bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of doubled CO2 and model basic state biases on the monsoon‐ENSO system. I: Mean response and interannual variability
Authors: Turner A. G. , Inness P. M. , Slingo J. M.
Published: July 2007

The impact of doubled CO2 concentration on the Asian summer monsoon is studied using a coupled ocean‐atmosphere model. Both the mean seasonal precipitation and interannual monsoon variability are found to increase in the future climate scenario presented. Systematic biases in current climate simulations of the coupled system prevent accurate representation of the monsoon‐ENSO teleconnection, of prime importance for seasonal prediction and for determining monsoon interannual variability. By applying seasonally varying heat flux adjustments to the tropical Pacific and Indian Ocean surface in the future climate simulation, some assessment can be made of the impact of systematic model biases on future climate predictions. In simulations where the flux adjustments are implemented, the response to climate change is magnified, with the suggestion that systematic biases may be masking the true impact of increased greenhouse gas forcing. The teleconnection between ENSO and the Asian summer monsoon remains robust in the future climate, although the Indo‐Pacific takes on more of a biennial character for long periods of the flux‐adjusted simulation. Assessing the teleconnection across interdecadal timescales shows wide variations in its amplitude, despite the absence of external forcing. This suggests that recent changes in the observed record cannot be distinguished from internal variations and as such are not necessarily related to climate change. Copyright © 2007 Royal Meteorological Society
Towards a possible ab initio molecular mechanics. Transferability of density matrix elements
Authors: Tchougréeff A. L. , Tokmachev A. M. , Mayer I.
Published: July 2007

Molecular structures are characterized by a large degree of additivity and transferability of various intramolecular interactions determining the shape and energetics of molecules. This property is constantly utilized by the different “molecular mechanics” (MM) schemes which allow one to obtain quite reliable molecular geometries and relative energy values for a wide range of molecular systems, which is especially remarkabke in the light of the simplicity of the assumptions made. Numerous MM schemes presented in the literature use different sets of parameters (force fields, etc.), which are adjusted empirically. The known success of MM models poses two important questions: first, one wishes to understand why do they work at all, and, second, one would like to develop schemes, in which the parameters of MM can be determined theoretically. Such an analysis could also give some deeper insight permitting to predict whether the given MM scheme is expected to be successful if applied to the class of problems actually at hand. From a more pragmatic point of view, having a bridge connecting a quantum mechanical (QM) description of molecular structure with a classical moldel (MM) can help to improve hybrid QM/MM methods by providing a systematic derivation of the form of the junction between the subsystems treated by MM and QM, respectively and by giving a priori estimates of the junction parameters. Our previous studies based on the semiempirical quantum chemical Hamiltonians of MINDO and MNDO types permitted us to draw the conclusion that the success of MM can indeed be understood on the basis of quantum mechanics. The analysis of the geminal‐type wave functions constructed by making use of oriented hybrid orbitals showed that the parameters of the wave function and the energy contributions of the individual bonds are indeed well transferable, in good agreement with the simple chemical picture of the systems studied. It seems to be desirable to develop a similar analysis also at the ab initio level of the theory, because that would connect together the chemical and physical description of molecules and explain the observed transferability of molecular interactions more rigorously than semiempirical theories can do it. On the other hand this treatment might be also useful for developing QM/MM junctions in the cases when the QM part of the systems are described at the ab initio level. We report here results of the first step of this analysis: the geminal parameters expressed in a symmetrically orthogonalized optimized minimal basis set exhibit a degree of stability similar to that observed in the semiempirical case. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007
Surface‐activated chemical ionization ion trap mass spectrometry for the analysis of cocaine and benzoylecgonine in hair after extraction and sample dilution
Authors: Cristoni Simone , Basso Elisa , Gerthoux Piermario , Mocarelli Paolo , Gonella Elisabetta , Brambilla Maura , Crotti Sara , Bernardi Luigi Rossi
Published: July 2007

Surface‐activated chemical ionization (SACI) was employed for the analysis of cocaine and its metabolite, benzoylecgonine, extracted from hair. Following decontamination and acid hydrolysis procedures on the hair sample, the sample solution was diluted (1:10) and directly analyzed by liquid chromatography/surface‐activated chemical ionization multiple collisional stage single reaction monitoring mass spectrometry (LC/SACI‐MS3‐SRM) without solid‐phase extraction (SPE) pre‐purification and concentration procedures. To increase the selectivity of the method, MS3 was chosen instead of the less selective MS/MS. This data was compared with that achieved using gas chromatography/mass spectrometry (GC/MS), the reference method used by the Italian Government Institute of Health protocol. The limits of detection (LODs) were 0.003 ng/(mg hair) for cocaine and 0.02 ng/(mg hair) for benzoylecgonine and the limits of quantitation (LOQs) were 0.01 ng/(mg hair) for cocaine and 0.04 ng/(mg hair) for benzoylecgonine. The squared correlation coefficient (R2) of the calibration curve was 0.9887–0.9980 for cocaine and 0.9987–0.9997 for benzoylecgonine. The percent accuracy error was 2–5% for both cocaine and benzoylecgonine using the LC/SACI‐MS3‐SRM approach, whereas it was higher for benzoylecgonine (20–25%) using the LC/SACI‐MS/MS‐SRM approach compared with the GC/MS data due to hair matrix contamination. In both cases, high precision was achieved (1–3% precision error), which confirmed the stability of the developed methods. Copyright © 2007 John Wiley & Sons, Ltd.
A Bayesian Semiparametric Latent Variable Model for Mixed Responses
Authors: Fahrmeir Ludwig , Raach Alexander
Published: July 2007

In this paper we introduce a latent variable model (LVM) for mixed ordinal and continuous responses, where covariate effects on the continuous latent variables are modelled through a flexible semiparametric Gaussian regression model. We extend existing LVMs with the usual linear covariate effects by including nonparametric components for nonlinear effects of continuous covariates and interactions with other covariates as well as spatial effects. Full Bayesian modelling is based on penalized spline and Markov random field priors and is performed by computationally efficient Markov chain Monte Carlo (MCMC) methods. We apply our approach to a German social science survey which motivated our methodological development.
Dextrose-Induced Subsynovial Connective Tissue Fibrosis in the Rabbit Carpal Tunnel: A Potential Model to Study Carpal Tunnel Syndrome?
Authors: Oh Sangho , Ettema Anke M. , Zhao Chunfeng , Zobitz Mark E. , An Kai-Nan , Amadio Peter C. , Wold Lester E.
Published: July 2007

In this pilot study, hypertonic dextrose solution was used to induce fibrosis of the subsynovial connective tissue (SSCT) and create an animal model of potential use in the study of carpal tunnel syndrome (CTS). The SSCT of the carpal tunnel in 15 New Zealand white rabbits were injected with 0.05 ml of 10% dextrose solution in 1 paw and 0.05 ml of saline in the contralateral paw, to serve as a control. The animals were killed at 1, 2, 4, 8, or 12 weeks. While the saline side showed minimal changes at any time period, the hypertonic dextrose side showed progressive noninflammatory SSCT fibrosis, with vascular proliferation and thickening of collagen bundles. Demyelination of the median nerve developed at 12 weeks after the injection on the dextrose side. These findings are similar to the progression of pathology noted in humans with CTS.
Personal information of adolescents on the Internet: A quantitative content analysis of MySpace
Authors: Hinduja Sameer , Patchin Justin W.
Published: July 2007

Many youth have recently embraced online social networking sites such as MySpace (myspace.com) to meet their social and relational needs. While manifold benefits stem from participating in such web‐based environments, the popular media has been quick to demonize MySpace even though an exponentially small proportion of its users have been victimized due to irresponsible or naïve usage of the technology it affords. Major concerns revolve around the possibility of sexual predators and pedophiles finding and then assaulting adolescents who carelessly or unwittingly reveal identifiable information on their personal profile pages. The current study sought to empirically ascertain the type of information youth are publicly posting through an extensive content analysis of randomly sampled MySpace profile pages. Among other findings, 8.8% revealed their full name, 57% included a picture, 27.8% listed their school, and 0.3% provided their telephone number. When considered in its proper context, these results indicate that the problem of personal information disclosure on MySpace may not be as widespread as many assume, and that the overwhelming majority of adolescents are responsibly using the web site. Implications for Internet safety among adolescents and future research regarding adolescent Internet use are discussed.
Examination of the interaction between peripheral lumiracoxib and opioids on the 1% formalin test in rats
Authors: Ortiz Mario I. , Castañeda‐Hernández Gilberto
Published: July 2007

It has been shown that the association of non‐steroidal anti‐inflammatory drugs (NSAIDs) with opioid analgesic agents can increase their antinociceptive activity, allowing the use of lower doses and thus limiting side effects. Therefore, the aim of the present study was to examine the possible pharmacological interaction between lumiracoxib and codeine or nalbuphine at the local peripheral level in the rat using the 1% formalin test and isobolographic analysis. Lumiracoxib, codeine, nalbuphine or fixed‐dose ratios lumiracoxib—codeine or lumiracoxib—nalbuphine combinations were administrated locally in the formalin‐injured paw and the antinociceptive effect was evaluated using the 1% formalin test. All treatments produced a dose‐dependent antinociceptive effect. ED40values were estimated for the individual drugs and an isobologram was constructed. The derived theoretical ED40's for the lumiracoxib—codeine and lumiracoxib—nalbuphine combinations were 423.4±31.3μg/paw and 310.9±24.2μg/paw, respectively, being significantly higher than the actually observed experimental ED40values, 233.2±30.9μg/paw and 132.7±11.6μg/paw, respectively. These results correspond to a synergistic interaction between lumiracoxib and opioids at the local peripheral level, potency being about two times higher with regard to that expected from the addition of the effects of the individual drugs. Data suggest that low doses of the lumiracoxib—opioids combination can interact synergistically at the peripheral level and therefore this drug association may represent a therapeutic advantage for the clinical treatment of inflammatory pain.
Wider application of prolonged nasotracheal intubation
Authors: Bos C. E. , Berkovits R. N. P. , Struben W. H.
Published: July 2007

ENCOURAGED by reports of the treatment of laryngotracheal obstruction with nasotracheal intubation (N.T.I.), we began in 1965 to use this method in patients presenting such problems. At the outset we decided to use unsterilized and siliconized P.V.C. tubes in order to avoid toxicity and to provide ‘boundary lubrication’. Some preliminary experiments on these matters are presented.

We found that by using this approach the range of indications for N.T.I, could be greatly extended. Forty-three out of forty-six patients, most of whom had chronic narrowings, were treated satisfactorily. The fact that eleven patients with obstructions caused by previous endotracheal intubation were cured by further intubation is noteworthy.
The utriculo-endolymphatic valve: its functional significance
Authors: Schuknecht Harold F. , Belal A. Aziz
Published: July 2007

A STUDY was made of the anatomical structure and functional significance of the ultriculo-endolymphatic (UE) valve in man. The material consists of 170 human temporal bones of which 75 were chosen to show normal structure through nine decades of life, 29 with endolymphatic hydrops, 22 with developmental defects and 44 with pertinent staining characteristics of the endolymphatic fluid. The studies show that the UE valve is ideally suited to preserve the humoral and anatomical features of the pars superior (utricle and canals) from the developmental, disease, and traumatic susceptibilities of the pars inferior (cochlear duct and saccule). Its function probably is to permit the occasional egress of excessive accumulation of endolymph to be processed in the endolymphatic sac and to accomplish this while preserving the normal endolymph volume and membrane anatomy of the utricle and canals.
Population genetics of anthelmintic resistance in parasitic nematodes
Authors: GILLEARD J. S. , BEECH R. N.
Published: July 2007

A key aim of anthelmintic resistance research is to identify molecular markers that could form the basis of sensitive and accurate diagnostic tests. These would provide powerful tools to study the origin and spread of anthelmintic resistance in the field and to monitor strategies aimed at preventing and managing resistance. Molecular markers could also form the basis of routine diagnostic tests for use in surveillance and clinical veterinary practice. Much of the research conducted to date has focused on the investigation of possible associations of particular candidate genes with the resistance phenotype. In the future, as full parasite genome sequences become available, there will be an opportunity to apply genome-wide approaches to identify the genetic loci that underlie anthelmintic resistance. Both the interpretation of candidate gene studies and the application of genome-wide approaches require a good understanding of the genetics and population biology of the relevant parasites as well as knowledge of how resistance mutations arise and are selected in populations. Unfortunately, much of this information is lacking for parasitic nematodes. This review deals with a number of aspects of genetics and population biology that are pertinent to these issues. We discuss the possible origins of resistance mutations and the likely effects of subsequent selection on the genetic variation at the resistance-conferring locus. We also review some of the experimental approaches that have been used to test associations between candidate genes and anthelmintic resistance phenotypes and highlight implications for future genome-wide studies.
ABC transporters and β-tubulin in macrocyclic lactone resistance: prospects for marker development
Authors: PRICHARD R. K. , ROULET A.
Published: July 2007

Macrocyclic lactones (MLs) are highly lipophilic anthelmintics which are known to bind to and open ligand-gated ion channels. However, these anthelmintics, and particularly the avermectin members of the ML class of endectocides, are potent substrates for ABC transporters and these transporters may regulate drug concentration in both the host and the parasite. There is accumulating evidence that ivermectin (IVM), and to a lesser extent moxidectin (MOX), selects for certain alleles of P-glycoprotein and other ABC transporter genes, selects for constitutive overexpression of some of these gene products, and induces overexpression of some P-glycoproteins in nematodes. However, such mechanisms of ML resistance do not easily lend themselves to the identification of SNP markers for resistance because of the diversity of ABC transporters in nematodes, the apparent diversity of effects of different MLs, and because regulatory elements for ABC transporter gene expression are not well understood in nematodes. Another non ligand-gated ion channel gene which appears to be under IVM selection, at least inOnchocerca volvulusandHaemonchus contortus, is β-tubulin, and a simple genetic test for this selection has been described inO. volvulus. However, further work is required to elucidate a reliable marker associated with this gene inH. contortusor other parasitic nematodes of livestock. The possible involvement of ABC transporter genes and β-tubulin in ML resistance provides a start in developing our understanding of this phenotype and markers for its detection in field populations of parasitic nematodes. However, more work is required before these leads can provide practical SNP markers for ML resistance.
Vitamin A status in Cuban children aged 6–11 years
Authors: Macías-Matos Consuelo , Pita-Rodríguez Gisela , Monterrey-Gutiérrez Pedro , Reboso-Pérez José
Published: July 2007

Objective and setting

A nationwide study was performed in Cuba to assess vitamin A status and the intake of vitamin-A-providing foods in children aged 6–11 years.

Design and subjects

The sample comprised 1191 schoolchildren from first to sixth grade, both sexes, from municipalities randomly selected from the five eastern provinces of Cuba in 2002 (first semester) and from the four western and four central provinces in 2003 (first semester). A food-frequency questionnaire was completed by 2038 mother-and-child pairs.

Results

Mean (±standard deviation) plasma retinol concentrations were 1.77 ± 0.48 μmol l−1in the western, 2.01 ± 0.56 μmol l−1in the central and 1.40 ± 0.41 μmol l−1in the eastern region. No child had plasma retinol concentration below 0.35 μmol l−1, indicative of a high risk of clinical deficiency. Subclinical deficiency, plasma retinol concentration of 0.35–0.7 μmol l−1, was seen in <2% of subjects in all three regions and was <5% even in the two provinces with the worst vitamin A status (Guantánamo, 4.6%; Las Tunas, 3.0%). Adequate status (>1.05 μmol l−1) was present in >90% of subjects in all western and central provinces, and in one of the eastern provinces (Holguín), whereas in the four remaining eastern provinces, adequate status was present in >75%. Only nine fruits and vegetables were consumed frequently (>3 times per week) by >50% of children. Thirty-seven per cent regularly consumed a supplement containing vitamin A.

Conclusions

Most Cuban children aged 6–11 years had adequate vitamin A status. Consumption of foods rich in vitamin and provitamin A, especially vegetables, was frequent but limited to a small variety of foods.
Initiation of antigen receptor endocytosis and B lymphocyte activation lie on independent biochemical pathways
Authors: SHULER RANDY L. , OWEN CHARLES S.
Published: July 2007

Peroxidase‐conjugated anti‐surface immunoglobulin (slg) was used quantitatively to monitor endocytosis of crosslinked sIg on murine B lymphocytes. The role of biochemical second messengers in the initiation of endocytosis was assessed by employing several inhibitors. A novel peroxidase detection system was used and temperature‐dependent decreases in sIg density on immunoperoxidase‐labelled murine lymphocytes were monitored. Metabolic inhibitors as well as colchicine and cytochalasin D were utilized to confirm that the internalization of sIg could be blocked by classical inhibitors of the endocytosis process. The role of tyrosine kinase activity was established by the fact that endocytosis was significantly reduced with 100 μg/mL genistein. Experiments using EGTA or 1,2‐bis(β‐aminophenoxy)ethane‐N‐N,N′‐tetraacetic acid (BAPTA) to chelate Ca2+ indicated that Ca2+ plays little role m endocytosis. Likewise, protein kinase C (PKC) was not found to be involved in endocytosis, as activation of PKC with 50 ng/mL phorbol 12‐myristate 13‐acetate, or inhibition of the enzyme with 1 nmol/L or 5 nmol/L staurosporin, did not modulate endocytosis. Taken together, results suggested that ligand‐induced endocytosis of antigen receptors is mediated primarily through localized membrane events and is not dependent upon the classical B lymphocyte activation signals, such as the biochemical events in the inositol phosphate cascade.
Recombinant viral vaccines for enzootic bovine leucosis
Authors: DANIEL R. C. W. , GATEI M. H. , GOOD M. F. , BOYLE D. B. , LAVIN M. F.
Published: July 2007

Recently published studies on the development and use of recombinant vaccinia virus (VV) vaccines incorporating either the complete envelope (env) gene or only a fragment of the env gene consisting of the coding sequence for the env glycoprotein 51 (gp51) and part of gp30 of the bovine leukaemia virus (BLV) are described. It has been reported that vaccination of sheep with recombinant VY vaccines containing the complete env gene appears to protect sheep against challenge infection with BLV. The evidence for this protection is based on the lack of persistence of high titres of anti‐gp51 antibodies compared with unvaccinated BLV infected controls, on the enhanced CD4 proliferative responses to specific BLV gp51 synthetic peptides in the vaccinated sheep, and on the inability to detect BLV pro‐virus by polymerase chain reaction in the vaccinated sheep after 4 months following challenge infection compared with continual detection in unvaccinated sheep over a 16 month trial period. It has been suggested that cell‐mediated immune responses may be an important aspect of protective immunity against BLV infection and it has been reported that large tracts of amino acid sequences within the env and pol genes are highly conserved in different isolates from different countries which is of importance in designing peptide derived vaccines.
Differential expression of surface antigens on activated endothelium
Authors: FAVALORO EMMANUEL J.
Published: July 2007

Endothelial cells lining the vasculature participate in a variety of physiological processes. Following cell activation, functional changes are accompanied by changes in the surface structure (or phenotype) of these cells. Studies to date have tended to concentrate on selective changes induced with one or two surface molecules. The following study uses a different approach, having assessed potential changes to the endothelial cell surface using a large number (> 120) of previously untested monoclonal antibodies, and the cytokines TNF‐α and γ‐IFN, as well as the proteolytic enzyme thrombin. Antibody representatives from all cluster of differentiation groups CD1 through to CD54 were assessed in these studies, which used human umbilical vein endothelial cells. In line with previous observations, antibodies within CD9, CD13, CD26, CD29, CD31, CD34, CD44, CD46, CD47, CD49, CD51 and CD54 gave significant and consistent reactivity using non‐stimulated (‘quiescent’) endothelium. Using parallel cells differentially stimulated with TNF‐α, γ‐IFN or thrombin, antibodies within CD1 through to CD15, CDwl7 to CD19, CD21 to CD23, CD26, CD27, CD29, CD30, CD33 to CD35, CD37, CD38, CD40, CD43 to CD46, CD48, CD51 to CD53 failed to provide any consistent alteration to reactivity patterns compared to non‐stimulated cells. There did, however, appear to be some activation induced changes using antibodies within the other CD groups (i.e. CD16, CD20, CD24, CD25, CD28, CD31, CD32, CD36, CD39, CD41, CD42, CD47, CD49, CD50 and CD54) which ranged from minor to significant in scope and magnitude.
Human natural killer (NK) cells: Requirements for cell proliferation and expansion of phenotypically novel subpopulations
Authors: WARREN HILARY S. , KINNEAR BEVERLEY F. , SKIPSEY LOUISE J.
Published: July 2007

Previous studies established that the high density (resting) natural killer (NK) cell subset (R‐NK) of peripheral blood NK cells is unresponsive to interleuk:in‐2 (IL‐2) but can be induced to proliferate when cultured with γ‐irradiated malignant melanoma (MM‐170) cells or mitomycin‐C treated activated T cells in the presence of an IL‐2 conditioned medium (IL‐2‐CM). This study has examined additional requirements of this activation process. The induction of proliferation was dependent on cell to cell contact with metabolically active stimulator cells, although no evidence was obtained that stimulation was effected by soluble factors produced by the stimulator cells. Compared with IL‐2‐CM, rIL‐2 was an inefficient costimulator for the induction of NK cell proliferation, suggesting that factors in IL 2‐CM were required in addition to IL‐2, but rIL‐2 was as efficient as IL‐2‐CM in maintaining the proliferation of activated NK cells. Under optimum culture conditions, NK growth of up to 3200‐fold occurred during a proliferation cycle of 18 days. Phenotypic analysis of the culture‐generated quiescent NK cells revealed novel heterogeneity in CD 16 (FcγRIII) and CD56 (N‐CAM) expression. Some NK cells lacked expression of both CD16 and CD56 (as identified using currently available monoclonal antibodies), while other NK cells showed differential CD 16 epitope expression. Since quiescent NK cells can be obtained in large numbers and high purity, they will be a convenient source of NK cells to study the molecular processes involved in initiating NK cell proliferation.
Natural killer and natural cytotoxic cells are present at the maternal‐fetal interface during murine pregnancy
Authors: CLARKE G. R. , ROBERTS T. K. , SMART Y. C.
Published: July 2007

NK cell activity has been detected in the early murine decidua, and hypothesized to be mediated by granulated metrial gland (GMG) cells. The possibility that natural cytotoxic (NC) cells are also present in the decidua has not been investigated. In this study mAb to NK cells (anti‐NK‐1.1) and NC cells (anti‐NC‐1.1) were used to characterize the decidual cells of days 8–14 pregnant (CBAxC57BL/6) Fl mice. Flow cytometric and immunohistological analyses showed predominantly NK‐1.1+ and NC‐1.1+ large and granular single nucleated decidual cells with abundant cytoplasm. A ‘bright’ and a ‘dim’ subset were identified for both NK‐1.1+ and NC‐1.1+ cells. The NC‐1.1dim and NK‐1.1dim cells increased in number and size as pregnancy progressed. When tested in 51Cr‐release assays, the decidual cells showed significant levels of both NK and NC activities which increased with progression of pregnancy. The NK and NC activities were partially inhibited (47 and 34%) by preincubation of the decidual cells with anti‐NC‐1.1 and complement (C), or anti‐NC‐1.1 alone. Results indicate that natural cell‐mediated cytotoxicity in the decidua is in part, at least, mediated by NK‐1.1+ and NC‐l.l+ cells, and that the NK‐1.1dim and NC‐1.1dim cells are very likely to be GMG cells. This is the first report of NC cells in the mouse uterus.
Single‐chain antibody variable region‐targeted interleukin‐2 stimulates T cell killing of human colorectal carcinoma cells
Authors: XIANG JIM , LIU ENWU , MOYANA TERENCE , QI YUMIN
Published: July 2007

Recombinant DNA techniques were used to clone, construct and express the bifunctional molecule FV/IL‐2. The FV/IL‐2 is a single‐chain 37kDa fusion protein expressed in Escherichia coli under control of the strong T7 bacteriophage promoter in the expression vector pT7‐7‐FV‐lL‐2. The fused gene fragment FV‐IL‐2 contains a single‐chain anti‐TAG72 FV gene fragment and the human recombinant cDNA fragment of the IL‐2 molecule. The renatured soluble form of FV/IL‐2 was purified from E. coli inclusion bodies using hydroxylapatite chromatography. The yield of this fusion protein was estimated at 2.0 mg/L. Our data showed that the FV/IL‐2 molecule retained the TAG72 antigen‐binding specificity and the IL‐2 activity as measured in the standard T cell proliferation as well as cytotoxicity assays. Therefore, it may prove to be useful in targeting the biological effect of lL‐2 to tumour cells and stimulating its immune destruction.
Plasmodium falciparum and blood monocyte induced abnormalities in human erythrocyte cation homeostasis
Authors: MOHAN K. , DUBEY M. L. , GANGULY N. K. , MAHAJAN R. C.
Published: July 2007

The role of Plasmodium falciparum and activated blood monocytes in bringing about erythrocyte membrane lipid peroxidation and in altering the enzyme activity associated with Ca2+ and K+ efflux was studied. An attempt was made to investigate the role of parasite and monocyte‐mediated reactive oxygen species (ROS) in inhibiting Ca2+ ‐Mg2+ ATPase and Na+‐K+ ATPase in order to find out the cause of reported high intra‐erythrocytic calcium and depleted potassium levels in parasitized erythrocytes (PRBC). The PRBC showed enhanced lipid peroxidation as indicated by increased malonyldialdehyde (MDA) formation which coincided with the maturity of the parasite. This was further enhanced following exposure of PRBC to activated blood monocytes. The Ca2+‐Mg2+ ATPase activity was decreased as the parasite matured and was further hampered significantly in mature parasite‐infected red cells exposed to activated blood monocytes. There was a good negative correlation between MDA formation and Ca2+‐efflux from red blood cells suggesting the negative influence of ROS on Ca2+‐efflux. The Na+‐K+ ATPase activity did not reveal any significant change, both during parasite maturation as well as upon exposure to ROS from activated monocytes. We therefore suggest that inhibition of Ca2+‐efflux and the resulting increased cytosolic Ca+ in PRBC might have a role in structural and functional abnormalities of red blood cell, thus enhancing the red cell loss during P. falciparum infection.
A cell‐surface opsonic receptor on leucocytes from the phylogenetically primitive vertebrate, Eptatretus stouti
Authors: RAISON ROBERT L. , COVERLEY JENNIFER , HOOK JEFFREY W. , TOWNS PETER , WESTON KATHRYN M. , RAFTOS DAVID A.
Published: July 2007

A humoral recognition molecule that is homologous to the mammalian complement components C3, C4 and C5 has recently been identified in the Pacific hagfish, Eptatretus stouti. One function of this complement‐like protein (CLP) is to opsonize foreign material for phagocytosis by hagfish leucocytes. Here, we demonstrate that CLP's opsonic activity can be abrogated by pre‐incubating phagocytes with an anti‐hagfish leucocyte mAb (IBI). Moreover, antigen‐activated CLP can block the binding of the IBI antibody to hagfish leucocytes. Flow cytometry and immunoprecipitation indicate that IBI recognizes a 105 kDa cell‐surface, monomeric protein that is expressed exclusively on phagocytic hagfish leucocytes. It is concluded that this 105 kDa protein represents the cell surface receptor by which CLP mediates the phagocytosis of opsonized targets.
Immunosuppression by lymphokine‐activated murine killer cell line with B‐lymphoblast‐lytic activity in vitro
Authors: IKEMOTO M. , SUZUKI H. , SUGIYAMA E. , YAMASHITA N. , TUNRU I. S. , MATSUI S. , KOBAYASHI M.
Published: July 2007

The in vitro immunosuppressive effect caused by a murine lymphokine‐activated killer cell line with B‐lymphoblast‐lytic activity was studied. The cloned cells (named BC‐1.10, phenotype Thy1.2+ LFA‐1+, TCR‐αβ−, TCR‐γδ−, FcγRII−, CD2−, CD3ε−, CD4−, CD8− and express mRNA of ζ chain) suppressed LPS‐induced Ig synthesis by B lymphoblasts previously stimulated with LPS. Phasecontrast microscopy indicated disappearance of B lymphoblasts at 24 h after the addition of BC‐1.10 cells. This suppressive effect was reduced when BC‐1.10 cells were pretreated with anti‐LFA‐1 mAb, which inhibits cytotoxicity of this clone. These data suggest that the immunosuppressive effect of BC‐1.10 is due to an elimination of B lymphoblasts, and that one of the physiological functions of lymphokine‐activated killer (LAK) cells, which are induced as a consequence of immune reactions, might be immunosuppression.
Lack of correlation between early intracellular calcium ion rises and the onset of apoptosis in thymocytes
Authors: BEAVER JOANNE P. , WARING PAUL
Published: July 2007

Apoptosis, a well‐recognized process of cell death, is usually defined by chromatin condensation, plasma membrane blebbing, reduction in cell volume, and in many cell types the cleavage of DNA into nucleosomal multiples, and finally the formation of apoptotic bodies. We have characterized the time of onset and the range of concentrations at which the toxins gliotoxin and thapsigargin induce apoptosis in thymocytes. We also looked for early changes in cytosolic calcium ion concentration ([Ca‐2+]i). Three methods were used to detect apoptosis: cellular morphology, DNA fragmentation and a flow cytometric method using ethidium bromide. Calcium fluxes were measured using both flow cytometry and bulk cell fluorimetry. Gliotoxin concentrations of 50 nmol/L to 10μmol/L induced significant numbers of cells to become apoptotic in a dose dependent manner. At these concentrations there was no observable increase in [Ca2+]i as determined by flow cytometry or in bulk cells. However, when thymocytes were treated with gliotoxin at concentrations greater than 500 μmol/L, rises in [Ca‐2+]i were apparent, but these cells died by necrosis. Thapsigargin induced low levels of apoptosis in thymocytes; the maximum effect observable after a 10 nmol/L treatment. Thapsigargin is known to inhibit the Ca2+‐ATPase in the endoplasmic reticulum thereby causing a sustained increase in [Ca2+]i in thymocytes. The rise in [Ca2+]i observed was quantitatively similar when thymocytes were treated with thapsigargin concentrations ranging between 10 and 100 nmol/L. These results led us to investigate the effect of dexamethasone on [Ca2+]i, In these experiments thymocytes showed no rises in [Ca2+]i above the control over 85 min following treatment with 10 μmol/L dexamethasone.
Production and characterization of muse thymic epithelial cell clones
Authors: GEORGIOU HARRY M. , CONSTANTINOU DORA
Published: July 2007

Four thymic epithelial cell lines (TEC) were derived from neonatal CBA and non‐obese diabetic (NOD) mouse thymus. From these cell lines a series of clones were produced by limit dilution and these have remained in stable culture for more than 1 year. Morphological characterization indicates that most cells are stellate with numerous short or long processes and ultrastructural studies show both active and quiescent cells with junctional complexes and bundles of tonofibrils. Immunohistochemical and flow cytometric analyses show that the cells express cytokeratin and appear to label for markers characteristic of cortical epithelial cells. Most clones express Thy‐1, Pgp‐l. ICAM‐1. HSA and B220 antigen, but are negative for LFA‐1. CD2, Mel 14, Fc receptor, Mac‐1, CD4 and CD8. All clones express low to moderate levels of class I MHC but are either negative or extremely low for class II MHC antigen. Most clones secrete IL‐6 and granulocyte‐macrophage‐CSF (GM‐CSF) in vitro, but generally do not produce IL‐2. IL‐3. IL‐4 or IFN‐γ.
Comparative analysis of the ability of leucocytes, endothelial cells and platelets to degrade the subendothelial basement membrane: Evidence for cytokine dependence and detection of a novel sulfatase
Authors: BARTLETT MARK R. , UNDERWOOD PATRICIA A. , PARISH CHRISTOPHER R.
Published: July 2007

The subendothelial basement membrane (BM) is regarded as an important barrier to the entry of leucocytes into inflammatory sites. This study compares the ability of leucocytes, platelets and endothelial cells (EC) to degrade a [35SO4]‐labelled subendothelial extracellular matrix (ECM) and assesses the effect of PMA and various pro‐inflammatory cytokines on this degradative activity. The different products of degradation, identified by fast protein liquid chromatography (FPLC) gel filtration chromatography, were indicative of protease, endoglycosidase (heparanase) and exoglycosidase and/or sulfatase activity. In terms of FCM degradation, EC and platelets were the most active, with PMA stimulation further enhancing the degradative activity of these two cell types. Platelets exhibited predominantly heparanase activity whereas the FC degradation products suggested a range of enzymic activities, namely proteases, heparanases and sulfatases. Interestingly, EC in suspension expressed these three enzymic activities whereas confluent EC monolayers only exhibited sulfatase activity, suggesting that the former situation might represent an angiogenic response. In the case of leucocytes, neutrophils and lymphocytes degraded the ECM to a much greater extent than monocytes. Each cell type also differed in the predominant enzymic activities it expressed, for example, heparanase activity by lymphocytes, protease activity by neutrophils and sulfatase activity by monocytes. Furthermore, PMA stimulation was shown to have differential effects on these enzymic activities.

Some pro‐inflammatory cytokines were found to be cell‐type specific in their effects on ECM degradation. Thus, lL‐1 + TNF enhanced neutrophil and EC degradation of the ECM but inhibited lymphocyte ECM degradation. In contrast, the chemokine IL‐8 enhanced ECM degradation by neutrophils, lymphocytes and EC. Of particular interest was the unique sulfatase activity expressed by EC and monocytes which was induced in FC by TNF + IL‐1 and IL‐8, whereas in monocytes the sulfatase activity was exclusively induced by the chemokine monocyte chemotactic and activating factor (MCAF).

Collectively, the results of this study show that leucocytes differ markedly in the enzymes they express to degrade the BM during extravasation and that PMA and cytokines are cell‐type specific in their induction of hydrolytic enzyme activity. These results also indicate that EC may play an important role, not only in the recruitment of leucocytes, but also via sulfatase activity in the preparation of vascular BM for leucocyte extra vasion.
Feedback suppression of B cell colony formation by supernatants of B colony cells: Role of immunoglobulin
Authors: FERNANDEZ L. A. , MACSWEEN J. M. , FALLOWS G. , ROBSON D. A.
Published: July 2007

We have reported previously that CD5+ B cells from mature B cell colonies provide a negative feedback signal to the growth of autologous B cell colonies. Now we have observed that supernatants from mature B cell colonies also provide a negative feedback signal to the growth of autologous B cell colonies. We investigated the mechanism of this effect by growing B cell colonies physically separated by a 0.45 μm filter from T cells in millicell‐CM chambers. Addition of colony supernatants to the T cell compartment reduced the number of B cell colonies by 28±6%. Colony numbers were reduced by 11±2 and 17±5% when the supernatants were added to the B cell or to both compartments, respectively. Pulsing T cells with the B cell colony supernatants before adding them to the colonies also decreased colony numbers by 33 ± 13%.

The addition of exogenous Ig classes and IgG subclasses to B cells decreased B cell colony numbers, although the effect was variable. In the presence of T cells, IgG had the greatest suppressive activity and the subclass IgG4 was most suppressive. In the absence of T cells, high concentrations of IgG almost abolished B cell colony formation.

We conclude that these supernatants provide a negative feedback signal either directly to B cells, or via T cells which may be mediated at least in part by Ig.
The trouble with transgenic mice
Authors: SINCLAIR NICHOLAS R. StC.
Published: July 2007

Observations on many antigen‐receptor transgenic models with anti‐self specificities have been interpreted as proof for clonal deletion or for mechanisms involved in clonal deletion. At the same time, there is increasing evidence that many lymphocytes that recognize self exist, are activated and produce end products, even in individuals without clinical autoimmunity. Except perhaps for the amount of anti‐self activity, there is little agreement on what distinguishes immune products normally recognizing self from those associated with clinical autoimmunity. To resolve this paradox, the tendency in immunology is to accept conclusions from transgenic models as normal, while judging those from the unmanipulated state as suspect. However, transgenics have a major weakness. Transgenes encoding antigen‐receptors are derived from highly selected mature lymphocytes and are expressed in developing lymphocytes that normally do not display the antigen‐receptors of mature lymphocytes. Such precocious expression of antigen‐receptors could have profound abnormal effects on lymphocyte development. Other transgenic models suggest that processes in lymphocyte differentiation not involving antigen‐receptor binding specificity exert powerful influences on lymphocyte development; therefore, mechanisms other than classical positive and negative selection are important.
Tissue expression, structure and function of the murine Ly‐6 family of molecules
Authors: GUMLEY THOMAS P , MCKENZIE IAN FC , SANDRIN MAURO S
Published: July 2007

Murine Ly‐6 molecules are a family of cell surface glycoproteins which have interesting patterns of tissue expression during haematopoiesis from multipotential stem cells to lineage committed precursor cells, and on specific leucocyte subpopulations in the peripheral lymphoid tissues. These interesting patterns of tissue expression suggest an intimate association between the regulation of Ly‐6 expression and the development and homeostasis of the immune system. Ly‐6 molecules are low molecular weight phosphatidyl inositol anchored glycoproteins with remarkable amino acid homology throughout a distinctive cysteine rich protein domain that is associated predominantly with O‐linked carbohydrate. These molecules are encoded by multiple tightly linked genes located on Chr. 15 which have conserved geneomic organization. The in vivo functions of Ly‐6 molecules are not known although in vitro studies suggest a role in cellular activation. This review will summarize our understanding of Ly‐6 with regard to tissue expression, molecular structure, gene organization and function.
Cytokine mediated effects in mucosal immunity
Authors: KRAMER DAVID R , SUTHERLAND ROBYN M , BAO SHISAN , HUSBAND ALAN J
Published: July 2007

The predominance of IgA antibodies in mucosal sites reflects a combination of high rate IgA isotype switching among precursor cells in induction sites, their selective localization in mucosal effector tissues and vigorous proliferation of these cells after extravasation. Each of these steps leading to IgA expression at the mucosa is under cytokine control. This paper will address the role of cytokines in induction and expression of IgA responses and strategies for manipulating cytokine expression. Therapeutic interventions based on this information may not only lead to improved vaccination responses and correction of immunodeficiencies but also, by invoking the phenomenon of oral tolerance, may assist in the management of autoimmune, allergic and alloreactive disease.
Histopathology of the lung following intratracheal challenge with live Pseudomonas aeruginosa in intestinally immunized rats
Authors: WILSON NR , DUNKLEY ML , BURET A , YOUNG B , CRIPPS AW
Published: July 2007

This paper examines the histology of rat lungs following intestinal immunization with killed mucoid Pseudomonas aerugtnosa and subsequent pulmonary challenge with live P. aeruginosa. The lungs of non‐immune challenged rats developed a confluent haemorrhagic pneumonitis with degeneration and sloughing of the mucosa of the airways; perivascular infiltration with mononuclear cells was apparent 1–2 h post‐challenge; some neutrophils were present by 2 h post‐challenge; by 12h post‐challenge oedema and intra‐alveolar haemorrhage were prominent and Gram‐negative organisms were seen in large quantities. In contrast, immunized challenged animals showed a pronounced neutrophilic response 1–2 h post‐challenge; by 12 h post‐challenge patchy abscesses were apparent with resolving inflammation and no organisms visible. The findings suggest that intestinal immunization prevents the development of fatal P. aeruginosa infections in the lung by accelerating the recruitment of polymorphonuclear neutrophils
cDNA cloning of porcine granulocyte‐macrophage colony‐stimulating factor
Authors: INUMARU S , TAKAMATSU H
Published: July 2007

Porcine granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) cDNA was cloned by using polymerase chain reaction (PCR) and sequenced. A coding sequence of the porcine GM‐CSF precursor protein, including the signal peptide sequence and stop codon, is 435 bp in length. The identities of the porcine GM‐CSF coding sequence when compared to ovine, bovine, human and murine sequences were 89, 86, 83 and 70% at the nucleotide level, and 80, 74, 73 and 56% at the amino acid level. The hydrophobicity profiles, putative glycosylation sites and positions of cysteine residues were highly conserved in porcine, ovine, bovine and human GM‐CSF but not murine. This is the first report of the porcine GM‐CSF cDNA cloning and sequence.
The ecology and pathology of Epstein‐Barr virus
Authors: SCHMIDT CHRISTOPHER W , MISKO IHOR S
Published: July 2007

Epstein‐Barr virus achieves its ubiquitous and uniform epidemiological distribution by a dual strategy of latency to guarantee lifelong persistence and intermittent replication to guarantee transmission. These two functions appear to dictate residence in different cell types: latency in B lymphocytes and replication in epithelial cells. Both of these cell compartments are potential sites for FBV‐associated malignancies.
Receptors for fibroblast growth factors
Authors: COUTTS JACQUELINE C , GALLAGHER JOHN T
Published: July 2007

The recent discovery of the involvement of heparan sulfate proteoglycans (HSPG) in the activation of fibroblast growth factor receptors (FGFR) has led to an intensification of study of this field. It appears that the HSPG act as low affinity receptors to which the fibroblast growth factors (FGF) must bind in order to successfully activate the high affinity FGFR. Heparan sulfate chains consisting of alternately arranged N‐acetylated or N‐sulfated glucosamine and uronic acid disaccharide regions, covalently attached to a core protein are found in two major families of cell surface HSPG, the syndecans and glypicans. A high affinity bFGF binding region has been isolated from fibroblast HS. There are four basic members of the FGFR family (FGFR 1–4), as well as a wealth of splice variants. The alternative forms of the basic receptors can have altered ligand binding or signalling qualities, depending on the region of the gene which is spliced. Investigations with null FGFR, incapable of signalling, have demonstrated the requirement for FGF in the organization of mammalian tissues and in embryonic patterning. Mutation of the FGFR genes has been recognized recently in human craniosynostoses where a single base pair mutation in the FGFR gene results in skeletal malformations specific to each syndrome. One suggestion is that the interaction of the mutant FGFR with the HSPG/FGF complex somehow contributes to the disease phenotype.
A mathematical formalism for the Kondo effect in Wess-Zumino-Witten branes
Authors: Hu Po , Kriz Igor
Published: July 2007

In the paper, we adapt our previous formalism for a mathematical treatment of branes to include processes, specifically the Kondo flow for Wess-Zumino-Witten (WZW) branes. In this framework, we give the precise mathematical definitions and formulate a mathematical conjecture relating WZW branes to nonequivariant twisted K theory in the case of the group SU(n). We also discuss regularization of the Kondo flow, thereby giving a first step toward proving our conjecture.