bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cyclooxygenase‐2 inhibitor, nimesulide, inhibits postinitiation phase of N‐nitrosobis(2‐oxopropyl)amine‐induced pancreatic carcinogenesis in hamsters
Authors: Furukawa Fumio , Nishikawa Akiyoshi , Lee In‐Seon , Kanki Keita , Umemura Takashi , Okazaki Kazushi , Kawamori Toshihito , Wakabayashi Keiji , Hirose Masao 
Published: February 2003

AbstractThe modification effects of nimesulide, a cyclooxygenase (COX)‐2 inhibitor, administration during the postinitiation phase of pancreatic carcinogenesis were investigated in hamsters treated with N‐nitrosobis(2‐oxopropyl)amine (BOP). Male Syrian hamsters were given 4 weekly s.c. injections of BOP at a dose of 10 mg/kg and thereafter administered 0, 100 or 400 ppm nimesulide in the diet for 36 weeks. Additional groups of hamsters were fed 400 ppm nimesulide without prior BOP initiation or nontreated. At week 40, all surviving animals were killed and development of neoplastic and preneoplastic lesions was assessed histopathologically. The incidence of pancreatic adenocarcinomas was significantly (p < 0.05) decreased in the BOP/400 ppm nimesulide group compared to the BOP alone group. The multiplicity of total lesions of pancreatic adenocarcinoma plus atypical hyperplasia was also significantly (p < 0.05) lowered. Immunohistochemically, COX‐2 was clearly expressed in pancreatic and lung tumor cells, whereas expression was not remarkably affected by the 400 ppm nimesulide treatment. Proliferating cell nuclear antigen labeling indices of pancreatic ducts were significantly (p < 0.01) reduced by nimesulide. The incidence and multiplicity of neoplastic lesions in other organs did not significantly differ among the BOP‐treated groups, though only the multiplicity of lung tumors showed a tendency to decrease. No neoplastic lesions were detected in animals receiving nimesulide alone. Our results clearly indicate that nimesulide protects against BOP‐induced pancreatic tumors in hamsters. © 2003 Wiley‐Liss, Inc.
Expression and role of MICA and MICB in human hepatocellular carcinomas and their regulation by retinoic acid
Authors: Jinushi Masahisa , Takehara Tetsuo , Tatsumi Tomohide , Kanto Tatsuya , Groh Veronika , Spies Thomas , Kimura Ritsuko , Miyagi Takuya , Mochizuki Kiyoshi , Sasaki Yutaka , Hayashi Norio 
Published: February 2003

AbstractNatural killer (NK) cells are important effector cells for the first line of defense against tumor, but the mechanisms by which they recognize and kill human hepatocellular carcinoma (HCC) remains to be elucidated. Distant MHC class I homologs MICA and MICB are recently identified human ligands for NK cell activating receptor NKG2D. In our present study, MICA or MICB transcript was detected in 6 of 10 human hepatocellular carcinoma tissues, but not in the surrounding non‐cancerous tissues. Immunohistochemical analysis showed that MICA/B were expressed in the tumor cells of the cancerous tissues. Huh7 and HepG2 hepatoma cells, but not Hep3B cells, substantially expressed MICA/B on their cell surface. MICA/B expressed on hepatoma cells contributed to their NK sensitivity, because Huh7 and HepG2 were less susceptible to NK cytolysis when MAb against MICA/B was added during the cytolysis assay. Of interest is the finding that retinoic acid upregulated expression of MICA/B in Huh7 and HepG2 cells. Retinoic acid‐treated hepatoma cells induced IFNγ production from cocultured NK cells and rendered themselves more susceptible to NK cells. This was clearly dependent on upregulation of MICA/B, because both the enhanced IFNγ production and NK cytolysis were completely abolished by MAb‐mediated masking of MICA/B. These results suggest that MICA/B, expressed on a subset of human HCCs, may play an important role in their susceptibility to NK cells. Furthermore, retinoic acid can function as a modulator of MICA/B expression and thereby further activate NK cells. © 2003 Wiley‐Liss, Inc.
The cytoplasmic tail of invariant chain modulates antigen processing and presentation
Authors: Gregers Tone F. , Nordeng Tommy W. , Birkeland Hanne C. G. , Sandlie Inger , Bakke Oddmund 
Published: February 2003

AbstractThe MHC class II‐associated invariant chain (Ii) has several important functions in antigen presentation. In this study, we have examined the effect of Iip33 expression on endocytic transport and antigen presentation. We find that degradation of both endocytosed antigen and Ii itself is delayed in cells expressing high levels of Ii, whereas a mutant Ii with an altered charge distributionin the cytoplasmic tail was unable to exert this effect. Furthermore, the Ii mutant did not enhance the presentation of an Ii‐dependent MHC class II‐restricted epitope to the same extent as the wild type. In a parallel study, we investigated the effect of charge in the cytoplasmic tail of Ii. We find that due to exposed negative charges, it promotes endosome fusion events, and we suggest thatthis causes endosomal retention (Nordeng et al., Mol. Biol. Cell 2002). Together, the data reveal an additional property of the Iip33 cytoplasmic tail that contributes to the modulation of antigen processing and presentation.
T cell recognition and therapeutic effect of a phosphorylated synthetic peptide of the 70K snRNP protein administered in MRL/lpr mice
Authors: Monneaux Fanny , Lozano José Manuel , Patarroyo Manuel E. , Briand Jean‐Paul , Muller Sylviane 
Published: February 2003

AbstractModifications of self antigens that occur during apoptosis might be involved in the generation of neo‐antigens, which can break tolerance and induce autoimmunity. We have previously identifiedan epitope at residues 131–151 of the U1‐70K snRNP protein, recognized by IgG antibodies and CD4+ T cells from at least two strains of lupus mice. With the aim of investigating the possible role of phosphorylation on the antigenicity of peptide 131–151 and to gain a better understanding of how this peptide can drive autoimmune response, we synthesized two peptides phosphorylated on Ser137 and 140, respectively. We show here that peptide P140 phosphorylated on Ser140 is recognized by both CD4+ T cells and antibodies from MRL/lpr mice. Furthermore, intravenous administration to lupus‐prone MRL/lpr mice of P140 in saline (but not of the non‐phosphorylated peptide) decreased proteinuria and anti‐DNA antibody production, and significantly prolonged survival of treated mice. We further demonstrated that P140 is recognized by antibodies from lupus patients and binds to various HLA DR molecules, offering new hope for manipulating T cell response in humans.
ICOS+ Th cells produce distinct cytokines in different mucosal immune responses
Authors: Bonhagen Kerstin , Liesenfeld Oliver , Stadecker Miguel J. , Hutloff Andreas , Erb Klaus , Coyle Anthony J. , Lipp Martin , Kroczek Richard A. , Kamradt Thomas 
Published: February 2003

AbstractT cell activation, differentiation and effector functions depend on signals delivered through the antigen‐specific TCR and non‐clonal costimulatory receptors on the T cell. Activated T cells express the inducible costimulator (ICOS). We examined the co‐expression of ICOS with Th cytokines in mucosal immune responses. ICOS+CD4+ Th cells expressed strikingly different cytokines depending on the type of infection encountered and the cells' anatomical localization. In the Th2‐dominated response to Schistosoma mansoni, ICOS expression of CD4+ cells isolated from the liver was strongly associated with the expression of IL‐5, IL‐10, IL‐13, and T1/ST2, but not with the chemokine receptor CXCR5, a pattern consistent with Th2 effector cells. In the secondary lymphatic organs of schistosome‐infected mice, ICOS expression was randomly correlated with Th2 effector‐cytokines, but positively correlated with CXCR5 expression; a pattern consistent with follicular Th cells. In Th cells isolated from gut or liver of mice infected with Toxoplasma gondii, ICOS expression was positively correlated with IFN‐γ production. Finally, in the severe combined immunodeficiency transfer colitis model, ICOS expression was strongly positively associated with IFN‐γ and IL‐2. Thus, ICOS appears to costimulate distinct effector functions in different immune responses, depending on factors such as the nature of the antigen encountered and localization and chronicity of the immune response.
Effect of anti‐macrophage inflammatory protein‐1α on leukocyte trafficking and disease progression in experimental autoimmune uveoretinitis
Authors: Crane Isabel J. , Xu Heping , Manivannan Ayyakkannu , McKillop‐Smith Susan , Lamont Graeme , Wallace Carol , Liversidge Janet , Sharp Peter F. , Forrester John V. 
Published: February 2003

AbstractThis study has enabled us to identify the influence of the chemokine, macrophage inflammatory protein‐1α (MIP‐1α), on leukocyte behavior at the blood‐retina barrier in vivo and its link with the inflammatory process and disease pathogenesis. MIP‐1α has not previously been thought to be effective under conditions of physiological shear flow. However, short‐term anti‐MIP‐1α treatment inhibited leukocyte slowing and accumulation and subsequent extravasation of leukocytes at the blood‐retina barrier in animals with experimental autoimmune uveoretinitis. This was effective predominantly in the post‐capillary venules which have been shown to be the main site of passage of leukocytes across the blood‐retina barrier. Long‐term anti‐MIP‐1α treatment also prevented decreased leukocyte velocity and reduced disease severity as measured clinically, histologically and in terms of blood‐retina barrier breakdown.
The ABC‐transporter signature motif is required for peptide translocation but not peptide binding by TAP
Authors: Hewitt Eric W. , Lehner Paul J. 
Published: February 2003

AbstractThe transporter associated with antigen processing (TAP) translocates peptides from their site of generation in the cytosol to the lumen of the endoplasmic reticulum for binding to MHC class Imolecules. TAP is a member of the ATP‐binding cassette (ABC) transporter family whose members utilize energy from ATP hydrolysis to translocate substrates across membranes. The highly conserved nucleotide‐binding domains of ABC transporters couple ATP hydrolysis to substrate translocation by the membrane domains. The conserved ‘signature motif’ can be identified in the nucleotide‐binding domains of all ABC transporters, and may play a role in ATP hydrolysis. Here we show that introduction of mutations into the signature motifs of either TAP1 or TAP2 inhibits the translocation of peptide without affecting binding of either peptide or ATP by TAP. We therefore conclude that the signature motifs in both TAP1 and TAP2 are required after peptide binding to facilitate peptide translocation by TAP.
Estradiol enhances primary antigen‐specific CD4 T cell responses and Th1 development in vivo. Essential role of estrogen receptor α expression in hematopoietic cells
Authors: Maret Arlette , Coudert Jérôme D. , Garidou Lucile , Foucras Gilles , Gourdy Pierre , Krust Andrée , Dupont Sonia , Chambon Pierre , Druet Philippe , Bayard Francis , Guéry Jean‐Charles 
Published: February 2003

AbstractIt is widely accepted that females have superior immune responses than males, but the ways by which sex hormones may enhance T cell responses are still poorly understood. In the present study,we analyzed the effect of estrogens on CD4 T cell activation and differentiation after immunization with exogenous antigens. We show that administration of low doses of 17ß‐estradiol (E2) to castrated female mice results in a striking increase of antigen‐specific CD4 T cell responses and in the selective development of IFN‐γ‐producing cells. Quantitative assessment of the frequency of T cells bearing a public TCR ß chain CDR3 motif demonstrated that the clonal size of primary antigen‐specific CD4 T cells was dramatically increased in immune lymph nodes from E2‐treated mice. By usingmice with disrupted estrogen receptor (ER) α or ß genes, we show that ERα, but not ERβ, was necessary for the enhanced E2‐driven Th1 cell responsiveness. Furthermore, ERα expressionin hematopoietic cells was essential, since E2 effects on Th1 responses were only observed in mice reconstituted with bone marrow cells from ERα+/+, but not ERα‐deficient mice. These results demonstrate that estrogen administration promotes strong antigen‐specific Th1 cell responses in a mechanism that requires functional expression of ERα in hematopoietic cells.
The C‐type lectin DC‐SIGN (CD209) is an antigen‐uptake receptor for Candida albicans on dendritic cells
Authors: Cambi Alessandra , Gijzen Karlijn , de Vries I. Jolanda M. , Torensma Ruurd , Joosten Ben , Adema Gosse J. , Netea Mihai G. , Kullberg Bart‐Jan , Romani Luigina , Figdor Carl G. 
Published: February 2003

AbstractDendritic cells (DC) that express the type II C‐type lectin DC‐SIGN (CD209) are located in the submucosa of tissues, where they mediate HIV‐1 entry. Interestingly, the pathogen Candida albicans,the major cause of hospital‐acquired fungal infections, penetrates at similar submucosal sites. Here we demonstrate that DC‐SIGN is able to bind C. albicans both in DC‐SIGN‐transfected cell lines and in human monocyte‐derived DC. The binding was shown to be time‐ as well as concentration‐dependent, and live as well as heat‐inactivated C. albicans were bound to the same extent. Moreover, in immature DC, DC‐SIGN was able to internalize C. albicans in specific DC‐SIGN‐enriched vesicles, distinct from those containing the mannose receptor, the other known C. albicans receptor expressed by DC. Together, these results demonstrate that DC‐SIGN is an exquisite pathogen‐uptake receptor that captures not only viruses but also fungi.
Lessons from success and/or failure of irrigation development
Authors: Hargreaves George H. 
Published: February 2003

AbstractWorld population is increasing, particularly in the developing countries. Groundwater reserves are being depleted; lands are being degraded. The required increase in food production must come principally from new supplies of water for irrigated lands. If irrigated lands fail to produce the required food, increased destruction of resources and degradation of the environment from increasing slash and burn agriculture is anticipated. Various countries and international agencies have recognized the possibility of future food shortage. This paper presents case studies and includes technical and scientific considerations. In Greece, important considerations were land consolidation, and the incentives provided encouraged private initiative. The construction of large dams facilitated reforestation. In Haiti, flooding and erosion resulting from slash and burn agriculture, and land fragmentation were serious problems. Land redistribution and failure of maintenance resulted in the rapid deterioration and failure of the once prosperous colonial irrigation systems. Agrarian reform and/or the establishment of cooperatives with government landownership produced a rapid decline in irrigated production in various countries. In Honduras, little use has been made of 20 cooperatives financed by the government of Japan and the FAO. Various countries and international agencies have financed resource inventories and project studies and have provided funds for development. However, World Bank experience indicates that favorable laws and policies frequently have more influence on development than the availability of financial assistance. Strength in the rule of law, a free market economy, local and user participation in planning and management, and encouragement of private enterprise are frequently more important than the amount of money available from loans. Some successful training courses are described. A World Water and Climate Atlas is now available and can be used for many planning and risk evaluation purposes. Copyright © 2003 John Wiley & Sons, Ltd.
A simple start with far‐reaching consequences
Authors: de Bruin Dick , Schultz Bart 
Published: February 2003

AbstractThe history of water management in The Netherlands shows how the original natural landscape was transformed into a man‐made landscape and has led to a never‐ending struggle with the water. Water comes from all directions into the lowlands: over land via rivers (floods), from the sea side (surges), from above (excessive rainfall) and from the subsoil (seepage). Human intervention is continuously needed to be able to survive with effective solutions. History has shown that since men started intervening in nature, in particular in the alluvial water‐saturated soft soils where Dutch society has settled and developed, the need for these measures will never stop. Any one measure leads to counter and correcting measures later on. This is clearly visible today and it will definitively continue in the future. It sets the mind of Dutch society in its continuous struggle for life and can be a lesson learned for others, living and developing in areas with similar water‐related characteristics. Copyright © 2003 John Wiley & Sons, Ltd.
The impact of the Russian transition on psychosocial resources and psychological distress
Authors: Shteyn Marina , Schumm Jeremiah A. , Vodopianova Natalia , Hobfoll Stevan E. , Lilly Roy 
Published: February 2003

AbstractStudies suggest that the difficult transition of the Russian economy has led to decreased physical health among Russians. However, the impact of economic turmoil on Russians' psychological health has not been examined. We used Hobfoll's (1988; 1998) Conservation of Resources (COR) theory to examine how economic losses deteriorate personal and social resources (e.g., mastery and social support), and how these deteriorated resources, in turn, impact psychological well being. Participants were Russian women working in the retail (n = 99) and medical (n = 99) fields, two poorly paid sectors. Structural equation modeling indicated that economic loss negatively impacted mastery, but not social support. Women with greater mastery and social support resources, in turn, reported less psychological distress. Economic loss had both direct and indirect effects, through mastery, on women's psychological distress. Results supported COR theory and point to the importance of building and sustaining personal and social resources in the face of major economic stress. © 2003 Wiley Periodicals, Inc.
Modification of uterine vasculature during pregnancy in macaques
Authors: Blankenship Thomas N. , Enders Allen C. 
Published: February 2003

AbstractEmbryonic development in macaques includes extensive modification of the uterine vasculature by fetal trophoblast cells. Soon after the onset of blastocyst attachment to the endometrium, syncytial trophoblast cells intrude between endometrial epithelial cells, resulting in focal epithelium loss. Trophoblast cells continue to move into the endometrial stroma and encounter superficial uterine capillaries. These capillaries are penetrated by trophoblast, which permits maternal blood to leave the maternal circulation and enter lacunae formed within the mass of trophoblast cells. Cytotrophoblast cells enter the uterine vessels and attach to the endothelium via cell adhesion molecules prior to migration into confluent spiral arterioles, against the flow of blood. As intra‐arterial cytotrophoblast cells migrate, they displace adjacent endothelium, produce matrix metalloproteinases, traverse the tunica intima, and reside in the tunica media as intramural trophoblast. Intramural trophoblast cells disrupt the tunica media and become surrounded by an extensive extracellular matrix. In areas proximal to the placenta, the entire circumferences of spiral arteries are modified in this way. In the same arteries, distal to the placenta and farther “upstream,” trophoblast‐mediated changes to the arterial wall are less extensive. Uterine veins are modified by trophoblast only in the area immediately next to the trophoblast shell, with no trophoblast migration. The functional consequence of this trophoblast activity may be to ensure an adequate flow of maternal blood to the placenta, thus enhancing the survival of the fetus. Microsc. Res. Tech. 60:390–401, 2003. © 2003 Wiley‐Liss, Inc.
Development of the utero‐placental circulation: The role of carbon monoxide and nitric oxide in trophoblast invasion and spiral artery transformation
Authors: Lyall Fiona 
Published: February 2003

AbstractIt is now well known that in order to establish human hemochorial placentation and to provide a progressive increase in blood supply to the growing fetus, the uterine spiral arteries must undergo considerable alterations. This physiological modification is thought to be brought about by the interaction of invasive cytotrophoblast with the spiral artery vessel wall. Despite intensive research our understanding of the mechanisms that control human trophoblast invasion in normal, let alone abnormal pregnancy, are sill poorly understood. This is partly due to difficulties in obtaining “true” placental bed biopsies and most investigators have relied on in vitro models of trophoblast invasion. This article describes the morphological changes that occur within the placental bed throughout human pregnancy along with a review of the various studies which have attempted to sample the placental bed. Thereafter, follows a review of the evidence that invasive trophoblast can release the vasoactive agents nitric oxide and/or carbon monoxide which, in turn, could contribute to early physiological changes in spiral arteries prior to destruction of the smooth muscle within the vessel wall. Current evidence supports the idea that trophoblast‐derived carbon monoxide may contribute to spiral artery modification. In contrast there is no evidence for a similar role by nitric oxide. Microsc. Res. Tech. 60:402–411, 2003. © 2003 Wiley‐Liss, Inc.
Endometrial arteriogenesis: Vascular smooth muscle cell proliferation and differentiation during the menstrual cycle and changes associated with endometrial bleeding disorders
Authors: Rogers Peter A.W. , Abberton Keren M. 
Published: February 2003

AbstractThe cyclical regrowth of the human endometrial vasculature every 28 days following menstruation provides an excellent opportunity for studying arteriogenesis in a human tissue. Despite this, very little has been published to date about temporal or spatial changes in endometrial arteriolar structure or function. Immunohistochemical studies using vascular smooth muscle cell (VSMC) differentiation markers have identified spatially organised differences in VSMC phenotype. However, these have not significantly increased our understanding of how or when arteriogenesis occurs. Endometrial VSMC proliferation continues at a steady rate throughout the cycle, increasing in the specialised spiral arterioles in the mid and late secretory phases. Although estrogen and progesterone play a dominant role in regulating endometrial growth and regression, their direct involvement in arteriogenesis is less clear. Estrogen and progesterone receptors have been reported in endometrial VSMC, although heterogeneity of expression occurs. The angiopoietin/Tie axis has been investigated in endometrium, although the results of 3 studies published to date are contradictory, making conclusions about a role in arteriogenesis problematic. Abnormalities of arteriogenesis may play a role in disorders such as menorrhagia and breakthrough bleeding in contraceptive and hormone replacement therapy users. There is evidence that VSMC proliferation is reduced in spiral arterioles of women with menorrhagia, along with reduced pulsatility index of the uterine artery as shown by Doppler ultrasound. In women taking progestin‐only contraception, endometrial perivascular alpha smooth muscle actin is reduced in those who suffer from breakthrough bleeding compared to those that don't. Considerable work is still required to elucidate when in the cycle, where in the tissue, and what mechanisms regulate endometrial arteriogenesis. Microsc. Res. Tech. 60:412–419, 2003. © 2003 Wiley‐Liss, Inc.