bluuebunny/crossref_metadata_2025 huggingface dataset:
Update on hepatic stem cells
Authors: Alison Malcolm R. , Poulsom Richard , Forbes Stuart J.
Published: March 2003

Abstract: The liver, like most organs in an adult healthy body, maintains a perfect balance between cell gain and cell loss. Though normally proliferatively quiescent, simple hepatocyte loss such as that caused by partial hepatectomy, uncomplicated by virus infection or inflammation, invokes a rapid regenerative response to restore liver mass. This restoration of moderate cell loss and ‘wear and tear’ renewal is largely achieved by hepatocyte self‐replication. Furthermore, cell transplant models have shown that hepatocytes can undergo significant clonal expansion. Such observations indicate that hepatocytes are the functional stem cells of the liver. More severe liver injury activates a facultative stem cell compartment located within the intrahepatic biliary tree, giving rise to cords of biliary epithelia within the lobules before these cells differentiate into hepatocytes. A third population of stem cells with hepatic potential resides in the bone marrow; these haematopoietic stem cells can contribute to the albeit low renewal rate of hepatocytes, make a more significant contribution to regeneration, and even completely restore normal function in a murine model of hereditary tyrosinaemia. How these three stem cell populations integrate to achieve a homeostatic balance is not understood. This review focuses on three aspects of liver stem cell biology: 1) the hepatic stem cell candidates; 2) models of cell transplantation into the liver; and 3) the therapeutic potential of hepatic stem cells.
Five‐year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking and abstinence
Authors: Pessione F. , Ramond M‐J. , Peters L. , Pham B‐N. , Batel P. , Rueff B. , Valla D‐C.
Published: March 2003

Abstract:  Aim: To evaluate 5‐year survival predictive factors in hospitalised patients with excessive alcohol intake and cirrhosis, including in a multivariate analysis the severity of the liver disease, gastrointestinal bleeding, concomitant viral B or C infection, smoking status, presence of alcoholic hepatitis at inclusion and abstinence from alcohol during follow‐up.

Methods: In a non‐concurrent cohort study, 122 patients with excessive alcohol intake and cirrhosis were followed up at least five years or till death. Two patients were lost to follow‐up. Results: The 5‐year survival rates were 43% in the 122 patients and 66%, 50% and 25% in Child–Pugh class A, B and C patients, respectively. In multivariate analysis, age (P = 0.01), Child–Pugh score (P = 0.0001), gastrointestinal bleeding (P = 0.01), presence of HBs Ag and/or anti‐HCV (P = 0.03), smoking (P = 0.01), absence of histologically proven alcoholic hepatitis (P = 0.05) and persistent alcohol intake (P = 0.002) were associated with significantly increased risk ratios of death.

Conclusions: In hospitalised patients with excessive alcohol intake and cirrhosis: (1) age, liver failure, gastrointestinal bleeding, concomitant viral B or C infection and persistent alcohol intake are independent poor prognostic markers, (2) smoking may contribute to the aggravation of cirrhosis, and (3) alcoholic hepatitis, being a potentially reversible cause of liver failure, has a favourable prognostic significance.
A rhesus monkey model of respiratory syncytial virus infection
Authors: McArthur‐Vaughan K. , Gershwin L.J.
Published: March 2003

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in infants and young children worldwide. To date, there is no single animal model that adequately reproduces all human disease states. Here, we have developed a model of experimental infection with human RSV in infantRhesus macaques. Infected animals demonstrated mild clinical disease including increased respiratory rates, fever and adventitious lung sounds. While more severe disease was not observed, preliminary virological and histopathological findings are promising. It is anticipated that with further optimization, this model will provide a useful system with which to study disease due to RSV infection and evaluate candidate vaccines.
Wettability of coal – a comparative study
Authors: Orumwense F. F. O.
Published: March 2003

A comparative study of the contact angles of air bubbles, hydrocarbon oils (benzene and dodecane – both in the absence and in the presence of water‐soluble dodecylamine (laurylamine) chloride), flocculants and coagulants drops on flat polished coal surfaces immersed in water was made. The effect of the hydrocarbon chain length of some n‐alkylamine chlorides on the coal‐oil‐water was also investigated. The relationship of the measured contact angles to the flocculants, coagulants and dodecylamide chloride concentrations and pH was established. Results obtained show that maximum contact angles for the coals studied occur in the alkaline pH range (pH>7) for the systems investigated. Evidence is also provided to show that benzene and dodecane do not spread spontaneously on wet coal surfaces, even in the presence of a water‐soluble cationic surfactant. The results further show that the coal‐benzene water contact angles increase with an increase in the hydrocarbon chain length of the surfactant. Coagulants probably affect flotation of coal fines adversely, whereas flocculants have a remarkable effect on contact angles similar to that of surfactants.
Implications of empirical data quality to metapopulation model parameter estimation and application
Authors: Moilanen Atte
Published: March 2003

Parameter estimation is a critical step in the use of any metapopulation model for predictive purposes. Typically metapopulation studies assume that empirical data are of good quality and any errors are so insignificant that they can be ignored. However, three types of errors occur commonly in metapopulation data sets. First, patch areas can be mis‐estimated. Second, unknown habitat patches may be located within or around the study area. Third, there may be false zeros in the data set, that is, some patches were observed to be empty while there truly was a population in the patch. This study investigates biases induced into metapopulation model parameter estimates by these three types of errors. It was found that mis‐estimated areas influence the scaling of extinction risk with patch area; extinction probabilities for large patches become overestimated. Missing patches cause overestimation of migration distances and colonization ability of the species. False zeros can affect very strongly all model components, the extinction risk in large patches, intrinsic extinction rates in general, migration distances and colonization ability may become all overestimated. Biases in parameter estimates translate into corresponding biases in model predictions, which are serious particularly if metapopulation persistence becomes overestimated. This happens for example when the migration capability of the species is overestimated. Awareness of these biases helps in understanding seemingly anomalous parameter estimation results. There are also implications for field work: it may be reasonable to allocate effort so that serious errors in data are minimized. It is particularly important to avoid observing false zeros for large and/or isolated patches.
Geographical variation in male genitalia inBrachyrhaphis episcopi(Poeciliidae): is it sexually or naturally selected?
Authors: Jennions Michael D. , Kelly Clint D.
Published: March 2003

Male poeciliid fishes inseminate females using an intromittent organ called the gonopodium. Here we report on natural variation in gonopodium size both within and between 12 populations of the freshwater fishBrachyrhaphis episcopi(Poeciliidae) in Panama. We show that males from sites with more predatory fish species have, on average, a relatively longer gonopodium than males inhabiting sites with fewer predatory fish. Gonopodium length was not correlated with the site‐specific adult sex ratio and the average sex ratio was more strongly female biased at sites with more predatory fish. The gonopodium exhibited lower phenotypic variance than the average for sexually selected traits and it generally showed negative allometry. Our results are similar to those reported for the guppyPoecilia reticulata. Two alternative hypotheses for these findings are discussed. First, that population differences are sexually selected. Second, that they are an incidental consequence of environmental differences between sites. Specifically, that higher water flow rates select for enlarged fin size and stockier bodies in downstream sites where predatory fish are more common.
The evolution of dispersal distance in spatially‐structured populations
Authors: Murrell David J. , Travis Justin M. J. , Dytham Calvin
Published: March 2003

Most evolutionary models of dispersal have concentrated on dispersal rate, with emigration being either global or restricted to nearest neighbours. Yet most organisms fall into an intermediate region where most dispersal is local but there is a wide range of dispersal distances. We use an individual‐based model with 2500 patches each with identical local dynamics and show that the dispersal distance is under selection pressure. The dispersal distance that evolves is critically dependent on the ecological dynamics. When the cost of dispersal increases linearly with distance, selection is for short‐distance dispersal under stable and damped local dynamics but longer distance dispersal is favoured as local dynamics become more complex. For the cases of stable, damped and periodic patch dynamics global patch synchrony occurs even with very short‐distance dispersal. Increasing the scale of dispersal for chaotic local dynamics increases the scale of synchrony but global synchrony does not neccesarily occur. We discuss these results in the light of other possible causes of dispersal and argue for the importance of incorporating non‐equilibrium population dynamics into evolutionary models of dispersal distance.
Exploring density‐dependent relationships in demographic parameters in populations of birds at a large spatial scale
Authors: Paradis Emmanuel , Baillie Stephen R. , Sutherland William J. , Gregory Richard D.
Published: March 2003

The importance of density‐dependent processes in natural populations is widely accepted, but the issue of the shape of density‐dependent relationships (such as influenced by vagueness, or time‐delay) remains unresolved. We explored the density‐dependent relationships in demographic parameters for 12 species of birds in Britain using large‐scale, long‐term data sets. We predicted that a negative relation between density and demographic parameters should be observed for the stable species, whereas the decreasing or increasing species should display a positive relation if the environment changes progressively through time bringing about a continuous change in density dependence. Our prediction was verified for nine species out of 12; however, we observed, for the three remaining species, a significant decrease of survival rates through time that seems to be involved in a long‐term population decline. In all cases where a density‐dependent relation was found, we observed an important variance around the relation. In one case, we showed that this variance increased significantly with density. We found evidence for time‐delayed effects of density dependence both for survival and breeding performance. In two species, our results suggest the existence of complex interactions (compensatory mechanisms) between survival and breeding performance or between the different components of breeding performance.
Microbial mediation of fruit fly–host plant interactions: is the host plant the “centre of activity”?
Authors: Raghu S. , Clarke A. R. , Bradley J.
Published: March 2003

Insects utilize resources in their environment with the aid of mutualistic or symbiotic mediation by microorganisms. Some insect species such as ants and termites often have complex ecological and evolutionary associations with their symbionts, while the nature and functional significance of such associations in non‐social insects is often unclear. In the Dacinae (Diptera: Tephritidae), specific Enterobacteriaceae (Erwiniaherbicola, Enterobactercloacae, Klebsiellaoxytoca) are believed to mediate interactions between the adult fruit flies and the larval host plant. This bacterial mediation is hypothesized as being integral to the larval host plant being the “centre of activity” of the fly. Using a non‐pest, monophagous fruit fly (Bactroceracacuminata [Hering]), we tested this hypothesis by manipulating the fruiting state of its larval host plant (Solanum mauritianum Scopoli) and subsequently assessing insect behaviour and phylloplane microflora on those hosts. On host plants that had never fruited, few flies or bacterial colonies were recorded, consistent with hypothesis expectations. On fruiting host plants or plants that had had their fruit removed, bacterial colonies were present; again consistent with expectation. However, few flies were recorded on fruit‐removed plants and all fly behaviours, other than resting or oviposition, were rare or absent on any hosts; inconsistent with expectation. The general pattern of results suggested that female flies coming to oviposit on fruiting hosts were spreading Enterobacteriaceae, but such spread was incidental and not part of some mutualistic interaction between fruit flies and bacteria.
Scale‐free dynamics in the movement patterns of jackals
Authors: Atkinson R. P. D. , Rhodes C. J. , Macdonald D. W. , Anderson R. M.
Published: March 2003

Using conventional radio‐tracking techniques employed by field ecologists, evidence for scale‐free (fractal) behaviour in the foraging trajectories of a species of African jackal is presented. It is believed that the particular form of foraging strategy observed here is a response by the jackal to its need to locate resources in an unpredictable environment. The methods used in this study are completely general and can be applied to other radio‐tracked species, thus beginning a systematic investigation of foraging strategies in mammals.
Impact on fruit removal and seed predation of a secondary metabolite, emodin, in Rhamnus alaternus fruit pulp
Authors: Tsahar Ella , Friedman Jacob , Izhaki Ido
Published: March 2003

There are two contradictory approaches to explaining the presence of secondary metabolites in ripe fruits. One holds that they evolved toward enhancing dispersal success (adaptive approach); the other claims that they evolved primarily to deter herbivores from eating leaves and seeds and that their presence in ripe fruits is a byproduct of that function (non‐adaptive approach). We tested the validity of three hypotheses of the adaptive approach that explain the presence of secondary metabolites in ripe fruits. We explored the current function of a secondary metabolite, emodin, in Mediterranean buckthorn (Rhamnus alaternus, Rhamnaceae) fruits by relating intraspecific variation and seasonal patterns of concentration to fruit removal and seed damage and by conducting feeding trials with captive birds presented artificial fruits that varied in emodin concentration. The concentration of emodin in the pulp of 10–13 Rhamnus plants from the same population was determined by HPLC every month during two fruiting seasons. Fruit removal by birds and seed predation by invertebrates and microbes were determined for the same plants. Emodin concentration rose during the first stages of ripening, reaching a peak before the fruits were ripe, and then decreased to a minimum when the fruits were ripe. No significant correlation between emodin concentration and ripe fruit removal rate among trees was observed in the first year, whereas in the second year the correlation was positive and significant. Thus, the impact of emodin on fruit selection varied between years, suggesting that emodin concentration does not solely govern fruit selection. A significant negative correlation was found in the first year between emodin concentration and seed predation during the first fruiting month. The yellow‐vented bulbul (Pycnonotus xanthopygos), a seed dispersing bird, distinguished between artificial foods that differed in emodin concentration (control, 0.001% and 0.002%), always preferring the lower concentration. In contrast, house sparrows, (Passer domesticus), a seed predator, did not detect such differences in emodin concentration but did distinguish between control foods and food with 0.005% and 0.001% emodin. We suggest that emodin has an ecological role, preventing seed predation by invertebrates and microbes without decreasing fruit removal by avian dispersers.
Female gigantism in a New Guinea population of the spider Nephila maculata
Authors: Higgins Linden
Published: March 2003

In many arthropods, female clutch size is positively correlated with female size but the benefits of increased size are presumed to be counterbalanced by the mortality risks incurred through delayed maturation. The orb‐weaving spiders of the genus Nephila are characterized in part by large female size, and among species female size declines with increasing latitude, suggesting that one important mortality risk associated with delayed female maturation is the end of the growing season. The best‐studied species inhabit strongly seasonal habitats. To explore the hypothesis that female size is limited by season length, I collected data concerning size‐dependent growth and development rates, prey capture success, predation risk, and female fecundity from a population of N. maculata inhabiting a nearly aseasonal habitat. Comparisons of these data with observations from another N. maculata population and from congeners inhabiting more seasonal sites support the hypothesis that female size in this genus may be limited primarily by seasons length. Combined with recent phylogenetic evidence that male size is an ancestral characteristic, these results indicate that sexual size dimorphism in this group has evolved due to fitness advantages of delayed female maturation.
Synergistic enhancement of collagenous protein synthesis by human gingival fibroblasts exposed to nifedipine and interleukin‐1‐beta in vitro
Authors: Johnson R. B. , Zebrowski E. J. , Dai X.
Published: March 2003

Abstract: Gingival overgrowth commonly occurs coincident to therapy with calcium channel blockers. The biologic mechanism for this condition is unknown; however, many clinicians suggest that poor oral hygiene may contribute to development of the overgrowth. This study tests the hypothesis that collagenous protein synthesis by gingival fibroblasts is synergistically enhanced when they are exposed to both nifedipine (N) and the pro‐inflammatory cytokine, interleukin‐1‐beta, a cytokine expressed in inflamed gingiva. Human gingival fibroblasts were isolated from biopsies of normal gingiva and cells separated into two groups. Group 1 was exposed to media containing 0, 5, 50, or 500 pg/ml IL‐1‐beta, or 10−7 M N for 7 days; Group 2 was exposed to those concentrations of IL‐1‐beta +10−7 M N. [3H]‐proline was added to the medium for the final 24 h. Cells and matrix were harvested and radioactivity determined by liquid scintillation analysis. Means (d.p.m./103 cells) were compared by factorial ANOVA and Scheffè comparisons. Collagenous protein synthesis was significantly reduced by 5 pg/ml IL‐1‐beta +10−7 M N and enhanced by 500 pg/ml IL‐1‐beta +10−7 M N as compared to N or IL‐1‐beta alone. Thus, patients may be more susceptible to gingival overgrowth coincident to nifedipine therapy as a result of the synergistic enhancement of connective tissue synthesis by these agents.
Detection of hepatitis C virus RNA in oral lichen planus and oral cancer tissues
Authors: Nagao Yumiko , Sata Michio , Noguchi Seiji , Seno'O Tamiko , Kinoshita Moritoshi , Kameyama Tadamitsu , Ueno Takato
Published: March 2003

Abstract: Hepatitis C virus (HCV) infection not only causes chronic liver diseases but shows extrahepatic manifestations as oral lichen planus (OLP) and oral cancer. To elucidate the direct relationships among these diseases and HCV infection, we investigated the detection of positive‐ and negative‐strand HCV‐RNA from serum, OLP (n=19), and oral cancer (n=17) tissues. We used a sensitive reverse transcription to polymerase chain reaction (RT‐PCR) method, and analyzed sequences from the HCV E1/E2 region of the genome from serum and tissue. Positive and negative HCV‐RNA strands were observed in 13 (92.9%) and 3 (21.4%) OLP tissues, respectively. In oral cancer tissues, positive HCV‐RNA strands were detected in all tissues from anti‐HCV positive patients. Negative HCV‐RNA strands were observed in 5 of 7 (71.4%) patient’s tissues. Furthermore, it was confirmed that the sequence from one of each OLP and oral cancer patient differed between serum and tissue HCV‐RNA. These results may indicate that HCV persists and replicates in these lesions, suggesting a pathological role for HCV, although the mechanisms are unclear.
Are myoepithelial cells responsible for the widespread expression of inducible nitric oxide synthase in pleomorphic adenoma? An immunohistochemical study
Authors: Brennan Peter A. , Umar Tijjani , Zaki Graeme A. , Langdon John D. , Spedding Anne , Buckley Jayne , Downie Ian P.
Published: March 2003

Abstract: Many of the actions of nitric oxide (NO) are still poorly understood. Recently, it has been shown that the inducible isoform of the enzyme nitric oxide synthase, iNOS, is expressed in both salivary ducts and pleomorphic adenoma. The current immunohistochemistry study determined whether or not this distribution correlated with smooth muscle actin (SMA) expression, thereby suggesting the expression by myoepithelial cells in both sites. Twenty cases of histologically confirmed pleomorphic adenoma, the sections of which contained adjacent normal salivary gland tissue, were stained for iNOS and smooth muscle actin (clone 1A4). The salivary ducts of all cases were stained intensely by both antibodies, with smooth muscle actin staining also being noted around acini in the normal gland parenchyma. Moderate or heavy staining for iNOS was found in all specimens of pleomorphic adenoma, with smooth muscle actin being distributed in a similar manner in 19 cases. Smooth muscle actin, but not iNOS, was also noted in blood vessels of both normal glands and tumours. The correlation between iNOS and SMA in pleomorphic adenoma was significant (P<0.001). The presence of iNOS in normal salivary ducts and pleomorphic adenoma is most likely due to expression by myoepithelial cells.
Cell proliferation markers in the odontogenic keratocyst: effect of inflammation
Authors: Paula Alfredo Maurício Batista , Carvalhais Júnia Noronha , Domingues Manoela Gallicchio , Barreto Diele Carine , Mesquita Ricardo Alves
Published: March 2003

Abstract: The immunohistochemical expression of PCNA and Ki‐67 proteins and the histochemical expression of AgNORs were studied in 20 odontogenic keratocysts in order to assess the relationship between epithelial cell proliferation and inflammation within the capsule. Immunostained cells were quantified by conventional methods, and both quantitative and morphometric analyses of AgNORs were performed by TV image analysis. Non‐inflamed odontogenic keratocysts showed a typical epithelial lining and inflamed odontogenic keratocysts were lined also by hyperplastic non‐keratinized stratified squamous epithelium. A statistically significant increase of PCNA+ and Ki‐67+ cells and of AgNOR numbers was detected in the linings of inflamed odontogenic keratocysts compared to non‐inflamed lesions. The results suggest the existence of greater proliferative activity in the epithelial cells of inflamed odontogenic keratocysts, which may be associated with the disruption of the typical structure of odontogenic keratocyst linings.
Odontogenic myxoma containing osteocement‐like spheroid bodies: report of a case with an unusual histopathological feature
Authors: Oygür Tülin , Dolanmaz Dogˇan , Tokman Benay , Bayraktar Serhat
Published: March 2003

Abstract: The odontogenic myxoma is a rare, benign, but locally invasive tumour of the jaws. Radiographically, it is a bone destroying lesion and has ill‐defined borders. Histological characteristics are spindle and stellate‐shaped tumour cells and a distinct myxomatous stroma. Bony islands that represent residual trabeculae are found scattered throughout the lesion. This report describes a case of odontogenic myxoma that shows diffusely dispersed osteocement‐like spherular calcified bodies, unlike residual bone trabeculae, and discusses its differential diagnosis.
Immunohistochemical and ultrastructural investigation of apoptotic cell death in granular cell ameloblastoma
Authors: Kumamoto Hiroyuki , Ooya Kiyoshi
Published: March 2003

Abstract: Apoptotic cell death in granular cell ameloblastomas was examined by immunohistochemistry using anti‐single‐stranded DNA (ssDNA) antibody and transmission electron microscopy. Routinely prepared sections of granular cell ameloblastomas showed various quantities of granular cells with some apoptotic nuclear fragments. Immunoreactivity for ssDNA was higher in granular cells than in other neoplastic cells. Ultrastructural examination revealed abundant lysosomes in the cytoplasm of granular cells. Numerous apoptotic cell fragments with condensed nuclei in granular cell clusters were phagocytosed by adjacent granular cells. On immunohistochemical characterization of cellular differentiation, granular cells were positive for cytokeratin, CD68, lysozyme and alpha‐1‐antichymotrypsin, but negative for vimentin, desmin, S‐100 protein, neuron‐specific enolase and CD15, indicating epithelial origin and lysosomal aggregation. These features suggest that the cytoplasmic granularity in granular cell ameloblastomas might be caused by increased apoptotic cell death of neoplastic cells and associated phagocytosis by neighboring neoplastic cells.
The unexplained survival of cells in oral cancer: what is the role of p53?
Authors: Whyte Donna A. , Broton Claire E. , Shillitoe Edward J.
Published: March 2003

In normal oral epithelium the cells divide, mature, differentiate, and die. This sequence is not normally followed in oral cancer. Instead, the death of the cells is somehow prevented, although the pathways toward cell death in normal oral epithelium and the defects in oral cancer are not well defined. However, several components in the system have been identified, and information on their interactions is becoming available. This review summarizes the evidence for cell death being due to apoptosis and the central role of thep53gene product in its regulation. Areas for future research are also identified.
Hepatocyte growth factor and c‐Met (HGF/c‐Met) in adenoid cystic carcinoma of the human salivary gland
Authors: Suzuki K. , Cheng J. , Watanabe Y.
Published: March 2003

Background:  Hepatocyte growth factor (HGF) enhances cell growth, morphogenesis, and scattering of various epithelial cells. The aim of this study was to evaluate the hypothesis that HGF/c‐Met plays a biological role in the invasive growth of adenoid cystic carcinoma (ACC).

Methods:  Immunohistochemically, expression of HGF and its receptor c‐Met was examined in 15 cases of ACC. To examine the direct effects of HGF on ACC, cell line derived from of ACC (ACC3) was used. The expression of HGF and c‐met in ACC3 was investigated by RT‐PCR. Analysis of mechanisms of invasion was done by performing scattering assay and matrigel invasion chamber assay.

Results:  Positive staining of HGF was found in all cases, and that of c‐Met was 67%. In ACC3, c‐met was expressed, but not HGF. Stimulation of ACC3 by rhHGF induced scattering and promoted invasion.

Conclusion:  The present results suggest that HGF/c‐Met increases tumor cell scattering and may play a part in invasiveness of ACC.
Emma's Incompetence as Madame Bovary
Authors: Champagne Roland A.
Published: March 2003

Pierre Bourdieu's social science orientation for the habitus and the hexis enables us to provide a relational model for situating the literary events of Madame Bovary. Emma's incompetence at being a wife according to the bourgeois habitus allows her to expand her competence as a woman by following the hexis of her female body. This struggle between hexis and habitus in Emma moves through five stages. First of all, her education in the convent provides her with the habitus of what a bourgeois wife should be and the separation of a woman's dreams from the reality of a housewife's tasks. Secondly, as a young married woman, Emma's suffering allows her to experience her individual opposition to the asphyxiation of marriage relative to the freedom of her womanhood. Thirdly, through language, Emma begins to externalize her struggle and in the fourth stage of her evolution to break the rules of the habitus. Finally, in the fifth stage, Emma chooses the competence of her hexis by appropriating her own space in dying. Nevertheless, the habitus reigns as Emma is buried in her wedding dress as if to enshrine in the code of marriage, and thus to disguise, the incompetence of her life.
Le thème de l'insularité dans Les îles des esclaves: roman documentaire de Thorkild Hansen*
Authors: Auchet M.
Published: March 2003

L'objectif du présent essai est de proposer quelques réflexions sur Slavernes Øer (Les Îles des esclaves), roman de Thorkild Hansen publié en 1970. Après avoir précisé son aspect réellement documentaire, nous nous efforçons surtout de montrer que, comme tout le reste de l'œuvre de Thorkild Hansen, le roman L'île aux esclaves a une très forte dimension subjective. Pour ce faire, nous appuyons notre démonstration sur la présence obsédante de l'élément aquatique dans l'ensemble de la production de l'auteur et nous appliquons àSlavernes Øer une grille de lecture symbolique. Nous défendrons surtout la thèse qu'on peut y identifier un « complexe insulaire » et que ce roman est très fortement ancré dans l'expérience existentielle de Thorkild Hansen. Nous espérons apporter ainsi une contribution à l'étude de sa technique d'écriture et de son inspiration, qui sont beaucoup moins « réalistes » quece que peut penser le lecteur superficiel lorsqu'il prend connaissance de la liste d'ouvrages qui sert de conclusion aux romans dits « documentaires » de l'auteur de Jens Munk et du Procès contre Hamsun.
BMP‐2 Stimulates Tyrosinase Gene Expression and Melanogenesis in Differentiated Melanocytes
Authors: BILODEAU MATTHEW L. , GREULICH JOHN D. , HULLINGER RONALD L. , BERTOLOTTO CORINE , BALLOTTI ROBERT , ANDRISANI OURANIA M.
Published: March 2003

Cells of the vertebrate neural crest (crest cells) differentiate in vitro to melanocytes and sympathoadrenal (SA) progenitor cells. We have shown previously, using primary J. quail neural crest cultures, the combinatorial effect of bone morphogenetic protein‐2 (BMP‐2) and cAMP signaling on SA cell development. Herein, we report that in primary J. quail neural crest cultures, BMP‐2 and cAMP signaling similarly exert a combinatorial effect on melanocyte development. We demonstrate that BMP‐2 treatment of neural crest cells increases melanogenesis by promoting the synthesis of melanin. This increased melanin synthesis by BMP‐2 is effected by the selective increase in the transcription of the tyrosinase gene, encoding the rate‐limiting enzyme of the melanin biosynthetic pathway. By contrast, BMP‐2 exerts no effect on the expression of the tyrosine‐related proteins 1 and 2 (Tyrpl and Dct), also involved in the melanin biosynthetic process, or on the expression of microphalmia (Mitf) gene, supporting the fact that BMP‐2 does not affect melanocyte differentiation. Employing transient transfection analysis of tyrosinase‐reporter constructs in B16 melanoma cells, we demonstrate that the BMP‐2 response‐element is localized between 900 and 1,100 bp upstream from the tyrosinase transcriptional start site. These studies support a role for BMP‐2 in melanogenesis by selectively targeting the expression of the tyrosinase gene involved in melanin biosynthesis.
The Ocular Albinism Type 1 Gene Product is an N‐Glycoprotein but Glycosylation is not Required for its Subcellular Distribution
Authors: Shen Bin , Orlow Seth J.
Published: March 2003

The ocular albinism type 1 (OA1) gene product is a membrane glycoprotein that may play a role in controlling melanosome growth and maturation. A number of mutations in the OA1 gene lead to ocular albinism due at least in part to retention of the aberrant protein in the endoplasmic reticulum. To examine whether N‐glycosylation plays a role in the post‐translational trafficking of the Oa1 protein, we constructed a series of mutant mouse Oa1 cDNAs encoding an Oa1‐green fluorescent protein fusion in which some or all of the potential glycosylation sites were eliminated by site‐directed mutagenesis. Biochemical studies in transfected cells treated with tunicamycin and peptide:N‐glycosidase F suggest that asparagine at amino acid 106 is essential for N‐glycosylation of the protein. Mutation at amino acid 106 that eliminated glycosylation did not affect the endo/lysosomal distribution of the Oa1 protein in either COS cells or cultured murine melanocytes.
Comparative Biochemistry of Eumelanogenesis and the Protective Roles of Phenoloxidase and Melanin in Insects
Authors: Sugumaran Manickam
Published: March 2003

The phenolic biopolymer eumelanin is an important skin pigment found throughout the animal kingdom. The enzyme, tyrosinase, initiates melanogenesis in mammals. The biogenesis is assisted by a number of mammalian protein factors including dopachrome tautomerase and 5,6‐dihydroxyindole‐2‐carboxylate oxidase. Invertebrates, such as insects, employ phenoloxidase and dopachrome (decarboxylating) isomerase for melanin biosynthesis. Recently generated molecular biological and biochemical data indicate that tyrosinase and phenoloxidase are distinctly different enzymes in spite of possessing both monophenol monooxygenase activity as well as o‐diphenoloxidase activity. Similarly, insect dopachrome isomerase also differs significantly from its mammalian counterpart in several of its properties including the nature of the enzymatic reaction. In addition, there are considerable differences in the eumelanogenic pathways of these two animal groups that include the utility of substrates, use of dihydroxyindoles and the nature of eumelanin pigment. Thus, the biochemistry and molecular biology of melanogenesis in mammals and insects are significantly different. The advantages of generating different eumelanin pigments and intermediates by the insects are discussed.
Effect of Boron Neutron Capture Therapy for Melanotic and Amelanotic Melanoma Transplanted into Mouse Brain
Authors: Iwakura Masaki , Kondoh Hirofumi , Hiratsuka Junichi , Ehara Kazumasa , Tamaki Norihiko , Mishima Yutaka
Published: March 2003

In order to develop a protocol to treat brain metastatic melanoma using our 10B‐p‐boronophenylalanine (BPA) boron neutron capture therapy (BNCT), we initiated the following studies (i), Comparative analyses of boron biodistribution between melanoma proliferating in the brain and skin among melanotic and amelanotic types, and (ii) Therapeutic evaluation of BPA–BNCT for brain melanoma models of both types, using survival times. Our present data have revealed that boron concentration in melanoma proliferating in the brain, the major prerequisite for successful BNCT, showed a positive correlation to melanin synthesizing activity in the same way as melanoma proliferating in skin. Further, the boron concentration ratio of melanoma to normal surrounding tissue for brain melanoma models was considerably higher than that for subcutaneous (s.c.) ones because of the existence of the blood–brain barrier (BBB). Additionally, from analyses of median and mean survival times following BNCT using low, middle, and high neutron doses, the therapeutic effect of BNCT for the amelanotic A1059 melanoma appeared at first glance to be higher than that for the highly BPA attracting and highly relative biological effect equivalent dose obtaining B15b melanoma. As the survival time was dependent on both regression and regrowth curves, and because the brain melanoma model in small animals made it difficult to evaluate these curves separately, we further examined the in vivo growth curve of both types of melanomas following implantation in s.c. tissue. The melanotic B15b melanoma was indeed found to possess much higher growth rate as compared with that of the amelanotic A1059 melanoma. The significance of boron biodistribution studies and BNCT survival curve analyses in forming an effective clinical protocol for individual human cases of melanoma brain metastasis is discussed.
The cAMP Signaling Pathway has Opposing Effects on Rac and Rho in B16F10 Cells: Implications for Dendrite Formation in Melanocytic Cells
Authors: Scott Glynis , Leopardi Sonya
Published: March 2003

A hallmark of melanocytic cells is their ability to form dendrites in response to growth factors and to ultraviolet irradiation. It is known that the cyclic adenosine monophosphate (cAMP) second messenger pathway stimulates melanocyte dendrite formation because agents that increase cAMP such as forskolin and dibutyrl cAMP induce dendrite formation in normal human and murine melanocytes and melanoma cell lines. The Rho family of guanosine triphosphate (GTP)‐binding proteins regulates cytoskeletal reorganization in all cells tested and Rac and Rho have both been shown to regulate melanocyte dendrite formation. In this report, we analyzed the effect of cAMP on the activation of Rac and Rho and show that elevation of cAMP stimulates Rac and inhibits Rho in B16F10 cells. The Rho GTP‐binding proteins have also been shown to either cross‐activate or inhibit each other and in this report we show that Rac activates Rho in B16F10 cells. Microinjection of C3 botulinum exoenzyme toxin, an agent that specifically inactivates Rho or microinjection of constitutively active mutant Rac protein‐induced dendricity in human melanocytes and in B16F10 and B16F1 murine melanoma cell lines. We conclude that cAMP‐mediated dendrite formation in melanocytic cells is mediated through upregulation of Rac activity and downregulation of Rho activity.
Effects of a bisphosphonate on the expression of bone specific genes after autogenous free bone grafting in rats
Authors: Myoung Hoon , Park Ju‐Yong , Choung Pill‐Hoon
Published: March 2003

The purpose of this study was to evaluate the clinical availability of a bisphosphonate in autogenous free bone grafts. Bisphosphonate (0.01 mg/kg/day) was administered daily after an autogenous free bone graft on a rat calvarium. The effects of a bisphosphonate on the resorption of grafted bone and mRNA expression in bone specific genes, i.e. bone morphogenetic protein 2, bone morphogenetic protein 4, alkaline phosphatase, osteocalcin, osteoclast inhibitory factor and calcitonin receptor, were studied via a reverse transcription‐polymerase chain reaction (RT‐PCR), real time RT‐PCR and tartrate‐resistant alkaline phosphatase (TRAP) staining. In a clinical and histomorphological review, bone resorption decreased in the experimental group in contrast to the control group where active bone resorption was observed. Bisphosphonate altered not only the mRNA expression of the bone resorption associated genes but also the bone formation associated genes. The expression of the calcitonin receptor (CTR) mRNA was not detected and the osteoclast inhibitory factor (OCIF) was significantly up‐regulated in the experimental group as opposed to the control group. The expressions of osteocalcin and alkaline phosphatase mRNAs were also higher in the experimental group. However, there was no significant difference in the mRNA expression of bone morphogenetic proteins between the two groups. The data suggest the possibility of a clinical application of bisphosphonates for decreasing resorption of grafted bone.
Selection of antimicrobial agents in periodontal therapy
Authors: Slots Jørgen
Published: March 2003

Background: The recognition over the past 3 decades of microbial specificity in periodontitis has afforded dental practitioners the ability to prevent and treat the disease with a variety of antimicrobial drugs. These include systemic antibiotics, topical antibiotics and topical antiseptics.

Results: Systemic antibiotic therapy can be essential in eliminating pathogenic bacteria that invade gingival tissue and in helping control periodontal pathogens residing in various domains of the mouth from where they may translocate to periodontal sites. Frequently used periodontal combination antibiotic therapies are metronidazole‐amoxicillin (250–375 mg of each 3 × daily for 8 days) and metronidazole‐ciprofloxacin (500 mg of each 2 × daily for 8 days). Microbiological analysis helps determine the optimal antibiotic therapy and effectiveness of treatment. Topical antibiotics that are commercially available as controlled release devices suffer from several potential problems, including insufficient spectrum of antimicrobial activity in some periodontal polymicrobial infections, risks of producing an antibiotic resistant microbiota, and high acquisition costs. Topical antiseptics of relevance in periodontal treatment include 10% povidone‐iodine placed subgingivally by a syringe for 5 min, and 0.1% sodium hypochlorite solution applied subgingivally by patients using an irrigation device.

Clinical implications: The present paper recommends periodontal treatment that includes a battery of professionally and patient‐administered antimicrobial agents (properly prescribed systemic antibiotics, povidone‐iodine and sodium hypochlorite subgingival irrigants, and chlorhexidine mouthrinse). Available chemotherapeutics can provide effective, safe, practical and affordable means of controlling subgingival colonization of periodontal pathogens and various types of periodontal disease.
Effects of TNFα and prostaglandin E2 on the expression of MMPs in human periodontal ligament fibroblasts
Authors: Nishikawa Masanori , Yamaguchi Yoshinori , Yoshitake Kazusada , Saeki Yukikazu
Published: March 2003

Accumulating evidence indicates that TNFα plays an important role in the pathogenesis of periodontitis, but the effect of TNFα on the degradation of the periodontal ligament is not well understood. This study used reverse transcriptase‐PCR to investigate the effects of TNFα on matrix metalloproteinase (MMP) mRNA expression in human periodontal ligament fibroblasts. TNFα increased MMP‐1, MMP‐3 and MMP‐13 mRNA levels in both a time‐dependent (0–24 h) and a dose‐dependent (0.1–10 ng/ml) manner. TNFα also increased COX‐2 mRNA levels. Because elevation of COX‐2 mRNA levels enhances the production of prostaglandins, we therefore investigated whether endogenous prostaglandins are involved in the MMP mRNA expression that is enhanced by TNFα. Pre‐treatment with the selective COX‐2 inhibitor, NS‐398, increased MMP‐13 mRNA levels, while prostaglandin E2 and dibutyryl cyclic AMP decreased MMP‐13 mRNA levels. Neither MMP‐1 nor MMP‐3 mRNA levels were affected by these chemicals. These findings indicate that prostaglandin E2 has a lowering effect on TNFα‐enhanced MMP‐13 mRNA levels, and that this effect is dependent on cAMP. Our results suggest that TNFα participates in periodontal ligament destruction by stimulating the production of MMPs (MMP‐1, MMP‐3 andMMP‐13), while endogenous prostaglandin E2 has a negative feedback role in TNFα‐enhanced MMP‐13 production.
Long‐Term Physical Exercise and Atrial Natriuretic Peptide in Obese Zucker Rats
Authors: Pörsti Ilkka , Kähönen Mika , Wu Xiumin , Arvola Pertti , Ruskoaho Heikki
Published: March 2003

Abstract: Endurance training increases natriuretic peptide synthesis in the hypertrophied myocardium of spontaneously hypertensive rats. We examined the effects of 22‐week‐long treadmill exercise on plasma and tissue atrial natriuretic peptide in Zucker rats, a model of genetic obesity and moderate hypertension without clear cardiac hypertrophy. The blood pressures of the animals were measured by the tail‐cuff method, and plasma and tissue samples for the peptide determinations were taken at the end of the study. The training increased heart weight to body weight ratio, while atrial natriuretic peptide contents in the right and left atrium, ventricular tissue, and plasma did not change. The exercise prevented the elevation of blood pressure, which was observed in non‐exercised obese Zucker rats, and also reduced blood pressure in the lean rats. In conclusion, these results suggest that in the absence of preceding myocardial hypertrophy, the long‐term exercise‐induced workload is not deleterious to the heart in experimental obesity, since no changes in plasma and tissue atrial natriuretic peptide were detected.
Imperatorin, a Furanocoumarin from Angelica dahurica (Umbelliferae), Induces Cytochrome c‐Dependent Apoptosis in Human Promyelocytic Leukaemia, HL‐60 Cells
Authors: Pae Hyun‐Ock , Oh Hyuncheol , Yun Young‐Gab , Oh Gi‐Su , Jang Seon Il , Hwang Kee‐Myoung , Kwon Tae‐Oh , Lee Ho‐Sub , Chung Hun‐Taeg
Published: March 2003

Abstract: Imperatorin, a biologically active furanocoumarin from the roots of Angelica dahurica (Umbelliferae), was found to induce apoptosis in human promyelocytic leukaemia, HL‐60 cells. DNA fragmentation assay, morphology‐based evaluation, and flow cytometric analysis demonstrated that imperatorin at micromolar concentrations was able to trigger apoptosis of HL‐60 cells. Neither necrosis nor differentiation was observed at cytotoxic micromolar concentrations of imperatorin. Further studies showed that the cytochrome c/caspase‐9 pathway was responsible for imperatorin‐induced apoptosis; i.e., mitochondrial membrane was depolarized, Bcl‐2 was down‐regulated, cytochrome c was released from mitochondria, caspase‐9 and caspase‐3 were activated, and poly(ADP‐ribose) polymerase was cleaved. Furthermore, imperatorin‐induced apoptosis was significantly blocked by Z‐VAD‐FMK (a broad spectrum caspase inhibitor), Z‐LEHD‐FMK (a caspase‐9 inhibitor) and Ac‐DMQD‐CHO (a caspase‐3 inhibitor), but not by Z‐IEDT‐FMK (a caspase‐8 inhibitor).
Pharmacological Treatment of Chronic Diabetes by Stimulating Pancreatic β‐Cell Regeneration with Systemic Co‐administration of EGF and Gastrin
Authors: Brand Stephen J. , Tagerud Sven , Lambert Philip , Magil Sheila G. , Tatarkiewicz Krystyna , Doiron Kathryn , Yan Yanhua
Published: March 2003

Abstract: Transgenic expression of gastrin and EGF receptor ligands stimulates islet neogenesis in adult mice, significantly increasing islet mass. The present study aimed to determine whether pharmacological treatment with gastrin and EGF can significantly stimulate β‐cell regeneration in chronic, severe insulin‐dependent diabetes. Diabetes was induced by intravenous streptozotocin, resulting in >95% β cell destruction. Four weeks later, blood glucose levels were restored to normal range by exogenous insulin therapy and rats were treated with EGF/gastrin in combination, gastrin alone, or EGF alone given subcutaneously. After 14 days treatment blood glucose was significantly lower in the EGF/gastrin group compared to the untreated diabetic controls. Along with improved glucose tolerance, EGF/gastrin treatment significantly increased plasma C peptide and pancreatic insulin content compared to diabetic controls. Histological analysis showed that EGF/gastrin treatment significantly increased β‐cell mass as determined by point counting morphometrics. The EGF/gastrin group had a significantly greater number of BrdU labelled β‐cells/section consistent with stimulation of β‐cell replication or neogenesis. An increased number of gastrin receptor positive cells were observed in the EGF/gastrin‐treated groups. In contrast to the effectiveness of the EGF/gastrin combination, neither gastrin nor EGF alone improved glucose tolerance in severely streptozotocin‐diabetic rats. These studies indicate that physiologically significant improvement in glucose tolerance can be achieved through stimulating β‐cell regeneration with gastrin/EGF administered systemically as conventional pharmacological therapy.