bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Pepper Transcription FactorCaPF1Confers Pathogen and Freezing Tolerance in Arabidopsis
Authors: Yi So Young , Kim Jee-Hyub , Joung Young-Hee , Lee Sanghyeob , Kim Woo-Taek , Yu Seung Hun , Choi Doil 
Published: September 2004

AbstractAn ERF/AP2-type transcription factor (CaPF1) was isolated by differential-display reverse transcription-PCR, following inoculation of the soybean pustule pathogen Xanthomonas axonopodis pv glycines 8ra, which induces hypersensitive response in pepper (Capsicum annuum) leaves. CaPF1 mRNA was induced under conditions of biotic and abiotic stress. Higher levels of CaPF1 transcripts were observed in disease-resistant tissue compared with susceptible tissue. CaPF1 expression was additionally induced using various treatment regimes, including ethephon, methyl jasmonate, and cold stress. To determine the role of CaPF1 in plants, transgenic Arabidopsis and tobacco (Nicotiana tabacum) plants expressing higher levels of CaPF1 were generated. Gene expression analyses of transgenic Arabidopsis and tobacco revealed that the CaPF1 level in transgenic plants affects expression of genes that contain either a GCC or a CRT/DRE box in their promoter regions. Furthermore, transgenic Arabidopsis plants expressing CaPF1 displayed tolerance against freezing temperatures and enhanced resistance to Pseudomonas syringae pv tomato DC3000. Disease tolerance was additionally observed in CaPF1 transgenic tobacco plants. The results collectively indicate that CaPF1 is an ERF/AP2 transcription factor in hot pepper plants that may play dual roles in response to biotic and abiotic stress in plants.
Cannabinoid receptor, CB1, expression follows neuronal differentiation in the early chick embryo
Authors: Begbie Jo , Doherty Patrick , Graham Anthony 
Published: September 2004

AbstractThe role of the CB1 cannabinoid receptor and endocannabinoid signalling has been widely studied in the adult nervous system. However, an emerging body of evidence suggests that the CB1 receptor may also play a role during development. Here we have scrutinized the expression profile of the CB1 receptor from the onset of neurogenesis in the chick embryo. We find that this gene exhibits a dynamic expression pattern that spatially and temporally follows neuronal differentiation in the early embryo.
Formation of cartilaginous foci in the central fibrous body of the heart in Syrian hamsters (Mesocricetus auratus)
Authors: Durán A. C. , López D. , Guerrero A. , Mendoza A. , Arqué J. M. , Sans‐Coma V. 
Published: September 2004

AbstractThe formation of cartilage in the mammalian heart has been studied in the aortic and pulmonary valves. The chondrogenetic process that takes place in the cardiac skeleton is still unknown. The present study was designed to illustrate the ontogeny of cartilaginous foci occurring in the central fibrous body of the Syrian hamster (Mesocricetus auratus) heart. Hearts from 472 animals aged 0–708 days were examined using histological, histochemical and immunohistochemical techniques. Cartilage was present in the central fibrous body of 118 (25%) specimens. A further 104 hamsters were used for the detection of calcific deposits in the central fibrous body. Six (5.8%) showed calcified cartilage. The first sign related to chondrogenesis was the presence of small groups of cells embedded in a type II collagen‐positive extracellular matrix. These cellular groups, which can appear as early as 2 days after birth, differentiate into hyaline cartilage or, less frequently, into fibrocartilage. The highest production of cartilaginous foci takes place between days 40 and 80. Thereafter, formation of new foci is uncommon. This indicates that appearance of cartilage in the central fibrous body of the heart is not a consequence of cardiac aging. The cartilaginous foci seem to act as pivots resisting mechanical tensions generated during the cardiac cycle. Deposition of calcium in the extracellular matrix of the foci can be regarded as a reinforcement of the cartilaginous tissue.
Smooth muscle actin and vimentin as markers of testis development in the harbour porpoise (Phocoena phocoena)
Authors: Holt W. V. , Waller J. , Moore A. , Jepson P. D. , Deaville R. , Bennett P. M. 
Published: September 2004

AbstractTesticular development in the harbour porpoise Phocoena phocoena was examined using animals (n = 192) stranded or by‐caught off the coast of England, Wales and Scotland. Classification of animals according to their stage of sexual development was undertaken using gonadal morphology and the distribution of cytoskeletal proteins. Smooth muscle actin (SMA) and vimentin proved particularly useful in this respect; SMA was prominent in the myoid peritubular cells of the adult testis, and two stages of peritubular cell SMA expression could be recognized (‘absent’ or ‘incomplete’). The initial appearance of SMA in peritubular cells was associated with significant increases in body length and body weight (P < 0.001), and occurred during the second year of life. Vimentin, which was prominent in prespermatogonia and spermatogonia, sometimes showed a polarized cytoplasmic distribution. This correlated with a developmental stage at which the seminiferous tubule epithelium becomes populated by germ cells (mean age 1.8 years). Several antibodies were tested for their utility as Sertoli cell markers, but none was found to be specific or useful. Nevertheless, immunohistochemical localization of desmin, GATA‐4, Ki67 and androgen receptor was possible despite the poor quality of tissue preservation. This study showed that immunohistochemical classification of these individuals provides a robust basis for the recognition of key physiological stages of sexual development in the male harbour porpoise. This may provide an alternative to the estimation of age, body weight and body length in future analyses aimed at detecting possible adverse effects of environmental pollutants on the reproductive potential of wild marine mammals.
Comparison of the pharmacokinetics of miconazole after administration via a bioadhesive slow release tablet and an oral gel to healthy male and female subjects
Authors: Cardot J.‐M. , Chaumont C. , Dubray C. , Costantini D. , Aiache J.‐M. 
Published: September 2004

AimsThe aim of this study was to compare salivary miconazole pharmacokinetics following once daily application of bioadhesive tablets (50 or 100 mg), vs the current treatment with a gel (3 times a day, 375 mg day−1).MethodsA three way cross over study was carried out in 18 healthy subjects (nine males, nine females) with a 1 week washout period between each treatment. Plasma and salivary pharmacokinetics of miconazole were assessed over a 24‐h period.ResultsIn all subjects the tablets gave higher and more prolonged salivary miconazole concentrations than the gel. Thus salivary miconazole AUC(0,24 h) was 37.2 times greater for the 100 mg tablet (90% confidence interval [CI] 22.9, 60.5) and 18.9 times greater for the 50 mg tablet (CI 11.7, 30.6) compared with the gel. Similarly, Cmax was 17.2 times greater (CI 11.8, 25.2) and 7.8 times greater (CI 5.3, 11.4) for the 100 mg tablet and 50 mg tablet, respectively. Comparison of the 100 mg and 50 mg tablets gave ratios of 2.2 and 2.0 for Cmax and AUC(0,24 h), respectively (CI 1.5, 3.2 and 1.2, 3.2). The mean time that salivary miconazole concentrations were above 0.4 µg ml−1 (the concentration reached 3 h after application of the oral gel according to published data) or above 1.0 µg ml−1 (the MIC of some Candida species) was greater for both bioadhesive tablets than for the oral gel (10–14 h vs 1.5 h and 7 h vs 0.6 h). Only 19 plasma samples from eight subjects had concentrations of miconazole above 0.4 µg ml−1. Ten of these were taken from five subjects after administration of the gel and nine from three subjects after administration of the tablets.ConclusionsThese data strongly support the further development of miconazole bioadhesive tablets as a sustained release formulation leading to improved antifungal exposure in the buccal cavity. A single daily application should improve compliance, whereas the low systemic absorption of miconazole will alleviate concerns regarding drug interactions and adverse effects.
Lack of effect of bezafibrate and fenofibrate on the pharmacokinetics and pharmacodynamics of repaglinide
Authors: Kajosaari Lauri I. , Backman Janne T. , Neuvonen Mikko , Laitila Jouko , Neuvonen Pertti J. 
Published: September 2004

AimsGemfibrozil markedly increases the plasma concentrations and blood glucose‐lowering effects of repaglinide, but the effects of other fibrates on repaglinide pharmacokinetics are not known. Our aim was to investigate the effects of bezafibrate and fenofibrate on the pharmacokinetics and pharmacodynamics of repaglinide.MethodsIn a randomized, three‐phase cross‐over study, 12 healthy subjects received 400 mg bezafibrate, 200 mg fenofibrate or placebo once daily for 5 days. On day 5, a single 0.25 mg dose of repaglinide was ingested 1 h after the last pretreatment dose. The concentrations of plasma repaglinide, bezafibrate and fenofibrate and blood glucose were measured up to 7 h postdose.ResultsDuring the bezafibrate and fenofibrate phases, the total area under the concentration‐time curve [AUC(0,∞)] of repaglinide was 99% (95% confidence interval of the ratio to the control phase 73, 143%) and 99% (85, 127%) of the corresponding value during the placebo (control) phase, respectively. Bezafibrate and fenofibrate had no significant effect on the peak concentration (Cmax) of repaglinide. The mean half‐life of repaglinide was 1.3 h in all phases. The blood glucose‐lowering effect of repaglinide was not affected by bezafibrate or fenofibrate. The AUC(0,8 h) values for bezafibrate and fenofibrate varied 3.0‐fold and 4.4‐fold between individual subjects, respectively. Neither bezafibrate nor fenofibrate affected the pharmacokinetic variables of repaglinide.ConclusionsBezafibrate and fenofibrate do not affect the pharmacokinetics or pharmacodynamics of repaglinide.
Effect of the oral renin inhibitor aliskiren on the pharmacokinetics and pharmacodynamics of a single dose of warfarin in healthy subjects
Authors: Dieterle Walter , Corynen Sophie , Mann Jessica 
Published: September 2004

AimsTo investigate the effects of aliskiren, an oral renin inhibitor, on the pharmacokinetics and pharmacodynamics of warfarin.MethodsIn a single‐blind, placebo‐controlled, randomized, two‐period crossover study, 15 healthy male and female subjects received a single oral dose of 25 mg racemic warfarin twice, once in the morning of the 8th day of treatment with 150 mg aliskiren and once at the same time point during treatment with placebo. Blood samples were collected for the measurement of prothrombin time (PT) and activated thromboplastin time (aPTT) and for determination of plasma concentrations of (R)‐ and (S)‐warfarin.ResultsAliskiren treatment had no effect on the blood coagulation parameters (PT, INR and aPTT). The ratios of least square means (90% CI) of pharmacokinetic parameters in the presence and absence of aliskiren for (R)‐ and (S)‐warfarin were Cmax 0.89 (0.82, 0.96) and 0.88 (0.80, 0.97), AUC(0,∞) 1.00 (0.94, 1.07) and 1.06 (0.96, 1.16) and t1/2 0.99 (0.92, 1.07) and 1.05 (0.96, 1.14).ConclusionsMultiple doses of aliskiren had no detectable effect on the pharmacokinetics or pharmacodynamics of a single dose of warfarin in healthy subjects.
Effect of ketoconazole on the pharmacokinetics of rosiglitazone in healthy subjects
Authors: Park Ji‐Young , Kim Kyoung‐Ah , Shin Jae‐Gook , Lee Ki Young 
Published: September 2004

AimsFungal infection is a significant comorbidity in patients with diabetes mellitus, and ketoconazole, an antifungal agent, causes a number of drug interactions with coadministered drugs. Rosiglitazone is a novel thiazolidinedione antidiabetic drug, mainly metabolized by CYP2C8 and to a lesser extent CYP2C9. We investigated the possible effect of ketoconazole on the pharmacokinetics of rosiglitazone in humans.MethodsTen healthy Korean male volunteers were treated twice daily for 5 days with 200 mg ketoconazole or with placebo, using a randomized, open‐label, two‐way crossover study. On day 5, a single dose of 8 mg rosiglitazone was administered orally, and plasma rosiglitazone concentrations were measured.ResultsKetoconazole increased the mean area under the plasma concentration–time curve for rosiglitazone by 47%[P = 0.0003; 95% confidence interval (CI) 23, 70] and the mean elimination half‐life from 3.55 to 5.50 h (P = 0.0003; 95% CI in difference 1.1, 2.4). The peak plasma concentration of rosiglitazone was increased by ketoconazole treatment by 17% (P = 0.03; 95% CI 5, 29). The apparent oral clearance of rosiglitazone decreased by 28% after ketoconazole treatment (P = 0.0005; 95% CI 18, 38).ConclusionsThis study revealed that ketoconazole affected the disposition of rosiglitazone in humans, probably by the inhibition of CYP2C8 and CYP2C9, leading to increasing rosiglitazone concentrations that could increase the efficacy of rosiglitazone or its adverse events.
European Surveillance of Antimicrobial Consumption (ESAC): Data Collection Performance and Methodological Approach
Authors: Vander Stichele R. H. , Elseviers M. M. , Ferech M. , Blot S. , Goossens H. ,   the ESAC Project Group
Published: September 2004

BackgroundEurope is a continent with strong public healthcare systems, but diverging antibiotic policies and resistance patterns.AimsTo describe the performance and methodological approach in a retrospective data collection effort (1997–2001), through an international network of surveillance systems, aiming to collect publicly available, comparable and reliable data on antibiotic use in Europe.MethodsA central multidisciplinary management team co‐ordinated a network of national representatives, liasing with national data providers and bodies responsible for antibiotic policy. The data collected were screened for bias, using a checklist. We focused on detection bias in sample and census data; errors in assigning medicinal product packages to the Anatomical Therapeutic Chemical Classification (ATC); errors in calculations of defined daily doses (DDD) per package; bias by over‐the‐counter sales and parallel trade; and bias in ambulatory care (AC)/hospital care (HC) mix. Datasets were corrected after national feedback, and classified as valid; valid but with minor bias; not valid.ResultsOf the 31 participating countries, 21 countries delivered AC data suitable for cross‐national comparison (14 for all 5 years). Of these, 17 countries provided data on a quarterly basis for at least 1 year. For HC, 14 countries were able to deliver valid data (nine for all 5 years). A valid estimate of the total exposure of national populations to human antibiotic consumption could be made in 17 countries.ConclusionIn cross‐national comparisons of antibiotic consumption in Europe, methodological rigour in correcting for various sources of bias and checking the validity of ATC/DDD assignment is needed.
Serial passage of MC3T3‐E1 cells down‐regulates proliferation during osteogenesis in vitro
Authors: Peterson W. J. , Tachiki K. H. , Yamaguchi D. T. 
Published: September 2004

Abstract.  Generally, fibroblast‐like cells and other types of human cells have been used to demonstrate the principles of replicative senescence in vitro and in vivo. These cells go through three stages of proliferation, including vigorous proliferation, declining proliferation and quiescence or no proliferation. Any variation of this process occurring in osteoprogenitor cells may offer insight into the mechanism of age‐related osteopaenia that predisposes individuals to osteoporosis and bone fractures. We selected MC3T3‐E1 cells derived from mouse calvaria to study the mechanism of replicative senescence of pre‐osteogenic cells because: (i) these cells constitute a well‐known model for studying osteogenesis in vitro; (ii) they undergo a developmental sequence of proliferation and differentiation similar to primary cells in culture; and (iii) they show signs of replicative senescence. These cells were aged by multiple passaging before their use for studying growth kinetics and the effects of population density, effect of extracellular matrix (ECM), size and phases of the cell cycle. Our results show that (i) MC3T3‐E1 cells go through the first two stages of proliferation in a manner similar to human cells, but escape the quiescent phase; (ii) the rate of proliferation is similar for low passage (LP) and high passage (HP) cells, but is decreased in very high passage cells (VHP); (iii) growth inhibition is observed using HP cells seeded at high density; (iv) HP ECM stimulates proliferation of both LP and HP cells; (v) a small increase in cell size is observed in HP cells, but no change is seen in the distribution analysis of their cell cycle; (vi) distribution analysis of the cell cycle of VHP cells reveals a decreased and an increased frequency of cells in S and G2 + M phases of their cell cycle, respectively. These results suggest that the mouse MC3T3‐E1 cell line exhibits many of the cellular and molecular markers associated with replicative senescence in culture as defined by human cells, such as fibroblast‐like cells. Alteration in the sensitivity of MC3T3‐E1 cells to intercellular contact and increase in cell size are the primary factors contributing to decreased proliferation of HP cells.
Counteraction of pRb‐dependent protection after extreme hypoxia by elevated ribonucleotide reductase
Authors: Graff P. , Seim J. , Åmellem Ø. , Arakawa H. , Nakamura Y. , Andersson K. K. , Stokke T. , Pettersen E. O. 
Published: September 2004

Abstract.  We have studied hypoxia‐induced cell cycle arrest in human cells where the retinoblastoma tumour suppressor protein (pRb) is either functional (T‐47D and T‐47DHU‐res cells) or abrogated by expression of the HPV18 E7 oncoprotein (NHIK 3025 cells). We have previously found that pRb is dephosphorylated and rebound in the nucleus in T‐47D cells arrested in S‐phase during hypoxia and that this binding is protracted even following re‐oxygenation. In the present study, however, we show that the long‐lasting arrest following re‐oxygenation induced by pRb‐binding in the cell nuclei may be overruled by an elevated level of ribonucleotide reductase (RNR). This seems to create a forced DNA‐synthesis, uncoordinated with cell division, which induces endoreduplication of the DNA. The data indicate that the cells initiating endoreduplication continue DNA‐synthesis until all DNA is replicated once and then may start cycling and cell division with a doubled DNA‐content. Corresponding data on the pRb‐incompetent NHIK 3025‐cells show similar endoreduplication in these. Thus, the data indicate that endoreduplication of DNA following re‐oxygenation may come, either as a result of hypoxic arrest of DNA‐synthesis when pRb‐function is absent in the cells, or if it is overruled by increased RNR. The present study further shows that pRb not only protects the culture by arresting most of the cells that are exposed to extreme hypoxia in S‐phase, but also increases cell survival by means of increased clonogenic ability of these cells. Interestingly, however, cells having an elevated level of RNR have equally high survival as wild‐type cells following 20 h extreme hypoxia. If RNR‐overruling of pRb‐mediated arrest following re‐oxygenation results in an unstable genome, this may therefore represent a danger of oncogenic selection as the protective effect of pRb on cell survival seems to be maintained.
Impact of tobacco smoke on interleukin-16 protein in human airways, lymphoid tissue and T lymphocytes
Authors: ANDERSSON A , QVARFORDT I , LAAN M , SJÖSTRAND M , MALMHÄLL C , RIISE G C , CARDELL L-O , LINDÉN A 
Published: September 2004

SUMMARYCD4+ and CD8+ lymphocytes are mobilized in severe chronic obstructive pulmonary disease (COPD) and the CD8+ cytokine interleukin (IL)-16 is believed to be important in regulating the recruitment and activity of CD4+ lymphocytes. In the current study, we examined whether tobacco smoke exerts an impact not only on IL-16 in the lower airways but also in CD4+ or CD8+ lymphocytes or in lymphoid tissue. The concentration of IL-16 protein was measured by enzyme-linked immunosorbent assay (ELISA) in concentrated bronchoalveolar lavage fluid (BALF) collected from 33 smokers with chronic bronchitis (CB), eight asymptomatic smokers (AS) and seven healthy never-smokers (NS). The concentrations of IL-16 and soluble IL-2 receptor alpha (sIL-2Rα) protein were also measured in conditioned medium from human blood CD4+ and CD8+ lymphocytes stimulated with tobacco smoke extract (TSE) in vitro. IL-16 mRNA was assessed in vitro as well, using reverse transcription–polymerase chain reaction (RT-PCR). Finally, the intracellular immunoreactivity for IL-16 protein (IL-16IR) was assessed in six matched pairs of palatine tonsils from smokers and non-smokers. BALF IL-16 was higher in CB and AS than in NS. TSE substantially increased the concentration of IL-16 but not sIL-2Rα in conditioned medium from CD4+ and CD8+ lymphocytes. There was no corresponding effect on IL-16 mRNA. IL-16IR in tonsils was lower in smokers than in non-smokers. The current findings demonstrate that tobacco smoke exerts a wide impact on the CD8+ cytokine IL-16, in the airway lumen, in blood CD4+ and CD8+ lymphocytes and in lymphoid tissue. The effect on IL-16 release may be selective for preformed IL-16 in CD4+ lymphocytes. New clinical studies are required to evaluate whether tobacco smoke mobilizes T lymphocytes via IL-16 in the lower airways and whether this mechanism can be targeted in COPD.
Cryptococcal capsular glucuronoxylomannan reduces ischaemia‐related neutrophil influx
Authors: Ellerbroek P. M. , Schoemaker R. G. , Van Veghel R. , Hoepelman A. I. M. , Coenjaerts F. E. J. 
Published: September 2004

AbstractBackground  The capsular polysaccharide glucuronoxylomannan (GXM) of Cryptococcus neoformans interferes with the chemotaxis and transendothelial migration of neutrophils. Intravenous administration of purified GXM has been shown to reduce the influx of inflammatory cells in an animal model of bacterial infection. Here we show that isolated GXM can also interfere with neutrophil migration in a model of inflammation not related to infection. We assessed the effects of intravenous GXM on neutrophil infiltration in a rat model of myocardial ischaemia, where neutrophil infiltration has been shown to contribute to postischaemic reperfusion injury.Materials and methods  Rats were subjected to coronary artery ligation followed by a 3‐h reperfusion period. Myeloperoxidase‐activity was measured in the ischaemic tissues as a marker of neutrophil infiltration.Results  Intravenous administration of GXM markedly reduced the influx of neutrophils in the ischaemic myocardium as measured by a 65% reduction of tissue MPO activity. This reduction of MPO activity was clearly correlated to the serum concentration of GXM. As complement activation by GXM was minimal at the doses applied in vivo, it is unlikely that generation of chemotactic C5a in the circulation by GXM caused the observed reduction in leucocyte migration.Conclusion  Purified cryptococcal GXM has the ability to reduce neutrophil influx even outside the scope of infection.