bluuebunny/crossref_metadata_2025_split 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

AbstractOmega‐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

AbstractWe 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

AbstractTwo 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

AbstractIdiopathic 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

AbstractThis 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

AbstractThe 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

AbstractAlthough 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

AbstractMalignant 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

AbstractHereditary 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

AbstractIt 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

AbstractFollicular 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

AbstractFettstoffwechselstörungen 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

AbstractDie 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

AbstractDie 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

AbstractFreies 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

Abstract…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.