bluuebunny/crossref_metadata_2025 huggingface dataset:
Cholangiopathy after short‐term administration of piperacillin and imipenem/cilastatin
Authors: Quattropani Cristiana , Schneider Marcel , Helbling Arthur , Zimmermann Arthur , Krähenbühl Stephan
Published: March 2003

Abstract: We describe a patient who suffered from intestinal perforation after abdominal trauma. Perioperatively, he was treated with a single dose of piperacillin and 9 doses of imipenem/cilastatin over 3 days. The patient was discharged 5 days after surgery in good clinical condition and with normal liver values except for a marginal elevation of alanine aminotransferase. Two weeks after discharge, he developed fatigue, fever and pruritus, necessitating rehospitalization. He was jaundiced and had elevated alkaline phosphatase and transaminases. After exclusion of an intra‐abdominal fluid collection, a vascular problem, and infectious or autoimmune liver disease, a liver biopsy was performed. The biopsy revealed centrizonal bilirubinostasis, a portal infiltrate rich in eosinophils and cholangitis. Lymphocyte transformation tests for piperacillin and imipenem/cilastatin were positive, suggesting an immunological mechanism for the observed hepatopathy. Cholestasis gradually decreased but was detectable for several weeks. The patient had a full clinical and biochemical recovery after 3 months. We conclude that short‐term therapy with piperacillin, imipenem/cilastatin or the combination of these drugs can lead to the same type of hepatopathy as described for amoxycillin/clavulanic acid or antistaphylococcal penicillins. Liver biopsy and positive lymphocyte transformation are compatible with an immunological mechanism.
Quantitative testing of liver function in relation to fibrosis in patients with chronic hepatitis B and C
Authors: Herold Christoph , Heinz Rudolf , Niedobitek Gerald , Schneider Thomas , Hahn Eckhart G. , Schuppan Detlef
Published: March 2003

Abstract: Background/Aim: Quantitative tests of liver function may be superior to conventional tests to assess the prognosis of patients with liver diseases. There are insufficient data from quantitative testing of liver function (QTLF) for patients with chronic hepatitis B and C, particularly with regard to fibrosis. Therefore, we applied a broad panel of QTLF to these patients. Methods: Three hundred and sixty‐seven consecutive patients with chronic hepatitis B or C underwent liver biopsy and QTLF, which included tests for hepatic metabolism (aminopyrine breath test, galactose elimination capacity) and for hepatic perfusion (sorbitol clearance, indocyanine green clearance). QTLF values were correlated with liver histology (grading and staging for inflammation and fibrosis) and Child–Pugh classification for liver cirrhosis. Results: In patients with no and moderate fibrosis, metabolic liver function was significantly decreased, whereas hepatic perfusion remained normal. Severe fibrosis and cirrhosis showed a significant decline in all QTLFs. Hepatic inflammation only reduced metabolic liver function, irrespective of the inflammatory grade. Viral etiology and HCV genotypes did not change QTLF. Conclusions: In summary, viral damage compromises hepatic metabolism before perfusion. Therefore, tests of metabolic liver function (aminopyrine breath test, galactose elimination capacity) should be useful to search for drugs that restore liver function in viral hepatitis irrespective of the fibrosis stage.
T cell receptor Vβ chain restriction and preferred CDR3 motifs of liver‐kidney microsomal antigen (LKM‐1)‐reactive T cells from autoimmune hepatitis patients
Authors: Arenz Monika , Pingel Sabine , Schirmacher Peter , Meyer zum Büschenfelde Karl‐Hermann , Löhr Hanns F.
Published: March 2003

Abstract: Aims/Background: The liver‐kidney‐microsomal antigen (LKM‐1) has been recognized as a major CD4+ T cell antigen in autoimmune hepatitis (AIH). The aim of this study was to characterize the antigen recognition sites of the variable T cell receptor β‐chain (TCRBV) of T cells specific to LKM‐1. Methods: By repeated stimulation of T cells with a recombinant LKM‐1 antigen or an LKM‐derived peptide followed by limited dilution, we generated T cell clones. Usage of TCRBV was analyzed by RT‐PCR and CDR3 antigen recognition sites were sequenced. Results: The 18 LKM‐1 specific T cell clones isolated from six AIH patients preferentially expressed the TCR elements BV9, BV5S2+S3, BV6, and BV13S1. Four BV9+ T cell clones rearranged the joining element JB1S3 within their CDR3 regions. JB2S3 was detected in another four clones together with BV5S2+S3 or BV13S1. A conserved sequence motif, Q(N)G(X)N, was seen in the diversity regions of five clones (36%). In order to identify T cells expressing the preferred TCRBV molecules in situ, immunohistologic examination of liver biopsies was performed. In AIH patients an accumulation of T cells expressing TCRBV 13S1, BV8 and BV5S3 was observed. Conclusions: Our data define TCRBV restriction and preferred CDR3 features of LKM‐1 specific T cells. The in situ localization of T cells expressing these restricted TCR molecules may suggest a pathogenic relevance of LKM‐1 specific cellular immune responses.
Caspase activation during hepatocyte apoptosis induced by tumor necrosis factor‐α in galactosamine‐sensitized mice
Authors: Osawa Yosuke , Banno Yoshiko , Nagaki Masahito , Nozawa Yoshinori , Moriwaki Hisataka , Nakashima Shigeru
Published: March 2003

Abstract: Background/Aims: To clarify the mechanism of hepatocyte apoptosis induced by tumor necrosis factor‐α (TNF‐α), caspase cascade and ceramide formation were investigated in the liver of D‐galactosamine (GalN)‐sensitized mice treated with TNF‐α. Methods: Seven‐week‐old male BALB/c mice were intraperitoneally injected with 20 mg GalN 30 min prior to the intravenous injection of recombinant mouse TNF‐α (0.5 μg/mouse). Cytochrome c release and processing of procaspases in the liver were analyzed by Western blotting. Activities of caspases were measured using chromogenic peptides as substrates. Ceramide content was determined using Escherichia coli diacylglycerol kinase. Results: Apoptosis of hepatocytes was observed in mice treated with both GalN and TNF‐α (GalN/TNF‐α), but not GalN or TNF‐α alone. Activation of caspases‐9 and ‐3, and cytochrome c release were observed only in liver from mice treated with GalN/TNF‐α. In a cell‐free system, processing of procaspases‐9 and ‐3, and cytochrome c release were observed in the postnuclear fraction of liver obtained from GalN/TNF‐α‐treated mice, but not in that from control mice. Processing of procaspase‐3 was inhibited by a caspase‐9 inhibitor, but not by inhibitor for caspase‐8 or ‐2. In a reconstitution assay system, procaspase‐9 processing occurred, when both cytosol and membrane fractions were obtained from the liver of mice treated with GalN/TNF‐α. Ceramide accumulation was observed only in apoptotic liver and preceded cytochrome c release and caspase activation. Conclusion: Cytochrome c release and caspase‐9 activation are required for the activation of executor caspase‐3 in TNF‐α‐induced hepatocyte apoptosis, but caspases‐8 and ‐2 play, if any, a minimal role. Ceramide may be implicated in this apoptotic process.
Early gene expression of hepatocyte growth factor in mononuclear phagocytes of rat liver after administration of carbon tetrachloride
Authors: Armbrust Thomas , Batusic Danko , Xia Liqun , Ramadori Giuliano
Published: March 2003

Abstract: Background: Hepatocyte growth factor (HGF) is a potent hepatocyte mitogen supposed to be a main stimulant of hepatocyte replication during liver regeneration. During acute liver injury, HGF has been detected in nonparenchymal cells of the liver.Methods:We performed in situ hybridization of HGF in rat livers after administration of carbon tetrachloride (CCl4). Mononuclear phagocytes (MNP) were isolated from normal and injured livers and HGF expression was analyzed by Northern blotting, in situ hybridization, and immunoprecipitation of 35S‐labeled proteins.Results:In situ hybridization of normal liver revealed few HGF positive cells within hepatic sinusoids. In injured livers, the number of cells containing HGF transcripts was increased at 6–24 h after CCl4.Hepatocyte growth factor transcripts in MNP from normal liver were detectable in trace amounts, but became clearly detectable at 6 h and persisted up to 24 h after CCl4 administration. In situ hybridization of MNP isolated from normal liver did not reveal positive cells. Mononuclear phagocytes became HGF‐positive when isolated 6 h after CCl4. Hepatocyte growth factor protein was detected in MNP isolated 24 h after CCl4. Conclusions: Hepatocyte growth factor in MNP is not directly induced by interferon‐α, interferon‐γ or tumour necrosis factor‐α (TNF‐α).Stimulated resident mononuclear phagocytes may play a significant role in the increase of HGF expression in liver regeneration after acute liver injury.
HFE gene mutations and iron metabolism in Wilson's disease
Authors: Erhardt Andreas , Hoffmann Arne , Hefter Harald , Häussinger Dieter
Published: March 2003

Abstract: Background: There is increasing evidence for an interaction between iron and copper metabolism. Methods: Iron indices (ferritin, transferrin saturation [TS], serum iron), liver parameters, the prevalence and significance of C282Y and H63D HFE mutations were studied in 40 unrelated, Caucasian patients with Wilson's disease and 295 healthy controls. Due to specific treatment Wilson's disease was well controlled in all but one patient. Results: The allele frequencies for the C282Y (11.3% vs. 6.2%) and the H63D (18.8% vs. 16.4%) mutation did not differ between patients with Wilson's disease and healthy controls. One patient with C282Y homozygous HH and Wilson's disease was identified showing progressive liver disease despite reasonable venesection and copper chelation therapy. No differences in iron indices and liver values were seen between HFE heterozygous and HFE wildtype patients with Wilson's disease. Higher serum ferritin levels were noticed in patients with Wilson's disease compared to healthy controls (149 ± 26 μg/l vs. 87 ± 8 μg/l; P < 0.03). Conclusions: It appears reasonable to assess iron indices in patients with Wilson's disease in order to detect iron overload. HFE mutations other than C282Y homozygosity seem to have no impact on iron indices and liver parameters as long as Wilson's disease is controlled.
Exposure of cynomolgus monkey embryos to retinoic acid causes thymic defects: effects on peripheral lymphoid organ development
Authors: Makori N. , Peterson P.E. , Lantz K. , Hendrickx A.G.
Published: March 2003

We have previously reported that exposure of monkey embryos to 13‐cis‐retinoic acid (cRA) results in thymic defects. In this study, we analyzed lymphocyte and antigen‐presenting cell populations at gestational days (GDs) 80–100 in the thymus, spleen, mesenteric lymph nodes, and gut‐associated lymphoid tissue following a teratogenic dosing regimen of cRA (2.5 and 5 mg/kg) at GD14–27. Tissue sections were immunostained for T‐cells (anti‐CD3), B‐cells (anti‐CD20), dendritic cells (p55), and major histocompatibility class II (anti‐HLA‐DR). Digital images of spleen sections were analyzed to obtain the relative area occupied by the cell subsets within the white pulp (WP). Compared with controls, the T‐cell dependent compartment of the spleen WP in specimens with perturbed thymic development (aplasia and severe hypoplasia) showed a reduction in size and proportion of CD3+ T cells. Our findings indicate that cRA‐induced thymic defects result in disrupted development of the splenic T‐cell dependent compartment.
Protection by SIV VLP DNA prime/protein boost following mucosal SIV challenge is markedly enhanced by IL‐12/GM‐CSF co‐administration
Authors: O'Neill E. , Martinez I. , Villinger F. , Rivera M. , Gascot S. , Colon C. , Arana T. , Sidhu M. , Stout R. , Montefiori D.C. , Martinez M. , Ansari A.A. , Israel Z.R. , Kraiselburd E.
Published: March 2003

Abstract:  The ever increasing number of people infected by human immunodeficiency virus (HIV) throughout the world renders the development of effective vaccines an urgent priority. Herein, we report on an attempt to induce and enhance antiviral responses using a deoxyribonucleic acid (DNA) prime/virus‐like particles (VLP) protein boost strategy adjuvanted with interleukin (IL)‐12/GM‐CSF in rhesus macaques challenged with simian immunodeficiency virus (SIV). Thus, groups of monkeys were administered three consecutive doses of pVecB7 a plasmid expressing VLP with or without plasmids expressing IL‐12 and GM‐CSF at weeks 0, 13 and 26. The VLP boost was administered at week 39 with or without IL‐12. All monkeys were challenged intrarectally with SIVsmE660 2 months following the protein boost. All except one immunized monkey became infected. While all immunized monkeys showed a marked reduction of acute viral peaks, reduction of viral load set points was only achieved in groups whose prime‐boost immunizations were supplemented with IL‐12/GM‐CSF (prime) and/or with IL‐12 (boost). Control of viremia correlated with lack of disease progression and survival. Detection of virus in rectal washes at 1 year post‐challenge was only successful in monkeys whose immunizations did not include cytokine adjuvant, but these loads did not correlate with plasma viral loads. In summary, use of IL‐12 and/or GM‐CSF was shown to provide significant differences in the outcome of SIV challenge of prime/boost immunized monkeys.
The influence of different calcium‐based additions on desulphurisation and inclusion characteristics
Authors: Andersson Margareta , Berlin Dean , Jönsson Pär , Löwnertz Martin
Published: March 2003

The size, distribution, and composition of inclusions during the desulphurisation and deoxidation steps were studied in laboratory experiments. 3 different calcium‐based desulphurisation mixtures were used. The number of inclusions and composition of inclusions were then determined using optical microscopy and scanning electron microscopy, respectively. The results show that 2 of the 3 proposed desulphurisation mixtures managed to render lower and roughly equivalent inclusion counts. The results also show that the composition of the inclusions in all 3 samples varied from the beginning to the end of the desulphurisation process. A desulphurisation mixture consisting of Al, CaO, CaCO3 and CaSi produced the overall best results with respect to desulphurisation and inclusion characteristics.
Kinetic study on the carbothermic reduction of zinc oxide
Authors: Chen Hsi‐Kuei
Published: March 2003

This study investigated the carbothermic reduction of zinc oxide with carbon powder under a nitrogen atmosphere (at 1 atm). The experimental results indicated that the reduction rate could be increased by increasing the molar ratio of C/ZnO, height of solid sample, density of solid sample or reaction temperature. The rate was also found to be increased by reducing the grain size of zinc oxide and carbon or the nitrogen gas flow rate. The empirical expressions of conversion rates of zinc oxide and carbon as well as the production rate of zinc were determined from the regression of the experimental data.
The influence of mechanical and laser cutting on the fatigue strengths of carbon and stainless sheet steels
Authors: Meurling Fredrik , Melander Arne , Linder Jan , Larsson Mats
Published: March 2003

The present study investigates the influence of laser cutting as compared to conventional mechanical cutting on the fatigue properties of steel sheet. 6 grades of steel sheet were included in the study; 1 deep drawing steel, 2 high strength steels of which 1 dual phase steel, 2 variants of austenitic and 1 of duplex stainless steels. Specimens manufactured through mechanical and laser cutting were fatigue tested both at constant stress amplitudes and at variable stress amplitudes using a truncated Gaussean spectrum. Defect distributions on the cut edges were measured quantitatively. The fatigue tests showed that the fatigue strength was higher after laser cutting than after mechanical cutting. The relative difference was larger for the higher strength steels than for the lower strength steels. A model to predict the fatigue strength was developed using defect distribution measurements on the cut edges combined with linear elastic fracture mechanics. The model could in a reasonable way describe the differences in fatigue strengths of specimens manufactured with the different cutting processes.
Activity of titanium oxide in CaO–SiO2–Ti3O5 slags at 1600°C
Authors: Ariyo Chris O. , Holappa Lauri E. K.
Published: March 2003

Activity of titanium oxide was determined in CaO–SiO2–Ti3O5 slags in the composition range 25–44% CaO, 30–46% SiO2, 10–39% TiO1.67 at 1600°C using electromotive force method. In the experiments, slags with different titanium oxide contents were equilibrated with liquid iron at 1873 K. Oxygen activity in the iron melt was measured and used with the titanium content in the metal to calculate titanium oxide activity in the slag. According to the results, it was concluded that the activity coefficient of titanium oxide (γ) is in the range of 0.39 to 1.68 depending on the titanium oxide content and slag basicity. It was evident from the experiments that the activity coefficient increases with the increase in basicity and tends to decrease with increasing SiO2.
The impact of silica to a SiO2–MgO–FeOx slag
Authors: Karlemo Ben Johan Waldemar , Taskinen Pekka Antero
Published: March 2003

The sensitivity of silica concentration from 20 to 50 wt% in SiO2–MgO–FeOx nickel smelting slags is studied at three Fe(tot)/MgO ratios of 4, 5 and 6 using calculated phase equilibria in slag‐cleaning conditions in an electric furnace. This study uses the thermodynamic software package MTDATA and the slag database of MIRO MTOX for covering the melting equilibria of the oxide system of Fe–O–MgO–SiO2 with limited modifying additions of CaO and Al2O3. According to the constructed phase diagrams, when the silica concentration exceeds 40 wt% SiO2 the liquidus temperature increases rapidly. The results also show that the addition of CaO decreases the liquidus temperature more than the addition of Al2O3 except for the area just in front of the steep liquidus temperature increase at SiO2 concentrations over 40 wt%. The primary precipitating phases are olivine at SiO2 concentrations less than 40 wt% and for concentrations over tridymite and cristobalite.
Take your profile mill into a new dimension (Interstand dimension control)
Authors: Dag Sollander
Published: March 2003

Industrial users of steel rod and bar are demanding more from these products at a time when competition between producers is growing stronger and the world is faced with a surplus of low and normal steel grades. Mill owners are therefore looking for new ways to achieve higher‐quality products more economically. Interstand dimension control (IDC) was developed to address this issue. By providing accurate and rapid feedback of dimensional data, IDC enables the roll gap and interstand speed to be controlled automatically, significantly reducing mill scrap and making rolling without loops a genuine option for most products.
Equilibrium between liquid iron and FetO‐containing solid solution
Authors: Hino Mitsutaka , Takahashi Kenji , Itoh Tsuneo , Kikuchi Ichiro , Nagasaka Tetsuya
Published: March 2003

Oxidation and reduction are utilized in the refining process of iron and steel. Therefore, the most important thermodynamic property is the activity of FetO in slag and especially in refractories, which contact with liquid iron and steel. It is well known that refractories easily form solid solutions with FetO, so that molten iron and steel would react with FetO in the refractories, non‐metallic inclusions and slag coexisting in the iron and steel production process. In the present work, the reaction of molten steel with the solid oxide phase will be discussed based on the activity of the constituents in MnO‐FetO and FetO.Cr2O3‐FetO solid solutions by way of examples of FetO‐containing solid solution.
Effects of nectar theft by flower mites on hummingbird behavior and the reproductive success of their host plant,Moussonia deppeana(Gesneriaceae)
Authors: Lara Carlos , Ornelas Juan Francisco
Published: March 2003

Hummingbird flower mites are transported in the nares of hummingbirds and may compete with them by “robbing” nectar secreted by the host plants. We have shown thatTropicoseiussp. flower mites consume almost half the nectar secreted by the long‐lived, protandrous flowers ofMoussonia deppeana(Gesneriaceae) pollinated byLampornis amethystinus(Trochilidae). In this paper, we ask whether mimicking nectar consumption of flower mites alters some aspects of hummingbird foraging patterns, and, if so, how this affects host plant seed production. We observed hummingbirds foraging on (a) plants in which nectar was removed from the flowers and then filled with a sugar solution to half the volume of nectar simulating nectar consumption by flower mites, and (b) plants where nectar was removed and then filled with the sugar solution up to normal nectar volumes. Flower mites were excluded from both groups of plants to control for mite activity. Hummingbirds made fewer but longer visits to plants and revisited more the flowers with nectar removal than those without the treatment. We then conducted a pollination experiment on pistillate flowers using a stuffedL. amethystinushummingbird to evaluate the effect of pollination intensity (number of bill insertions into one flower) on seed production. Flowers with more insertions produced significantly more seeds than those flowers that received fewer insertions. We conclude that the simulation of nectar consumption by hummingbird flower mites can influence the behavior of the pollinator, and this may positively affect seed production.
Cone abortion in Pinus halepensis: the role of pollen quantity, tree size and cone location
Authors: Goubitz Shirrinka , Werger Marinus J. A. , Shmida Avi , Ne'eman Gidi
Published: March 2003

This study describes the seasonal patterns of seed and cone abortion in natural Pinus halepensis trees and assesses the effects of pollen quantity, tree size and cone location on seed and cone abortion. The cone‐set ratio was similar to the expected value, based on literature on woody perennials. The seed‐ovule ratio, however, was almost twice as high as its expected value. The investment in protective cone elements was high and did not vary with the seed‐ovule ratio of a cone. Pollination factors influenced cone abortion, as indicated by the high abortion rate at the end of the pollination period. Furthermore, abortive cones had lower pollination rates and lower pollen loads than well developed cones. Effects of resource availability were assessed as effects of tree size and cone position on twigs. Small trees aborted more cones than big trees and cone abortion was higher in apical cones than in basal cones. Abortion in P. halepensis is selective, mediated by both pollen quantity and resource availability. The relative importance of pollen and resources is suggested to be flexible, probably varying between trees and years. The high seed‐ovule ratio of P. halepensis is the result of high pollination rate and selective abortion. The selective abortion might be due to the high allocation to protective cone elements relative to the allocation to seeds.
Cyanobacterial lichen symbiosis: the fungal partner as an optimal harvester
Authors: Hyvärinen Marko , Härdling Roger , Tuomi Juha
Published: March 2003

Lichen symbiosis has been traditionally treated as a model case of mutualism in which both partners, the fungus and the photobiont, gain benefits reciprocally. Some recent evidence, however, supports an alternative view that lichen symbiosis may represent an association largely controlled by the commensal or even parasitic fungal partner. The latter gains photosynthates from the photobiont (algae and/or cyanobacteria) which may not always substantially benefit from the symbiosis. We analyze from this perspective how a lichen fungus may maximize photosynthetic gains in bipartite and tripartite associations. We treat the frequency of nitrogen‐fixing cells called heterocysts in cyanobacteria and the relative proportion of green algal cells vs. that of cyanobacteria per unit fungus as the variables to be manipulated for maximal carbon gain. The model predicts that even with a negligible cost of cephalodia (compartments containing cyanobacteria) it is in the interest of the tripartite lichen, first, to increase the heterocyst frequency, and second, keep the relative number of cyanobacteria considerably lower than that of green algae. Hence, the lichen fungus achieves higher fitness by making the cyanobacterial partner to specialize on N fixation. The available empirical data support these predictions as the reported heterocyst frequencies in bipartite lichens range from 2 to 8%, and in tripartite lichens between 10 and 55%. It is concluded that interaction asymmetry (i.e. commensalism or parasitism rather than mutualism) provides a sound basis to understand the high phenotypic plasticity expressed by fungi‐forming bipartite and tripartite associations with cyanobacteria and green algae.
Growth and hare, Lepus timidus, resistance of white birch, Betula pendula, clones grown in different soil types
Authors: Laitinen Jaana , Rousi Matti , Tahvanainen Jorma
Published: March 2003

Carbon‐nutrient balance (CNB) hypothesis predicts that improved nutrient availability increases the growth of woody plants at the expense of herbivore resistance due to carbon‐based secondary metabolites. We tested this hypothesis by growing five clones of white birch (Betula pendula Roth) in two different habitats (mineral and peat soil) for eight years. The growth parameters of the clones and their resistance to hare (Lepus timidus) browsing were measured and compared with the growth/resistance relationship of same clones tested previously at the age of 1 year. The resistance of birches was evaluated in feeding choice experiments with both captive and free‐ranging hares. Experiments using caged or free‐ranging hares gave identical results on the feeding pattern by hares indicating that both methods are reliable in measuring the relative palatability of types of woody browse.  The number of resin droplets on birch twigs is a good indicator of hare resistance, and our results are partly in accordance with the CNB hypothesis: trees grown in mineral soil (optimal conditions) had fewer resin droplets than trees grown in peat soil. Two of the five clones tested were significantly more palatable to hares when grown in mineral soil than the same clones grown in peat soil. Trees grown in mineral soil were also taller and had greater biomass than trees grown in peat soil. However, the significant clone×habitat interaction in the production of resin droplets and growth/palatability relationships indicates that different tree genotypes can have individualistic responses to environmental variations, and thus the responses of all birch clones do not follow the predictions of the CNB hypothesis.  Similar rank order in the palatability of the studied birch clones at the age of one and eight years indicates a strong genetic basis for resistance. However, the relationship between height and palatability of birches was negative in the 1‐year‐old plants but positive in the 8‐year‐old birches used in this experiment. This may indicate that first‐year seedlings attain both optimal growth and high resistance at high nutrient supply with no trade‐off between growth and resistance. On the whole, more experiments are needed to determine the mechanisms of resistance, especially in young seedlings and older saplings grown in different environments.
Coevolution of host immune defence and parasite‐induced mortality: relative spleen size and mortality in altricial birds
Authors: Møller Anders Pape , Erritzøe Johannes
Published: March 2003

Animal hosts defend themselves against parasites by the antibodies produced by an immune system. It is an inherent assumption that parasites constitute the selection pressure that has given rise to and maintains the immune system. Thus, greater impact by parasites on host fitness should result in greater investment in immune function across species. We tested this prediction by using field estimates of parasite‐induced nestling mortality in altricial birds as an estimate of the fitness cost of parasitism and the relative size of the spleen as an estimate of investment in immune function. The spleen is a peripheral lymphoid tissue that acts as the main site of lymphocyte differentiation and proliferation, and these B‐ and T‐cells are involved in the production of humoral and cell‐mediated immune responses. In a comparative study of 21 species of altricial birds we found a significant positive relationship between relative spleen size and parasite‐induced mortality, accounting for a third of the variance, even when controlling for potentially confounding variables. This finding provides evidence for the level of investment in immune function being related to the natural selection pressure imposed by parasites.
Invasibility and compositional stability in a grassland community: relationships to diversity and extrinsic factors
Authors: Foster Bryan L. , Smith Val H. , Dickson Timothy L. , Hildebrand Terri
Published: March 2003

We present results from an ongoing field study conducted in Kansas grassland to examine correlates of invasibility and community stability along a natural gradient of plant diversity. Invasibility was evaluated by sowing seeds of 34 plant species into 40 experimental plots and then measuring colonization success after two growing seasons. Compositional stability, defined as resistance to change in species relative abundances over two growing seasons and in response to experimental disturbance, was measured in a separate set of 40 plots.  We found that community susceptibility to invasion was greatest in high diversity microsites within this grassland. Multiple regression analyses suggested that the positive correlation between invasibility and plant diversity was due to the direct influences of the extrinsic factors that contribute to spatial variation in diversity (soil disturbances; light availability), not to any direct impact of diversity. In addition, we found that compositional stability in response to disturbance was greatest within low diversity microsites and was strongly related to the dominance (evenness) component of diversity.
Density dependence and stochastic variation in a newly established population of a small songbird
Authors: Sæther Bernt‐Erik , Engen Steinar , Lande Russell , Both Christiaan , Visser Marcel E.
Published: March 2003

Models describing fluctuations in population size should include both density dependence and stochastic effects. We examine the relative contribution of variation in parameters of the expected dynamics as well as demographic and environmental stochasticity to fluctuations in a population of a small passerine bird, the pied flycatcher, that was newly established in a Dutch study area. Using the theta‐logistic model of density regulation, we demonstrate that the estimated quasi‐stationary distribution including demographic stochasticity is close to the stationary distribution ignoring demographic stochasticity, indicating a long expected time to extinction. We also show that the variance in the estimated quasi‐stationary distribution is especially sensitive to variation in the density regulation function. Reliable population projections must therefore account for uncertainties in parameter estimates which we do by using the population prediction interval (PPI). After 2 years the width of the 90% PPI was already larger than the corresponding estimated range of variation in the quasi‐stationary distribution. More precise prediction of future population size than can be derived from the quasi‐stationary distribution could only be made for a time span less than about five years.
Oral and skin keratinocytes are stimulated to secrete monocyte chemoattractant protein‐1 by tumour necrosis factor‐α and interferon‐γ
Authors: Li Jie , Farthing Paula M. , Thornhill Martin H.
Published: March 2003

Abstract: Monocyte chemoattractant protein‐1 (MCP‐1) is a member of the CC subfamily of chemokines. It is chemoattractant for monocytes, activated memory T cells and dendritic cells. We studied MCP‐1 mRNA and protein production in cultured human oral keratinocytes (OK) and skin keratinocytes (SK). MCP‐1 production was undetectable in resting keratinocytes. However, stimulation with tumour necrosis factor‐α (TNF‐α) or interferon‐γ (IFN‐γ) induced MCP‐1 mRNA and protein synthesis in both cell types. Together, TNF‐α and IFN‐γ acted synergistically to increase MCP‐1 production. In each case MCP‐1 production was greater for SK than OK. The kinetics of IFN‐γ‐induced MCP‐1 production were similar for both cell types, peaking around 72 h. In contrast, TNF‐α induced a more rapid increase in MCP‐1 production by SK than OK, peak production occurring after 24 and 72 h, respectively. IL‐1α and IL‐4 did not induce MCP‐1 production. However, in combination with IFN‐γ, they induced a small extra increase in MCP‐1 production in SK but not OK.
Pathology of the desmoplastic ameloblastoma
Authors: Kishino Mitsunobu , Murakami Shumei , Fukuda Yasuo , Ishida Takeshi
Published: March 2003

Abstract: Desmoplastic ameloblastoma is a rare variant of ameloblastoma and only 54 cases have been previously reported in the English literature. We report ten cases of desmoplastic ameloblastoma of the jaw observed between 1972 and 1998 and discuss the pathogenesis of the tumor. Eight of the ten tumors were located in the anterior region of the jaw. Radiographically, six cases showed mixed radiolucent/radiopaque appearance with ill‐defined margins and the other four cases lacked typical findings of ameloblastomas. The tumors were located mainly in the alveolar region and occupied the tooth‐bearing area, without tooth resorption or impacted teeth. Histologically, the desmoplastic ameloblastomas were characterized by extensive stromal desmoplasia, and small tumor nests of odontogenic epithelium were scattered in the stroma. Oxytalan fibers stained by potassium monopersulfate‐aldehyde fuchsin were demonstrated in the stroma of all desmoplastic ameloblastomas. From these findings, we presumed that the desmoplastic ameloblastomas might have developed in the periodontal membrane.
Evaluation of premalignant potential in oral lichen planus using interphase cytogenetics
Authors: Kim Jin , Yook Jong In , Lee Eun Ha , Ryu Mi Heon , Yoon Jung Hoon , Hong Jun Chul , Kim Dong Ju , Kim Hyun Sil
Published: March 2003

Abstract: This study attempted to evaluate whether oral lichen planus (OLP) has the potential to progress to oral squamous cell carcinoma (OSCC) by comparing the degree of genetic instability between clinically‐curable OLP and lesions that progressed to OSCC. Fifteen cases of steroid‐responsive OLP and two cases of lichenoid dysplasia (LD) that progressed to OSCC were used for this study. Chromosome in situ hybridization (CISH) was performed for chromosomes 9 and 17. The fraction of polysomic and monosomic cells for chromosome 9 increased in mucosal epithelium compared to those of lymphocytes in OLP. This difference was statistically significant (P=0.0017, 0.0054, respectively). Two LD patients showed 15.38% and 22.58% of PI for chromosome 9. In OSCC that developed from LD, the fraction of monosomic cells for chromosome 9 increased by more than 70%. We concluded that LD should be treated as a high‐risk premalignant lesion and strongly suggest that the monosomy of chromosome 9 may have a critical role in progress to malignancy from LD.
Immune competent cells in non‐irradiated autologous jejunal grafts used for reconstruction of the oral cavity and oropharynx
Authors: Millesi Werner , Formanek Michael , Moser Doris , Kornfehl Johannes
Published: March 2003

Abstract: Autologous jejunal grafts used for primary reconstruction in cases of extensive soft tissue defects following tumor resection in the upper aerodigestive tract were investigated by immunhistochemistry (APAAP technique). Biopsies from eight patients were taken intra‐operatively, at the time of transplantation and 2, 4, and 6 months post‐operatively. A panel of monoclonal antibodies directed against surface antigens of the major subpopulations of the immune system was used. In all of the patients, a remarkable increase of all antigens investigated was detected 2 months post‐operatively, which remained unchanged in the following biopsies (4 and 6 months postoperatively). Significantly higher numbers of CD45RA+ and CD45RO+ (P<0.05) leukocytes were detectable. This increase was due to both subsets of T and B cells, but only for CD19+ B cells was the increase significant. In addition, NK cells (CD16+ lymphocytic cells, P<0.01) and mature macrophages (25F9+ cells, P<0.01) increased. The first post‐operative biopsy showed a significantly higher expression of activation‐associated antigens (ICAM‐1, VCAM, and HLA‐DR) on monocytes/macrophages and endothelial cells. Our findings indicate that autologous jejunal grafts facilitate immunological function in the new microenvironment.
Heterogeneity in antifungal susceptibility of clones of Candida albicans isolated on single and sequential visits from a HIV‐infected southern Chinese cohort
Authors: Samaranayake Y. H. , Samaranayake L. P. , Tsang P. C. , Wong K. H. , Yeung K. W. S.
Published: March 2003

Abstract: The increased frequency and severity of candidal infections in human immunodeficiency virus (HIV)‐infected individuals has prompted the wide use of antifungals, such as amphotericin B, ketoconazole, and fluconazole, resulting in the emergence of drug‐resistant strains of Candida albicans. To study this phenomenon in an ethnic Chinese cohort, we isolated multiple colonies of Candida from the oral cavities of 16 HIV‐infected patients on single and subsequent sequential visits over a period of 12 months. Ten of the 16 patients had sporadic episodes of oropharyngeal candidiasis (Group A), while the remainder were asymptomatic with respect to this condition (Group B). Oral rinses were collected and immediately processed in the laboratory for the isolation of C. albicans in a standard manner. A total of 433 C. albicans isolates were tested for their susceptibility to amphotericin B, ketoconazole and fluconazole by an agar diffusion method using the commercially available E‐test. All tested isolates demonstrated variable susceptibility to amphotericin B, ketoconazole and fluconazole. The minimum inhibitory concentration (MIC) of the isolates for amphotericin B, ketoconazole and fluconazole ranged from <0.002–1.5 μg/ml, <0.002–4.0 μg/ml and <0.016–32 μg/ml, respectively. Sequential isolates of a few patients demonstrated variable susceptibility to all the antifungals, and no discernible MIC pattern emerged either in group A or B over time. Interestingly, significant variation in antifungal susceptibility was also noted in isolates obtained from the same patient on a single visit. Sequential yeast isolates in 9 of 16 patients (56%) demonstrated significant differences in MIC within and between visits for both amphotericin B and ketoconazole, while a lower percentage – 44% (7/16) – exhibited this trait for fluconazole. Our study demonstrates the diversity in antifungal susceptibility in either commensal or “infective” oral strains of C. albicans in HIV disease, and shows the need for vigilance for the emergence of resistant strains, and for frequent antifungal susceptibility studies.
Expression of telomerase RNA in oesophageal and oral cancer
Authors: Downey M. G. , Going J. J. , Stuart R. C. , Keith W. N.
Published: March 2003

Background: Telomerase is detectable in 85% of cancers, but is largely repressed in normal tissues. Human telomerase RNA (hTR) inhibition is a promising anti‐cancer strategy, but requires differential expression between malignant and normal tissue.

Method: Archival paraffin sections from 48 oral squamous cell carcinomas (SCC) (23 floor of mouth, 25 tongue) and 56 oesophageal carcinomas (41 SCC, 15 adenocarcinomas) were evaluated for hTR expression using a radiolabelled riboprobe. Results were compared with expression in controls and adjacent histologically normal tissue. Statistical analysis was by the χ2 test.

Results: hTR was detectable in 76% of oral SCC overall (floor of mouth 65%, tongue 88%, P=0.61), and in 54% of oesophageal cancers (SCC 51%, adenocarcinoma 60%, P=0.56). Detectable hTR expression was significantly more frequent in oral SCC than oesophageal SCC (P=0.01). hTR expression was only detected in normal tissue at low levels in basal squamous epithelium. There was agreement of hTR expression between 8/9 surgically excised carcinomas and their initial diagnostic biopsies.

Conclusion: Tumour‐specific hTR expression confirms hTR inhibition as a possible therapeutic strategy in some if not all oesophageal and oral cancers. Generally concordant hTR status between biopsy and resection suggest that biopsy may have a role in selecting candidates for telomerase inhibition therapy.
Immunohistochemical analysis of apoptosis‐related factors (Fas, Fas ligand, caspase‐3 and single‐stranded DNA) in ameloblastomas
Authors: Kumamoto Hiroyuki , Kimi Kenji , Ooya Kiyoshi
Published: March 2003

Background: To clarify the possible role of apoptotic cell death in oncogenesis and cytodifferentiation of odontogenic epithelium, apoptosis‐related factors – Fas, Fas ligand (FasL), caspase‐3 and single‐stranded DNA (ssDNA) – were analyzed in ameloblastomas as well as in tooth germs.

Methods: Specimens of 5 tooth germs, 29 benign ameloblastomas and 5 malignant ameloblastomas were examined by immunohistochemistry using anti‐Fas, FasL, caspase‐3 and ssDNA polyclonal antibodies.

Results: Immunoreactivity for Fas and FasL was detected in normal and neoplastic odontogenic epithelial cells. Fas expression in ameloblastomas was slightly lower than that in tooth germs, whereas FasL expression was similar in tooth germs and ameloblastomas. Malignant ameloblastomas showed downregulation of Fas expression and upregulation of FasL expression, as compared with benign ameloblastomas, indicating escape from cell death attack by immune cells. Immunoreactivity for caspase‐3 was detected chiefly in cells neighboring the basement membrane in tooth germs and ameloblastomas. Expression of caspase‐3 and Fas tended to be low in basal cell ameloblastomas and high in desmoplastic ameloblastomas, as compared with other variants of ameloblastomas. Caspase‐3 expression was more intense in malignant ameloblastomas than in tooth germs and benign ameloblastomas. Apoptotic bodies reactive with anti‐ssDNA antibody were detected in normal and neoplastic odontogenic epithelial cells detached from the basement membrane. Keratinizing cells in acanthomatous ameloblastomas and granular cells in granular cell ameloblastomas showed increased numbers of apoptotic bodies and increased expression of Fas and caspase‐3, as compared with other neoplastic cells. Apoptotic reactions in malignant ameloblastomas were less frequent than in benign ameloblastomas, indicating abnormal regulation of cell turnover in odontogenic epithelial cells.

Conclusion: These apoptosis‐related factors were detected in various patterns in normal and neoplastic odontogenic epithelium, suggesting that these factors might be associated with oncogenesis and cytodifferentiation of epithelial odontogenic tumors.
Nucleolar organizer regions (NORs) evaluation of lingual salivary glands of chronic alcoholics
Authors: Severgnini M. , Ferraris M. E. , Carranza M.
Published: March 2003

Background:  Chronic alcoholism has been associated with structural and physiological changes in salivary glands. Studies on a variety of pathologies have suggested that variation in number of nucleolar organizer regions (NORs) reveals conditions of cellular activity. The aim of this work was to examine, through the AgNOR technique, changes in number and size of NORs in lingual salivary glands of chronic alcoholics.

Methods:  Samples of mucous and serous lingual salivary glands were obtained from tongues from autopsies of individuals whose cause of death was hepatic alcoholic cirrhosis. Lingual organs from individuals whose cause of death was accidental were used as controls. Number and size of the AgNORs and nuclear area, in ductal and acinar cells, were evaluated through a digital image analyzer.

Results:  Statistical analysis revealed differences (P ≤ 0.05) in number of AgNORs in mucous acini and ductal cells. Also, we observed changes in the area of the NORs.

Conclusion:  These results suggest that in alcoholics the activity of glandular cells, mainly in ductal epithelium, could be affected, modifying synthesis, transport and salivary secretions.
Effects of locally injected interferon‐β on palatal mucoperiosteal wound healing
Authors: Cornelissen A. M. H. , Von den Hoff J. W. , Maltha J. C. , Kuijpers‐Jagtman A. M.
Published: March 2003

Background:   Wound contraction and scar formation in the palatal mucoperiosteum after cleft palate surgery impair maxillary growth. The aim of this study was to determine the effects of IFN‐β on palatal mucoperiosteal wound healing in growing rats.

Methods:   Standardized wounds were made in the palatal mucoperiosteum of young rats. Either IFN‐β or vehicle were injected at the wound site between 4 and 29 days after wounding. The results were compared with control wounds. Tissue samples were collected at 8, 15, 30, and 60 days PW for biochemical and microscopic analysis.

Results:   IFN‐β stimulated re‐epithelialization but did not reduce the number of myofibroblasts or scar tissue formation. Surprisingly, the injection of vehicle alone delayed the healing process.

Conclusion:   IFN‐β might be suitable to stimulate re‐epithelialization but it does not reduce scar tissue formation in rat palatal wound healing. The injection of agents into palatal wounds might severely impair the healing process.
AgNOR count as objective marker for dysplastic features in oral leukoplakia
Authors: Chattopadhyay Amit , Ray Jay G. , Caplan Daniel J.
Published: March 2003

Background:   Dysplasia is an important feature of leukoplakia. Because agreement among oral pathologists is poor regarding lesional diagnosis, silver stainable nucleolar organizer regions (AgNORs) as replicatory markers may have a place in objectively characterizing dysplasia in tissue specimens.

Methods:   We studied 41 normal oral epithelia, 51 oral leukoplakia (26 dysplastic, 25 non‐dysplastic), and 51 cases of squamous cell carcinoma specimens for their mean AgNOR counts.

Results:   Mean AgNOR counts increased gradually from normal epithelium to non‐dysplastic to dysplastic leukoplakia to squamous cell carcinoma. Using ROC analysis, we determined a mean AgNOR count cut‐point (2.37) that can be used to distinguish between dysplastic and non‐dysplastic leukoplakia. The test had a sensitivity of 75% and specificity of 83% with area under the curve being 88%.

Conclusions:  Mean AgNOR count could be a valuable criterion for defining objective parameters for diagnosis/determination of dysplasia distinguishing between dysplastic and non‐dysplastic leukoplakia.