bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a dosage strategy in patients receiving enoxaparin by continuous intravenous infusion using modelling and simulation
Authors: Feng Yan , Green Bruce , Duffull Stephen B. , Kane‐Gill Sandra L. , Bobek Mary B. , Bies Robert R.
Published: April 2006

Aim

To develop an appropriate dosing strategy for continuous intravenous infusions (CII) of enoxaparin by minimizing the percentage of steady‐state anti‐Xa concentration (Css) outside the therapeutic range of 0.5–1.2 IU ml−1.

Methods

A nonlinear mixed effects model was developed with NONMEM® for 48 adult patients who received CII of enoxaparin with infusion durations that ranged from 8 to 894 h at rates between 100 and 1600 IU h−1. Three hundred and sixty‐three anti‐Xa concentration measurements were available from patients who received CII. These were combined with 309 anti‐Xa concentrations from 35 patients who received subcutaneous enoxaparin. The effects of age, body size, height, sex, creatinine clearance (CrCL) and patient location [intensive care unit (ICU) or general medical unit] on pharmacokinetic (PK) parameters were evaluated. Monte Carlo simulations were used to (i) evaluate covariate effects on Css and (ii) compare the impact of different infusion rates on predicted Css. The best dose was selected based on the highest probability that the Css achieved would lie within the therapeutic range.

Results

A two‐compartment linear model with additive and proportional residual error for general medical unit patients and only a proportional error for patients in ICU provided the best description of the data. Both CrCL and weight were found to affect significantly clearance and volume of distribution of the central compartment, respectively. Simulations suggested that the best doses for patients in the ICU setting were 50 IU kg−1 per 12 h (4.2 IU kg−1 h−1) if CrCL < 30 ml min−1; 60 IU kg−1 per 12 h (5.0 IU kg−1 h−1) if CrCL was 30–50 ml min−1; and 70 IU kg−1 per 12 h (5.8 IU kg−1 h−1) if CrCL > 50 ml min−1. The best doses for patients in the general medical unit were 60 IU kg−1 per 12 h (5.0 IU kg−1 h−1) if CrCL < 30 ml min−1; 70 IU kg−1 per 12 h (5.8 IU kg−1 h−1) if CrCL was 30–50 ml min−1; and 100 IU kg−1 per 12 h (8.3 IU kg−1 h−1) if CrCL > 50 ml min−1. These best doses were selected based on providing the lowest equal probability of either being above or below the therapeutic range and the highest probability that the Css achieved would lie within the therapeutic range.

Conclusions

The dose of enoxaparin should be individualized to the patients’ renal function and weight. There is some evidence to support slightly lower doses of CII enoxaparin in patients in the ICU setting.
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

Aims

To 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.

Methods

We 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.

Results

In 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.

Conclusions

Genetic 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

Aims

This 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.

Methods

In 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.

Results

In 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.

Conclusions

Coadministration 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

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

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 < 0·001 and P < 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

Dendritic 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

Aim  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

Aim  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

Aim  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

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.
Diagnostic and prognostic value of glycosyltransferase mRNA in glioblastoma multiforme patients
Authors: Oblinger J. L. , Pearl D. K. , Boardman C. L. , Saqr H. , Prior T. W. , Scheithauer B. W. , Jenkins R. B. , Burger P. C. , Yates A. J.
Published: April 2006

Glioblastoma multiforme (GBM) is the most common and aggressive primary human brain tumour in adults with an average survival of 11 months. The 2‐year survival is less than 10%, and only a small proportion of patients are alive at 3 years. Despite improved treatment strategies and aggressive therapy, the prognosis of GBM has changed little in past decades. Thus, any test that can reliably and rapidly diagnose the tumour and predict patient survival could be a valuable tool. Herein we report the use of quantitative real‐time polymerase chain reaction (PCR) to quantify five glycosyltransferase transcripts in gliomas. Our results indicate that measuring GM1 synthase (β‐1,3 galactosyltransferase) mRNA may provide a useful method for segregating GBMs from other types of gliomas. In these studies, 97% of gliomas (36/37 tumours) below a threshold value had a diagnosis of GBM compared with 49% (52/106 tumours) above the threshold. More importantly, the increased expression of GD3 synthase mRNA in combination with decreased GalNAcT message correlated with increased survival in 79 GBM patients (proportional hazards model controlling for age, P = 0.02). These data were further corroborated by a data analysis from one of our previous studies on gangliosides of 80 GBMs, in which increased amounts of GM3 and GD3 (which accumulate in the absence of GalNAcT) correlated with a longer survival (P < 0.01). Thus, measuring GalNAcT and GD3 transcripts may provide a rapid method to assess prognosis in GBM patients. In summary, the data indicate that measuring glycosyltransferase mRNA levels by real‐time PCR may be clinically useful for determining both diagnosis and prognosis in GBM patients.
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

Hypoxia‐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

One 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.
Characterization of some Asian isolates of Phytophthora infestans
Authors: Gotoh K. , Akino S. , Maeda A. , Kondo N. , Naito S. , Kato M. , Ogoshi A.
Published: April 2006

A total of 401 isolates of Phytophthora infestans were collected from eight Asian regions (Korea, India, Taiwan, Indonesia, Thailand, Nepal, China and Japan) between 1992 and 2000 – 318 from potato and 83 from tomato. The isolates were analysed for mating type, metalaxyl resistance, RG57 fingerprinting, mitochondrial DNA (mtDNA) haplotype and the polymorphism of three allozyme loci, i.e. glucose‐6‐phosphate isomerase (Gpi), peptidase (Pep) and malic enzyme (Me). The isolates were multilocus‐genotyped based on RFLP (RG57) fingerprint, dilocus allozyme genotype, mtDNA haplotype and mating type. Twenty multilocus genotypes were identified among 125 isolates. Of these genotypes, 14 had not been previously reported. Some of the multilocus genotypes were common to isolates from several geographical regions, suggesting migration. The metalaxyl‐resistant isolates belonged to the multilocus genotypes JP‐1, JP‐2, and JP‐3. Multilocus genotypes coexisting in a single field were found in following regions: Thailand (1994), central China (1996), Nepal (1997) and Japan (1998 and 2000). The possible origins of certain genotypes are discussed, including the possibility of sexual recombination within the P. infestans populations in Nepal and perhaps Thailand.
AtCHIP functions as an E3 ubiquitin ligase of protein phosphatase 2A subunits and alters plant response to abscisic acid treatment
Authors: Luo Jinhua , Shen Guoxin , Yan Juqiang , He Cixin , Zhang Hong
Published: April 2006

CHIP proteins are E3 ubiquitin ligases that promote degradation of Hsp70 and Hsp90 substrate proteins through the 26S proteasome in animal systems. A CHIP‐like protein in Arabidopsis, AtCHIP, also has E3 ubiquitin ligase activity and has important roles to play under conditions of abiotic stress. In an effort to study the mode of action of AtCHIP in plant cells, proteins that physically interact with it were identified. Like its animal orthologs, AtCHIP interacts with a unique class of ubiquitin‐conjugating enzymes (UBC or E2) that belongs to the stress‐inducible UBC4/5 class in yeast. AtCHIP also interacts with other proteins, including an A subunit of protein phosphatase 2A (PP2A). This PP2A subunit appears to be a substrate of AtCHIP, because it can be ubiquitylated by AtCHIP in vitro and because the activity of PP2A is increased in AtCHIP‐overexpressing plants in the dark or under low‐temperature conditions. Unlike the rcn1 mutant, that has reduced PP2A activity due to a mutation in one of the A subunit genes of PP2A, AtCHIP‐overexpressing plants are more sensitive to ABA treatment. Since PP2A was previously shown to be involved in low‐temperature responses in plants, the low‐temperature‐sensitive phenotype observed in AtCHIP‐overexpressing plants might be partly due to the change in PP2A activity. These data suggest that the E3 ubiquitin ligase AtCHIP may function upstream of PP2A in stress‐responsive signal transduction pathways under conditions of low temperature or in the dark.
Incident rates of colonic neoplasia in older patients: When should we stop screening?
Authors: Harewood Gavin C , Lawlor Garrett O , Larson Mark V
Published: April 2006

Introduction:  Current guidelines endorse colon cancer screening every 5–10 years in patients over 50 years of age. However, there is no consensus regarding what age is appropriate to stop screening. The aim of this study was to characterize neoplasia occurrence/recurrence in a large cohort of patients ≥70 years of age undergoing colonoscopy.

Methods:  The Mayo Rochester endoscopic database was reviewed to determine the incidence of colonic neoplasia in patients ≥70 years undergoing two colonoscopies at least 12 months apart between January 1996 and December 2000. Patients were classified based on (i) age: 70–74, 75–79, ≥80 years; and (ii) polyp detection on initial examination, that is, subsequent examination for screening or surveillance.

Results:  Overall, 1353 patients underwent two colonoscopies at least 12 months apart (median interval 140 weeks) with removal of polyp on initial examination in 726 (53.7%) patients (surveillance cohort). On subsequent endoscopy, polyps ≥10 mm were detected in 54 (4.0%) and cancer in 13 (1.0%) patients. All age groups were well matched with respect to detection of neoplasia on index examination (P = 0.9) and polyp size on initial colonoscopy among the surveillance group (P = 0.9). Using a Cox proportional hazards model, adjusted hazard ratios (95% confidence interval [CI]) for neoplasia (polyps ≥10 mm) were: 2.0 (1.50–2.73, P < 0.0001) (surveillance vs screening), 1.33 (0.96–1.79, P = 0.08) (≥80 vs 70–74), and 1.05 (0.78–1.38, P = 0.75) (75–79 vs 70–74). Adjusted hazard ratios for development of cancer were: 1.87 (1.03–3.97, P = 0.04) (surveillance vs screening), 1.73 (0.84–3.56, P = 0.13) (≥80 vs 70–74), and 1.38 (0.71–2.77, P = 0.34) (75–79 vs 70–74).

Conclusions:  Prior history of neoplasia remains a strong risk factor for colorectal neoplasia development in elderly patients and should be considered when deciding the need for continuing screening/surveillance. Incident neoplasia rates in a previously screened elderly population rise slowly with advancing age although cancer rates rise more sharply. Therefore, screening still retains a role in elderly patients; however, clinical judgment is still required to individualize screening practice. As the risk of competing comorbid illnesses continues to increase over time, the threshold to perform colon screening should increase accordingly.
Suppression of Helicobacter pylori‐induced interleukin‐8 production in vitro and within the gastric mucosa by a live Lactobacillus strain
Authors: Tamura Akira , Kumai Hideshi , Nakamichi Noboru , Sugiyama Toshirou , Deguchi Ryozo , Takagi Atsusi , Koga Yasuhiro
Published: April 2006

Background:  Accumulating evidence indicates that interleukin‐8 (IL‐8) plays a major role in the mucosal inflammation caused by Helicobacter pylori infection. The purpose of the present study was to examine whether Lactobacillus gasseri OLL2716 (LG21) can inhibit the H. pylori‐induced production of IL‐8.

Methods:  A coculture system including MKN45 cells, H. pylori, and LG21 was established for an in vitro analysis. Biopsy specimens were obtained from H. pylori‐infected human subjects consisting of 19 men and six women.

Results:  When LG21 was 1/100 less than H. pylori in a coculture system, LG21 significantly suppressed both the IL‐8 mRNA and protein generation in the coculture. Live, but not heat‐ or UV‐treated LG21, could exert the suppressive effect. However, this amount of LG21 could not suppress either the adhesion of H. pylori to the cell surface or the IL‐8 production by tumor necrosis factor‐α, which induces IL‐8 generation through the activation of the transcription. These results thus suggest that LG21 suppresses an event leading to IL‐8 production, which is specific for H. pylori‐induced IL‐8 generation, and this event is located upstream from the IL‐8 transcription but downstream from the adhesion. The measurement of the IL‐8 level using gastric biopsy specimens from H. pylori‐infected subjects demonstrated that LG21 also suppresses the production of IL‐8 in the gastric mucosa.

Conclusions:  Live LG21 were found to suppress H. pylori‐induced IL‐8 production in both a gastric cell line and within gastric mucosa.
Tolerance to H2 receptor antagonist correlates well with the decline in efficacy against gastroesophageal reflux in patients with gastroesophageal reflux disease
Authors: Furuta Kenji , Adachi Kyoichi , Komazawa Yoshinori , Mihara Takafumi , Miki Masaharu , Azumi Takane , Fujisawa Tomoo , Katsube Tomoko , Kinoshita Yoshikazu
Published: April 2006

Background and Aim: The attenuated antisecretory activity of H2 receptor antagonists (H2RA) during continuous administration is known as the tolerance phenomenon. The authors recently clarified that presence or absence ofHelicobacter pyloriinfection influences the occurrence of the tolerance phenomenon. The aim of this study was to clarify whether tolerance to H2RA is correlated with attenuation of the inhibitory effect against gastroesophageal acid reflux in patients with gastroesophageal reflux disease (GERD).

Methods: Ten male patients with GERD symptoms and abnormal gastroesophageal reflux were investigated by pH monitoring on days 1 and 15 of continuous oral famotidine administration at 20 mg twice daily, andH. pyloriinfection was examined using the urea breath test.

Results: Intragastric and intraesophageal acidity were significantly decreased on the first day of famotidine administration, but then increased during the 15‐day administration period in seven patients who were negative forH. pylori. In contrast, the efficacy of famotidine against gastric acid secretion and gastroesophageal acid reflux was not attenuated in threeH. pylori‐positive patients. The changes in GERD symptoms were correlated with the change in the degree of gastroesophageal reflux.

Conclusion: The presence or absence of tolerance to H2RA during 15‐day administration is correlated with the efficacy for inhibition of gastroesophageal acid reflux.
Does the pancreas move with respiration?
Authors: Bhasin Deepak Kumar , Rana Surinder Singh , Jahagirdar Sujeet , Nagi Birinder
Published: April 2006

Background and Aim:  The pancreas is a retroperitoneal organ and has been classically considered to be immobile on respiration. Recent radiological studies assessing the mobility of the pancreas have challenged this traditional concept. The present study was conducted to assess the movement of pancreas with respiration using fluoroscopy, a simple and inexpensive method.

Methods:  Patients with chronic pancreatitis who had either pancreatic calcification evident on fluoroscopy or an indwelling pancreatic duct stent were studied. The movement of the pancreas was assessed under fluoroscopy by measuring the displacement of the stent or calcification in relationship to the spine in maximum inspiration followed by maximum expiration.

Results:  Twenty‐two patients (mean age 35.45 ± 11.29 years, 17 men) with chronic pancreatitis were included in the study. Ten patients had pancreatic calcification and 12 had an indwelling pancreatic duct stent (two in the dorsal duct, 10 in the ventral duct). In all patients, the pancreas moved downward in the craniocaudal direction on deep inspiration. Pancreatic excursion from maximum inspiration to maximum expiration ranged from 0.1 to 3.4 cm. In addition, a medial movement of the head of pancreas was also noted in most of the patients. On univariate analysis, no association was found between the range of movement and the age or sex of the patient, duration or etiology of disease, presence or absence of calcification, severity of ductal changes of chronic pancreatitis and the length or diameter of the pancreatic stent placed.

Conclusion:  The pancreas moves craniocaudally with respiration and the head moves medially on inspiration.
Effects of perindopril and valsartan on expression of transforming growth factor‐β‐Smads in experimental hepatic fibrosis in rats
Authors: Xu Wei , Song Shiling , Huang Yanqing , Gong Zuojiong
Published: April 2006

Background:  Previous studies have shown that the renin‐angiotensin system (RAS) plays an important role in the pathogenesis of hepatic fibrosis, and blockers of the RAS may be active as an antifibrogenic goal. However, the potential role of RAS inhibition on expression transforming growth factor (TGF)‐β‐Smads in hepatic fibrosis remains unknown. The aim of this study was to investigate the effect and mechanism of an angiotensin‐converting enzyme inhibitor (perindopril) and an angiotensin II receptor blocker (valsartan) on TGF‐β1 and TGF receptor II (TRII) mRNA, Smad3 and Smad7 in fibrotic hepatic livers in rats.

Methods:  Sixty Wistar rats were randomly divided into four study groups (n = 15 for each group), including normal controls, hepatic fibrosis models, and two treated groups with either perindopril or valsartan, starting from the fourth week after being exposed to carbon tetrachloride (CCl4) for 4 weeks. The levels of TGF‐β and TRII mRNA in liver tissue were analyzed by RT‐PCR. The expressions of TGF‐β1, Smad3 and Smad7 in liver tissues were evaluated by immunohistochemistry. The liver histopathology was examined by hematoxylin and eosin (HE) staining and by electron microscopy, respectively. The liver function and serum hyaluronic acid were also assayed by biochemistry and radioimmunoassay.

Results:  Compared with the hepatic fibrosis models, the levels of TGF‐β1, TRII mRNA and the expression Smad3 significantly decreased in the two treated groups, and the expression of Smad7 was significantly increased in the liver of rats treated with perindopril or valsartan (P < 0.05 or P < 0.01). The histological changes and ultrastructure of fibrotic liver, liver function and hyaluronic acid also remarkably improved in the treated rats.

Conclusions:  The angiotensin‐converting enzyme inhibitors perindopril and valsartan have a protective effect on liver injury and can ameliorate hepatic fibrosis in rats induced by CCl4. The mechanisms may be associated with their effects of down‐regulating TGF‐β1, TRII mRNA and smad3, and up‐regulating Smad7.
Study of arteriosclerosis in patients with hiatal hernia and reflux esophagitis
Authors: Furuta Kenji , Adachi Kyoichi , Arima Noriyuki , Yagi Junko , Tanaka Shino , Miyaoka Youichi , Miki Masaharu , Azumi Takane , Koshino Kenji , Ishihara Shunji , Amano Yuji , Kinoshita Yoshikazu
Published: April 2006

Background and Aim:  It has been reported that the prevalence of hiatal hernia (HH) and reflux esophagitis (RE) increases with age, as does the degree of arteriosclerosis. However, it has not been investigated whether or not arteriosclerosis is correlated with the presence of HH and RE. Therefore, we prospectively investigated the degree of arteriosclerosis in patients with HH and RE compared with subjects without HH and RE.

Methods:  We prospectively enrolled 1683 people who visited Shimane Environment and Health Public Corporation for annual medical check‐ups. All subjects were investigated by upper gastrointestinal endoscopy for the possible presence of HH and RE. Factors used for assessing cardiovascular risk were sex, age, body mass index (BMI), smoking and drinking habits, serum total cholesterol, triglyceride (TG), and high‐density lipoprotein cholesterol (HDLC). Arteriosclerosis was investigated by measuring systolic blood pressure, heart‐carotid pulse wave velocity (HCPWV), bilateral ankle brachial index (ABI) and heart‐ankle PWV (HAPWV).

Results:  The number of patients with HH and RE was 624 (37.1%) and 143 (8.5%), respectively. The HDLC level of the patients with HH was significantly lower, and the levels of BMI, TG and arteriosclerotic parameters were higher than those of the subjects without HH after adjusting for confounding factors (sex, age and smoking and drinking habits). Cardiovascular and arteriosclerosis parameters except for TG did not differ between the subjects with and without RE.

Conclusion:  Levels of arteriosclerosis parameters in patients with HH were higher than in those without HH. However, the association between arteriosclerosis and presence of RE was not clarified.
Single‐session, graded esophageal dilation without fluoroscopy in outpatients with lower esophageal (Schatzki’s) rings: A prospective, long‐term follow‐up study
Authors: Sgouros Spiros N , Vassiliadis Konstantinos , Bergele Christina , Vlachogiannakos Jiannis , Stefanidis Gerasimos , Mantides Apostolos
Published: April 2006

Background:  Distal esophageal (Schatzki’s) ring is a frequent cause of dysphagia. Bougienage is generally effective but relapses are common. The aim of this study was to evaluate the safety and long‐term efficacy of single‐session graded esophageal dilation with Savary dilators, without fluoroscopic guidance, in outpatients who presented with Schatzki’s ring.

Methods:  The study was performed on 44 consecutive patients with symptomatic Schatzki’s ring, detected endoscopically and/or radiologically. Graded esophageal dilation was performed as an outpatient procedure in a single session with Savary dilators, without fluoroscopic guidance. After appropriate assessment with esophageal manometry and 24 h ambulatory pHmetry, patients with documented gastroesophageal reflux disease (GERD) were treated with omeprazole continuously. All results, including clinical follow up and technical aspects of bougienage, were recorded prospectively. The necessity for re‐dilation after documentation of the ring with endoscopy and/or radiology was considered as a relapse of the ring.

Results:  In four (9%) patients a second session was necessary to ensure complete symptom relief. Two (4.5%) patients developed post‐dilation bacteremia and were managed with antibiotics as outpatients. Patients with (n = 14) or without (n = 30) GERD were comparable with respect to sex, age, body mass index, smoke and ethanol consumption, diameter of the esophageal lumen at the level of the ring, resting lower esophageal sphincter pressure, duration of dysphagia, need for taking antacids during the follow‐up period, and duration of follow‐up. There was no recurrence of the ring in patients with GERD during a mean follow‐up period of 43.8 ± 9.3 months (range 27–62 months); however, in patients without GERD, during a mean follow‐up period of 40.6 ± 12.2 months (range 10–58 months), 32% of patients relapsed after a mean 19.9 ± 10.6 months (P = 0.04).

Conclusions:  Single‐session graded esophageal dilation with large caliber Savary dilators without fluoroscopic guidance can be safely used for the symptomatic relief in patients with lower esophageal (Schatzki’s) rings. GERD should be treated if present in order to prevent a symptomatic recurrence of the ring.
Analysis of differential gene expression between chronic hepatitis B patients and asymptomatic hepatitis B carriers
Authors: Tang Cuilan , Chen Zhi , Peng Guoping , Yang Zhenggang , Zhou Linfu
Published: April 2006

Background and Aims:  Chronic hepatitis B virus (HBV) infection remains a serious global health problem, inducing a spectrum of diseases, including asymptomatic HBV carriage (ASC) and chronic hepatitis B (CHB). ASC and CHB represent different immunological states and their prognoses are diverse. To clarify molecular mechanisms underlying the two infection states, the differentially expressed genes between the two states were screened and identified.

Methods:  Subtracted complementary DNA libraries by suppression subtractive hybridization, dot blot hybridization and quantitative real‐time PCR were used to identify the differentially expressed genes between subjects with CHB and those with ASC.

Results:  RNA from peripheral blood mononuclear cells from CHB and ASC subjects was subjected to suppression subtractive hybridization and resulted in isolation of subtracted complementary DNA clones. Eighty‐eight randomly sampled clones were rescreened by dot blot hybridization, from which 29 clones were identified as differentially expressed genes. The differential expression of three genes was confirmed by real‐time PCR in 23 subjects with CHB and 21 with ASC.

Conclusions:  Differentially expressed genes in peripheral blood mononuclear cells between CHB and ASC have been isolated by suppression subtractive hybridization, including some new genes. Of the up‐regulated genes in CHB, most are known to be responsive to inflammatory conditions. These genes might provide clues in elucidating the mechanisms of the two different HBV infection states and designing therapeutic targets for HBV infection.