bluuebunny/crossref_metadata_2025 huggingface dataset:
HLA genotype in patients with acquired haemophilia A
Authors: PAVLOVA A. , ZEITLER H. , SCHARRER I. , BRACKMANN H.‐H. , OLDENBURG J.
Published: April 2010

Summary.  Acquired haemophilia A (AH) is a rare bleeding disorder caused by an auto‐antibody to coagulation factor VIII. It is associated with various autoimmune diseases, pregnancy, cancer or drug ingestion; however, in 50% of patients, no underlying disorder is found. In the present study, we investigated the association of HLA class I (A, B and Cw) and class II (DRB1 and DQB1) alleles with AH in a cohort of 57 patients. While no association with any class I allele was detected, a significantly higher frequency of DRB1*16 [odds ratio (OR) 10.2, 95%CI: 5.32–19.57, P < 0.0001] and DQB1*0502 (OR 2.2, 95%CI: 1.12–4.54, P < 0.05) was observed. In contrast, the frequency of DRB1*15 and DQB1*0602 alleles was found to be decreased in patients with AH corresponding to an OR of 0.4 for both HLA loci. Upon comparing the frequencies of these alleles with those of patients with congenital haemophilia A with inhibitors, the data demonstrate that the high risk alleles in patients with AH DRB1*16 and DQB1*0502 are found to be low risk alleles in patients with congenital haemophilia A with inhibitors (OR 1.1 and 1.5 respectively). Conversely, the alleles that exhibit low risk in AH DRB1*15 and DQB1*0602 are found to be high risk for haemophilia A inhibitor patients (OR 2.2 and 3.7 respectively). The pathophysiological reason for this finding remains unknown. It might be speculated that the presence or absence of the FVIII antigen and the various ability of HLA molecules to present the FVIII antigen to the T‐cell receptor contribute to these findings.
Variable region heavy chain glycosylation determines the anticoagulant activity of a factor VIII antibody
Authors: JACQUEMIN M.
Published: April 2010

Summary.  The mechanism of action of antibodies inhibiting partially factor VIII (FVIII) activity (type II inhibitor) is still poorly understood. We produced an unusual type II monoclonal antibody, called LE2E9, derived from a patient with mild haemophilia A. The antibody displayed several unexpected structural and functional properties such as glycosylation in the variable region, binding to the FVIII C1 domain, inhibition of maximum 80–90% FVIII activity when in excess over FVIII, and prevention of FVIII binding to von Willebrand factor (VWF). Those unusual characteristics of the antibody prompted multidisciplinary studies to determine its mechanism of action and the role of the FVIII C1 domain. Enzymatic deglycosylation and site‐directed mutagenesis indicated that the oligosaccharides do not determine the affinity of the antibody but enhanced its FVIII neutralizing activity. Modification of glycosylation in the variable region of antibodies therefore contributes to the diversity of FVIII type II inhibition and provides a novel strategy with which to modulate the functional activity of antibodies. Investigation of the FVIII C1 domain function led to identification of mutations located in that domain and impairing FVIII binding to VWF as a common cause of mild/moderate haemophilia A. Finally, the cloning of human monoclonal antibodies inhibiting partially FVIII activity opened the way to evaluate such antibodies as a novel type of anticoagulant drug. This concept was validated in animal models of thrombosis. Those studies are expected to have a significant impact on the optimization of treatments for patients with inhibitor as well as for patients with thrombophilia.
Wound healing in haemophilia – breaking the vicious cycle
Authors: HOFFMAN M. , MONROE D. M.
Published: April 2010

Summary.  Our group has been studying how haemostasis interacts with repair processes and also how to optimize treatment of bleeding disorders in a mouse model of haemophilia B. We have found that cutaneous wounds heal more slowly in haemophilic mice than in wild‐type mice, and also exhibit histological abnormalities, even after closure of the skin defect. The haemophilic wounds showed reduced influx of inflammatory cells and increased angiogenesis. Even after surface closure, the haemophilic animals experienced repeated episodes of re‐bleeding and progressive accumulation of iron in the wound bed and deeper tissues. A dose of replacement or bypassing therapy sufficient to establish initial haemostasis did not normalize wound healing. In fact, daily dosing for 7 days was required to normalize wound closure. Thus, normal healing requires adequate haemostatic function for an extended period of time. We have hypothesized that this is because angiogenesis during healing predisposes to bleeding, especially in the setting where haemostasis is impaired. Thus, normalizing haemostasis, until the process of angiogenesis has resolved, may be required to prevent re‐bleeding and additional tissue damage.
Genetic markers in acquired haemophilia
Authors: OLDENBURG J. , ZEITLER H. , PAVLOVA A.
Published: April 2010

Summary.  Acquired haemophilia (AH) is a rare autoimmune bleeding disorder, which arises as a result of the spontaneous production of autoantibodies against endogenous factor VIII. The breakdown in immune tolerance is thought to be a result of a combination of genetic and environmental factors. Both human leucocyte antigen (HLA) and cytotoxic T lymphocyte antigen 4 (CTLA‐4) play an important role in the maintenance of peripheral T‐cell tolerance. A higher frequency of HLA class II alleles and single nucleotide polymorphisms of the CTLA‐4 gene have been observed in some autoimmune diseases and severe haemophilia A. In 57 patients with AH, significantly higher frequencies of the HLA class II alleles DRB*16 [odds ratio (OR) 10.2] and DQB1*0502 (OR 2.5) have been detected when compared with controls. The CTLA‐4 + 49 G allele has also presented with a significantly higher frequency in the same cohort of patients with AH (OR 2.17). This observation was mainly because of a higher frequency of the CTLA‐4 + 49 G allele in female patients. These findings suggest that immune response genes may contribute to the development of anti‐factor VIII autoantibodies in AH.
Biogeographic synthesis of secondary succession rates in eastern North America
Authors: Wright Justin P. , Fridley Jason D.
Published: April 2010

Aim Mechanistic models of old‐field plant succession have generally lacked a broader biogeographic context in which climate, soils and species pools could play a significant role in mediating succession rates. We examine broad‐scale patterns in old‐field succession and introduce a hierarchical conceptual model to incorporate potential mechanisms operating at multiple spatial scales.

Location We reviewed secondary succession studies across the Eastern Deciduous Forest (EDF) of North America.

Methods We collected data from all published studies that reported the time necessary for woody species to reach either 10% or 50% cover in old‐field systems throughout the EDF. We used regression approaches to determine whether rates of succession are controlled by climatic and edaphic factors that vary at broad spatial scales.

Results We found that the rate at which woody species colonize and dominate old fields decreases significantly with latitude. Rates of woody succession were highly correlated with both annual temperature (growing degree‐days for years to 10% and 50% cover) and measures of soil fertility (cation exchange capacity and reported pre‐agroindustrial (1930) maize yields for years to 10% cover), all of which show a significant latitudinal trend across the EDF.

Main conclusions We suggest that the driver of this pattern is geographic variation in the intensity of competition between herbaceous and woody species, which we relate to the effects of (1) temperature regime, (2) edaphic factors related to soil fertility, and (3) plant traits, which may vary latitudinally in response to climate and edaphic factors. Although insufficient data exist to evaluate the relative importance of these factors, we argue that research in this area is necessary to gain an understanding of how future landscapes will be affected by global climate and land use change.
The use of chronosequences in studies of ecological succession and soil development
Authors: Walker Lawrence R. , Wardle David A. , Bardgett Richard D. , Clarkson Bruce D.
Published: April 2010

1. Chronosequences and associated space‐for‐time substitutions are an important and often necessary tool for studying temporal dynamics of plant communities and soil development across multiple time‐scales. However, they are often used inappropriately, leading to false conclusions about ecological patterns and processes, which has prompted recent strong criticism of the approach. Here, we evaluate when chronosequences may or may not be appropriate for studying community and ecosystem development.

2. Chronosequences are appropriate to study plant succession at decadal to millennial time‐scales when there is evidence that sites of different ages are following the same trajectory. They can also be reliably used to study aspects of soil development that occur between temporally linked sites over time‐scales of centuries to millennia, sometimes independently of their application to shorter‐term plant and soil biological communities.

3. Some characteristics of changing plant and soil biological communities (e.g. species richness, plant cover, vegetation structure, soil organic matter accumulation) are more likely to be related in a predictable and temporally linear manner than are other characteristics (e.g. species composition and abundance) and are therefore more reliably studied using a chronosequence approach.

4. Chronosequences are most appropriate for studying communities that are following convergent successional trajectories and have low biodiversity, rapid species turnover and low frequency and severity of disturbance. Chronosequences are least suitable for studying successional trajectories that are divergent, species‐rich, highly disturbed or arrested in time because then there are often major difficulties in determining temporal linkages between stages.

5. Synthesis.We conclude that, when successional trajectories exceed the life span of investigators and the experimental and observational studies that they perform, temporal change can be successfully explored through the judicious use of chronosequences.
Cancer imaging: novel concepts in clinical magnetic resonance imaging
Authors: Kwee T. C. , Takahara T. , Klomp D. W. J. , Luijten P. R.
Published: April 2010

Abstract.  Kwee TC, Takahara T, Klomp DWJ, Luijten PR. (University Medical Center Utrecht, Utrecht, The Netherlands). Cancer imaging: novel concepts in clinical magnetic resonance imaging. J Intern Med 2010; 268: 120–132.

Cancer is a major public health problem in the Western world. Imaging is of crucial importance in oncology, because it may reduce cancer‐related morbidity and mortality. To improve tumour evaluation, there is a need for functional imaging modalities that go beyond gross assessment of anatomical abnormalities and allow visualization and quantification of biochemical processes in vivo. Magnetic resonance imaging (MRI) not only provides anatomical information, but also offers a wide range of functional sequences that may aid the evaluation of cancerous lesions. Furthermore, MRI provides the opportunity to guide and monitor anticancer therapies noninvasively. The aim of this review is to highlight some of the most promising developments of MRI in the functional assessment of cancer and the guidance and monitoring of (novel) anticancer therapies.
Photometric calibration for quantitative spectral microscopy under transmitted illumination
Authors: THIGPEN J. , MERCHANT F.A. , SHAH S.K.
Published: April 2010

Over the past decade, there have been significant developments in the mechanisms for examination of biological and material samples. These developments exploit techniques in light microscopy to elucidate specific parts of cells and tissues, as well as inorganic particles. In recent years, spectral microscopy has become more prevalent for characterization of samples. Simultaneously, sensor technology has progressed as well and modern charge‐coupled devices (CCD) cameras are now capable of achieving high spatial resolution and high sensitivity measurements of signals in the optical microscope. One major impediment in obtaining absolute quantitative information of imaged samples is the lack of automated photometric calibration mechanisms for spectral microscopes. In this paper, we present a methodology for achieving photometric calibration of an automated spectral imaging system targeted towards examination of biological samples. By acquiring spatial and spectral data simultaneously, spectral imaging allows one to exploit physical connections between a particle's morphology and its characteristic response to the optical spectrum. In composite biological material, the interpretation of the spectra is a complicated problem. This is because any light source and charge‐coupled device camera used for data acquisition does not have a uniform illumination spectra and quantum efficiency, respectively, across the emitted light spectra. To balance the spectral response across individual wavelengths, our method modulates the exposure duration for the charge‐coupled device camera during image acquisition. We present an image similarity based method to calibrate the system. Experiments to test the effectiveness of the calibration method under the various image similarity metrics are presented along with results to show the calibrated system's ability to accurately measure spectra based on the measured transmission profiles of optical filters.
The Cpx envelope stress response both facilitates and inhibits elaboration of the enteropathogenic Escherichia coli bundle‐forming pilus
Authors: Vogt Stefanie L. , Nevesinjac Anna Z. , Humphries Romney M. , Donnenberg Michael S. , Armstrong Glen D. , Raivio Tracy L.
Published: April 2010

The Cpx envelope stress response is induced by the misfolding of periplasmic proteins and restores envelope homeostasis by upregulating several periplasmic protein folding and degrading factors. The Cpx response also regulates the expression of a variety of envelope‐spanning protein complexes, including flagella, secretion systems and pili, which play an important role in pathogenesis. In a previous study, we inactivated the Cpx response in enteropathogenic Escherichia coli (EPEC), a causative agent of infant diarrhoea, and observed decreased expression of its major adhesin, the bundle‐forming pilus (BFP). Here, we examined the mechanism underlying this BFP expression defect, and found that this phenotype can be attributed to insufficient expression of periplasmic folding factors, such as DsbA, DegP and CpxP. Hence, a low level of Cpx pathway activity promotes BFP synthesis by upregulating factors important for folding of BFP component proteins. Conversely, we found that full induction of the Cpx response inhibits BFP expression, mainly by repressing transcription of the bfp gene cluster. In combination with a previous report examining EPEC type III secretion, our results demonstrate that the Cpx response co‐ordinates the repression of cell‐surface structures during periods of envelope stress.
Tubules and donuts: a type VI secretion story
Authors: Bönemann Gabriele , Pietrosiuk Aleksandra , Mogk Axel
Published: April 2010

The recently identified type VI secretion systems (T6SSs) are present in many pathogenic proteobacteria and are encoded by a conserved gene cluster. T6SSs contribute to virulence development of various pathogens and are often activated upon contact with target cells. Since the identification of the T6SS, substantial progress has been made at all levels, including gene regulation, its impact on bacterial virulence, the function of effector proteins and the mechanism of secretion. Recent structural and mechanistic studies revealed unique features of the T6SS that distinguish it from other secretion systems. Structural similarities between the T6SS‐specific exoproteins Hcp and VgrG and components of the cell‐puncturing device of tailed bacteriophages suggest that the T6SSs mimic a bacteriophage machinery to puncture target cell membranes and to translocate effector proteins, representing a novel mechanism of effector delivery. In bacteriophages contraction of the tail sheath, which engulfs the tail tube, causes ejection of the cell‐puncturing machinery. The T6SS components VipA/VipB form tubular structures, which might function as tail sheaths by engulfing Hcp proteins. The severing of VipA/VipB complexes by the AAA+ chaperone ClpV is essential for type VI protein secretion and might be linked to VipA/VipB tubule contraction, leading to the export of Hcp and VgrG.
A post‐translational, c‐di‐GMP‐dependent mechanism regulating flagellar motility
Authors: Fang Xin , Gomelsky Mark
Published: April 2010

Elevated levels of the second messenger cyclic dimeric GMP, c‐di‐GMP, promote transition of bacteria from single motile cells to surface‐attached multicellular communities. Here we describe a post‐translational mechanism by which c‐di‐GMP initiates this transition in enteric bacteria. High levels of c‐di‐GMP induce the counterclockwise bias in Escherichia coli flagellar rotation, which results in smooth swimming. Based on co‐immunoprecipitation, two‐hybrid and mutational analyses, the E. coli c‐di‐GMP receptor YcgR binds to the FliG subunit of the flagellum switch complex, and the YcgR–FliG interaction is strengthened by c‐di‐GMP. The central fragment of FliG binds to YcgR as well as to FliM, suggesting that YcgR–c‐di‐GMP biases flagellum rotation by altering FliG‐FliM interactions. The c‐di‐GMP‐induced smooth swimming promotes trapping of motile bacteria in semi‐solid media and attachment of liquid‐grown bacteria to solid surfaces, whereas c‐di‐GMP‐dependent mechanisms not involving YcgR further facilitate surface attachment. The YcgR–FliG interaction is conserved in the enteric bacteria, and the N‐terminal YcgR/PilZN domain of YcgR is required for this interaction. YcgR joins a growing list of proteins that regulate motility via the FliG subunit of the flagellum switch complex, which suggests that FliG is a common regulatory entryway that operates in parallel with the chemotaxis that utilizes the FliM‐entryway.
Reduced myoelectric activity in the sphincter of Oddi in a new model of chronic cholangitis in rabbits: an in vivo and in vitro study
Authors: Liu Y‐k. , Li Z‐h. , Liu N‐z. , He Q. , Lin H. , Wang X‐j. , Li X‐w. , Dong J‐h.
Published: April 2010

Background  Chronic cholangitis caused by hepatolithiasis is a common disease in Southeast Asia. Few studies have addressed the effects of chronic cholangitis on cyclic activity of the sphincter of Oddi (SO). In this study, we investigated the changes of myoelectric activity in rabbits with chronic cholangitis in vivo and in vitro.

Methods  Chronic cholangitis was induced in rabbits by initially introducing three pieces of 2–0 silk suture and sequentially injecting E. coli into the choledochus through the tube in ductus cysticus. In in vivo experiments, myoelectric activity of SO was recorded by a circular electrode through the jejunum stump in conscious animals. In in vitro experiments, the SO was completely isolated and the myoelectric activity was recorded by a circular electrode in a 10‐mL organ bath filled with Krebs solution, with or without addition of cholecystokinin‐8 (CCK‐8), KCl, ionomycin or induction of capacitative calcium entry (CCE).

Key Results  In comparison with control and non‐infected rabbits, the rabbits with chronic cholangitis showed higher levels of alkaline phosphatase and γ‐glutamyltransferase and significant pathological changes including increased inflammatory infiltration and collagen deposition in mucosae or muscular layer. Cyclic myoelectric activity of SO at phases 2 and 3 of migrating motor complex and the excitatory response to CCK‐8 were dramatically decreased in animals with chronic cholangitis. Myoelectric activity of SO was also significantly decreased in vitro with or without agonists or with induction of CCE.

Conclusions & Inferences  Myoelectric activity of SO and its response to agonists are decreased in rabbits with chronic cholangitis both in vivo and in vitro.
Molecular mechanisms of cross‐inhibition between nicotinic acetylcholine receptors and P2X receptors in myenteric neurons and HEK‐293 cells
Authors: Decker D. A. , Galligan J. J.
Published: April 2010

Background  P2X2 and nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic excitation in the enteric nervous system. P2X receptors and nAChRs are functionally linked. This study examined the mechanisms responsible for interactions between P2X2 and α3β4subunit‐containing nAChRs.

Methods  The function of P2X2 and α3β4 nAChRs expressed by HEK‐293 cells and guinea pig ileum myenteric neurons in culture was studied using whole‐cell patch clamp techniques.

Key Results  In HEK‐293 cells expressing α3β4 nAChRs and P2X2 receptors, co‐application of ATP and acetylcholine caused inward currents that were 56 ± 7% of the current that should occur if these channels functioned independently (P < 0.05, n = 9); we call this interaction cross‐inhibition. Cross‐inhibition did not occur in HEK‐293 cells expressing α3β4 nAChRs and a C‐terminal tail truncated P2X2 receptor (P2X2TR) (P > 0.05, n = 8). Intracellular application of the C‐terminal tail of the P2X2 receptor blocked nAChR‐P2X receptor cross‐inhibition in HEK‐293 cells and myenteric neurons. In the absence of ATP, P2X2 receptors constitutively inhibited nAChR currents in HEK‐293 cells expressing both receptors. Constitutive inhibition did not occur in HEK‐293 cells expressing α3β4 nAChRs transfected with P2X2TR. Currents caused by low (≤30 μmol L−1), but not high (≥100 μmol L−1) concentrations of ATP in cells expressing P2X2 receptors were inhibited by co‐expression with α3β4 nAChRs.

Conclusions & Inferences  The C‐terminal tail of P2X2 receptors mediates cross‐inhibition between α3β4 nAChR‐P2X2 receptors. The closed state of P2X2 receptors and nAChRs can also cause cross‐inhibition. These interactions may modulate transmission at enteric synapses that use ATP and acetylcholine as co‐transmitters.
Sexual coevolution in the traumatically inseminating plant bug genus Coridromius
Authors: TATARNIC N. J. , CASSIS G.
Published: April 2010

Sexual conflict has recently been proposed as a driving force behind the rapid diversification of genitalia among sexually reproducing organisms. In traumatically inseminating insects, males stab females in the side of the body with needle‐like genitalia, ejaculating into their body cavity. Such mating is costly to females and has led to the evolution of cost‐reducing ‘paragenitalia’ in some species. Whereas some consider this evidence of sexually antagonistic coevolution, others remain unconvinced. Variation in the reproductive morphology of both sexes – particularly males – is alleged to be negligible, contradicting the expectations of a coevolutionary arms race. Here, we use a phylogeny of the traumatically inseminating plant bug genus Coridromius to show that external female paragenitalia have evolved multiply across the genus and are correlated with changes in male genital shape. This pattern is characteristic of an evolutionary arms race driven by sexual conflict.
Geographic variation in sperm traits reflects predation risk and natural rates of multiple paternity in the guppy
Authors: ELGEE K. E. , EVANS J. P. , RAMNARINE I. W. , RUSH S. A. , PITCHER T. E.
Published: April 2010

Guppies (Poecilia reticulata) are models for understanding the interplay between natural and sexual selection. In particular, predation has been implicated as a major force affecting female sexual preferences, male mating tactics and the level of sperm competition. When predation is high, females typically reduce their preferences for showy males and engage more in antipredator behaviours, whereas males exploit these changes by switching from sexual displays to forced matings. These patterns are thought to account for the relatively high levels of multiple paternity in high‐predation populations compared to low‐predation populations. Here, we assess the possible evolutionary consequences of these patterns by asking whether variation in sperm traits reflect differences in predation intensity among four pairs of Trinidadian populations: four that experience relatively low levels of predation from a gape‐limited predator and four that experience relatively high levels of predation from a variety of piscivores. We found that males in high‐predation populations had faster swimming sperm with longer midpieces compared to males in low‐predation populations. However, we found no differences among males in high‐ and low‐predation populations with respect to sperm number, sperm head length, flagellum length and total sperm length.
Transfused stored platelets have the same haemostatic function as circulating native platelets
Authors: Roeloffzen W. W. H. , Kluin‐Nelemans H. C. , Veeger N. J. G. M. , Bosman L. , De Wolf J. Th. M.
Published: April 2010

Background and objectives  As thrombelastography® (TEG) measures haemostasis in whole blood, we used this instrument to study whether transfused platelets (PLTs) have the same haemostatic function compared to native circulating PLTs. Further, we studied the effect of storage time on the haemostatic potential of platelet concentrates (PCs).

Materials and methods  During the decrease in PLT count after chemotherapy, TEG parameters were measured serially until the transfusion trigger was reached in 92 patients. TEG parameters for different ranges of native circulating PLTs could be assessed, which were compared to ranges obtained in the thrombocytopenic period in which the patient received PLT transfusions. Finally, we compared the haemostatic potential of fresh PCs (1–3 days) with PCs with longer storage time (4–5 days).

Results  No differences could be found in haemostatic potential between native PLTs and transfused stored PLTs (all P‐values ≥ 0·1). The transfusion of fresh PLTs demonstrated better haemostatic effects than longer stored PLTs, measured 1 h after transfusion. Both the time until a fixed level of clot firmness was reached (K‐time) and the rate of clot growth (alpha angle) were superior for fresh PCs.

Conclusion  TEG is able to monitor the haemostatic effects of PLT transfusion, with comparable haemostatic properties of native circulating and transfused stored‐PLTs. Further, our data suggest that limited storage time is associated with a better haemostatic capacity. However, before TEG can be applied as a qualitative test in PLT transfusion, further research is needed with focus on clinical outcomes like bleeding episodes.
Application of Laser‐Assisted Microdissection for Gene Expression Analysis of Mammalian Germ Cells
Authors: Kenngott R. , AL‐Banaw A. , Vermehren M. , Wendl J. , Sinowatz F.
Published: April 2010

With 1 figure and 2 tables

Laser‐assisted microdissection (LAM) is an important method to provide new significant insights into many embryological processes. To understand these processes, it is important to obtain specific populations of cells from complex tissue in an efficient and precise manner and to combine with many different molecular biological methods. During the last few years, the sophistication of the techniques of LAM has increased significantly and made the procedure easy to use. New micro‐extraction protocols for DNA, RNA and proteins now allow broad downstream applications in the fields of genomics, transcriptomics and proteomics. In this review, we give a short overview of the application of LAM in combination with quantitative qPCR for the analysis of gene expression in mammalian germ cells.
Tail Autotomy Plays No Important Role in Influencing Locomotor Performance and Anti‐Predator Behavior in a Cursorial Gecko
Authors: Lu Hong‐Liang , Ding Guo‐Hua , Ding Ping , Ji Xiang
Published: April 2010

We used the frog‐eyed sand gecko (Teratoscincus scincus) as a model system to evaluate the locomotor costs of tail loss, and to examine whether tailless geckos use alternative anti‐predator behavior to compensate for the costs of tail loss. Of the 16 field‐captured geckos, eight were used as experimental animals and the remaining ones as controls. Locomotor performance, activity level and anti‐predator behavior were measured for experimental geckos before and after the tail‐removing treatment. Control geckos never undergoing the tail‐removing manipulation were measured to serve as controls for the measurements taken at the same time for experimental geckos. Experimental geckos did not differ from controls in activity level before they underwent the tail‐removing manipulation, but became less active thereafter. The mean locomotor stamina of tailless geckos was reduced by about 30% of the mean value for tailed ones. However, as the maximum stamina predicted from the laboratory trials is seldom required in nature, we expect that the costs associated with the reduced locomotor stamina may be relatively minor in T. scincus. All other examined locomotor (overall speed, maximal speed and stride length) and behavioral (distance to refuge, approach distance and flight distance) traits were not affected by the tail‐removing manipulation. Overall, our results suggest that tail autotomy plays no important role in influencing locomotor performance and anti‐predator behavior in lizards where the tail has no direct role in locomotion but is used to direct predatory strikes away from the torso.
Development of pyramided lines with two resistance genes, Pish and Pib, for blast disease (Magnaporthe oryzae B. Couch) in rice (Oryza sativa L.)
Authors: Koide Y. , Kawasaki A. , Telebanco‐Yanoria M. J. , Hairmansis A. , Nguyet N. T. M. , Bigirimana J. , Fujita D. , Kobayashi N. , Fukuta Y.
Published: April 2010

With 2 figures and 4 tables

Gene pyramiding is considered one of the most effective strategies for achieving durable resistance against blast disease (Magnaporthe oryzae B. Couch) in rice (Oryza sativa L.), although few studies have evaluated the combining effect of the resistance genes. We report the development of pyramided lines with two major blast resistance genes, Pish and Pib, and the evaluation of the combining effect of them. The two genes pyramided lines were selected from the progenies of a cross between one near isogenic line (NIL), which harbours Pish, and another NIL, which harbours Pib, in the genetic background of blast susceptible variety, CO 39. The presence of the resistance genes was confirmed by DNA markers linked to them. To obtain DNA markers for Pish, we genetically mapped the Pish locus. We confirmed the additive effect of Pish and Pib in the pyramided lines by their reaction patterns to blast isolates, suggesting the potential availabilities of the combinations of these genes. In addition, we provide DNA markers linked to Pish for marker aided selection in rice blast resistance breeding.
Analysis of the microflora in the stomach of Mongolian gerbils infected with Helicobacter pylori
Authors: Zaman Cynthia , Osaki Takako , Hanawa Tomoko , Yonezawa Hideo , Kurata Satoshi , Kamiya Shigeru
Published: April 2010

Background and Aims:  Mongolian gerbils are frequently used to study Helicobacter pylori‐induced gastritis and its consequences. The presence of some gastric flora with a suppressive effect on H. pylori suggests inhibitory microflora against H. pylori infection. The aim of the present study was to analyze the microflora in the stomach of Mongolian gerbils with H. pylori infection.

Methods:  H. pylori ureA was detected by polymerase chain reaction (PCR) in the fecal samples of infected Mongolian gerbils. H. pylori was isolated from the gastric mucosa of the gerbils by microaerophilic cultivation. Gastric microflora were isolated by aerobic and anaerobic culture, and the identification of gastric bacterial species was performed by API20E and API20A.

Results:  Oral administration of H. pylori TK1402 induced colonization and gastric inflammation of the stomach of the Mongolian gerbils. According to the frequency of detection of H. pylori ureA in fecal samples, the gerbils were divided into three groups (frequently detected, moderately detected and infrequently detected). According to the analysis of the gastric microflora in the frequently and infrequently detected groups, Lactobacillus spp. and Eubacterium limosum were isolated from the former and latter group, respectively.

Conclusion:  Some gastric flora, such as Lactobacillus spp., may inhibit colonization by H. pylori.
Colorectal cancer screening in evolution: Japan and the USA
Authors: Ross William A
Published: April 2010

Colorectal cancer (CRC) is one of the most common cancers in both Japan and the USA. Age‐adjusted incidence of CRC has been in decline in the USA since 1985, while rates in Japan have been increasing. The decline in the USA is commonly attributed to CRC screening programs but there is little direct evidence to support this assertion. The current screening recommendations in the USA cover several options including colonoscopy and computerized tomographic colonography (CTC). The Japanese CRC screening program is centered on fecal immunochemistry testing (FIT). The US government Medicare program's approval of colonoscopy as a primary screening test has lead to a large increase in the number of patients undergoing the procedure. However, the benefit achieved from this change in screening program emphasis is not clear. Simulation models demonstrate that a screening program centered on FIT achieves 94% of the benefit that an all‐colonoscopy program is able to accomplish but at a lower cost per life year gained. Clinical studies of colonoscopy have failed to demonstrate the 76–90% declines in CRC incidence predicted by the National Polyp Study published in 1993. A potential reason for this failure is the quality of colonoscopy performance. Until more compelling data becomes available demonstrating the utility of colonoscopy as a primary screening modality, there is little incentive to alter the proven cost‐effective approach to CRC screening currently in practice in Japan.
Protective effect of lafutidine, a histamine H2 receptor antagonist, against loxoprofen‐induced small intestinal lesions in rats
Authors: Amagase Kikuko , Ochi Akimu , Sugihara Tetsuya , Kato Shinichi , Takeuchi Koji
Published: April 2010

Background and Aims:  We examined the effect of lafutidine, a histamine H2 receptor antagonist with a mucosal protective action mediated by capsaicin‐sensitive sensory neurons (CSN), on intestinal lesions produced by loxoprofen administration in rats.

Methods:  Animals were given loxoprofen (10–100 mg/kg p.o.) and killed 24 h later. Lafutidine (10 and 30 mg/kg), cimetidine (100 mg/kg) or famotidine (30 mg/kg) was given twice p.o. at 0.5 h before and 6 h after loxoprofen. Omeprazole (100 mg/kg) was given p.o. once 0.5 h before. Ampicillin (800 mg/kg) was given p.o. twice at 24 h and 0.5 h before loxoprofen, while 16,16‐dimethyl prostaglandin E2 (dmPGE2; 0.01 mg/kg) was given i.v. twice at 5 min before and 6 h after.

Results:  Loxoprofen dose‐dependently produced hemorrhagic lesions in the small intestine, accompanied by invasion of enterobacteria and increased inducible nitric oxide synthase (iNOS) expression as well as myeloperoxidase activity in the mucosa. The ulcerogenic response to loxoprofen (60 mg/kg) was significantly prevented by lafutidine (30 mg/kg), similar to dmPGE2 and ampicillin, and the effect of lafutidine was totally attenuated by ablation of CSN. Neither cimetidine, famotidine nor omeprazole had a significant effect against these lesions. Lafutidine alone increased mucus secretion and reverted the decreased mucus response to loxoprofen, resulting in suppression of bacterial invasion and iNOS expression. In addition, loxoprofen downregulated Muc2 expression, and this response was totally reversed by lafutidine mediated by CSN.

Conclusion:  Lafutidine protects the small intestine against loxoprofen‐induced lesions, essentially mediated by the CSN, and this effect may be functionally associated with increased Muc2 expression/mucus secretion, an important factor in the suppression of bacterial invasion.
Impact of upper gastrointestinal lesions in patients on low‐dose aspirin therapy: Preliminary study
Authors: Kawai Takashi , Watanabe Masataka , Yamashina Akira
Published: April 2010

Background and Aims:  We investigated the incidence of upper gastrointestinal lesions in the esophagus, stomach and duodenum in patients on low‐dose aspirin (LDA) therapy.

Methods:  The subjects were 101 consecutive outpatients who had been on LDA therapy (average age 67.2 ± 8.3 years; male : female ratio 3.8:1). All subjects underwent endoscopy without ceasing their antiplatelet or anticoagulant therapy. We investigated the rates of endoscopic peptic ulcer, reflux esophagitis (RE) and malignant lesion.

Results:  RE was detected in eight subjects and esophageal ulcer in one subject. The severity of RE, according to the Los Angeles classification, was grade A in one subject, B in four, C in two and D in one. All nine subjects (8.9%) with RE and esophageal ulcer were negative for Helicobacter pylori infection. Gastric ulcer was detected in 12 subjects (six H. pylori positive, six negative) and duodenal ulcer in four (one H. pylori positive, three negative). The incidence of gastroduodenal ulcer was 15.8% (16/101). The incidence of esophageal and gastric cancers was high at 5.9% (6/101). Subjects were surveyed using the gastrointestinal symptom rating scale, with no differences in scores for acid reflux, abdominal pain or indigestion according to the presence or absence of RE, gastric ulceration or duodenal ulceration.

Conclusion:  Upper gastrointestinal mucosal injuries and neoplasm were found in not only the stomach, but also the esophagus and duodenum in LDA taking subjects. These results emphasize the importance of endoscopic surveillance in patients on LDA therapy.
New method of inducing intestinal lesions in rats by intraduodenal administration of aspirin
Authors: Nonoyama Kenichi , Nakagawa Kanako , Amagase Kikuko , Takeuchi Koji , Nakamura Masahiko , Okabe Susumu
Published: April 2010

Background and Aims:  Enteroscopic observation has clearly demonstrated that non‐steroidal anti‐inflammatory drugs/low‐dose aspirin (usually enteric‐coated) induces hemorrhagic lesions, including ulcers and bleeding, in the small intestine of patients at a high incidence. Such intestinal lesions induced by NSAIDs have been confirmed in animal experiments. With aspirin, however, it has long been believed that it is difficult to induce any damage in the intestinal mucosa of laboratory animals. Therefore, we established a new method of inducing intestinal hemorrhagic lesions in rats by injecting aspirin into the proximal duodenum.

Methods:  Under ether anesthesia, aspirin (50–200 mg/body), suspended in 2% methylcellulose (with or without 0.1 N HCl), was injected into the proximal duodenum of normally fed or 20‐h non‐fed rats (male Sprague–Dawley, 9 weeks old). At 1 h after treatment, the animals were killed with ether and the entire small intestine was removed for histological examination. In some experiments, 1% Evans blue was injected (i.v.) into the rats 1 h after aspirin treatment to visualize the lesions. An image analyzer determined the total area of the intestinal lesions. Oral proton pump inhibitors and histamine H2‐receptor blockers were given 1 h before aspirin injection. 16,16‐dimethyl prostaglandin E2 (dmPGE2) was given s.c. 30 min before aspirin injection.

Results:  Aspirin alone clearly induced severe lesions (including bleeding and ulcers) mainly in the jejunum at 100% incidence. Total score of lesions per rat obtained by histological examination was similar to the damaged area quantified with the dye method. Dose‐related induction of lesions by aspirin was confirmed both by the histological and dye methods. The irritable effect of aspirin suspended in 0.1 N HCl solution was the same as that of aspirin alone; 0.1 N HCl alone induced only minor lesions in the intestine. Both proton pump inhibitors and histamine H2‐receptor blockers, at doses that inhibit gastric acid secretion, had no or little effect on aspirin‐induced intestinal lesions. Pretreatment with dmPGE2 (3, 10, 30 µg/kg) showed significant prevention of both aspirin‐ and HCl/aspirin‐induced intestinal lesions.

Conclusion:  This new aspirin lesion model will be useful for screening defensive drugs against aspirin‐induced intestinal lesions and to elucidate the underlying mechanism.
Helicobacter pylori infection and reflux esophagitis in young and middle‐aged Japanese subjects
Authors: Kawai Takashi , Yamamoto Kei , Fukuzawa Mari , Yamagishi Tetsuya , Yagi Kenji , Fukuzawa Masakatsu , Kataoka Mikinori , Kawakami Kohei , Itoi Takao , Sakai Yoshihiro , Moriyasu Fuminori , Takagi Yu , Aoki Tatsuya
Published: April 2010

Background and Aims:  Helicobacter pylori infection rates are reported to be high in people over the age of 40 years, but are decreasing in younger age groups. A negative correlation has been reported between H. pylori infection and reflux esophagitis (RE).

Methods:  The subjects were 418 patients who underwent esophagogastroduodenoscopy and measurement of serum immunoglobulin G H. pylori antibodies examined as part of their routine health checks. Their mean age was 39.2 ± 8.3 years (range 22–58). We analyzed the RE findings (Los Angeles classification: A, B, C, D).

Results:  The total H. pylori infection rate was 33.7% (141/418). By age group, infection rates were 15.7% in the 20–29 years group, 28.0% in the 30–39 group, 34.3% in the 40–49 group and 69.1% in the 50–59 group. The proportion of H. pylori‐negative subjects with RE was 23.5% (20–29, 22.9%; 30–39, 31.7%; 40–49, 32.4%; 50–59, 41.7%), significantly higher than that (12.1%) in H. pylori‐positive subjects (20–29, 0%; 30–39, 16.7%; 40–49, 12.2%; 50–59, 10.5%). The severity of RE increased with advancing age in H. pylori‐positive subjects, but not in H. pylori‐negative subjects.

Conclusion:  In this study, higher rates of RE were seen in H. pylori‐negative subjects. It may be, however, that the presence of H. pylori infection influences the progression of RE.
Clinicopathological characteristics of colorectal cancer less than 10 mm in diameter and invading submucosa and below
Authors: Beppu Kazuko , Nagahara Akihito , Terai Takeshi , Matsumoto Kenshi , Shibuya Tomoyoshi , Sakamoto Naoto , Osada Taro , Kawabe Masato , Otaka Michiro , Ogihara Tatsuo , Watanabe Sumio
Published: April 2010

Background and Aims:  Identifying the invasive depth of cancers less than 10 mm in diameter remains a challenge. This study examines the clinicopathological characteristics of colorectal cancers less than 10 mm in diameter and invading submucosal layer (SM)3 and below, which require surgery and must never be treated by endoscopic mucosal resection.

Methods:  We studied 54 cases of colorectal cancer less than 10 mm in diameter and invading the submucosa and deeper tissues, by dividing them into two groups: those invading SM1 and SM2 versus those invading SM3 and below. We investigated the clinicopathological characteristics of cancers invading SM3 and below by comparing them with cancers invading SM1 and SM2. Similarly, 38 cases, whose endoscopic findings could be analyzed, were selected and examined.

Results:  In cases invading SM3 and below, the rates of moderately to poorly differentiated adenocarcinoma, lymphatic and venous permeation and lymph node metastasis were significantly higher than those invading SM1 and SM2. Among cases invading SM3 and below, the presence of endoscopic findings—including white spots of the protruded type, and fullness, white spots, hardness and protruded lesions in the depressed area of the depressed type—was significantly higher than among those invading SM1 and SM2.

Conclusion:  Colorectal cancers less than 10 mm in diameter and invading SM3 and below have high malignant potential. Cancers of this invasive depth can be identified by looking for characteristics such as white spots, fullness, hardness and protruded lesions in the depressed area. Careful endoscopic observation for these signs aids in determining the appropriate treatment.
Enteral nutrition decreases hospitalization rate in patients with Crohn's disease
Authors: Watanabe Osamu , Ando Takafumi , Ishiguro Kazuhiro , Takahashi Hironao , Ishikawa Daisuke , Miyake Nobuyuki , Kato Tsuyoshi , Hibi Satoshi , Mimura Shunya , Nakamura Masanao , Miyahara Ryoji , Ohmiya Naoki , Niwa Yasumasa , Goto Hidemi
Published: April 2010

Background and Aims:  Crohn's disease (CD) is a chronic inflammatory bowel disease with relapse and remission. CD patients are admitted to hospital when bowel inflammation flares up severely, which lowers their quality of life. Enteral nutrition (EN) with an elemental diet plays an important role in the treatment for CD patients in Japan, because of its few adverse effects, and it is thought to be effective in maintaining remission. We investigated the effectiveness of EN with an elemental diet with regard to the avoidance of hospitalization.

Methods:  A total of 268 patients with CD who visited hospital from 2003–2008 were enrolled. The relationship between the caloric content of an elemental diet and hospitalization as an end‐point was examined retrospectively using Cox regression analysis. Cumulative non‐hospitalization rates were calculated by the Kaplan–Meier method.

Results:  Of the 268 patients, 155 received an elemental diet providing 900 kcal/day or more. Among 237 patients with ileal involvement, 135 patients receiving an elemental diet providing 900 kcal/day or more showed a statistically significant improvement in cumulative non‐hospitalization rate. Among 31 patients without ileal involvement, in contrast, the cumulative non‐hospitalization rate did not differ among those receiving an elemental diet of less or more than 900 kcal/day.

Conclusion:  The use of an elemental diet of 900 kcal/day may be effective in avoiding hospitalization in CD patients with ileal lesions. This diet may be useful in improving the long‐term convalescence of these patients.
Indoor exposure to environmental cigarette smoke, but not other inhaled particulates associates with respiratory symptoms and diminished lung function in adults
Authors: HERSOUG Lars‐Georg , HUSEMOEN Lise L.N. , SIGSGAARD Torben , MADSEN Flemming , LINNEBERG Allan
Published: April 2010

Background and objective:  Exposure to particulate matter (PM) can induce airway inflammation and exacerbation of asthma. However, there is limited knowledge about the effects of exposure to indoor sources of PM. We investigated the associations between self‐reported exposure to indoor sources of PM and lower airway symptoms and lung function.

Methods:  A population‐based cross‐sectional study of 3471 persons aged 18–69 years was conducted. Information about exposure to indoor sources of PM and airway symptoms was obtained from a self‐administered questionnaire.

Results:  Exposure to wood stoves, candles and gas cookers was not significantly associated with an increased prevalence of lower respiratory symptoms or decreased lung function. In contrast, persons exposed to environmental tobacco smoke for >5 h/day had a significantly increased risk of ‘wheeze’ (OR 1.69, 95% CI: 1.24–2.30) and ‘chronic cough’ (OR 1.57, 95% CI: 1.12–2.20), as well as decreased lung function (FEV1% predicted), compared with those who were not exposed. Similar trends were observed in never smokers.

Conclusions:  In this cross‐sectional study of an adult general population, self‐reported exposure to environmental tobacco smoke, but not self‐reported exposure to wood stoves, candles or gas cookers, appeared to be associated with an increased prevalence of lower airway symptoms and decreased lung function.