bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semi‐mechanistic pharmacokinetic/pharmacodynamic modelling of the antimalarial effect of artemisinin
Authors: Gordi Toufigh , Xie Rujia , Jusko William J. 
Published: August 2010

PurposeTo characterize artemisinin pharmacokinetics (PK) and its antimalarial activity in vivo.MethodsArtemisinin salivary concentration and parasite count data were obtained from Vietnamese malaria patients receiving two different dosage regimens. PK data were analysed using a previously developed semiphysiological model incorporating autoinduction of eliminating enzymes. A pharmacodynamic (PD) model reflecting different stages of the parasite life‐cycle was developed and fitted to the data. The model included visible and invisible compartments as well as sensitive, insensitive, and injured parasite stages. Salivary artemisinin concentrations functioned as the driving force for the observed decrease in the number of parasites.ResultsLarge interindividual variability was observed in both PK and PD data. The PK model described reasonably well the observed decrease in salivary concentrations after repeated drug administration. The preinduction hepatic extraction ratio of artemisinin was estimated to be 0.87 with a volume of distribution of 27 L. Artemisinin half‐life averaged 0.7 h. Incorporation of a saturable hepatic elimination affecting the first‐pass extraction as well as a higher intrinsic clearance in female patients resulted in the best fit of the model to the data. The PD model described the decrease in the number of parasites during the course of treatment well. The longest mean transit time of parasites from sensitive, visible to invisible to insensitive visible stages was found to be 34.5 h through one life‐cycle. The half‐life of injured parasites was 2.7 h.ConclusionsThe proposed semimechanistic PK/PD model successfully described the time course of both salivary artemisinin concentrations after repeated dosing and the number of parasites in patients treated with the drug.
Detection of prognostically relevant genetic abnormalities in childhood B‐cell precursor acute lymphoblastic leukaemia: recommendations from the Biology and Diagnosis Committee of the International Berlin‐Frankfürt‐Münster study group
Authors: Harrison Christine J. , Haas Oskar , Harbott Jochen , Biondi Andrea , Stanulla Martin , Trka Jan , Izraeli Shai 
Published: August 2010

SummaryTreatment of childhood acute lymphoblastic leukaemia (ALL) has improved considerably in recent years. A contributing factor has been the improved stratification for treatment according to a number of factors, including genetic determinants of outcome. Here we review the current diagnostic criteria of genetic abnormalities in precursor B‐ALL (BCP‐ALL), including the relevant technical approaches and the application of the most appropriate methods for the detection of each abnormality. The abnormalities with the most significant impact for treatment and management of BCP‐ALL are t(9;22)(q34;q11)/BCR‐ABL1, t(4;11)(q21;q23)/MLL‐AFF1 and near‐haploidy/low hypodiploidy for high risk stratification and, to a lesser extent, t(12;21)(p13;q22)/ETV6‐RUNX1 and high hyperdiploidy for good risk management. Apart from the numerical abnormalities, these can be routinely tested for by reverse transcription polymerase chain reaction, providing a basic yet informative screen. However, cytogenetics, particularly fluorescence in situ hybridization may provide reliable alternative detection methods dependent upon the preferred technical approach within each protocol.
MicroRNA‐21 expression in neonatal blood associated with antenatal immunoglobulin E production and development of allergic rhinitis
Authors: Chen R.‐F. , Huang H.‐C. , Ou C.‐Y. , Hsu T.‐Y. , Chuang H. , Chang J.‐C. , Wang L. , Kuo H.‐C. , Yang K. D. 
Published: August 2010

SummaryBackground
The prevalence of allergic diseases has increased in the past decades. It is unknown whether expression of certain microRNAs (miRNAs) in neonatal leucocytes is correlated to IgE production and/or allergic diseases.Objective
This study investigated the association of miRNA expression in neonatal leucocytes with cord blood IgE (CBIgE) elevation and development of allergic disease.Methods
We screened for the expression of a panel of 157 miRNAs in mononuclear leucocytes from human umbilical cord blood (CB) samples with elevated CBIgE and tracked the association of down‐regulated miRNA expression to the miRNA‐targeted gene expression and to children with allergic rhinitis (AR).Results
Among the initial screen of 10 CB samples with elevated CBIgE, expression of eight of the 157 miRNAs was low. Of these eight down‐expressed miRNAs, three remained down‐regulation in a validation with other 20 CB samples, and two of the three miRNAs, miR‐21 and miR‐126, were significantly lower in monocytes from AR children. Further analysis of mRNA expression of the miR‐21‐targeted genes identified that TGFBR2 expression on monocytes was significantly up‐regulated in CB with elevated CBIgE, and in AR patients. Transfection of miR‐21 precursor into monocytes from patients with AR increased miR‐21 expression and decreased TGFBR2 expression.Conclusion
This study demonstrated the first in the literature that lower miR‐21 expression in CB and increased TGFBR2 expression is associated with antenatal IgE production and development of AR. Cite this as: R.‐F. Chen, H.‐C. Huang, C.‐Y. Ou, T.‐Y. Hsu, H. Chuang, J.‐C. Chang, L. Wang, H.‐C. Kuo and K. D. Yang, Clinical & Experimental Allergy, 2010 (40) 1482–1490.
Cytokine receptors: structure and signal transduction
Authors: FOXWELL B M J , BARRETT K , FELDMANN M 
Published: August 2010

SUMMARYIn the past 2–3 years, a number of cytokine receptors have been partly characterized and the cDNA for the ligand binding chains cloned. This has revealed that cytokine receptors are complex. Many are known to be multichain receptors (e.g. IL-2) and since their mechanism of signal transduction is not obvious, it is likely that other proteins yet to be defined take part in the signalling process. The cloning of the receptor ligand binding chain has revealed that (unlike cytokines), there are major families of receptors. Some are members of the Ig supergene family (e.g. IL-1 receptor), others are members of the nerve growth factor receptor family (e.g. TNF), but the majority are members of the haematopoietic growth factor family (e.g. IL-3, GM-CSF). Yet other cytokine receptors do not belong to a family, e.g. IFN-γ.
Soluble apoptosis molecules in primary biliary cirrhosis: analysis and commitment of the Fas and tumour necrosis factor-related apoptosis-inducing ligand systems in comparison with chronic hepatitis C
Authors: Pelli N , Floreani A , Torre F , Delfino A , Baragiotta A , Contini P , Basso M , Picciotto A 
Published: August 2010

SummaryApoptosis in the liver is generated mainly by the Fas system. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has been proposed recently as a new apoptotic inducer. In the liver environment hepatocytes and biliary epithelial cells express TRAIL receptors which are up-regulated by increased levels of bile acids and during viral hepatitis. As for FasL, a soluble form of TRAIL has been described. To explore the commitment and level of activation of these two apoptotic systems in patients affected by primary biliary cirrhosis (PBC) or chronic hepatitis C (CH-C), a comparative study was drawn. Thirty patients with PBC on ursodeoxycholic acid have been enrolled. This group was compared with 30 patients with CH-C and with 20 healthy subjects. Soluble Fas ligand (sFasL) and soluble TRAIL (sTRAIL) levels were evaluated by double determinant immune assay and enzyme-linked immunosorbent assay (ELISA), respectively. Soluble FasL molecules were higher in PBC compared to CH-C (P = 0·009). Soluble FasL was not detected in controls. Soluble TRAIL was significantly higher in CH-C patients compared to PBC (P = 0·0001). Soluble TRAIL levels were higher in PBC and in CH-C than in controls (P = 0·015 and P &lt; 0·001, respectively). No correlation between sFasL and sTRAIL, stage of disease, liver histology in each disease and cytolysis was present. Our data show different levels of commitment of TRAIL and Fas apoptosis-inducing systems in CH-C and PBC. Thus a different prominent role of TRAIL and Fas systems in the pathogenesis of these two conditions can be speculated: the former by inducing the death of infected hepatocytes, the latter by mediating the disappearance of bile duct.
The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease
Authors: Afzali B , Lombardi G , Lechler R I , Lord G M 
Published: August 2010

SummaryUncommitted (naive) murine CD4+ T helper cells (Thp) can be induced to differentiate towards T helper 1 (Th1), Th2, Th17 and regulatory (Treg) phenotypes according to the local cytokine milieu. This can be demonstrated most readily both in vitro and in vivo in murine CD4+ T cells. The presence of interleukin (IL)-12 [signalling through signal transduction and activator of transcription (STAT)-4] skews towards Th1, IL-4 (signalling through STAT-6) towards Th2, transforming growth factor (TGF)-β towards Treg and IL-6 and TGF-β towards Th17. The committed cells are characterized by expression of specific transcription factors, T-bet for Th1, GATA-3 for Th2, forkhead box P3 (FoxP3) for Tregs and RORγt for Th17 cells. Recently, it has been demonstrated that the skewing of murine Thp towards Th17 and Treg is mutually exclusive. Although human Thp can also be skewed towards Th1 and Th2 phenotypes there is as yet no direct evidence for the existence of discrete Th17 cells in humans nor of mutually antagonistic development of Th17 cells and Tregs. There is considerable evidence, however, both in humans and in mice for the importance of interferon (IFN)-γ and IL-17 in the development and progression of inflammatory and autoimmune diseases (AD). Unexpectedly, some models of autoimmunity thought traditionally to be solely Th1-dependent have been demonstrated subsequently to have a non-redundant requirement for Th17 cells, notably experimental allergic encephalomyelitis and collagen-induced arthritis. In contrast, Tregs have anti-inflammatory properties and can cause quiescence of autoimmune diseases and prolongation of transplant function. As a result, it can be proposed that skewing of responses towards Th17 or Th1 and away from Treg may be responsible for the development and/or progression of AD or acute transplant rejection in humans. Blocking critical cytokines in vivo, notably IL-6, may result in a shift from a Th17 towards a regulatory phenotype and induce quiescence of AD or prevent transplant rejection. In this paper we review Th17/IL-17 and Treg biology and expand on this hypothesis.
Reduced apoptosis and increased inflammatory cytokines in granulomas caused by tuberculous compared to non-tuberculous mycobacteria: role of MPT64 antigen in apoptosis and immune response
Authors: Mustafa T , Wiker H G , Mørkve O , Sviland L 
Published: August 2010

SummaryInhibition of apoptosis of infected macrophages by pathogenic mycobacteria is suggested to be an important virulence mechanism, but little is known about the mycobacterial proteins involved in the inhibition of apoptosis. In this study we investigated differences in apoptosis and immune response and their correlation with the expression of Mycobacterium tuberculosis complex-specific secretory protein MPT64 in lesions caused by tuberculous or non-tuberculous mycobacteria by analysing the in situ expression of apoptosis-related proteins (FasL, Fas, Bax, Bcl-2), apoptotic cells, inflammatory cytokines [tumour necrosis factor (TNF)-α, interleukin (IL)-10, transforming growth factor (TGF)-β, interferon (IFN)-γ] and MPT64 antigen. The discrimination of mycobacteria was made by nested polymerase chain reaction (PCR) amplification of IS6110, which is specific for M. tuberculosis complex organisms. Forty-seven cases of lymphadenitis with necrotic granulomas were evaluated. With nested PCR, 30/47 cases were positive for M. tuberculosis. MPT64 antigen was detected specifically in the PCR-positive cases. Granulomas caused by tuberculous mycobacteria had fewer apoptotic cells, higher numbers of cells expressing TNF-α and TGF-β and less extensive necrosis than granulomas caused by non-tuberculous mycobacteria. There was a significant negative correlation between apoptotic cells and the number of cells expressing MPT64 antigens, suggesting a role for MPT64 protein in the inhibition of apoptosis. Granulomas with higher amounts of MPT64 also showed a greater number of cells expressing TGF-β than those with lower amounts of MPT64. In conclusion, this study supports the hypothesis that inhibition of apoptosis is a virulence mechanism for tuberculous mycobacteria. Correlation of MPT64 antigen with expression of macrophage deactivating cytokines and reduced apoptosis suggests its role in pathogenesis and bacillary persistence.
The use of liquid chromatography in the study of cadmium speciation in soil solutions from polluted soils
Authors: TILLS ALISON R. , ALLOWAY B. J. 
Published: August 2010

SummaryChromatographic methods were used in an attempt to identify the various species of cadmium in soil solution. Exclusion and reverse‐phase chromatography using HPLC showed that cadmium existed in the form of low‐molecular weight, highly polar species. Ion‐exchange chromatography was used to divide soil solution cadmium into cationic, anionic and neutral species. Cadmium was found to be mainly in the form of inorganic cationic species, including the free ionic form, Cd2+, and some as neutral species, possibly organic as well as inorganic, especially in soils of higher pH. Anionic species were relatively unimportant. These results showed general agreement with those of other authors using computer models to predict cadmium speciation in soil solution.
Soil solution aluminium activity related to theoretical A1 mineral solubilities in four Australian soils
Authors: HELYAR K. R. , CONYERS M. K. , MUNNS D. N. 
Published: August 2010

SUMMARYFour soils were treated with HNO3, CaCO3and K2SO4to enable observation of the response of the soil solution composition and the solution A1 ion activity (Al3+) to the treatments and to time. The clay fraction of three of the soils was dominated by illite, kaolinite and quartz. The fourth was minated by kaolinite and iron oxides. The initial pH in 0.01 M CaCl2varied between 4.0 and 5.0 and the organic carbon content from 0.7 to 1.1%. The soil solutions from soils dominated by kaolinite, illite and quartz were generally supersaturated with respect to quartz and well ordered kaolinite, and unsaturated with respect to illite. The soil solutions from the soil dominated by kaolin and iron oxide were generally unsaturated with respect to quartz but still saturated with respect to ell crystallized kaolin. Within mineral groups such as Al2SiO5compounds, A12Si2O5(OH)4(kaolinite group), and Al(OH)3(A1 oxide) minerals, the more soluble forms became less supersaturated or unsaturated with time for many treatments.Lime treatment usually increased the ion activity product of AI(OH)3in all soils, and of minerals with the composition, Al2SiO5, in the illite/kaolinite soils. Acid treatment reduced the apparent solubility of Al(OH)3, and the A1 silicates in the Al2SiO5, and Al2, Si2, O5,(OH)4, mineral groups on all soils. These results are interpreted to indicate that lime treatment led to the formation of trace quantities of more soluble A1 minerals that subsequently controlled (Al3+), whereas acid treatment dissolved trace quantities of such minerals leaving less soluble minerals to control (Al3+). The results suggest that, in mineral soils such as these, (Al3+) is under the control of inorganic dissolution and precipitation processes. These processes conform to expectations given the free energy of various inorganic aluminium compounds. Furthermore the sequence of dissolution and formation processes appears to be governed by the Gay‐Lussac—Ostwald step rule.
Lobster larval transport in the southern Gulf of St. Lawrence
Authors: CHASSÉ JOËL , MILLER ROBERT J. 
Published: August 2010

AbstractA bio‐physical semi‐Langrangian model was developed to follow the drift and abundance of lobster larvae from hatching to settlement as post‐larvae. The geographic domain encompasses Northumberland Strait and the areas surrounding Prince Edward Island in the southern Gulf of St. Lawrence. The model was run for ten larval seasons, 1983–87 and 1997–2001, representing two periods of egg production. The model was forced with tides, winds, heat fluxes, and marine and freshwater fluxes at open boundaries. Biological inputs were location, date, and density of larvae at hatching, development rates, a time window and a minimum bottom temperature required for successful settlement, and two scenarios of daily mortality. Net drift was west to east but stronger on the north than the south side of Prince Edward Island. The hatch was greater in the second 5‐yr period, but the spatial patterns of settlement were similar. For both mortality scenarios, the same five of the 24 larval source areas were important in providing settlers. Horizontal shear of larval distribution indicates fishing communities were dependent on the hatch from fishing grounds of multiple upstream communities. Variation in daily and annual post‐larval settlement was greatest north of Prince Edward Island. From the 24 source areas there was an eightfold range in the fraction of larvae surviving to settlement, with advection into deep water an important cause of mortality. Four to five possible fishery management areas were identified using multidimensional scaling to group sink areas having shared source areas. We hypothesize leaky discontinuity in connectivity between these groups.
Distribution and drift pathways of Greenland halibut (Reinhardtius hippoglossoides) during early life stages in the eastern Bering Sea and Aleutian Islands
Authors: SOHN D. , CIANNELLI L. , DUFFY‐ANDERSON J. T. 
Published: August 2010

AbstractWe describe the spatial distribution and dispersal pathways of Greenland halibut (Reinhardtius hippoglossoides) early life stages based on historical field data from the eastern Bering Sea and adjacent water along the eastern Aleutian Islands. Our results indicate that Greenland halibut from preflexion larvae to newly settled juveniles have a long pelagic duration and are subject to extended drift pathways. Hatching may occur in deep water, below 530 m, and larvae rise in the water column as they grow. Flexion/postflexion larvae are mostly found around the Pribilof Islands over the middle shelf (50–100‐m isobaths) in July, and settling occurs during late summer on the middle shelf near St. Matthew Island. However, given that age‐1 individuals were primarily found on the outer shelf, it appears that Greenland halibut actively move to deeper water with age (or size). The mechanisms of slope–shelf connectivity in preflexion larvae may be related to the Bering Slope Current in the vicinity of both Bering and Pribilof Canyons. This study shows that Greenland halibut early life stages have extensive horizontal ontogenetic migrations in the Bering Sea, and utilize a range of geographic areas over the basin and slope along the Aleutian Islands and in the eastern Bering Sea. Based on these results, it is hypothesized that settlement success and recruitment of Greenland halibut may be influenced by variability in currents and flows of the Bering Sea slope and shelf during their transport.
Thermal habitat of striped bass (Morone saxatilis) in coastal waters of northern Massachusetts, USA, during summer
Authors: NELSON GARY A. , ARMSTRONG MICHAEL P. , STRITZEL‐THOMSON JENNIFER , FRIEDLAND KEVIN D. 
Published: August 2010

AbstractStriped bass, Morone saxatilis, were captured and released with temperature‐measuring data storage tags in Salem Sound, Massachusetts, to collect data on their thermal preferences in coastal and marine waters and to identify environmental factors that may influence temperatures experienced during their summer residence. Striped bass recaptured during summer of 2006 (21 of 151 releases) experienced a wide range of temperatures (6.5–28.0°C) while at‐large for 1–53 days. Overall mean temperature and standard deviation selected by striped bass recaptured in Salem Sound during the longest commonly‐shared duration of time (3–12 July) were 17.8 and 3.57°C, respectively. Comparison of temperature data between fish and 13 vertical arrays in Salem Sound revealed that striped bass experienced higher and more variable temperatures, and that daily changes in temperature actually experienced were unrelated to daily changes in surrounding ambient temperature. Regular cyclical changes in temperature of all striped bass and vertical arrays were identified as influences of the local tide, which contributed about a 2°C change in temperature, on average, over the complete cycle. Most striped bass appeared to limit their activities to depths shallower than the lower limit of the thermocline, above which temperatures generally exceed 9.0°C in Salem Sound. Therefore, it is likely that the vertical distribution of striped bass is restricted by the low temperatures below this depth. An implication of this finding is that the spatial distribution of striped bass may be defined coarsely by knowledge of the distribution of temperature in coastal areas.
Seasonal spawning and wind‐regulated retention‐dispersal of early life stage Atlantic cod (Gadus morhua) in a Newfoundland fjord
Authors: KNICKLE D. CRAIG , ROSE GEORGE A. 
Published: August 2010

AbstractSequential ichthyoplankton surveys were used to determine the spatial and temporal distribution of eggs and larvae over coastal spawning grounds of Atlantic cod (Gadus morhua) in Smith Sound, Trinity Bay, Newfoundland, during the spring and summer of 2006 and 2007. Egg densities showed similar patterns for both years with two peaks in abundance in spring (March–April) and late summer (late July). A clear progression of development stages (1–4) was observed in spring and summer in 2006 and summer in 2007, suggesting retention of eggs within the Sound during these periods. Modelled predictions of vertical egg distributions indicated eggs were broadly distributed near the surface during spring (March–April), but were concentrated below the pycnocline (>10 m) within the inner portions of the Sound during the summer months (July–August). Back‐calculated peaks in spawning based on water temperatures were estimated at 11 and 4 April for 2006 and 2007, respectfully, with late season peaks centred on 21–24 July for both years. Environmental data indicated cooler water temperatures and periods of high wind stress in spring, and warmer, calmer periods late summer, consistent with higher retention and faster development times on the spawning grounds later in the season. We conclude that spring and summer spawning events result in different distributions of early life stages and may lead to different distributions of juvenile and adult fish.