bluuebunny/crossref_metadata_2025 huggingface dataset:
The regulatory role of dietary ω‐3 essential fatty acids on oxidant/antioxidant balance in rat hippocampus
Authors: Sarsimaz Mustafa , Songur Ahmet , Kus Ilter , Ozyurt Birsen , Gulec Mukaddes , Sogut Sadik , Ilhan Atilla , Akyol Omer
Published: October 2003

Omega‐3 essential fatty acids (ω‐3 EFA) contains eicosapentaenoic acid and docosahexaenoic acid (DHA). DHA is one of the building structures of membrane phospholipids of brain and necessary for continuity of neuronal functions. ω‐3 EFA has been suggested to be protective against neuropsychiatric disorders including schizophrenia. This study proposed to assess the changes in superoxide dismutase (SOD), xanthine oxidase (XO), malondialdehyde (MDA), and nitric oxide (NO) in the hippocampus of rats fed with ω‐3 diet (0.4 g/kg/day) for 30 days. Eight control rats and nine rats fed with ω‐3 EFA were decapitated under ether anesthesia, and hippocampus was removed immediately.

Rats treated with ω‐3 EFA had significatly lower XO activity (p<0.002) and NO level (p<0.0001) whereas higher SOD activity (p<0.002) and MDA levels (p<0.019) than the control rats. These results suggest that the dietary ω‐3 EFA may act on the oxidant/antioxidant parameters in hippocampus. On the other hand, although the mechanism is not clear, ω‐3 EFA may enhance one of the most important antioxidant enzymes, SOD. Further studies are needed to clarify the molecular mechanism involved and the therapeutic implication of ω‐3 EFA in animal psychosis models and clinical studies.
The role of L‐type calcium channels in spinal reflex responses in cats
Authors: Taşçi Niyazi , Genç Osman , Bağırıcı Faruk
Published: October 2003

We have investigated the effects of verapamil, which blocks L‐type calcium channels on spinal monosynaptic reflexes in spinalized cats. Adult cats (n=10) weighing 1.5–3 kg were anaesthetized with ketamine (50 mg/kg, IM) and the ventral and dorsal roots of segment L5‐S2 were isolated after laminectomy. The lateral and medial gastrocnemius nerves were placed on an Ag‐AgCl wire electrode for stimulation through an isolation unit. The reflex potentials were recorded from the ipsilateral L7 ventral root. The intraperitoneal administration of verapamil significantly decreased the amplitude of the reflex response (P<0.05). Our results suggest that L‐type calcium channels in the spinal cord may play an important role in regulating the reflex response.
Nuclear β‐catenin is a molecular feature of type I endometrial carcinoma
Authors: Scholten AN , Creutzberg CL , van den Broek LJCM , Noordijk EM , Smit VTHBM
Published: October 2003

Two types of endometrial carcinoma can be distinguished: type I tumours, which are oestrogen‐related and are typically low‐grade endometrioid carcinomas; and type II tumours, which are unrelated to oestrogen stimulation and are often non‐endometrioid carcinomas. The molecular abnormalities involved in carcinogenesis appear to be different for these tumour types. The aim of this study was to test the hypothesis that an abnormality in the Wnt/β‐catenin signalling pathway is a molecular feature of type I endometrial carcinoma. This study investigated nuclear β‐catenin by immunohistochemistry in 233 endometrial carcinomas and analysed its correlation with several immunohistochemical, histological, and clinical parameters, such as proliferation rate (Ki‐67), expression of oestrogen and progesterone receptors, and survival. Nuclear β‐catenin expression was observed in 39 cases (16%). All tumours expressing nuclear β‐catenin were endometrioid adenocarcinomas, were significantly better differentiated, and were more often hormone receptor‐positive than tumours without nuclear β‐catenin. No correlation with proliferation rate was found. It was found that several features of type I endometrial carcinoma occur significantly more often in tumours expressing nuclear β‐catenin, suggesting that an abnormality in the Wnt/β‐catenin signalling pathway, resulting in nuclear β‐catenin immunopositivity, is a molecular feature of a subset of type I endometrial carcinomas. Copyright © 2003 John Wiley & Sons, Ltd.
Pathogenetic mechanisms in usual interstitial pneumonia/idiopathic pulmonary fibrosis
Authors: White Eric S , Lazar Michael H , Thannickal Victor J
Published: October 2003

Idiopathic pulmonary fibrosis (IPF) is a progressive, usually fatal, form of interstitial lung disease characterized by failure of alveolar re‐epithelialization, persistence of fibroblasts/myofibroblasts, deposition of extracellular matrix, and distortion of lung architecture which ultimately results in respiratory failure. Clinical IPF is associated with a histopathological pattern of usual interstitial pneumonia (UIP) on surgical lung biopsy. Therapy for this disease with glucocorticoids and other immunomodulatory agents is largely ineffective and recent trials of newer anti‐fibrotic agents have been disappointing. While the inciting event(s) leading to the initiation of scar formation in UIP remain unknown, recent advances in our understanding of the mechanisms underlying both normal and aberrant wound healing have shed some light on pathogenetic mechanisms that may play significant roles in this disease. Unlike other fibrotic diseases of the lung, such as those associated with collagen vascular disease, occupational exposure, or chemotherapeutic agents, UIP is not associated with a significant inflammatory response; rather, dysregulated epithelial–mesenchymal interactions predominate. Identification of pathways crucial to fibrogenesis might offer potentially novel therapeutic targets to slow or halt the progression of IPF. This review focuses on evolving concepts of cellular and molecular mechanisms in the pathogenesis of UIP/IPF. Copyright © 2003 John Wiley & Sons, Ltd.
MSI‐low, a real phenomenon which varies in frequency among cancer types
Authors: Halford Sarah ER , Sawyer Elinor J , Lambros Maryou B , Gorman Patricia , Macdonald Nicola D , Talbot Ian C , Foulkes William D , Gillett Cheryl E , Barnes Diana M , Akslen Lars A , Lee Kwok , Jacobs Ian J , Hanby Andrew M , Ganesan Trivadi S , Salvesen Helga B , Bodmer Walter F , Tomlinson Ian PM , Roylance Rebecca R
Published: October 2003

This study assessed whether low‐level microsatellite instability (MSI‐L) is a phenomenon specific to colorectal cancers or is also present in other tumour types. Breast (grade III ductal and lobular), endometrial and ovarian carcinomas, as well as colorectal cancers, were analysed for MSI‐L using eight microsatellite markers. The markers were selected from a panel that had previously been shown to be sensitive for the detection of MSI‐L in colorectal cancers. It was found that MSI‐L was present in 30 of 87 (35%) colorectal cancers, 2 of 59 (3%) grade III breast carcinomas, 1 of 35 (3%) lobular breast cancers, 16 of 50 (32%) endometrial cancers, and 9 of 34 (26%) ovarian cancers. These results suggest that MSI‐L is a very rare occurrence in breast carcinomas, but does occur as a real phenomenon in colorectal, endometrial, and ovarian carcinomas, which are all part of the hereditary non‐polyposis colon cancer (HNPCC) syndrome. PCR artefact was also found to masquerade as MSI‐L; criteria for the assessment of MSI‐L are suggested to eliminate this problem. Copyright © 2003 John Wiley & Sons, Ltd.
Inactivating I kappa B epsilon mutations in Hodgkin/Reed–Sternberg cells
Authors: Emmerich Florian , Theurich Sebastian , Hummel Michael , Haeffker Antje , Vry Magnus S , Döhner Konstanze , Bommert Kurt , Stein Harald , Dörken Bernd
Published: October 2003

The pathogenesis of Hodgkin lymphoma (HL) is still unclear. Previous investigations have demonstrated constitutive nuclear activity of the transcription factor NF kappa B (NF‐κB) in Hodgkin/Reed–Sternberg (HRS) cells as an important prerequisite in protecting these cells from apoptosis. As a molecular mechanism leading to constitutive NF‐κB activity in HRS cells, mutations of the NF‐κB inhibitor I kappa B alpha (IκBα) have recently been identified in classical (c) HL‐derived cell lines in a patient with cHL. In the present study, the NF‐κB inhibitor I kappa B epsilon (IκBε) has been analysed for somatic mutations in the same group of six patients already studied for IκBα mutations, as well as in cHL‐derived cell lines. In one cHL‐derived cell line (L428), a hemizygous frame‐shift mutation generating a pre‐terminal stop codon resulting in a severely truncated protein was found. Moreover, in the HRS cells of one patient, a hemizygous mutation affecting the 5′‐splicing site of intron 1 of the IκBε gene was found. These results, in combination with recently described IκBα mutations, indicate that defective NF‐κB inhibitors appear more frequent than previously thought and might explain the constitutive nuclear activity of NF‐κB in a significant proportion of cHL cases. Copyright © 2003 John Wiley & Sons, Ltd.
Induction of contact‐dependent endothelial apoptosis by osteosarcoma cells suggests a role for endothelial cell apoptosis in blood‐borne metastasis
Authors: McEwen A , Emmanuel C , Medbury H , Leick A , Walker DM , Zoellner H
Published: October 2003

Although tumour cells are believed to migrate between endothelial cells early in metastasis, the possibility remains that endothelial apoptosis may also contribute to the tumour's breach of the vascular barrier. Although seemingly inconsistent with tumour angiogenesis, one publication describes the induction of contact‐dependent apoptosis in cultured endothelium by tumour cells. The cell culture data are, however, open to challenge on technical grounds while there are no confirmatory reports. The present paper describes experiments overcoming these limitations. SAOS‐2 human osteosarcoma cells and two rat carcinoma cell lines were co‐cultured with human umbilical vein endothelial cells (HUVECs) and cultures labelled by surface lectin histochemistry for endothelium. The HUVEC culture density was determined and SAOS‐2 cells, but not rat carcinoma cells, were found significantly to reduce HUVEC survival despite the release of potent growth factors as determined in separate experiments with tumour cell conditioned medium. Lectin labelling combined with light microscopy, transmission electron microscopy, flow cytometry for both lectin binding and DNA content, and DNA gel electrophoresis of SAOS‐2/HUVEC co‐cultures revealed extensive HUVEC apoptosis. These findings indicate contact‐dependent endothelial apoptosis by SAOS‐2, while this activity appeared weaker and overwhelmed by HUVEC proliferation with rat carcinoma cells. Importantly, this study supports the suggestion that endothelial apoptosis may be important for metastasis and suggests a complex interplay between endothelial proliferation and apoptosis in tumours. Copyright © 2003 John Wiley & Sons, Ltd.
Cadherins, catenins and APC in pleural malignant mesothelioma
Authors: Abutaily AS , Collins JE , Roche WR
Published: October 2003

Malignant mesothelioma is an aggressive disease of the pleura, and less commonly the peritoneum, with a very poor prognosis. The present study has examined the expression of cell adhesion molecules including cadherins, catenins, and APC in order to determine whether abnormal expression of components of the Wnt signalling pathway contribute to the variable phenotype of malignant mesothelioma. Sixty‐three malignant mesotheliomas and nine cases of reactive mesothelial hyperplasia were analysed by immunohistochemistry for E‐cadherin, N‐cadherin, α‐catenin, β‐catenin, and the C‐ and N‐terminals of APC. In addition, DNA was extracted from formalin‐fixed, paraffin wax blocks, and a 226 bp fragment of exon 3 of the β‐catenin gene was amplified, sequenced, and screened for activating mutations in the glycogen synthase kinase 3β (GSK‐3β) phosphorylation targets. E‐cadherin expression was detected in 48% of the epithelioid mesotheliomas but was observed in only 7% of sarcomatoid mesotheliomas. N‐cadherin, α‐catenin, β‐catenin, and the C‐ and N‐terminals of APC did not show differential expression between the mesothelioma phenotypes. Abnormal nuclear localization of β‐catenin was demonstrated in 19% of mesotheliomas. Mutations of β‐catenin phosphorylation sites were not detected in any of the 62 mesotheliomas examined. Positive staining for the N‐terminal of APC was seen in all of the cases of reactive mesothelial hyperplasia, as well as in all the mesotheliomas. Staining for the C‐terminal of APC was negative in 23% mesotheliomas, despite being present in all the cases of reactive hyperplasia. The present study provides the first evidence that β‐catenin accumulates in the nucleus in malignant mesotheliomas. In addition, APC expression was altered in some mesotheliomas, suggesting that a truncated APC gene product may contribute to abnormal Wnt signalling and dysregulation of cell proliferation in malignant mesothelioma. Copyright © 2003 John Wiley & Sons, Ltd.
SDHD mutations in head and neck paragangliomas result in destabilization of complex II in the mitochondrial respiratory chain with loss of enzymatic activity and abnormal mitochondrial morphology
Authors: Douwes Dekker PB , Hogendoorn PCW , Kuipers‐Dijkshoorn N , Prins FA , van Duinen SG , Taschner PEM , van der Mey AGL , Cornelisse CJ
Published: October 2003

Hereditary head and neck paragangliomas are tumours associated with the autonomic nervous system. Recently, mutations in genes coding for subunits of mitochondrial complex II, succinate‐ubiquinone‐oxidoreductase (SDHB, SDHC, and SDHD), have been identified in the majority of hereditary tumours and a number of isolated cases. In addition, a fourth locus, PGL2, has been mapped to chromosome 11q13 in an isolated family. In order to characterize phenotypic effects of these mutations, the present study investigated the immunohistochemical expression of the catalytic subunits of complex II (flavoprotein and iron protein), SDH enzyme activity, and mitochondrial morphology in a series of 22 head and neck paragangliomas. These included 11 SDHD‐, one SDHB‐, two PGL2‐linked tumours, and eight sporadic tumours. In the majority of the tumours (∼90%), the enzyme‐histochemical SDH reaction was negative and immunohistochemistry of catalytic subunits of complex II showed reduced expression of iron protein and enhanced expression of flavoprotein. Ultrastructural examination revealed elevated numbers of tightly packed mitochondria with abnormal morphology in SDHD‐linked and sporadic tumours. Immuno‐electron microscopy showed localization of the flavoprotein on the remnants of the mitochondrial inner membranes, whereas virtually no signal for the iron protein was detected. These results indicate that the function of mitochondrial complex II is compromised in the majority of head and neck paragangliomas. Copyright © 2003 John Wiley & Sons, Ltd.
Apoptosis of terminal hypertrophic chondrocytes in an in vitro model of endochondral ossification
Authors: Cheung JOP , Grant ME , Jones CJP , Hoyland JA , Freemont AJ , Hillarby MC
Published: October 2003

It is widely accepted that growth plate chondrocytes undergo apoptosis when they reach the terminal hypertrophic stage of their differentiation during the process of endochondral ossification in vivo. In this report, an established chondrocyte cell culture model of mammalian endochondral ossification was utilized to investigate the fate of chondrocytes after they had entered hypertrophy in vitro. Fetal bovine epiphyseal chondrocytes were treated with the demethylating agent, 5‐azacytidine, for 48 h and then cultured under azacytidine‐depleted conditions. There was evidence for apoptosis in azacytidine‐treated cells, as demonstrated by nuclear condensation and fragmentation (days 27 and 35) using transmission electron microscopy, and the detection of exposed phosphatidylserine on the plasma membrane surface of apoptotic chondrocytes (day 27) using fluorescence‐labelled annexin V. Treated cultures on days 10 and 20 and untreated cultures at all corresponding time‐points showed no morphological characteristics of apoptosis. In situ hybridization studies of treated cultures revealed that expression of the apoptotic suppressor, bcl‐2, remained consistently high throughout the culture period, whilst the apoptotic inducer, bax, was not expressed until day 23. Quantification of these data showed a gradual shift in the ratio of the expression level of bcl‐2 and bax in favour of bax with time in culture, particularly from day 23 onwards. Taken together, the results indicate that azacytidine‐treated epiphyseal chondrocytes entered terminal hypertrophy from day 23 onwards in culture and died by apoptosis. This study confirms this culture system as a successful recapitulation of the entire mammalian chondrocyte differentiation pathway, including apoptosis. The culture model will prove valuable for studies of the apoptotic fate of terminally differentiated chondrocytes in the growth plate with a view to providing a better understanding of the underlying mechanisms of skeletal malformations and other pathological disorders such as osteoarthritis. Copyright © 2003 John Wiley & Sons, Ltd.
Germinal centre‐like versus undifferentiated stromal immunophenotypes in follicular lymphoma
Authors: Chang Kong‐Chao , Huang Xuelin , Medeiros L Jeffrey , Jones Dan
Published: October 2003

Follicular dendritic cells (FDCs) in reactive germinal centres (GCs) show modulated expression of antigens indicative of step‐wise maturation from more undifferentiated stroma. The present study compared the expression of FDC markers CD21, CD23, CD35, and chemokine CXCL13 and the stromal markers low‐affinity nerve growth factor receptor (LNGFR) and CNA.42 in 35 follicular lymphoma (FL) cases with reactive lymphoic tissue. CXCL13 was expressed by follicular stroma in all FLs but most cases showed either partial (11/35 cases, 31%) or complete (10/35 cases, 29%) absence of other FDC antigens, most commonly CD23, followed by CD21 and CD35, with variable patterns of LNGFR and CNA.42 immunostaining. Only a minority of FL cases (14/35, 40%) showed stroma that resembled mature FDCs (CD23+, CD21+, CD35+) and these tumours were always associated with numerous intrafollicular T‐cells, similar to reactive GCs. In the 25 FL cases that had identifiable extrafollicular tumour cells, the immunophenotype of follicular stroma showed the same variability but the extrafollicular stroma showed an absence of FDC markers, with the exception of frequent strong LNGFR staining. Stromal phenotypic changes in FL were not correlated with mean follicle size, percentage of diffuse growth, tumour mitotic rate or the proliferation index as determined by PCNA immunostaining. Serial biopsy specimens analysed in a subset of 15 patients showed either a stable stromal phenotype (seven cases, 47%) or loss of FDC antigens in tumour‐associated stroma over time (seven cases, 47%). The GC‐like subset of FLs, having both abundant intrafollicular T‐cells and fully differentiated CD23+ FDCs, comprises a minority of FL cases that likely have different growth requirements from FLs that lack these features. The pattern of FDC antigen loss in stroma of FL is a readily assessable biological feature that appears independent of architectural growth pattern and may serve as a useful surrogate marker of tumour progression. Copyright © 2003 John Wiley & Sons, Ltd.
Welchen Einfluss hat die Ernährung auf die Lipide? Lipidsenkung ohne Medikamente
Authors: Vogt Anja , Steinhagen‐Thiessen Elisabeth
Published: October 2003

Fettstoffwechselstörungen sind ein bedeutender Risikofaktor für kardiovaskuläre Krankheiten, die in der westlichen Welt unvermindert die Mortalitäts‐ und Morbiditätsstatistik anführen. Die Bedeutung des Lebensstils zur Beeinflussung der Fettstoffwechselstörungen wie auch der atherosklerotischen Folgekrankheiten ist sehr gut belegt. Hierzu gehören Nikotinverzicht, körperliche Bewegung, eine ausgewogene Ernährung und Vermeiden von Übergewicht. Die Ernährung soll fettreduziert, fettmodifiziert, cholesterinreduziert und ballaststoffreich sein. Die Verbesserung des Risikoprofiles hat sowohl primär‐ wie sekundärpräventiven Wert.

Auch wenn heute eine Vielzahl effektiver lipidsenkender Medikamente zur Verfügung stehen, darf die Bedeutung der richtigen Ernährung nicht vergessen werden. Besonders Menschen mit ernährungsabhängigen Krankheiten wie den Fettstoffwechselstörungen müssen immer wieder unterstützt und bestätigt werden, auf eine möglichst gesunde Ernährung zu achten.
Endothelfunktion, Morphologie und Biochemie der Atherosklerose: Ursachen der Gefäßschäden
Authors: Kostner Gerhard M.
Published: October 2003

Die Atherogenese wird durch ein multifaktorielles pathogenes Geschehen verursacht, bei dem genetische Defekte sowie eine Unzahl von Risikofaktoren, wie Störungen des Cholesterinstoffwechsels, der Blutgerinnung, der Immunabwehr und der Abwehr von oxidativem Stress, beteiligt sind. Eine vordergründige Rolle bei der Atherogenese spielt die endotheliale Dysfunktion, die durch inflammatorische Stimuli ausgelöst wird. EDF aktiviert das Abwehrsystem. Bei chronischer Stimulierung gerät die zunächst physiologische Abwehr in einen pathologischen Zustand, der mit Proliferation der SMC, Synthese von Bindegewebe, Bildung von Schaumzellen, Ablagerung von Cholesterin und Calciumsalzen einhergeht. Dieses Geschehen kann sich über Jahre unbemerkt hinziehen. Besonders gefährlich ist die Ausbildung von „vulnerablen plaques”︁, die, mechanisch oder durch Metalloproteasen verursacht, plötzlich aufbrechen und eine unmittelbare Plättchenaktivierung und Thrombusbildung auslösen. Die Folge ist der Gefäßverschluss mit Herzinfarkt oder Schlaganfall.
Pleiotrope Effekte der Statine: Wirken Statine nur über LDL‐Senkung?
Authors: Thiery Joachim , Brügel Mathias
Published: October 2003

Die Hauptwirkung einer Statintherapie liegt in der ausgeprägten Senkung des Plasma‐LDL‐Cholesterins. Diese LDL‐Senkung ist für den Erfolg der Statintherapie in der Prävention der Koronaren Herzkrankheit von zentraler Bedeutung.

Aufgrund der Interaktion von Statinen mit dem Mevalonsäurestoffwechsel kommt es zusätzlich zu Effekten auf die posttranslationale Modifikation einer Vielzahl von Signalproteinen. Dies erklärt die multiplen Zusatzeffekte von Statinen, die auch unabhängig von der Höhe des Plasma‐Cholesterins wirksam sein können.

Da bisher alle Statine eine ausgeprägte LDL‐Cholesterin senkende Wirkung aufweisen, ist eine Abtrennung dieser pleiotropen Effekte zur Beurteilung der klinischen Relevanz sehr schwierig.

Vergleichende Untersuchungen mit neuen Wirkstoffen der Cholesterinresorptionshemmung werden hilfreich sein, die klinische Relevanz der pleiotropen Statineffekte zu klären.
Tödliches Cholesterin
Authors: Zündorf Ilse
Published: October 2003

Freies Cholesterin stört die Funktion der Plasmamembran und induziert dadurch letztendlich Apoptose bei Makrophagen. Das war die bisherige Meinung. Dass dem doch nicht so ist, konnten Wissenschaftler an der New Yorker Columbia University eindrucksvoll zeigen.
Gut und Böse liegen oft nahe beieinander …
Authors: Unger Matthias
Published: October 2003

…sagt ein altes Sprichwort und die Forschung lehrt uns, dass dies auch für ansonsten harmlose Pflanzenextrakte gilt. Nachdem Grapefruit‐Saft aufgrund seiner schweren Arzneimittelinteraktionen in der wissenschaftlichen Fachwelt eher durch Negativ‐Schlagzeilen in den Mittelpunkt des Interesses gerückt war, scheint sich das Blatt jetzt zu wenden.
The five‐factor personality inventory: cross‐cultural generalizability across 13 countries
Authors: Jolijn Hendriks A. A. , Perugini Marco , Angleitner Alois , Ostendorf Fritz , Johnson John A. , De Fruyt Filip , Hřebíčková Martina , Kreitler Shulamith , Murakami Takashi , Bratko Denis , Conner Mark , Nagy Janos , Rodríguez‐Fornells Antoni , Ruisel Imrich
Published: October 2003

In the present study, we investigated the structural invariance of the Five‐Factor Personality Inventory (FFPI) across a variety of cultures. Self‐report data sets from ten European and three non‐European countries were available, representing the Germanic (Belgium, England, Germany, the Netherlands, USA), Romance (Italy, Spain), and Slavic branches (Croatia, Czech Republic, Slovakia) of the Indo‐European languages, as well as the Semito‐Hamitic (Israel) and Altaic (Hungary, Japan) language families. Each data set was subjected to principal component analysis, followed by varimax rotation and orthogonal Procrustes rotation to optimal agreement with (i) the Dutch normative structure and (ii) an American large‐sample structure. Three criteria (scree test, internal consistency reliabilities of the varimax‐rotated components, and parallel analysis) were used to establish the number of factors to be retained for rotation. Clear five‐factor structures were found in all samples except in the smallest one (USA, N = 97). Internal consistency reliabilities of the five components were generally good and high congruence was found between each sample structure and both reference structures. More than 80% of the items were equally stable within each country. Based on the results, an international FFPI reference structure is proposed. This reference structure can facilitate standardized communications about Big Five scores across research programmes. Copyright © 2003 John Wiley & Sons, Ltd.
Preparation and characterisation of biodegradable starch‐based nanocomposite materials
Authors: McGlashan Stewart A , Halley Peter J
Published: October 2003

Different formulations of biodegradable starch–polyester blend nanocomposite materials have been film blown on a pilot scale film blowing tower. The physical properties of different films have been examined by thermal and mechanical analysis and X‐ray diffraction. The results show that the addition of an organoclay (from 0 to 5 wt%) significantly improves both the processing and tensile properties over the original starch blends. Wide angle X‐ray diffraction (WAXD) results indicate that the best results were obtained for 30 wt% starch blends, and the level of delamination depends on the ratio of starch to polyester and amount of organoclay added. The crystallisation temperature of the nanocomposite blends is significantly lower than the base blend. This is probably due to the platelets inhibiting order, and hence crystallisation, of the starch and polyester. The mechanical and thermal properties of the blends are also sensitive to the way the clay particles are dispersed. Copyright © 2003 Society of Chemical Industry
Polyethylene‐layered silicate nanocomposites for rotational moulding
Authors: Martin Darren , Halley Peter , Truss Rowan , Murphy Michael , Jackson Oliver , Kwon Oh‐Yun
Published: October 2003

A series of polyethylene‐layered silicate nanocomposites has been studied as possible new candidates for rotational moulding. Two organically treated layered silicates were melt‐compounded into a maleated linear low‐density polyethylene host polymer at loadings of 6 and 9%, by weight. The morphology and properties of the nanocomposites were assessed by using dynamic mechanical thermal analysis, parallel‐plate rheometry, wide‐angle X‐ray diffraction and transmission electron microscopy. The sintering behaviour of the nanocomposites was qualitatively assessed via hot‐stage microscopy, indicating that the choice of nanofiller will play an important role in terms of producing nanocomposite materials with acceptable processability for rotational moulding. Copyright © 2003 Society of Chemical Industry
NMR characterization of blends of poly(hydroxybutyrate–co‐hydroxyvalerate) with poly(vinyl acetate)
Authors: Hill David JT , Markotsis Martin , Whittaker Andrew K , Wong Kathy W
Published: October 2003

The extent of mixing in blends of poly(hydroxybutyrate‐co‐hydroxyvalerate) (PHBV) (27% HV) and poly(vinyl acetate) (PVAc) has been measured using a number of different techniques, principally solid‐state NMR. Differential scanning calorimetry DSC measurements indicated effective mixing of the polymer chains on a scale of several nanometres. The results of 1H T1 and 1H T1ρ measurements confirm intimate mixing of the chains. A change on blending in the 1H T1ρ, and the 1H NMR line width of the signal from the protons of PVAc was consistent with an increase in the amplitude and frequency of motion of this component. The PVAc chains reside within the inter‐lamellar space, as confirmed by spin diffusion measurements after 1H T1ρ preparation. Copyright © 2003 Society of Chemical Industry
Early propagation kinetics in the free radical polymerization of methacrylonitrile investigated by a nitroxide trapping technique
Authors: Ewing Katrina , Busfield W Ken , Jenkins Ian D , Zetterlund Per B
Published: October 2003

The first seven addition products in the free radical polymerization of methacrylonitrile initiated by AIBN have been trapped by using a nitroxide trapping technique. In this experiment, the concentration of trap is maintained at a level sufficiently high to prevent the formation of high polymer, yet low enough to allow competitive monomer addition to form the lower members of the propagation series before being trapped to form the oligomeric addition products. These oligomers have been identified and quantified by electrospray ionization‐mass spectrometry (ESI‐MS) in series with HPLC–UV. The results have allowed individual propagation rate coefficients in the early stages of polymerization to be estimated. The variation in kpn for n = 1 and n = 3–7, where n is the number of monomer units in the propagating radical, is less than the experimental precision, with an average value at 75°C of 1.9 ± 1.0 × 104 l mol−1 s−1. As with other monomers, however, kpn for the first few propagation steps is significantly greater than the value for high polymer measured by the pulsed laser polymerization technique. Copyright © 2003 Society of Chemical Industry
N‐substituent effect of maleimides on acrylate polymerization initiated by three‐component systems
Authors: Clark SC , Hill DJT , Hoyle CE , Jönsson S , Miller CW , Shao LY
Published: October 2003

In this paper, the relative photopolymerization efficiency for polymerization of a difunctional acrylate initiated by various N‐substituted maleimides in the presence of amine and benzophenone are compared on the basis of a photo‐differential scanning calorimetry (photo‐DSC) study. The trends in the polymerization rates were obtained from the photopolymerization profiles and expressed in terms of a photoinitiation index, Ip. An N‐substituent index, Is, which indicates whether each N‐substituent plays either a positive (when Is > 1) or a negative (when Is < 1) role in the initiation process relative to MI (unsubstituted maleimide), was determined. Copyright © 2003 Society of Chemical Industry
Radical formation on γ‐radiolysis of poly [(methacrylic acid)‐co‐acrylonitrile]
Authors: Fox Peter A , Hill David JT , Lang Anthony P , Pomery Peter J
Published: October 2003

The radicals formed on γ‐radiolysis of a series of copolymers of methacrylic acid and acrylonitrile have been investigated by ESR spectroscopy. This series of copolymers spanned the full composition range and the study was carried out at 77 K and ambient temperature. The radicals formed in the copolymers at 77 and 303 K were found to be similar to those found in the two homopolymers, but in the intermediate composition range the presence of acrylonitrile propagation radicals was also detected. These radicals were not observed to be formed in significant quantities on the radiolysis of polyacrylonitrile. They are believed to result from a scission of the main chain at methacrylic acid/acrylonitrile diad sequences following loss of the methacrylic acid carboxyl group. At 77 K, the copolymers with high methacrylic acid contents were found to be more sensitive to radical formation than the methacrylic acid homopolymer, but this enhanced sensitivity was not evident at ambient temperature, where the G‐values for radical formation for the copolymers were slightly less than the values for the homopolymers. Copyright © 2003 Society of Chemical Industry
Chain scission and branching in irradiated poly(tetrafluoroethylene‐co‐hexafluoropropylene)
Authors: Hill DJT , Mohajerani S , Whittaker AK , Scheler U
Published: October 2003

The radiation chemistry of poly(tetrafluoroethylene‐co‐hexafluoropropylene) (FEP) with a TFE mole fraction of 0.90 has been studied under vacuum using 60Co γ‐radiation over a range of temperatures and absorbed doses. The radiolysis temperatures were 300, 363, 423, 523 and 543 K. New structure formation in the copolymers was analysed by solid‐state 19F NMR spectroscopy. The new structures formed in the copolymers have been identified and the G‐values for the formation of new chemical structures have been investigated at 363 and 523 K. These two temperatures are just above and just below the polymer Tg and Tm, respectively. At the lower temperature, there was no evidence for any chain branching and an estimate of G(S) of 1.0 was obtained. A value of G(S) of 1.3 and a minimum value of G(X)Y of 1.3 were obtained at 523 K. Copyright © 2003 Society of Chemical Industry
Profiling and imaging proteins in the mouse epididymis by imaging mass spectrometry
Authors: Chaurand Pierre , Fouchécourt Sophie , DaGue Beverly B. , Xu Baogang J. , Reyzer Michelle L. , Orgebin‐Crist Marie‐Claire , Caprioli Richard M.
Published: October 2003

Different aspects of matrix‐assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) have been used as discovery tools to obtain global and time‐correlated information on the local proteomic composition of the sexually mature mouse epididymis from both qualitative and semiquantitative points of view. Tissue sections and laser captured microdissected cells and secretory products were analyzed by MALDI‐MS and from the recovered protein profiles, over 400 different proteins were monitored. Over 50 of these, some of which have been identified, displayed regionalized behavior from caput to cauda within the epididymis. Combining the information obtained from high‐resolution imaging mass spectrometry and laser captured microdissection experiments, numerous proteins were localized within the epididymis at the cellular level. Furthermore, from the signal intensities observed in the different protein profiles organized in space, semiquantitative information for each protein was obtained.
Protein arrays for autoantibody profiling and fine‐specificity mapping
Authors: Robinson William H. , Steinman Lawrence , Utz Paul J.
Published: October 2003

Protein arrays provide a powerful approach to study autoimmune disease. Autoimmune responses activate B cells to produce autoantibodies that recognize self‐molecules termed autoantigens, many of which are proteins or protein complexes. Protein arrays enable profiling of the specificity of autoantibody responses against panels of peptides and proteins representing known autoantigens as well as candidate autoantigens. In addition to identifying autoantigens and mapping immunodominant epitopes, proteomic analysis of autoantibody responses will further enable diagnosis, prognosis, and tailoring of antigen‐specific tolerizing therapy.
Protein microarrays: Molecular profiling technologies for clinical specimens
Authors: Espina Virginia , Mehta Arpita I. , Winters Mary E. , Calvert Valerie , Wulfkuhle Julia , Petricoin Emanuel F. , Liotta Lance A.
Published: October 2003

Proteomics, the study of protein function within biologic systems, will further our understanding of cancer pathogenesis. Coupled with transcript profiling, proteomics can herald the advent of molecular therapy tailored to the individual patient's neoplasm. Protein microarrays, one emerging class of proteomic technologies, have broad applications for discovery and quantitative analysis. This technology is uniquely suited to gather information about the post‐translational modifications of proteins reflecting the activity state of signal pathways and networks. Protein microarrays now make it feasible to conduct signal network profiling within cellular samples. Nevertheless, to be successful, design and use of protein microarrays must take into consideration enormous analytical challenges. A subclass of protein microarrays, Reverse Phase Arrays, created to meet these challenges, has been optimized for use with tissue specimens, and is now in use for the analysis of biopsy samples for clinical trial research.
Signal pathway profiling of prostate cancer using reverse phase protein arrays
Authors: Grubb Robert L. , Calvert Valerie S. , Wulkuhle Julia D. , Paweletz Cloud P. , Linehan W. Marston , Phillips John L. , Chuaqui Rodrigo , Valasco Alfredo , Gillespie John , Emmert‐Buck Michael , Liotta Lance A. , Petricoin Emanuel F.
Published: October 2003

Reverse phase protein arrays represent a new proteomics microarray technology with which to study the fluctuating state of the proteome in minute quantities of cells. The activation status of cell signaling pathways controls cellular fate and deregulation of these pathways underpins carcinogenesis. Changes in pathway activation that occur between early stage prostatic epithelial lesions, prostatic stroma and the extracellular matrix can be analyzed by obtaining pure populations of cell types by laser capture microdissection (LCM) and analyzing the relative states of several key phosphorylation points within the cellular circuitry. We have applied reverse phase protein array technology to analyze the status of key points in cell signaling involved in pro‐survival, mitogenic, apoptotic and growth regulation pathways in the progression from normal prostate epithelium to invasive prostate cancer. Using multiplexed reverse phase protein arrays coupled with LCM, the states of signaling changes during disease progression from prostate cancer study sets were analyzed. Focused analysis of phospho‐specific endpoints revealed changes in cellular signaling events through disease progression and between patients. We have used a new protein array technology to study specific molecular pathways believed to be important in cell survival and progression from normal epithelium to invasive carcinoma directly from human tissue specimens. With the advent of molecular targeted therapeutics, the identification, characterization and monitoring of the signaling events within actual human biopsies will be critical for patient‐tailored therapy.
Identification of repertoires of surface antigens on leukemias using an antibody microarray
Authors: Belov Larissa , Huang Pauline , Barber Nicole , Mulligan Stephen P. , Christopherson Richard I.
Published: October 2003

We have previously described a microarray of cluster of differentiation (CD) antibodies that enables concurrent determination of more than 60 CD antigens on leukocytes. This procedure does not require protein purification or labeling, or a secondary detection system. Whole cells are captured by a microarray of 10 nL antibody dots immobilized on a nitrocellulose film on a microscope slide. Distinct patterns of cell binding are observed for different leukemias or lymphomas. These haematological malignancies arise from precursor cells of T‐ or B‐lymphocytic, or myeloid lineages of hematopoiesis. The dot patterns obtained from patients are distinct from those of peripheral blood leukocytes from normal subjects. This microarray technology has recently undergone a number of refinements. The microarray now contains more CD antibodies, and a scanner for imaging dot patterns and software for data analysis provide an extensive immunophenotype sufficient for diagnosis of common leukemias. The technology is being evaluated for diagnosis of leukemias with parallel use of conventional diagnostic criteria.
Protein microarrays: Promising tools for proteomic research
Authors: Templin Markus F. , Stoll Dieter , Schwenk Jochen M. , Pötz Oliver , Kramer Stefan , Joos Thomas O.
Published: October 2003

Miniaturized and parallelized ligand binding assays are of great interest in postgenomic research because microarray technology allows the simultaneous determination of a large number of parameters from a minute amount of sample within a single experiment. Assay systems based on this technology are used for the identification and quantification of proteins as well as for the study of protein interactions. Protein affinity assays have been implemented that allow the analysis of interactions between proteins with other proteins, peptides, low molecular weight compounds, oligosaccharides or DNA. Microarray technology is an emerging technology used in global analytical approaches and has a considerable impact on proteomic research.
Carbohydrate microarrays
Authors: Wang Denong
Published: October 2003

Sugar chains are abundantly expressed on the outer surfaces of the vast majority of viral, bacterial, protozoan and fungal pathogens, as well as on the membranes of mammalian cells. This class of carbohydrate molecule is without peer in structural diversity and is characteristically suitable for storing and displaying biological signals for molecular and cellular recognition. Exploring the biological information contained in sugar chains is an important topic of current postgenomic research. To facilitate these investigations, we have focused on the establishment of a carbohydrate‐based microarray technology. Recently, we reported that a large panel of carbohydrate‐containing macromolecules, including polysaccharides, natural glycoconjugates, and the mono‐ and oligosaccharides coupled to carrier molecules, can be stably immobilized on a microglass slide to produce a large‐scale carbohydrate microarray. In this review, we attempt to summarize our recent progress in using this technology to uncover the carbohydrate‐based biological signals that are recognized by the human and animal immune systems. We also discuss the potential of various platforms of carbohydrate microarrays that were recently established and analyze the challenges to future development of carbohydrate microarray technologies and their applications.
Current status of protein chip development in terms of fabrication and application
Authors: Seong Seung‐yong , Choi Cheol‐young
Published: October 2003

Sequencing of the human genome revealed that more than 30 000 genes encode proteins comprising the human proteome. “Proteomics” can be defined as a field of research studying proteins in terms of their function, expression, structure, modification and their interaction in physiological and in pathological states. The concentration, modification and interaction of proteins in cells, plasma, and in tissues are crucial in determining the phenotype of living organisms. Although fluctuation of protein concentration is essential to maintain homeostasis, protein expression levels are also pathognomonic features. Estimating protein concentration by analyzing the quantity of mRNA in cells through conventional technologies, such as DNA chips, does not provide precise values since the half‐life and translation efficacy of mRNA is variable. In addition, polypeptides undergo post‐translational modification. For these reasons, novel techniques are needed to analyze multiple proteins simultaneously using protein microarrays. In the near future, protein chips may allow construction of complete relational databases for metabolic and signal transduction pathways. This article reviews the current status of technologies for fabricating protein microarrays and their applications.
Microarrays of tumor cell derived proteins uncover a distinct pattern of prostate cancer serum immunoreactivity
Authors: Bouwman Kerri , Qiu Ji , Zhou Heping , Schotanus Mark , Mangold Leslie A. , Vogt Robert , Erlandson Erik , Trenkle John , Partin Alan W. , Misek David , Omenn Gilbert S. , Haab Brian B. , Hanash Samir
Published: October 2003

The broad characterization of the immune responses elicited by tumors has valuable applications in diagnostics and basic research. We present here the use of microarrays of tumor‐derived proteins to profile the antibody repertoire in the sera of prostate cancer patients and controls. Two‐dimensional liquid chromatography was used to separate proteins from the prostate cancer cell line LNCaP into 1760 fractions. These fractions were spotted in microarrays on coated microscope slides, and the microarrays were incubated individually with serum samples from 25 men with prostate cancer and 25 male controls. The amount of immunoglobulin bound to each fraction by each serum sample was quantified. Statistical analysis revealed that 38 of the fractions had significantly higher levels of immunoglobulin binding in the prostate cancer samples compared to the controls. Two fractions showed higher binding in the control samples. The significantly higher immunoglobulin reactivity from the prostate cancer samples may reflect a strong immune response to the tumors in the prostate cancer patients. We used multivariate analysis to classify the samples as either prostate cancer or control. In a cross‐validation study, recursive partitioning classified the samples with 84% accuracy. A decision tree with two levels of partitioning classified the samples with 98% accuracy. Additional studies will allow further characterization of tumor antigens in prostate cancer and their significance for diagnosis. These results suggest that microarrays of fractionated proteins could be a powerful tool for tumor antigen discovery and cancer diagnosis.
The emerging field of protein microarrays
Authors: Hanash Sam
Published: October 2003

No abstracts.
CH and NH bond dissociation energies of five‐ and six‐membered ring aromatic compounds
Authors: Feng Yong , Wang Jin‐Ti , Liu Lei , Guo Qing‐Xiang
Published: October 2003

CH and NH bond dissociation energies (BDEs) of various five‐ and six‐membered ring aromatic compounds were calculated using composite ab initio CBS‐Q, G3 and G3B3 methods. It was found that all these composite ab initio methods provided very similar BDEs, despite the fact that different geometries and different procedures in the extrapolation to complete incorporation of electron correlation and complete basis set limit were used. Therefore, the calculated BDEs should be reliable. In addition, we found interesting dependences of the CH BDEs on the bond angles, spins and charges. A good quantitative structure–activity relationship (QSAR) model for the CH BDEs of aromatic compounds was also established. Copyright © 2003 John Wiley & Sons, Ltd.
New permanently charged phenanthridinium–nucleobase conjugates. Interactions with nucleotides and polynucleotides and recognition of ds‐polyAH+
Authors: Tumir Lidija‐Marija , Piantanida Ivo , Cindrić Iva Juranović , Hrenar Tomica , Meić Zlatko , Žinić Mladen
Published: October 2003

N‐Methyl‐8‐aminophenathridinium–uracil and –adenine conjugates possessing a nucleobase attached at the phenanthridinium 8‐amino group by a trimethylene spacer were prepared in the form of water‐soluble hydrogensulfate salts. Spectroscopic characteristics of the conjugates reveal the formation of folded conformations in water characterized by intramolecular aromatic stacking between the phenanthridinium unit and the tethered nucleobase. The conjugates form 1:1 complexes in water with either complementary or non‐complementary nucleotides, giving log Ks values between 1 and 2 and showing a lack of any base recognition. Also, the binding studies with single‐stranded polynucleotides showed no preference of conjugates to polynucleotides containing complementary nucleobases. At pH 5, the N‐methylphenanthridinium–adenine conjugate exhibited preferred binding to double‐stranded (ds‐) polyAH+, whereas its protonated analogue bound preferably to polyU. The results reveal that the presence of protonated or permanently charged intercalator units in the conjugates dramatically changes their binding preferences for polynucleotides. Copyright © 2003 John Wiley & Sons, Ltd.