bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of STAT6 in mast cell IL‐4 production
Authors: Sherman Melanie A.
Published: March 2003

Summary: Interleukin (IL)‐4 has an important role in regulating antibody production and inflammation. The major IL‐4 producers are CD4+ T cells, but the development of an IL‐4‐producing phenotype in these cells requires IL‐4 signaling through the STAT6 pathway during differentiation. The cellular source of this early IL‐4 is not known, but mast cells are a possible candidate due to their immediate and indiscriminate release of IL‐4 upon activation. In this review we summarize the evidence that STAT6 signaling is not required for mast cell IL‐4 production, which is consistent with their possible role as a link between the innate immune response and T‐cell activation. We also describe an isoform of STAT6 that is expressed in mast cells and that appears to act as a repressor of IL‐4 transcription. This STAT6 signaling pathway may be part of a feedback mechanism to protect surrounding tissues from IL‐4‐mediated inflammation during an infection.

The author would like to thank Dr. Melissa Brown for her generous support, helpful discussions and critical review of the manuscript and Dr. Virginia Secor for her collaboration with this project. Drs. Andrew Neish, Jeremy Boss and S. Wright Caughman provided helpful comments. M.A.S. was a fellow of the Cancer Research Institute and this project is currently supported by the National Institutes of Health (KO1 AR 02157‐01).
Ribosomes and secretory granules in human mast cells: close associations demonstrated by staining with a chelating agent
Authors: Dvorak Ann M. , Morgan Ellen S.
Published: March 2003

Summary: The distribution of ribosomes was investigated in mature human mast cells with a chelation‐based staining protocol known to bleach DNA‐rich structures, leaving RNA‐rich structures unbleached. With this method, electron‐dense ribosomes were adjacent to, attached to, and within secretory granules, which were also bleached with the chelation method that we used. The finding of these ribosome–secretory granule relationships suggests that secretory granules in mature human mast cells may participate in RNA metabolism.

This work was supported by a grant (AI 33372) from the National Institutes of Health. We thank Peter K. Gardner for editorial assistance in the preparation of the manuscript and Patricia Fox for printing the electron micrographs.
Eosinophil trafficking to sites of allergic inflammation
Authors: Broide David , Sriramarao P.
Published: March 2003

Eosinophils play a prominent pro‐inflammatory role in allergic inflammation. Studies utilizing flow chambers, intravital videomicroscopy, and cytokine and adhesion molecule‐deficient mice have provided important insight into the mechanisms of eosinophil trafficking in inflamed blood vessels and into tissues in vivo. While the bone marrow generation of eosinophils is finely regulated by interleukin (IL)‐5, the trafficking of eosinophils into tissues is regulated by several cytokines, chemokines, and adhesion molecules with overlapping functions. Prospects for therapeutically inhibiting eosinophilic inflammation by inhibiting eosinophil adhesion to endothelium are dependent on an improved understanding of the relative importance of individual cytokines and adhesion molecules in regulating eosinophil adhesion to endothelium. Alternative strategies to inhibit eosinophilic inflammation include the use of immunostimulatory DNA sequences containing a CpG motif to act as a Th1 adjuvant to prevent Th2 responses associated with IL‐5 and eosinophilia. Immunostimulatory DNA sequences do not induce eosinophil apoptosis, but function at the level of the bone marrow to inhibit the IL‐5‐induced bone marrow generation and release of eosinophils.

This research was supported by NIH grants AI 38425 and AI 33977 (DHB) and AI 35796 to (PS).
The thymus and negative selection
Authors: Sprent Jonathan , Kishimoto Hidehiro
Published: March 2003

Summary: Maintenance of tolerance to self antigens is presumed to reflect a combination of central and peripheral tolerance. For T cells, central tolerance occurs during early T cell development in the thymus and causes cells with strong reactivity to self antigens to be destroyed in situ (negative selection). Here, we summarize evidence that negative selection can occur in the thymic medulla and affects a population of semimature HSA+ T cells. The influence of costimulatory molecules, Fas and cytokines on negative selection is discussed.
Molecular versatility of antibodies
Authors: Metzger Henry
Published: March 2003

Summary: As immunology developed into a discrete discipline, the principal experimental efforts were directed towards uncovering the molecular basis of the specificity exhibited by antibodies and the mechanism by which antigens induced their production. Less attention was given to how antibodies carry out some of their effector functions, although this subject presents an interesting protein‐chemical and evolutionary problem; that is, how does a family of proteins that can bind a virtually infinite variety of ligands, many of which the species producing that protein has never encountered, reproducibly initiate an appropriate response? The experimental data persuasively suggested that aggregation of the antibody was a necessary and likely sufficient initiating event, but this only begged the question: how does aggregation induce a response? I used the IgE:mast cell system as a paradigm to investigate this subject. Data from our own group and from many others led to a molecular model that appears to explain how a cell ‘senses’ that antigen has reacted with the IgE. The model is directly applicable to one of the fundamental questions cited above, i.e. the mechanism by which antigens induce the production of antibodies. Although the model is conceptually simple, incorporating the actual molecular events into a quantitatively accurate scheme represents an enormous challenge.
Effective therapeutic anticancer vaccines based on precision guiding of cytolytic T lymphocytes
Authors: Melief Cornelis J. M. , Van Der Burg Sjoerd H. , Toes Rene E. M. , Ossendorp Ferry , Offringa Rienk
Published: March 2003

Summary: In natural immune responses CD4+ T helper (Th) cells, reactive with peptide antigens presented by major histocompatibility complex (MHC) class II molecules on dendritic cells (DC), can drive the maturation of DC that is required for induction of CD8+ cytolytic T‐lymphocyte (CTL) immunity. Proper induction, expansion and maintenance of CTL responses are achieved through delicate interactions between CD4+ T cells, DC and CD8+ T cells involving several ligand–receptor pairs. Th cells to a large extent operate through up‐regulation of CD40L, which then interacts with CD40 on DC to cause DC maturation. Subsequent CTL induction by activated DC requires CD80/CD86 on the DC to interact with the CD28 costimulatory receptor on CD8+ T cells. For maintenance and full expansion of CTL, interaction of the DC‐expressed 4–1BB ligand with its receptor 4–1BB on CTL is also important. Alternative molecular triggers of DC activation that can support induction of powerful CTL responses include agonistic anti‐CD40 antibody or ligands of Toll‐like receptors (TLR) such as LPS (TLR4 ligand) or oligodeoxynucleotides containing CpG‐motifs (TLR9 ligand). The combination of CpG adjuvant with a 35 amino acid long synthetic peptide comprising both tumor‐specific CTL and Th epitopes proved to be a highly effective vaccine formulation capable of inducing therapeutic immunity against human papillomavirus‐induced mouse tumors. The recently acquired insights into antigen presentation and costimulatory signals have made possible the development of a new generation of therapeutic anticancer vaccines.
Single nucleotide polymorphisms in innate immunity genes: abundant variation and potential role in complex human disease
Authors: Lazarus Ross , Vercelli Donata , Palmer Lyle J. , Klimecki Walt J. , Silverman Edwin K. , Richter Brent , Riva Alberto , Ramoni Marco , Martinez Fernando D. , Weiss Scott T. , Kwiatkowski David J.
Published: March 2003

Summary: Under selective pressure from infectious microorganisms, multicellular organisms have evolved immunological defense mechanisms, broadly categorized as innate or adaptive. Recent insights into the complex mechanisms of human innate immunity suggest that genetic variability in genes encoding its components may play a role in the development of asthma and related diseases. As part of a systematic assessment of genetic variability in innate immunity genes, we have thus far have examined 16 genes by resequencing 93 unrelated subjects from three ethnic samples (European American, African American and Hispanic American) and a sample of European American asthmatics. Approaches to discovering and understanding variation and the subsequent implementation of disease association studies are described and illustrated. Although highly conserved across a wide range of species, the innate immune genes we have sequenced demonstrate substantial interindividual variability predominantly in the form of single nucleotide polymorphisms (SNPs). Genetic variation in these genes may play a role in determining susceptibility to a range of common, chronic human diseases which have an inflammatory component. Differences in population history have produced distinctive patterns of SNP allele frequencies, linkage disequilibrium and haplotypes when ethnic groups are compared. These and other factors must be taken into account in the design and analysis of disease association studies.
The immunogenomics of minor histocompatibility antigens
Authors: Roopenian Derry , Choi Eun Young , Brown Aaron
Published: March 2003

Summary: Minor histocompatibility (H) antigens are a diverse assemblage of major histocompatibility complex (MHC)‐bound peptides with the unifying property of acting as alloantigens that induce allogeneic tissue rejection. They are a consequence of any form of accumulated genetic variation that translates to differential MHC‐presented peptide epitopes, the most common form of which is simple sequence polymorphisms. The universe of potential minor H antigens is large when transplantation is performed between genetically unrelated, MHC‐matched individuals, especially considering the remarkable discriminative sensitivity of T cells. However, the phenomenon of immunodominance greatly simplifies immune responses that ensue. One mouse minor H antigen, H60, stands out in that the preponderance of the CD8 T cell response elicited in a complex alloantigenic setting is directed against this single minor H antigen epitope. Its immunodominance is because mice lacking H60 develop an unusually robust T cell repertoire dedicated to this single minor H antigen. The now well‐characterized mouse minor H antigen system should provide a vehicle to assess the degree to which immunodominant alloantigens contribute to transplant rejection.
Central and systemic haemodynamic effects of terlipressin in portal hypertensive patients
Authors: Møller Søren , Hansen Erik F. , Becker Ulrik , Brinch Kim , Henriksen Jens H. , Bendtsen Flemming
Published: March 2003

Abstract: Aims/Background: Cirrhotic patients exhibit a hyperdynamic and hyporeactive circulation with central hypovolaemia which may influence the course of the disease. As terlipressin, a vasopressin analogue, may modify systemic haemodynamics in these patients, the aim of the present study was to assess the acute effects of terlipressin on central and systemic haemodynamics. Methods: Sixteen patients with alcoholic cirrhosis and portal hypertension had their systemic, central, and splanchnic haemodynamics determined at baseline and after a blind randomised bolus infusion (2 mg) of terlipressin/placebo. Results: After terlipressin, the arterial blood pressure and the systemic vascular resistance increased by 26% and 61%, respectively (both p<0.001), and the cardiac output, heart rate, and arterial compliance decreased by 18%, 11%, and 32%, respectively (all p<0.001). The central circulation time increased by 36% (p<0.001), whereas the central and arterial blood volume only increased by 4% (p=0.07). As expected, both portal pressure and hepatic blood flow decreased (17% and 29%, both p<0.001). The decrease in portal pressure after terlipressin was significantly related to the increase in systemic vascular resistance (r=−0.52, p<0.05) and the central circulation time (r=−0.80, p<0.0001). Conclusions: Terlipressin significantly attenuates the hyperdynamic circulation in portal hypertensive patients without a further contraction of the central and arterial blood volume. The systemic haemodynamic response to terlipressin is moreover associated with the decrease in portal pressure. Terlipressin may therefore have potentially beneficial effects on the hyperdynamic circulation in cirrhosis in addition to its effects on portal pressure.
Characterization of hepatocyte‐derived mitogenic activity on hepatic stellate cells
Authors: Skrtic Stanko , Wallenius Kristina , Gressner Axel M. , Jansson John‐Olov
Published: March 2003

Abstract: Background/Aims: Hepatic stellate cells (HSC) are located in close proximity to hepatocytes in Disse's space. Hepatocyte derived factors have earlier been implicated in the paracrine regulation of HSC proliferation. The aim of the present study was to further characterize this mitogenic activity of the parenchymal cell conditioned medium (PCcM). Methods: Primary rat HSC were cultured for 4 days. DNA synthesis was measured by 3H‐thymidine incorporation. TGFβ1 immunoreactivity was quantified by ELISA. PCcM was obtained from hepatocytes cultured in medium without serum or hormones for two days. Results: Incubation of 4‐day‐old HSC on plastic surface with PCcM for 2 days increased DNA synthesis, while no effect was seen in HSC cultured on Matrigel. Heat‐, acid‐, and protease‐treatment of PCcM abolished its stimulatory effect. Size fractionations with spin columns indicated that the stimulatory effect was contained in the fractions of a molecular size between 30 and 100 kD. The addition of LY 294002, a phosphatidylinositol 3‐kinase (PI3‐K) inhibitor, dose‐dependently inhibited the PCcM induced increase in DNA synthesis to about 9% of the control values. The specific MAP kinase (MAPK) inhibitor, PD 98059 only suppressed the PCcM induced DNA synthesis to 35% of control cultures at the highest dose (10 μM). DNA content in the cultures was not affected by either blocker. HSC seemed to produce immunoreactive TGFβ1. However, addition of latency‐associated peptide (LAP), a potent TGFβ1 blocker, stimulated DNA synthesis to a much less extent than PCcM. Conclusions: The factor(s) that stimulate DNA synthesis in HSC from hepatocytes are most likely protein(s) with a molecular size between 30–100 kD. These factor(s) rely more on PI3‐K than on MAPK for their mitogenic effect and are probably not acting via TGFβ1 inhibition.
The capability of isolated hepatocytes and liver slices of donor livers to predict graft function after liver transplantation
Authors: Olinga Peter , Maring John K. , Merema Marjolijn , Hof Ingrid H. , Slooff Maarten J. H. , Meijer Dirk K. F. , Groothuis Geny M. M.
Published: March 2003

Abstract: Aims/Background: In liver transplantation, adequate function tests for donor livers and transplanted livers are of utmost importance to provide an objective basis for decision‐making. Isolated hepatocyte and/or slice preparations from human donor liver tissue may be suitable to test the quality of the organ to be transplanted. Methods: Surgical waste material remaining after reduced size or split liver transplantation in children was used to prepare slices and isolated hepatocytes. The viability of these preparations as well as drug transport and metabolism functions were determined and related to graft function in 32 liver recipients. Results: The in vitro tests used in the present study apparently did not select non‐viable livers. In vitro preparations of the primary non‐function grafts which occurred in the investigated group showed normal viability, metabolic and uptake function. Conclusion: These results indicate that either the presently used viability tests are not sensitive enough to detect potential organ failure or that other factors besides the hepatocyte viability at the time of transplantation are of paramount importance to the graft function of the recipient, such as complications during and after transplantation or the viability of the non‐parenchymal cells.
Endothelial nitric oxide synthase and caveolin‐1 are co‐localized in sinusoidal endothelial fenestrae
Authors: Yokomori Hiroaki , Oda Masaya , Ogi Mariko , Kamegaya Yoshitaka , Tsukada Nobuhiro , Ishii Hiromasa
Published: March 2003

Abstract: Background/Aims: Nitric oxide is synthesized in diverse mammalian tissues by a family of calmodulin‐dependent nitric oxide synthases (NOS). Caveolin, the principal structural protein in caveolae, interacts with endothelial NOS leading to enzyme inhibition in a reversible process modulated by Ca++‐calmodulin. The aim of the present study was to clarify the ultrastructural localization of eNOS and caveolin‐1 in hepatic sinusoidal endothelium by an electron immunogold method. Methods: Male Wistar rats were used. Liver tissues and hepatic sinusoidal endothelial cells isolated from rat livers by collagenase infusion were studied. For immunohistochemistry, liver specimens were reacted with anti‐eNOS or anti‐caveolin‐1 antibody. The ultrastructural localization of eNOS or caveolin‐1 was identified by electron microscopy using an immunogold post‐embedding method. Results: Immunohistochemical studies using liver tissues localized endothelial NOS in hepatic sinusoidal lining cells, portal veins and hepatic arteries; and caveolin‐1 in sinusoidal lining cells, bile canaliculi, portal vein and hepatic arteries. Immunogold particles indicating the presence of eNOS and caveolin‐1 were demonstrated on the plasma membrane of sinusoidal endothelial fenestrae in liver tissue and also in isolated sinusoidal endothelial cells. Conclusion: Endothelial NOS and caveolin are co‐localized on sinusoidal endothelial fenestrae, suggesting that interaction of the two may modulate cellular regulation of NO synthesis.
Fatal liver infarction after transjugular intrahepatic portosystemic shunt procedure
Authors: Mayan Haim , Kantor Rami , Rimon Uri , Golubev Nina , Heyman Zahava , Goshen Elinor , Shalmon Bruria , Weiss Peretz
Published: March 2003

Abstract: Hepatic infarction is a rare disease. We describe here a cirrhotic patient with end‐stage renal failure and recurrent tense ascites with fatal hepatic infarction after transjugular intrahepatic portosystemic shunt (TIPS) procedure. Abdominal ultrasound, radionuclide liver scan, abdominal computed tomography scan, and finally liver biopsy established the diagnosis. The mechanism causing the infarct is not clear. However, as the infarct appeared after the patient had an episode of shock and disseminated intravascular coagulation, it could well be that the concomitant hepatic arterial insufficiency contributed to the infarct. Physicians should be aware of this possible catastrophic complication.
Minimal liver injury in chronic hepatitis C virus infection is associated with low levels of soluble TNF‐α/Fas receptors and acquisition in childhood
Authors: Macías J. , Sánchez‐Quijano A. , Pineda J. A. , Abad M. A. , Rubio A. , Rosa R. , Leal M. , Lissen E.
Published: March 2003

Abstract: Background/Aims: The rate of progression to cirrhosis of chronic hepatitis C might be related to an upregulation of TNF‐α/Fas pathways. Methods: The serum levels of soluble TNF‐α type II receptor (sTNFr‐II) and soluble Fas antigen (sFas) were analyzed in patients with different histological outcomes of chronic parenterally acquired HCV infection of similar duration. Results: One hundred and forty‐five HCV‐infected patients had a known duration of infection. Twelve (8.3%) patients had minimal changes and were assigned to the case group. The control group was selected from the 24 (17%) patients with cirrhosis and the 54 (37%) with chronic active hepatitis (CAH). Two controls, one with CAH and one with cirrhosis, were paired with the cases following these criteria: duration of infection, transmission route and sex. The proportions of genotype 1b and HCV RNA serum levels were similar among the groups. The median serum levels of sTNFr‐II and sFas were significantly lower in the case group than in the control groups. The cases were significantly younger when they became infected than the control groups. Indeed, most cases were infected within the first 10 years of life. sTNFr‐II and age at infection were independently associated with the minimal injury case group. When sTNFr‐II was excluded from the logistic regression model, sFas and age at infection were independently associated with the case group. Conclusion: The rate of progression of parenterally acquired chronic hepatitis C to end‐stage liver disease might be related to an upregulation of the TNF‐α/Fas pathways and an age‐dependent host response.
Quantitative versus morphological assessment of liver fibrosis: semi‐quantitative scores are more robust than digital image fibrosis area estimation
Authors: Wright Mark , Thursz Mark , Pullen Rebecca , Thomas Howard , Goldin Robert
Published: March 2003

Abstract: Background/Aim: Digital image analysis (DIA) allows quantitative assessment of fibrosis on liver biopsy. Accurate determination of a threshold greyscale level representing fibrous tissue is critical. This method has not been fully evaluated in clinical practice.

Methods: Digital images of stained liver biopsy sections were captured by microscopy and converted to greyscale. A novel method of determining the threshold greyscale value at which to measure fibrosis area was developed (peak proportion area change (PPAC)). Reproducibility was tested in comparison with standard interactive thresholding and with semi‐quantitative scoring using the Histological activity index (HAI) system by a histopathologist. Fibrosis areas for different sections from the same biopsy core were also compared by each method.

Results: Comparison between PPAC and interactive thresholding method demonstrated superior reproducibility of the PPAC method: r > 0.7, P < 0.001 compared with r = 0.19–0.64 (not all reaching significance). On a single section, reproducibility was similar for PPAC and the modified HAI system. When different sections from the same core were compared, the HAI system was more robust.

Conclusions: The PPAC method is superior to standard interactive thresholding. However, variability in DIA scores between sections invalidates the technique for clinical use and semi‐quantitative scoring systems remain the gold standard for fibrosis assessment.
Longitudinal follow up of SIVmac pathogenesis in rhesus macaques of Chinese origin: emergence of B cell lymphoma
Authors: Ling B. , Veazey R.S. , Penedo C. , Xu K. , Lifson J.D. , Marx P.A.
Published: March 2003

Abstract: Two subspecies of rhesus (Rh) macaques, the Chinese (Ch) and Indian (Ind) subspecies were infected intravenously with 100TCID50 SIVmac239. CD4+, CD8+ T cells, plasma viral loads, depletion of intestinal lymphocytes with memory phenotype, humoral immune responses and clinical courses were monitored for 600 days. The pathogenesis of SIVmac was also compared with primary human immunodeficiency virus (HIV) infection of humans. Plasma viral loads in Ch Rh were lower in the acute and chronic phases compared with Ind Rh. SIVmac pathogenesis in Ch Rh was closer to virus loads in untreated HIV infected humans. Ch Rh had higher CD4/CD8 ratios, stronger antibody responses and interestingly, less depletion of intestinal memory CCR5+ CD4+ T lymphocytes compared with Ind Rh. One Ch Rh developed B cell origin lymphoma at 570 days post‐infection, the first such report in this subspecies. Three of four Ind Rh developed AIDS within 6 months. The findings indicate that Ch Rh are more resistant to SIVmac pathogenesis compared with Ind Rh and that Ch Rh paralleled HIV‐1 infections in untreated adult humans. The SIVmac infected Ch Rh subspecies are an acceptable model for HIV/AIDS.
Urinary steroids, FSH and CG measurements for monitoring the ovarian cycle and pregnancy in the chimpanzee
Authors: Shimizu Keiko , Douke Chisato , Fujita Shiho , Matsuzawa Tetsuro , Tomonaga Masaki , Tanaka Masayuki , Matsubayashi Kiyoaki , Hayashi Motoharu
Published: March 2003

Non‐invasive methods for monitoring reproductive status of chimpanzee based on the measurement of urinary steroids and gonadotropins were examined. A typical pre‐ovulatory urinary estrone conjugate (E1C) surge and post‐ovulatory increase in pregnandiol glucuronide (PdG) were seen during the menstrual cycle. Urinary follicle stimulating hormone (FSH) showed two peaks over the infertile menstrual cycle. The earliest changes indicating pregnancy were a coincident rise in E1C and chorionic gonadotropin (CG) levels and a concomitant fall in FSH levels. Urinary PdG levels showed a prolonged rise. Urinary E1C in the pregnant chimpanzee was higher than during the menstrual cycle and increased with advancing gestation, with maximum levels occurring near term. In the case of stillbirth, E1C and CG levels from mid‐ through late‐pregnancy were low and the prepartum progressive increase in E1C was not shown. The data presented here are of great practical value in captive breeding management of chimpanzees.
Properties of as‐cast and heat‐treated nodular graphite cast irons, melts treated with CaSi–CaF2 alloy
Authors: Imasogie B. I. , Afonja A. A. , Ali J. A.
Published: March 2003

An attempt has been made to evaluate the microstructure and mechanical properties of as‐cast and heat‐treated grades of nodular graphite cast irons produced through nodularising treatment with CaSi‐CaF2 alloy. The results showed that up to 92% nodularity in graphite could be obtained by using a pre‐alloy inoculant with 8.10 wt% CaSi‐CaF2 (ratio 5:2) optimum concentration. An average hardness of 327 Hv, Charpy‐V‐Impact energy of 5.60 J, tensile strength of 611 MPa and a corresponding elongation of 3.05% have been obtained for the as‐cast iron, whereas the microstructure appeared completely ferritic. Although annealing and normalizing treatments produced significant growth and enhancement in nodularity of graphite, there was little improvement in mechanical properties. The iron’s response to the applied marquenching transformation schedules was equally poor, with a maximum strength of 830 MPa and a corresponding elongation of 2.10% obtainable after 45 min of transformation. The iron’s poor response to heat treatment and mechanical properties resulting thereof, were apparently due to the effect of the rather high silicon content (4.05%) on movement of the reaction fronts and hardenability in the case of marquenching and ductility in other heat treatments. Excessive grain boundary cleavage, accompanied by large smooth areas separated by wide cleavage steps and other characteristic features of brittle fracture, appear to be the main mode of fracture, for both as‐cast and heat treated grades of the iron.
Grain size as influenced by process parameters in copper extrusion
Authors: Ssemakula Hamzah , Ståhlberg Ulf
Published: March 2003

Today, different methods and materials are investigated for the manufacturing of large canisters meant for encapsulation of nuclear waste. One method of interest includes hot extrusion of coarse‐grained copper ingots. It has been shown that the grain size in the final product must be small in order to enable ultrasonic testing and to guarantee high resistance towards creep and corrosion. Different codes are being developed for predicting the final grain size as influenced by temperature, strain and strain rate. In the present work, these parameters have been determined by simulations for different material elements during extrusion of cylindrical copper billets. Elements, located at various distances from the central axis of the initial workpiece, were traced from the inlet to the outlet of the die by utilizing the FE‐code FORM2D. In this way, the parameters describing the deformation history of the elements were determined as functions of time. Experiments corresponding to the simulations were carried out. Starting with billets in as‐cast condition, the final grain sizes were evaluated. It is concluded that the initial grain size of an as‐cast cylindrical billet is heavily decreased for all the extrusion conditions studied. The investigation was carried out for different working temperatures, 550, 650 and 750°C and extrusion ratios, 10 and 15. The final grain size was found within the interval 23–37 μm. The smallest grain size was, for each working condition, located close to the surface of the extrudate where the largest strains and temperature increases occurred. Low extrusion temperatures gave the best results.
Contribution to the knowledge of the Cu‐Zn‐Ti system for compositions close to brass alloys
Authors: Soares D. , Vilarinho C. , Castro F.
Published: March 2003

The effect of titanium addition to Cu‐Zn alloys (in the zone of the chemical composition of commercial brasses) has been studied. Ternary alloys were melted from a Cu‐Zn base alloy (with 40 wt.% Zn) and with titanium additions up to ∼6 at.%. Simultaneous differential thermal analysis and termogravimetry (SDT) and isothermal homogenisation with rapid cooling have been employed to determine the equilibrium phases at different temperatures and the invariant reactions. The alloys were studied by scanning electron microscopy (SEM) and the chemical analysis of the phases have been determined by energy‐dispersive spectroscopy (EDS). The microstructure obtained shows the existence of an eutectic reaction in the studied region. The temperature and the chemical composition of the phases present in the reaction were determined. This eutectic reaction has not been referred to in previous works on the ternary system.
CVM calculations of phase equilibria in the Fe‐Cu‐Co system including both chemical and magnetic interactions
Authors: Antoni‐Zdziobek A. , Colinet C.
Published: March 2003

Phase equilibria in the Fe‐Cu‐Co system are investigated in the temperature range 723K–1273K using the cluster variation method (CVM) in the irregular tetrahedron approximation in the bcc lattice and in the regular tetrahedron approximation in the fcc lattice. Previous calculations of the binary limiting systems have shown the interest of introducing both chemical and magnetic interactions to treat the equilibrium between phases of different structures in the case of ferromagnetic alloys. This treatment is extended here in the case of the ternary system. Magnetic interactions are considered explicitly between nearest neighbours in a spin‐1/2 treatment. The considered system in the CVM is thus a quinary system Fe+ Fe− Cu Co+ Co−. The input parameters of the model are obtained from available thermodynamic data: mixing enthalpies, Curie temperatures and binary diagrams. As a result several isothermal sections of the Fe‐Cu‐Co system are calculated between 723K and 1273K which compare favourably with literature data concerning the binary systems and experimental results recently established in our laboratory.
Thermophysical properties of solid and liquidInconel 718 Alloy*
Authors: Pottlacher G. , Hosaeus H. , Kaschnitz E. , Seifter A.
Published: March 2003

Enthalpy, resistivity, density, specific heat capacity, and normal spectral emissivity as a function of temperature of Inconel 718 alloy were measured by a fast resistive pulse heating technique up into the liquid phase, thus obtaining data on thermal conductivity and thermal diffusivity. The high‐speed measurements are compared with results of quasistatic measurements of specific heat obtained by differential‐scanning calorimetry and expansion measurements by dilatometry.
Most relevant mechanisms of inclusion growth in an induction–stirred ladle
Authors: Söder Mats , Jönsson Pär , Alexis Jonas
Published: March 2003

The purpose of this study has been to theoretically evaluate which inclusion growth mechanisms are important in an inductively stirred ladle. This has been done using data from a computational fluid dynamics model of a real ladle. The data was utilized as the input to the different collision equations. It was concluded that diffusion of oxygen and deoxidant to the inclusion surface, diffusion coalescence and Brownian motion collisions contribute very little to growth of inclusions during the stirring period in the ladle. This was in accordance with earlier findings in the literature. This study also showed that laminar shear collisions could be excluded from a growth model. The major growth mechanism is turbulent collisions. It was also shown that a 700–A stirring current leads to more growth due to turbulent collisions than a 500–A stirring current. The importance of a correct value of the collision efficiency coefficient for turbulent collisions was pointed out. If a large difference in inclusion size exists then collisions due to difference in buoyancy (Stokes collisions) also need to be considered in a growth model. Finally, it is concluded that the variation in fluid flow and turbulent properties in different parts of the ladle should be incorporated into a growth model, since it can affect average turbulent collision volumes by 25–30%.
Grazing decisions of Soay sheep, Ovis aries, on St Kilda: a consequence of parasite distribution?
Authors: Hutchings Michael R. , Milner Jos M. , Gordon Iain J. , Kyriazakis Ilias , Jackson Frank
Published: March 2003

Relationships between the height of grass swards and herbage intake have been established for a number of large herbivores and sward height plays a major role in determining the selection of herbivore diets. However, tall grass swards also represent a more stable damp microclimate for gastrointestinal parasite larvae and tall swards contain generally greater numbers of parasites than short swards. Herbivores may then trade‐off the need to maximise nutrient intake through the selection of tall swards with the need to avoid parasite ingestion. Stratified sward sampling techniques were used to determine the distribution of nutrients and parasites in a heterogeneous sward structure on the island of Hirta, St Kilda, which is grazed by a population of feral Soay sheep. The disparity between the short gap vegetation and the tall tussock vegetation was greatest in spring, when gap vegetation was some three‐fold shorter than tussock vegetation; this led to tussocks offering greater nutrient and energy intake rate when compared to gap vegetation in spring. Parasites were concentrated in tussocks in spring, thus creating trade‐offs. Such trade‐offs were not present in summer when parasites were more evenly distributed across the gap/tussock sward structure and the nutritional advantages associated with grazing tussocks were diminished. The diet selection of the resident population of sheep was determined by recording the number of bites taken from gap and tussock vegetation by randomly selected focal animals over repeated 5‐min grazing periods. Overall, all animals avoided grazing tussocks, which were most strongly avoided in the spring, and older animals avoided grazing tussocks to a greater extent. Overall, females with lambs and males avoided tussocks to a similar degree and both avoided them less than barren females. Faecal egg counts (FEC) of female sheep were negatively correlated with tussock selectivity and vice versa for male sheep. The interaction between the grazing behaviour of each sex and FEC is discussed in relation to the immunocompetence and nutrient requirements of the different sexes. The maximum disparity between the costs and benefits of the trade‐off studied occurred in late winter/early spring which also represents the time of greatest nutrient demand in the Soay sheep, since many are close to starvation and/or are in the advanced stages of pregnancy. Grazing decisions of individuals at this time, determining relative nutrient and parasite intake, may then be related to subsequent fitness and survival.
The role of herbivory by wood‐boring insects in mangrove ecosystems in Belize
Authors: Feller Ilka C.
Published: March 2003

The roles wood‐boring insects play in modifying mangrove ecosystems were examined on small, offshore mangrove islands in Belize. Several species of xylem‐ and phloem‐feeding woodborers consume the wood of living mangrove trees. By girdling, pruning, and hollowing, woodborers killed over 50% of the Rhizophora mangle canopy in experimental plots arrayed across a tidal‐elevation gradient. In contrast, leaf‐feeding herbivores removed less than 6% of the canopy. In the plots, stem girdlers killed over three branches per tree. The patterns of herbivory by three functional feeding groups were heterogeneous and did not vary consistently with tidal elevation. Because R. mangle lacks viable axillary buds or the ability to produce epicormic shoots to replace pruned branches, the canopy architecture was significantly modified by this damage. The branches that were pruned by stem girdlers created numerous small holes or gaps in the mangrove canopy. Shoot growth and flowering increased in R. mangle trees with 50% of their branches experimentally girdled. Because branches and twigs attacked by woodborers lost their leaves prematurely as greenfall, the quantity and quality of leaf litter were altered when a leaf‐bearing branch was girdled or hollowed. These changes suggest that wood‐boring insects also significantly affect internal and external nutrient cycling processes in mangrove ecosystems.
Does variation in patch use among butterfly species contribute to nestedness at fine spatial scales?
Authors: Summerville Keith S. , Veech Joseph A. , Crist Thomas O.
Published: March 2003

A nested pattern occurs whenever the species observed in depauperate habitat patches are a subset of those found in more species‐rich patches. Ecologists have documented many instances of nestedness caused by population‐level processes such as colonization and extinction at biogeographic scales. However, few researchers have examined whether nestedness may exist at fine scales due to the ways in which individual organisms discriminate among potential habitat patches. In 1999, we experimentally fragmented an old‐field habitat into patches of varying size to test whether nestedness could exist on a fine spatial scale. Five treatments of differing patch size were replicated five times in a Latin square design by selectively mowing 15×15 m2 plots within an old‐field (patch areas: 225, 180, 135, 90, and 45 m2). Specifically, we tested whether butterflies foraging within a network of patches differing in area conformed to a nested subset structure. We also classified species according to (1) their flight height while foraging (high or low), and (2) their adult habitat breadth (ubiquitous, general, or restricted) to determine whether nestedness could be explained by difference in species’ tendency to discriminate among patches differing in area.

 We found significant evidence that a community of foraging Lepidoptera conformed to a nested subset structure based on the difference between the observed nestedness within the butterfly community and the nestedness obtained from randomly generated species presence/absence matrices. Poisson regression analyses demonstrated that high‐flying, habitat‐restricted species avoided the smallest patches (90 and 45 m2) in favor of larger remnants, whereas low‐flying, habitat generalists used all patch sizes. Thus, our study is one of the first to demonstrate that nestedness among species subsets can be observed at fine spatial scales (within a single 1.5 hectare field) and may be maintained by species behavioral differences: discriminating species (i.e. high‐flying, habitat restricted) avoided the smallest patches, and less discriminating species (i.e. low‐flying, ubiquitous) were distributed throughout the field without regard to patch size. Our results also suggest that nestedness should be viewed as yet another scalar pattern in ecology, generated by variation in patch use by individuals at fine‐scales as well as the more traditionally invoked processes of extinction and colonization of species at broad‐scales.
The taste of nectar – a neglected area of pollination ecology
Authors: Gardener Mark C. , Gillman Michael P.
Published: March 2003

Nectar is an important biological resource that is utilized by a wide range of animals as a food source. Amino acids are the second most abundant class of compound (after sugars) to be found in nectar. In foraging for nectar, animals carry out the vital role of pollination. Many animal taxa visit flowers, but the most abundant pollinators are insects. Although amino acids are detectable by insects, little work has focussed on the role of taste in the ecology of pollination (with most studies concentrating on foraging choice). The idea that different amino acids elicit different responses in insect taste receptors was used to characterize nectar samples from 65 plant species from a wide range of families according to their amino acid profile (determined by high performance liquid chromatography). A ternary classification system was used to map the amino acids present in nectar samples. There is a wide range of taste profiles with most plant species having their own characteristic taste value. How nectar tastes to pollinating insects is of great importance in understanding the foraging choices of insect pollinators and there are many avenues that remain to be explored.
Modification of adverse conditions by insects
Authors: Danks Hugh V.
Published: March 2003

Many insects modify their environments directly, rather than merely choosing available sites that are already favourable. The modifications are carried out by making excavations in soil and other substrates, constructing feeding or resting shelters, inducing plant responses such as galls, aggregating, building colonial nests, and through parental actions. Such environmental modifications are briefly reviewed and related to the conditions that they modify. Some of the modifications offset physical factors such as dryness or flooding and cool or freezing temperatures. Others reduce the effects of natural enemies or enhance food resources. These effects have seldom been quantified and much of the evidence is anecdotal, but preliminary generalizations are made from existing information. Although potential roles often overlap, excavations and shelters protect especially against physical factors, while aggregations, colonies and parental actions more often influence the acquisition of resources. How modifications affect the impact of natural enemies differs among different kinds of enemies and is especially difficult to test. In any event, adaptive local modifications of the environment by insects are shown to be widely distributed and important. However, their specific roles have often been assumed rather than tested, or have been overlooked along with the potential interdependence of different effects. Therefore, environmental modifications should be considered explicitly and examined with greater rigour during the study of insect life cycles.
A histopathological study of lymphoepithelial island formation in labial salivary glands in patients with primary Sjögren’s syndrome
Authors: Yamamura Yukiko , Onodera Ken , Ichinohasama Ryo , Ooya Kiyoshi
Published: March 2003

Abstract: The proliferative status of lymphoepithelial islands in the labial salivary glands of primary Sjögren’s syndrome (pSS) patients was investigated by counting the number of argyrophilic nucleolar organizer regions (AgNORs) in epithelial cells constituting the islands. The islands were classified into four groups and evaluated in terms of total area and three discrete zones of the islands. In each pSS group, the mean AgNOR number per total island epithelial cell nucleus was significantly higher than in control ductal epithelial cells. The zonal AgNOR number fluctuated during the process of island formation but became more uniform as the islands developed. Furthermore, statistically significant trends among the four pSS groups were observed in the ratio of T lymphocytes, B lymphocytes and plasma cells surrounding the islands. The results indicated that the islands are highly proliferative once island formation begins and that zonal island cell proliferation may be associated with the inflammatory cells.
Solitary fibrous tumour of the oral cavity: clinicopathological and immunohistochemical characterization of three cases
Authors: Lukinmaa Pirjo‐Liisa , Hietanen Jarkko , Warfvinge Gunnar , Sane Juha , Tuominen Susanne , Henriksson Vincent , Larsson Åke
Published: March 2003

Abstract: Solitary fibrous tumour (SFT) is an uncommon mesenchymal neoplasm rarely located in the oral cavity. To characterize further oral SFT, we describe three new cases. Each tumour originated in the buccal mucosa of a middle‐aged/elderly patient. Histological examination showed well‐circumscribed tumours with densely cellular areas alternating with hypocellular areas in a variedly collagenous, vascular stroma. Mast cells were abundant. The spindle‐shaped, neoplastic cells immunostained strongly for CD34 antigen and vimentin and weakly for bcl‐2, but not for epithelial cell markers, α‐smooth muscle actin, or neurofilament or S‐100 proteins. Compatible with the virtual absence of mitoses and of marked nuclear atypia, the overall frequency of proliferating cells expressing Ki‐67 was low. The expression of CD34 was useful in the differential diagnosis. The consistent location in the cheek and expansion of one tumour after local trauma does not preclude a traumatic element in the development of oral SFT.
The relationship of genetic aberrations detected by comparative genomic hybridization to DNA ploidy and tumor size in human oral squamous cell carcinomas
Authors: Okafuji Masaki , Ita Masamichi , Oga Atsunori , Hayatsu Yoshikazu , Matsuo Akira , Shinzato Yuichi , Shinozaki Fumihiko , Sasaki Kohsuke
Published: March 2003

Abstract: We have examined genetic alterations in 11 surgically removed oral squamous cell carcinomas (OSCCs) using comparative genomic hybridization (CGH) and laser scanning cytometry (LSC), which allow quantitative analysis of chromosomal abnormalities. CGH analysis revealed gains and/or losses of DNA sequence copy number in all tumors. Gains in DNA sequence copy number were detected frequently for chromosome arms 3q25–28 (6/11), 5p (6/11) and 8q (5/11), and losses in chromosome arms 18q (4/11), 19q (4/11), 17p (3/11), and 19p (3/11). Amplification of 5p was observed in two tumors. LSC detected DNA aneuploidy with DNA indices ranging from 1.30 to 1.82 in 6 of 11 tumors. The number of chromosomal aberrations was higher in DNA aneuploid tumors than in diploid tumors (8.17 vs 3.60/tumor, P<0.05). Furthermore, the average number of chromosomal aberrations was significantly higher in stage T2 tumors and larger tumors than in stage T1 tumors (7.71 vs 3.25/tumor, P<0.05). Our results suggest that DNA aneuploidy and large tumor size reflect an underlying chromosomal instability.