bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of peptides to multiple sclerosis research
Authors: Alcaro Maria Claudia , Papini Anna Maria
Published: March 2006

Multiple sclerosis (MS) is an autoimmune disease associated with chronic inflammatory demyelination of the central nervous system in genetically susceptible individuals. Because of the disease complexity and heterogeneity, its pathogenesis remains unknown despite extensive research efforts, and specific effective treatments have not yet been developed. Peptide‐based research has been important in attempts to unravel particular aspects of this complex disease, including the characterization of the different molecular mechanisms of MS, with the goal of providing useful products for immune‐mediated therapies. In fact, in the past decade, peptide‐based research has been predominant in research aimed to identify and/or develop target antigens as synthetic probes for specific biomarkers as well as innovative immunomodulating therapies. This review presents an overview of the contributions of peptide science to MS research and discusses future directions of peptide‐based investigations. © 2006 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 84: 349–367, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Meta-analysis of observational studies of ileorectal versus ileal pouch–anal anastomosis for familial adenomatous polyposis
Authors: Aziz O , Athanasiou T , Fazio V W , Nicholls R J , Darzi A W , Church J , Phillips R K S , Tekkis P P
Published: March 2006

Background

Surgery for familial adenomatous polyposis (FAP) aims to minimize cancer risk while providing good functional outcome. Colectomy with ileorectal anastomosis and proctocolectomy with ileal pouch–anal anastomosis both offer this, but there is no clear consensus about which is better.

Methods

This is a meta-analysis of comparative studies published between 1991 and 2003 reporting early and late postoperative adverse events, functional outcomes and quality of life.

Results

Twelve studies containing 1002 patients (53·4 per cent ileal pouch, 46·6 per cent ileorectal anastomosis) were identified. Bowel frequency (weighted mean difference 1·62 (95 per cent confidence interval (c.i.) 1·05 to 2·20)), night defaecation (odds ratio (OR) 6·64 (95 per cent c.i. 2·99 to 14·74)) and use of incontinence pads (OR 2·72 (95 per cent c.i. 1·02 to 7·23)) were significantly less in the ileorectal group, although faecal urgency was reduced with the ileal pouch (odds ratio 0·43 (95 per cent c.i. 0·23 to 0·80)). Reoperation within 30 days was more common after ileal pouch construction (23·4 versus 11·6 per cent; OR 2·11 (95 per cent c.i. 1·21 to 3·70)). There was no significant difference between the techniques in terms of sexual dysfunction, dietary restriction, or postoperative complications. Rectal cancer was a diagnosis only in the ileorectal group (5·5 per cent).

Conclusion

Ileal pouch and ileorectal anastomoses have individual merits. Further research is needed to determine which most benefits patients with FAP.
Optimisation of the treatment conditions of cocoa butter in order to reduce non‐quality
Authors: Assidjo Emmanuel , Yao Benjamin , Akou Etienne , Ado Gossan
Published: March 2006

The interest of the use of the experimental designs for the improvement of an industrial process in a real context of production was highlighted by the optimisation of the demucilagination and deodorisation conditions of the cocoa butter using complete factorial designs. The study carried out enabled to obtain a reduction of non‐conformity of the final product (cocoa butter) of 28% in times of intensive production to less than 5%. The models obtained for each operation were validated in real industrial context. Copyright © 2006 John Wiley & Sons, Ltd.
Aryldithioethyloxycarbonyl (Ardec): A New Family of Amine Protecting Groups Removable under Mild Reducing Conditions and Their Applications to Peptide Synthesis
Authors: Lapeyre Milaine , Leprince Jérôme , Massonneau Marc , Oulyadi Hassan , Renard Pierre‐Yves , Romieu Anthony , Turcatti Gerardo , Vaudry Hubert
Published: March 2006

The development of phenyldithioethyloxycarbonyl (Phdec) and 2‐pyridyldithioethyloxycarbonyl (Pydec) protecting groups, which are thiol‐labile urethanes, is described. These new disulfide‐based protecting groups were introduced onto the ε‐amino group of L‐lysine; the resulting amino acid derivatives were easily converted into Nα‐Fmoc building blocks suitable for both solid‐ and solution‐phase peptide synthesis. Model dipeptide(Ardec)s were prepared by using classical peptide couplings followed by standard deprotection protocols. They were used to optimize the conditions for complete thiolytic removal of the Ardec groups both in aqueous and organic media. Phdec and Pydec were found to be cleaved within 15 to 30 min under mild reducing conditions: i) by treatment with dithiothreitol or β‐mercaptoethanol in Tris⋅HCl buffer (pH 8.5–9.0) for deprotection in water and ii) by treatment with β‐mercaptoethanol and 1,8‐diazobicyclo[5.4.0]undec‐7‐ene (DBU) in N‐methylpyrrolidinone for deprotection in an organic medium. Successful solid‐phase synthesis of hexapeptides Ac‐Lys‐Asp‐Glu‐Val‐Asp‐Lys(Ardec)‐NH2 has clearly demonstrated the full orthogonality of these new amino protecting groups with Fmoc and Boc protections. The utility of the Ardec orthogonal deprotection strategy for site‐specific chemical modification of peptides bearing several amino groups was illustrated firstly by the preparation of a fluorogenic substrate for caspase‐3 protease containing the cyanine dyes Cy 3.0 and Cy 5.0 as FRET donor/acceptor pair, and by solid‐phase synthesis of an hexapeptide bearing a single biotin reporter group.
Structural Variations in the Solid‐Solution Series LnxCa2‐xAl [Al1+xSi1‐xO7] with 0 ≤ x ≤ 1 and Ln: La, Eu, Er.
Authors: Peters L. , Knorr K. , Depmeier W.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Chemical Vapor Transport of Solid Solutions. Part 25. Formation of Mixed Phases and Chemical Vapor Transport in the Systems TiS2/MoS2, TiSe2/MoSe2, TaS2/MoS2 and TaSe2/MoSe2.
Authors: Hotje U. , Wartchow R. , Binnewies M.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis, Resolution, and Aldol Reactions of a Planar‐Chiral Lewis Acid Complex.
Authors: Liu Shih‐Yuan , Hills Ivory D. , Fu Gregory C.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Titanium‐Catalyzed Iminohydrazination of Alkynes.
Authors: Banerjee Sanjukta , Shi Yanhui , Cao Changsheng , Odom Aaron L.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis and Evaluation of 5‐Phenyl‐1H‐1,4‐benzodiazepin‐2(3H)‐one‐Based Palladium Complexes as Precatalysts in C—C Bond Forming Reactions.
Authors: Spencer John , Sharratt David P. , Dupont Jairton , Monteiro Adriano L. , Reis Vinicius I. , Stracke Marcelo P. , Rominger Frank , McDonald Iain M.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
tert‐Butyl (Phenylsulfonyl)alkyl‐N‐hydroxycarbamates: The First Class of N‐(Boc) Nitrone Equivalents.
Authors: Guinchard Xavier , Vallee Yannick , Denis Jean‐Noel
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Highly Regio‐ and Enantioselective Palladium‐Catalyzed Allylic Alkylation and Amination of Dienyl Esters with 1,1′‐P,N‐Ferrocene Ligands.
Authors: Zheng Wen‐Hua , Sun Na , Hou Xue‐Long
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis of N‐Substituted Isoindolinones via a Palladium‐Catalyzed Three‐Component Carbonylation—Amination—Michael Addition Cascade.
Authors: Grigg Ronald , Gai Xinjie , Khamnaen Tossapol , Rajviroongit Shuleewan , Sridharan Visuvanathar , Zhang Lixin , Collard Simon , Keep Ann
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Ruthenium‐Catalyzed Cycloaddition of Alkynes and Organic Azides.
Authors: Zhang Li , Chen Xinguo , Xue Peng , Sun Herman H. Y. , Williams Ian D. , Sharpless K. Barry , Fokin Valery V. , Jia Guochen
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Azinyl Sulfides. Part 89. Synthesis and Structure of Dipyrido‐1,4‐dithiins
Authors: Morak Beata , Pluta Krystian , Suwinska Kinga , Grymel Miroslawa , Besnard Celine , Schiltz Marc , Kloc Christian , Siegrist Theo
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Transformation of Double Hydrogen‐Bonding Motifs of TTF‐Uracil System by Redox Change.
Authors: Miyazaki Eigo , Morita Yasushi , Umemoto Yoshikazu , Fukui Kozo , Nakasuji Kazuhiro
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis by Microwave Irradiation and Antidiarrhoeal Activity of Benzotriazinone and Saccharine Derivatives.
Authors: Fiorino Ferdinando , Caliendo Giuseppe , Perissutti Elisa , Severino Beatrice , Frecentese Francesco , Preziosi Barbara , Izzo Angelo A. , Capasso Raffaele , Santagada Vincenzo
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthetic Utilization of Polynitroaromatic Compounds. Part 3. Preparation of Substituted Dibenz[b,f][1,4]oxazepine‐11(10H)‐ones from 2,4,6‐Trinitrobenzoic Acid via Nucleophilic Displacement of Nitro Groups.
Authors: Samet Alexander V. , Marshalkin Victor N. , Kislyi Konstantine A. , Chernysheva Natalya B. , Strelenko Yuri A. , Semenov Victor V.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Kinetic Resolution of Chiral Secondary Alcohols by Dehydrogenative Coupling with Recyclable Silicon‐Stereogenic Silanes.
Authors: Rendler Sebastian , Auer Gertrud , Oestreich Martin
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis of Fluorous Trialkyl Phosphines with the Complete Exclusion of PH3.
Authors: Vlad Gabor , Richter Frank U. , Horvath Istvan T.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Employment of Palladium Pincer‐Complexes in Phenylselenylation of Organohalides.
Authors: Wallner Olov A. , Szabo Kalman J.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis and Biological Activity of Some 17a‐Substituted Homolactones of Androst‐5‐ene Derivatives.
Authors: Penov Gasi Katarina M. , Stojanovic Srdjan Z. , Sakac Marija N. , Djurendic Evgenija A. , Csanadi Janos J. , Molnar‐Gabor Dora , Lazar Dusan , Kovacevic Radmila M.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Vinylsulfones versus Alkylsulfones in the Addition to Chiral Imines. Synthesis of N‐(tert‐Butoxycarbonyl)‐L‐homophenylalanine.
Authors: Diez David , Garcia Pilar , Marcos Isidro S. , Basabe Pilar , Garrido Narciso M. , Broughton H. B. , Urones Julio G.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Convenient Preparation of Highly Active Phase‐Transfer Catalyst for Catalytic Asymmetric Synthesis of α‐Alkyl‐ and α,α‐Dialkyl‐α‐amino Acids: Application to the Short Asymmetric Synthesis of BIRT‐377.
Authors: Han Zhenfu , Yamaguchi Yukako , Kitamura Masanori , Maruoka Keiji
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Facile One‐Step Syntheses of Modified O‐Glycoprotein Galβ1‐3GaINAc Structures by Transglycosylation Employing Three β‐Galactosidases from Bovine Testes, Xanthomonas manihotis, and Bacillus circulans.
Authors: Kroeger Lars , Thiem Joachim
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Synthesis of (.+‐.)‐Coerulescine (Ia) and a Formal Synthesis of (.+‐.)‐Horsfiline (Ib).
Authors: Chang Meng‐Yang , Pai Chun‐Li , Kung Yung‐Hua
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Deprotection of α‐Imidazole/Benzimidazole Ribonucleosides by Catalytic Carbon Tetrabromide Initiated Photolysis.
Authors: Chandra Tilak , Brown Kenneth L.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Concise Synthesis and Antiviral Activity of Novel Unsaturated Acyclic Pyrimidine Nucleosides.
Authors: Oh Chang‐Hyun , Beak Tae‐Rim , Hong Joon Hee
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Biologically Active Glycosides from Asteroidea. Part 41. Isolation and Structure Determination of Glucocerebrosides from the Starfish Linckia laevigata.
Authors: Maruta Tomoki , Saito Takeshi , Inagaki Masanori , Shibata Osamu , Higuchi Ryuichi
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
BiBr3‐Initiated Cyclization—Addition Reactions: Effect of π‐Nucleophile on Oxocarbenium Ion Addition and Total Syntheses of (+)‐(S,S)‐(cis‐6‐Methyltetrahydropyran‐2‐yl)acetic Acid and Its trans‐Diastereomer.
Authors: Hinkle Robert J. , Lian Yajing , Litvinas Nichole D. , Jenkins Alex T. , Burnette Daniel C.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Glimmers of Research in Metallurgy
Authors: Holappa Lauri
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Principles of Phosphate Dissolution and Precipitation
Authors: Koutsoukos P. G. , Valsami‐Jones E.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Corrosion Protection by Chemical Vapor Deposition: A Review
Authors: Sathiyanarayanan S. , Rajagopal G. , Palaniswamy N. , Raghavan M.
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Phase Behavior and Microstructure of Liquid Crystals in Mixed Surfactant Systems
Authors: Rodriguez Carlos , Kunieda Hironobu
Published: March 2006

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
The Potential of P1 Site Alterations in Peptidomimetic Protease Inhibitors as Suggested by Virtual Screening and Explored by the Use of CC‐Coupling Reagents
Authors: Weik Steffen , Luksch Torsten , Evers Andreas , Böttcher Jark , Sotriffer Christoph A. , Hasilik Andrej , Löffler Hans‐Gerhard , Klebe Gerhard , Rademann Jörg
Published: March 2006

A synthetic concept is presented that allows the construction of peptide isostere libraries through polymer‐supported C‐acylation reactions. A phosphorane linker reagent is used as a carbanion equivalent; by employing MSNT as a coupling reagent, the C‐acylation can be conducted without racemization. Diastereoselective reduction was effected with L‐selectride. The reagent linker allows the preparation of a norstatine library with full variation of the isosteric positions including the P1 side chain that addresses the protease S1 pocket. Therefore, the concept was employed to investigate the P1 site specificity of peptide isostere inhibitors systematically. The S1 pocket of several aspartic proteases including plasmepsin II and cathepsin D was modeled and docked with ≈500 amino acid side chains. Inspired by this virtual screen, a P1 site mutation library was designed, synthesized, and screened against three aspartic proteases (plasmepsin II, HIV protease, and cathepsin D). The potency of norstatine inhibitors was found to depend strongly on the P1 substituent. Large, hydrophobic residues such as biphenyl, 4‐bromophenyl, and 4‐nitrophenyl enhanced the inhibitory activity (IC50) by up to 70‐fold against plasmepsin II. In addition, P1 variation introduced significant selectivity, as up to 9‐fold greater activity was found against plasmepsin II relative to human cathepsin D. The active P1 site residues did not fit into the crystal structure; however, molecular dynamics simulation suggested a possible alternative binding mode.
Overexpression in colorectal carcinoma of two lysosomal enzymes, CLN2 and CLN1, involved in neuronal ceroid lipofuscinosis
Authors: Tsukamoto Toshihiko , Iida Juri , Dobashi Yoh , Furukawa Taiji , Konishi Fumio
Published: March 2006

BACKGROUND

Lysosomal proteases are implicated in cancer progression and metastasis. In the current study, using subtraction cloning for genes that are differentially expressed in metastasis, the authors isolated a clone encoding ceroid lipofuscinosis, neuronal 2 (CLN2), which is a lysosomal serine protease defective in neuronal ceroid lipofuscinosis (NCL). Increased CLN2 activity has been reported in breast carcinoma and the antiapoptotic effect of another causative gene of NCL, ceroid lipofuscinosis, neuronal 1 (CLN1), is known.

METHODS

The mRNA levels of CLN2, CLN1, and cathepsins B, D, H, and L were investigated in colorectal carcinoma patients with different clinical stages using real‐time quantitative reverse transcriptase polymerase chain reaction. A polyclonal antibody was raised against a recombinant CLN2 protein for immunoblotting and immunohistochemistry.

RESULTS

The mRNA levels of CLN1 and cathepsins B, D, and L were significantly higher in metastatic lesions than in primary tumors. In the primary tumors, mRNA expressions of CLN2 and cathepsin D were associated with advanced clinical stages (P < .015 and P < .031, respectively). Among the lysosomal enzymes examined, only the mRNA expression of CLN2 in both the primary tumors of all patients and the pT3 tumors was correlated with the presence of liver metastases (P < .0049 and P < .029, respectively). The polyclonal antibody prepared in the current study demonstrated CLN2 overexpression by immunoblotting and immunohistochemistry.

CONCLUSIONS

The results indicate that there is a close correlation between CLN2 and CLN1 expression and colorectal carcinoma progression and metastasis and suggest that they may be potential molecular targets. Cancer 2006. © 2006 American Cancer Society.
Results of postoperative reirradiation for recurrent or second primary head and neck carcinoma
Authors: Kasperts Nicolien , Slotman Ben J. , Leemans C. Rene , de Bree Remco , Doornaert Patricia , Langendijk Johannes A.
Published: March 2006

BACKGROUND

In this prospective study, the effects of a second course of postoperative radiation therapy on locoregional control, survival, toxicity, and quality of life were investigated in patients who underwent resection of a second primary or locoregional recurrent head and neck tumor in a previously irradiated area.

METHODS

In total, 39 patients who underwent surgery for second primary tumors (n = 19 patients) or for recurrent locoregional tumors (n = 20 patients) were retreated with postoperative radiotherapy (RE‐PORT). Indications for RE‐PORT were extranodal spread (49%), positive surgical margins (44%), and/or other risk factors (8%). The target volume for RE‐PORT was confined to the high‐risk area. No elective radiotherapy was applied in regions that were situated in the formerly high‐dose area. A total dose of 46 grays (Gy) was given to elective areas with boosts from 60 Gy to 66 Gy to the high‐risk region with conventional fractionation. The results of RE‐PORT were compared with the results from patients who were treated in the same period with primary adjuvant radiotherapy (PRI‐PORT) at the authors' institution.

RESULTS

The mean follow‐up was 32 months (range, 3‐84 mos). The locoregional control rate after 3 years in the RE‐PORT group was 74%, and the 3‐year overall survival rate was 44%. This did not differ significantly compared with survival rates in the PRI‐PORT group. Although a higher rate of late radiation‐induced morbidity and more head and neck symptoms were observed in the RE‐PORT group compared with the PRI‐PORT group, no differences were observed with regard to the more general dimensions of quality of life.

CONCLUSIONS

RE‐PORT after surgery for recurrent locoregional tumors and/or second primary tumors should be considered in patients who have high‐risk histopathologic features. Cancer 2006. © 2006 American Cancer Society.
Proteomic‐based prediction of clinical behavior in adult acute lymphoblastic leukemia
Authors: Albitar Maher , Potts Steven J. , Giles Francis J. , O'Brien Susan , Keating Michael , Thomas Deborah , Clarke Charlotte , Jilani Iman , Aguilar Christine , Estey Elihu , Kantarjian Hagop
Published: March 2006

BACKGROUND

Response in adult acute lymphoblastic leukemia (ALL) can be achieved in a majority of patients. However, unlike pediatric ALL, recurrence is common in adult ALL, and the ability to predict at an early stage which patients are most likely to experience recurrence may help in devising new therapeutic approaches to prevent recurrence.

METHODS

Peripheral blood plasma from 57 patients with confirmed ALL was obtained before induction therapy for proteomic analysis. Follow‐up continued for a median period of 71 weeks. For each plasma sample, 4 fractions eluted from a strong anion column were applied to 3 different ProteinChip array surfaces, and 12 surface‐enhanced laser desorption/ionization (SELDI) spectra were generated. Peaks that correlated with recurrence were identified and decision trees were constructed and evaluated, using only 2 peaks per predictive tree.

RESULTS

The best decision trees provided strong positive prediction of recurrence, with correct predictions 84% to 92% of the time, whereas negative prediction of patients who did not experience recurrence was less robust, with 62% to 74% accuracy. Prediction of recurrence was independent of cytogenetics, bone marrow blast count, lactate dehydrogenase, β‐2‐microglobulin, or surface markers. Positive prediction of L3 morphological classification was achieved in 80% of test cases.

CONCLUSIONS

Peripheral blood plasma is adequate to predict clinical behavior in ALL patients irrespective of the percentage of bone marrow blasts. Proteomic analysis of plasma offers a useful approach for profiling patients with ALL. Cancer 2006. © 2006 American Cancer Society.
CD4+CD25+ regulatory T cells control the magnitude ofT‐dependent humoral immune responses to exogenous antigens
Authors: Eddahri Fouad , Oldenhove Guillaume , Denanglaire Sébastien , Urbain Jacques , Leo Oberdan , Andris Fabienne
Published: March 2006

CD4+CD25+ T reg cells are critical for peripheral tolerance and prevention of autoimmunity. Here we show that CD4+CD25+ T reg also regulate the magnitude of humoral responses against a panel of T‐dependent antigens of foreign origin during both primary and secondary immune responses. Depletion of CD4+CD25+ T cells leads to increased antigen‐specific antibody production and affinity maturation but does not affect T‐independent B cell responses, suggesting that CD4+CD25+ T reg exert a feedback mechanism on non‐self antigen‐specific antibody secretion by dampening the T cell help for B cell activation. Moreover, we show that CD4+CD25+ T reg also suppress in vitro B cell immunoglobulin production by inhibiting CD4+CD25– T cell help delivery, and that blockade of TGF‐β activity abolishes this suppression.
Regional distribution in the fatty acids of triacylglycerols and phospholipids within soybean seeds (Glycine max L.)
Authors: Yoshida Hiromi , Kanei Sako , Tomiyama Yuka , Mizushina Yoshiyuki
Published: March 2006

The fatty acid distribution of triacylglycerols (TAG) and major phospholipids (PL) within soybean seeds (Glycine max L.) was investigated in relation to their tocopherol contents. The lipids extracted from four cultivars were separated by thin‐layer chromatography into seven fractions. Tocopherols were predominantly detected in the axis, followed by cotyledons and seed coat. The major lipid components were TAG and PL, while hydrocarbons, steryl esters, free fatty acids and diacylglycerols (sn‐1,3 and sn‐1,2) were also present in minor proportions. With a few exceptions, the dominant PL components were phosphatidylcholine, followed by phosphatidylethanolamine or phosphatidylinositiol. Significant differences (p <0.05) in fatty acid distribution existed when different soybean cultivars were examined. However, the principal characteristics of the fatty acid distribution in the TAG were evident among four cultivars; unsaturated fatty acids were predominantly concentrated in the sn‐2 position, and saturated fatty acids primarily occupied the sn‐1 or sn‐3 position in the oils of the soybeans.
Characteristic genomic imbalances in pediatric pheochromocytoma
Authors: Hering Antje , Guratowska Monika , Bucsky Peter , Claussen Uwe , Decker Jochen , Ernst Guenther , Hoeppner Wolfgang , Michel Susanne , Neumann Hartmut , Parlowsky Thomas , Loncarevic Ivan
Published: March 2006

Pheochromocytoma (PCC) in children is rare, genetically not well described, and often related to a poor prognosis. We detected genomic imbalances in all 14 tumors from children analyzed by comparative genomic hybridization. A combinatorial loss of chromatin from 3p and 11p was a common feature in 10 of 14 (72%) patients, which was a result of either a loss of a total chromosome 3 and a total chromosome 11 in 6 of 10 patients, or confined deletions of their p arms in 4 of 10 patients. All patients exhibiting a loss of 3p and 11p carried VHL mutations. The VHL mutations were constitutive in 9 cases and somatic and restricted to tumor DNA in the remaining tumor. On the other hand, VHL mutations were absent in 4 patients, 2 who had other familial syndromes (NF1, SDHD) and 2 with unknown etiology. Our data show that the pattern of imbalances in the tumor DNA of PCC patients strongly correlated with an underlying familial VHL mutation. Furthermore, we show that true sporadic PCC is rare in childhood. Thus, children with PCC should be checked for a related predisposing gene. This would also identify familial syndrome patients requiring long‐term monitoring for other syndrome‐related malignancies. © 2006 Wiley‐Liss, Inc.
Correlation of Mississippian (Upper Viséan) foraminiferan, conodont, miospore and ammonoid zonal schemes, and correlation with the Asbian–Brigantian boundary in northwest Ireland
Authors: Cózar P. , Somerville I. D. , Mitchell W. I. , Medina‐Varea P.
Published: March 2006

The microbiota of the upper Viséan (Asbian–Brigantian) rocks in the Lough Allen Basin in northwest Ireland is analysed. The Middle Mississippian sequence studied extends from the upper part of the Dartry Limestone/Bricklieve Limestone formations of the Tyrone Group to the Carraun Shale Formation of the Leitrim Group. The rocks have been traditionally dated by ammonoid faunas representing the B2a to P2c subzones. The Meenymore Formation (base of the Leitrim Group) also contains conodont faunas of the informal partial‐range Mestognathus bipluti zone. The upper Brigantian Lochriea nodosa Conodont Zone was recognized by previous authors in the middle of the Carraun Shale Formation (Ardvarney Limestone Member), where it coincides with upper Brigantian ammonoids of the Lusitanoceras granosus Subzone (P2a). Foraminifera and algae in the top of the Dartry Limestone Formation are assigned to the upper Cf6γ Foraminifera Subzone (highest Asbian), whereas those in the Meenymore Formation belong to the lower Cf6δ Foraminifera Subzone (lower Brigantian). The Dartry Limestone Formation–Meenymore Formation boundary is thus correlated with the Asbian–Brigantian boundary in northwest Ireland. For the first time, based on new data, a correlation between the ammonoid, miospore, foraminiferan and conodont zonal schemes is demonstrated. The foraminiferans and algae, conodonts and ammonoids are compared with those from other basins in Ireland, northern England, and the German Rhenish Massif. Historically, the Asbian–Brigantian boundary has been correlated with several levels within the P1a Ammonoid Subzone. However, the new integrated biostratigraphical data indicate that the Asbian–Brigantian boundary in northwest Ireland is probably located within the B2a Ammonoid Subzone and the NM Miospore Zone, but the scarcity of ammonoids in the Tyrone Group precludes an accurate placement of that boundary within this subzone. Copyright © 2006 John Wiley & Sons, Ltd.
AMP‐dependent protein kinase alpha 2 isoform promotes hypoxia‐induced VEGF expression in human glioblastoma
Authors: Neurath Kathryn M. , Keough Martin P. , Mikkelsen Tom , Claffey Kevin P.
Published: March 2006

Tumor cells respond to hypoxic stress by upregulating a variety of genes involved in glucose uptake, glycolysis, and angiogenesis, all essential to maintaining nutrient availability and intracellular ATP levels. Adenosine monophosphate‐dependent kinase (AMPK) is a key sensor for cellular homeostasis and is highly sensitive to changes in AMP:ATP ratios. The two catalytic AMPK alpha isoforms (AMPKα1, AMPKα2) were investigated with respect to their expression, cellular distribution, and contribution to VEGF expression under hypoxic stress in human U373 glioblastoma cells. Quantitative real‐time PCR analysis showed AMPKα1 mRNA to be constitutively expressed in normoxia and hypoxia, whereas AMPKα2 mRNA levels were low in normoxia and significantly induced in hypoxia. Fluorescent immunohistochemistry showed that AMPKα2 protein redistributed to the nucleus under hypoxia, whereas AMPKα1 remained distributed throughout the cell. The AMPK chemical inhibitor, 5‐iodotubericidin, effectively repressed the hypoxic induction of VEGF mRNA levels and hypoxia inducible factor‐1 dependent transcription. AMPKα2 repression with RNA interference reduced hypoxia‐induced VEGF mRNA and HIF‐1 transcription, whereas AMPKα1 repression did not. Human glioblastoma cell lines U118 and U138 also showed hypoxia‐induction of AMPKα2 as well as VEGF. Immunohistochemistry analysis of human astrocytoma/glioma samples revealed AMPKα2 present in high grade gliomas within hypoxic pseudopalisading microenvironments. These data suggest that prolonged hypoxia promotes the expression and functional activation of AMPKα2 and VEGF production in glioma cell lines and glioblastoma multiform tumors, thus contributing to tumor survival and angiogenesis in high grade human gliomas. © 2006 Wiley‐Liss, Inc.
Regeneration of whole meniscus using meniscal cells and polymer scaffolds in a rabbit total meniscectomy model
Authors: Kang Sun‐Woong , Sun‐Mi Son , Jae‐Sun Lee , Eung‐Seok Lee , Kwon‐Yong Lee , Sang‐Guk Park , Jung‐Ho Park , Byung‐Soo Kim
Published: March 2006

The current treatments of meniscal lesion in knee joint are not perfect to prevent adverse effects of meniscus injury. Tissue engineering of meniscus using meniscal cells and polymer scaffolds could be an alternative option to treat meniscus injury. This study reports on the regeneration of whole medial meniscus in a rabbit total meniscectomy model using the tissue engineering technique. Biodegradable scaffolds in a meniscal shape were fabricated from polyglycolic acid (PGA) fiber meshes that were mechanically reinforced by bonding PGA fibers at cross points with 75:25 poly(lactic‐co‐glycolic acid). The compressive modulus of the bonded PGA scaffold was 28‐fold higher than that of nonbonded scaffold. Allogeneic meniscal cells were isolated from rabbit meniscus biopsy and cultured in vitro. The expanded meniscal cells were seeded onto the polymer scaffolds, cultured in vitro for 1 week, and transplanted to rabbit knee joints from which medial menisci were removed. Ten or 36 weeks after transplantation, the implants formed neomenisci with the original scaffold shape maintained approximately. Hematoxylin and eosin staining of the sections of the neomenisci at 6 and 10 weeks revealed the regeneration of fibrocartilage. Safranin‐O staining showed that abundant proteoglycan was present in the neomenisci at 10 weeks. Masson's trichrome staining indicated the presence of collagen. Immunohistochemical analysis showed that the presence of type I and II collagen in neomenisci at 10 weeks was similar to that of normal meniscal tissue. Biochemical and biomechanical analyses of the tissue‐engineered menisci at 36 weeks were performed to determine the quality of the tissue‐engineered menisci. Tissue‐engineered meniscus showed differences in collagen content and aggregate modulus in comparison with native meniscus. This study demonstrates, for the first time, the feasibility of regenerating whole meniscal cartilage in a rabbit total meniscectomy model using the tissue engineering method. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Modulating cell adhesion and spreading by control of FnIII7–10 orientation on charged self‐assembled monolayers (SAMs) of alkanethiolates
Authors: Wang Hua , He Yi , Ratner Buddy D. , Jiang Shaoyi
Published: March 2006

In this work, we demonstrate that surface charge can be used to modulate cell adhesion/spreading through the control of the orientation of adsorbed FnIII7–10, which is a cell‐adhesive protein containing RGD residues. Carboxylic acid (COOH) and amine (NH2)‐terminated self‐assembled monolayers (SAMs) of alkanethiolates were used as model negatively and positively charged surfaces, respectively. The adsorbed amount of FnIII7–10 is controlled to be equivalent on both SAMs as confirmed by the adsorption isotherms determined using I125‐radiolabeled FnIII7–10. The binding of a monoclonal antibody specific for the cell‐binding domain of FnIII7–10 was measured by surface plasmon resonance (SPR) to evaluate FnIII7–10 orientations on different SAMs. Results indicate that adsorbed FnIII7–10 on NH2‐SAM has an orientation with more cell‐binding domains accessible than on COOH‐SAM, confirming our predictions from Monte Carlo simulations. Both phase contrast images and Vybrant® MTT cell proliferation assays show that the adhesion/spreading of bovine aortic endothelial cells (BAECs) on the NH2‐SAM is significantly better than that on the COOH‐SAM coated with an equivalent amount of FnIII7–10. These results indicate that surface charge can be used to specifically orient cell adhesive proteins such as FnIII7–10, thus providing a promising strategy to increase the activity of materials incorporating biological moieties. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Effects of in vitro bone formation on the mechanical properties of a trabeculated hydroxyapatite bone substitute
Authors: Kazakia Galateia J. , Nauman Eric A. , Ebenstein Donna M. , Halloran Bernard P. , Keaveny Tony M.
Published: March 2006

This study was designed to test the hypothesis that the mechanical properties of a trabecular bone substitute can be enhanced through in vitro tissue formation. Our specific objectives were to (1) determine the effects of in vitro marrow stromal cell‐mediated tissue deposition upon a trabeculated hydroxyapatite scaffold on the strength and toughness of the resulting bone substitute; and (2) identify and characterize regions of newly deposited matrix and mineral. This work provides a basis for future investigations aimed at transforming a brittle hydroxyapatite scaffold into an osteoinductive, biomechanically functional implant through in vitro bone deposition. As hypothesized, the mechanical properties of the trabecular bone substitutes were significantly enhanced by in vitro tissue formation. As a result of cell seeding and a 5 week culture protocol, mean strength increased by 85% (p = 0.008) and energy to fracture increased by 130% (p = 0.003). Accompanying the enhancement of mechanical properties was the deposition of significant amounts of bone matrix and mineral. Fluorescence imaging, scanning electron microscopy, electron probe microanalysis, and nanoindentation confirmed the presence of bonelike mineral with Ca/P ratio, modulus, and hardness similar to that within human and rat trabecular bone tissue. This new mineralization was found to exist within a newly deposited parallel‐fibered matrix both encasing and bridging between scaffold trabeculae. Taken as a whole, our results establish the feasibility of the production of an osteoinductive hydroxyapatite‐based trabecular bone substitute with mechanical properties enhanced through in vitro bone deposition. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Biodegradable implantable fluconazole delivery rods designed for the treatment of fungal osteomyelitis: Influence of gamma sterilization
Authors: Soriano I. , Martín A. Y. , Évora C. , Sánchez E.
Published: March 2006

Fluconazole poly(D,L‐lactic) acid (PLA) and poly(L‐lactic) acid (L‐PLA) implantable delivery rods were studied, in vitro and in vivo, as an alternative treatment of fungal osteomyelitis. Implantable rods loaded with 5% fluconazole (FLU) were prepared by the injection‐molding method and sterilized by γ‐irradiation at a dose of 25 kGy. Loading efficiency, physical chemistry (high performance liquid chromatography, X‐ray diffraction, gel permeation chromatography), and in vitro and in vivo release assays were performed to evaluate the novel delivery systems and the sterilization effect on implant characteristics. In spite of polymer degradation after γ‐irradiation, the loading efficiency, chemical stability, and crystallographic structure of FLU were not affected. In vivo studies were carried out in femoral bone marrow of rabbits. Approximately 85 and 80% of the total dose were released within 12 and 4 weeks from PLA and L‐PLA rods, respectively. This showed a faster release rate of FLU in vivo than in vitro, showing almost zero‐order kinetics from PLA rods. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Biodegradability and thermal stabilityof poly(propylene carbonate)/starch composites
Authors: Lu X. L. , Du F. G. , Ge X. C. , Xiao M. , Meng Y. Z.
Published: March 2006

Poly(propylene carbonate)/starch (PPC/starch) composites with different starch contents were prepared by melt compounding. The biodegradability of the composites was studied by soil burial for a period of 6 months. FTIR study, thermal analysis and morphology observation indicated clearly the changes of the buried specimens. The weight loss curves and the molecular weight changes of the specimens revealed a three‐stage biodegradation, corresponding to the propagation of microorganisms, the degradation of starch and the degradation of PPC. The experimental results showed that the addition of starch accelerated the degradation of PPC. Specimens with higher starch content exhibited greater weight loss in the second stage and smaller weight loss in the third stage. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Assessment of the effect of a biphasic ceramic on bone response in a rat calvarial defect model
Authors: Develıoğlu Hakan , Saraydin Serpil Ünver , Bolayir Giray , Dupoirieux Laurent
Published: March 2006

Calcium phosphate ceramics are being extensively used for orthopedic, periodontal, and dental applications. This study aimed to assess the effect of a biphasic ceramic such as Ceraform® on the osteogenesis in a rat calvarial defect model. 20 Wistar rats were enrolled in the study. Two symmetrical, circular, and 5‐mm‐wide full thickness defects were created in the parietal bones of each animal. The left defect was left empty as a control and the right defect was filled with the particular implant material. Animals were divided into two groups, and 10 animals were sacrificed at month 3 and the rest were sacrificed at month 6. The calvarial specimens were harvested for histological examinations. Defect area samples were stained with hematoxylin–eosin and Masson Thrichrom. A semiquantitative method was used to quantify the bone regeneration. The defects were mostly filled with fibrous connective tissue (3–6 months) in the control site. A loose, fibrovascular tissue was observed at the side of ceraform implantation at month 3. By 6 month, a dense collagenous tissue was observed at the same area. Multinuclear giant cells (MNGC) were detected around the implant bed at month 3 and month 6. No necrosis, tumorigenesis, or infection was observed at the implantation site at any time. There was no statistically meaningful difference regarding bone regeneration between the two defects at each observation period (p>0.05). This study showed that Ceraform® is biocompatible. However, this study indicates that biphasic ceramic do not offer any advantage over hydroxyapatite ceramics. It was also revealed that it had no effects on bone regeneration and that it seemed to be a space maintainer. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Bone morphogenetic protein‐4 enhances vascular endothelial growth factor secretion by human retinal pigment epithelial cells
Authors: Vogt Rhonda R. , Unda Richard , Yeh Lee‐Chuan C. , Vidro Eileen K. , Lee John C. , Tsin Andrew T.
Published: March 2006

Retinal pigment epithelial (RPE) cells secrete vascular endothelial growth factor (VEGF), a cytokine known to promote angiogenesis. Results from RNase protection assays (RPAs) show that RPE from non‐diabetic human donors and from adult retinal pigment epithelium‐19 (ARPE‐19) cells expressed significant bone morphogenetic protein‐4 (BMP‐4) message. In addition, ARPE‐19 cells cultured in high glucose (25 mM), compared to those in physiological glucose (5.5 mM) released significantly more BMP‐4 into the conditioned media (CM). However, the effect of BMP‐4 on the release of VEGF by ARPE‐19 cells has not been studied. Accordingly, ARPE‐19 cells were treated with BMP‐4 to determine VEGF secretion. BMP‐4 and VEGF levels in the CM and cell lysates were measured by enzyme‐linked immunosorbent assay (ELISA). Cells treated with exogenous BMP‐4 had higher VEGF in the CM and this treatment effect was dose‐ and time‐dependent, while cell lysates had low levels of VEGF. Addition of cycloheximide (CHX) or actinomycin‐D (ACT) significantly reduced VEGF secretion from cells treated with BMP‐4, suggesting that the BMP‐4‐induced secretion of VEGF requires new RNA and protein synthesis. Our results suggest that BMP‐4 may play a role in the regulation of ocular angiogenesis associated with diabetic retinopathy (DR) by stimulating VEGF release from RPE cells. J. Cell. Biochem. 98: 1196–1202, 2006. © 2006 Wiley‐Liss, Inc.
p21Waf1/Cip1 plays a critical role in modulating senescence through changes of DNA methylation
Authors: Zheng Quan Hui , Ma Li Wei , Zhu Wei Guo , Zhang Zong Yu , Tong Tan Jun
Published: March 2006

It has been reported that genomic DNA methylation decreases gradually during cell culture and an organism's aging. However, less is known about the methylation changes of age‐related specific genes in aging. p21Waf1/Cip1 and p16INK4a are cyclin‐dependent kinase (Cdk) inhibitors that are critical for the replicative senescence of normal cells. In this study, we show that p21Waf1/Cip1 and p16INK4a have different methylation patterns during the aging process of normal human 2BS and WI‐38 fibroblasts. p21Waf1/Cip1 promoter is gradually methylated up into middle‐aged fibroblasts but not with senescent fibroblasts, whereas p16INK4a is always unmethylated in the aging process. Correspondently, the protein levels of DNA methyltransferase 1 (DNMT1) and DNMT3a increase from young to middle‐aged fibroblasts but decrease in the senescent fibroblasts, while DNMT3b decreases stably from young to senescent fibroblasts. p21Waf1/Cip1 promoter methylation directly represses its expression and blocks the radiation‐induced DNA damage‐signaling pathway by p53 in middle‐aged fibroblasts. More importantly, demethylation by 5‐aza‐CdR or DNMT1 RNA interference (RNAi) resulted in an increased p21Waf1/Cip1 level and premature senescence of middle‐aged fibroblasts demonstrated by cell growth arrest and high β‐Galactosidase expression. Our results suggest that p21Waf1/Cip1 but not p16INK4a is involved in the DNA methylation mediated aging process. p21Waf1/Cip1 promoter methylation may be a critical biological barrier to postpone the aging process. J. Cell. Biochem. 98: 1230–1248, 2006. © 2006 Wiley‐Liss, Inc.