bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection
Authors: De Milito Angelo , Nilsson Anna , Titanji Kehmia , Thorstensson Rigmor , Reizenstein Elisabet , Narita Mitsuo , Grutzmeier Sven , Sönnerborg Anders , Chiodi Francesca 
Published: November 2003

Abstract
Hypergammaglobulinemia and defective humoral immunity are hallmarks of HIV-1 infection. Naive B cells have been recently suggested as the major source of hypergammaglobulinemia in chronic viral infections. We recently reported that HIV-1–infected patients carry low levels of memory B cells. Here we studied whether defects in the naive and memory B cells in HIV-1–infected patients translated into hypergammaglobulinemia and defective humoral immunity against specific antigens. Naive B cells from HIV-1–infected patients exhibited abnormal expression of the activation/differentiation markers CD70 and leukocyte-associated Ig-like receptor (LAIR-1). Activated naive B cells from patients showed a significant increase in the intracellular immunoglobulin G (IgG) content ex vivo and this activated phenotype correlated to hypergammaglobulinemia and to the ability of naive B cells from patients to secrete IgG in vitro. We analyzed the levels of antibodies to tetanus toxoid, measles, and HIV-1 in relation to memory B cells and observed a significant reduction of antigen-specific antibodies in patients with low-memory B lymphocytes. Nevertheless, hypergammaglobulinemia and levels of polyspecific self-reactive antibodies were comparable in patients with normal and low memory B cells. We conclude that reduction of memory B lymphocytes in HIV-1 infection correlates with defective humoral immunity and that hyperactivated naive B cells may represent the source of abnormal IgG production in HIV-1 infection. Our results may be relevant to the design of HIV-1 therapeutical vaccines and to the clinical management of HIV-1–infected patients.
The Phytoestrogen Genistein Enhances Osteogenesis and Represses Adipogenic Differentiation of Human Primary Bone Marrow Stromal Cells
Authors: Heim M. , Frank O. , Kampmann G. , Sochocky N. , Pennimpede T. , Fuchs P. , Hunziker W. , Weber P. , Martin I. , Bendik I. 
Published: November 2003

AbstractIn the present study, we investigated the role of the phytoestrogen genistein and 17β-estradiol in human bone marrow stromal cells, undergoing induced osteogenic or adipogenic differentiation. Profiling of estrogen receptors (ERs)-α, -β1, -β2, -β3, -β4, -β5, and aromatase mRNAs revealed lineage-dependent expression patterns. During osteogenic differentiation, the osteoblast-determining core binding factor-α1 showed a progressive increase, whereas the adipogenic regulator peroxisome proliferator-activated receptor γ (PPARγ) was sequentially decreased. This temporal regulation of lineage-determining marker genes was strongly enhanced by genistein during the early osteogenic phase. Moreover, genistein increased alkaline phosphatase mRNA levels and activity, the osteoprotegerin:receptor activator of nuclear factor-κB ligand gene expression ratio, and the expression of TGFβ1. During adipogenic differentiation, down-regulation in the mRNA levels of PPARγ and CCAAT/enhancer-binding protein-α at d 3 and decreased lipoprotein lipase and adipsin mRNA levels at d 21 were observed after genistein treatment. This led to a lower number of adipocytes and a reduction in the size of their lipid droplets. At d 3 of adipogenesis, TGFβ1 was strongly up-regulated by genistein in an ER-dependent manner. Blocking the TGFβ1 pathway abolished the effects of genistein on PPARγ protein levels and led to a reduction in the proliferation rate of precursor cells. Overall, genistein enhanced the commitment and differentiation of bone marrow stromal cells to the osteoblast lineage but did not influence the late osteogenic maturation markers. Adipogenic differentiation and maturation, on the other hand, were reduced by genistein (and 17β-estradiol) via an ER-dependent mechanism involving autocrine or paracrine TGFβ1 signaling.
sFlt-1 Gene Therapy of Follicular Thyroid Carcinoma
Authors: Ye Caisheng , Feng Chong , Wang Shenming , Wang Kent Z. Q. , Huang Nancy , Liu Xiaoning , Lin Yongjie , Li Mengfeng 
Published: November 2003

Abstract
Tumor progression largely depends on blood supply and neovessel formation, and angiogenesis is emerging as a promising target for cancer therapy. Vascular endothelial growth factor (VEGF), a major proangiogenic molecule, stimulates angiogenesis via promoting endothelial proliferation, survival and migration. VEGF has been found to be up-regulated in various types of tumors and to be associated with tumor progression and poor prognosis. Inhibition of VEGF or its signaling pathway has been shown to suppress tumor angiogenesis and tumor growth. In the present study, we tested the antiangiogenic and antitumor effects of soluble VEGF receptor-1 [soluble Flt (sFlt)-1] on the growth of follicular thyroid carcinoma (FTC). We constructed a 293 embryonic kidney cell line (293-Flt1–3d) that expresses sFlt-1, which is composed of the first three extracellular domains of Flt-1. The 293-Flt1–3d cells inhibited the in vitro growth of human umbilical vein endothelial cells in a paracrine manner. The in vivo antitumor and antiangiogenic activities of the 293-Flt1–3d cells were tested. When 293-Flt1–3d cells were inoculated at a site remote to the FTC-133 tumor transplant, the growth of FTC-133 tumors were inhibited by 70.37%, as compared with the control treatment with 293 cells expressing control gene LacZ. Immunohistochemical analysis of microvessel densities in treated tumors demonstrated that 293-Flt1–3d cells robustly suppressed intratumoral angiogenesis. Our data suggest that a mammalian cell-mediated approach could effectively deliver sFlt-1 gene therapy and inhibit tumor angiogenesis and tumor growth.
Rapid, Nongenomic Effects of Aldosterone in the Heart Mediated by ε Protein Kinase C
Authors: Mihailidou Anastasia S. , Mardini Mahidi , Funder John W. 
Published: November 2003

Abstract
Aldosterone elevates Na+/K+/2Cl− cotransporter activity in rabbit cardiomyocytes within 15 min, an effect blocked by K-canrenoate and thus putatively mineralocorticoid receptor mediated. Increased cotransporter activity raises intracellular [Na+] sufficient to produce a secondary increase in Na+-K+ pump activity; when this increase in intracellular [Na+] is prevented, a rapid effect of aldosterone to lower pump activity is seen. Addition of transcription inhibitor actinomycin D did not change basal or aldosterone-induced lowered pump activity, indicating a direct, nongenomic action of aldosterone. We examined a possible role for protein kinase C (PKC) in the rapid nongenomic effects of aldosterone. Single ventricular myocytes and pipette solutions containing 10 mm intracellular [Na+] were used in patch clamp studies to measure Na+-K+ pump activity. Aldosterone lowered pump current, an effect abolished by ε PKC (εPKC) inhibition but neither αPKC nor scrambled εPKC; addition of εPKC activator peptide mimicked the rapid aldosterone effect. In rabbits chronically infused with aldosterone, the lowered pump current in cardiomyocytes was acutely (≤15 min) restored by εPKC inhibition. These studies show that rapid effects of aldosterone on Na+-K+ pump activity are nongenomic and specifically εPKC mediated; in addition, such effects may be prolonged (7 d) and long-lived (∼4 h isolated cardiomyocyte preparation time). The rapid, prolonged, long-lived effects can be rapidly (≤15 min) reversed by εPKC blockade, suggesting a hitherto unrecognized complexity of aldosterone action in the heart and perhaps by extension other tissues.
Carboxy Terminus of Glucose Transporter 3 Contains an Apical Membrane Targeting Domain
Authors: Inukai Kouichi , Shewan Annette M. , Pascoe Wendy S. , Katayama Shigehiro , James David E. , Oka Yoshitomo 
Published: November 2003

AbstractWe previously demonstrated that distinct facilitative glucose transporter isoforms display differential sorting in polarized epithelial cells. In Madin-Darby canine kidney (MDCK) cells, glucose transporter 1 and 2 (GLUT1 and GLUT2) are localized to the basolateral cell surface whereas GLUTs 3 and 5 are targeted to the apical membrane. To explore the molecular mechanisms underlying this asymmetric distribution, we analyzed the targeting of chimeric glucose transporter proteins in MDCK cells. Replacement of the carboxy-terminal cytosolic tail of GLUT1, GLUT2, or GLUT4 with that from GLUT3 resulted in apical targeting. Conversely, a GLUT3 chimera containing the cytosolic carboxy terminus of GLUT2 was sorted to the basolateral membrane. These findings are not attributable to the presence of a basolateral signal in the tails of GLUTs 1, 2, and 4 because the basolateral targeting of GLUT1 was retained in a GLUT1 chimera containing the carboxy terminus of GLUT5. In addition, we were unable to demonstrate the presence of an autonomous basolateral sorting signal in the GLUT1 tail using the low-density lipoprotein receptor as a reporter. By examining the targeting of a series of more defined GLUT1/3 chimeras, we found evidence of an apical targeting signal involving residues 473–484 (DRSGKDGVMEMN) in the carboxy tail. We conclude that the targeting of GLUT3 to the apical cell surface in MDCK cells is regulated by a unique cytosolic sorting motif.
Intranasal steroid sprays in the treatment of rhinitis: is one better than another?
Authors: Waddell A. N. , Patel S. K. , Toma A. G. , Maw A. R. 
Published: November 2003

The treatment of allergic rhinitis has been revolutionized by the introduction of topical nasal steroids, which are one of the commonest prescriptions from otolaryngology departments. With so many different sprays available on the market, the literature was reviewed for the efficacy, side-effect profile and relative cost of each product and the following conclusions made:(1) A meta-analysis of randomized controlled trials comparing the efficacy of intranasal corticosteroids and oral antihistamines in the treatment of allergic rhinitis showed a clear benefit in favour of intranasal steroids in relieving nasal symptoms.(2) There is no clear evidence to support the suggestion that one steroid spray is more effective than another in the treatment of seasonal or perennial allergic rhinitis.(3) All the sprays have a similar side-effect profile; the commonest being epistaxis with a reported incidence between 17 and 23 per cent. In all the clinical trials, the placebo spray had an appreciable rate of epistaxis of between 10 to 15 per cent.(4) Fluticasone causes a reduction in endogenous cortisol secretion but no significant adrenal suppression was seen with triamcinolone, beclomethasone, budesonide or mometasone.(5) There is little evidence that skeletal growth is restricted by the administration of topical nasal steroid sprays.(6) There is considerable variation in the daily cost of each spray. Beclomethasone, dexamethasone and budesonide are significantly cheaper than fluticasone, mometasone or triamcinolone.
Experimental verification of the role of interstitial fluid pressurization in cartilage lubrication
Authors: Krishnan Ramaswamy , Kopacz Monika , Ateshian Gerard A. 
Published: November 2003

AbstractThe objective of the current study was to measure the friction coefficient simultaneously with the interstitial fluid load support in bovine articular cartilage, while sliding against glass under a constant load. Ten visually normal 6‐mm‐diameter cartilage plugs harvested from the humeral head of four bovine shoulder joints (ages 2–4 months) were tested in a custom friction device under reciprocating linear motion (range of translation ± 2 mm; sliding velocity 1 mm/s), subjected to a 4.5 N constant load. The frictional coefficient was found to increase with time from a minimum value of μmin = 0.010 ± 0.007 (mean ± SD) to a maximum value of 0.243 ± 0.044 over a duration ranging from 920 to 19,870 s (median: 4,560 s). The corresponding interstitial fluid load support decreased from a maximum of 88.8 ± 3.8% to 8.7 ± 8.6%. A linear correlation was observed between the frictional coefficient and interstitial fluid load support (r2 = 0.96 ± 0.03). These results support the hypothesis that the temporal variation of the frictional coefficient correlates negatively with the interstitial fluid load support and that consequently interstitial fluid load support is a primary mechanism regulating the frictional response in articular cartilage. Fitting the experimental data to a previously proposed biphasic boundary lubrication model for cartilage yielded an equilibrium friction coefficient of μeq = 0.284 ± 0.044. The fraction of the apparent contact area over which the solid cartilage matrix was in contact with the glass slide was predicted at π = 1.7 ± 6.3%, significantly smaller than the solid volume fraction of the tissue, πs = 13.8 ± 1.8%. The model predictions suggest that mixed lubrication prevailed at the contact interface under the loading conditions employed in this study. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
The Italian colonial cinema: agendas and audiences
Authors: Ben-Ghiat Ruth 
Published: November 2003

SummaryWhat role has culture played in shaping Italians’ experiences of Italian colonialism before and after the Second World War? How can the tools of cultural analysis be employed to understand the place and space Italian colonialism has had within Italian and European history? This article draws on and discusses the growing body of scholarly work about colonial narratives and representations (exhibitions, travel writings, etc.) but is centred on the Italian colonial cinema. It focuses, in particular, on the issue of the double-edged power of the visual in colonial films with respect to both Italian and African audiences. The article explores spectatorship under colonial conditions but also how the visual elements of colonial films contributed to or complicated the production of ‘colonial experiences’ among the many Italians who never set foot in Africa.
From territorial to ethnographic colonies and back again: the politics of Italian expansion, 1890–1912
Authors: Choate Mark I. 
Published: November 2003

SummaryFor Italy, unprecedented mass migration in the late nineteenth century overshadowed the European Scramble for Africa. To secure Italy's place in the new imperial order, Francesco Crispi proposed to harness emigration for colonial expansion, by settling Italy's East African colonies with the surplus Italian population. Defeat at Adwa in 1896 shattered Crispi's project, and turned attention to colonial possibilities elsewhere. Luigi Einaudi and other Liberals trumpeted the value of Italian collectivities or colonie across the Atlantic, where Italy exerted only indirect influence. In theory, these ‘spontaneous colonies’ would boost the Italian economy at little expense. Italian colonialist societies turned from Africa to the Americas, working to make Italian migration more prestigious, successful and profitable. After 1908, however, Enrico Corradini and the Italian Nationalists mocked these initiatives, and called upon the Italian state to return to traditional imperialism in Africa.
Region‐dependent changes in endocannabinoid transmission in the brain of morphine‐dependent rats
Authors: GONZÁLEZ SARA , SCHMID PATRICIA , FERNÁNDEZ‐RUIZ JAVIER , KREBSBACH RANDY , SCHMID HARALD , RAMOS JOSÉ 
Published: November 2003

AbstractIt has been suggested recently that the endocannabinoid system might be a component of the brain reward circuitry and thus play a role not only in cannabinoid tolerance/dependence, but also in dependence/withdrawal to other drugs of abuse. Here we have examined the changes in endocannabinoid ligands and their receptors in different brain regions, with particular attention to those areas related to reinforcement processes, during dependence on the powerful addictive drug, morphine. Thus, we analysed the brain contents of N‐arachidonoylethanolamine (anandamide, AEA), the first discovered endocannabinoid, in rats subjected to daily injections of increasing doses of morphine, according to a schedule designed to render the animals opiate‐dependent. Although evidence of physical dependence was assured by the appearance of somatic and neurovegetative responses in these animals after an acute challenge with naloxone, there were no changes in the contents of this endocannabinoid in any of the brain regions analysed. By contrast, we observed a significant decrease in the specific binding for CB 1 receptors in the midbrain and the cerebral cortex of morphine‐dependent rats, with no changes in the other regions. The decrease in the cerebral cortex was, however, accompanied by a rise in the activation of signalling mechanisms by CB 1 receptor agonists, as revealed by WIN‐55,212‐2‐stimulated [35 S]GTPγS binding, whereas a reduction in this parameter was measured in the brainstem of morphine‐dependent rats. In summary, the present data are indicative of the existence of an alteration of the endocannabinoid transmission during morphine dependence in rats, although the changes observed were region‐dependent and affected exclusively CB 1 receptors with no changes in endocannabinoid levels. Because the changes occurred in regions of the midbrain, the cerebral cortex and the brainstem, which have been implicated in drug dependence, our data suggest that pharmacological manipulation of the endocannabinoid system might be a novel tool to reduce morphine addiction.
Selective d‐opioid receptor antagonist N,N(CH 3) 2 ‐Dmt‐Tic‐OH does not reduce ethanol intake in alcohol‐preferring AA rats
Authors: INGMAN KIMMO , SALVADORI SEVERO , LAZARUS LARRY , KORPI ESA , HONKANEN AAPO 
Published: November 2003

AbstractWe studied the effect of a novel δ‐opioid receptor antagonist N,N(CH 3) 2 Dmt‐Tic‐OH (Me 2 ‐Dmt‐Tic‐OH) on voluntary ethanol intake in an alcohol‐preferring AA (Alko, Alcohol) rat line using a 4‐hour limited access paradigm. Acute injections of Me 2 ‐Dmt‐Tic‐OH (10 and 30 mg/kg, i.p.) did not reduce 1‐hour or 4‐hour ethanol intake. Subtype non‐selective opioid receptor antagonist naltrexone [0.1 and 0.3 mg/kg, subcutaneously (s.c.)] significantly reduced 1‐hour ethanol drinking but had no effect on 4‐hour ethanol consumption. Locomotor stimulation induced by the δ‐opioid receptor agonist Tyr‐D‐Pen‐Gly‐Phe‐D‐Pen (DPDPE; 15 μg, intracerebroventricularly) was significantly attenuated by Me 2 ‐Dmt‐Tic‐OH (10 and 30 mg/kg, i.p.), which confirmed its efficacy as a δ‐opioid receptor antagonist in rat brain. Our results support the idea that δ‐opioid receptors do not mediate alcohol reward in AA rats.
A pilot study on the effects of treatment with acamprosate on craving for alcohol in alcohol‐dependent patients
Authors: WEINSTEIN AVIV , FELDTKELLER BARBARA , FEENEY ADRIAN , LINGFORD‐HUGHES ANNE , NUTT DAVID 
Published: November 2003

AbstractThis study investigated the effects of treatment with acamprosate on craving for alcohol by using a contextual priming task with alcohol and neutral words and craving questionnaires (ACQ, OCDS) in alcohol‐dependent patients who abstained from alcohol for 6 weeks. The acamprosate‐treated group (n =16) were given 666 mg t.d.s. with standard group‐work aimed at abstinence. The unmedicated control group (n =13) received only standard group therapy. The results showed that the acamprosate treated group was faster in their responses to craving‐related stimuli and scored lower on craving questionnaires during week 6 compared with week 2. Our results suggest that acamprosate may play a role in reduction of craving for alcohol after 6 weeks of treatment.
Ethanol consumption in mice with a targeted disruption of the dopamine‐3 receptor gene
Authors: MCQUADE JOHN‐ANDREWS , XU MING , WOODS STEPHEN , SEELEY RANDY , BENOIT STEPHEN 
Published: November 2003

AbstractConsiderable evidence suggests that the mesolimbic dopaminergic system is an important substrate for the rewarding effects of ethanol consumption. Previous data have demonstrated that pharmacological agents that alter dopamine signaling also influence the self‐administration of ethanol. The present experiments were designed to assess the role of the dopamine‐3 receptor (D3‐R) on voluntary ethanol consumption in C57BL/6 mice. Mice with targeted disruption of the D3‐R gene (D3‐R −/−) were compared to wild‐type controls in an ethanol intake paradigm. In Experiment 1, mice had 24‐hour access to ethanol each day in a two‐bottle choice paradigm for a period of 7 days per concentration. The concentrations tested were 3, 6, 10 and 15%. In Experiment 2, mice had 1 hour of access to ethanol each day in a two‐bottle paradigm for a period of 7 days per concentration. The same concentrations in Experiment 1 were compared in Experiment 2. In Experiment 3 we sought to test the development of a conditioned taste aversion (CTA) after receiving an intraperitoneal (i.p.) injection of 2.0 g/kg ethanol. In Experiment 4, blood ethanol levels where assessed following a 2.0 g/kg i.p. injection of ethanol. Experiment 5 assessed taste preference for saccharine and quinine in wild‐type and D3‐R −/− mice. Contrary to our predictions, both D3‐R −/− and wild‐types on a C57BL/6 background had similar intakes of ethanol, at all concentrations tested, in the 24‐hour and 1‐hour intake paradigms. Wild‐type and D3‐R −/− mice respond to injected ethanol similarly by developing a conditioned taste aversion. Metabolic analysis revealed mutant mice are slower in metabolizing a bolus injection of ethanol. Lastly, wild‐type and D3‐R −/− mice showed similar consumption to increasing concentration of both sweet and bitter tastes. These data suggest that deletion of the D3‐R gene does not increase ethanol consumption above that found on the C57BL/6 genetic background. Furthermore, the D3‐R −/− mice adequately learn a CTA to ethanol and do not have differing taste reactivity to saccharin or quinine. However, D3‐R −/− mice do appear to have a slower rate of ethanol metabolism.
Blood morphine levels in naltrexone‐exposed compared to non‐naltrexone‐exposed fatal heroin overdoses
Authors: ARNOLD‐REED DIANE , HULSE GARY , HANSSON ROBERT , MURRAY SEAN , O'NEIL GEORGE , BASSO MARIA , HOLMAN C D'ARCY J. 
Published: November 2003

AbstractThe aim of this study was to investigate the association between prior exposure to naltrexone and increased risk of fatal heroin overdose using a review of toxicology reports for heroin‐related fatalities between July 1997 to August 1999 for two groups: those treated with oral naltrexone and those who were not treated. Additional information for the oral naltrexone group was obtained from clinic files. Naltrexone‐treated deaths were identified from the patient database at the Australian Medical Procedures Research Foundation (AMPRF), Perth, Western Australia (WA) through the Western Australian Department of Health, Data Linkage Project. Non‐treated cases were identified from the database at the Forensic Science Laboratory, State Chemistry Centre (WA). We identified and investigated blood morphine concentrations following 21 fatal heroin overdoses with prior exposure to naltrexone and in 71 non‐naltrexone‐exposed cases over the same time period. The proportion of deaths where heroin use was a major contributing factor was little different in the non‐naltrexone compared to the naltrexone‐exposed group. Furthermore, in ‘acute opiate toxicity’ deaths, blood morphine levels were lower in non‐naltrexone‐exposed compared with naltrexone‐exposed cases. Although there was a higher number of deaths designated as rapid (i.e. occurring within 20 minutes) in the naltrexone‐exposed (89%) compared with the non‐exposed group (72%) this was not statistically significant. Other drug use in relation to heroin‐related fatalities is discussed. Findings do not support the hypothesis that prior exposure to naltrexone increases sensitivity to heroin toxicity.