bluuebunny/crossref_metadata_2025_split huggingface dataset:
A population pharmacokinetic meta‐analysis of maraviroc in healthy volunteers and asymptomatic HIV‐infected subjects
Authors: Chan Phylinda L. S. , Weatherley Barry , McFadyen Lynn 
Published: March 2008

AIMSTo develop a population pharmacokinetic model for maraviroc, a noncompetitive CCR5 antagonist, after oral administration of tablets to healthy volunteers and asymptomatic HIV‐infected subjects and to quantify the inherent variability and influence of covariates on the parameters of the model.METHODSRich pharmacokinetic data available from 15 studies in healthy volunteers (n = 365) and two studies in asymptomatic HIV‐infected subjects (n = 48) were analysed using NONMEM. Maraviroc was administered as single or multiple oral tablet doses under fasted and fed conditions. Doses ranged from 100 to 1800 mg day−1.RESULTSA two‐compartment model parameterized to separate out absorption and clearance components on bioavailability was used. Absorption was described by a lagged first‐order process. A sigmoid Emax model described the effect of dose on absorption. A visual predictive check and nonparametric bootstrap evaluation confirmed that the model was a good description of the data. Typical CL, Vc and Vp values for a 30‐year‐old non‐Asian are 51.5 l h−1, 132 l and 277 l, respectively.CONCLUSIONSFor the typical non‐Asian subject, fasted bioavailability increased asymptotically with dose from 24% at 100 mg to 33% at 600 mg. A high‐fat meal taken with maraviroc reduced exposure by 43% for a 100‐mg dose to approximately 25% at doses of 600 mg. The typical Asian subject had a 26.5% higher AUC than the typical non‐Asian subject irrespective of dose, a difference not considered to be clinically relevant. None of the other covariates tested had any clinically relevant effects on exposure.
p21Cip1 expression is increased in ambient oxygen, compared to estimated physiological (5%) levels in rat muscle precursor cell culture
Authors: Lees S. J. , Childs T. E. , Booth F. W. 
Published: March 2008

Abstract.  Objective: While it is common practice to culture cells in the presence of ambient oxygen (~21% O2), O2 level observed in the physiological environment is often much lower. Previous efforts to culture a variety of different stem cells, including muscle precursor cells (MPC), under O2 conditions that better mimic in vivo conditions have resulted in enhanced proliferation. In the present study, we hypothesized that 20% O2 in culture represents a sufficient stimulus to cause increased expression of two key negative regulators of the cell‐cycle Cip/Kip family of cyclin‐dependent kinase inhibitors, p21Cip1 and p27Kip1, in MPCs. Materials and methods: MPCs were isolated from Fischer 344 × Brown Norway F1 hybrid male rats and O2 was adjusted in culture using a tri‐gas incubator. Results: 5‐Bromo‐2′‐deoxyuridine incorporation, cell number and nuclear proliferating cell nuclear antigen expression were all decreased after 48 h culture in 20% O2, compared to 5% O2. Twenty per cent O2 had no effect on either p27Kip1 promoter activity or protein expression. Although p21Cip1 promoter activity remained unchanged between 5% and 20% O2, there were significant increases in both p21Cip1 mRNA and protein expression. Furthermore, 20% O2 caused an increase in p21Cip1 mRNA stability and p53 transcription factor activity. Conclusion: These findings are considered important because they reveal p21Cip1 as a critical regulatory protein that needs to be considered when interpreting proliferation data from MPCs studied in culture. In addition, O2‐dependent regulation of MPC proliferation is relevant to conditions, including sarcopenia, heart failure, cancer and muscular dystrophy, where increased oxidative stress exists.
Human plasma accelerates immortalization of B lymphocytes by Epstein–Barr virus
Authors: Manor E. 
Published: March 2008

Abstract.  Objective: Serum and plasma contain species‐specific factors that modulate cell population growth and function, and that are required for proliferation of most cell cultures. Foetal calf serum (FCS) is the most common source of these growth factors. We studied the effect of human plasma (HP) on the immortalization process of B lymphocytes by Epstein–Barr virus (EBV) was studied. Materials and methods: The effect of HP as compared to FCS was done through assessment of cell proliferation. Results: It was found that HP (autologous and non‐autologous plasma) is more effective than FCS in generating lymphoblastoid cell lines, regardless of EBV status of the donors: 65% of HP‐supplemented cultures developed into lymphoblastoid cell lines by 7–14 culture days, as compared to 16% of cultures with FCS. In addition, 6% of HP‐supplemented cultures did not achieve becoming lymphoblastoid cell lines by day 35 in comparison to 94% of cultures with FCS. The higher proliferative effect of HP was not altered by heat inactivation or filtration. HP maintained its proliferative activity at 4 °C over 8 months, thus indicating that HP contains a stable growth factor(s), which accelerates B‐lymphocyte immortalization. Conclusion: The results support other studies that recommend the use of autologous plasma for tissue culture, mainly in the case of autologous transplantation. Furthermore, the use of HP allows preparation of lymphoblastoid cell lines from a small amount of peripheral blood in a shorter period of time and with a higher rate of success.
Influence of supramammary lymph node extract on in vitro cell proliferation
Authors: Duffy D. M. , Garrett S. M. , Ellis S. E. , Scott T. R. 
Published: March 2008

Abstract.  Objectives: Experiments were conducted to evaluate whether or not bovine supramammary lymph node extract (LNE) could support cell proliferation when it was substituted for bovine growth serum (BGS) in cell culture media. Materials and Methods: Two different preparations of LNE were tested. The first yielded protein concentration of 3 mg/mL and the second contained 27 mg/mL protein. Three cell lines (MDA‐MB‐435, MAC‐T and 1C6) were used in serum starvation assays to evaluate LNE. Cell proliferation assays were used to determine growth stimulation in the presence of LNE, and short‐term or rapid adaptation cultures were evaluated for LNE effects on cell survival. Results: Heat‐inactivated preparation 1 supported cell proliferation as well as or better (12–39%) than BGS following 2 days of serum starvation in culture. The second lymph node preparation provided a stimulatory effect (263–702% greater than BGS across all cell lines) following serum starvation at 2.7 and 5.4 mg/mL protein supplementation. A gradual adaptation process with lymph node supplementation into media maintained cell population growth on a short‐term basis. However, once cells were trypsinized or scraped and re‐seeded into 2.7 mg/mL LNE protein containing media, cells were unable to re‐adhere, leaving them detached, and eventually appearing to be dead. Conclusions: Substitution of BGS with LNE protein dramatically stimulated cells to proliferate, but did not allow for rapid cell population growth adaptation in vitro.
Conjugated linoleic acids differentially alter polyp number and diameter in the Apcmin/+ mouse model of intestinal cancer
Authors: Mandir N. , Goodlad R. A. 
Published: March 2008

Abstract.  Objective: Dietary conjugated linoleic acids (CLA) have had many health benefits claimed for them, including antineoplastic actions. Materials and methods: The effects of the predominant forms of CLA, namely the c9t11 and t10c12 isomers, or a mixture of these on polyp development, were investigated in the ApcMin/+ mouse. CLAs have also been linked to altered rates of cell renewal and cell proliferation so this was also studied, as was a further means of increasing tissue mass, namely crypt fission. Results: The stomach and small intestine were significantly heavier in the t10c12, and in the mixture‐treated groups (P < 0.001). Crypt fission was increased in the middle small intestine by the t10c12 diet while colonic weight was reduced by c9t11 provision and crypts were 20% shorter. The t10c12 and the mixture significantly reduced polyp number in the proximal small intestine but they increased polyp diameter in the middle and distal small intestine, to an extent that the polyp burden was significantly increased at these sites. All CLAs significantly reduced polyp number in the colon, but the mixture significantly increased polyp diameter in the colon. Conclusion: Increased polyp diameter associated with t10c12 diet and especially with the mixture is a cause of concern, as this is the commercially available form. The naturally occurring isomer, c9t11 decreased colonic polyp number and did not increase diameter, suggesting that this natural isomer is the most likely to be protective.
Long‐term prognosis of medullary thyroid carcinoma
Authors: Rendl G. , Manzl M. , Hitzl W. , Sungler P. , Pirich C. 
Published: March 2008

SummaryObjective  The clinical course of patients with medullary thyroid carcinoma (MTC) is variable, even in the subgroup of patients after surgery with curative intent and postoperatively persistent elevated calcitonin levels. This study aimed to evaluate the long‐term prognosis of survival in patients with MTC.Patients  Long‐term survival was analysed in 32 patients with MTC being treated in an endocrine centre over a 40‐year period. Patients were classified as having sporadic MTC, familial MTC (FMTC), multiple endocrine neoplasia (MEN) IIA or MEN IIB.Results  Seventeen patients had sporadic MTC (53·1%), eight had MEN IIA (25%) and three had MEN IIB (9·4%); the remaining four patients (12·5%) had not undergone genetic analysis until now. The overall average age at diagnosis was 42·0 years, and the median follow‐up time was 9·5 years (range 0·5–39 years). Mortality due to progressive MTC was 15·6%. The 5‐year survival rate was 96% (95% CI 89–100), the 10‐year survival rate 91% (95% CI 79–100), and the 15‐year survival rate 85% (95% CI 78–100). The estimated mean survival time after initial diagnosis was 31 years (95% CI 26·7–37·0). There is a significant difference in survival time between patients achieving complete remission compared with patients with biochemical persistent disease (P = 0·038) or metastasis (P = 0·0003). In five patients, advanced imaging with positron emission tomography/computed tomography (PET/CT) identified additional sites of tumour load. Eight more lymph node metastases were found in four patients and one local tumour recurrence in one patient by PET/CT.Conclusion  The overall prognosis of MTC is favourable, even if the rate of biochemical cure is lower in MTC than in differentiated types of thyroid cancer. This is also true for patients with biochemically persistent disease. Whether the identification of further tumour sites by advanced imaging procedures such as PET/CT translates into a better prognosis in patients with persistently elevated calcitonin levels remains to be investigated.
Restoration options for potential persistence of submersed aquatic vegetation: combining ecological, hydrodynamic and sediment transport modelling
Authors: BEST ELLY P. H. , TEETER ALLEN M. , LANDWEHR KEVIN J. , JAMES WILLIAM F. , NAIR SHYAM K. 
Published: March 2008

Summary1. Restoration of shallow turbid lakes to promote growth of submersed aquatic vegetation (SAV) requires knowledge of the environmental factors affecting SAV growth and persistence, and a means to predict the success of SAV reestablishment under different management scenarios to improve these environmental conditions. We used a dynamic ecological modelling approach relating SAV responses to changes in physical and chemical conditions, with information on water level, flow and transparency being provided by hydrodynamic and sediment transport models.2. The potential persistence of Vallisneria americana was similar under simulated environmental conditions in 1946 and in 1954, as was the potential persistence of Potamogeton pectinatus, indicating that the disappearance of V. americana from Peoria Lake (U.S.A.) previously attributed to an extended spring flood in 1954, may have been related to the combined effects of changes in water level, flow and water transparency as well as possibly other factors.3. Recent environmental conditions (for 2000) proved not to be conducive for the colonization and persistence potential of V. americana, but would allow colonization by P. pectinatus. The construction of a hypothetical levee along the eastern descending line of the navigation channel in Upper Peoria Lake, which was expected to reduce fetch‐ and navigation‐related turbidity, did not improve the situation for V. americana and overall deteriorated the situation for P. pectinatus. Thus, such a hydraulic alteration, generally considered as beneficial for SAV restoration, may not always be successful.4. The results of the simulations indicated that the environmental conditions for potential persistence in Peoria Lake were generally less favourable for V. americana than for P. pectinatus. Measures suggested to restore SAV communities in such a lake should aim at reducing concentrations of total suspended solids at the point of inflow by a factor of three to four and limiting fetch‐ and navigation‐related resuspension.
Effects of agriculture on wood breakdown and microbial biofilm respiration in southern Appalachian streams
Authors: MCTAMMANY M. E. , BENFIELD E. F. , WEBSTER J. R. 
Published: March 2008

Summary1. Agriculture causes high sediment, nutrient and light input to streams, which may affect rates of ecosystem processes, such as organic matter decay. In the southern Appalachians, socioeconomic trends over the past 50 years have caused widespread abandonment of farmland with subsequent reforestation. Physical and chemical properties of streams in these reforested areas may be returning to pre‐agriculture levels thereby creating the potential for recovery of ecosystem processes.2. We examined wood breakdown and microbial activity on wood substrata in streams with different historical and current agricultural activity in their catchments. We analysed historical (1950) and recent (1998) forested land cover from large areas of the southern Appalachians and categorized streams based on percent forested land cover in these two time periods. Categories included a gradient of current agriculture from forested to heavily agricultural and reforestation from agriculture due to land abandonment. We compared microbial respiration on wood veneer substrata and breakdown of wood veneers among these land‐use categories. We also compared temperature, sediment accumulation and nitrogen and phosphorus concentrations.3. Streams with current agriculture had higher concentrations of dissolved inorganic nitrogen than forested streams. Despite reforestation from agriculture, nitrogen concentrations were also elevated in streams with agricultural histories relative to forested streams. Temperature was also higher in agricultural streams but appeared to recover from historical agriculture through reforestation and stream shading.4. Wood breakdown rates ranged from 0.0015 to 0.0076 day−1 and were similar to other studies using wood veneers to determine breakdown rate. Microbial respiration increased with incubation time in streams up to approximately 150 days, after which it remained constant. Neither wood breakdown nor microbial respiration was significantly different among land‐use categories, despite the observed physical and chemical differences in streams based on land‐use. Wood breakdown rates could be predicted by microbial respiration indicating microbial control of wood breakdown in these streams. Both breakdown and microbial respiration were negatively correlated with the amount of inorganic sediment accumulated on wood veneers.5. Higher nutrients and temperature led us to expect faster breakdown and higher microbial respiration in agricultural streams, but sediment in these streams may be limiting microbial activity and breakdown of organic material resulting in little net effect of agriculture on wood breakdown. Wood may not be desirable as a tool for functional assessment of stream integrity due to its unpredictable response to agriculture.
Multi‐scale assessment of macroinvertebrate richness and composition in Mediterranean‐climate rivers
Authors: BONADA NÚRIA , RIERADEVALL MARIA , DALLAS HELEN , DAVIS JENNY , DAY JENNY , FIGUEROA RICARDO , RESH VINCENT H. , PRAT NARCÍS 
Published: March 2008

Summary1. Similar constraints in distant, but climatically comparable, regions may be expected to yield biotic assemblages with similar attributes. Environmental factors that constrain communities at smaller scales, however, may be different between climatically similar regions. Thus, patterns observed at large scales may differ from those detected at small scales, and international comparisons should be focussed at multiple scales.2. Mediterranean‐climate regions (MCRs) are characterized by remarkable seasonal variability in precipitation and temperature. Accordingly, rivers in these regions have seasonal and predictable floods and droughts, and temporary reaches are frequent. Present in six geographical regions of the world, MCRs have similar environmental constraints and are ideal for testing intercontinental similarities between macroinvertebrate communities.3. We examined aquatic macroinvertebrate taxon richness and composition in MCRs at three scales: regional, reach and macrohabitat. At the regional scale, the Mediterranean Basin had the highest taxon richness at family level, and southwestern Australia the lowest. Taxonomic composition showed c. 85% similarity between the northern hemisphere MCRs of California and the Mediterranean Basin, which were followed in similarity by South Africa. The two Australian MCRs (South west and South) showed a similarity to each other of about 70% whereas the Chilean fauna was the most distinct.4. At the reach scale, taxon richness was not significantly different between permanent and temporary reaches in any MCR, whereas taxonomic composition was significantly different among northern hemisphere MCRs. At the macrohabitat scale, taxon richness was not significantly different between lotic and lentic macrohabitats within any of the MCRs, but differences in macroinvertebrate communities were found between macrohabitats when considering regions.5. Our results show that the strength of similarity between distant but climatically similar regions is scale‐dependent, being highest at the macrohabitat scale. Although the similarities in richness and composition at the macrohabitat scale are presumed to be universal, the seasonal predictability of drought in MCRs is expected to result in characteristic macroinvertebrate responses at the reach scale. We suggest, however, that regional evolutionary history and environmental characteristics may override this general pattern of a similar response of MCRs at different scales. The Mediterranean Basin and California, having similar historical and environmental condition, thus appeared as the most similar MCRs at all scales.
Climate change affects colonization dynamics in a metacommunity of three Daphnia species
Authors: ALTERMATT FLORIAN , PAJUNEN V. ILMARI , EBERT DIETER 
Published: March 2008

AbstractClimate change is expected to alter the range and abundance of many species by influencing habitat qualities. For species living in fragmented populations, not only the quality of the present patches but also access to new habitat patches may be affected. Here, we show that colonization in a metacommunity can be directly influenced by weather changes, and that these observed weather changes are consistent with global climate change models. Using a long‐term dataset from a rock pool metacommunity of the three species Daphnia magna, Daphnia longispina and Daphnia pulex with 507 monitored habitat patches, we correlated a four‐fold increase in colonization rate with warmer, drier weather for the period from 1982 to 2006. The higher colonization rate after warm and dry summers led to an increase in metacommunity dynamics over time. A mechanistic explanation for the increased colonization rate is that the resting stages have a higher exposure to animal and wind dispersal in desiccated rock pools. Although colonization rates reacted in the same direction in all three species, there were significant species‐specific effects that resulted in an overall change in the metacommunity composition. Increased local instability and colonization dynamics may even lead to higher global stability of the metacommunity. Thus, whereas climate change has been reported to cause a unidirectional change in species range for many other species, it changes the dynamics and composition of an entire community in this metacommunity, with winners and losers difficult to predict.
A critical analysis of media discourse on information technology: preliminary results of a proposed method for critical discourse analysis
Authors: Cukier Wendy , Ngwenyama Ojelanki , Bauer Robert , Middleton Catherine 
Published: March 2008

AbstractSince the 1980s, there has been a growing body of critical theory in information systems research. A central theoretical foundation of this research is Habermas’ theory of communicative action, which focuses on implications of speech and proposes general normative standards for communication. Habermas also places particular emphasis on the importance of the public sphere in a democratic society, critiquing the role of the media and other actors in shaping public discourse. While there has been growing emphasis on critical discourse analysis (CDA), there has been limited effort to systematically apply Habermas’ validity claims to empirical research. Moreover, while critical research in information systems has examined communication within the organizational context, public discourse on information technology has received little attention. The paper makes three primary contributions: (1) it responds to Habermas’ call for empirical research to ground and extend his theory of communication in every day critical practice; (2) it proposes an approach to applying Habermas’ theory of communication to CDA; and (3) it extends the reach of critical research in information systems beyond micro‐level organizational concerns and opens up to critical reflection and debate on the impact of systematically distorted communication about technology in the public sphere.
Association between polymorphisms in the prostate‐specific antigen (PSA) promoter and release of PSA
Authors: Sävblom C. , Giwercman A. , Malm J. , Halldén C. , Lundin K. , Lilja H. , Giwercman Y. 
Published: March 2008

SummaryVariations in serum prostate‐specific antigen (PSA) have been ascribed to A/G nucleotide polymorphisms located at −158 bp (rs266882) and −4643 bp (rs925013), relative to the transcription start site within the promoter of the PSA gene. PSA is also an androgen receptor target (AR) gene and polymorphisms in AR gene are known to affect AR function. Our objective was to compare the impact of these A/G polymorphisms separately or in combination with AR CAG micro satellite on regulation of PSA secretion into seminal plasma and blood in young men. Leukocyte DNA was extracted from 291 conscripts and genotyping performed with the Sequenom Mass Array System. PSA was measured with an immunofluorometric assay. Linear regression analysis was used to test the association of polymorphism frequencies with serum and seminal plasma levels of PSA. PSA gene polymorphisms at −158 bp or −4643 bp did not alone influence total PSA (tPSA) levels in seminal plasma or in blood. Homozygotes for the A‐allele at −158 bp in combination with CAG > 22 had significantly higher serum levels of tPSA than subjects carrying the G‐allele (p = 0.01). In conclusion, the PSA gene polymorphisms did not importantly influence the levels of tPSA in seminal plasma or in blood. tPSA in serum was influenced by interactions between PSA promoter variants and AR CAG polymorphism.