bluuebunny/crossref_metadata_2025_split huggingface dataset:
Papaya ringspot virus‐P: characteristics, pathogenicity, sequence variability and control
Authors: TRIPATHI SAVARNI , SUZUKI JON Y. , FERREIRA STEPHEN A. , GONSALVES DENNIS 
Published: February 2008

SUMMARYTaxonomy:  Papaya ringspot virus (PRSV) is an aphid‐transmitted plant virus belonging to the genus Potyvirus, family Potyviridae, with a positive sense RNA genome. PRSV isolates belong to either one of two major strains, P or W. The P strains infect both papaya and cucurbits whereas the W strains infect only cucurbits.Geographical distribution:  PRSV‐P is found in all major papaya‐growing areas.Physical properties:  Virions are filamentous, non‐enveloped and flexuous measuring 760–800 × 12 nm. Virus particles contain 94.5% protein and 5.5% nucleic acid. The protein component consists of the virus coat protein (CP), which has a molecular weight of about 36 kDa as estimated by Western blot analysis. Density of the sedimenting component in purified PRSV preparations is 1.32 g/cm3 in CsCl.Genome:  The PRSV genome consists of a unipartite linear single‐stranded positive sense RNA of 10 326 nucleotides with a 5′ terminus, genome‐linked protein, VPg.Transmission:  The virus is naturally transmitted via aphids in a non‐persistent manner. Both the CP and helper component (HC‐Pro) are required for vector transmission. This virus can also be transmitted mechanically, and is typically not seed‐transmitted.Hosts:  PRSV has a limited number of hosts belonging to the families Caricaceae, Chenopodiaceae and Cucurbitaceae. Propagation hosts are: Carica papaya, Cucurbita pepo and Cucumis metuliferus cv. accession 2459. Local lesion assay hosts are: Chenopodium quinoa and Chenopodium amaranticolor.Control:  Two transgenic papaya varieties, Rainbow and SunUp, with engineered resistance to PRSV have been commercially grown in Hawaii since 1998. Besides transgenic resistance, tolerant varieties, cross‐protection and other cultural practices such as isolation and rogueing of infected plants are used to manage the disease.Virus code:  00.057.0.01.045.Virus accession number:  57010045.Useful link:  http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/57010045.htm
Population pharmacokinetics of chloroquine and sulfadoxine and treatment response in children with malaria: suggestions for an improved dose regimen
Authors: Obua Celestino , Hellgren Urban , Ntale Muhammed , Gustafsson Lars L. , Ogwal‐Okeng Jasper W. , Gordi Toufigh , Jerling Markus 
Published: February 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Both chloroquine (CQ) and sulfadoxine/ pyrimethamine (SDx/PYR) remain important drugs in the control of malaria.• The available data on CQ, SDx and PYR are summary pharmacokinetic parameters based on classical/traditional methods, mostly in adults.• No study has described the population pharmacokinetics of a fixed‐dose CQ + SDx/PYR combination in children with falciparum malaria. WHAT THIS STUDY ADDS • This study presents population pharmacokinetic data on CQ and SDx in children with uncomplicated falciparum malaria.• The study demonstrates that in age‐based fixed‐dose regimens with CQ and SDx, drug exposures and outcomes may be correctly predicted, although correlation with body weight is poor.• The study proposes dose modification to improve response with the CQ + SDx/PYR combination.AIMSTo describe the pharmacokinetics of chloroquine (CQ) and sulfadoxine (SDx), and to identify predictors of treatment response in children with malaria given the CQ + SDx and pyrimethamine (PYR) combination.METHODSEighty‐six Ugandan children with uncomplicated falciparum malaria, 6 months to 5 years old, were randomly treated with prepacked fixed‐dose CQ + SDx/PYR. The youngest children (<24 months) received half strength and the older (>24 months) full strength treatment. The reported day 14 failure rates were 48% and 18%, respectively. Capillary blood (100 μl) applied on to filter paper was collected on eight occasions during 28 days of follow up. Concentrations of CQ and SDx were determined. A population approach was used for the pharmacokinetic analysis.RESULTSA two‐compartment model adequately described the data for both CQ and SDx. For CQ, the typical apparent clearance (CL/F) and volume of distribution (VC/F) values were estimated to be 2.84 l h−1 and 230 l. The typical CL/F for SDx was 0.023 l h−1, while the factor relating its VC/F to normalized body weight was 1.6 l kg−1. Post hoc parameter estimates for both drugs showed lower maximum concentrations (Cmax) and concentration‐time curve areas (AUC(0,336 h)) in younger children. The AUC(0,336 h) for SDx and CQ were independently significant factors for prediction of cure. Simulations suggest that giving the higher dose to the youngest children would result in higher CQ and SDx concentrations and improved outcome.CONCLUSIONSThe study results suggest that full‐strength combination to all children would improve the cure rate.
Prescription drug use among fathers and mothers before and during pregnancy. A population‐based cohort study of 106 000 pregnancies in Norway 2004–2006
Authors: Engeland Anders , Bramness Jørgen G. , Daltveit Anne Kjersti , Rønning Marit , Skurtveit Svetlana , Furu Kari 
Published: February 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Mothers are using medicines during pregnancies; the extent varies across the world and is generally difficult to compare.• In this registry‐based study, we examined more than 100 000 Norwegian pregnancies and described the drug prescription pattern of both fathers and mothers around conception and during pregnancy (mothers). WHAT THIS STUDY ADDS • In every trimester of pregnancy, about 30% of the mothers was dispensed a drug.• The total drug exposure did not seem to diminish throughout pregnancy.• One‐quarter of the fathers was dispensed drugs during the last 3 months prior to conception.AIMSThe primary aim of this study was to describe the use of prescribed drugs in both mothers and fathers before and during pregnancy in Norway.METHODSThis population‐based cohort study was based on data retrieved from the Medical Birth Registry of Norway and the Norwegian Prescription Database. These registries cover the entire population of Norway. Information on >100 000 births during 2004–2006 in the birth registry was linked to prescription data. Prescriptions issued to mothers just prior to, during and after the pregnancies as well as prescriptions to fathers just prior to conception were identified.RESULTSAmong mothers, 83% were prescribed drugs during the period 3 months prior to estimated conception until 3 months after giving birth. The mothers who received drugs were prescribed on average 3.3 different Anatomical Therapeutic Chemical (ATC) codes (range 1–38). During pregnancy, 57% were prescribed drugs. In the first trimester, 33% of mothers were dispensed drugs, while the figure was 29% for mothers in the last trimester. Among fathers, 25% used prescribed drugs during the 3 months prior to conception, with on average 1.9 different ATC codes (range 1–22).CONCLUSIONLarge proportions of both fathers and mothers were dispensed drugs prior to conception or during pregnancy. While there is a high awareness of the issues involved in maternal drug use in pregnancy, possible teratogenic effects of drug use in fathers shortly before conception should be further explored.
Increased omeprazole metabolism in carriers of the CYP2C19*17 allele; a pharmacokinetic study in healthy volunteers
Authors: Baldwin R. Michael , Ohlsson Staffan , Pedersen Rasmus Steen , Mwinyi Jessica , Ingelman‐Sundberg Magnus , Eliasson Erik , Bertilsson Leif 
Published: February 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The only existing study of CYP2C19*17‐associated alterations in drug pharmacokinetics was retrospective and compared probe drug metabolic ratios.• The CYP2C19*17 allele had been associated with a two‐ and fourfold decrease in omeprazole and S/R‐mephenytoin metabolic ratios. WHAT THIS STUDY ADDS • This study characterized the single‐dose pharmacokinetics of omeprazole, along with the 5‐hydroxy and sulphone metabolites, in CYP2C19*17/*17 and CYP2C19*1/*1 subjects.• The observed differences in omeprazole AUC∞ suggest that the CYP2C19*17 allele is an important explanatory factor behind individual cases of therapeutic failure.AIMSTo investigate the influence of the CYP2C19*17 allele on the pharmacokinetics of omeprazole, a commonly used CYP2C19 probe drug, in healthy volunteers.METHODSIn a single‐dose pharmacokinetic study, 17 healthy White volunteers genotyped as either CYP2C19*17/*17 or CYP2C19*1/*1 received an oral dose of 40 mg of omeprazole. Plasma was sampled for up to 10 h postdose, followed by quantification of omeprazole, 5‐hydroxy omeprazole and omeprazole sulphone by high‐performance liquid chromatography.RESULTSThe mean omeprazole AUC∞ of 1973 h nmol l−1 in CYP2C19*17/*17 subjects was 2.1‐fold lower [95% confidence interval (CI) 1.1, 3.3] than in CYP2C19*1/*1 subjects (4151 h nmol l−1, P = 0.04). A similar trend was observed for the sulphone metabolite with the CYP2C19*17/*17 group having a mean AUC∞ of 1083 h nmol l−1, 3.1‐fold lower (95% CI 1.2, 5.5) than the CYP2C19*1/*1 group (3343 h nmol l−1, P = 0.03). A pronounced correlation (r2 = 0.95, P < 0.0001) was seen in the intraindividual omeprazole AUC∞ and omeprazole sulphone AUC∞ values.CONCLUSIONSThe pharmacokinetics of omeprazole and omeprazole sulphone differ significantly between homozygous CYP2C19*17 and CYP2C19*1 subjects. For clinically important drugs that are metabolized predominantly by CYP2C19, the CYP2C19*17 allele might be associated with subtherapeutic drug exposure.
Interleukin‐12 is necessary for the priming of CD4+ T cells required during the elicitation of HIV‐1 gp120‐specific cytotoxic T‐lymphocyte function
Authors: Gupta Shalini , Boppana Ramanamurthy , Mishra Gyan C. , Saha Bhaskar , Mitra Debashis 
Published: February 2008

SummaryThe mechanism of the T‐cell response and cytokine induction to restrict human immunodeficiency virus 1 (HIV‐1) infection is not clear. During early infection, HIV‐infected individuals have a high frequency of virus‐specific cytotoxic T lymphocytes (CTLs) that effectively reduces the viral load. However, the CTLs are unable to clear the virus at later stages of infection, leading to disease progression. Dysregulation of cytokines like interleukin‐12 (IL‐12) and interferon‐γ (IFN‐γ) as a result of the interaction of HIV‐1‐specific T cells with antigen‐presenting cells is one of the possible causes of CTL dysfunction. Secretion of IL‐12 is reduced with the progression of HIV infection, correlating with impaired CTL function; however, the role of IL‐12 in CTL regulation awaits elucidation. Here, we have studied the role of IL‐12 in CTL dysfunction by using DNA immunization of wild‐type (WT) and IL‐12‐deficient mice with HIV‐1 gp120 complementary DNA. It was observed that the CTL response in IL‐12‐deficient mice was significantly less than that in WT mice. Our results further demonstrated that coimmunization with IL‐12 vector restored the impaired CTL response in IL‐12‐deficient mice. However, immunization with IL‐12 vector failed to rescue the CTL response in IFN‐γ deficient mice, suggesting that the CTL‐promoting function of IL‐12 is IFN‐γ‐mediated. Our data suggest a phase‐specific role of IL‐12 in the CTL response, specifically in the priming of CD4+ T cells that provide help to CD8+ T cells. Our results also suggest that IL‐12 is vital for the priming of antigen‐specific T cells and plays an essential role in IFN‐γ induction in T cells.
Comparison of operative procedure variables on pulpal viability in an ex vivo model
Authors: Murray P. E. , Smith A. J. , Garcia‐Godoy F. , Lumley P. J. 
Published: February 2008

AbstractAim  To measure and compare the responses of pulp tissue to cavity preparation and restoration variables using a novel tooth slice culture model.Methodology  Experimental cavities (265) were continuously cut, under carefully controlled conditions, into the dentine of the labial aspect of 28‐day‐old Wistar rat incisors, and slices of these teeth maintained in organ culture for up to 2 weeks. The experimental variables examined were: the preparation method, remaining dentine thickness, coolant, drill speed, conditioning with EDTA and filling materials. The reactions of the dentine–pulp complex to the experimental variables were measured using pathohistometric analysis and the correlations between variables were determined using analysis of variance statistical tests.Results  In rank order of surgically induced restorative pulpal injury, from the most to the least injurious were: remaining dentine thickness, absence of coolant during cavity preparation, bur speed, cavity conditioning treatments and the filling material.Conclusions  To reduce pulp injury and to promote pulpal repair activity, the correct use of appropriate materials are important. However, of relatively greater importance is the operative technique adopted, the need to avoid the excess removal of dentine and to minimize trauma during preparation.
In vitro fluoride uptake by bovine enamel from aesthetic restorative materials
Authors: AHIROPOULOS VASILIS , HELVATJOGLU‐ANTONIADES MARIA , PAPADOGIANNIS YANNIS 
Published: February 2008

Objectives.  The purposes of this in vitro study were to determine whether different types of fluoride‐containing restoratives produce differing levels of fluoride uptake by bovine enamel, and to determine the effect of time on this uptake.Methods.  Seven aesthetic restorative materials were evaluated. Forty bovine enamel slabs were prepared for each tested material, five of which were used to determine baseline fluoride concentrations. Each slab was attached to a disc of the tested material and suspended in synthetic saliva for up to 64 days. After removal, the specimens were acid etched with perchloric acid, and the dissolved enamel was analysed for fluoride and calcium. Fluoride was determined by direct potensiometric analysis, whereas the amount of calcium was evaluated by means of atomic absorption spectrophotometry.Results.  Higher values of fluoride uptake, not significantly different, were recorded in the first two groups. A statistically significant difference was found in fluoride uptake between Fuji II LC and the three compomers in all test intervals. No significant differences were found in the amounts of fluoride uptake between the three compomers. The highest fluoride uptake from all compomers was recorded by F2000.Conclusion.  Enamel acquired significant amounts of fluoride from all materials with variations during the test intervals.
Correlation of bone age, dental age, and chronological age in survivors of childhood acute lymphoblastic leukaemia
Authors: MARTIN MARY BETH , LI CHIN‐SHANG , ROWLAND CHRISTOPHER C. , HOWARD SCOTT C. , KASTE SUE C. 
Published: February 2008

Background. There is little information about oncotherapy‐related dental development in childhood acute lymphoblastic leukaemia (ALL).Objective.  The objective of this study was to compare bone age (BA) and dental age (DA) to chronological age (CA) in childhood ALL survivors.Methods.  We retrospectively reviewed hand–wrist and panoramic radiographs of patients treated on contemporary single institution protocols for ALL between 1991 and 2004. We recorded patient demographics, therapeutic protocol, CA, DA, and BA. The cohort was divided into three categories based on age at diagnosis (< 6 years, 6–9 years, > 9 years).Results.  Of 73 patients, 39 (53.4%) were boys; 55 (75.3%) were Caucasian. Median CA at diagnosis was 4.5 years (range: 0.1–11.0 years); time to study was 4.1 years (range: 0.3–11.4 years). BA was normal in 61 (83.6%), delayed in 10 (13.7%), and advanced in 2 (2.7%). DA was normal in 41 (56.9%), delayed in 8 (11.1%), and advanced in 23 (31.9%). Abnormal BA, abnormal DA, and discrepancy between BA and DA are not statistically significantly associated with investigated patient or treatment factors.Conclusions.  DA may be altered in 43.1% of patients treated for ALL. A large prospective study is warranted to better define our observations and to determine their impact on dental and orthodontic management.
A clinical and histological study of dental defects in a 10‐year‐old girl with pseudoxanthoma elasticum and amelogenesis imperfecta
Authors: MORRIER JEAN‐JACQUES , ROMEAS ANNICK , LACAN EMILIE , FARGES JEAN‐CHRISTOPHE 
Published: February 2008

Background.  The prominent dental feature of a 10‐year‐old girl was severely hypoplastic enamel in permanent teeth.Case report.  Severe dental defects were detected in a 10‐year‐old female patient affected by pseudoxanthoma elasticum and amelogenesis imperfecta. An orthopantomographic examination revealed a reduction of enamel thickness on the crown of all erupted and unerupted teeth, agenesis of the maxillary right second premolar, delayed eruption of mandibular first premolars, and the presence of large calcifications in all tooth pulp chambers. A detailed histological analysis of permanent mandibular first molars showed that pulp calcifications presented a concentric laminate organization and merged to almost completely obliterate the pulp chamber. Osteodentine was visible all along the pulpal surface of the radicular dentine. Broad resorption areas were present in the outermost dentine at both coronal and radicular levels. Radicular resorption areas presented a typical rectangular form and were filled with acellular cementum. Cementum thickness was highly increased on the root surface. Apposition of cellular cementum‐like tissue was also observed on the coronal dentine surface.Conclusion.  Before treating patients affected by amelogenesis imperfecta and/or pseudoxanthoma elasticum, paediatric dentists should be aware of the presence of pulp calcifications that add to the complexity of endodontic procedures.
Heat‐treated glass ionomer cement fissure sealants: retention after 1 year follow‐up
Authors: SKRINJARIC KRISTINA , VRANIC DUBRAVKA NEGOVETIC , GLAVINA DOMAGOJ , SKRINJARIC ILIJA 
Published: February 2008

Objective.  The aim of this study was to assess the retention rate of glass ionomer cement (GIC) fissure sealants heated during setting time.Methods.  One hundred and twelve teeth with well‐delineated fissure morphology were sealed with composite resin and GIC. Composite resin (Helioseal F, Vivadent) was used in control group A (56 teeth). GIC (Fuji VII, GC) was applied using split‐mouth design with conditioning in group B (26 teeth) and without surface conditioning in group C (30 teeth). GIC was heated with external heat source (Elipar Trilight, Espe) for 40 s during the setting time according to the manufacturer's instructions. Fissure sealants were evaluated 1 year after clinical service.Results.  Retention rate in group A was 80.4% after 1 year of clinical service. Group B showed retention rate of 30.8%, and group C of 26.7%. Two new caries lesions were detected in groups B and C. Significant differences in retention between the composite group and GIC groups were obtained by Kruskal–Wallis and Mann–Whitney tests.Conclusion.  It could be concluded that retention rate of GIC sealing treated with heat during setting time was significantly lower than retention of conventional composite resin. The heating procedure during setting of GIC sealants cannot be recommended as routine treatment in clinical practice.
Functional characterization of the Aspergillus fumigatus CRZ1 homologue, CrzA
Authors: Soriani Frederico Marianetti , Malavazi Iran , Da Silva Ferreira Márcia Eliana , Savoldi Marcela , Von Zeska Kress Marcia Regina , De Souza Goldman Maria Helena , Loss Omar , Bignell Elaine , Goldman Gustavo Henrique 
Published: February 2008

SummaryThe protein phosphatase calcineurin is an important mediator connecting calcium‐dependent signalling to various cellular responses in multiple organisms. In fungi calcineurin acts largely through regulating Crz1p‐like transcription factors. Here we characterize an Aspergillus fumigatus CRZ1 homologue, CrzA and demonstrate its mediation of cellular tolerance to increased concentrations of calcium and manganese. In addition to acute sensitivitiy to these ions, and decreased conidiation, the crzA null mutant suffers altered expression of calcium transporter mRNAs under high concentrations of calcium, and loss of virulence when compared with the corresponding complemented and wild‐type strains. We use multiple expression analyses to probe the transcriptional basis of A. fumigatus calcium tolerance identifying several genes having calA and/or crzA dependent mRNA accumulation patterns. We also demonstrate that contrary to previous findings, the gene encoding the Aspergillus nidulans calcineurin subunit homologue, cnaA, is not essential and that the cnaA deletion mutant shares the morphological phenotypes observed in the corresponding A. fumigatus mutant, ΔcalA. Exploiting the A. nidulans model system, we have linked calcineurin activity with asexual developmental induction, finding that CrzA supports appropriate developmental induction in a calcineurin and brlA‐dependent manner in both species.
Requirements for ATP binding and hydrolysis in RecA function in Escherichia coli
Authors: Renzette Nicholas , Sandler Steven J. 
Published: February 2008

SummaryRecA is essential for recombination, DNA repair and SOS induction in Escherichia coli. ATP hydrolysis is known to be important for RecA's roles in recombination and DNA repair. In vitro reactions modelling SOS induction minimally require ssDNA and non‐hydrolyzable ATP analogues. This predicts that ATP hydrolysis will not be required for SOS induction in vivo. The requirement of ATP binding and hydrolysis for SOS induction in vivo is tested here through the study of recA4159 (K72A) and recA2201 (K72R). RecA4159 is thought to have reduced affinity for ATP. RecA2201 binds, but does not hydrolyse ATP. Neither mutant was able to induce SOS expression after UV irradiation. RecA2201, unlike RecA4159, could form filaments on DNA and storage structures as measured with RecA–GFP. RecA2201 was able to form hybrid filaments and storage structures and was either recessive or dominant to RecA+, depending on the ratio of the two proteins. RecA4159 was unable to enter RecA+ filaments on DNA or storage structures and was recessive to RecA+. It is concluded that ATP hydrolysis is essential for SOS induction. It is proposed that ATP binding is essential for storage structure formation and ability to interact with other RecA proteins in a filament.