bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiopulmonary exercise testing screening and pre‐operative pulmonary rehabilitation reduce postoperative complications and improve fast‐track recovery after lung cancer surgery: A study for 342 cases
Authors: Gao Ke , Yu Peng‐ming , Su Jian‐hua , He Cheng‐qi , Liu Lun‐xu , Zhou Yu‐bin , Pu Qiang , Che Guo‐wei
Published: December 2014

Background

An evaluation of cardiopulmonary exercise testing (CPET) screening and pre‐operative pulmonary rehabilitation in reducing postoperative complications and improving fast‐track recovery in high‐risk patients who undergo resection for lung cancer.

Methods

Of 342 potential lung cancer cases, 142 high‐risk patients were finally divided into two groups: group R (n = 71) underwent an intensive pre‐operative pulmonary rehabilitation program (PRP), followed by lobectomy; group S (n = 71) underwent only lobectomy with conventional management. Postoperative complications, average days in hospital, postoperative days in hospital, and cost were analyzed.

Results

The 142 high‐risk patients were screened by smoking history and CPET. Sixty‐eight patients had bronchial hyperresponsiveness (BHR) and 47 patients had peak expiratory flow <250 L/minute by CPET. The rate of postoperative total complications in group R (16.90%) was significantly lower than in group S (83.31%) (P = 0.00), as was the rate of postoperative pulmonary complications PPC: group R (12.81%) versus S (13.55%) (P = 0.009); the PPC in the left lung (17.9%) was higher than in the right lung (2.3%) (P = 0.00). The average days in hospital in group S was significantly higher than in group R (P = 0.03). There was no difference between groups in average hospital cost (P = 0.304).

Conclusion

Pre‐operative screening using CPET is conducive to identifying high‐risk patients for lung resection. Pre‐operative pulmonary rehabilitation is helpful to reduce postoperative complications and improve fast‐track recovery.
Land‐use Change Dynamics, Soil Type and Species Forming Mono‐dominant Patches: the Case of Pteridium aquilinum in a Neotropical Rain Forest Region
Authors: Suazo‐Ortuño Ireri , Lopez‐Toledo Leonel , Alvarado‐Díaz Javier , Martínez‐Ramos Miguel
Published: December 2014

Deforestation and agricultural land degradation in tropical regions can create conditions for growth of perennial plant species forming mono‐dominated patches (MDP). Such species might limit forest regeneration, and their proliferation forces the abandonment of fields and subsequent deforestation to establish new fields. Therefore, identifying factors fostering MDP species is critical for biodiversity conservation in human‐modified landscapes. Here, we propose a conceptual framework to identify such factors and apply it to the case of Pteridium aquilinum (bracken fern), a light‐demanding species, tolerant of low soil fertility and fire. We hypothesize that bracken proliferation is promoted by land‐use changes that increase light availability, especially in sites with low soil fertility and land uses involving fire. We assessed this idea using agricultural fields in southeastern Mexico with different land‐use change histories and quantifying prevalence and cover of bracken. Five different land‐use change histories resulted from transitions among forest, crop, pasture, and fallow field stages. Of the 133 fields sampled, 71 percent had P. aquilinum; regression tree analysis indicated that 65 percent of inter‐field variation in prevalence and 90 percent in cover was explained by land‐use change history and soil type. Maximum prevalence, cover, and rates of increase in bracken were found on fields with low fertility sandy/clay soils, which had been used for crops and pasture, were frequently burned, and had high levels of light. Fields on fertile alluvial soil never used for pasture were bracken‐free. Agriculture promoting high light environments on less fertile soils is a major cause of bracken proliferation and likely that of other MDP species.
Ant Diversity in Dominant Vegetation Types of Southern Cameroon
Authors: Fotso Kuate Apollin , Hanna Rachid , Tindo Maurice , Nanga Samuel , Nagel Peter
Published: December 2014

Ants have been shown as particularly affected by land disturbance through deforestation and conversion of forest to agriculture. The effect of land use change on ant diversity in the Congo Basin is not well known. We conducted intensive sampling along a gradient of increasing vegetation disturbance to test the effect of habitat disturbance on ant diversity and Functional Groups composition. Sampling was conducted in 30 plots (5 study sites × 3 habitat × 2 plots/habitat), replicated six times in 1 year. In each plot, ants were monitored with pitfall traps, quadrats and baits. We recorded 237 ant morphospecies grouped in 10 subfamilies and 43 genera. Myrmicaria opaciventris was the most abundant species followed by Anoplolepis tenella. Forest had greater ant diversity compared with fallows and mixed‐crop fields. Functional groups were dominated by Opportunists, followed by Omnivorous Arboreal Dominants and Generalized Mymicinae. Their composition was not affected by the disturbance, but occurrence of Specialist Predators decreased with increasing disturbance. Occurrence of Generalized Myrmicinae, Opportunists and Subordinate Camponotini increased with disturbance. These results indicate that forest conversion into mixed‐crop fields reduce ant diversity. It can also increase abundance of species with generalized diet that predominates where stress and disturbance limits other ants.
Consistent Effects of Disturbance and Forest Edges on the Invasion of a Continental Rain Forest by Alien Plants
Authors: Dawson Wayne , Burslem David F. R. P. , Hulme Philip E.
Published: December 2014

Continental tropical forests are thought to be resistant to alien plant invasion due to a lack of disturbance, or low propagule pressure from introduced species. We assessed the importance of disturbance and edge effects by surveying areas of submontane and lowland forest of Amani Nature Reserve in the East Usambara mountains, Tanzania. These areas are in the vicinity of Amani Botanic Garden (ABG)—a propagule source for many alien plant species. We surveyed three edges in the vicinity of the ABG plantations, using plots interspersed along multiple 250 m transects. Survey plots were either in secondary or seminatural forest, representing a difference in past disturbance). Alien plant species richness and abundance declined with increasing distance from forest edges, indicating that edge effects were important. In addition, the effect of distance on richness and abundance of alien species as adults was much smaller in seminatural than secondary forest, emphasizing that invasion of seminatural forest is less likely to occur. Abundance and occurrence of individual species showed broadly similar declines with increasing distance from the forest edge, and lower abundance in seminatural compared to secondary forest. Alien species were dominant in 15 percent of plots surveyed. As 28 percent of the Amani nature reserve forest is within 250 m of an edge, the importance of disturbance and edges could make a potentially large proportion of the forest vulnerable to alien species invasion.
Role of mtDNA‐related mitoepigenetic phenomena in cancer
Authors: Ferreira André , Serafim Teresa L. , Sardão Vilma A. , Cunha‐Oliveira Teresa
Published: December 2014

Background

Abnormal mitochondrial function has long been associated with the development and the progression of cancer. Multiple defects in the mitochondrial genome have been reported for various cancers, however the often disregarded mitochondrial epigenetic landscape provides an additional source of deregulation that may contribute to carcinogenesis.

Design

This article reviews the current understanding of mitochondrial epigenetics and how it may relate to cancer progression and development. Relevant studies were found through electronic databases (Web of Science and PubMed).

Results and conclusions

The remarkably unexplored field of mitochondrial epigenetics has the potential to shed light on several cancer‐related mitochondrial abnormalities. More studies using innovative, genome‐wide sequencing technologies are highly warranted to assess whether and how altered mtDNA methylation patterns affect cancer initiation and progression.
Species‐specific PCR for rapid identification of Ganoderma philippii and Ganoderma mastoporum from Acacia mangium and Eucalyptus pellita plantations in Indonesia
Authors: Yuskianti V. , Glen M. , Puspitasari D. , Francis A. , Rimbawanto A. , Gafur A. , Indrayadi H. , Mohammed C. L.
Published: December 2014

DNA sequence variation in the rDNA internal transcribed spacers (ITS) was exploited to design species‐specific primers for Ganoderma philippii and Ganoderma mastoporum, two fungi associated with red root rot in Acacia mangium and other perennial crops. Specificity was verified against five other Ganoderma species, 34 other basidiomycete species and two ascomycete species. The PCR tests assisted in the identification of 822 fungal isolates obtained from A. mangium and Eucalyptus pellita plantations in Indonesia. These tests have provided a high level of confidence in the identification of the major root rot pathogens, information that can be used to support the development of management options for their control in A. mangium plantations.
Selective processing of buildings and faces during working memory: the role of the ventral striatum
Authors: Haeger Alexa , Lee Hweeling , Fell Juergen , Axmacher Nikolai
Published: December 2014

The ventral striatum seems to play an important role during working memory (WM) tasks when irrelevant information needs to be filtered out. However, the concrete neural mechanisms underlying this process are still unknown. In this study, we investigated these mechanisms in detail. Eighteen healthy human participants were presented with multiple items consisting of faces or buildings. They either had to maintain two or four items from one category (low‐ and high‐memory‐load condition), or two from one category and suppress (filter out) two items from the other category (distraction condition). Striatal activity was increased in the distraction as compared with the high‐load condition. Activity in category‐specific regions in the inferior temporal cortex [fusiform face area (FFA) and parahippocampal place area (PPA)] was reduced when items from the other category needed to be selectively maintained. Furthermore, functional connectivity analysis showed significant reduction of striatal–PPA correlations during selective maintenance of faces. However, striatal–FFA connectivity was not reduced during maintenance of buildings vs. faces, possibly because face stimuli are more salient. Taken together, our results suggest that the ventral striatum supports selective WM maintenance by reduced gating of task‐irrelevant activity via attenuating functional connectivity without increasing task‐relevant activity correspondingly.
Host plants of Anoplophora glabripennis, a review
Authors: van der Gaag D. J. , Loomans A. J. M.
Published: December 2014

Anoplophora glabripennis (Asian longhorned beetle) attacks many different broadleaf tree species. Although there is no doubt that A. glabripennis can complete its life cycle on species belonging to various genera such as Acer, Populus, Salix and Ulmus, there is conflicting information about the host plant status of many other species. Plant species may have been listed because of maturation feeding or oviposition, without evidence that A. glabripennis can actually complete its life cycle on these species. In the present review, 34 plant taxa that have been listed as A. glabripennis‐hosts are placed in four different categories based on information available through literature search and by personal communication with experts. The categories are: (I) plant species on which A. glabripennis has been reported to complete its life cycle (from oviposition to emergence of new beetles) under field conditions, (II) plant species on which A. glabripennis has completed its life cycle in laboratory or semi‐field experiments (i.e. plants and beetles reared in cages), (III) plant species on which A. glabripennis has been reported to complete part of its life cycle, and (IV) others. The following genera were placed in category I: Acer, Aesculus, Betula, Cercidiphyllum, Fraxinus, Platanus, Populus, Salix and Ulmus. The species Albizia julibrissin, Corylus colurna, Elaeagnus angustifolia, Fagus sylvatica, Koelreuteria paniculata, Malus domestica, Pyrus bretschneideri and Sorbus aucuparia were also placed in category I, although records on exit holes were limited. These species may be rather poor or unattractive hosts on which A. glabripennis may only incidentally oviposit and/or complete its life cycle or the species may be rather uncommon in outbreak areas thus far and, therefore, not frequently attacked. Elaeagnus angustifolia has also been reported to be resistant. For some of the species listed the host plant status may need confirmation. The list of category I species may also become longer in the future because several of the plant species listed only recently appeared to be true hosts, i.e. supporting completion of the full life cycle of A. glabripennis.
Descriptive assessment of uncertainties of qualitative real‐time PCR for detection of plant pathogens and quality performance monitoring
Authors: Mehle N. , Dreo T. , Jeffries C. , Ravnikar M.
Published: December 2014

In most cases, plant pest diagnostic methods are interpreted as providing qualitative data. However, although qualitative, it is still important to identify all the sources and components of uncertainty in the diagnostic process and to ensure that appropriate measures are taken to reduce the uncertainty and that the form of reporting the result does not give the wrong impression of the uncertainty. This process was illustrated using real‐time PCR testing of grapevine yellows phytoplasma. Some additional quality performance monitoring of real‐time PCR is also described. This approach has been used by the National Institute of Biology, Slovenia, since 2012, in support of accreditation under ISO 17025, and it can also be applied to other detection methods and other pests.
Interlaboratory tests for resistance toSynchytrium endobioticumin potato by theGlynne‐Lemmerzahl method
Authors: Flath K. , Przetakiewicz J. , van Rijswick P. C. J. , Ristau V. , van Leeuwen G. C. M.
Published: December 2014

Synchytrium endobioticumis a major quarantine pathogen of potato causing potato wart disease. In Europe, the pathotypes 1(D1), 2(G1), 6(O1) and 18(T1) are the most widespread and occur locally in almost all countries. Resistance to this disease in potato cultivars is tested for in the majority of theEUcountries by the Glynne‐Lemmerzahl method. This paper describes the results of testing two different protocols of this method in five laboratories of three different countries (Germany, Poland, and the Netherlands). The four pathotypes 1(D1), 2(G1), 6(O1) and 18(T1) were tested mainly on the cultivars described in theEPPOStandard PM 7/28Synchytrium endobioticum. For pathotype 1(D1) and in most cases also for pathotype 18(T1), the results of the cultivars tested were identical to the rating in theEPPOStandard for both protocols. For pathotypes 2(G1) and 6(O1), the cultivars Désirée, Delcora and Miriam showed different results between laboratories as well as between the two protocols. In conclusion, further research is needed to develop one harmonised methodology for resistance testing of potato cultivars to the pathotypes 2(G1), 6(O1) and 18(T1) and to develop a new differential set of potato cultivars for the identification of pathotypes ofS. endobioticum.
Preventing a new invasive alien plant from entering and spreading in the Euro‐Mediterranean region: the case study of Parthenium hysterophorus
Authors: Brunel S. , Panetta D. , Fried G. , Kriticos D. , Prasad R. , Lansink A. O. , Shabbir A. , Yaacoby T.
Published: December 2014

Parthenium or famine weed (Parthenium hysterophorus L.) is an annual plant originating from the Americas, which is a major invasive alien plant in almost all continents. While the deleterious impacts of the species on agriculture, human and animal health have been well documented, information on the pathways of entry of the species is only occasionally mentioned in the literature. As this invasive alien plant is only recorded as established in Israel and Egypt within the Euro‐Mediterranean region, the European and Mediterranean Plant Protection Organization identified P. hysterophorus as an emerging threat. EPPO therefore performed a Pest Risk Analysis on this species to assess the risk it represents and to consider appropriate management options. The EPPO Pest Risk Analysis main outputs are summarized in this article, indicating the probability of entry of the species via the different pathways within the EPPO region, its probabilities of establishment and spread, and the magnitude of its potential agricultural, environmental and social impacts.
Do geographic, climatic or historical ranges differentiate the performance of central versus peripheral populations?
Authors: Pironon Samuel , Villellas Jesús , Morris William F. , Doak Daniel F. , García María B.
Published: December 2014

Aim

The ‘centre–periphery hypothesis’ (CPH) predicts that species performance (genetics, physiology, morphology, demography) will decline gradually from the centre towards the periphery of the geographic range. This hypothesis has been subjected to continuous debate since the 1980s, essentially because empirical studies have shown contrasting patterns. Moreover, it has been proposed that species performance might not be higher at the geographic range centre but rather at the environmental optimum or at sites presenting greater environmental stability in time. In this paper we re‐evaluate the CPH by disentangling the effects of geographic, climatic and historical centrality/marginality on the demography of three widely distributed plant species and the genetic diversity of one of them.

Location

Europe and North America.

Methods

Based on a species distribution modelling approach, we test whether demographic parameters (vital rates, stochastic population growth rates, density) of three plant species of contrasting life‐forms, and the genetic diversity of one of them, are higher at their geographic range centres, climatic optima or projected glacial refugia.

Results

While geographic, climatic and historical centre–periphery gradients are often not concordant, overall, none of them explain well the distribution of species demographic performance, whereas genetic diversity responds positively only to a historical centrality, related to post‐glacial range dynamics.

Main conclusions

To our knowledge, this is the first assessment of the response of species performance to three centrality gradients, considering all the components of different species life cycles and genetic diversity information across continental distributions. Our results are inconsistent with the idea that geographically, climatically or historically marginal populations generally perform worse than central ones. We particularly emphasize the importance of adopting an interdisciplinary approach in order to understand the relative effects of contemporary versus historical and geographic versus ecological factors on the distribution of species performance.
The distribution‐free newsboy problem and the demand skew
Authors: Kamburowski Jerzy
Published: December 2014

We consider the newsboy problem when the information about the probability distribution of random demand is limited to its support, mean, variance, and skewness. Sharp lower and upper bounds on the maximum expected profit are derived that lead to the corresponding optimal order quantities found under the worst‐case and best‐case scenarios. In addition, some special cases are solved by reducing the scope of knowledge about the demand distribution. Consequently, we generalize all results presented so far in the literature for the two scenarios, and present several new results. A numerical example illustrates the impact of available information on the quality of approximations. Extensions of our results are indicated.
A consensus‐ and harmony‐based feedback mechanism for multiple attribute group decision making with correlated intuitionistic fuzzy sets
Authors: Wu Jian , Liu Yujia , Liang Changyong
Published: December 2014

In this study, an interactive consensus model is proposed for correlated multiple attribute group decision making (MAGDM) problems with intuitionistic triangular fuzzy numbers (ITFNs). The harmony degree (HD) is investigated to determine the degree of maintaining experts' original information while the consensus level is defined as the proximity degree (PD) between an expert and other experts on three levels: evaluation elements of alternatives, alternatives, and decision matrices. Combining HD and PD, a three‐dimensional feedback mechanism is proposed to identify discordant experts, alternatives, and corresponding preference values that contribute less to consensus, and provides advice to reach a higher consensus level. Additionally, visual representation of experts' consensus position within the group is provided. Furthermore, a graphical simulation of future consensus and harmony status, if the recommended values were to be implemented, is also provided. Therefore, our proposed feedback mechanism guarantees that it increases the consensus level of the set of experts while maintaining, as much as possible, experts' original information. Then, the PD‐induced intuitionistic triangular fuzzy correlated averaging (PD‐IITFCA) operator is investigated to aggregate the interactive individual opinions between experts. Finally, the intuitionistic triangular fuzzy correlated averaging (ITFCA) operator is developed to aggregate the evaluation elements of alternatives under correlative attributes. Based on the score and accurate functions of ITFNs, an order relation is proposed to obtain the final solution of alternatives.
Phylogenetic and biogeographical patterns in defensive strategies and quantitative allocation to chemical defences in Palaearctic and Nearctic pine trees
Authors: Carrillo‐Gavilán Amparo , Moreira Xoaquín , Zas Rafael , Gonzalez‐Voyer Alejandro , Vilà Montserrat , Sampedro Luis
Published: December 2014

Aim

Using pine trees as a long‐lived woody plant model, we analysed the extent to which constitutive and induced allocation to chemical defences were conserved across the phylogeny, and tested the hypothesis that patterns of defensive allocation and defensive strategies differ between Palaearctic and Nearctic pines.

Location

Common‐environment study with Palaearctic and Nearctic pine species.

Methods

We grew 17 pine species (eight Palaearctic and nine Nearctic) in a common environment and measured the stem and needle concentrations of phenolics and non‐volatile resin, two major quantitative chemical defences in pines. In particular, we studied the constitutive allocation to chemical defences (in control plants) and the potential inducibility of those traits in response to elicitation with hormonal analogues of the jasmonic acid (methyl jasmonate) and salicylic acid (benzothiadiazole) pathways of plant defence against herbivorous insects and pathogens.

Results

We found a strong phylogenetic signal in the constitutive concentration of phenolics in the needles and resin in the stem, but not elsewhere. We found that Nearctic pines showed 70% greater concentration of constitutive needle phenolics than Palaearctic species. In contrast, the inducibility potential of defences did not differ between Nearctic and Palaearctic pine species.

Main conclusions

Our findings suggest that macroevolutionary history (phylogeny and biogeographical origin combined) has played an important role in the evolution of needle constitutive defences among pine species, but not in that of induced defences. Specifically, constitutive allocation to pine chemical defences seems to be well preserved across the phylogeny. In contrast, the inducibility of chemical defensive traits was evolutionarily labile and may depend more on the particular climate, biotic interactions and resource availability in each species’ range.
Prostaglandin pathways in duodenal chemosensing
Authors: Akiba Yasutada , Kaunitz Jonathan D
Published: December 2014

Acid‐sensing pathways, which trigger mucosal defense mechanisms in response to luminal acid, involve the rapid afferent‐mediated “capsaicin pathway” and the sustained “prostaglandin (PG) pathway.” Luminal acid quickly increases protective PG synthesis and release from epithelia, although the mechanism by which luminal acid induces PG synthesis is still mostly unknown. Acid exposure augments purinergic ATP‐P2Y signaling by inhibition of intestinal alkaline phosphatase activity. Since P2Y activation increases intracellular Ca2+, we further hypothesized that ATP‐P2Y signals increase the generation of H2O2 derived from dual oxidase, a member of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family activated by Ca2+. Our recent studies suggest that acid exposure increases H2O2 output, followed by phospholipase A2 and cyclooxygenase activation, increasing PG synthesis. Released prostaglandin E2 augments protective HCO3− and mucus secretion via EP4 receptor activation. Thus, the PG pathway as a component of duodenal acid sensing consists of acid‐related intestinal alkaline phosphatase inhibition, ATP‐P2Y signals, dual oxidase 2‐derived H2O2 production, phospholipase A2 activation, prostaglandin E2 synthesis, and EP4 receptor activation. The PG pathway is also involved in luminal bacterial sensing in the duodenum via activation of pattern recognition receptors, including Toll‐like receptors and nucleotide‐binding oligomerization domain 2. The presence of acute mucosal responses to luminal bacteria suggests that the duodenum is important for host defenses and may reduce bacterial loading to the hindgut using H2O2, complementing gastric acidity and anti‐bacterial bile acids.
Naturally occurring phenethyl isothiocyanate‐induced inhibition of gastric cancer cell growth by disruption of microtubules
Authors: Øverby Anders , Zhao Chun‐Mei , Bones Atle Magnar , Chen Duan
Published: December 2014

Background and Aim

Phenethyl isothiocyanate (PEITC) derives from vegetables commonly consumed by man and has been demonstrated as a promising chemopreventive agent against several types of cancer. However, the potential in preventing gastric cancer as well as the underlying mechanisms are to date not fully understood. The present study aimed at elucidating the cellular effects induced by PEITC in gastric cancer cells leading to apoptosis.

Methods

The human gastric cancer cell lines Kato‐III and MKN74 were employed. Cell proliferation was assayed using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Morphology and migration were investigated through a contrast microscope. Cell cycle distribution was analyzed using flow cytometry of PI‐stained cells. Microtubules were studied by confocal detection of Kato‐III cells transfected to express GFP‐tagged microtubules. Commercial kits were employed to study the effect of PEITC on apoptosis, caspase‐3 activity, and glutathione content in MKN74 cells.

Results

Kato‐III and MKN74 cells responded, with different sensitivity, dose‐ and time‐dependently in inhibition of cell proliferation to PEITC treatment. Further, PEITC induced aberrated cell morphologies and inhibited migration of MKN74 cells. Kato‐III cells treated with PEITC accumulated in G2/M phase and displayed a loss of microtubuli with the subsequent formation of apoptotic bodies. Although weak responses, MKN74 cells also accumulated in G2/M phase, became apoptotic, increased caspase‐3 activity, and suffered a reduction of glutathione pool.

Conclusion

Our findings demonstrate that PEITC induces disintegration of microtubules in human gastric cancer cells contributing to cell cycle arrest and ultimately apoptosis, contributing to an increased understanding of PEITC‐induced inhibition of gastric cancer cell growth.
Lymphangiogenesis in early and advanced gastric cancer: Is there any difference?
Authors: Rudno‐Rudzińska Julia , Donizy Piotr , Frejlich Ewelina , Kotulski Krzysztof , Dzięgiel Piotr , Hałoń Agnieszka , Kielan Wojciech
Published: December 2014

Background and Aim

Gastric cancer (GC) in Poland is on the third place of men's mortality and on the fifth place of women's mortality in malignant neoplasms, and the percentage of diagnosed early GC is less than 20%.

In this study, the relationship among lymphatic vessel density, marked with D2‐40, expression of vascular endothelial growth factor (VEGF)‐C/D, VEGF receptor 3 VEGFR‐3, and the stage of GC patient were investigated.

Methods

This study examined the relationships between the peritumoral lymphatic vessels (PTL) density and intratumoral lymphatic vessels (ITL) density stained immunohistochemically with D2‐40/podoplanin, the expression of VEGF‐C/D and VEGFR‐3, and the stage of 58 GC patients.

Results

Lymphatic vessel density measured by D2‐40 decreases outside the tumor (PTL) and increases within the tumor (ITL) as the staging grows from I to III, whereas in the case of patients belonging to stage IV group, lymphatic vessel density decreases outside the tumor as well as within the tumor in comparison with the stage III group (not statistically significant). We observed a difference between morphology of the vessels within the tumor (ITLs) and vessels that are located outside the tumor (PTLs). PTLs were enlarged and unsqueezed as opposed to ITLs, which were collapsed.

Conclusions

(i) There is no significant correlation between the density of ITL nor PTL marked with D2‐40 and the stage of GC. (ii) We did not observe relationship between expression of VEGF‐C/D and VEGFR‐3 and the stage of GC. (iii) Further studies are needed to fully determine the role of PTL and ITL.
Angiogenesis in gastric mucosa: An important component of gastric erosion and ulcer healing and its impairment in aging
Authors: Tarnawski Andrzej S , Ahluwalia Amrita , Jones Michael K
Published: December 2014

Angiogenesis (also referred to as neovascularization—formation of new blood vessels from existing vessels) is a fundamental process essential for healing of tissue injury and ulcers because regeneration of blood microvessels is a critical requirement for oxygen and nutrient delivery to the healing site. This review article updates the current views on angiogenesis in gastric mucosa following injury and during ulcer healing, its sequential events, the underlying mechanisms, and the impairment of angiogenesis in aging gastric mucosa. We focus on the time sequence and ultrastructural features of angiogenesis, hypoxia as a trigger, role of vascular endothelial growth factor signaling (VEGF), serum response factor, Cox2 and prostaglandins, nitric oxide, and importin. Recent reports indicate that gastric mucosa of aging humans and experimental animals exhibits increased susceptibility to injury and delayed healing. Gastric mucosa of aging rats has increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin, and other non‐steroidal anti‐inflammatory drugs because of structural and functional abnormalities including: reduced gastric mucosal blood flow, hypoxia, reduced expression of vascular endothelial growth factor and survivin, and increased expression of early growth response protein 1 (egr‐1) and phosphatase and tensin homolog (PTEN). Until recently, postnatal neovascularization was assumed to occur solely through angiogenesis sprouting of endothelial cells and formation of new blood vessels from pre‐existing blood vessels. New studies in the last decade have challenged this paradigm and indicate that in some tissues, including gastric mucosa, the homing of bone marrow‐derived endothelial progenitor cells to the site of injury can also contribute to neovascularization by a process termed vasculogenesis.
Importance of cyclooxygenase‐1/prostacyclin in modulating gastric mucosal integrity under stress conditions
Authors: Amagase Kikuko , Izumi Nahoko , Takahira Yuka , Wada Tomoko , Takeuchi Koji
Published: December 2014

Background and Aim

We investigated the roles of cyclooxygenase (COX) isozymes and prostaglandins (PGs) and their receptors in mucosal defense against cold‐restraint stress (CRS)‐induced gastric lesions.

Methods

Male C57BL/6 wild‐type (WT) mice and those lacking COX‐1 or COX‐2 as well as those lacking EP1, EP3, or IP receptors were used after 18 h fasting. Animals were restrained in Bollman cages and kept in a cold room at 10°C for 90 min.

Results

CRS induced multiple hemorrhagic lesions in WT mouse stomachs. The severity of these lesions was significantly worsened by pretreatment with the nonselective COX inhibitors (indomethacin, loxoprofen) or selective COX‐1 inhibitor (SC‐560), while neither of the selective COX‐2 inhibitors (rofecoxib and celecoxib) had any effect. These lesions were also aggravated in animals lacking COX‐1, but not COX‐2. The expression of COX‐2 mRNA was not detected in the stomach after CRS, while COX‐1 expression was observed under normal and stressed conditions. The gastric ulcerogenic response to CRS was similar between EP1 or EP3 knockout mice and WT mice, but was markedly worsened in animals lacking IP receptors. Pretreating WT mice with iloprost (the PGI2 analog) significantly prevented CRS‐induced gastric lesions in the presence of indomethacin. PGE2 also reduced the severity of these lesions, and the effect was mimicked by the EP4 agonist, AE1‐329.

Conclusions

These results suggest that endogenous PGs derived from COX‐1 play a crucial role in gastric mucosal defense during CRS, and this action is mainly mediated by PGI2/IP receptors and partly by PGE2/EP4 receptors.
Effect of supplementation with rebamipide for Helicobacter pylori eradication therapy: A systematic review and meta‐analysis
Authors: Nishizawa Toshihiro , Nishizawa Yuko , Yahagi Naohisa , Kanai Takanori , Takahashi Masahiko , Suzuki Hidekazu
Published: December 2014

Background and Aim

Several studies have reported that the application of rebamipide during the eradication of Helicobacter pylori can improve the eradication rate. However, the efficacy and safety are controversial. The present study systematically evaluated whether rebamipide improves the eradication rate of H. pylori by conducting a meta‐analysis based on randomized controlled trials (RCTs).

Methods

Literature searches were conducted in the following database: PubMed, the Cochrane Library, and the Igaku‐chuo‐zasshi database in Japan. A meta‐analysis of all RCTs comparing rebamipide supplementation with non‐rebamipide‐containing therapy was performed.

Results

We identified six randomized trials (611 patients). Pooled H. pylori eradication rates by per‐protocol analysis were 73.3% and 61.4% for patients with or without rebamipide, respectively. The odds ratio was 1.74 (95% confidence interval. 1.19–2.53).

Conclusions

Supplementation with rebamipide might be effective in increasing the H. pylori eradication rates of proton‐pump inhibitor–amoxicillin dual therapy.
Single nucleotide polymorphism markers for low‐dose aspirin‐associated peptic ulcer and ulcer bleeding
Authors: Shiotani Akiko , Murao Takahisa , Fujita Yoshihiko , Fujimura Yoshinori , Sakakibara Takashi , Nishio Kazuto , Haruma Ken
Published: December 2014

Background and Aim

In our previous study, the SLCO1B1 521TT genotype and the SLCO1B1*1b haplotype were significantly associated with the risk of peptic ulcer in patients taking low‐dose aspirin (LDA). The aim of the present study was to investigate pharmacogenomic profile of LDA‐induced peptic ulcer and ulcer bleeding.

Methods

Patients taking 100 mg of enteric‐coated aspirin for cardiovascular diseases and with a peptic ulcer or ulcer bleeding and patients who also participated in endoscopic surveillance were studied. Genome‐wide analysis of single nucleotide polymorphisms (SNPs) was performed using the Affymetrix DME Plus Premier Pack. SLCO1B1*1b haplotype and candidate genotypes of genes associated with ulcer bleeding or small bowel bleeding identified by genome‐wide analysis were determined using TaqMan SNP Genotyping Assay kits, polymerase chain reaction‐restriction fragment length polymorphism, and direct sequencing.

Results

Of 593 patients enrolled, 111 patients had a peptic ulcer and 45 had ulcer bleeding. The frequencies of the SLCO1B1*1b haplotype and CHST2 2082 T allele were significantly greater in patients with peptic ulcer and ulcer bleeding compared to the controls. After adjustment for significant factors, the SLCO1B1*1b haplotype was associated with peptic ulcer (OR 2.20, 95% CI 1.24–3.89) and CHST2 2082 T allele with ulcer bleeding (2.57, 1.07–6.17).

Conclusion

The CHST2 2082 T allele as well as SLCO1B1*1b haplotype may identify patients at increased risk for aspirin‐induced peptic ulcer or ulcer bleeding.
Mucosal expression of aquaporin‐4 in the stomach of histamine type 2 receptor knockout mice and Helicobacter pylori‐infected mice
Authors: Fukuhara Seiichiro , Matsuzaki Juntaro , Tsugawa Hitoshi , Masaoka Tatsuhiro , Miyoshi Sawako , Mori Hideki , Fukushima Yasushi , Yasui Masato , Kanai Takanori , Suzuki Hidekazu
Published: December 2014

Background and Aim

Basolateral water channel, aquaporin‐4 (AQP4), is known to be expressed in gastric parietal cells, especially in the basal side of gastric mucosa. However, the role of AQP4 in the stomach is still unknown. Histamine type 2 receptor (H2R) knockout mice, which are characterized by suppressed gastric acid secretion, are known as formation of mucosal hyperplasia with cystic dilatation and spasmolytic polypeptide‐expressing metaplasia (SPEM) in the stomach. The aim of the present study is to investigate whether the expression of AQP4 is changed by the condition of acid suppression and Helicobacter pylori infection.

Methods

Male H2R knockout mice and their controls (C57BL/6) were used. H. pylori was orally infected at the age of 5 weeks. The distributions of AQP4 and H+/K+‐ATPase in the gastric mucosa were investigated by fluorescent immunohistochemistry. The mRNA expressions of AQP4, H+/K+‐ ATPase, sonic hedgehog (Shh), and trefoil factor‐2 (TFF2) were investigated by quantitative reverse transcription polymerase chain reaction (RT‐PCR).

Results

In the H2R knockout mice, the distribution of AQP4‐positive parietal cells was extended toward the surface of the fundic glands. Although the mRNA expression levels of AQP4 and H+/K+ ATPase were elevated in H2R knockout mice at the age of 20 weeks, the elevations were not maintained by aging or H. pylori infection. In H2R knockout mice with H. pylori infection, the expression level of TFF2 mRNA was elevated while the ratio between AQP4 and H+/K+ ATPase mRNA expression was decreased compared with the H2R knockout mice without H. pylori infection.

Conclusions

In the H2R knockout mice, massive SPEM was induced by H. pylori colonization and the ratio between AQP4 and H+/K+ ATPase mRNA expression was decreased.
Usefulness of Helicobacter pylori eradication for precancerous lesions of the gastric remnant
Authors: Sakakibara Masatoshi , Ando Takafumi , Ishiguro Kazuhiro , Maeda Osamu , Watanabe Osamu , Hirayama Yutaka , Morise Kazuhiro , Maeda Keiko , Matsushita Masanobu , Furukawa Kazuhiro , Funasaka Kohei , Nakamura Masanao , Miyahara Ryoji , Goto Hidemi
Published: December 2014

Background and Aim

Secondary stomach cancer in lesions of the remnant stomach occurs relatively soon after distal gastrectomy using the Billroth I reconstruction procedure. Prophylactic eradication of Helicobacter pylori after endoscopic resection of early gastric cancer should be used to prevent the development of metachronous gastric carcinoma. However, the effect of H. pylori eradication on the gastric remnant has not been clearly determined.

Methods

Eight patients who were H. pylori‐positive after distal gastrectomy for primary gastric cancer underwent eradication therapy and were followed by endoscopy for 9 years. Upper gastroenteroscopy series were done before and at 1, 3, 5, 7 and 9 years after eradication, and biopsy specimens were taken from the lesser and greater curvatures, respectively. Histological changes, including chronic inflammation, activity, atrophy, and intestinal metaplasia, were evaluated using the updated Sydney system.

Results

Successful eradication was confirmed using the urea breath test in all eight patients. Chronic inflammation scores were improved after eradication at both the lesser (mean scores ± SD: before eradication, 2.9 ± 0.5; 1 year after, 2.3 ± 0.4; 3 years, 1.8 ± 0.3; 5 years, 1.5 ± 0.3; 7 years, 1.3 ± 0.3; and 9 years, 1.0 ± 0.3) and greater curvatures (before, 2.9 ± 0.4; 1 year after, 1.9 ± 0.3; 3 years, 1.4 ± 0.4; 5 years, 1.3 ± 0.3; 7 years, 1.1 ± 0.2; and 9 years, 0.6 ± 0.3). Atrophy scores improved more quickly after eradication than chronic inflammation scores at both the lesser (before, 2.4 ± 0.5; 1 year after, 1.8 ± 0.4; 3 years, 0.8 ± 0.3; 5 years, 0.3 ± 0.1; 7 years, 0.0; and 9 years, 0.0) and greater curvatures (before, 2.2 ± 0.4; 1 year after, 1.3 ± 0.3; 3 years, 0.5 ± 0.3; 5 years, 0.0; 7 years, 0.0; and 9 years, 0.0). No secondary stomach cancers were found on endoscopy.

Conclusions

Undergoing H. pylori eradication improved possible precancerous lesions of the gastric remnant among patients who had undergone distal gastrectomy. Prophylactic H. pylori eradication in the gastric remnant may be useful in preventing the development of metachronous gastric carcinoma.
Decrease of serum level of gastrin in healthy Japanese adults by the change of Helicobacter pylori infection
Authors: Shimoyama Tadashi , Chinda Daisuke , Matsuzaka Masashi , Takahashi Ippei , Nakaji Shigeyuki , Fukuda Shinsaku
Published: December 2014

Background and Aim

In Japan, the prevalence of Helicobacter pylori infection is decreasing and the number of patients who receive eradication therapy is increasing. Although the serum level of gastrin is affected by H. pylori infection, the normal level has been unchanged for more than 20 years. The aim of this study was to study whether the present normal range for the serum gastrin level is appropriate for Japanese at present or in the near future.

Methods

We studied 810 adults (40–80 years old) who participated in a health survey in 2012. We measured H. pylori stool antigen, titer of serum antibody to H. pylori, and serum level of gastrin. The patient's H. pylori status was defined as positive or negative when the results of both stool antigen and serology were concordant. Subjects who were taking proton‐pump inhibitor and had a previous history of gastric surgery were excluded.

Results

Mean serum level of gastrin was 66.2 ± 49.6 pg/mL in 281 H. pylori‐negative subjects and 69.7 ± 42.2 pg/mL in 115 patients who had H. pylori eradicated at least 2 years ago. The level of gastrin was 134.4 ± 145.6 pg/mL in 224 patients with H. pylori infection and the level was significantly higher when compared with those in uninfected subjects and eradicated patients (P < 0.01).

Conclusions

Because the situation of H. pylori infection has changed remarkably in Japan, a new appropriate normal range of gastrin should be established using current Japanese populations.
Effect of rebamipide on gastric bleeding and ulcerogenic responses induced by aspirin plus clopidogrel under stimulation of acid secretion in rats
Authors: Takeuchi Koji , Takayama Shinichi , Hashimoto Erika , Itayama Misaki , Amagase Kikuko , Izuhara Chitose
Published: December 2014

Background and Aim

We examined the prophylactic effect of rebamipide on gastric bleeding induced by the perfusion of aspirin (acetylsalicylic acid [ASA]) plus clopidogrel under the stimulation of acid secretion in rats.

Methods

Under urethane anesthesia, acid secretion was stimulated by the i.v. infusion of histamine (8 mg/kg/h), and the stomach was perfused with 25 mmol/L ASA at a rate of 0.4 mL/min. Gastric bleeding was evaluated as the concentration of hemoglobin in the perfusate. Clopidogrel (30 mg/kg) was given p.o. 24 h before the perfusion. Rebamipide (3–30 mg/kg) or other antiulcer drugs were given i.d. before the ASA perfusion.

Results

Slight gastric bleeding or damage was observed with the perfusion of ASA under the stimulation of acid secretion, whereas these responses were significantly increased in the presence of clopidogrel. Both omeprazole and famotidine inhibited acid secretion and prevented these responses to ASA plus clopidogrel. Rebamipide had no effect on acid secretion, but dose‐dependently prevented gastric bleeding in response to ASA plus clopidogrel, with the degree of inhibition being almost equivalent to that of the antisecretory drugs, and the same effects were obtained with the gastroprotective drugs, irsogladine and teprenone. These agents also reduced the severity of gastric lesions, although the effects were less than those of the antisecretory drugs.

Conclusions

These results suggest that the antiplatelet drug, clopidogrel, increases gastric bleeding induced by ASA under the stimulation of acid secretion, and the gastroprotective drug, rebamipide, is effective in preventing the gastric bleeding induced under such conditions, similar to antisecretory drugs.
Acetic acid induces cell death: An in vitro study using normal rat gastric mucosal cell line and rat and human gastric cancer and mesothelioma cell lines
Authors: Okabe Susumu , Okamoto Toshihiro , Zhao Chun‐Mei , Chen Duan , Matsui Hirofumi
Published: December 2014

Background and Aim

We recently reported that topical application of acetic acid promptly caused tumor necrosis in a mouse model of gastric cancer. The aim of the present study was to examine whether acetic acid can directly induce cancer cell death.

Methods

Rat gastric epithelial cell line (RGM‐1), rat gastric carcinoma cell line (RGK‐1), human gastric cancer cell line (KATO III), and human mesothelioma cell lines (ACC‐MESO1 and MSTO‐211H) were used. Acetic acid was added into the cell culture at different concentrations for different time periods. Cell death was analyzed by MTT assay, flow cytometry, and trypan blue exclusion test.

Results

Acetic acid promptly induced the cell death of RGM‐1, RGK‐1 cells, and KATO III cells in a concentration‐dependent manner from 0.01% to 0.5%. Acetic acid at 0.5% for 1 min induced the cell death by 80%. RGK‐1 cells were more sensitive to acetic acid than RGM‐l cells. KATO III cells were more sensitive to acetic acid than RGK‐1 cells. Acetic acid at 0.5% for 10 min induced almost complete cell death of ACC‐MESO1 and MSTO‐211H.

Conclusions

Acetic acid is a powerful anticancer agent. Topical application of acetic acid may be a feasible approach for the treatments of gastric cancer and possibly other malignancies.