bluuebunny/crossref_metadata_2025 huggingface dataset:
Separation of decay‐accelerating and cofactor functional activities of Kaposi's sarcoma‐associated herpesvirus complement control protein using monoclonal antibodies
Authors: Mark Linda , Proctor David G. , Blackbourn David J. , Blom Anna M. , Spiller O. Brad
Published: September 2007

Complement is an essential part of the innate immune system, which clears pathogens without requirement for previous exposure, although it also greatly enhances the efficacy and response of the cellular and humoral immune systems. Kaposi's sarcoma‐associated herpesvirus (KSHV) is the most recently identified human herpesvirus and the likely aetiological agent of Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. We previously reported that the KSHV complement control protein (KCP) was expressed on infected cells and virions, and could inhibit complement through decay‐accelerating activity (DAA) of the classical C3 convertase and cofactor activity (CFA) for factor I (FI)‐mediated degradation of C4b and C3b, as well as acting as an attachment factor for binding to heparan sulphate on permissive cells. Here, we determined the ability of a panel of monoclonal anti‐KCP antibodies to block KCP functions relative to their recognized epitopes, as determined through binding to recombinant KCP containing large (entire domain) or small (2–3 amino acid residue) alterations. One antibody recognizing complement control protein (CCP) domain 1 blocked heparin binding, DAA and C4b CFA, but was poor at blocking C3b CFA, while a second antibody recognizing CCP4 blocked C3b CFA and 80% DAA, but not C4b CFA or heparan sulphate binding. Two antibodies recognizing CCP2 and CCP3 were capable of blocking C3b and C4b CFA and heparan sulphate binding, but only one could inhibit DAA. These results show that, while KCP is a multifunctional protein, these activities do not completely overlap and can be isolated through incubation with monoclonal antibodies.
Balancing ecological complexity in predictive models: a reassessment of risk models in the mountain pine beetle system
Authors: Nelson William A. , Potapov Alex , Lewis Mark A. , Hundsdörfer Anina E. , He Fangliang
Published: September 2007

The nature of ecological risk assessment is to predict the probability of an event, such as extinction or invasion, in a location where the event has rarely occurred. This typically requires developing risk models from data on events in different locations. One perplexing challenge in developing these models is to find the optimal balance of model complexity that reflects the tactical details of a system, but is sufficiently strategic to be applicable under a wide range of situations.

Here we address the balance of complexity in risk models for the mountain pine beetle system. Mountain pine beetles (Dendroctonus ponderosaeHopkins) are destructive pests of pine forests in western North America. Much effort has gone into collecting empirical evidence and developing mechanistic models of infestation dynamics, which has resulted in a wealth of process‐based information. Current risk models, however, are based solely on indices of stand susceptibility that do not incorporate much of this ecological understanding. In practice, current risk models have proven ineffective at predicting the risk or extent of an infestation.

We assemble an ecological framework of the beetle–host interaction that allows us to compare across phenomenological and mechanistic models. We demonstrate that current risk models predict only ranked risk among forest stands, as opposed to absolute risk, and thereby provide an explanation for their limited ability to predict risk in practice. By comparing existing models with the ecological framework, we identify the primary factors determining risk, and propose which dynamical processes should be modelled explicitly, and which might be strategically abstracted.

Synthesis and applications. Balancing model complexity in predictive risk models is challenging for systems with complex ecology and imperfect information. Here we draw together a wide range of empirical and modelling work in the mountain pine beetle system to develop a strategic framework of the ecological interactions. Through this framework, we demonstrate why current risk models have been ineffective in predicting risk, and suggest a starting point for future risk models that explicitly describe the dynamical processes necessary to predict absolute risk.
Empirical photometric redshifts of luminous red galaxies and clusters in the Sloan Digital Sky Survey
Authors: Lopes P. A. A.
Published: September 2007

In this work I discuss the necessary steps for deriving photometric redshifts for luminous red galaxies (LRGs) and galaxy clusters through simple empirical methods. The data used are from the Sloan Digital Sky Survey (SDSS). I show that with three bands only (gri) it is possible to achieve results as accurate as the ones obtained by other techniques, generally based on more filters. In particular, the use of the (g−i) colour helps improving the final redshifts (especially for clusters), as this colour monotonically increases up to z∼ 0.8. For the LRGs I generate a catalogue of ∼1.5 million objects at z < 0.70. The accuracy of this catalogue is σ= 0.027 for z≤ 0.55 and σ= 0.049 for 0.55 < z≤ 0.70. The photometric redshift technique employed for clusters is independent of a cluster selection algorithm. Thus, it can be applied to systems selected by any method or wavelength, as long as the proper optical photometry is available. When comparing the redshift listed in literature to the photometric estimate, the accuracy achieved for clusters is σ= 0.024 for z≤ 0.30 and σ= 0.037 for 030 < z≤ 0.55. However, when considering the spectroscopic redshift as the mean value of SDSS galaxies on each cluster region, the accuracy is at the same level as found by other authors: σ= 0.011 for z≤ 0.30 and σ= 0.016 for 030 < z≤ 0.55. The photometric redshift relation derived here is applied to thousands of cluster candidates selected elsewhere. I have also used galaxy photometric redshifts available in SDSS to identify groups in redshift space and then compare the redshift peak of the nearest group to each cluster redshift. This procedure provides an alternative approach for cluster selection, especially at high redshifts, as the cluster red sequence may be poorly defined.
Biological functions of glucan‐binding protein B of Streptococcus mutans
Authors: Fujita K. , Matsumoto‐Nakano M. , Inagaki S. , Ooshima T.
Published: September 2007

Introduction:  Streptococcus mutans has been implicated as a major causative agent of dental caries in humans. Bacterial components associated with the adhesion phase of S. mutans include glucosyltransferases, protein antigen C and proteins that bind glucan. At least four glucan‐binding proteins (Gbp) have been identified; GbpA, GbpB, GbpC and GbpD.

Methods:  In our previous study, the contributions of GbpA and GbpC to the virulence of S. mutans were investigated; however, the biological function of GbpB and its role in the virulence of S. mutans remain to be elucidated. Using a GbpB‐deficient mutant strain (BD1), we demonstrated in the present study that GbpB has a role in the biology of S. mutans.

Results:  The growth rate of BD1 was lower than that of other strains, while it was also shown to be less susceptible to phagocytosis and to form longer chains than the parental strain MT8148. In addition, electron microscope observations of the cell surfaces of BD1 showed that the cell‐wall layers were obscure.

Conclusion:  These results suggest that GbpB may have an important role in cell‐wall construction and be involved in cell separation and cell maintenance.
Candida albicans THI13 disruption affects production of monocytic cytokines
Authors: Zhu Z. Y. , Cao Y. Y. , Wang Y. , Quan H. , Zhao J. X. , Jia X. M. , Cao Y. B. , Gao P. H. , Xu Z. , Jiang Y. Y.
Published: September 2007

Introduction:  The Candida albicansTHI13 gene was identified by its homology to the Candida tropicalis CtNMT1 gene, which is involved in pyrimidine precursor biosynthesis.

Methods:  Disruption of THI13 revealed that this gene played a minor role in thiamin biosynthesis in C. albicans. Purified human monocytes were incubated with C. albicans at the optimal Candida: monocyte ratio of 0.5 and cytokines in the supernatants were measured by enzyme‐linked immunosorbent assay.

Results and discussion:  This experiment showed that the wild‐type strain significantly induced interleukin‐10 (IL‐10) production but had little effect on IL‐12 production, and that THI13 mutants had no significant effect on IL‐10 production, though the IL‐12 level was increased in the supernatants. These results suggest that THI13 is involved in the host effective immune response by regulating IL‐10 and IL‐12 production.
Activity of anti‐Porphyromonas gingivalis egg yolk antibody against gingipains in vitro
Authors: Yokoyama K. , Sugano N. , Rahman A. K. M. S. , Oshikawa M. , Ito K.
Published: September 2007

Introduction:  We investigated the effect of anti‐Porphyromonas gingivalis egg yolk antibody against gingipains [immunoglobulin Y (IgY)‐GP] on gingipain activity in vitro.

Methods:  IgY‐GP was isolated from the yolks of White Leghorn hens immunized with purified gingipains. Control antibody (IgY) was isolated from the yolks of non‐immunized hens. Gingipain activity was assessed according to the rate of enzymatic substrate hydrolysis. Human epithelial cells were cultured with or without gingipains and with gingipains pretreated with either IgY‐GP or IgY.

Results:  Hydrolytic activity decreased in the presence of IgY‐GP. Cells incubated with gingipains showed a dose‐dependent loss of adhesion activity. Pretreatment of gingipains with IgY‐GP was associated with strong inhibition of cell detachment, whereas pretreatment with IgY was not.

Conclusion:  Our findings suggest that IgY‐GP may be an effective immunotherapeutic agent in the treatment of periodontitis.
Susceptibility of oral obligate anaerobes to telithromycin, moxifloxacin and a number of commonly used antibacterials
Authors: Tomás I. , Tomás M. , Álvarez M. , Velasco D. , Potel C. , Limeres J. , Diz P.
Published: September 2007

Introduction:  Obligate anaerobes are closely involved in the pathogenesis of oral and focal infections. The objective of this study was to evaluate the susceptibility profiles of obligate anaerobes of oral origin to telithromycin (TLM), moxifloxacin (MXF), and other antibiotics that are commonly used in dentistry.

Methods:  The study sample comprised 172 obligate anaerobes isolated from the saliva of 43 adult volunteers. The minimum inhibitory concentrations (MICs) were determined by the agar dilution technique in Brucella agar medium supplemented with vitamin K, haemin and 5% (volume/volume) laked sheep blood, and incubated under anaerobic conditions. The Clinical and Laboratory Standards Institute methodology was followed and its criteria were used for the qualitative interpretation of the results. The antibiotics evaluated were: amoxicillin (AMX), amoxicillin‐clavulanic acid (AMX‐CLA), clindamycin (CM), metronidazole (MTZ), azithromycin (AZM), TLM and MXF.

Results:  Resistance to AMX (MIC90  16 mg/l) was observed in 45.3% of the obligate anaerobes and resistance to CM (MIC90  16 mg/l) was found in 18.6%. All the isolates were sensitive to MTZ (MIC90 = 1 mg/l) and 98.8% were sensitive to AMX‐CLA (MIC90 = 2 mg/l). The MIC90 values for AZM, TLM and MXF were 16, 8 and 2 mg/l, respectively.

Conclusion:  Pathogenic, opportunistic and non‐pathogenic obligate anaerobes showed high percentages of resistance to AMX and CM, and high MIC values for AZM in the absence of recently administered antibiotics. MXF showed a higher activity than TLM, similar to that detected for AMX‐CLA and MTZ. In consequence, MXF could represent a possible alternative antimicrobial against obligate anaerobes of oral origin, particularly in those patients with allergy, intolerance or lack of response to AMX‐CLA or MTZ.
The role of cytokines in a Porphyromonas gingivalis‐induced murine abscess model
Authors: Alayan J. , Gemmell E. , Ford P. , Hamlet S. , Bird P. S. , Ivanovski S. , Farah C. S.
Published: September 2007

Introduction:  Porphyromonas gingivalis is an important periodontopathic bacterium that is strongly associated with periodontal disease and is part of human dental plaque. Periodontal disease results from the interaction of the host with bacterial products, and T‐cell‐derived cytokines remain critical in the immunoregulation of periodontal disease.

Methods:  The aim of this study was to examine the role of T helper type 1 [interleukin‐12p40 (IL‐12p40), interferon‐γ, tumour necrosis factor (TNF)] and type 2 (IL‐4, IL‐10) cytokines in the immune response to a subcutaneous challenge with P. gingivalis using a well‐established murine abscess model, in genetically modified cytokine‐specific knockout mice.

Results:  IL‐12p40−/− mice exhibited more advanced tissue destruction and a reduced inflammatory cell infiltrate after subcutaneous P. gingivalis challenge. Deficiency of IL‐4 or IL‐10 did not result in increased susceptibility to P. gingivalis‐mediated tissue destruction. Furthermore, TNF deficiency appeared to reduce local tissue destruction. Interestingly, serum‐specific antibodies suggested a strong T helper type 2 response.

Conclusion:  The results of our study indicate an important role for IL‐12 in a primary P. gingivalis subcutaneous challenge.
Herpesviruses in asymptomatic apical periodontitis lesions: an immunohistochemical approach
Authors: Saboia‐Dantas C. J. , Coutrin de Toledo L. F. , Sampaio‐Filho H. R. , Siqueira J. F.
Published: September 2007

Introduction:  Human cytomegalovirus (HCMV) and Epstein–Barr virus (EBV) have been recently detected in samples from apical periodontitis lesions by means of molecular biology techniques and a role in the pathogenesis of this disease has been suggested. The present study was designed to survey asymptomatic primary apical periodontitis lesions for the presence of HCMV‐ and/or EBV‐infected cells by means of immunohistochemistry.

Methods:  Apical periodontitis lesions were obtained from 35 patients [26 human immunodeficiency virus (HIV) ‐seronegative patients and nine HIV‐seropositive patients] after tooth extraction and subjected to immunohistochemical analysis using monoclonal antibodies specific for HCMV and EBV.

Results:  Fifteen of the 35 apical periodontitis lesions were positive for the target herpesviruses. Overall, EBV was found in 31% of the samples and HCMV in 23%, with 14% of the lesions showing EBV and HCMV dual infection. No association was found between HCMV or EBV with any particular histopathological type of apical periodontitis (P > 0.05). HCMV was significantly more frequent in apical periodontitis lesions from HIV‐positive patients (67%) than in lesions from HIV‐negative patients (8%) (P = 0.001). EBV was detected in 44% of lesions from HIV‐positive patients and in 27% of lesions from HIV‐negative patients, but this difference was not significant (P = 0.91).

Conclusion:  Our results showed that cells infected by HCMV and EBV can be found in apical periodontitis lesions, with a higher prevalence in HIV‐positive patients. The specific role that these viruses play in the pathogenesis of apical periodontitis remains to be described.
Further evidence that major outer membrane proteins homologous to OmpA in Porphyromonas gingivalis stabilize bacterial cells
Authors: Iwami J. , Murakami Y. , Nagano K. , Nakamura H. , Yoshimura F.
Published: September 2007

Introduction:  Porphyromonas gingivalis is one of the most important bacteria in the progression of chronic periodontal disease. We hypothesized that the major outer membrane proteins Pgm6/7, which are homologous to the OmpA protein in Escherichia coli, might contribute to the stabilization of the cell surface. In this study, the effects of Pgm6/7 on the cell surface were examined morphologically.

Methods:  Deletion mutants of Pgm6/7 (Δ694, Δ695 and Δ695–694) were constructed using the polymerase chain reaction‐based overlap extension method. Wild‐type ATCC 33277 and Pgm6/7 mutants were grown under anaerobic conditions. Whole cells and thin sections of fixed cells were stained and examined by transmission electron microscopy.

Results:  Compared with the wild‐type, numerous vesicles released from cells were observed in each deletion mutant. The outer membrane appeared wavy and irregular. Increased numbers of vesicles were confirmed after their preparation from the culture supernatant. Total gingipain activity in vesicles was increased five‐ to 10‐fold in the deletion mutants.

Conclusion:  This report provides further evidence that Pgm6/7 proteins in P. gingivalis play an important role in the maintenance of bacterial outer membrane integrity.
Steroid 5α‐reductase activity of Treponema denticola
Authors: Clark D. T. , Soory M.
Published: September 2007

Introduction:  Previously we have shown that reference and freshly isolated Treponema denticola cultures possess 5α‐reductase (5α‐R) and 3β‐ and 17β‐hydroxysteroid dehydrogenase activity. A gene matching the 3‐oxo‐5α‐steroid 4‐dehydrogenase family protein (gene ID: 2739284; locus tag: TDE2697) has been identified in T. denticola ATCC 35405. The aim of the work presented here was to optimize assay conditions and determine steroid substrate specificities for the 5α‐R activity of T. denticola ATCC 33520.

Methods:  5α‐R activity of cell‐free preparations was assayed with radioactive steroid substrates. 5α‐R‐reduced products were identified using thin‐layer chromatography and a radioisotope scanner. Assay conditions were optimized for co‐factor, buffer and pH requirements. Apparent substrate specificities were determined for progesterone, 4‐androstenedione, testosterone and corticosterone. The time–course for metabolism of radiolabelled progesterone and cholesterol substrates was investigated with anaerobic cultures.

Results:  The optimum pH for 5α‐R was 5.5 and the preferred co‐factor was NADPH. The order of the steroids with respect to their 5α‐R substrate specificities was (in descending order): progesterone, 4‐androstenedione, testosterone and corticosterone. There are at least two intermediates in the synthesis of 5α‐dihydrocholesterol from cholesterol.

Conclusion:  These results suggest that the 3‐oxo‐5α‐steroid 4‐dehydrogenase family protein gene of T. denticola codes for a functional protein that resembles mammalian 5α‐R isoenzyme 2 with regard to co‐factor requirement and pH optimum.
Antibiotic resistance in an in vitro subgingival biofilm model
Authors: Sedlacek M. J. , Walker C.
Published: September 2007

Introduction:  The purpose of this study was to utilize an in vitro biofilm model of subgingival plaque to investigate resistances in subgingival biofilm communities to antibiotics commonly used as adjuncts to periodontal therapy.

Methods:  Biofilms were grown on saliva‐coated hydroxyapatite supports in trypticase‐soy broth for 4 h–10 days and then exposed for 48 h to either increasing twofold concentrations of tetracycline, amoxicillin, clindamycin, and erythromycin or therapeutically achievable concentrations of tetracycline, doxycycline, minocycline, amoxicillin, metronidazole, amoxicillin/clavulanate, and amoxicillin/metronidazole.

Results:  Concentrations necessary to inhibit bacterial strains in steady‐state biofilms were up to 250 times greater than the concentrations needed to inhibit the same strains grown planktonically. In the presence of therapeutically available antibiotic concentrations, significantly higher proportions of the biofilms remained viable as the biofilms reached steady‐state growth. The combinations of amoxicillin/clavulanate and amoxicillin/metronidazole were the most effective in suppressing growth. These combinations were particularly effective against biofilms up to and including 7 days of age and inhibited 90% or more of the bacteria present relative to untreated controls. As the biofilms approached steady state, these combinations were less effective with 50–60% of the bacteria retaining viability.

Conclusion:  Most, but not all, species of subgingival bacteria are considerably more resistant in biofilms than in planktonic cultures. Resistance appeared to be age‐related because biofilms demonstrated progressive antibiotic resistance as they matured with maximum resistance coinciding with the steady‐state phase of biofilm growth.
Synthetic bromated furanone inhibits autoinducer‐2‐mediated communication and biofilm formation in oral streptococci
Authors: Lönn‐Stensrud J. , Petersen F. C. , Benneche T. , Scheie A. Aamdal
Published: September 2007

Introduction:  Autoinducer‐2 (AI‐2) is a widespread communication‐signal molecule that allows bacteria to sense and react to environmental factors. In some streptococci AI‐2 is reported to be involved in virulence expression and biofilm formation. It has earlier been shown that the alga Delisea pulchra produces bromated furanones, which prevent bacterial colonization of the algae.

Methods and results:  We have previously published a novel and simple synthesis of (Z)‐5‐bromomethylene‐2(5H)‐furanone. In this study we showed that our synthesized furanone inhibited biofilm formation and bioluminescence induction by Streptococcus anginosus, Streptococcus intermedius, and Streptococcus mutans, as well as bioluminescence induction by Vibrio harveyi BB152.

Conclusion:  We suggest that the effect is linked to interference with the AI‐2 signaling pathway because adding furanone to the medium had no effect on the ability of the AI‐2‐defective S. anginosus luxS and S. intermedius luxS mutants to form biofilms.
Human cytomegalovirus is present in odontogenic cysts
Authors: Andric M. , Milasin J. , Jovanovic T. , Todorovic L.
Published: September 2007

Introduction:  Recent studies suggest that some viruses, including human cytomegalovirus (CMV), may be involved in the pathogenesis of periapical lesions. Since periapical cysts (PCs) represent the next stage in the evolution of periapical granuloma, it seemed reasonable to investigate the presence of CMV in PCs and any possible relationship between its presence and the clinical features of those cysts, as well as to compare the results obtained with corresponding findings in non‐inflammatory lesions, like odontogenic keratocysts (OKCs).

Methods:  Samples of 33 PCs and 10 OKCs, obtained at the time of surgery, were used for the detection of CMV DNA by polymerase chain reaction. Presence of the virus was correlated with clinical and radiographic features of the cysts.

Results:  CMV was detected in 18 PCs (54.5%) and six OKCs (60%). The presence of CMV was more frequent in cyst samples collected from patients who reported previous episodes of acute infection. The presence of sinus tract was more frequent in CMV‐positive cysts and CMV presence was less frequent in a group of cysts showing signs of acute inflammation at the time of sample collection. The mean sizes of CMV‐positive and CMV‐negative PCs were almost the same; CMV‐positive OKCs were slightly larger than CMV‐negative OKCs. None of these results proved to be statistically significant.

Conclusion:  The presence of CMV in the cystic wall is a common feature of both inflammatory and non‐inflammatory odontogenic cysts. Although this study has not proved that CMV affects pathogenesis of odontogenic cysts, such a possibility could not be ruled out.
Morphometric and Ultrastructural Changes in Ciliated Cells of the Oviductal Epithelium in Prolific Chinese Meishan and Large White Pigs during the Oestrous Cycle
Authors: Abe H , Hoshi H
Published: September 2007

Contents

There are some differences in reproductive features between the Chinese Meishan (CM) pig and Large White (LW) pig. The aim of the present study was to investigate the quantitative changes and ultrastructural features of ciliated cells in the various regions of the CM and LW pig oviduct during the follicular and luteal phases of the oestrous cycle. In the fimbrial and ampullar epithelia at the follicular phase, the ciliated cells were more plentiful than in the isthmic region in both pigs. In the CM pigs, there was a striking decrease in the percentage and cell height of ciliated cells in the luteal phase compared with the follicular phase. Although similar quantitative changes were observed in the LW pig oviduct, these changes were less dramatic than that in the CM pig oviduct. In both pigs, the percentage and cell height of ciliated cells in the isthmus were unchanged between the follicular and luteal phases. The ultrastructure of ciliogenic and ciliated cells was observed. In the fimbrial and ampullar epithelia during the follicular phase, most of the ciliated cells showed normal morphology, having many elongated cilia and mitochondria, but in the CM pig oviduct during the luteal phase many of the ciliated cells possessed immature cilia and swollen mitochondria. Cells undergoing ciliogenesis were frequently observed in the fimbriae and ampulla, and occasionally in the isthmus. Cytoplasmic protrusions containing variable numbers of ciliary axonemal complexes occurred in the fimbrial and ampullar epithelium in the CM pigs at the luteal phase, suggesting that deciliation of cells occurs by membrane‐bound cilia packets forming at the apices of cells and pinching off. These results demonstrate that there are regional variations in the cyclic changes associated with the oviductal ciliated cells of the pigs, while there are marked morphometrical and ultrastructural changes in oviductal ciliated cells of the CM pigs compared with that of the LW pigs.
Oral administration of taurine improves experimental pancreatic fibrosis
Authors: Shirahige Akinori , Mizushima Takaaki , Matsushita Koki , Sawa Kiminari , Ochi Koji , Ichimura Mitsuko , Tanioka Hiroaki , Shinji Toshiyuki , Koide Norio , Tanimoto Mitsune
Published: September 2007

Background and Aim: The mechanism of pancreatic fibrosis is unclear. Taurine is used in the clinical treatment of a wide variety of diseases, but its effect on improving pancreatic fibrosis is unknown. We examined whether a diet with added taurine improves pancreatic fibrosis induced by dibutyltin dichloride (DBTC) in an experimental chronic pancreatitis rat model. In addition, we examined the influence of taurine on pancreatic stellate cells.

Methods: Pancreatic fibrosis was induced by DBTC. Rats were fed a taurine‐containing diet or a normal diet and were killed at 4 weeks. Pancreatic stellate cells were isolated from male Wistar rats. Cultured pancreatic stellate cells were incubated with or without taurine chloramine. Type I collagen and transforming growth factor‐β1 secretion was evaluated by ELISA, and matrix metalloproteinase activity was assessed by gelatin zymography. Interleukin‐6, interleukin‐2, and transforming growth factor‐β1 levels in the supernatants of pancreatic tissue homogenates were measured.

Results: Pancreatic fibrosis induced by DBTC was improved remarkably by the oral administration of the taurine‐containing diet. Taurine chloramine decreased type I collagen, transforming growth factor‐β1, and matrix metalloproteinases 2 of the pancreatic stellate cell culture supernatant. Increased interleukin‐6 and decreased interleukin‐2 were found in the supernatants of the pancreatic tissue homogenates of DBTC‐induced pancreatitis rats compared with other groups.

Conclusion: The oral administration of taurine improves pancreatic fibrosis. Taurine chloramine inhibits transforming growth factor‐β1 produced from activated pancreatic stellate cells and improves pancreatic fibrosis.
Pathophysiological role of the activation of p38 mitogen‐activated protein kinases in poorly differentiated gastric cancer
Authors: Atsumi Tomoaki , Kato Katsuaki , Uno Kaname , Iijima Katsunori , Koike Tomoyuki , Imatani Akira , Ohara Syuichi , Shimosegawa Tooru
Published: September 2007

p38 mitogen‐activated protein kinases (MAPK) contribute to the loss of cell–cell contact and the round cell shape characteristic of poorly differentiated gastric cancer. In the present study it is demonstrated that phospho‐p38 MAPK level significantly increased in poorly differentiated gastric cancers in comparison to differentiated cancers and normal gastric mucosa by immunohistochemistry. Next, the pathophysiological roles of p38 MAPK activation were investigated in differentiated gastric cancer cell lines MKN7 and MKN28 and poorly differentiated gastric cancer cell lines KATO‐III and MKN45 cells by incubating with specific p38 inhibitor SB203580 or inactivating analog SB202474. The distribution of F‐actin on phalloidin staining was identified as fine cytoskeletal filaments in MKN7 and MKN28, but as dense membranous accumulation in KATO‐III and MKN45 cells. The treatment with SB203580 but not SB202474 reduced irregular accumulation of F‐actin in KATO‐III and MKN45 cells. The expression of E‐cadherin, ZO‐1, occludin and claudin 4 was higher in MKN7 and MKN28 than KATO‐III and MKN45 cells. The expression of E‐cadherin in KATO‐III cells was increased following treatment with SB203580, suggesting the suppression of E‐cadherin at the transcriptional level independent of its genetic alterations. Thus, p38 MAPK signaling might contribute to the acquisition of malignant properties in poorly differentiated phenotypes.
Involvement of Escherichia coli in pathogenesis of xanthogranulomatous cholecystitis with scavenger receptor class A and CXCL16–CXCR6 interaction
Authors: Sawada Seiko , Harada Kenichi , Isse Kumiko , Sato Yasunori , Sasaki Motoko , Kaizaki Yasuharu , Nakanuma Yasuni
Published: September 2007

Xanthogranulomatous cholecystitis (XGC) is characterized by the infiltration of numerous foamy macrophages. Bacterial infection is thought to be involved in the pathogenesis of XGC. Using XGC and cultured murine biliary epithelial cells (BEC), the participation of E. coli and the role of the scavenger receptor class A (SCARA), as well as chemokine(C‐X‐C motif) ligand 16 (CXCL16) and its receptor chemokine(C‐X‐C motif) receptor 6 (CXCR6), were examined in the pathogenesis of XGC. E. coli components and genes were detected in XGC on immunohistochemistry and polymerase chain reaction (PCR), respectively. SCARA‐recognizing E. coli was found in foamy macrophages aggregated in xanthogranulomatous lesions. CXCL16, which functions as a membrane‐bound molecule and soluble chemokine to induce adhesion and migration of CXCR6+ cells, was detected on gallbladder epithelia, and CXCR6+/CD8+ T cells and CXCR6+/CD68+ macrophages were also accumulated. In cultured BEC, CXCL16 mRNA and secreted soluble CXCL16 were constantly detected and upregulated by treatment with E. coli and lipopolysaccharide through Toll‐like receptor 4. These suggest that SCARA in macrophages is involved in the phagocytosis of E. coli followed by foamy changes and that bacterial infection causes the upregulation of CXCL16 in gallbladder epithelia, leading to the chemoattraction of macrophages via CXCL16–CXCR6 interaction and formation of the characteristic histology of XGC.
PIK3CA mutation and amplification in human lung cancer
Authors: Okudela Koji , Suzuki Masaya , Kageyama Shinji , Bunai Tomoyasu , Nagura Kiyoko , Igarashi Hisaki , Takamochi Kazuya , Suzuki Kazuya , Yamada Takeshi , Niwa Hiroshi , Ohashi Riuko , Ogawa Hiroshi , Mori Hiroki , Kitamura Hitoshi , Kaneko Takeshi , Tsuneyoshi Toshihiro , Sugimura Haruhiko
Published: September 2007

To explore the significance of phosphatidylinositol‐3‐kinase, catalytic, alpha (PIK3CA) in the carcinogenesis in human lung, mutations and copy number changes were investigated in 148 Japanese patients with primary cancer of the lung. For biological validation, the effects of exogenously expressed wild‐type and mutated PIK3CA were studied in an immortalized human airway epithelial cell line. Mutations in PIK3CA were found in five (3.6%) of the 139 available patients, and copy number gains were found in 21 (18.3%) of 115 patients, respectively. Overall, mutations or copy number gains were detected in 24 of the 106 patients (22.6%) for whom results in both analyses were available. The prevalence of copy number gains was higher in men, smokers, and in patients with squamous cell carcinoma than in the opposite categories. The copy number changes showed a trend toward higher prevalence in the earlier stages (P = 0.038). Interestingly, the presence of mutations and of copy number alterations were mutually exclusive in the present patients, implying that both entail equivalent oncogenic potential. Over‐expressed wild‐type PIK3CA and its two common mutants, K545E and H1047R, significantly enhanced the anchorage‐independent growth activity and migration activity of immortalized airway epithelium 16HBE14o– cells, but the effects of the K545E and H1047R mutants were more remarkable than those of the wild‐type. The present demonstrates an important role of PIK3CA in human lung carcinogenesis.
Senile EBV‐associated B‐cell lymphoproliferative disorder of indolent clinical phenotype with recurrence as aggressive lymphoma
Authors: Shiozawa Eisuke , Saito Bungo , Yamochi‐Onizuka Toshiko , Makino Reiko , Takimoto Masafumi , Nakamaki Tsuyoshi , Tomoyasu Shigeru , Ota Hidekazu
Published: September 2007

Senile EBV‐associated B‐cell lymphoproliferative disorder (LPD) was proposed as a new disease entity in 2003. This condition has a high incidence in elderly people without underlying immunodeficiencies, and is characterized by EBV‐positive B‐cell proliferation with a polymorphic composition. Histologically, the disease has two subtypes. The polymorphic LPD (PLPD) subtype has a preferable prognosis, whereas the large cell lymphoma (LCL) subtype involves aggressive disease progression. Reported herein is a case of senile EBV‐BLPD with indolent clinical features and PLPD subtype in the initial phase that recurred as an aggressive lymphoma 3 years after the initial diagnosis. In the recurrent phase, Southern blotting confirmed monoclonal proliferation of large lymphoid B‐cells. In both the initial and recurrent phases, polymerase chain reaction (PCR) yielded a single discrete band of a similar size due to an immunoglobulin heavy‐chain gene rearrangement, indicating that the large lymphoid B‐cells retained identical monoclonality throughout the histological progression and over the whole clinical course. These results suggest that the PLPD subtype is a histological finding in early phase senile EBV‐BLPD and that the LCL subtype reflects the progressive phase of the disease.
Pulmonary pleomorphic carcinoma producing hCG
Authors: Hirano Hiroshi , Yoshida Toshimi , Sakamoto Toshihito , Yoshimura Hitoshi , Fukuoka Masato , Tachibana Shiro , Saito Hiroshi , Ohkubo Eriko , Nakasho Keiji , Nishigami Takashi
Published: September 2007

An 80‐year‐old woman with a pleomorphic carcinoma (PC) producing hCG was admitted to Nippon Steel Hirohata Hospital because of an abnormal shadow on CT seen during a follow‐up examination after surgery for breast cancer. A right upper lobectomy was performed due to rapid growth of the shadow 3 months later. Macroscopically the tumor was a 4.8 × 4.0 cm well‐circumscribed grayish‐white mass. On histology the tumor consisted mostly of intermingled spindle and polygonal cells, while evidence of poorly differentiated adenocarcinoma was seen in a few areas. A diagnosis of PC was made due to hCG expression in approximately 20% of the spindle and polygonal cells on immunohistology. Six months after the operation metastasis to the liver and adrenal gland was seen on CT. The patient died due to metastases 1 year after the operation, even though the patient had been at stage 1B at the time of the operation and appropriate chemotherapy had been given. PC patients with immunohistochemical hCG expression have elevated risk of local recurrence and metastasis.
The discovery of prostate‐specific antigen
Authors: Rao Amrith Raj , Motiwala Hanif G. , Karim Omer M.A.
Published: September 2007

The discovery of prostate‐specific antigen (PSA) was beset with controversy; as PSA is present in prostatic tissue and semen, it was independently discovered and given different names, thus adding to the controversy. In this review we document the early research in this field to describe the chronology of the discovery of PSA. Using a comprehensive Medline search of the historical aspects of PSA, all relevant papers were reviewed; communication with the scientists involved in the discovery of PSA was an invaluable contribution. In 1960, Flocks was the first to experiment with antigens in the prostate and 10 years later Ablin reported the presence of precipitation antigens in the prostate. In 1971, Hara characterized a unique protein in the semen fluid, γ‐seminoprotein. Li and Beling, in 1973, isolated a protein, E1, from human semen in an attempt to find a novel method to achieve fertility control. In 1978, Sensabaugh identified semen‐specific protein p30, but proved that it was similar to E1 protein, and that prostate was the source. In 1979, Wang purified a tissue‐specific antigen from the prostate (‘prostate antigen’). PSA was first measured quantitatively in the blood by Papsidero in 1980, and Stamey carried out the initial work on the clinical use of PSA as a marker of prostate cancer. Thus the discovery of PSA is interesting and surrounded by controversy. Although the credit for purifying PSA goes to Wang, other eminent scientists published research on this antigen. The initial work on PSA in semen was to asses its properties as a forensic marker for rape victims, but soon its potential as a marker for prostate cancer became evident.
IMAGINING A NEW WORLD: USING INTERNATIONALISM TO OVERCOME THE 10/90 GAP IN BIOETHICS
Authors: CAPRON ALEXANDER MORGAN
Published: September 2007

The IAB Presidential Address was delivered by Alexander Capron to the internationally gathered audience at the Closing Ceremony of the 8th World Congress of Bioethics, Beijing on 9th August 2006.
PLAYING GOD AND THE ETHICS OF DIVINE NAMES: AN ISLAMIC PARADIGM FOR BIOMEDICAL ETHICS
Authors: SHAHZAD QAISER
Published: September 2007

The notion of ‘playing God’ frequently comes to fore in discussions of bioethics, especially in religious contexts. The phrase has always been analyzed and discussed from Christian and secular standpoints. Two interpretations exist in the literature. The first one takes ‘God’ seriously and playing ‘playfully’. It argues that this concept does state a principle but invokes a perspective on the world. The second takes both terms playfully. In the Islamic Intellectual tradition, the Sufi concept of ‘adopting divine character traits’ provides a legitimate paradigm for ‘playing God’. This paradigm is interesting because here we take both terms ‘God’ and ‘playing’ seriously. It is significant for the development of biomedical ethics in contemporary Islamic societies as it can open new vistas for viewing biotechnological developments.
TRANSHUMANISM AND MORAL EQUALITY
Authors: WILSON JAMES
Published: September 2007

Conservative thinkers such as Francis Fukuyama have produced a battery of objections to the transhumanist project of fundamentally enhancing human capacities. This article examines one of these objections, namely that by allowing some to greatly extend their capacities, we will undermine the fundamental moral equality of human beings. I argue that this objection is groundless: once we understand the basis for human equality, it is clear that anyone who now has sufficient capacities to count as a person from the moral point of view will continue to count as one even if others are fundamentally enhanced; and it is mistaken to think that a creature which had even far greater capacities than an unenhanced human being should count as more than an equal from the moral point of view.
Rolling Back the African State: Implications for Social Development in Ghana
Authors: Laird Siobhan E.
Published: September 2007

The New Policy Agenda of the Reagan and Thatcher years has profoundly influenced aid flows from the industrialized countries of North America and Western Europe to the developing nations of sub‐Saharan Africa. The application of neo‐liberal principles to the disbursement of multilateral and bilateral aid for social development has resulted in the diversion of donor funding away from the public sector towards non‐governmental organizations. The consequences of relegating the role of the public sector in social development is explored through qualitative research conducted in Ghana with state‐employed community development workers. The study exposes how severe financial constraint within the state sector distorts the targeting of beneficiaries and social development activity. This differs from findings revealed by interviews with social development workers employed by international non‐governmental organizations. These indicate that such agencies are able to sustain effectively resourced fieldworkers who are in a position to form positive working relationships with beneficiaries. The circumstances of the Department of Community Development and its relationships with non‐governmental agencies in Ghana are used to explore the effects on state‐building of the New Policy Agenda in the sub‐Saharan region.
The Organization of Decision‐making and the Dynamics of Policy Drift: A Canadian Health Sector Example
Authors: Gildiner Alina
Published: September 2007

This historical‐institutionalist case study of public–private change in the rehabilitation health sector in Ontario, Canada, seeks to build on literature about the politics of policy drift, particularly with respect to health care systems. Rather than turning to higher‐order institutional factors, such as federalism and overall financing agreements between states and the medical profession, or to economic indicators such as change in expenditures, however, it posits that the particularities of how welfare‐policy sectors are organized with respect to their decision‐making contribute to drift. Such organization is framed by two factors. The first is the set of rules by which the public–private boundary is drawn, and the second is the structuring of public institutions that set legislation and regulation, and organize the policy networks attendant on them, around these boundaries. The degree of coordination or fragmentation among these, this case suggests, is a factor in the politics and dynamics of drift.
From Transgression to Suppression: Implications of Moral Values and Societal Norms on Emotional Labour
Authors: Syed Jawad
Published: September 2007

This article endeavours to develop a conceptual perspective of moral values and societal norms, and how they impact on emotion regulation within employment contexts. The article draws on social psychology and emotional labour literature to explore the concept of contextual emotional labour. I argue that the conflicting requirements of one's societal and employment contexts may require one to transgress one's moral values to fulfil job requirements. I also argue that it is important to examine the aversive state(s) that may follow one's transgression and how this is managed in the workplace.
The mycorrhiza helper bacteria revisited
Authors: Frey‐Klett P. , Garbaye J. , Tarkka M.
Published: September 2007

In natural conditions, mycorrhizal fungi are surrounded by complex microbial communities, which modulate the mycorrhizal symbiosis. Here, the focus is on the so‐called ‘mycorrhiza helper bacteria’ (MHB). This concept is revisited, and the distinction is made between the helper bacteria, which assist mycorrhiza formation, and those that interact positively with the functioning of the symbiosis. After considering some examples of MHB from the literature, the ecological and evolutionary implications of the relationships of MHB with mycorrhizal fungi are discussed. The question of the specificity of the MHB effect is addressed, and an assessment is made of progress in understanding the mechanisms of the MHB effect, which has been made possible through the development of genomics. Finally, clear evidence is presented suggesting that some MHB promote the functioning of the mycorrhizal symbiosis. This is illustrated for three critical functions of practical significance: nutrient mobilization from soil minerals, fixation of atmospheric nitrogen, and protection of plants against root pathogens. The review concludes with discussion of future research priorities regarding the potentially very fruitful concept of MHB.

Contents

Summary
22

I.
Introduction
23

II.
Evidence for the occurrence of MHB
23

III.
Ecological and evolutionary implications of MHB
23

IV.
The question of MHB specificity
27

V.
Mechanisms of the MHB effect
28

VI.
Role of MHB in mycorrhizal functions
31

VII.
Conclusions and research priorities
32

References
33
Sentinels at the wall: cell wall receptors and sensors
Authors: Humphrey Tania V. , Bonetta Dario T. , Goring Daphne R.
Published: September 2007

The emerging view of the plant cell wall is of a dynamic and responsive structure that exists as part of a continuum with the plasma membrane and cytoskeleton. This continuum must be responsive and adaptable to normal processes of growth as well as to stresses such as wounding, attack from pathogens and mechanical stimuli. Cell expansion involving wall loosening, deposition of new materials, and subsequent rigidification must be tightly regulated to allow the maintenance of cell wall integrity and co‐ordination of development. Similarly, sensing and feedback are necessary for the plant to respond to mechanical stress or pathogen attack. Currently, understanding of the sensing and feedback mechanisms utilized by plants to regulate these processes is limited, although we can learn from yeast, where the signalling pathways have been more clearly defined. Plant cell walls possess a unique and complicated structure, but it is the protein components of the wall that are likely to play a crucial role at the forefront of perception, and these are likely to include a variety of sensor and receptor systems. Recent plant research has yielded a number of interesting candidates for cell wall sensors and receptors, and we are beginning to understand the role that they may play in this crucial aspect of plant biology.

Contents

Summary
7

I.
Introduction
8

II.
Cell expansion and plant growth
8

III.
Cell wall responses to stress
11

IV.
Pathogen attack and mechanical stimuli
11

V.
Lessons from yeast
12

VI.
Candidate sensors and receptors in plants
14

VII.
Conclusions
17

Acknowledgements
17

References
17
Regulatory proteins of eukaryotic initiation factor 2‐alpha subunit (eIF2α) phosphatase, under ischemic reperfusion and tolerance
Authors: García‐Bonilla Lidia , Cid Cristina , Alcázar Alberto , Burda Jozef , Ayuso Irene , Salinas Matilde
Published: September 2007

Phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α), which is one of the substrates of protein phosphatase 1 (PP1), occurs rapidly during the first minutes of post‐ischemic reperfusion after an episode of cerebral ischemia. In the present work, two experimental models of transient global ischemia and ischemic tolerance (IT) were used to study PP1 interacting/regulatory proteins following ischemic reperfusion. For that purpose we utilized PP1 purified by microcystin chromatography, as well as 2D DIGE of PP1α and PP1γ immunoprecipitates. The highest levels of phosphorylated eIF2α found after 30 min reperfusion in rats without IT, correlated with increased levels in PP1 immunoprecipitates of the inhibitor DARPP32 as well as GRP78 and HSC70 proteins. After 4 h reperfusion, the levels of these proteins in PP1c complexes had returned to control values, in parallel to a significant decrease in eIF2α phosphorylated levels. IT that promoted a decrease in eIF2α phosphorylated levels after 30 min reperfusion induced the association of GADD34 with PP1c, while prevented that of DARPP32, GRP78, and HSC70. Different levels of HSC70 and DARPP32 associated with PP1α and PP1γ isoforms, whereas GRP78 was only detected in PP1γ immunoprecipitates. Here we suggest that PP1, through different signaling complexes with their interacting proteins, may modulate the eIF2α phosphorylation/dephosphorylation during reperfusion after a transient global ischemia in the rat brain. Of particular interest is the potential role of GADD34/PP1c complexes after tolerance acquisition.