bluuebunny/crossref_metadata_2025_split huggingface dataset:
Torsemide renal clearance and genetic variation in luminal and basolateral organic anion transporters
Authors: Vormfelde Stefan V. , Schirmer Markus , Hagos Yohannes , Toliat Mohammad R. , Engelhardt Sabine , Meineke Ingolf , Burckhardt Gerhard , Nürnberg Peter , Brockmöller Jürgen 
Published: April 2006

AimsTo investigate the association between torsemide renal clearance and genetic variation in the basolaterally expressed renal organic anion transporters OAT1 and OAT3 and in the luminally situated OAT4.MethodsWe analysed 22 polymorphisms in the OAT coding genes SLC22A6, SLC22A8 and SLC22A11 and their haplotypes and measured torsemide renal clearance in 95 healthy men. In addition, the effect of torsemide on the OAT‐mediated transport was studied in vitro.ResultsIn stably transfected HEK293 cells torsemide (100 µm) inhibited the uptake by human OAT1, OAT3 and OAT4 by 63.1, 58.1 and 68.0%, respectively. Torsemide renal clearance ranged from 6.5 to 43.1 ml min−1 with a log‐normal distribution and a geometric mean of 15.6 ml min−1 (15.0–16.1 ± SEM). No clear outlier group was observed. AA carriers of the polymorphism rs11231809 in SLC22A11 had a torsemide renal clearance of 13.3 ml min−1 (12.7–13.9) compared with 15.1 ml min−1 (14.5–15.8) in AT and 18.0 ml min−1 (16.7–19.5) in TT carriers (P = 0.002). The two most frequent haplotypes at SLC22A11 showed an association with torsemide renal clearance. Homozygous carriage of these two haplotypes resulted in renal clearances of 21.2 ml min−1 (19.0–23.7) and 11.8 ml min−1 (10.5–13.5), respectively. No association between reanl clearance and genetic variation in SLC22A6 or SLC22A8 was observed.ConclusionsGenetic variation in the gene encoding the luminally expressed OAT4 rather than in the basolaterally expressed OATs may affect the renal clearance of torsemide.
The effects of ritonavir and lopinavir/ritonavir on the pharmacokinetics of a novel CCR5 antagonist, aplaviroc, in healthy subjects
Authors: Adkison Kimberly K. , Shachoy‐Clark Anne , Fang Lei , Lou Yu , Otto Vicky R. , Berrey M. Michelle , Piscitelli Stephen C. 
Published: April 2006

AimsThis study assessed the effects of the CYP3A inhibitors lopinavir/ritonavir (LPV/r) on the steady‐state pharmacokinetics (PK) of aplaviroc (APL), a CYP3A4 substrate, in healthy subjects.MethodsIn Part 1, APL PK was determined in eight subjects who received a single oral 50‐mg APL test dose with/without a single dose of 100 mg ritonavir (RTV). Part 2 was conducted as an open‐label, single‐sequence, three‐period repeat dose study in a cohort of 24 subjects. Subjects received APL 400 mg every 12 h (b.i.d.) for 7 days (Period 1), LPV/r 400/100 mg b.i.d. for 14 days (Period 2) and APL 400 mg + LPV/r 400/100 mg b.i.d. for 7 days (Period 3). All doses were administered with a moderate fat meal. PK sampling occurred on day 7 of Periods 1 and 3 and day 14 of Period 2.ResultsIn Part 1, a single RTV dose increased the APL AUC0–∞ by 2.1‐fold [90% confidence interval (CI) 1.9, 2.4]. Repeat dose coadministration of APL with LPV/r increased APL exposures to a greater extent with the geometric least squares mean ratios (90% CI) being 7.7 (6.4, 9.3), 6.2 (4.8, 8.1) and 7.1 (5.6, 9.0) for the APL AUC, Cmax, and Cmin, respectively. No change in LPV AUC or Cmax and a small increase in RTV AUC and Cmax (28% and 32%) were observed. The combination of APL and LPV/r was well tolerated and adverse events were mild in severity with self‐limiting gastrointestinal complaints most commonly reported.ConclusionsCoadministration of APL and LPV/r was well tolerated and resulted in significantly increased APL plasma concentrations.
Cytokines differentially regulate ICAM-1 and VCAM-1 expression on human gingival fibroblasts
Authors: Hosokawa Y , Hosokawa I , Ozaki K , Nakae H , Matsuo T 
Published: April 2006

Abstract
The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) on human gingival fibroblasts (HGF) may be important for migration and retention of inflammatory cells in periodontally diseased tissue. This study aimed to assess which cytokines regulate ICAM-1 and VCAM-1 expression on HGF. Tumour necrosis factor (TNF)-α and interferon (IFN)-γ enhanced both ICAM-1 and VCAM-1 expression on HGF. Interleukin (IL)-1β mainly up-regulated ICAM-1 expression. On the other hand, IL-4 and IL-13 enhanced only VCAM-1 expression on HGF. IL-10 did not modulate both ICAM-1 and VCAM-1 expression. Transforming growth factor (TGF)-β1 enhanced ICAM-1 expression. However, TGF-β1 inhibited the VCAM-1 expression induced by TNF-α or IL-4. Both ICAM-1 and VCAM-1 expression by HGF was inhibited by nuclear factor-kappaB (NF-κB) activation inhibitor (MG-132). Mitogen-activated protein kinases (MAPK) inhibitors did not influence ICAM-1 expression induced by TNF-α. Interestingly, VCAM-1 expression was enhanced by MEK inhibitor (PD98059) and c-Jun NH2-terminal kinase (JNK) inhibitor (SP600125). These results mean that the balance of cytokines in periodontally diseased tissue may be essential for control of ICAM-1 and VCAM-1 expression on HGF, and the balance of ICAM-1 and VCAM-1 expression might be important for regulation of leucocytes infiltration and retention in periodontally diseased tissue.
Immunological properties of complex conjugates based on Vibrio cholerae O1 Ogawa lipopolysaccharide antigen
Authors: Paulovic̆ová E , Machová E , Hos̆tacká A , Bystrický S 
Published: April 2006

Summary
Host protection by humoral immunity against Vibrio cholerae O1 confers lipopolysaccharide (LPS)-specific vibriocidal antibodies. Levels of relevant specific antibodies are closely related to complement-mediated inactivation of the vibrios inoculum, especially on the mucosal surface of intestine. We have tested complex V. cholerae O1 Ogawa-detoxified lipopolysaccharide (dLPS) conjugates. The first conjugate contained glucan both as the immunomodulator and the matrix; the second conjugate contained immunologically inert amylose as matrix. Both d-LPS conjugates contain multiply attached dLPS antigen. These conjugates elicited a statistically significant increase of antigen-specific IgG levels in mice (P &lt; 0·001 and P &lt; 0·05, respectively). The specific anti-conjugate IgG and IgA response after the second (booster) dose were significantly higher compared to pre-immune and whole-cell response. The most effective vibriocidal activity was observed in the case of conjugate, with glucan as the matrix. The highest correlation was found between vibriocidal activity and specific IgG2b (r = 0·765) and IgA (r = 0·887) sera levels. The determination of specific IgG subclasses and IgG2a + 2b/IgG1 ratio revealed a dominant TH1 cell response crucial for effective vaccine candidate.
Maturation of dendritic cells by necrotic thyrocytes facilitates induction of experimental autoimmune thyroiditis
Authors: Li H S , Verginis P , Carayanniotis G 
Published: April 2006

SummaryDendritic cell (DC) maturation is required for efficient presentation of autoantigens leading to autoimmunity. In this report, we have examined whether release of tissue antigens from necrotic thyroid epithelial cells can trigger DC maturation and initiation of a primary antiself response. DC were cocultured with either viable (VT/DC) or necrotic (NT/DC) thyrocytes, and their phenotypic and functional maturation as well as immunopathogenic potential were assessed. Significant up-regulation of surface MHC class II and costimulatory molecule expression was observed in NT/DC but not in VT/DC. This was correlated with a functional maturation of NT/DC, determined by IL-12 secretion. Challenge of CBA/J mice with NT/DC, but not with VT/DC, elicited thyroglobulin (Tg)-specific IgG as well as Tg-specific CD4+ T-cell responses and led to development of experimental autoimmune thyroiditis. These results support the view that thyroid epithelial cell necrosis may cause autoimmune thyroiditis via maturation of intrathyroidal DC.
Concept analysis of perspective‐taking: meeting informal caregiver needs for communication competence and accurate perception
Authors: Lobchuk Michelle M. 
Published: April 2006

Aim.  This paper is a report of an analysis of perspective‐taking as presented in the nursing and psychological literature between 1972 and 2004.Background.  Little is known about the caregiving processes that drive communication competence in patient and informal caregiver relationships. Evidence to date suggests that the empathic perspective‐taking process plays a key role in promoting communication competence, perceptual accuracy and enhanced ability by caregivers to meet patients’ needs arising in illness. Perspective‐taking is a concept that has been explored extensively in health or social psychology, but not in nursing literature.Method.  Guided by Morse's typology of attributes and rules of relation, the concept of perspective‐taking is explored as it is presented in nursing and social psychology literature, and in accordance with Davis's empathy model.Findings.  Extant research and theory suggest that perspective‐taking is an interpersonal empathic process involving a conscious effort in differentiating one's view from the view of another that can bring the caregivers’ viewpoints in closer alignment with patients’ viewpoints. Beginning evidence suggests that observers might achieve accurate perceptual accuracy about patients’ illness experiences if they are prompted to imagine how patients perceive the situation and how they feel as a result. Research also needs to analyse the characteristics of the patient, informal caregiver and illness situation in order to comprehend more fully which caregiver dyads need assistance with perspective‐taking to optimize their skill in providing sufficient patient care.Conclusion.  The current emphasis for empirical research in caregiving is to uncover underlying caregiving processes that exist in pre‐existing patient and informal caregiver relationships. Once further evidence is found to further corroborate the perspective‐taking process and perceptual accuracy linkage and factors that moderate this linkage, then evidence‐based interventions can be designed and tested to optimize empathic processes that minimize perceptual differences between patients and informal caregivers.
Relationships of subalpine forest fires in the Colorado Front Range with interannual and multidecadal‐scale climatic variation
Authors: Sibold Jason S. , Veblen Thomas T. 
Published: April 2006

AbstractAim  An understanding of past relationships between fire occurrence and climate variability will help to elucidate the implications of climate‐change scenarios for future patterns of wildfire. In the present study we investigate the relationships between subalpine‐zone fire occurrence and climate variability and broad‐scale climate patterns in the Pacific and Atlantic Oceans at both interannual and multidecadal time‐scales.Location  The study area is the subalpine zone of Engelmann spruce (Picea engelmannii) and subalpine fir (Abies lasiocarpa), and lodgepole pine (Pinus contorta) in the southern sector of the Rocky Mountain National Park, which straddles the continental divide of the northern Colorado Front Range.Methods  We compared years of widespread fire from AD 1650 to 1978 for the subalpine zone of southern Rocky Mountain National Park, with climate variables such as measures of drought, and indices such as the El Niño–Southern Oscillation (ENSO), the Pacific Decadal Oscillation (PDO), and the Atlantic Multidecadal Oscillation (AMO).Results  Years of extensive subalpine‐zone fires are significantly related to climate variability, phases of ENSO, the PDO, and the AMO, as well as to phase combinations of ENSO, the PDO, and the AMO at both interannual and centennial time‐scales.Main conclusions  Years of extensive fires are related to extreme drought conditions and are significantly related to the La Niña phase of ENSO, the negative (cool) phase of the PDO, and the positive (warm) phase of the AMO. The co‐occurrence of the phase combination of La Niña‐negative PDO‐positive AMO is more important to fire occurrence than the individual influences of the climate patterns. Low‐frequency trends in the occurrence of this combination of climate‐pattern phases, resulting from trends in the AMO, are the primary climate pattern associated with periods of high fire occurrence (1700–89 and 1851–1919) and a fire‐free period (1790–1850). The apparent controlling influence of the AMO on drought and years of large fires in the subalpine forests of the Colorado Front Range probably applies to an extensive area of western North America.
Environment, dispersal and patterns of species similarity
Authors: Steinitz Ofer , Heller Joseph , Tsoar Asaf , Rotem Dotan , Kadmon Ronen 
Published: April 2006

AbstractAim  The aim of this paper is to evaluate the combined effects of geographical distance and environmental distance on patterns of species similarity (similarity in species composition between sites), and to identify factors affecting the rate of decay in species similarity with each type of distance.Location  Israel.Methods  Data on species composition of land snails and land birds were recorded in 27 sites of 1 × 1 km scattered across a rainfall gradient in Israel. Matrices of similarity in species composition between all pairs of sites were computed and analysed with respect to corresponding matrices of geographical distance and rainfall distance (defined as the difference in mean annual rainfall between sites, and used as a measure of environmental distance). Mantel tests were applied to determine the correlation between species similarity and each type of distance. Factors affecting the decay in species similarity were investigated by comparing different subsets of the data using randomization tests.Results  Both rainfall distance and geographical distance had negative effects on species similarity. The effect of rainfall distance was statistically significant even after controlling for differences in geographical distance, and vice versa. The per‐unit effect of rainfall distance on species similarity decreased with increasing geographical distance, indicating that the two types of distances interacted in determining the similarity in species composition. Snails showed a higher rate of decay in species similarity with geographical distance than birds, and large snails showed a higher rate of decay than small snails, which are better passive dispersers. The per‐unit effects of both rainfall distance and geographical distance on species similarity were higher in the desert region than in the Mediterranean region. Analyses focusing on a grain size of 10 × 10 m showed a lower similarity in species composition and a lower rate of decay in species similarity with rainfall distance than analyses carried out at a grain size of 1 × 1 km.Main conclusions  Patterns of similarity in species composition are influenced by the combined effects of environmental variation, the position of the area along environmental gradients, the dispersal properties of the component species, and the scale (both spatial extent and grain size) at which the patterns are examined.
Panbiogeography of Nothofagus (Nothofagaceae): analysis of the main species massings
Authors: Heads Michael 
Published: April 2006

AbstractAim  The aim of this paper is to analyse the biogeography of Nothofagus and its subgenera in the light of molecular phylogenies and revisions of fossil taxa.Location  Cooler parts of the South Pacific: Australia, Tasmania, New Zealand, montane New Guinea and New Caledonia, and southern South America.Methods  Panbiogeographical analysis is used. This involves comparative study of the geographic distributions of the Nothofagus taxa and other organisms in the region, and correlation of the main patterns with historical geology.Results  The four subgenera of Nothofagus have their main massings of extant species in the same localities as the main massings of all (fossil plus extant) species. These main massings are vicariant, with subgen. Lophozonia most diverse in southern South America (north of Chiloé I.), subgen. Fuscospora in New Zealand, subgen. Nothofagus in southern South America (south of Valdivia), and subgen. Brassospora in New Guinea and New Caledonia. The main massings of subgen. Brassospora and of the clade subgen. Brassospora/subgen. Nothofagus (New Guinea–New Caledonia–southern South America) conform to standard biogeographical patterns.Main conclusions  The vicariant main massings of the four subgenera are compatible with largely allopatric differentiation and no substantial dispersal since at least the Upper Cretaceous (Upper Campanian), by which time the fossil record shows that the four subgenera had evolved. The New Guinea–New Caledonia distribution of subgenus Brassospora is equivalent to its total main massing through geological time and is explained by different respective relationships of different component terranes of the two countries. Global vicariance at family level suggests that Nothofagaceae/Nothofagus evolved largely as the South Pacific/Antarctic vicariant in the breakup of a world‐wide Fagales ancestor.
Noradrenaline and albumin in paracentesis‐induced circulatory dysfunction in cirrhosis: a randomized pilot study
Authors: SINGH V. , KUMAR B. , NAIN C. K. , SINGH B. , SHARMA N. , BHALLA A. , SHARMA A. K. 
Published: April 2006

Abstract.Objective.  Therapeutic paracentesis in patients with cirrhosis is associated with a circulatory dysfunction. Intravenous albumin has been used to prevent the circulatory dysfunction; however, the use of albumin is controversial and costly. Splanchnic vasodilation is mainly responsible for circulatory dysfunction in these patients. There are no reports of use of noradrenaline, a vasoconstrictor, on the prevention of paracentesis‐induced circulatory dysfunction in patients with cirrhosis. Therefore, we studied the preventive effect of noradrenaline on paracentesis‐induced circulatory dysfunction in patients with cirrhosis after therapeutic paracentesis and compared it with that of intravenous albumin in a randomized pilot study.Methods.  Forty patients with cirrhosis and tense ascites underwent therapeutic paracentesis with albumin or noradrenaline in a randomized controlled trial at a tertiary centre. Effective arterial blood volume was assessed by measuring plasma renin activity at baseline and at 6 days after treatment.Results.  Effective arterial blood volume as indicated by plasma renin activity before and 6 days after paracentesis did not differ in the two groups (20.62 ± 10.27–22.02 ± 10.15 ng mL−1 h−1; P = 0.11 in the albumin group and 19.66 ± 8.91–20.78 ± 9.41 ng mL−1 h−1; P = 0.37 in the noradrenaline group). Plasma aldosterone concentration before and 6 days after paracentesis were also similar in both groups (1196.5 ± 434.2–1217.0 ± 405.7 pg mL−1; P = 0.7 in the albumin group and 1206.0 ± 522.5–1273.5 ± 444.8 pg mL−1; P = 0.22 in the noradrenaline group). The cost of noradrenaline treatment was significantly lower when compared with that of albumin (P < 0.001).Conclusions.  Noradrenaline is as effective as albumin in preventing paracentesis‐induced circulatory dysfunction in patients with cirrhosis after therapeutic paracentesis, but at a fraction of the cost.
Microelectrode ion and O2 fluxes measurements reveal differential sensitivity of barley root tissues to hypoxia
Authors: PANG JIA YIN , NEWMAN IAN , MENDHAM NEVILLE , ZHOU MEIXUE , SHABALA SERGEY 
Published: April 2006

ABSTRACTHypoxia‐induced changes in net H+, K+ and O2 fluxes across the plasma membrane (PM) of epidermal root cells were measured using the non‐invasive microelectrode ion flux measurement (MIFE) system in elongation, meristem and mature root zones of two barley (Hordeum vulgare L.) varieties contrasting in their waterlogging (WL) tolerance. The ultimate goal of this study was to shed light on the mechanisms underlying effects of WL on plant nutrient acquisition and mechanisms of WL tolerance in barley. Our measurements revealed that functionally different barley root zones have rather different O2 requirements, with the highest O2 influx being in the elongation zone of the root at about 1 mm from the tip. Oxygen deprivation has qualitatively different effects on the activity of PM ion transporters in mature and elongation zones. In the mature zone, hypoxic treatment caused a very sharp decline in K+ uptake in the WL sensitive variety Naso Nijo, but did not reduce K+ influx in the WL tolerant TX9425 variety. In the elongation zone, onset of hypoxia enhanced K+ uptake from roots of both cultivars. Pharmacological experiments suggested that hypoxia‐induced K+ flux responses are likely to be mediated by both K+ ‐inward‐ (KIR) and non‐selective cation channels (NSCC) in the elongation zone, while in the mature zone K+ ‐outward‐ (KOR) channels are the key contributors. Overall, our results suggest that oxygen deprivation has an immediate and substantial effect on root ion flux patterns, and that this effect is different in WL‐sensitive and WL‐tolerant cultivars. To what extent this difference in ion flux response to hypoxia is a factor conferring WL tolerance in barley remains to be answered in future studies.
An insect countermeasure impacts plant physiology: midrib vein cutting, defoliation and leaf photosynthesis
Authors: DELANEY KEVIN J. , HIGLEY LEON G. 
Published: April 2006

ABSTRACTOne type of specialised herbivory receiving little study even though its importance has frequently been mentioned is vein cutting. We examined how injury to a leaf’s midrib vein impairs gas exchange, whether impairment occurs downstream or upstream from injury, duration of impairment, compared the severity of midrib injury with non‐midrib defoliation, and modelled how these two leaf injuries affect whole‐leaf photosynthesis. Leaf gas exchange response to midrib injury was measured in five Asclepiadaceae (milkweed), one Apocynaceae (dogbane), one Polygonaceae and one Fabaceae species, which have been observed or reported to have midrib vein cutting injury in their habitats. Midrib vein injury impaired several leaf gas exchange parameters, but only downstream (distal) from the injury location. The degree of gas exchange impairment from midrib injury was usually more severe than from manually imposed and actual insect defoliation (non‐midrib), where partial recovery occurred after 28 d in one milkweed species. Non‐midrib tissue defoliation reduced whole‐leaf photosynthetic activity mostly by removing photosynthetically active tissue, while midrib injury was most severe as the injury location came closer to the petiole. Midrib vein cutting has been suggested to have evolved as a countermeasure to deactivate induced leaf latex or cardenolide defences of milkweeds and dogbanes, yet vein cutting effects on leaf physiology seem more severe than the non‐midrib defoliation the defences evolved to deter.