bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of three 11p11.2 candidate liver tumor suppressors through analysis of known human genes
Authors: Ricketts Sharon L. , Carter Jennifer C. , Coleman William B.
Published: January 2003

We have previously mapped a liver tumor suppressor locus to human chromosome 11p11.2‐p12 using a functional model of tumor suppression. Using this model system, we have employed a candidate gene approach to identify potential liver tumor suppressor genes. Thirty‐eight known genes have been positioned in human 11p11.2‐p12 by the Human Genome Project. Here we show that four of these genes (guanine nucleotide binding protein gamma 3; mitochondrial carrier homolog 2; p53‐induced protein (PIG11), and pRDI‐BF1‐rIZ1 domain containing 11) localized to the minimal liver tumor suppressor region within 11p11.2‐p12. In fact, all of these genes mapped to human 11p11.2, allowing refinement of the liver tumor suppressor region to this cytogenetic band. Three of the four genes (mitochondrial carrier homolog 2, PIG11, and pRDI‐BF1‐rIZ1 domain containing 11) were uniformly expressed by an index panel of suppressed microcell hybrid cell lines, identifying them as candidate liver tumor suppressor genes. In a preliminary analysis of four human hepatocellular carcinoma cell lines (HepG2, Hep3B, SNU398, and SNU449), the transcript for PIG11 was lost or significantly decreased in two of these cell lines (HepG2 and Hep3B), suggesting the potential involvement of PIG11 in some human hepatocellular carcinomas. The results of this study extended our previous knowledge of genes located in the minimal liver tumor suppressor region of human 11p11.2 and identified several candidate liver tumor suppressor genes from this region. Further characterization of these candidates will provide new insight into the role of human 11p11.2 in the molecular pathogenesis of human liver cancer. © 2003 Wiley‐Liss, Inc.
High‐performance bismaleimide matrices: cure kinetics and mechanism
Authors: Rozenberg Boris A. , Dzhavadyan Emma A. , Morgan Roger , Shin Eugene
Published: January 2003

Kinetics and mechanism of equifunctional 4,4′‐(N,N′‐bismaleimide)‐diphenylmethane/2,2′‐diallyl‐bisphenol A (BMDM/DABPA) and model (phenylmaleimide/2,2′‐diallylphenol) (PMI/AP) systems have been studied in the temperature range 140–400 °C using IR‐, 1H‐ and ­13C‐NMR spectroscopy, gas chromatography–mass spectrometry GCMS), differential scanning calorimetry (DSC) and isothermal calorimetry. It was established that the cure mechanism consists a unique combination of step‐wise and chain polymerization and polycondensation reactions: step‐wise “ene” addition reaction of allyl group to maleimide one and consecutive/parallel chain polymerization of maleimide and propenyl groups generated by first reaction. The latter reaction is the main crosslinking reaction. The second source of crosslinking is a dehydration reaction of phenol groups that proceeds with mandatory participation as one of the component 1:1 adduct (product of step‐wise polymerization). Homopolymerization of maleimide groups proceeds autocatalytically under the action of free radicals generated by thermal decomposition of maleimide‐propenyl groups' donor–acceptor pairs. Steric hindrance in 2,2′‐diallyl‐bisphenol A prevents the reversible Diels–Alder reaction but this reaction proceeds in model systems. Some thermodynamic and kinetic parameters of the reactions are determined. Copyright © 2003 John Wiley & Sons, Ltd.
Polymer‐encapsulated engineered adult mesenchymal stem cells secrete exogenously regulated rhBMP‐2, and induce osteogenic and angiogenic tissue formation
Authors: Zilberman Yoram , Turgeman Gadi , Pelled Gadi , Xu Nong , Moutsatsos Ioannis K. , Hortelano Gonzalo , Gazit Dan
Published: January 2003

We have previously shown that genetically engineered adult mesenchymal stem cells (AMSCs) expressing recombinant human bone morphogenetic protein –2 (rhBMP‐2), under tet‐regulation, can induce bone formation and regeneration. We showed that these cells induce bone formation via paracrine and autocrine effect of the secreted rhBMP‐2 protein. To distinguish between these two effects, and to develop a platform for continuous delivery of rhBMP‐2 by engineered cells protected from the immune system, we have used hydrogel polymer (alginate) in order to encapsulate the AMSCs. Mixing of the cells with potassium alginate, followed by sedimentation in Ca2+ solution, results in polymerization of the alginate around the cells, forming microcapsules composed of a membrane allowing diffusion of small molecule and proteins. Encapsulated engineered AMSCs were able to survive inside the capsules in vitro and in vivo and secrete rhBMP‐2 under tet‐regulation. Transplantation of capsules both subcutaneously and into bone defect elicited physiological response manifested in osteogenic tissue composed of bone trabeculae and cartilage. Inside the capsules, engineered AMSCs differentiated to chondrocytes (autocrine effect), but not to osteoblasts. Newly formed bone has developed around the polymeric external layer without any observed intermediate layer of tissue. There was no evidence of immune response in the transplants area. We therefore conclude that engineered AMSCs can be efficiently encapsulated within polymeric alginate microcapsules, maintain viability, differentiate by autocrine effect, secrete rhBMP‐2 under exogenous regulation, and induce bone formation by paracrine effect, with no adverse or immune response to the transplanted capsules. Copyright © 2003 John Wiley & Sons, Ltd.
Some Remarks on Polymer Actuators (Résumé)
Authors: de Gennes Pierre‐Gilles
Published: January 2003

This paper is a summary of some curent research on soft actuators (such as nematic rubbers) and semi soft actuators (such as nafions).
Controlled uptake and release of proteins by polyelectrolyte gels
Authors: Zezin A. , Rogacheva V. , Skobeleva V. , Kabanov V.
Published: January 2003

The equilibrium and kinetics of proteins sorption and desorption by oppositely charged lightly crosslinked polyelectrolytes (#PE) were studied. The driving force of the sorption is provided by interpolyelectrolyte addition reaction (IPAR) between oppositely charged ionic groups of protein and #PE resulting in protein–#PE complex (#PPEC) formation. The capacity of different #PEs with respect to the proteins in neutral salt‐free aqueous solutions is rather high, exceeding that of the known heterogeneous crosslinked polyelectrolyte sorbents commonly used for protein sorption in practice. The dependence of the capacity of #PE on pH and the salt concentration in the environmental solution has been revealed and investigated. The equilibrium of IPAR is shifted to the original components under the corresponding pH shift or adding a simple salt. As a result the protein releases into the surrounding solution. The rate of protein uptake and release is also controlled by the pH or/and the ionic strength of the solution. The data obtained show that #PE can be used to design the crosslinked polyelectrolyte constructs for controlled uptake and release of proteins. Copyright © 2003 John Wiley & Sons, Ltd.
Study of water diffusion in polyacrylonitrile using IR fiber optic evanescent wave spectroscopy
Authors: Bormashenko Edward , Sheshnev Avigdor , Pogreb Roman , Sutovski Semion , Reichlin Yosef , Shulzinger Eugene , Katzir Abraham
Published: January 2003

This work presents a new approach to the investigation of mass transport processes in polymers. The coefficient of water diffusion in polyacrilonitrile was measured using fiber optic evanescent wave spectroscopy (FEWS). Unclad AgClBr fibers of 0.9 mm diameter were dip‐coated by PAN layers of 1–10 µm thickness. The transmission of the fibers in the mid‐IR was measured using a Fourier transform infrared (FTIR) spectrometer. The penetration of water into these layers gave rise to significant changes in the measured spectrum. These changes were used for diffusion studies in situ. The novel statistical approach to the analysis of spectra was developed for the purpose of calculating the diffusion coefficient, D, using spectral data. This analysis reveals the specific wavelengths which have been taken into account for the calculation of D. The FEWS procedure, combined with statistical treatment of the spectral data, offers a high accuracy in the calculation of parameters of diffusion. It must be emphasized that the cylindrical symmetry of our fibers renders them especially suitable for the diffusion study and allows us to obviate the difficulties caused by end effects. Copyright © 2003 John Wiley & Sons, Ltd.
Surrogate‐stoppered [2]rotaxanes: a new route to larger interlocked architectures
Authors: Rowan Stuart J. , Stoddart J. Fraser
Published: January 2003

A novel synthetic strategy for exchanging stoppers on rotaxanes, without them losing their integrity as interlocked molecules, is presented. The surrogate‐stoppered [2]rotaxane contains one inert stopper and a triphenylphosphonium group attached to a benzylic position as a second reactive stopper in the dumbbell‐shaped component which contains an ammonium (NH2+) ion recognition site, encircled by a crown ether (24C8 or 25C8) component. The strategy for exchanging stoppers relies upon the ability of a benzylic triphenylphosphonium function to undergo a Wittig reaction with a bulky aromatic aldehyde to form a ‘stilbenoid’ [2]rotaxane as a mixture of cis and trans isomers, without the occurrence of any dethreading of the crown ether ring component. The CC double bonds can then be hydrogenated, using Adams' catalyst, to afford a new covalently modified [2]rotaxane with two inert stoppers. Utilizing this strategy, larger interlocked molecular structures including a two‐stationed [2]rotaxane and a branched [4]rotaxane have been prepared. Furthermore, initial studies, aimed at using this methodology to gain access to poly[n]rotaxane architectures, are presented. Two ammonium ion/crown ether‐based [2]rotaxane monomers–each incorporating (i) a dumbbell‐shaped component, possessing the surrogate benzylic triphenylphosphonium stopper, and (ii) a crown ether ring component, bearing an aldehyde function on a fused benzenoid ring–undergo a sequence of Wittig reactions in which the surrogate benzylic triphenylphosphonium stopper is exchanged for a crown ether ring component either, (i) in the same rotaxane molecule, to give cyclic daisy‐chains by an intramolecular, chain‐terminating reaction or, (ii) in another rotaxane molecule, to give acyclic daisy chains by an intermolecular chain‐propagating reaction. Copyright © 2003 John Wiley & Sons, Ltd.
Double emulsions stabilized by new molecular recognition hybrids of natural polymers
Authors: Benichou Axel , Aserin Abraham , Garti Nissim
Published: January 2003

Water‐in‐oil‐in‐water (W/O/W) double emulsions with improved stability and less polydispersity in droplet size distribution were prepared using polyglycerol polyricinoleate (PGPR) as emulsifier in the inner aqueous phase and replacing the common nonionic hydrophilic monomeric emulsifiers by a “protein–polysaccharide hybrid” in the outer interface.

Amphiphilic macromolecular hybrids with specific interfacial recognition capabilities to be termed “biomacro‐molecular‐recognition hybrids” have been prepared in aqueous solution by interacting whey protein isolate (WPI) with hydrocolloids (xanthan gum, galactomannans) at selected pH and weight ratios. The binary aqueous mixtures do not coacervate or precipitate but form stable molecular adducts.

At pH lower than the isoelectric point of the protein (pH 4.6), the yield of encapsulation of glucose (a model marker) in the inner phase of the double emulsion is close to 95%. The emulsion droplets are stabilized by both steric and electrostatic contributions (zeta potential is close to +30 mV). Rheological measurements indicate that, at low pH, such systems behave as viscous ones with G″ (loss modulus) greater than G′ (storage modulus). When the pH is close or greater than the isoelectric point of the protein, the system exhibits a more pronounced elastic behavior (G′ < G″) that can explain the reduction in emulsification capabilities of such mixtures. In this case the yield of encapsulation is less than 10% and the double emulsion droplets are larger than 10 µm.

At pH ≤ 2, the adducts can efficiently stabilize double emulsions and serve as an efficient and thick barrier against the release of vitamin B1 entrapped in the core of the W/O/W double emulsions. The release of the vitamin was less than 18% after three weeks of storage at room temperature (against 100% of release at neutral pH). Copyright © 2003 John Wiley & Sons, Ltd.
Networks for recognition of biomolecules: molecular imprinting and micropatterning poly(ethylene glycol)‐ Containing films
Authors: Byrne Mark E. , Oral Ebru , Zachary Hilt J. , Peppas Nicholas A.
Published: January 2003

Engineering the molecular design of biomaterials by controlling recognition and specificity is the first step in coordinating and duplicating complex biological and physiological processes. Studies of protein binding domains reveal molecular architectures with specific chemical moieties that provide a framework for selective recognition of target biomolecules in aqueous environment. By matching functionality and positioning of chemical residues, we have been successful in designing biomimetic polymer networks that specifically bind biomolecules in aqueous environments. Our work addresses the preparation, behavior, and dynamics of the three‐dimensional structure of biomimetic polymers for selective recognition via non‐covalent complexation. In particular, the synthesis and characterization of recognitive gels for the macromolecular recognition of D‐glucose is highlighted. Novel copolymer networks containing poly(ethylene glycol) (PEG) and functional monomers such as acrylic acid, 2‐hydroxyethyl methacrylate, and acrylamide were synthesized in dimethyl sulfoxide (polar, aprotic solvent) and water (polar, protic solvent) via UV‐free radical polymerization. Polymers were characterized by single and competitive equilibrium and kinetic binding studies, single and competitive fluorescent and confocal microscopy studies, dynamic network swelling studies, and ATR‐FTIR. Results qualitatively and quantitatively demonstrate effective glucose‐binding polymers in aqueous solvent. Owing to the presence of template, the imprinting process resulted in a more macroporous structure as exhibited by dynamic swelling experiments and confocal microscopy. Polymerization kinetic studies suggest that the template molecule has more than a dilution effect on the polymerization, and the effect of the template is related strongly to the rate of propagation. In addition, PEG containing networks were micropatterned to fabricate microstructures, which would be the basis for micro‐diagnostic and tissue engineering devices. Utilizing photolithography techniques, polymer micropatterns of a variety of shapes and dimensions have been created on polymer and silicon substrates using UV free‐radical polymerizations with strict spatial control. Micropatterns were characterized using optical microscopy, SEM, and profilometry. The processes and analytical techniques presented are applicable to other stimuli‐sensitive and recognitive networks for biomolecules, in which hydrogen bonding, hydrophobic, or ionic contributions will direct recognition. Further developments are expected to have direct impact on applications such as analyte controlled and modulated drug and protein delivery, drug and biological elimination, drug targeting, tissue engineering, and micro‐ or nano‐devices. This work is supported by NSF Grant DGE‐99‐72770. Copyright © 2003 John Wiley & Sons, Ltd.
Enzymatically controlled responsive drug delivery systems
Authors: Goldbart Riki , Traitel Tamar , Lapidot Smadar A. , Kost Joseph
Published: January 2003

This paper discusses two approaches for the preparation of enzymatically controlled drug delivery systems: (i) a calcium‐responsive biodegradable drug delivery system based on a mixture of starch with HPMC (hydroxypropyl methyl cellulose ether) (biodegradable) and the starch hydrolytic enzyme, α‐amylase, in its non‐active form; (ii) a glucose‐responsive insulin delivery system based on the hydrogel poly(2‐hydroxyethyl methacrylate‐co‐N,N‐dimethylaminoethyl methacrylate), with entrapped glucose oxidase, catalase and insulin. In both systems, the sensitivity to a trigger molecule (calcium or glucose) was achieved by the incorporation of a specific enzyme that reacts with the trigger molecule. Based on these interactions we propose two different enzyme‐controlled drug release mechanisms for responsive drug delivery systems. Copyright © 2003 John Wiley & Sons, Ltd.
Differential scanning calorimetry studies on poly(ethylene glycol) with different molecular weights for thermal energy storage materials
Authors: Pielichowski Krzysztof , Flejtuch Kinga
Published: January 2003

Melting and crystallization behaviour of poly(ethylene glycol) (PEG) with different molecular weights (from 1000 to 35 000) and chosen blends of PEG is investigated by means of differential scanning calorimetry (DSC) operating in dynamic mode at different heating rates. The influence of the molecular weight of PEG on its melting point and enthalpy of fusion is evaluated; from the DSC data the degree of crystallinity is calculated–it is found that there is an increased tendency of higher‐molecular‐weight PEGs towards the formation of crystalline phase owing to their lower segmental mobility and more convenient geometrical alignment. During the freezing cycle, an increase in the molecular weight of PEG causes an increase in the solidification temperature and heat of crystallization. Thermal transition data are supplemented by optical microscopy–numerous small sphere‐shaped crystalline structures are observed to join together and impinge on their neighbours, forming eventually a multilayered lamellar texture. By implementing second polymeric component the polydispersity of the system increases, thus lowering the crystallization degree during preparation phase. It influences also the course of solidification by lowering the crystallization temperature, Tc. An additional effect observed in the case of the blend's freezing is associated with larger supercooling, probably due to morphological constraints and entanglements in interlamellar regions. The possible advantage of using PEG blends to replace pure components is connected with the possibility of changing the temperature range and heat associated with melting/freezing. Copyright © 2003 John Wiley & Sons, Ltd.
New types of microspheres and microsphere‐related materials for medical diagnostics
Authors: Slomkowski Stanislaw , Basinska Teresa , Miksa Beata
Published: January 2003

Polymer microspheres are used in diagnostics as “reagents” and as elements of diagnostic devices. In this paper we compare properties of microspheres with aldehyde, carboxyl and hydroxyl groups in their surface layers. Microspheres with aldehyde groups were obtained by radical emulsion copolymerization of styrene and acrolein and in sequential redox polymerization of pyrrole followed with radical polymerization of acrolein. Microspheres with hydroxyl groups were synthesized by radical emulsion copolymerization of styrene and α‐t‐butoxy‐ω‐vinylbenzyl‐polyglycidol macromonomer.­Microspheres with hydroxyl and carboxyl groups were synthesized by radical emulsion copolymerization of methylmethacrylate, acrylic acid and 2‐hydroxyethylmethacrylate. X‐Ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) revealed that microspheres had the core–shell morphology with surface layers enriched in polymeric units with reactive groups. The above mentioned microspheres were used as supports for adsorption and covalent immobilization of human and animal proteins–human serum albumin (HSA), gamma globulins (γG; human, rabbit and goat), human fibrinogen (Fb), and enzymes: glucose oxidase (GOD) and urease (Urs). The applicability of microspheres with attached antigens and/or antibodies (γG) for turbidimetric aggregation tests and for a new type of test based on changes of electrophoretic mobility of microspheres is discussed. Potential applications of microspheres with immobilized enzymes for the construction of biosensors are described. Copyright © 2003 John Wiley & Sons, Ltd.
Discriminative validity of the behavior assessment system for children‐parent rating scales in children with recurrent abdominal pain and matched controls
Authors: ROBINS PAUL M. , SCHOFF KRISTIN M. , GLUTTING JOSEPH J. , ABELKOP A. SHAYNE
Published: January 2003

Examined discriminative validity of the Parent Rating Scale (PRS) of the Behavior Assessment System for Children (BASC; Reynolds & Kamphaus, 1992, Circle Pines, MN: American Guidance Services). Two groups were compared: a cohort with recurrent abdominal pain (RAP) (n= 49) and children from the BASC‐PRS standardization sample (n = 49) matched on the background characteristics of age, race/ethnicity, and gender. A multivariate, two‐group discriminant function analysis was used to compare groups across standard scores from the nine clinical scales of the PRS. Results demonstrated that children with RAP could be differentiated (Wilks λ = .642, F = 6.45, df (9, 88), p < .001), and demonstrated higher scores on the Somatization, Depression, Anxiety, Attention Problems, and Withdrawal scales. Subsequent jackknifed classification analysis, diagnostic efficiency statistics, and an odds ratio for the classification analysis added to the overall validity of results. The practical utility of the BASC‐PRS is further supported in light of expanding roles for school psychologists in the assessment and treatment of children with health problems. © 2003 Wiley Periodicals, Inc. Psychol Schs 40: 145–154, 2003.
Comparative properties of a three‐dimensional model of Plasmodium falciparum ornithine decarboxylase
Authors: Birkholtz L. , Joubert F. , Neitz A.W.H. , Louw A.I.
Published: January 2003

The ornithine decarboxylase (ODC) component of the bifunctional S‐adenosylmethionine decarboxylase/ornithine decarboxylase enzyme (PfAdoMetDC‐ODC) of Plasmodium falciparum was modeled on the crystal structure of the Trypanosoma brucei enzyme. The homology model predicts a doughnut‐shaped active homodimer that associates in a head‐to‐tail manner. The monomers contain two distinct domains, an N‐terminal α/β‐barrel and a C‐terminal modified Greek‐key domain. These domains are structurally conserved between eukaryotic ODC enzymes and are preserved in distant analogs such as alanine racemase and triosephosphate isomerase‐like proteins. Superimposition of the PfODC model on the crystal structure of the human enzyme indicates a significant degree of deviation in the carbon α‐backbone of the solvent accessible loops. The surface locality of the ab initio modeled 38 amino acid parasite‐specific insert suggests a role in the stabilization of the large bifunctional protein complex. The active site pockets of PfODC at the interface between the monomers appear to be conserved regarding the binding sites of the cofactor and substrate, but each contains five additional malaria‐specific residues. The predicted PfODC homology model is consistent with mutagenesis results and biochemical studies concerning the active site residues and areas involved in stabilizing the dimeric form of the protein. Two competitive inhibitors of PfODC could be shown to interact with several parasite‐specific residues in comparison with their interaction with the human ODC. The PfODC homology model contributes toward a structure‐based approach for the design of novel malaria‐specific inhibitors. Proteins 2003;50:464–473. © 2003 Wiley‐Liss, Inc.
Effect of alcohol extract of Achyranthes aspera Linn. on acute and subacute inflammation
Authors: Vetrichelvan T. , Jegadeesan M.
Published: January 2003

The antiinflammatory activity of an alcohol extract of Achyranthes aspera was tested on carrageenin‐induced hind paw oedema and cotton pellet granuloma models in albino male rats. The paw volume was measured plethysmometrically at 0, 1, 2, 3, 4 and 5 h. In the subacute model cotton pellet granuloma was produced by implantation of 50 ± 1 mg sterile cotton in the axilla under ether anaesthesia. The animals were fed with an alcohol extract at various dose levels (125, 250, 375 and 500 mg/kg). Diclofenac sodium was used as a standard drug. The alcohol extract (375 and 500 mg/kg) showed the maximum inhibition of oedema of 65.38% and 72.37% at the end of 3 h with carrageenin‐induced rat paw oedema, respectively. Using a chronic test, the extract exhibited a 40.03% and 45.32% reduction in granuloma weight. Copyright © 2003 John Wiley & Sons, Ltd.
Prevention of diet‐induced type 2 diabetes in the C57BL/6J mouse model by an antidiabetic herbal formula
Authors: Huo Yushu , Winters Wendell D. , Yao Da‐lin
Published: January 2003

Significant positive effects of an antidiabetes herbal formula (ADHF) on the prevention of progressive diet‐induced type 2 diabetes (NIDDM) in the well recognized C57BL/6J mouse model were demonstrated. The results of the present studies confirm that C57BL/6J mice, through a genetic predisposition, developed NIDDM‐like symptoms on a regular schedule when fed solely on a diabetes induction diet containing high fat, high simple carbohydrate and low fibre. Blood glucose levels consistent with type 2 diabetes were detected after 8 weeks on this induction diet. In contrast, no members of the prevention study groups of C57BL/6J mice, which had ADHF mixed into their diabetes induction diet, developed progressive evidence of NIDDM‐like symptoms. Specific parameters observed to be significantly reduced in mice in the prevention diet groups fed ADHF mixed into the diabetes induction diet compared with the diabetes positive control groups fed diabetes induction diet only were clinical signs, blood glucose and serum insulin levels, insulin resistance and histopathological changes in major organs. This is the first report to our knowledge to show in vivo evidence for the successful prevention of progressive NIDDM‐like symptoms by the addition of an anti‐diabetes herbal formula to a effective diabetes induction diet. Copyright © 2003 John Wiley & Sons, Ltd.
Biological activities of synthetic saponins and cardiac glycosides
Authors: Takechi Masayuki , Doi Kyoko , Wakayama Yoshiki
Published: January 2003

Comparisons of the biological activities of diosgenyl (DIO) β‐D‐xylopyranosyl‐ (1 → 2)‐α‐D‐glucopyranoside (2DXα) and β‐D‐glucopyranosyl‐ (1 → 3)‐β‐D‐glucopyranoside (3GLβ) or methyl glycyrrhetinate (GAM) 2DXα and 3GLβ with those of the other DIO‐ or GAM‐ glycosides confirmed our assumption that both haemolytic and antifungal activities of DIO‐glycosides (steroid saponins) generally parallel each other, while almost all haemolytic GAM‐glycosides (triterpenoid saponins) have no antifungal activity. By comparisons of digitoxigenyl (DIG) 2DXα, β‐D‐xylopyranosyl‐ (1 → 2)‐β‐D‐glucopyranoside (2DXβ) and 3GLβ with the other DIG‐glycosides, the previous supposition on DIG‐diglycosides (cardiac diglycosides) has been developed into the assumption that those having a (1 → 4), (1 → 3) or (1 → 2)β sugar linkage show stronger anti‐ATPase and antiviral activities than those with a (1 → 6) or (1 → 2)α linkage. Copyright © 2003 John Wiley & Sons, Ltd.
The effect of a water extract and anthocyanins of hibiscus sabdariffa L. on paracetamol‐induced hepatoxicity in rats
Authors: Ali B. H. , Mousa H. M. , El‐Mougy S.
Published: January 2003

We investigated the effect of the water extract of the dried flowers of Hibiscus sabdariffa L. and Hibiscus anthocyanins (HAs) (which are a group of natural pigments occurring in the dried calyx of H. sabdariffa) on paracetamol‐induced hepatotoxicity in rats. The water extract was given in lieu of drinking water for 2, 3 or 4 consecutive weeks, and the HAs were given orally at doses of 50, 100 and 200 mg/Kg for five consecutive days. Paracetamol was given orally at a dose of 700 mg/Kg to induce hepatotoxicity at the end of the water extract and HAs treatments. Six hours thereafter the rats were killed and their liver function evaluated biochemically and histologically. Given for 4 weeks (but not for 2 or 3 weeks) the extract significantly improved some of the liver function tests evaluated, but did not alter the histology of the paracetamol‐treated rats or the pentobarbitone‐induced sleeping time. At a dose of 200 mg/Kg, the hepatic histology and the biochemical indices of liver damage were restored to normal. Lower does were ineffective. Pending more evaluation for safety and efficacy, the HAs can potentially be used in mitigating paracetamol‐induced hepatotoxicity. Copyright © 2003 John Wiley & Sons, Ltd.
The comparative effect of novel Pelargonium essential oils and their corresponding hydrosols as antimicrobial agents in a model food system
Authors: Lis‐Balchin M. , Steyrl H. , Krenn E.
Published: January 2003

Essential oils and their corresponding hydrosols, obtained after distillation of various scented Pelargonium (Geraniaceae) leaves were assessed for their antimicrobial activity in a model food system. Both the essential oils and hydrosols were used at 1000 ppm in broccoli soup, previously inoculated with Enterobacter aerogenes (at 105 cfu g−1) and Staphylococcus aureus (at 104 cfu g−1). The results showed a complete inhibition of S. aureus in the broccoli soup by the essential oils of ‘Sweet Mimosa’, ‘Mabel Grey’, P. graveolens, ‘Atomic Snowflake’, ‘Royal Oak’, ‘Attar of Roses’ and a lesser effect by ‘Chocolate Peppermint’ and ‘Clorinda’; the hydrosols, however, had a potentiating effect on the bacterial population in the food. Both extracts showed a complete inhibition of S. aureus in the Maximum Recovery Diluent (MRD). Antibacterial activity against E. aerogenes in the broccoli soup was generally very much reduced: only the essential oil of ‘Mabel Grey’ showed complete inhibition and virtually no reductions in colonies were seen with the other essential oils; the hydrosols again caused an increase in bacterial colonies. All the essential oils, bar Chocolate Peppermint showed complete inhibition of E. aerogenes in MRD, but the hydrosols showed no effect. The results strongly suggest that the residual hydrosols from distillation of these plant essential oils have no potential as antibacterial agents in foods, in contrast to most of the essential oils, which show potential against some micro‐organisms, but only in some food systems. The problem of food component interference and its possible management is discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Downregulation of hepatitis B surface antigen expression in human hepatocellular carcinoma cell lines by HD‐03, a polyherbal formulation
Authors: Yeh S. F. , Gupta Monika , Sarma D. N. K. , Mitra S. K.
Published: January 2003

Hepatitis B virus is associated with chronic or acute liver diseases and with hepatocellular carcinoma. In the present study, we examined the activity of HD‐03, a polyherbal formulation, on two hepatitis B surface antigen (HBsAg) expressing human hepatocellular carcinoma cell lines, PLC/PRF/5 and HepG2/A2. We observed that HD‐03 downregulates HBsAg expression from these cell lines. Our studies have also shown that this effect is neither due to cytotoxicity on the cell lines nor due to blockade of the release of the antigen from the cells nor due to binding of the substance with the antigen. The possible mode of its antiviral activity is explained. Copyright © 2003 John Wiley & Sons, Ltd.
Design, implementation and verification through a real‐time test‐bed of a multi‐rate CDMA adaptive interference mitigation receiver for satellite communication
Authors: Fanucci Luca , De Gaudenzi Riccardo , Giannetti Filippo , Luise Marco , Rovini Massimo
Published: January 2003

This paper presents the design, the implementation, and the main performance results of a multi‐rate code division multiple access (CDMA) interference mitigation receiver for satellite communication. Such activity was performed within a research project supported by the European Space Agency (ESA), whose aim was to demonstrate the suitability of the linear adaptive interference mitigation detector (IMD) named extended complex‐valued blind anchored interference‐mitigating detector (EC‐BAID) for single‐user detection of a CDMA signal in third‐generation (3G) satellite networks. Such a detector, which exhibits a remarkable robustness to multiple access interference, operates in a blind mode, i.e. it only requires knowledge of the timing of the wanted user's signature code, and is therefore very well suited for integration into handheld user terminals.

Experimental results in terms of bit error rate with respect to the theoretical behaviour were derived through a specifically developed test bed. Signal plus multiple access interference generation is performed via a computer‐controlled arbitrary waveform generator, followed by frequency up‐conversion to the standard intermediate frequency of 70 MHz. Additive white Gaussian noise is then injected with the aid of a precision noise generator. The core of the test bed is a flexible digital receiver prototype featuring the EC‐BAID detector plus all functions ancillary to IMD (multi‐rate front‐end, automatic gain control, code acquisition and tracking, carrier synchronization, etc.). Those functions were implemented through careful mixing of different technologies: field programmable gate arrays (FPGAs) for computing‐intensive signal processing functions, digital signal processor (DSP) for housekeeping and monitoring, and application specific integrated circuit (ASIC) for adaptive IMD. The adopted design flow also allows an easy re‐use of the prototype architecture to come to an overall integration of the receiver into a single ASIC with modest complexity and power consumption increase with respect to a conventional detector. Copyright © 2003 John Wiley & Sons, Ltd.
Regulation of CRE‐mediated transcription in mouse brain by amphetamine
Authors: Shaw‐Lutchman Tamara Z. , Impey Soren , Storm Daniel , Nestler Eric J.
Published: January 2003

Previous work has demonstrated that acute and chronic administration of amphetamine causes phosphorylation of the transcription factor CREB, the cAMP response element (CRE) binding protein, in striatum, a brain region important for the behavioral actions of the drug. To determine whether such phosphorylation is associated with changes in CREB transcriptional activity, we mapped β‐galactosidase (β‐gal) expression in a CRE‐LacZ transgenic mouse, in which the β‐gal reporter is downstream of CRE sequences, following acute or chronic amphetamine administration. We found that acute amphetamine induced β‐gal expression in a relatively small number of brain regions, including nucleus accumbens (ventral striatum), amygdala, ventral tegmental area, and locus coeruleus. Chronic amphetamine generally produced greater changes in CRE‐mediated transcription in most brain regions and induced CRE‐transcription in several regions unaffected by acute drug exposure. Interestingly, amphetamine regulation of CRE activity differed dramatically between males and females. In nucleus accumbens, β‐gal expression colocalized predominantly with dynorphinergic neurons after acute amphetamine administration, while chronic administration induced β‐gal expression in both dynorphinergic and enkephalinergic neurons. In ventral tegmental area, acute and chronic amphetamine induced β‐gal expression mainly in dopaminergic neurons, while induction in the locus coeruleus occurred mainly in nonnoradrenergic neurons. This study identifies several brain regions where CRE‐mediated transcription may play a key role in the development of neuronal plasticity associated with amphetamine administration. Synapse 48:10–17, 2003. © 2003 Wiley‐Liss, Inc.
Electrophysiological and pharmacological characteristics of nigral dopaminergic neurons in the conscious, head‐restrained rat
Authors: Fà Mauro , Mereu Giampaolo , Ghiglieri Veronica , Meloni Alessandra , Salis Paola , Gessa Gian Luigi
Published: January 2003

Extracellular single‐unit recordings of nigral dopamine (DA) neurons were obtained from conscious rats habituated to having their body suspended in a cloth jacket and their head immobilized in the stereotaxic frame by means of a “restraining platform” permanently fixed to the skull. The electrophysiological characteristics of DA neurons from head‐restrained rats and their responses to apomorphine and haloperidol were compared with single‐unit recordings obtained from rats lightly and deeply anesthetized with chloral hydrate and from mesencephalic slices. Head‐restrained rats showed a higher number of spontaneously active DA neurons and a higher percentage of bursting neurons than lightly and deeply anesthetized rats. Indeed, bursting activity was rare in deeply anesthetized rats and was totally absent in slices. Haloperidol was more potent and effective in stimulating the firing rate and bursting activity in head‐restrained than in lightly anesthetized rats, while it was virtually ineffective in deeply anesthetized rats and totally ineffective in slices. On the other hand, DA neurons in head‐restrained rats showed the same average firing rate as DA neurons in lightly and deeply anesthetized rats and in slices. The potency of apomorphine in inhibiting the firing rate, and that of haloperidol in reversing apomorphine effect, did not vary among the different in vivo preparations. The results suggest that chloral hydrate anesthesia blunts or suppresses not only the excitatory inputs which normally sustain the number of spontaneously active DA neurons and their bursting activity, but also the feedback excitation of DA neurons following haloperidol‐induced D2 receptor blockade. On the other hand, chloral hydrate anesthesia modifies neither D2 autoreceptor sensitivity to apomorphine and haloperidol nor the automatic genesis of action potentials. The head‐restrained rat appears to be an important model for studies into the pharmacology and physiology of DA neurons. Synapse 48:1–9, 2003. © 2003 Wiley‐Liss, Inc.
Graphical analysis of 2‐[18F]FA binding to nicotinic acetylcholine receptors in rhesus monkey brain
Authors: Chefer Svetlana I. , London Edythe D. , Koren Andrei O. , Pavlova Olga A. , Kurian Varughese , Kimes Alane S. , Horti Andrew G. , Mukhin Alexey G.
Published: January 2003

External imaging of nicotinic acetylcholine receptors (nAChRs) using techniques such as PET would help to clarify the roles of these receptors in the physiology and pathology of brain function. Here we report the results of quantitative PET studies of cerebral nAChRs with 2‐[18F]fluoro‐A‐85380 (2‐[18F]FA) in rhesus monkeys. Data from dynamic PET scans were analyzed using graphical methods. Binding potential (BP) values of 2.0, 0.4, 0.3, and 0.03 observed in the thalamus (Th), cortex (Cx), striatum (Str), and cerebellum (Cb), respectively, were consistent with the pattern of α4β2 nAChR distribution in monkey brain. The high value of 2‐[18F]FA‐specific binding in the rhesus monkey Th and low level of that in Cb compared with nonspecific accumulation of radioactivity in these structures allowed use of Cb as a reference region for calculation of BP and volume of distribution of specific binding (VDsb) in Th by graphical methods, both with and without the plasma input function. In contrast, estimation of 2‐[18F]FA specific binding in low‐receptor‐density regions such as Cx and Str required assessment of nondisplaceable volume of distribution (VDnd) in a separate study and measurement of nonmetabolized radioligand concentrations in the plasma. For accurate quantitation of 2‐[18F]FA‐specific binding by graphical analysis, PET studies should last up to 7 h due to the slow kinetics of 2‐[18F]FA brain distribution. Further, to avoid substantial underestimation in measured BP values the doses of administered 2‐[18F]FA should not exceed 0.1 nmol/kg body weight. The findings suggest that 2‐[18F]FA is a promising ligand for quantitation of nAChRs in human brain. Synapse 48:25–34, 2003. Published 2003 Wiley‐Liss, Inc.
Role of phosphatidylinositol 3‐phosphate in formation of forespore membrane in Schizosaccharomyces pombe
Authors: Onishi Masayuki , Koga Takako , Morita Rika , Nakamura Yoko , Nakamura Taro , Shimoda Chikashi , Takegawa Kaoru , Hirata Aiko , Fukui Yasuhisa
Published: January 2003

Phosphatidylinositol (PI) 3‐kinase (encoded by the pik3+ gene) in Schizosaccharomyces pombe has been identified as a homologue of VPS34p, a protein required for proper vesicular protein sorting. The clone defective in this protein carries enlarged vacuoles and exhibits sensitivity to high temperature or high ion concentration. The effect of disruption of pik3+ on sporulation of Sz. pombe was examined. The diploid cells underwent G1 arrest and meiosis. However, the spores formed by the Δpik3 cells were not viable. Electron‐microscopic analysis revealed that the growth of the forespore membrane of Δpik3 cells was not correctly orientated, failing to engulf the nucleus or forming extremely small spores, as was confirmed by the use of Spo3p–GFP and GFP–Psy1p, which are markers of the forespore membrane. The coating materials found along the forespore membrane of the wild‐type were greatly reduced in these cells. PI 3‐P, the product of Pik3p, was detected on the forespore membrane, suggesting that PI 3‐P‐dependent vesicle transport may take place in formation of the forespore membrane. Misshaped forespore membrane, accumulation of vesicles, formation of small non‐viable spores, and suppression by over expression of Psy1p were the phenotypes commonly seen in Δpik3 and Δspo3 cells, suggesting a relationship between the functions of Pik3p and Spo3p in formation of the forespore membrane in Sz. pombe. Copyright © 2003 John Wiley & Sons, Ltd.
Transcription patterns of PMA1 and PMA2 genes and activity of plasma membrane H+‐ATPase in Saccharomyces cerevisiae during diauxic growth and stationary phase
Authors: Fernandes Alexandra R. , Sá‐Correia Isabel
Published: January 2003

PMA1 and PMA2 genes encode Saccharomyces cerevisiae plasma membrane H+‐ATPase (PM‐H+‐ATPase), an enzyme with critical physiological roles both in the absence or presence of environmental stress. The two PM‐H+‐ATPase isoforms differ in their biochemical characteristics but, under all the growth conditions that were examined so far, PMA2 expression is negligible and Pma1p accounts for practically the totality of cell PM‐H+‐ATPase activity. In the present work, we have compared gene expression levels and activity of this proton pump in yeast cells cultivated under fermentative or respiratory growth and under carbon starvation. The expression levels of both PMA1 and PMA2 genes were consistently higher (2.5–4.5‐fold) in cells cultivated under respiratory metabolism (in ethanol‐based medium or after the diauxic shift), than in cells cultivated under fermentative metabolism (during the full period of growth in a medium where glucose is not the limiting nutrient or during the first period of diauxic growth in low‐glucose‐based medium). The moderate upregulation of PMA1 and PMA2 transcription in cells grown on ethanol compared with those grown on glucose was reflected in the increased content and activity of PM‐H+‐ATPase. In diauxic growth, during transition to stationary phase after ethanol depletion, a further strong activation (eight‐fold) of PMA2 gene transcription was observed. Although PMA2 transcription still remains quite below (20‐fold) PMA1 transcription, this is the first environmental condition, identified so far, that leads to a significant PMA2 expression, suggesting that this PM‐H+‐ATPase isoform may play some role during carbon starvation. Copyright © 2003 John Wiley & Sons, Ltd.
Transcriptome characterization of the dimorphic and pathogenic fungus Paracoccidioides brasiliensis by EST analysis
Authors: Felipe M. S. S. , Andrade R. V. , Petrofeza S. S. , Maranhão A. Q. , Torres F. A. G. , Albuquerque P. , Arraes F. B. M. , Arruda M. , Azevedo M. O. , Baptista A. J. , Bataus L. A. M. , Borges C. L. , Campos E. G. , Cruz M. R. , Daher B. S. , Dantas A. , Ferreira M. A. S. V. , Ghil G. V. , Jesuino R. S. A. , Kyaw C. M. , Leitão L. , Martins C. R. , Moraes L. M. P. , Neves E. O. , Nicola A. M. , Alves E. S. , Parente J. A. , Pereira M. , Poças‐Fonseca M. J. , Resende R. , Ribeiro B. M. , Saldanha R. R. , Santos S. C. , Silva‐Pereira I. , Silva M. A. S. , Silveira E. , Simões I. C. , Soares R. B. A. , Souza D. P. , De‐Souza M. T. , Andrade E. V. , Xavier M. A. S. , Veiga H. P. , Venancio E. J. , Carvalho M. J. A. , Oliveira A. G. , Inoue M. K. , Almeida N. F. , Walter M. E. M. T. , Soares C. M. A. , Brígido M. M.
Published: January 2003

Paracoccidioides brasiliensis is a pathogenic fungus that undergoes a temperature‐dependent cell morphology change from mycelium (22° C) to yeast (36° C). It is assumed that this morphological transition correlates with the infection of the human host. Our goal was to identify genes expressed in the mycelium (M) and yeast (Y) forms by EST sequencing in order to generate a partial map of the fungus transcriptome. Individual EST sequences were clustered by the CAP3 program and annotated using Blastx similarity analysis and InterPro Scan. Three different databases, GenBank nr, COG (clusters of orthologous groups) and GO (gene ontology) were used for annotation. A total of 3938 (Y = 1654 and M = 2274) ESTs were sequenced and clustered into 597 contigs and 1563 singlets, making up a total of 2160 genes, which possibly represent one‐quarter of the complete gene repertoire in P. brasiliensis. From this total, 1040 were successfully annotated and 894 could be classified in 18 functional COG categories as follows: cellular metabolism (44%); information storage and processing (25%); cellular processes—cell division, posttranslational modifications, among others (19%); and genes of unknown functions (12%). Computer analysis enabled us to identify some genes potentially involved in the dimorphic transition and drug resistance. Furthermore, computer subtraction analysis revealed several genes possibly expressed in stage‐specific forms of P. brasiliensis. Further analysis of these genes may provide new insights into the pathology and differentiation of P. brasiliensis. All EST sequences have been deposited in GenBank under Accession Nos CA580326–CA584263. Copyright © 2003 John Wiley & Sons, Ltd.
Structural characterization of the O‐chain polysaccharide isolated from Bordetella avium ATCC 5086: variation on a theme
Authors: Larocque Suzon , Brisson Jean-Robert , Thérisod Hélène , Perry Malcolm B , Caroff Martine
Published: January 2003

The O‐chain polysaccharide (O‐PS) of Bordetella avium was isolated from the lipopolysaccharide by mild acid hydrolysis to remove the lipid A, followed by hydrofluorolysis to remove the lipopolysaccharide core oligosaccharide leaving a residual O‐PS for structural analysis. High resolution 1H and 13C NMR and MALDI studies showed the O‐chain to be a polymer composed of 1,4‐linked 2‐acetamidino‐3‐[3‐hydroxybutanamido]‐2,3‐dideoxy‐β‐D‐glucopyranosyluronic acid residues.
BCR‐ABL binds to IRS‐1 and IRS‐1 phosphorylation is inhibited by imatinib in K562 cells
Authors: Traina Fabı́ola , Carvalheira José Barreto C , Saad Mario J.A , Costa Fernando F , Saad Sara T.O
Published: January 2003

In the present study we used K562 cells to demonstrate that insulin receptor substrate 1 (IRS‐1) is expressed and constitutively phosphorylated in BCR‐ABL+ cells. We observed association between BCR‐ABL/IRS‐1, IRS‐1/phosphoinositide 3′‐kinase (PI3‐kinase), and IRS‐1/Grb2 in the K562 cell line. Our findings demonstrate that imatinib treatment resulted in marked attenuation of BCR‐ABL/IRS‐1 association and of IRS‐1‐stimulated PI3‐kinase activity in K562 cells. We concluded that the IRS‐1 protein is involved in the signalling pathway of the BCR‐ABL tyrosine kinase.