoximes in the Cleavage of p-Nitrophenyl Acetate: Kinetics and Mechanism
Authors: Pícha Jan , Cibulka Radek , Hampl František , Liška František , Pařík Patrik , Pytela Oldřich 
Published: February 2004

Eleven p-substituted benzaldoximes (p-XC6H4CH=NOH, where X = H, CH3, CF3, F, Cl, Br, OCH3, N(CH3)2, COOCH3, CN, NO2) have been synthesized and their dissociation constants determined in 10% (v/v) aqueous dioxane at 35 °C. Under the same conditions, the pseudo-first order rate constants kobs of their reactions with p-nitrophenyl acetate (PNPA) were measured at pH values from 7.8 to 10.8 and at concentrations coxime ranging from 0 to 4.00 × 10-3 mol l-1. The kinetic model and mechanism of the said reaction was proposed by means of mathematical statistical modelling of the dependences of kobs on pH and coxime. The mechanism involves a pre-equilibrium (k-1/k1) in which PNPA forms a tetrahedral intermediate (THI) with the deprotonated form of oxime. In the given medium, THI is in equilibrium with the non-reactive conjugated acid THIH (dissociation constant Ka,THIH) which is stabilized by intramolecular hydrogen bond. Depending on pH, the rate-limiting step consists either in formation of THI from educts (pH < pKa,oxime) or in its spontaneous (k2) and oxime-catalyzed (k3, general acid catalysis) decomposition to products (pH > pKa,oxime). Evaluation of substituent effects on dissociation constants (Ka,oxime) of the oximes showed that there is no direct conjugation between the substituent and the reaction centre (the found reaction constant ρ(Ka,oxime) = 0.91). The transmission coefficient of the transfer of these effects through C=N-O grouping corresponds approximately to one bond. The reaction constants in the Hammett equation obtained from the regression model are: ρ(k-1Ka,THIH/k1) = 1.29, ρ(k2Ka,THIH) = 0.20 and ρ(k3Ka,THIH) = 0.67. These reaction constants have been discussed with the regard to the reaction mechanism suggested.
Association of endothelial constitutive nitric oxide synthase gene polymorphism with acute coronary syndrome in Koreans
Authors: Park K-W , You K-H , Oh S , Chae I-H , Kim H-S , Oh B-H , Lee M-M , Park Y-B 
Published: February 2004

Objective: To examine the effects of two polymorphisms of the endothelial constitutive nitric oxide synthase (ecNOS) gene, 4a/4b(A:B) located in intron 4 and Glu298Asp(G:T) located in exon 7, on the development of acute coronary syndromes (ACS).Methods: 164 patients with ACS and 142 control participants were investigated for genotype and conventional risk factors. Genotype was determined by polymerase chain reaction and restriction fragment length polymorphism analysis.Results: Genotype and allele frequencies of the A:B polymorphism in the ACS group (0.15:0.85 for AA+AB:BB, 0.09:0.91 for A:B) differed from those in the control group (0.26:0.74 for AA+AB:BB, 0.15:0.85 for A:B). However, genotype and allele frequencies of the G:T polymorphism in the ACS group (0.22:0.78 for TT+TG:GG, 0.11:0.89 for T:G) were similar to those in the control group (0.17:0.83 for TT+TG:GG, 0.09:0.91 for T:G). Multiple logistic regression analysis showed that the non-BB (AA+AB) and the non-BB+GG genotypes were significant protective factors against ACS (odds ratios 0.49 and 0.34, 95% confidence intervals 0.26 to 0.93 and 0.14 to 0.83, respectively). In addition, linear association analysis showed that the percentage of ACS patients was significantly lower in the genotype group non-BB+GG than in the genotype group BB+non-GG (39.6% v 62.7%, p  =  0.01).Conclusions: The non-BB genotype of the ecNOS 4a/4b gene polymorphism is a protective factor against the development of ACS. The GG genotype of the ecNOS Glu298Asp polymorphism exerts a benefit in addition to the non-BB genotype in the Korean population.
Relation between left ventricular contractile reserve during low dose dobutamine echocardiography and plasma concentrations of natriuretic peptides
Authors: Schinkel A F L , Vourvouri E C , Bax J J , Boomsma F , Bountioukos M , Rizzello V , Biagini E , Agricola E , Elhendy A , Roelandt J R T C , Poldermans D 
Published: February 2004

Background: In ischaemic cardiomyopathy, raised plasma concentrations of natriuretic peptides are associated with a poor long term prognosis, while the presence of contractile reserve is a favourable sign.Objective: To assess the relation between plasma natriuretic peptides and contractile reserve.Design: Prospective observational study.Setting: Tertiary referral centre.Patients: 66 consecutive patients undergoing low dose dobutamine stress echocardiography to evaluate contractile reserve in regions with contractile dysfunction at rest, divided into two groups: group 1, 31 patients with ischaemic cardiomyopathy (left ventricular ejection fraction ⩽ 40%) and heart failure symptoms; group 2, 35 patients with normal left ventricular function.Main outcome measures: Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), measured using immunoradiometric assays. Contractile reserve was defined as an improvement in segmental wall motion score during infusion of low dose dobutamine.Results: Plasma ANP and BNP concentrations were higher in group 1 than in group 2 (mean (SD): ANP, 17.8 (32.8) v 7.2 (9.7), p < 0.005; BNP, 24.4 (69.0) v 5.0 (14.3) pmol/l, respectively; p < 0.001). In group 1, the presence of contractile reserve was inversely related to ANP and BNP levels; however, patients with contractile reserve had lower ANP and BNP concentrations than patients without contractile reserve (ANP, 14.2 (9.1) v 24.2 (44.2), p < 0.05; BNP, 20.2 (25.5) v 37.5 (93.8) pmol/l, respectively; p < 0.05).Conclusions: Plasma natriuretic peptide concentrations are raised in patients with left ventricular dysfunction, but in the presence of preserved myocardial contractile reserve, relatively low levels of ANP and BNP are present.
Aberrant tendinous chords with tethering of the tricuspid leaflets: a congenital anomaly causing severe tricuspid regurgitation
Authors: Kobza R , Kurz D J , Oechslin E N , Prêtre R , Zuber M , Vogt P , Jenni R 
Published: February 2004

Objective: To define the entity of tricuspid regurgitation caused by tethering of the tricuspid valve leaflets by aberrant tendinous chords.Design: Retrospective study.Setting: Tertiary care centre (university teaching hospital).Patients: 10 patients with unexplained severe tricuspid regurgitation.Methods: The last 13 500 echocardiographic studies from our facility were reviewed to identify patients with severe unexplained tricuspid regurgitation. Tethering was defined by the presence of aberrant tendinous chords to the tricuspid valve leaflets limiting the mobility of the tricuspid leaflet and resulting in incomplete coaptation and apical displacement of the regurgitant jet origin. Aberrant tendinous chords were defined as those inserting at the clear zone of the tricuspid leaflet and not originating from the papillary muscle. Patients fulfilling the diagnostic criteria for Ebstein’s anomaly were excluded.Results: 10 patients with aberrant tendinous chords tethering one or more tricuspid valve leaflets were identified. There were short non-aberrant tendinous chords in seven patients, five of whom also had right ventricular or tricuspid annulus dilatation.Conclusions: Tethering of the tricuspid valve leaflets by aberrant tendinous chords can be the sole mechanism of congenital tricuspid regurgitation. It is often associated with short non-aberrant tendinous chords, which may develop secondary to right ventricular or tricuspid annulus dilatation. Awareness of tethering as a cause of tricuspid regurgitation may be important in planning reconstructive surgery.
Prognostic relations between inflammatory markers and mortality in diabetic patients with non-ST elevation acute coronary syndrome
Authors: Sanchez P L , Morinigo J L , Pabon P , Martin F , Piedra I , Palacios I F , Martin-Luengo C 
Published: February 2004

Objective: To determine the differences in the inflammatory status between diabetic and non-diabetic patients and to evaluate the usefulness of C reactive protein, fibrinogen, and leucocyte count as predictors of death in diabetic patients with unstable coronary disease.Design: Nested case-control comparisons of the inflammatory status between diabetic and non-diabetic patients. Prospective cohort analysis of C reactive protein concentration, fibrinogen concentration, and leucocyte count as predictors of cardiovascular death in diabetic patients.Setting: Coronary care unit in Spain.Participants: 83 diabetic patients with non-ST elevation acute coronary syndrome and 83 sex and aged matched patients selected from 361 non-diabetic patients with non-ST elevation acute coronary syndrome.Main outcome measures: Plasma concentrations of C reactive protein and fibrinogen, and leucocyte count. Investigators contacted patients to assess clinical events.Results: Concentrations of C reactive protein and fibrinogen, and leucocyte count on admission were higher in diabetic than in non-diabetic patients (7 mg/l v 5 mg/l, p  =  0.020; 3.34 g/l v 2.90 g/l, p  =  0.013; and 8.8 × 109/l v 7.8 × 109/l, p  =  0.040). Among diabetic patients, these values were also higher in those who died during the 22 month follow up (13 mg/l v 6 mg/l, p  =  0.001; 3.95 g/l v 3.05 g/l, p < 0.001; and 11.4 × 109/l v 8.4 × 109/l, p  =  0.005). After adjustment for confounding factors, diabetic patients in the highest tertile of C reactive protein had a hazard ratio for cardiovascular death of 4.51 (95% confidence interval (CI) 1.62 to 12.55). Similar hazard ratios were for fibrinogen 3.74 (95% CI 1.32 to 10.62) and for leucocyte count 3.64 (95% CI 1.37 to 9.68).Conclusions: Inflammation appears more evident in diabetic than in non-diabetic patients with acute coronary syndrome. C reactive protein concentration, fibrinogen concentration, and leucocyte count constitute independent predictors of cardiovascular death in diabetics with unstable coronary disease.
Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK
Authors: Stewart S , Murphy N , Walker A , McGuire A , McMurray J J V 
Published: February 2004

Objective: To evaluate the cost of atrial fibrillation (AF) to health and social services in the UK in 1995 and, based on epidemiological trends, to project this estimate to 2000.Design, setting, and main outcome measures: Contemporary estimates of health care activity related to AF were applied to the whole population of the UK on an age and sex specific basis for the year 1995. The activities considered (and costs calculated) were hospital admissions, outpatient consultations, general practice consultations, and drug treatment (including the cost of monitoring anticoagulant treatment). By adjusting for the progressive aging of the British population and related increases in hospital admissions, the cost of AF was also projected to the year 2000.Results: There were 534 000 people with AF in the UK during 1995. The “direct” cost of health care for these patients was £244 million (~€350 million) or 0.62% of total National Health Service (NHS) expenditure. Hospitalisations and drug prescriptions accounted for 50% and 20% of this expenditure, respectively. Long term nursing home care after hospital admission cost an additional £46.4 million (~€66 million). The direct cost of AF rose to £459 million (~€655 million) in 2000, equivalent to 0.97% of total NHS expenditure based on 1995 figures. Nursing home costs rose to £111 million (~€160 million).Conclusions: AF is an extremely costly public health problem.
Aortic pressure–area relation in Marfan patients with and without β blocking agents: a new non-invasive approach
Authors: Nollen G J , Westerhof B E , Groenink M , Osnabrugge A , van der Wall E E , Mulder B J M 
Published: February 2004

Objective: To investigate the heterogeneous response to β blockade in patients with Marfan syndrome by non-invasive assessment of the aortic pressure–area curve.Design and patients: 25 patients with the Marfan syndrome who used β blocking agents (mean (SD) age, 29 (10) years; 20 men, five women), seven without β blockade (34 (14) years; five men, two women), and 10 controls (29 (5) years; seven men, three women) underwent magnetic resonance imaging and non-invasive continuous blood pressure measurement. Pressure–area curves were constructed at the level of the descending thoracic aorta. A transition point was defined as the pressure at which the pressure–area relation deviated from its elastic (linear) to the collagen (exponential) course.Setting: Tertiary referral centre for adult congenital heart disease.Results: In six patients (five with and one without β blockade), a transition point in the pressure–area curve was observed, indicating that the load bearing component was not only elastin but also collagen. In the remaining 26 Marfan patients and in the control subjects a linear pressure–area relation was observed.Conclusions: This new non-invasive method to derive aortic pressure–area curves showed that most patients with Marfan syndrome have a similar pressure–area curve to controls with similar blood pressures. Five patients on β blockade showed a transition point in the pressure–area curve which could play a crucial role in the heterogeneous response to β blocker treatment in Marfan patients. Patients with a transition at low blood pressures may not benefit from β blocking agents.
Risk factors for non-fatal myocardial infarction in young South Asian adults
Authors: Ismail J , Jafar T H , Jafary F H , White F , Faruqui A M , Chaturvedi N 
Published: February 2004

Objective: To determine the risk factors for premature myocardial infarction among young South Asians.Design and setting: Case–control study in a hospital admitting unselected patients with non-fatal acute myocardial infarction.Methods and subjects: Risk factor assessment was done in 193 subjects aged 15–45 years with a first acute myocardial infarct, and in 193 age, sex, and neighbourhood matched population based controls.Results: The mean (SD) age of the subjects was 39 (4.9) years and 326 (84.5%) were male. Current smoking (odds ratio (OR) 3.82, 95% confidence interval (CI) 1.47 to 9.94), use of ghee (hydrogenated vegetable oil) in cooking (OR 3.91, 95% CI 1.52 to 10.03), raised fasting blood glucose (OR 3.32, 95% CI 1.21 to 8.62), raised serum cholesterol (OR 1.67, 95% CI 1.14 to 2.45 for each 1.0 mmol/l increase), low income (OR 5.05, 95% CI 1.71 to 14.96), paternal history of cardiovascular disease (OR 4.84, 95% CI 1.42 to 16.53), and parental consanguinity (OR 3.80, 95% CI 1.13 to 1.75) were all independent risk factors for acute myocardial infarction in young adults. Formal education versus no education had an independently protective effect on acute myocardial infarction (OR 0.04, 95% CI 0.01 to 0.35).Conclusions: Tobacco use, ghee intake, raised fasting glucose, high cholesterol, paternal history of cardiovascular disease, low income, and low level of education are associated with premature acute myocardial infarction in South Asians. The association of parental consanguinity with acute myocardial infarction is reported for the first time and deserves further study.