bluuebunny/crossref_metadata_2025 huggingface dataset:
Estrogen modulates synaptic N‐methyl‐D‐aspartate receptor subunit distribution in the aged hippocampus
Authors: Adams Michelle M. , Fink Susan E. , Janssen William G.M. , Shah Ravi A. , Morrison John H.
Published: May 2004

Estrogen interacts with N‐methyl‐D‐aspartate (NMDA) receptors to regulate multiple aspects of morphological and functional plasticity. In hippocampus, estrogen increases both dendritic spine density and synapse number, and NMDA antagonists block these effects. Thus, estrogen‐mediated hippocampal plasticity may be of particular importance in the context of age‐related changes in endocrine status and cognitive performance. NR1 levels per synapse are increased in CA1 by estrogen in aged rats but not young rats, although no information is available on estrogen‐induced synaptic alterations in other NMDA receptor subunits that might impact function. Therefore, the present study was designed to investigate the effect of estrogen on the synaptic and subsynaptic distributions of the NMDA receptor subunits, NR2A and NR2B in CA1 pyramidal cells, within the context of aging. Our results demonstrated that the overall synaptic levels of NR2A and NR2B are similar in young and aged female rats, regardless of estrogen treatment. However, in the aged CA1, estrogen restores NR2B levels back to young levels in the lateral portions of the active synaptic zone. Thus, estrogen may impact the mobility of NMDA receptors across the synapse and, in the process, restore a more youthful synaptic profile. These findings have important implications for the mechanism of estrogen‐induced alterations in NMDA receptor‐mediated processes, particularly in the context of aging. J. Comp. Neurol. 474:419–426, 2004. © 2004 Wiley‐Liss, Inc.
Expression of VIP and/or PACAP receptor mRNA in peptide synthesizing cells within the suprachiasmatic nucleus of the rat and in its efferent target sites
Authors: Kalamatianos Theodosis , Kalló Imre , Piggins Hugh D. , Coen Clive W.
Published: May 2004

The suprachiasmatic nucleus (SCN) contains the predominant circadian pacemaker in mammals. Considerable evidence indicates that VPAC2 and PAC1, receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase‐activating peptide (PACAP), play critical roles in maintaining and entraining circadian rhythms. Retinal projections to the rat SCN contain PACAP and terminate mostly in the ventral SCN, the site of VIP neurons. The incidence of VPAC2 and PAC1 mRNAs within distinct neuronal populations of the rat SCN has been determined using double‐label in situ hybridization. VPAC2 mRNA was detected in almost all arginine‐vasopressin (AVP) neurons of the dorsomedial SCN and in 41% of the VIP neurons; somatostatin (SST) neurons, predominantly in dorsomedial and intermediate regions, showed a decreased incidence (23%). PAC1 mRNA was present in nearly half of the VIP and SST neurons (45% and 40%, respectively) and in one‐third of the AVP neurons (32%). Cells expressing VPAC2 mRNA also were detected in diencephalic areas that receive VIP‐immunoreactive SCN efferents, such as the peri‐suprachiasmatic region, lateral subparaventricular zone, parvocellular hypothalamic paraventricular subdivisions, dorsomedial hypothalamic nucleus, and anterior thalamic paraventricular and paratenial nuclei. The extensive distribution of PAC1 mRNA within the SCN suggests that actions of PACAP are not restricted to the predominantly retinorecipient region. The presence of VPAC2 mRNA in nearly half the VIP neurons, in almost all the AVP neurons, and at sites receiving VIP‐immunoreactive SCN efferents suggests that the SCN VIP neurons are coupled and/or autoregulated and also influence the AVP‐containing dorsomedial SCN and distal sites via VPAC2. J. Comp. Neurol. 475:19–35, 2004. © 2004 Wiley‐Liss, Inc.
Individual differences in the accuracy of autobiographical memory
Authors: Horselenberg Robert , Merckelbach Harald , Breukelen Gerard van , Wessel Ineke
Published: May 2004

In recent literature on ‘false memories’, autobiographical memory distortions are often linked to manipulations such as hypnosis or imagination. However, Barclay and Wellman (1986) demonstrated that such distortions might also occur more or less spontaneously. The current study sought to replicate this phenomenon. In addition, it examined whether certain personality traits, (i.e. fantasy proneness, dissociation, absorption, suggestibility and depression) might contribute to such spontaneous pseudo‐memories. Volunteers (N = 38) kept a diary of self‐selected, outstanding events for a 2‐week period. Six months later, they were unexpectedly given a recognition test consisting of original memories and several types of foils. Participants performed relatively well on the recognition task, although they had some difficulties differentiating original items from foil items. Curiously enough, fantasy proneness was related to superior recognition performance. Copyright © 2004 John Wiley & Sons, Ltd.
Obsessive beliefs and their relation to obsessive–compulsive symptoms
Authors: Faull Matthew , Joseph Stephen , Meaden Alan , Lawrence Tony
Published: May 2004

Relationships between obsessive–compulsive symptoms and beliefs identified as relevant to obsessive–compulsive disorder (OCD) are investigated among university students and a small clinical sample. One hundred and fifty‐four participants completed measures of OCD‐related beliefs, OCD symptoms, and anxiety and depression symptoms. Results showed that belief domains were strongly interrelated and were not sufficiently separate to use individually in further analysis. The summed obsessive beliefs score was significantly correlated with all measured obsessional symptom subtypes, after controlling for anxiety and depression. Possible explanations and clinical implications of the results are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Cognitive behaviour therapy for good and poor prognosis generalized anxiety disorder: a clinical effectiveness study
Authors: Durham Robert C. , Fisher Peter L. , Dow Michael G. T. , Sharp Donald , Power Kevin G. , Swan John S. , Morton R. Victor
Published: May 2004

Cognitive behaviour therapy (CBT) for generalized anxiety disorder produces variable results. It would be valuable to identify which patients respond well to brief CBT and whether increased intensity of therapy improves outcome for those with a poor prognosis. This clinical effectiveness study was designed to address these issues using a prognostic index developed from earlier research. Suitable patients were given five sessions of CBT if they had a good prognosis and either 9 or 15 sessions of CBT if they had a poor prognosis. There was no evidence that increasing the intensity of therapy for poor prognosis patients improved outcome and 60% remained cases at 6 month follow‐up. In contrast, only 12% of good prognosis patients remained cases at follow‐up despite receiving only brief therapy. Patient characteristics are a more powerful influence on outcome than the length of therapy. Prognostic indices may have an important place in routine clinical practice. Copyright © 2004 John Wiley & Sons, Ltd.
Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: Objectivity, reproducibility, malignancy‐associated changes, and human papillomavirus
Authors: Guillaud Martial , Cox Dennis , Adler‐Storthz Karen , Malpica Anais , Staerkel Gregg , Matisic Jasenka , Van Niekerk Dirk , Poulin Neal , Follen Michele , MacAulay Calum
Published: May 2004

Background

Background: As part of a project to evaluate emerging optical technologies for cervical neoplasia, our group is performing quantitative histopathological analyses of biopsy specimens from 1,190 patients. Objectives in the interim analysis are (a) quantitatively assessing progression of the neoplastic process of cervical intraepithelial neoplasia (CIN)/squamous intraepithelial lesions (SIL), (b) detecting malignancy‐associated changes (MACs), and (c) phenotypically measuring human papillomavirus (HPV) detected by DNA testing.

Methods

The diagnostic region of interest (ROI) from immediately adjacent sections were imaged, and the basal lamina and surface of the superficial layer were delimited. Nonoverlapping quantitatively stained nuclei were selected from 1,190 samples with histopathological characteristics of normal (929), koilocytosis (130), CIN 1 (40), CIN 2 (23), and CIN 3/carcinoma in situ (CIS) (68). A fully automatic procedure located and recorded the center of every nucleus in the region of interest (ROI). We used linear discriminant analysis to assess the changes between normal and CIN 3/CIS.

Results

Scores computed from the cell‐by cell features and the clinical grade of CIN/SIL were highly correlated, as were those of the architectural features and the clinical grade of CIN/SIL. We found even higher correlations between a combination of cell‐by‐cell and architectural scores, and clinical grade. Using these scores, we found MACs in the normal biopsy specimens from patients with high‐grade CIN/SIL. Furthermore, the same scores correlated with the molecular detection of HPV.

Conclusions

Quantitative histopathology can be used in large clinical trials as an objective and reproducible measure of CIN/SIL. Detectable phenotypic changes correlate well with CIN/SIL neoplastic progression. It can also be used to infer the presence of CIN/SIL (MACs) and molecular changes associated with increased risk of cancer development (high‐risk HPV). © 2004 Wiley‐Liss, Inc.
The High‐Intrinsic Diels−Alder Reactivity of (−)‐Galiellalactone; Generating Four Quaternary Carbon Centers under Mild Conditions
Authors: von Nussbaum Franz , Hanke Roman , Fahrig Thomas , Benet‐Buchholz Jordi
Published: May 2004

The Interleukin‐6 (IL‐6) responsive JAK/STAT pathway seems to be correlated with major diseases such as chronic inflammation, arteriosclerosis, liver fibrosis, Parkinson and Alzheimer disease. In order to take a look at (−)‐galiellalactone as a potential low‐molecular‐weight lead structure for non‐proteinogenic IL‐6 antagonists we carried out a microderivatization program that was aiming at bioactive congeners of the natural product and a preliminary structure‐activity relationship. During this effort, galiellalactone showed reactivity generally governed by convex‐concave face selectivity. O‐Acyl derivatives of galiellalactone turned out to be precursors of bis(dehydratogaliellalactone), a novel oligocyclic Diels−Alder product of complicated architecture. During this extraordinary Diels−Alder‐type conversion four quaternary carbon centers were generated at room temperature under mild conditions in a regio‐ and stereoselective fashion. The novel Diels−Alder transformation was used for a stereoselective hetero‐derivatization of the natural product leading to an aza congener of altered IL‐6 antagonistic activity in HepG2 hepatoma cells. The absolute (4S,5aR,7aR,7bS) configuration of natural (−)‐galiellalactone was confirmed by X‐ray crystallography with Cu‐Kα radiation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Analysis of the essential oil of Thymus eriocalyx from Iran
Authors: Kalvandi R. , Seﬁdkon F. , Atri M. , Mirza M.
Published: May 2004

Essential oils isolated by hydrodistillation from the aerial parts of Thymus eriocalyx (Ronniger) Jalas, before ﬂowering and full ﬂowering stage, were analysed by a combination of capillary GC and GC–MS. Seventy components were identiﬁed, constituting approximately 92.5% of the oil. The main constituents of the essential oil were thymol (42.8% and 43.1%), linalool (11.1% and 4.0%), γ‐terpinene (6.0% and 6.3%), 1,8‐cineole (5.6% and 3.3%), borneol (3.4% and 4.9%) and α‐terpineol (1.8% and 7.1%) at before ﬂowering (10 days before bloom formation) and full ﬂowering stage, respectively. Copyright © 2004 John Wiley & Sons, Ltd.
The essential oil composition of anise hyssop grown in India
Authors: Mallavarapu G. R. , Kulkarni R. N. , Baskaran K. , Ramesh S.
Published: May 2004

The composition of the essential oil of anise hyssop [Agastache foeniculum (Pursh) Kuntze] plants grown at Bangalore (India) was investigated by GC and GC–MS. The essential oils obtained from hydrodistillation of aerial parts of plants harvested at two plant growth stages, at the end of the vegetative stage and at full bloom, were found to contain methyl chavicol (91.7% and 95.2%) and limonene (3.6% and 3.9%) as the major constituents. Copyright © 2004 John Wiley & Sons, Ltd.
Superheated water extraction of fragrance compounds from Rosa canina
Authors: Özel Mustafa. Z. , Clifford Anthony A.
Published: May 2004

Floral oil of Rosa canina was isolated using superheated water extraction (SWE). The effects of different temperatures (50 °C, 100 °C and 150 °C) and pressures (25, 50 and 75 bar) on the recovery of fragrance compounds were investigated. The components of rose oil were removed from the aqueous extract by C18 solid phase extraction. Qualiﬁcation and quantiﬁcation were carried out by fast gas chromatography–time of ﬂight/mass spectroscopy (GC–TOF/MS) and gas chromatography–ﬂame ionization detection (GC–FID), respectively. SWE of rose petal oils shows a highest extraction efﬁciency at 100 °C, 2 ml/min ﬂow rate and 50 bar pressure for 2 h. The SWE‐based method is quicker, more environmentally friendly and more efﬁcient than the Soxhlet extraction method. Copyright © 2004 John Wiley & Sons, Ltd.
Score test for detecting linkage to complex traits in selected samples
Authors: Lebrec J. , Putter H. , Houwelingen J.C. van
Published: May 2004

We present a unified approach to selection and linkage analysis of selected samples, for both quantitative and dichotomous complex traits. It is based on the score test for the variance attributable to the trait locus and applies to general pedigrees. The method is equivalent to regressing excess IBD sharing on a function of the traits. It is shown that when population parameters for the trait are known, such inversion does not entail any loss of information. For dichotomous traits, pairs of pedigree members of different phenotypic nature (e.g., affected sib pairs and discordant sib pairs) can easily be combined as well as populations with different trait prevalences. © 2004 Wiley‐Liss, Inc.
A Report on the 30th Symposium on Heteroatom Chemistry of the Chemical Society of Japan
Authors: Sugihara Yoshiaki , Ishii Akihiko , Nakayama Juzo
Published: May 2004

The 30th domestic Chemical Society of Japan Symposium on Heteroatom Chemistry was held at Kuroda Auditorium of Toyama University during the period of December 11–13, 2003, under the management of Prof. Toshiaki Yoshimura and Dr. Takayoshi Fujii. More than 250 chemists from various academic institutes and industries enjoyed 4 plenary lectures, 48 oral presentations, and 62 poster presentations. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:347–361, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20020
Phosphorus heterocycles from 2‐(2‐hydroxyphenyl)‐1H‐benzimidazole
Authors: Hernández‐Díaz Julio , Flores‐Parra Angelina , Contreras Rosalinda
Published: May 2004

Sixteen different P(III) and P(V) heterocycles derived from 2‐(2‐hydroxyphenyl)‐1H‐benzimidazole (1) are reported. In these heterocycles the phosphorus atom is part of a six‐membered unsaturated ring. They were mainly studied by multinuclear NMR. The X‐ray diffraction of 3,4‐ benzimidazole‐5,6‐benzo‐2‐dimethylamino‐2‐seleno‐ 1,3,2‐oxazaphosphorinane is reported. Phosphoranes derived from 1 and 3,5‐di‐tert‐butylcatechol, and bearing Cl, NMe2, or phenyl as substituent at phosphorus are presented. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:307–320, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20021
Murine hepatocyte cell lines promote expansion and differentiation of NK cells from stem cell precursors
Authors: Bordoni Veronica , Alonzi Tonino , Agrati Chiara , Poccia Fabrizio , Borsellino Giovanna , Mancino Giorgio , Fimia Gian Maria , Piacentini Mauro , Fantoni Antonio , Tripodi Marco
Published: May 2004

While fetal liver is a major hematopoietic organ, normal adult liver provides a suitable microenvironment for a variety of immune cells and, in several pathological conditions, may become a site of extramedullary hematopoiesis. The direct influence of hepatocytes on hematopoietic cell differentiation is poorly understood. We have previously reported that the Met murine hepatocyte (MMH) untransformed hepatocytic lines retain several morphological and functional features of hepatocytes in vivo and are able to support the survival, self-renewal, and differentiation of hematopoietic precursors in a cell-cell contact system. Here we report the effects of soluble factors released by MMH lines on bone marrow-derived cells. Lymphohematopoietic cells were cultured in two different cell contact-free systems: transwell inserts on MMH feeder layers, and MMH conditioned medium (MMH-CM). Both culture systems were able to promote a substantial expansion of bone marrow-derived cells and their differentiation to natural killer (NK) cells that express the NK1.1 and U5A2-13 markers. Purified hematopoietic stem cells (Sca-1+Lin-), either plated as a bulk population or as single cells, were also able to differentiate into NK cells, when cultured in MMH-CM; thus, soluble factors secreted by MMH lines promote the expansion and differentiation of NK precursor cells. MMH-CM-derived NK cells are functionally active; stimulation by interleukin (IL)-12 together with IL-18 was required to induce interferon-gamma (IFNγ) expression and to enhance their cytotoxic activity. In conclusion, our findings may imply a direct role of hepatocytes in NK cell development, and the system we have used may provide a tool for studying the molecular mechanisms of NK cell differentiation. (Hepatology 2004;39:1508-1516.)
Effects of dilutional hyponatremia on brain organic osmolytes and water content in patients with cirrhosis
Authors: Restuccia Tea , Gómez-Ansón Beatriz , Guevara Mónica , Alessandria Carlo , Torre Aldo , Alayrach Elena M. , Terra Carlos , Martín Marta , Castellví Magda , Rami Lorena , Sainz Aitor , Ginès Pere , Arroyo Vicente
Published: May 2004

In advanced cirrhosis there is a reduction in the brain concentration of many organic osmolytes, particularly myo-inositol (MI). Hyponatremia could theoretically aggravate these changes as a result of hypo-osmolality of the extracellular fluid. The aim of this study was to determine the effects of hyponatremia on brain organic osmolytes and brain water content in cirrhosis. Brain organic osmolytes, measured by 1H-magnetic resonance spectroscopy, and brain water content, as estimated by magnetization transfer ratio (MTR) and measurement of brain volume were determined in 14 patients with dilutional hyponatremia, 10 patients without hyponatremia, and eight healthy subjects. Patients with hyponatremia had remarkable lower levels of MI compared with values in nonhyponatremic patients and healthy subjects. Brain MI levels correlated directly with serum sodium and osmolality. Serum sodium was the only independent predictor of low brain MI levels. Serum sodium also correlated directly with other brain organic osmolytes, such as choline-containing compounds, creatine/phosphocreatine, and N-acetyl-aspartate. By contrast, brain glutamine/glutamate levels were higher in patients with cirrhosis compared with values in healthy subjects and correlated with plasma ammonia levels but not with serum sodium or osmolality. No significant differences were found in MTR values and cerebral volumes between patients with and without hyponatremia. In conclusion, dilutional hyponatremia in cirrhosis is associated with remarkable reductions in brain organic osmolytes that probably reflect compensatory osmoregulatory mechanisms against cell swelling triggered by a combination of high intracellular glutamine and low extracellular osmolality. These findings may be relevant to the pathogenesis of encephalopathy in hyponatremic patients. (Hepatology 2004;39:1613-1622.)
Oxidative damage is increased in human liver tissue adjacent to hepatocellular carcinoma
Authors: Jüngst Christoph , Cheng Bin , Gehrke Ralph , Schmitz Volker , Nischalke Hans Dieter , Ramakers Jan , Schramel Peter , Schirmacher Peter , Sauerbruch Tilman , Caselmann Wolfgang Helmut
Published: May 2004

Accumulation of genetic alterations in hepatocarcinogenesis is closely associated with chronic inflammatory liver disease. 8-oxo-2′-deoxyguanosine (8-oxo-dG), the major promutagenic DNA adduct caused by reactive oxygen species (ROS), leads to G:C → T:A transversions. These lesions can be enzymatically repaired mainly by human MutT homolog 1 (hMTH1), human 8-oxo-guanine DNA glycosylase (hOGG1) and human MutY homolog (hMYH). The aim of this study was to evaluate the extent of oxidative damage and its dependence on the cellular antioxidative capacity and the expression of specific DNA repair enzymes in tumor (tu) and corresponding adjacent nontumor (ntu) liver tissue of 23 patients with histologically confirmed hepatocellular carcinoma. 8-oxo-dG levels, as detected by high-pressure liquid chromatography with electrochemical detection, were significantly (P = .003) elevated in ntu tissue (median, 129 fmol/μg DNA) as compared to tu tissue (median, 52 fmol/μg DNA), and were closely associated with inflammatory infiltration. In ntu tissue, the hepatic iron concentration and malondialdehyde levels were significantly (P = .001) higher as compared to tu tissue. Glutathione content, glutathione peroxidase activity and manganese superoxide dismutase messenger RNA (mRNA) expression did not show statistical differences between ntu and tu tissue. Real-time reverse transcription polymerase chain reaction revealed in tu tissue significantly (P = .014) higher hMTH1 mRNA expression compared to ntu tissue. In contrast, hMYH mRNA expression was significantly (P < .05) higher in ntu tissue. No difference in hOGG1 mRNA expression was seen between tu and ntu. In conclusion, these data suggest that ROS generated by chronic inflammation contribute to human hepatocarcinogenesis. The role of DNA repair enzymes appears to be of reactive rather than causative manner. (Hepatology 2004;39:1663-1672.)
Hepatitis B virus X protein is essential for the activation of Wnt/β-catenin signaling in hepatoma cells
Authors: Cha Man-Young , Kim Chang-Myeong , Park Young-Min , Ryu Wang-Shick
Published: May 2004

Wnt/β-catenin signaling contributes to diverse cellular functions, such as Drosophila wing development and colon carcinogenesis. Recently, stabilizing mutations of β-catenin, a hallmark of Wnt signaling, were documented in significant numbers of primary hepatocellular carcinomas (HCC). However, whether the β-catenin mutation leads to the activation of Wnt/β-catenin signaling in hepatoma cells has not been established. We found that Wnt/β-catenin signaling could be activated by ectopic expression of Wnt-1 in some hepatoma cells, such as Hep3B and PLC/PRF/5 cells, but not in others, such as Huh7 and Chang cells. Importantly, we noted that the former were derived from hepatitis B virus (HBV)-infected livers, whereas the latter were derived from HBV-negative livers. It was then speculated that HBx, a viral regulatory protein of HBV, is involved in activating Wnt/β-catenin signaling in hepatoma cells. In agreement with this notion, ectopic expression of HBx along with Wnt-1 activated Wnt/β-catenin signaling in Huh7 cells by stabilizing cytoplasmic β-catenin. Further, we showed that such stabilization of β-catenin by HBx was achieved by suppressing glycogen synthase kinase 3 activity via the activation of Src kinase. In conclusion, the data suggest that Wnt-1 is necessary but insufficient to activate Wnt/β-catenin signaling in hepatoma cells and the enhanced stabilization of β-catenin by HBx, in addition to Wnt-1, is essential for the activation of Wnt/β-catenin signaling in hepatoma cells. (Hepatology 2004;39:1683-1693.)
Informal payment for health care and the theory of ‘INXIT’
Authors: Gaal Peter , McKee Martin
Published: May 2004

Informal payments are known to be widespread in the post‐communist health care systems of Central and Eastern Europe. However, their role and nature remains contentious, with the debate characterized by much polemic. This paper steps back from this debate to examine the theoretical basis for understanding the persistence of informal payments.

The authors develop a cognitive behavioural model of informal payment, which draws on the theory of government failure and extends Hirschman's theory of ‘exit, voice, loyalty’, the behavioural responses to ‘decline in firms, organizations and states’. It is argued that informal payment represents another possible behavioural reaction: ‘inxit’, which becomes important when the channels of exit and voice are blocked.

The theory is applied to explain informal payments in Hungary, but can be shown to be relevant to other countries facing similar issues. The paper examines the proposed policies to tackle informal payments, and on the basis of the theory of ‘inxit’ it advocates that solutions should contain an appropriate balance between exit and voice to optimize the chances of maintaining a good standard of public services. Copyright © 2004 John Wiley & Sons, Ltd.
Sensitivity of myofibroblasts to H2O2‐mediated apoptosis and their antioxidant cell network
Authors: Larochelle Sébastien , Langlois Céline , Thibault Isabelle , Lopez‐Vallé Carlos A. , Roy Michel , Moulin Véronique
Published: May 2004

During wound healing, the transition from granulation to scar tissue shows a decrease in myofibroblast cellularity. Previous results have correlated the disappearance of these cells with the induction of apoptotic cell death by some unknown stimuli. In contrast, hypertrophic scar appearance after wound healing is thought to be linked to a disorder of apoptotic function which induces myofibroblast persistence in granulation tissue. Oxidative stress being an important mediator of apoptosis, we have evaluated the apoptotic response of normal and pathological wound myofibroblasts (WMyo and HMyo respectively) in their interaction with two oxidative stress inducers: hydrogen peroxide, using a high concentration as a single dose, and sodium ascorbate which induced a continuous release of H2O2 at a low concentration. Our results showed that, according to the H2O2 treatment type, HMyo were more sensitive (after ascorbate treatment) or less sensitive (after H2O2 treatment) when compared to WMyo and Fb. We next assessed the presence of several molecules known to be involved in the antioxidant network protecting cells against H2O2 injury and found HMyo to have a higher level of activity of glutathione peroxidase and a lower level of activity of catalase than WMyo. These results can help explain the contradictory responses of myofibroblasts according to the oxidative stress treatment. This is the first study linking refractory oxidative stress mediated cell death to cellular phenotype in hypertrophic myofibroblasts, and indicates a pivotal role for the antioxidant enzyme system in this type of resistance. © 2004 Wiley‐Liss, Inc.
Positive margins following surgical resection of breast carcinoma: Analysis of pathologic correlates
Authors: Miller Alexander R. , Brandao Guillermo , Prihoda Thomas J. , Hill Cheryl , Cruz Anatolio B. , Yeh I‐Tien
Published: May 2004

Background and Objectives

Histologic margin positivity represents a significant source of adverse clinical outcome affecting breast conservation therapy for in situ or invasive malignancy. Elucidation of factors associated with positive margin status might clarify and improve local therapy strategies. In order to define our experience with margin positivity and to identify relevant pathologic criteria, we retrospectively analyzed the cases of 143 patients who underwent resections for carcinoma with intent of breast conservation between 1995 and 1999.

Methods

Histologic features and indices of biologic aggressiveness were compared among tumors resected with positive versus negative margins in order to determine whether such markers could be used to anticipate outcome.

Results

Twenty‐eight pathologic specimens were identified to possess histologically positive margins. Twenty‐six patients underwent additional operative procedures. Of the 26 re‐excision specimens, 17 (65%) contained residual malignancy. Statistical analysis demonstrated that margin positivity correlated with in situ histology and with Her 2/neu positivity.

Conclusions

These data suggest certain pathologic factors that may portend difficulty in achieving negative resection margins in patients in whom breast conservation therapy is considered. J. Surg. Oncol. 2004;86:134–140. © 2004 Wiley‐Liss, Inc.
Assessment of autonomic dysfunction in Parkinson's disease: The SCOPA‐AUT
Authors: Visser Martine , Marinus Johan , Stiggelbout Anne M. , Van Hilten Jacobus J.
Published: May 2004

We developed a questionnaire to assess autonomic symptoms in patients with Parkinson's disease (PD) and evaluated its reliability and validity. Based on the results of a postal survey in 46 PD patients, 21 multiple system atrophy patients, and 8 movement disorders specialists, items were included according to their frequency, burden, and clinical relevance. The questionnaire was evaluated in 140 PD patients and 100 controls, and test–retest reliability was established in a sample of 55 PD patients. The SCOPA‐AUT consists of 25 items assessing the following regions: gastrointestinal (7), urinary (6), cardiovascular (3), thermoregulatory (4), pupillomotor (1), and sexual (2 items for men and 2 items for women) dysfunction. Test–retest reliability was good. Autonomic problems increased significantly with increasing disease severity for all autonomic regions, except sexual dysfunction. We conclude that SCOPA‐AUT is a reliable and valid questionnaire that evaluates autonomic dysfunction in PD. © 2004 Movement Disorder Society
Abnormalities of dopaminergic neurotransmission in SCA2: A combined 123I‐βCIT and 123I‐IBZM SPECT study
Authors: Boesch Sylvia M. , Donnemiller Eveline , Müller Jörg , Seppi Klaus , Weirich‐Schwaiger Helga , Poewe Werner , Wenning Gregor K.
Published: May 2004

Extrapyramidal features may occur in spinocerebellar ataxias consistent with neuropathological evidence of nigrostriatal involvement. Recently, striatal dopaminergic neurotransmission was found to be abnormal in the uncommon parkinsonian presentation of spinocerebellar ataxia type 2 (SCA2). We have investigated, therefore, striatal dopamine transporter and D2 receptor function in a series of 9 patients with the more common ataxic presentation of SCA2 using single photon emission computed tomography and β‐CIT as well as IBZM. Age‐matched healthy subjects and patients with Parkinson's disease (PD) served as controls. All except 1 SCA2 patient exhibited slowness of limb movements without rigidity or rest tremor. In addition, cervical dystonia was present in 5 and dystonic head tremor in 2 SCA2 patients. Striatocerebellar (S/C) ratios of β‐CIT binding were significantly reduced in SCA2 patients compared to control subjects, and they were within the range of PD patients. S/C ratios of IBZM binding were significantly reduced in SCA2 patients compared to control subjects. We conclude that dopaminergic neurotransmission is impaired in the ataxic presentation of SCA2, with a prominent loss of striatal dopamine transporter function. Both slowness of limb movements as well as dystonia in the ataxic SCA2 phenotype may reflect dysfunction not only at cerebellar but also at basal ganglia level. © 2004 Movement Disorder Society
Applications of proteomic methodologies to human pregnancy research: A growing gestation approaching delivery?
Authors: Shankar Renu , Cullinane Fiona , Brennecke Shaun Patrick , Moses Eric Keith
Published: May 2004

Maternal and perinatal morbidity and mortality rates are significantly higher in pregnancies complicated by preterm labor, pre‐eclampsia and fetal growth restriction. Decades of research have not translated into a clear understanding of the underlying pathophysiologies or effective identification of women who are at high risk of developing these complications. Often the severity of these diseases does not correlate with the clinical symptoms, and current diagnostic methods are unable to accurately predict the conditions prior to clinical presentation. Though several potential markers have been proposed for each of these disorders, to date none have proven clinical utility. Emerging proteomic technology is only beginning to be employed in pregnancy research. A comprehensive analysis of gestational tissues can be expected to contribute to the elucidation of the complex molecular mechanisms of pregnancy and related complications. Comparison of the expression profiles of normal and pathogenic tissues and biofluids may also highlight novel candidate marker proteins that have so far remained undetected. More interestingly, rapidly evolving technologies using sophisticated bioinformatic tools are demonstrating their potential in disease diagnostics by using overall protein profiles to detect diseases. The clinical significance of these methodological advances is enormous. Early diagnosis together with improved understanding of underlying molecular mechanisms can enhance outcomes and increase effective management and therapeutic options.
Proteomic approaches in endometriosis research
Authors: Poliness Anne E. , Healey Martin G. , Brennecke Shaun P. , Moses Eric K.
Published: May 2004

To date, the quest to develop a noninvasive diagnostic test for endometriosis has mostly concentrated on the levels of cytokines and growth factors that are involved in inflammation, angioneogenesis and tissue remodeling, present in serum, peritoneal fluid, endometrium and endometriotic lesions. As this has not yet translated into the development of such a diagnostic test, proteomic techniques are now being employed to identify proteins that are potential biomarkers for the disease. As proteomics allows the comprehensive analysis of complex fluid and tissue samples with good sensitivity and resolution, it has promise in delivering markers associated with endometriosis. Once identified, the challenge will be in translating these markers into a clinically useful test for endometriosis, as the pathophysiology of this disease is unknown and likely to be complex and multifactorial. Also, with variation between individuals and the influences of steroid hormones during the menstrual cycle, it could be difficult to validate findings relating to a single protein or small groups of proteins differentially expressed in the disease state. Proteomic profiling, using mass spectrometry in combination with sophisticated bioinformatics software to identify protein patterns, may be where a significant clinical diagnostic contribution can be made.
Block copolymer nanoparticles of controlled sizes via ring‐opening metathesis polymerization
Authors: Carrillo Alvaro , Kane Ravi S.
Published: May 2004

This article describes the formation and characterization of self‐assembled nanoparticles of controlled sizes based on amphiphilic block copolymers synthesized by ring‐opening metathesis polymerization. We synthesized a novel hydrophobic derivative of norbornene; this monomer could be polymerized using Grubbs' catalyst [Cl2Ru(CHPh)(PCy3)2] forming polymers of controlled molecular weight. We synthesized amphiphilic block copolymers of controlled composition and showed that they assemble into nanoparticles of controlled size. The nanoparticles were characterized using dynamic light scattering and transmission electron microscopy. Tuning the composition of the block copolymer enables the tuning of the diameters of the nanoparticles in the 30‐ to 80‐nm range. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3352–3359, 2004
Facile synthesis and characterization of the copolymers and their pure nanoparticles from aniline with 4‐sulfonic diphenylamine
Authors: Li Xin‐Gui , Zhou Hai‐Jun , Huang Mei‐Rong , Zhu Mei‐Fang , Chen Yan‐Mo
Published: May 2004

Copolymer nanoparticles from aniline (AN) and 4‐sulfonic diphenylamine (SDP) were simply synthesized for the first time by an oxidative precipitation polymerization with inorganic oxidants in an acidic aqueous medium without any external emulsifier or stabilizer. The polymerization yield, intrinsic viscosity, solubility, solvatochromism, electrical conductivity, and thermal stability of the copolymers were systematically studied through changes in the AN/SDP ratio, polymerization temperature, oxidant species, monomer/oxidant ratio, and acidic medium. The molecular structure of the copolymers was characterized with elemental analysis, IR, and ultraviolet–visible spectra. The polymers exhibited very good solubility in polar solvents, water, and NH4OH, and this was mainly attributable to the presence of sulfonic acid side groups. The electrical conductivity of the copolymers increased greatly, from 6.00 × 10−4 to 2.55 × 10−1 S/cm, with increasing AN content. The size of the copolymer particles, determined by laser particle analysis and atomic force microscopy (AFM), strongly depended on the polymer state and oxidant/monomer ratio. Pure dedoped particles of the AN/SDP (50/50) copolymer at an oxidant/monomer ratio of 1/2 exhibited minimum length/diameter ratios of 62/44 and 45/30 nm by AFM and transmission electron microscopy, respectively. The copolymers showed typical four‐step weight‐loss behavior in nitrogen and air and higher thermostability in nitrogen. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3380–3394, 2004
Ultrahigh‐molecular‐weight‐polyethylene‐fiber surface treatment by electron‐beam‐irradiation‐induced graft polymerization and its effect on adhesion in a styrene–butadiene rubber matrix
Authors: Sakurai K. , Kondo Y. , Miyazaki K. , Okamoto T. , Irie S. , Sasaki T.
Published: May 2004

Aiming to develop a high‐performance fiber‐reinforced rubber from styrene–butadiene rubber (SBR), we applied a special technique using electron‐beam (EB)‐irradiation‐induced graft polymerization to ultrahigh‐molecular‐weight‐polyethylene (UHMWPE) fibers. The molecular interaction between the grafted UHMWPE fibers and an SBR matrix was studied through the evaluation of the adhesive behavior of the fibers in the SBR matrix. Although UHMWPE was chemically inert, two monomers, styrene and N‐vinyl formamide (NVF), were examined for graft polymerization onto the UHMWPE fiber surface. Styrene was not effective, but NVF was graft‐polymerized onto the UHMWPE fibers with this special method. A methanol/water mixture and dioxane were used as solvents for NVF, and the effects of the solvents on the grafting percentage of NVF were also examined. The methanol/water mixture was more effective. A grafting percentage of 16.4% was the highest obtained. This improved the adhesive force threefold with respect to that of untreated UHMWPE fibers. These results demonstrated that EB irradiation enabled graft polymerization to occur even on the inert surface of UHMWPE fibers. However, the mechanical properties of the fibers could be compromised according to the dose of EB irradiation. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 2595–2603, 2004
Antioxidant activity of three extracts of Morus nigra
Authors: Naderi Gholam Ali , Asgary Seddigheh , Sarraf‐Zadegan Nizal , Oroojy Heshmatallah , Afshin‐Nia Farsad
Published: May 2004

The antioxidant effect of three different extracts of Morus nigra fruit (fruit juice, hydroalcoholic and polyphenolic) on haemoglobin glycosylation, peroxidative damage to human erythrocytes, liver hepatooytes of rats and human low‐density lipoprotein (LDL) were studied. The results show that all three extracts inhibited haemoglobin glycosylation induced by glucose to differing degrees. The haemolysis of human erythrocytes induced by hydrogen peroxide was also inhibited. The production of malondialdehyde (MDA) during peroxidative damage to plasma membranes of isolated rat hepatocytes induced by tert‐butyl hydroperoxide (tBH) was also inhibited. Inhibition of lipid peroxidation of LDL induced by copper (II) ion was achieved during the study.

The results suggest that Morus nigra fruit has a protective action against peroxidative damage to biomembranes and biomolecules. Copyright © 2004 John Wiley & Sons, Ltd.
Evaluation of the anticarcinogenic activity of Swertia chirata Buch.Ham, an Indian medicinal plant, on DMBA‐induced mouse skin carcinogenesis model
Authors: Saha Prosenjit , Mandal Suvra , Das Ashes , Das Prabhas C. , Das Sukta
Published: May 2004

Considerable attention has been focused on plants which are sources of natural anti‐oxidant compounds, because most of them have a modulatory role on physiological functions and biotransformation reactions involved in the detoxiﬁcation process. Such compounds are likely to afford protection from cytotoxic, genotoxic and metabolic actions of environmental toxicant thereby reducing the risk for cancer. The present study reports the anticarcinogenic activity of Swertia chirata Buch.Ham, an Indian medicinal plant. All the four detoxiﬁcation enzymes studied viz, GST, GPx, SOD and CAT were found to be activated in different degrees following treatment with infusion of Swertia chirata, its crude extract and a puriﬁed ‘Amarogentin’ rich extract. The activation of the enzymes was accompanied by signiﬁcant reduction in lipid peroxidation and inhibition of incidence as well as multiplicity of Dimethylbenz(a)anthracene (DMBA) induced papillomas. The effect of S.chirata on apoptosis and cell proliferation was also studied in mice skin exposed to DMBA. Both the crude and puriﬁed extracts signiﬁcantly inhibited cell proliferation and induced apoptosis. This is the ﬁrst report of its kind and the observation suggests the chemopreventive potential of Swertia chirata. Copyright © 2004 John Wiley & Sons, Ltd.
Prevention of bone loss by oil extract of garlic (Allium sativum Linn.) in an ovariectomized rat model of osteoporosis
Authors: Mukherjee M. , Das A. S. , Mitra S. , Mitra C.
Published: May 2004

The effects of oil extract of garlic (Allium sativum Linn.) on different primary and secondary osteoporotic marker changes were tested in an ovariectomized rat model of osteoporosis. Experiments were performed on three different rat models: sham‐operated control, ovariectomized and ovariectomized supplemented with garlic oil. In ovariectomized group, there has been a signiﬁcant increase in different relative organ weights compared to sham‐operated control, while the uterine weight was found to be decreased. Supplementation with oil extract of garlic could effectively reverse these changes. Also low bone densities that developed in the ovariectomized group were signiﬁcantly recovered in the garlic oil supplemented group. In our study, the development of high rate of bone turnover and osteoporosis in the ovariectomized animals were conﬁrmed by signiﬁcant alteration of serum alkaline phosphatase activity, serum tartrate resistant acid phosphatase activity, urinary excretion of calcium, phosphate, hydroxyproline and urinary calcium to creatinine ratio, when compared with the sham‐operated control group. Garlic oil extract supplementation, apart from its unique inﬂuence in lowering blood cholesterol, could also prevent ovariectomy‐induced rise in all the above‐mentioned marker changes. The results of this study emphasize that oil extract of garlic possibly has a positive role in suppressing ovariectomy‐induced bone resorption. Copyright © 2004 John Wiley & Sons, Ltd.
Nimbidin suppresses functions of macrophages and neutrophils: relevance to its antiinﬂammatory mechanisms
Authors: Kaur Gurpreet , Sarwar Alam M. , Athar M.
Published: May 2004

Nimbidin is a mixture of tetranortriterpenes and is the major active principle of the seed oil of Azadirachta indica A. Juss (Meliaceae) possessing potent antiinﬂammatory and antiarthritic activities. The present study revealed that nimbidin signiﬁcantly inhibited some of the functions of macrophages and neutrophils relevant to the inﬂammatory response following both in vivo and in vitro exposure. Oral administration of 5–25 mg/kg nimbidin to rats for 3 consecutive days signiﬁcantly inhibited the migration of macrophages to their peritoneal cavities in response to inﬂammatory stimuli and also inhibited phagocytosis and phorbol‐12‐myristate‐13‐acetate (PMA) stimulated respiratory burst in these cells. In vitro exposure of rat peritoneal macrophages to nimbidin also inhibited phagocytosis and PMA stimulated respiratory burst in these cells. Nimbidin also inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS) stimulated macrophages following in vitro exposure, whereas interleukin 1 (IL‐1) was only weakly inhibited. Probing the mechanism of NO inhibition revealed that nimbidin ameliorated the induction of inducible NO synthase (iNOS) without any inhibition in its catalytic activity. In addition, nimbidin also attenuated degranulation in neutrophils assessed in terms of release of β‐glucuronidase, myeloperoxidase and lysozyme. The results suggest that nimbidin suppresses the functions of macrophages and neutrophils relevant to inﬂammation. Thus nimbidin can be valuable in treating inﬂammation/inﬂammatory diseases. Copyright © 2004 John Wiley & Sons, Ltd.
An investigation on the role of 3‐hydroxykynurenine in pigment formation by matrix‐assisted laser desorption/ionization mass spectrometry
Authors: Vogliardi Susanna , Bertazzo Antonella , Comai Stefano , Costa Carlo V. L. , Allegri Graziella , Seraglia Roberta , Traldi Pietro
Published: May 2004

In order to investigate the role of tryptophan and its metabolites in biogenesis of melanins, a study on the enzymatic reaction of 3‐hydroxykynurenine with tyrosinase and peroxidase was performed. The reaction at different pH values was monitored by sampling at different times, with ultrafiltration used before analysis by matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS). The data obtained in this way showed that oligomerization processes take place with both enzymes, but with different behaviour, also depending on pH. 3‐Hydroxykynurenine in the presence of tyrosinase at pH 6.0 leads to formation of xanthommatin, and at pH 8.0 hydroxanthommatin is formed in the first step of the reaction followed by formation of black‐brown pigments. In contrast, the formation of oligomerization products by peroxidase action is observed in high yields under both acidic and basic conditions; however, at pH 6.0, a more extensive oligomerization process is observed. Thus peroxidase is able to activate oligomerization analogous to that observed in the case of tyrosinase without depending on the variation of pH. Due to the early formation of decarboxylated hydroxykynurenine, hydroxanthommatin and decarboxylated hydroxanthommatin, the enzymatic reaction leads to mixed oligomers, which can be considered as precursors of new pathways in pigment production. Copyright © 2004 John Wiley & Sons, Ltd.
A new continuous flow isotope ratio mass spectrometry system for the analysis of δ2H, δ17O and δ18O of small (120 μg) water samples in atmospheric applications
Authors: Franz Peter , Röckmann Thomas
Published: May 2004

A new continuous‐flow system for the analysis of the complete stable isotopic composition of water vapor has been developed. The sample size is reduced to only 120 μg (≡120 nL of liquid substance) of water, yielding precisions of about 0.7, 1.3 and 7‰ for δ17O, δ18O and δ2H, respectively. The total time for the analysis of a sample is about 150 min including purging times. Oxidized steel surfaces can be a source of memory effects which can be corrected for. The system is predestined for atmospheric applications in the tropopause region, as the sample can be directly introduced into the system from a cryogenic trap. Copyright © 2004 John Wiley & Sons, Ltd.