bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative profiling of highly enriched 22L and Chandler mouse scrapie prion protein preparations
Authors: Moore Roger A. , Timmes Andrew , Wilmarth Phillip A. , Priola Suzette A.
Published: November 2010

This article was originally published in Proteomics 2010, 10, 2858–2869, DOI 10.1002/pmic.201000104
Peptidomic profiling of human cerebrospinal fluid identifies YPRPIHPA as a novel substrate for prolylcarboxypeptidase
Authors: Zhao Xuemei , Southwick Katie , Cardasis Helene L. , Du Yi , Lassman Michael E. , Xie Dan , El‐Sherbeini Mohamed , Geissler Wayne M. , Pryor KellyAnn D. , Verras Andreas , Garcia‐Calvo Margarita , Shen Dong‐Ming , Yates Nathan A. , Pinto Shirly , Hendrickon Ronald C.
Published: November 2010

This article was originally published in Proteomics 2010, 10, 2882–2886, DOI 10.1002/pmic.201000145
Combinatorial peptide ligand library plasma treatment: Advantages for accessing low‐abundance proteins
Authors: Beseme Olivia , Fertin Marie , Drobecq Hervé , Amouyel Philippe , Pinet Florence
Published: November 2010

This article was originally published in Electrophoresis 2010, 31, 2697–2704, DOI 10.1002/elps.201000188
Proteomic profiling of human colon cancer cells treated with the histone deacetylase inhibitor belinostat
Authors: Beck Hans Christian , Petersen Jørgen , Nielsen Søren Jensby , Morszeck Christian , Jensen Peter B. , Sehested Maxwell , Grauslund Morten
Published: November 2010

This article was originally published in Electrophoresis 2010, 31, 2714–2721, DOI 10.1002/elps.201000033
Recombinant clotting factor VIII concentrates: Heterogeneity and high‐purity evaluation
Authors: D'Amici Gian Maria , Timperio Anna Maria , Gevi Federica , Grazzini Giuliano , Zolla Lello
Published: November 2010

This article was originally published in Electrophoresis 2010, 31, 2730–2739, DOI 10.1002/elps.201000216
Two‐dimensional air‐bridged silicon photonic crystal slab devices
Authors: Gan Lin , Zhou Chang‐Zhu , Wang Chen , Liu Rong‐Juan , Zhang Dao‐Zhong , Li Zhi‐Yuan
Published: November 2010

As silicon has a large refractive index and low loss in infrared wavelengths, it becomes an important optical material that has been widely used for integrated photonics applications. In this paper, we present some of our recent experimental works on infrared two‐dimensional air‐bridged silicon photonic crystal (PhC) slab devices that are based on both the band gap and band structure engineering. We have designed, fabricated, and characterized a series of PhC waveguides with novel geometries, resonant microcavities with fine tunability, and channel drop filters utilizing resonant coupling between waveguide and cavity. These devices are aimed to construct a more flexible network of transport channels for infrared light at micrometer/nanometer scale. We have also explored the remarkable dispersion properties of PhCs by engineering the band structures to achieve negative refraction, self‐collimation, superprism, and other anomalous dispersion behaviors of infrared light beams. We have designed and fabricated a PhC structure with negative refraction effect and used scanning near‐field optical microscopy to observe the negative refraction beam.
Dynamics of photoinduced phase transitions in hexacyanoferrate studied by infrared and Raman spectroscopy
Authors: Suemoto T. , Fukaya R. , Asahara A. , Nakajima M. , Tokoro H. , Ohkoshi S.
Published: November 2010

Unrevealed aspects of the photoinduced phase transition are discussed with a special emphasis placed on domains and domain boundaries. The CN− vibration spectroscopy, which is sensitive to the phase changes and boundaries, is applied to photomagnetic phase transition material, RbMn[Fe(CN)6]. From time‐resolved IR measurements for photoinduced low temperature to high temperature phase transition, the transient appearance of the boundaries as well as the new phase within 1 ps is observed. The growth processes of the low temperature phase and boundaries during UV irradiation on the sample in high temperature phase are investigated by Raman spectroscopy at room temperature. The result suggests that the new phase appears preferably in the fresh area and a lot of unpaired fragments of high temperature phase are left behind after a prolonged irradiation.

magnified image

Typical distribution of two phases and boundaries in hexacyanoferrate during photoinduced phase transition (simulation). Blue: initial phase; red: new phase; green: boundary.
Identity‐based multi‐receiver threshold signcryption scheme
Authors: Qin Huawang , Dai Yuewei , Wang Zhiquan
Published: November 2010

An identity‐based threshold signcryption scheme for multiple receivers is proposed. For thenspecified receivers, the ciphertext can be decrypted and verified when arbitrarytor more receivers work together. The steps of the private keys extraction, the signcryption, the decryption, and the verification are introduced in detail. The chosen‐ciphertext security of the scheme is proved formally. The comparisons to the existing schemes show that the proposed scheme is more secure, more flexible, and the simulative game of the security proof in the scheme is more perfect. Copyright © 2010 John Wiley & Sons, Ltd.
A semi‐competing risks model for data with interval‐censoring and informative observation: An application to the MRC cognitive function and ageing study
Authors: Barrett Jessica K. , Siannis Fotios , Farewell Vern T.
Published: November 2010

Semi‐competing risks data occur frequently in medical research when interest is in simultaneous modelling of two or more processes, one of which may censor the others. We consider the analysis of semi‐competing risks data in the presence of interval‐censoring and informative loss‐to‐followup. The work is motivated by a data set from the MRC UK Cognitive Function and Ageing Study, which we use to model two processes, cognitive impairment and death. Analysis is carried out using a multi‐state model, which is an extension of that used by Siannis et al. (Statist. Med. 2007; 26:426–442) to model semi‐competing risks data with exact transition times, to data which is interval‐censored. Model parameters are estimated using maximum likelihood. The role of a sensitivity parameter k, which influences the nature of informative censoring, is explored. Copyright © 2010 John Wiley & Sons, Ltd.
A Bayesian subgroup analysis with a zero‐enriched Polya Urn scheme
Authors: Sivaganesan S. , Laud Purushottam W. , Müller Peter
Published: November 2010

We introduce a new approach to inference for subgroups in clinical trials. We use Bayesian model selection, and a threshold on posterior model probabilities to identify subgroup effects for reporting. For each covariate of interest, we define a separate class of models, and use the posterior probability associated with each model and the threshold to determine the existence of a subgroup effect. As usual in Bayesian clinical trial design we compute frequentist operating characteristics, and achieve the desired error probabilities by choosing an appropriate threshold(s) for the posterior probabilities. Copyright © 2010 John Wiley & Sons, Ltd.
Application of aerosol‐spray deposition for determination of fine structure of barley starch using atomic force microscopy
Authors: Maley Jason , Asare Eric K. , Båga Monica , Rossnagel Brian G. , Chibbar Ravindra N. , Sammynaiken Ramaswami
Published: November 2010

Starch samples extracted from barley cultivars with varying AM concentrations were imaged by AFM using intermittent contact mode. Two different deposition methods were used: a simple solution drop and an aerosol spray deposition. Using the drop deposition method, starch appeared mainly as small particles and aggregated globules, with average heights of 1.8 ± 0.2, 2.7 ± 0.7, and 5.5 ± 1.0 nm, for starch solutions containing increased (38%), normal (25.8%), and undetectable (0%) AM, respectively. The aerosol spray deposition method allowed analysis of individual biopolymer chains of AM and biopolymer fibrils of AP. The image of normal starch showed individual AM chains with an average height of 0.8 ± 0.2 nm, and an average contour length of 178 ± 127 nm. For increased AM starch, the height of individual AM chains was similar to normal starch, but the average contour length was shorter (140 ± 70 nm). All barley starches showed fibril bundles of AP with average heights of 1.9 to 2.9 nm and lengths in the micron size range.
An inverse function theorem in Fréchet spaces
Authors: Ekeland Ivar
Published: November 2010

I present an inverse function theorem for differentiable maps between Fréchet spaces which contains the classical theorem of Nash and Moser as a particular case. In contrast to the latter, the proof does not rely on the Newton iteration procedure, but on Lebesgue's dominated convergence theorem and Ekeland's variational principle. As a consequence, the assumptions are substantially weakened: the map

F

to be inverted is not required to be

C^{2}

, or even

C^{1}

, or even Fréchet-differentiable.

Je présente un théorème d'inversion pour des applications différentiables entre espaces de Fréchet, qui contient le théorème classique de Nash et Moser. Contrairement à ce dernier, la démonstration donnée ici ne repose pas sur l'algorithme itératif de Newton, mais sur le théorème de convergence dominée de Lebesgue et le principe variationnel d'Ekeland. Comme conséquence, les hypothèses sont substantiellement affaiblies : on ne demande pas que l'application

F

à inverser soit de classe

C^{2}

, ni même

C^{1}

, ni même différentiable au sens de Fréchet.
Economics fit for the Queen: a pessimistic assessment of its prospects
Authors: Earl Peter E.
Published: November 2010

The widespread failure of economists to predict the 2008 credit crunch and subsequent Global Financial Crisis led Her Majesty the Queen to ask what had gone wrong. She received very different responses from representatives of mainstream and heterodox perspectives. The mainstream economists' perspective on the crisis contained elements of truth, but it did not concede that there is any need for fundamental reform of how the discipline is taught and the kind of research that is conducted. This paper critically examines ways in which the degenerating mainstream research programme can attempt to fend off claims that major changes are needed. It also considers barriers to curriculum change in economics and the incentive structures that work against economics becoming more pluralistic and focused on real‐world problems. It concludes by suggesting ways in which pressures might be imposed from the outside for reform within the economics discipline.
Occult innovations in higher education: corporate magic and the mysteries of managerialism
Authors: Wood Felicity
Published: November 2010

This study maintains that, as institutions of higher education have converted themselves into corporatised institutions under managerial governance, they have taken on occult qualities. These tendencies are analysed in the light of Jean and John Comaroff's theory of occult economies: wealth‐generating enterprises involved in areas of mystery and magic. Modern universities, it is argued, have become occult economies, and this study examines the ways in which various distinctive features of contemporary academic discourse and procedure have become steeped in areas of ritual and enchantment. Paradoxically, then, although the commodification of higher education has been depicted as a process based on real world principles of rationalisation, cost effectiveness and accountability, it has drawn universities closer to the otherworldly.
Drugs policy: rhetoric and political reality
Authors: McKeganey Neil
Published: November 2010

Neil McKeganey is the founding director of the Centre for Drug Misuse Research within the University of Glasgow and has directed the research programme of the Centre since 1994. For the last 15 years, Professor McKeganey has concentrated on research within the drug misuse field and has undertaken work on drug injectors and HIV, prostitution, and drugs and young people. He has acted as an advisor to the UK Home Office, the World Health Organisation and the United States Department of Justice.
Of heroin and alcohol
Authors: Gilmore Ian
Published: November 2010

Professor Sir Ian Gilmore is a liver specialist, which goes some way towards explaining his long‐term interest in the medical problems arising from excessive alcohol consumption. He chaired the working party of the Royal College of Physicians that producedAlcohol: Can the NHS Afford it? A Blueprint for a Coherent Alcohol Strategyin 2001. Professor Gilmore was elected president of the Royal College of Physicians in 2006 and has just stepped down from this position.
Downregulation of runt‐related transcription factor 3 associated with poor prognosis of adenoid cystic and mucoepidermoid carcinomas of the salivary gland
Authors: Sasahira Tomonori , Kurihara Miyako , Yamamoto Kazuhiko , Bhawal Ujjal K. , Kirita Tadaaki , Kuniyasu Hiroki
Published: November 2010

Runt‐related transcription factor 3 (RUNX3) is a transcription factor of the transforming growth factor (TGF)‐β superfamily and acts as a tumor suppressor gene, which is silenced by hypermethylation of the promoter region in various cancers. In this study, we examined the expression and methylation status of RUNX3 in the salivary gland cancers pleomorphic adenoma (PA), adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC). The cytoplasmic expression rates of RUNX3 in PA, ACC and MEC were 65% (13/20), 22.2% (8/36) and 20.6% (7/34), respectively. Low expression or deletion of RUNX3 in ACC and MEC was significantly associated with tumor progression and poor prognosis. Using microdissected cDNA, we found that RUNX3 mRNA expression was lower in ACC and MEC than in PA and noncancerous salivary glands; furthermore, hypermethylation of RUNX3 was detected more frequently in PA (2/8, 25%), ACC (6/8, 75%) and MEC (7/8, 87.5%) than in noncancerous salivary glands (0/8, 0%). Our results suggest that low expression or deletion of RUNX3 in salivary gland tumors might play a pivotal role in tumorigenesis and tumor progression and poor prognosis in the case of salivary gland ACC and MEC. Recovery of the tumor suppressive function of RUNX3 might inhibit tumorigenesis and cancer progression in the human salivary gland. (Cancer Sci 2011; 102: 492–497)
Transcutaneous nicotine does not prevent postoperative nausea and vomiting: a randomized controlled trial
Authors: Czarnetzki Christoph , Schiffer Eduardo , Lysakowski Christopher , Haller Guy , Bertrand Daniel , Tramèr Martin R.
Published: November 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• There is empirical evidence that smokers are less likely to suffer from postoperative nausea and vomiting (PONV).

• Tobacco smoke is known to induce enzymes, for instance, cytochrome P450, and this may partially explain the PONV‐protecting effect of smoking.

• Chronic exposure to nicotine that is contained in the tobacco may lead to a desensitization of central nicotine receptors, and, subsequently, to an increased tolerance to the emetogenic effects of surgery and anaesthesia.

WHAT THIS STUDY ADDS

• In non‐smokers undergoing surgery under general anaesthesia, pre‐operatively administered transcutaneous nicotine did not decrease the incidence of PONV within 24 h.

• Patients receiving nicotine had a tendency to develop PONV symptoms earlier than controls.

• Exposure to transcutaneous nicotine significantly increased the risk of insomnia during the first postoperative night.

AIMS There is empirical evidence that smokers are less likely to suffer from postoperative nausea and vomiting (PONV). We sought to investigate whether transcutaneus nicotine prevents PONV.

METHODS Non‐smokers receiving general anaesthesia for surgery were randomly allocated to Nicotinell® Patch 10 cm2 (TTS 10), containing 17.5 mg of nicotine (average delivery rate, 7 mg 24 h−1) or matching placebo patch. Patches were applied 1 h before surgery and were left in situ until 24 h after surgery (or until the first PONV symptoms occurred).

RESULTS We randomized 90 patients (45 nicotine, 45 placebo). In the post‐anaesthetic care unit, the incidence of nausea was 22.2% with nicotine and 24.4% with placebo (P= 0.80), and the incidence of vomiting was 20.0% with nicotine and 17.8% with placebo (P= 0.78). Cumulative 24 h incidence of nausea was 42.2% with nicotine and 40.0% with placebo (P= 0.83), and of vomiting was 31.1% with nicotine and 28.9% with placebo (P= 0.81). PONV episodes tended to occur earlier in the nicotine group. Postoperative headache occurred in 17.8% of patients treated with nicotine and in 15.6% with placebo (P= 0.49). More patients receiving nicotine reported a low quality of sleep during the first postoperative night (26.7% vs. 6.8% with placebo; P= 0.01).

CONCLUSIONS Non‐smokers receiving a prophylactic nicotine patch had a similar incidence of PONV during the first 24 h and tended to develop PONV symptoms earlier compared with controls. They had a significantly increased risk of insomnia during the first postoperative night.
Pharmacokinetics of oral neratinib during co‐administration of ketoconazole in healthy subjects
Authors: Abbas Richat , Hug Bruce A. , Leister Cathie , Burns Jaime , Sonnichsen Daryl
Published: November 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Neratinib is a potent, low‐molecular‐weight, orally administered, irreversible pan‐ErbB (ErbB‐1, ‐2, ‐4) receptor tyrosine kinase inhibitor that has shown anti‐tumour activity in patients with advanced ErbB‐2‐positive breast cancer both with and without prior trastuzumab exposure.

• Neratinib is in phase III development for the treatment of patients with ErbB‐2‐positive breast cancer.

• Preclinical data suggest that neratinib is predominantly metabolized by CYP3A4.

WHAT THIS STUDY ADDS

• The pharmacokinetic profile of neratinib was evaluated in healthy subjects after a single oral administration of neratinib with and without the potent CYP3A4 inhibitor, ketoconazole.

• Exposure to neratinib increased more than 3‐fold during co‐administration of ketoconazole, indicating that neratinib is a substrate of CYP3A and is susceptible to interactions with potent CYP3A inhibitors and, thus, dose adjustments may be needed if neratinib is administered with such compounds.

AIM The primary objective was to evaluate the pharmacokinetics of a single dose of neratinib, a potent, low‐molecular‐weight, orally administered, irreversible pan‐ErbB (ErbB‐1, ‐2, ‐4) receptor tyrosine kinase inhibitor, during co‐administration with ketoconazole, a potent CYP3A4 inhibitor.

METHODS This was an open‐label, randomized, two‐period, crossover study. Fasting healthy adults received a single oral dose of neratinib 240 mg alone and with multiple oral doses of ketoconazole 400 mg. Blood samples were collected up to 72 h after each neratinib dose. Plasma concentration data were analyzed using a noncompartmental method. The least square geometric mean ratios [90% confidence interval (CI)] of Cmax(neratinib+ketoconazole) : Cmax(neratinib alone), and AUC(neratinib+ketoconazole) : AUC(neratinib alone) were assessed.

RESULTS Twenty‐four subjects were enrolled. Compared with neratinib administered alone, co‐administration of ketoconazole increased neratinib Cmax by 3.2‐fold (90% CI: 2.4, 4.3) and AUC by 4.8‐fold (3.6, 6.5). Median tmax was 6.0 h with both regimens. Ketoconazole decreased mean apparent oral clearance of neratinib from 346 l h−1 to 87.1 l h−1 and increased mean elimination half‐life from 11.7 h to 18.0 h. The incidence of adverse events was comparable between the two regimens (50% neratinib alone, 65% co‐administration with ketoconazole).

CONCLUSION Co‐administration of neratinib with ketoconazole, a potent CYP3A inhibitor, increased neratinib Cmax by 3.2‐fold and AUC by 4.8‐fold compared with administration of neratinib alone. These results indicate that neratinib is a substrate of CYP3A and is susceptible to interaction with potent CYP3A inhibitors and, thus, dose adjustments may be needed if neratinib is administered with such compounds.
Intraocular pressure: a comparative analysis in two sexes
Authors: Qureshi I. A.
Published: November 2010

Some investigators have reported higher intraocular pressure (IOP) levels in women and others in men, while some have failed to find any sex difference. It has been reported that IOP increases with age in Western populations, whereas it decreases in Japanese. Because of these contrasts, this study was planed to determine the influence of sex on IOP in various age groups in an apparently healthy population from Rawalpindi, Pakistan. Depending upon age, 5307 men and 2388 women were divided into seven groups. All subjects were examined according to standard protocols. IOP was measured by Goldmann applanation tonometer. IOP progressively increased until the age interval of 61–70 years in both sexes. The increase became statistically significant in the age interval of 51–60 years in men, while in women it was one decade earlier. The difference between the two sexes increased significantly after the age of 40 years. Ocular hypertension (IOP>21 mmHg) was found in 5.3% and 2.1% of women and men respectively. In both sexes, distribution of IOP did not fit a normal bell‐shaped curve but skewed to the right. In Pakistan, IOP increases with age in both sexes, but more markedly in women. Left eye IOP was negligibly higher in all age groups of both sexes. Ocular hypertension was found more in female than in male subjects. Menopause is associated with an increase in IOP. Menstrual cycle had no influence on IOP. Knowledge of the normal level of IOP in various age groups of both sexes may help glaucoma screeners.
Post‐exercise depression of baroreflex slowing of the heart in humans
Authors: Ulman L. G. , Potter E. K. , McCloskey D. I. , Morris M. J.
Published: November 2010

In normal human subjects, we tested whether a 20‐ to 30‐min period of rhythmic exercise, intended to provoke strong activation of the sympathetic nerves, would lead to prolonged inhibition of vagally mediated bradycardia evoked reflexly by stimulation of the baroreceptors by neck suction. Negative pressure within the neck cuff (−40 to −80 mmHg) reflexly evoked a reproducible increase in pulse interval. Following exercise, this increase in pulse interval was reduced from 444±104 ms to 76±57 ms (mean±SEM). Recovery time was 42±9 min. These findings demonstrate a prolonged attenuation of cardiac vagal action following rhythmic exercise in normal human subjects. It is known that neuropeptide Y (NPY) is released from cardiovascular sympathetic nerves, that it attenuates cardiac vagal action and that plasma levels of NPY are elevated for a prolonged period after exercise. Therefore, it is proposed that NPY, released from sympathetic nerves during exercise, attenuates reflexly evoked cardiac vagal action for a prolonged period after exercise ends.
CD2‐mediated stimulation of the naive CD4+ T‐cell subset promotes the development of skin‐associated cutaneous lymphocyte antigen‐positive memory cells
Authors: LIU L. , FOER A. , SESTERHENN J. , REINHOLD U.
Published: November 2010

Directed migration of lymphocytes from blood into lymph nodes and organ‐associated lymphatic tissue, also referred to as homing, is initiated by T‐cell adhesion to specialized high endothelial cells of postcapillary vessels. Here, we demonstrate that selective signal transduction pathways specifically modulate the expression of the cutaneous lymphocyte antigen (CLA), the putative skin‐homing receptor, during naive to memory transition of CD4+ T cells in vitro. The results show that the expression of CLA is strongly induced by activation via CD2 [T11.1+T11.2 monoclonal antibodies (mAb)]. Addition of transforming growth factor‐β1 (TGF‐β1), interleukin‐6 (IL‐6), and, to a lesser extent, IL‐2 further enhanced the generation of CLA+ T cells, whereas the induction of this antigen was markedly inhibited by IL‐4. Periodic restimulation via CD2 and long‐term culture of activated cells in the presence of IL‐2 and TGF‐β1 resulted in stable expression of CLA during a culture period of more than 100 days. In contrast, activation of naive CD4+ T cells via CD3, CD28 or by mitogens induced a rapid naive to memory phenotype transition but a much lower percentage of CLA+ T cells showing only weak expression of the antigen. Furthermore, activation of purified CD4+ memory T cells by CD2 strongly induced expression of activation‐related antigens CD25 and HLA‐DR, but failed to up‐regulate CLA expression. Our results show that primary stimulation conditions highly modulate the development of skin‐associated T cells and indicate a new functional role for costimulatory adhesion pathways in regulating the expression of molecules associated with T‐cell homing.
Alloantigen‐specific T‐cell anergy induced by human keratinocytes is abrogated upon loss of cell‐cell contact
Authors: OTTEN H. G. , BOR B. , VERVERS C. , VERDONCK L. F. , DE BOER M. , DE GAST G. C.
Published: November 2010

The activation of primary human T cells largely depends on the expression of both major histocompatibility complex (MHC) class II and B7 molecules on antigen‐presenting cells (APC), whereas APC expressing HLA class II but not B7 antigens are expected to induce anergy. According to this concept, interferon‐γ (IFN‐γ)‐activated keratinocytes (KC) expressing HLA class II but not B7 costimulatory antigens should be able to induce anergy. However, in terms of anergy versus activation contradicting data have been published on the outcome of interaction between T cells and human KC. In addition, it has been shown that human KC can express a B7‐like molecule with unknown function, whereas MHC expression may be functionally impaired. To evaluate this item we transfected the human A431 KC cell line with B7‐1 coding sequences and up‐regulated HLA‐DR by treatment with IFN‐γ, yielding A431DR,B7‐1 cells. Irradiated A431DR,B7‐1 cells were found to be capable of inducing vigorous proliferative primary T‐cell responses in resting allogeneic T cells, whereas A431DR cells could induce proliferation only when interleukin‐2 (IL‐2) was added. These data indicate that KC can present alloantigens, and that lack of costimulatory molecules on KC is the main reason why these cells cannot induce primary T‐cell responses. Surprisingly, however, no evidence could be obtained of stable anergy induction by A431DR cells, as T cells contacted with A431DR cells and then transferred to A431DR,B7‐1 cells clearly demonstrated alloresponsiveness. T‐cell non‐responsiveness was maintained only when T cells remained in contact with A431DR cells. These data indicate that, despite expression of HLA class II in the absence of B7 costimulatory molecules, human KC cannot induce stable anergy but rather induce short‐term anergy in primary resting T cells.
Sensitization of T‐cell receptor‐αβ+ T cells recovered from long‐term T‐cell receptor downmodulation
Authors: OMOTO K. , KONG Y.‐Y. , NOMOTO K. , UMESUE M. , MURAKAMI Y. , ETO M. , NOMOTO K.
Published: November 2010

Although the survival of fully allogeneic skin grafts was prominently prolonged by adult thymectomy in anti‐T‐cell receptor‐αβ monoclonal antibody (TCR‐αβ mAb)‐treated mice compared with that of non‐adult thymectomized (ATX) mice, the skin allografts were eventually rejected. In the anti‐TCR‐αβ mAb‐treated ATX mice, as shown in the present study, most of TCR‐αβ+ cells were promptly activated on day 2 and then rapidly disappeared by day 7, but some TCR‐αβ− Thy‐1+ cells remained at that time. These TCR‐αβ− Thy‐1+ cells which have downmodulated their TCR‐αβ expression may be refractory to depletion events by the mAb treatment. Although these downmodulated T cells re‐expressed their TCR‐αβ on day 50, they could not respond to stimuli via TCR such as TCR cross‐linking or alloantigens. However, they recovered the reactivity to donor antigens on day 85. These results indicate that the downmodulated T cells by anti‐TCR‐αβ mAb treatment are long‐lived and re‐express their TCR‐αβ at a late stage to be sensitized to donor antigen, which suggests that additional regimens may be required to get permanent, or very long‐term, graft acceptance.
Tumour necrosis factor receptor II (p75) signalling is required for the migration of Langerhans' cells
Authors: WANG B. , KONDO S. , SHIVJI G. M. , FUJISAWA H. , MAK T. W. , SAUDER D. N.
Published: November 2010

Langerhans' cells (LC) represent the major antigen‐presenting cells within the epidermis. Following exposure of the skin to antigen, LC take up antigen, migrate into draining lymph nodes (DLN) and present processed antigen to T lymphocytes, thereby initiating an immune response. The molecular mechanisms responsible for LC migration remain unclear. Cytokines, in particular tumour necrosis factor‐α (TNF‐α) have been suggested to influence LC migration. There are two distinct membrane receptors for TNF‐α, TNF receptor I (TNF‐R1, p55) and TNF receptor II (TNF‐R2, p75), thought to be responsible for distinct TNF‐α activities. It is believed that most of TNF biological activities are mediated via TNF‐R1. In order to examine the role of TNF‐R1 signalling in LC migration, we utilized TNF‐R1 gene‐targeted mutant mice. Following application of the hapten fluorescein isothiocyanate (FITC), FITC‐bearing cells in DLN were examined by flow cytometry. A normal number of FITC+/Ia+ cells (LC) were found in DLN from TNF‐R1‐deficiency mice, suggesting that TNF‐R1‐dependent signalling is not crucial for LC migration. To investigate the possibility of signalling through TNF‐R2, blocking studies using a neutralizing anti‐TNF‐α antibody were performed. The results revealed that anti‐TNF‐α antibody significantly inhibited LC accumulation in DLN in TNF‐R1‐deficient mice, thus suggesting that TNF‐R2 signalling is involved in LC migration from skin to DLN and that murine LC express TNF‐R2.
CD27/CD70 interaction directly induces natural killer cell killing activity
Authors: YANG F.C. , AGEMATSU K. , NAKAZAWA T. , MORI T. , ITO S. , KOBATA T. , MORIMOTO C. , KOMIYAMA A.
Published: November 2010

The CD27 molecule is expressed on a portion of natural killer (NK) cells as well as T and B cells. To provide the functional capacity of CD27 molecule on NK cells, we here highly purified CD3− CD56+ NK cells by flow cytometry (purity >98%), and investigated their NK cell activity via CD27/CD70 interaction using a CD70‐transfectant by a 4h 51Cr‐release assay. The enhancement of NK activity by purified NK cells in the presence of interleukin‐2 (IL‐2) or interleukin‐12 (IL‐12) against CD70/Nalm‐6 was not recognized as compared to against mock/Nalm‐6. However, after a coculture with the fixed CD70/300‐19, the purified NK cells increased the NK cell activity against K562, the value being 10 to 20% higher than coculture with the mock/300‐19 in the presence of IL‐2 or IL‐12. The enhancement of NK activity was blocked by the addition of anti‐CD70 monoclonal antibody (mAb). In addition, conjugation of NK cells to the target was increased by coculture with the CD70/300‐19 without increased expression of adhesion molecules. In the parallel experiment, there was no increase in the killing capacity of NK cells. These results strongly show that CD27/CD70 interaction directly enhances NK activity in the presence of IL‐2 or IL‐12 by increasing the effector and target conjugate formation, indicating that CD27/CD70 interaction plays an important role in the cytotoxic function of NK cells.
Analysis of recombinant human tumour necrosis factor‐α‐induced CD4 expression on human eosinophils
Authors: HOSSAIN M. , OKUBO Y. , HORIE S. , SEKIGUCHI M.
Published: November 2010

We examined the hypothesis that one of the pro‐inflammatory cytokines, tumour necrosis factor‐α (TNF‐α), could induce expression of the adhesion molecule CD4 on human eosinophils. We further examined the effector function of CD4 and the mechanisms regulating CD4 expression.

Human eosinophils were cultured with various concentrations of recombinant human TNF‐α (rhTNF‐α) with or without various drugs for 24 hr. After culture, eosinophils were stained for CD4 using a monoclonal antibody and then analysed by flow cytometry. Eosinophil‐derived neurotoxin (EDN) release as eosinophil degranulation was examined by cross‐linking of CD4 on eosinophils.

The rhTNF‐α induced CD4 expression on human eosinophils in a dose‐ and time‐dependent fashion; rhTNF‐α‐induced CD4 expression was significantly inhibited by 10−6 M cycloheximide, 10−8M dexamethasone, or 10−6M herbimycin A. Recombinant human interferon‐γ inhibited rhTNF‐α‐induced CD4 expression in a dose‐dependent manner. However, cross‐linking of CD4 on eosinophils did not evoke EDN release, suggesting that newly expressed CD4 molecules on human eosinophils do not play any role in triggering degranulation. Our data indicate that TNF‐α‐induced CD4 expression on human eosinophils is dependent on protein synthesis and may be dependent on tyrosine kinase activity.
Acerola and cashew apple as sources of antioxidants and dietary fibre
Authors: Rufino Maria do Socorro M. , Pérez‐Jiménez Jara , Tabernero María , Alves Ricardo E. , De Brito Edy S. , Saura‐Calixto Fulgencio
Published: November 2010

Several tropical fruits have been described as natural sources of dietary fibre (DF) and phenolic compounds, associated with different health effects. The aim of this work was to ascertain the DF, phenolic compounds content (including non‐extractable polyphenols, mostly associated with DF) and antioxidant capacity in acerola fruits and cashew apples from selected clones. ‘BRS 236’ acerola fruits presented a high antioxidant capacity because of the combination of both extractable polyphenols and l‐ascorbic acid (providing together a Folin value of 170 kg−1 g d.m.). ‘CCP 76’ cashew apples contained 28 g kg−1 d.m. of extractable polyphenols and 13 g kg−1 d.m. of ascorbic acid as well as a high amount of non‐extractable condensed tannins (52 g kg−1 d.m.). DF content was of 260 g kg−1 d.m. in acerola fruit and of 209 g kg−1 d.m. in cashew apple. Acerola fruits and cashew apple should therefore be considered as new natural sources of DF and phenolic compounds.
Solvent effects on antioxidant properties of persimmon (Diospyros kaki L. cv. Daebong) seeds
Authors: Akter Mst. Sorifa , Ahmed Maruf , Eun Jong‐Bang
Published: November 2010

The aim of this study was to investigate the antioxidant activities of persimmon seed extracts (PSE) using different solvents such as ethanol, methanol, acetone, and their aqueous 80% solvents. The EC50 values of the extracts from absolute ethanol (EE) and methanol (ME) in 2, 2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical–scavenging assay were 49.71 and 51.15 μg mL−1, respectively, while the EC50 of butylated hydroxyanisole (BHA) was 70.82 μg mL−1. However, the EC50 value of reducing power for the absolute acetone extract (AE) was higher (210.06 μg mL−1) than that of BHA (212.67 μg mL−1). Although the absolute ME had the highest antioxidant activity, it exhibited the lowest total phenolics and flavonoids. In contrast, the antioxidant activities of the aqueous solvent extracts showed a good correlation with total phenolics and flavonoids when compared to the absolute solvent extracts. The results showed that PSE could potentially be used as an inexpensive source of natural antioxidant in food and pharmaceutical industries.
Effect of fermentation on biochemical and sensory characteristics of millet flour supplemented with whey protein
Authors: Mallasy Limya O. , El Tinay Abdullahi H. , Elkhalifa Abd Elmoneim O. , Ali Maha A. M. , Mohiedeen Iman E. , Yousif Nabila E.
Published: November 2010

Pearl millet like other cereals shows qualitative and quantitative deficiency in protein. The main objective of this study was to obtain the food of high nutritive value with high protein content and biological value by supplementing pearl millet, with whey protein. Two levels of whey protein were considered (20% and 25% protein content). Supplemented samples and control were fermented in the presence of starter for 14 h according to the traditional method utilised in Sudan. The pH, crude protein, in vitro protein digestibility (IVPD) and protein fractions of the fermented and supplemented pearl millet were determined at 2‐ h intervals. Supplementation of whey protein resulted in significant increase in protein content compared to the control, i.e. 14.8%, 23.9% and 28.7% for Ashana control (AC), Ashana plus whey protein (20% protein content) (AW1) and Ashana plus whey protein (25% protein content) (AW2), respectively. Fermentation was found to cause a highly significant (P ≤ 0.05) improvement in IVPD for AC, AW1 and AW2. The major protein fraction in the whey protein supplemented doughs was the globulin. This would indicate an improvement in the nutritional quality of pearl millet. Sensory evaluation revealed higher acceptability for whey protein supplemented formulas compared to control.
Improving acetic acid production of Acetobacter pasteurianus AC2005 in hawthorn vinegar fermentation by using beer for seed culture
Authors: Zheng Yu , Zhang Keping , Wang Chunxia , Liu Hongxiang , Luo Jianmei , Wang Min
Published: November 2010

Fruit vinegar can be obtained biologically from the fermentation of fruit wine using species of the genera Acetobacter. However, the productivity of vinegar is generally low because of the inhibition by substrate ethanol and product acetic acid. In this research, the yield of acetic acid, as well as the cell growth, in hawthorn vinegar fermentation was enhanced using beer for seed preparation. The higher yield of acetic acid of AC2005 was because of the higher alcohol dehydrogenase and aldehyde dehydrogenase activities caused by using beer for seed preparation. Furthermore, Acetobacter pasteurianus AC2005 showed acid stability during the fed‐batch fermentation of hawthorn vinegar.
Encoding and Decoding Mechanisms of Pulsatile Hormone Secretion
Authors: Walker J. J. , Terry J. R. , Tsaneva‐Atanasova K. , Armstrong S. P. , McArdle C. A. , Lightman S. L.
Published: November 2010

Ultradian pulsatile hormone secretion underlies the activity of most neuroendocrine systems, including the hypothalamic‐pituitary adrenal (HPA) and gonadal (HPG) axes, and this pulsatile mode of signalling permits the encoding of information through both amplitude and frequency modulation. In the HPA axis, glucocorticoid pulse amplitude increases in anticipation of waking, and, in the HPG axis, changing gonadotrophin‐releasing hormone pulse frequency is the primary means by which the body alters its reproductive status during development (i.e. puberty). The prevalence of hormone pulsatility raises two crucial questions: how are ultradian pulses encoded (or generated) by these systems, and how are these pulses decoded (or interpreted) at their target sites? We have looked at mechanisms within the HPA axis responsible for encoding the pulsatile mode of glucocorticoid signalling that we observe in vivo. We review evidence regarding the ‘hypothalamic pulse generator’ hypothesis, and describe an alternative model for pulse generation, which involves steroid feedback‐dependent endogenous rhythmic activity throughout the HPA axis. We consider the decoding of hormone pulsatility by taking the HPG axis as a model system and focussing on molecular mechanisms of frequency decoding by pituitary gonadotrophs.
Glutamine‐enriched enteral nutrition in very low birthweight infants and allergic and infectious diseases at 6 years of age
Authors: Van Zwol Annelies , Moll Henriëtte A. , Fetter Willem P. F. , Van Elburg Ruurd M.
Published: November 2010

van Zwol A, Moll HA, Fetter WPF, van Elburg RM. Glutamine‐enriched enteral nutrition in very low birthweight infants and allergic and infectious diseases at 6 years of age. Paediatric and Perinatal Epidemiology 2010.

In a previous randomised controlled trial, we found that glutamine‐enriched enteral nutrition in 102 very low birthweight (VLBW) infants decreased both the incidence of serious infections in the neonatal period and the risk of atopic dermatitis during the first year of life. We hypothesised that glutamine‐enriched enteral nutrition in VLBW infants in the neonatal period influences the risk of allergic and infectious disease at 6 years of age. Eighty‐eight of the 102 infants were eligible for the follow‐up study (13 died, 1 chromosomal abnormality). Doctor‐diagnosed allergic and infectious diseases were assessed by means of validated questionnaires. The association between glutamine‐enriched enteral nutrition in the neonatal period and allergic and infectious diseases at 6 years of age was based on univariable and multivariable logistic regression analyses. Seventy‐six of the 89 (85%) infants participated, 38 in the original glutamine‐supplemented group and 38 in the control group. After adjustment, we found a decreased risk of atopic dermatitis in the glutamine‐supplemented group: adjusted odds ratio (aOR) 0.23 [95% CI 0.06, 0.95]. No association between glutamine supplementation and hay fever, recurrent wheeze and asthma was found. A decreased risk of gastrointestinal tract infections was found in the glutamine‐supplemented group (aOR) 0.10 [95% CI 0.01, 0.93], but there was no association with upper respiratory, lower respiratory or urinary tract infections. We concluded that glutamine‐enriched enteral nutrition in the neonatal period in VLBW infants decreased the risk of atopic dermatitis and gastrointestinal tract infections at 6 years of age.
Hodgkin disease relapse discovered at the time of liver transplant for acute liver failure
Authors: Hope B. C. , Chau K. Y. , Evans H. M. , Mouat S. , Munn S. , Yeong M. L. , Chin S. E.
Published: November 2010

Hope BC, Chau KY, Evans HM, Mouat S, Munn S, Yeong ML, Chin SE. Hodgkin disease relapse discovered at the time of liver transplant for acute liver failure.  Pediatr Transplantation 2012: 16: E10–E14. © 2010 John Wiley & Sons A/S.

Abstract:  Lymphoma is a recognized cause of liver damage and in rare instances presents as ALF. In such cases, the underlying malignancy is often difficult to detect. Historically, the prognosis has been poor. Cure has occasionally been achieved with chemotherapy alone. LT in this setting is controversial, but has contributed to successful outcomes, as in the case of the five‐yr‐old girl reported here.
Iron deficiency anaemia and delayed diagnosis of colorectal cancer: a retrospective cohort study
Authors: Damery S. , Ryan R. , Wilson S. , Ismail T. , Hobbs R. ,   On behalf of the Improving Colorectal Outcomes (ICOS) Group
Published: November 2010

Aim  The extent to which different referral pathways following a primary care diagnosis of iron deficiency anaemia (IDA) are associated with delay in diagnosis of colorectal cancer (CRC) was determined.

Method  Eligible patients aged 40 or more years, with IDA diagnosed in primary care, and a subsequent diagnosis of CRC, were studied retrospectively. Referral pathways were identified using the specialty of first recorded GP referral following IDA diagnosis. Differences in time to diagnosis of CRC were assessed by referral specialty. Differences in the proportion of cases referred before and after the re‐issue of the NICE urgent referral guidelines for suspected lower gastrointestinal (GI) cancer were also assessed.

Results  Of 628 882 eligible patients, 3.1% (n = 19 349) were diagnosed with IDA during the study period; 3.0% (n = 578) were subsequently diagnosed with CRC. Two hundred and fifty‐nine (44.8%) patients had no recorded referral or a referral unrelated to anaemia or the GI tract. Only 35% (n = 201) of patients were referred to a relevant specialty. Median time to CRC diagnosis ranged from 2.5 months (referral to a relevant surgical specialty) to 31.9 months (haematology). Time to diagnosis was longer in patients referred to a medical compared with a relevant surgical specialty (P = 0.024). There was no significant difference in time to CRC diagnosis before and after the NICE guidelines were re‐issued in 2005.

Conclusion  Significant differences exist between referral specialties in time to CRC diagnosis following a primary care diagnosis of IDA. Despite NICE referral recommendations, a significant proportion of patients are still not managed within recommended care pathways to CRC diagnosis.
Macroscopic and histological evaluation of tunica vaginalis dorsal grafting in the first stage of Bracka’s urethroplasty: an experimental study in rabbits
Authors: Rosito Tiago E. , Pires Jesus A.S. , Delcelo Rosana , Ortiz Valdemar , Macedo Jr Antonio
Published: November 2010

What’s known on the subject? and What does the study add?

Complex urethral reconstruction done in two steps requires a dorsal component for the first procedure. Classically, preputial skin and buccal mucosa are used. We tested the tunica vaginalis for the same purpose.

Tunica vaginalis proved to be feasible as dorsal graft, histological properties showed metaplasia of the tunica vaginalis into an epithelium that resemble urothelium without clinically significant retraction.

OBJECTIVE

• To evaluate the use of tunica vaginalis as a dorsal free graft in the first stage of Bracka’s urethroplasty in a rabbit animal model using macroscopic and histological analysis.

MATERIAL AND METHODS

• Surgery was performed on 16 rabbits, divided into four groups of four according to the number of weeks after surgery at which they were killed (2, 4, 8 and 12 weeks).

• The penile urethra was removed and only the ventral aspect of the urethra was reconstructed using a tunica vaginalis free graft dorsally fixed in the corpora cavernosa.

• Epithelial, inflammatory and fibrotic changes in the graft were evaluated macroscopically then histologically at the point when each rabbit group was killed.

RESULTS

• Macroscopic evaluation showed good graft uptake with minimal retraction (P > 0.05).

• Histological evaluation showed a reduction in the inflammatory process during the first 4 weeks, after which inflammation stabilized.

• The mesothelium was partially healed at 2 and 8 weeks with a metaplasia defined by a stratified squamous, non‐keratinized lining. The grafted area was thinner than the surrounding penile skin and similar to urothelial native epithelium.

CONCLUSION

• Tunica vaginalis used as a free graft placed dorsally on the corpora cavernosa in the first stage of Bracka’s urethroplasty shows good tissue integration and develops into a stratified non‐ keratinized epithelium (metaplasia) without significant retraction, despite exposure to the external environment.
Comparative analysis of permanent post‐disaster houses constructed in Çankırı and Dinar
Authors: Dikmen Nese
Published: November 2010

A major challenge after an earthquake is how to establish a new residential area of a similar or even improved standard for people who have suffered psychological, social and economic impacts and witnessed significant damage to the physical environment. As part of a research project conducted in 2005 and 2008, questionnaires were administered to the permanent occupiers of post‐disaster houses in the Turkish cities of Çankırı and Dinar. They were asked to compare the comfort levels and other characteristics of the houses in which they now reside with those of the traditional houses in which they used to live. The survey revealed that such aspects do not differ between the two types of accommodation. However, differences were identified between the two areas under review (Çankırı and Dinar). In addition, average scores for traditional houses were higher than those for post‐disaster houses in both places.