bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single nucleotide polymorphism (SNP) markers for benzimidazole resistance in veterinary nematodes
Authors: VON SAMSON-HIMMELSTJERNA G. , BLACKHALL W. J. , McCARTHY J. S. , SKUCE P. J. 
Published: July 2007

SUMMARYResistance to the benzimidazole class of anthelmintics in nematodes of veterinary importance has a long history. Research into the mechanisms responsible for this resistance is subsequently at a more advanced stage than for other classes of anthelmintics. The principal mechanism of resistance to benzimidazoles is likely to involve changes in the primary structure of β-tubulins, the building blocks of microtubules. Specifically, point mutations in the β-tubulin isotype 1 gene leading to amino acid substitutions in codons 167, 198, and 200 of the protein have been associated with resistance in nematodes. These single nucleotide polymorphisms offer a means of detecting the presence of resistance within populations. In this mini-review, we focus on the prevalence and importance of these polymorphisms in three groups of nematodes: trichostrongylids, cyathostomins, and hookworms. A brief overview of existing strategies for genotyping single nucleotide polymorphisms is also presented. The CARS initiative hopes to exploit these known polymorphisms to further our understanding of the phenomenon of BZ resistance.
Foreword: Towards markers for anthelmintic resistance in helminths of importance in animal and human health
Authors: PRICHARD R. K. , von SAMSON-HIMMELSTJERNA G. , BLACKHALL W. J. , GEARY T. G. 
Published: July 2007

SUMMARYAnthelmintic resistance is a serious problem in veterinary medicine and appears to be developing in some helminths of importance to human health. Anthelmintic drugs remain the principal means of control of helminth infections in animals and humans and the continued dependence on these pharmaceuticals will continue to impose selection pressure for resistance development. Our ability to detect anthelmintic resistance before control breaks down and to monitor the spread of anthelmintic resistance is quite limited. We are currently dependent on biological methods which are not sufficiently sensitive to detect low levels of drug resistance and are particularly difficult to perform on helminth parasites of humans. There is a serious need for new molecular markers for detecting and monitoring for anthelmintic resistance. The problem of anthelmintic resistance is already very serious in nematode parasites of livestock. In addition, there should be great concern about possible anthelmintic resistance development and the lack of tools and efforts for monitoring it as part of the major worldwide programmes to control helminth parasites in people. An international Consortium has been formed to develop Anthelmintic Resistance Single nucleotide polymorphism markers (CARS). Discussions within the Consortium have addressed the need for such markers, the current state of knowledge about them, possible mechanisms of anthelmintic resistance and approaches and constraints to the development of markers. Summaries of the state of the art in these areas are presented in a series of papers in this Special Issue of Parasitology.
Labelling the salt content in foods: a useful tool in reducing sodium intake in Finland
Authors: Pietinen Pirjo , Valsta Liisa M , Hirvonen Tero , Sinkko Harri 
Published: July 2007

AbstractObjectiveTo estimate the impact of choosing food products labelled either as low or high in salt on salt intake in the Finnish adult population.Setting and subjectsThe National FINDIET 2002 survey with 48-hour recalls from 2007 subjects aged 25–64 years. Sodium intake was calculated based on the Fineli® food composition database including the sodium content of natural and processed foods as well as the salt content of recipes. The distribution of salt intake was calculated in different ways: the present situation; assuming that all breads, cheeses, processed meat and fish, breakfast cereals and fat spreads consumed would be either ‘lightly salted’ or ‘heavily salted’ based on the current labelling practice; and, in addition, assuming that all foods would be prepared with 50% less or more salt.ResultsExcluding underreporters, the mean salt intake would be reduced by 1.8 g in men and by 1.0 g in women if the entire population were to choose lightly salted products and further by 2.5 and 1.8 g, respectively, if also salt used in cooking were halved. Choosing heavily salted products would increase salt intake by 2.1 g in men and by 1.4 g in women. In the worst scenarios, salt intake would be further increased by 2.3 g in men and by 1.6 g in women.ConclusionsThese calculations show that the potential impact of labelling and giving consumers the possibility to choose products with less salt is of public health importance. In addition, strategies to reduce the salt content of all food groups are needed.
Validating a nutrient profile model
Authors: Arambepola Carukshi , Scarborough Peter , Rayner Mike 
Published: July 2007

AbstractObjectiveTo assess the validity of nutrient profiling Model WXYfm – developed for the purpose of regulating the promotion of ‘less healthy’ foods to children. The model ranks foods according to their healthiness and categorises foods into ‘healthier’ and ‘less healthy’ foods.DesignConvergent and discriminant validity was tested by comparing the way Model WXYfm categorises foods with the way the UK’s national food guide – the Balance of Good Health (BGH) – categorises foods. Construct validity was assessed by testing a hypothesis relating the constructs of ‘healthiness’ of foods (as measured by Model WXYfm) and the ‘healthiness’ of diets (measured using the Diet Quality Index) and assessing whether this hypothesis was confirmed or refuted by using data on the dietary patterns of subjects (n= 1117) of the National Diet and Nutrition Survey of adults carried out in Great Britain in 2000–01.ResultsModel WXYfm showed good convergent and discriminant validity: the level of agreement between the way the model categorises foods and the way the BGH categorises foods was good (κ= 0.69). Model WXYfm also showed good construct validity: the energy intake from ‘less healthy’ foods amongst subjects with the least healthy diets was nearly twice the energy intake from ‘less healthy’ foods amongst the subjects with the healthiest diets.ConclusionsModel WXYfm demonstrated good validity in categorising foods in a way that is related to the healthiness of diets both recommended and achieved. The methods for assessing the validity of a nutrient profile model used in this paper have not, to our knowledge, been used before.
Patterns of resistance to Candida albicans in inbred mouse strains
Authors: ASHMAN R. B. , BOLITHO ERIN M. , PAPADIMITRIOU J. M. 
Published: July 2007

Summary Candida albicans infections were established in eight inbred strains of mice. Using established histological criteria, only two strains (AKR and CBA/CaH) were found to exhibit severe lesions. The remainder showed only mild tissue damage. Deaths occurred in three strains: CBA/CaH, A/J and DBA/2. The last two strains lack the important complement component C5. Colony counts in the brain varied widely between strains and showed no correlation with the extent or severity of tissue destruction. However, strains lacking C5 had a significantly greater fungal burden in the brain than C5‐sufficient mice. The data are discussed in relation to concepts of susceptibility and resistance to C. albicans in experimental infections in mice.
Activated CD19+ B cell lamina propria lymphocytes in ulcerative colitis
Authors: YACYSHYN B. R. 
Published: July 2007

SummaryAlthough isotype differences in lamina propria lymphocyte (LPL) immunoglobulin production has been recognized between normal, ulcerative colitis (UC) and Crohn's patients, differences in B cell activation between these conditions has not been described. Using flow cytometry, we studied B cell LPL activation using the CD71 (transferrin receptor), CD25 (interleukin‐2 receptor) and 4F2 (early B and T cell activation marker) monoclonal antibodies. CD19+ B cells from patients with UC had relatively increased expression of CD71, CD25 and 4F2 compared with patients with Crohn's disease or normal mucosa. This finding corresponds to an increased proportion of transitional (activated) B cells as defined by the co‐expression of CD45RA and CD45RO found in UC LPL compared with normal or Crohn's patient LPL. Such data may identify an important link between the cellular state of activation of UC LPL B cells and the differences in immunoglobulin production between the inflammatory bowel diseases and normal intestine. Such findings may have further diagnostic or pathophysiologic importance in the study of these diseases. This work also provides further support for the CD45 transition of CD19 B cells from the high to low molecular weight isoform.
Vaccination against tuberculosis: Is BCG more sinned against than sinner?
Authors: GRIFFIN J. FRANK T. , BUCHAN GLENN S. 
Published: July 2007

SummaryWhile extensive experimental studies of tuberculosis (Tb) have provided the foundation data for the discovery of cell‐mediated immunity, there remains much to be disclosed about the critical pathways of immunity involved in this infectious process and the factors necessary to produce protective immunity. Studies on the actiology and pathology of this disease have failed to elucidate the mechanisms of protective immunity. Although Tb research has been neglected for the past 30 years, the re‐emergence of Tb worldwide as a significant zoonotic disease has re‐focused research in this area. Scientific solutions for the control of Tb in man or domestic animals have not been found using empirical methods. Composite studies involving animal models of experimental infection will be necessary to critically evaluate vaccine efficacy and elucidate the basic immunological mechanisms involved in both disease and immunity. Available data which suggest that disease‐related hypersensitivity and immunity are dissociable highlight the prospect that immunity to infection may be induced without compromising the continued need for ongoing systems of immunodiagnosis to exclude disease. In populations with a high prevalence of disease it is likely that a combination of immunodiagnosis, chemotherapy and immunoprophylaxis will be required to eradicate the disease.
Recombinant vaccines against ovine footrot
Authors: O'MEARA T. J. , EGERTON J. R. , RAADSMA H. W. 
Published: July 2007

SummaryFor the past 20 years footrot vaccines have evolved from simple bacterins to highly specific recombinant DNA (rDNA) fimbrial vaccines. The development of these vaccines has left a trail of discoveries, challenges and solutions; these processes continue as we move closer to understanding the requirements of a footrot vaccine. The initial whole cell vaccines were unsuccessful due to the short duration of immunity and incorporation of limited serotypes. A multistrain vaccine eliminated the problem of serotype inclusion, although the duration of immunity in many cases is still inadequate. The proteases of Dichelobacter nodosus appear to be cross protective; however, little is known of their ability to protect sheep against footrot. The major protective immunogen is the bacterial fimbriae, which also forms the basis for the K‐agglutination serotyping system. K‐agglutinin titre correlates directly with resistance to challenge. The protective fimbrial epitope is conformationally dependent, suggesting little advantage in the development of synthetic peptide vaccines. To enhance the efficiency of vaccine production D. nodosus fimbrial genes were eventually cloned and successfully expressed in Ps. aeruginosa. Monovalent vaccines based on recombinant fimbriae are omnipotent, inducing high levels of agglutinins and long lasting immunity. In multivalent vaccines, on the other hand, incorporation of each additional serogroup into the vaccine results in reduced efficacy both in terms of reduced K‐agglutinin titres and reduced protection following challenge. The least effective are multivalent formulations representing all major serogroups. In addition, considerable genetic variation has been observed in the ability of sheep to respond optimally to each serogroup in a multivalent vaccine. Results show that the limitation of the sheep to mount an effective immune response, rather than the quality or quantity of the immunogen, limits the efficacy of current footrot vaccines. Studies are being undertaken to examine in detail the immune response of sheep to potentially highly effective footrot vaccines.
Functional and phenotypic assessment of neonatal human leucocytes expressing natural killer cell‐associated antigens
Authors: BRADSTOCK K. F. , LUXFORD C. , GRIMSLEY P. G. 
Published: July 2007

SummaryA subpopulation of mononuclear leucocytes was prepared from umbilical cord venous blood by immunomagnetic depletion of lymphocytes and monocytes using monoclonal antibodies to CD2, CD3, CD14 and CD19 antigens, and examined for NK cell‐associated phenotypic and functional properties. The depleted population was enriched for the NK markers CD16 (mean 53.6% positive) and CD56 (mean 42.7% positive). While there was considerable overlap of these two markers, approximately one‐third of CD16+ cells were CD56−; in contrast, few CD56+ CD16− cells were found. CD16+/CD56+ cells also co‐expressed CD7 and CD45RA antigens, while a minority weakly expressed CD8. Another marker of adult NK cells, CD57, was virtually absent from CD16+/GD56+ cells, as was MHG Class 2. Freshly depleted cord cells had virtually absent natural cytotoxicity to K562 targets in a chromium release assay, but NK activity could he induced after 18 h exposure to recombinant human IL‐2, without significant change in phenotype. These findings confirm the phenotypic differences and functional defects of NK cells in cord blood as compared to adult blood, and identify a subset of cells with unique phenotype (GD2− CD3− CD7+ CD16+ CD56− GD57−). The precise relationship of this subset of cells to NK lineage remains to be defined.
A comprehensive analysis of peripheral blood lymphocytes in healthy aged humans by flow cytometry
Authors: XU XIAONING , BECKMAN IAN , AHERN MICHAEL , BRADLEY JOHN 
Published: July 2007

SummaryThis study used a panel of mAb and multiparameter flow cytometry to assess the composition of PBL from healthy aged individuals. The results showed that while total lymphocyte numbers altered only marginally in the aged (≥ 70 years) there were significant changes in the distribution of various sub‐populations; for example, there were lower numbers of CD3+ and CD8+ cells, and higher numbers of CD16+ (NK) cells. As a direct result of these changes the numbers of CD2+ cells remained unchanged in the aged compared with young adult controls (18–25 years). The number of CD4+ T cells expressing CD45RO isoform (memory cells) exceeded the number of CD4+ CD45RA+ (naive) cells in aged donors, whereas the converse was true for young donors. In addition, associated with this increase in CD45RO+ cells, the aged showed an expanded population of CD45RO+ T cells displaying low surface levels of CD45RO. These data suggest that shifts in the distribution of regulatory T cell subsets may play a role in age‐related changes in immune response.
Electroporation and DNA‐dependent cell death in murine macrophages
Authors: STACEY KATRYN J. , ROSS IAN L. , HUME DAVID A. 
Published: July 2007

SummaryThe difficulty of transfecting primary macrophages and macrophage ceil lines has meant that relatively few studies on regulation of gene expression have been performed in these cells. This study has optimized an electroporation procedure for the macrophage cell line RAW 264, but shows that introduction of DNA into the cytoplasm of primary macrophages by electroporation is toxic to the cells. It is proposed that this cell death may have a physiological role in defence against certain viral infections which result in accumulation of cytoplasmic DNA. RAW 264 cells were efficiently transfected by electroporation, but electroporated bone marrow derived macrophages (BMM) showed large scale cell death over a period of 12 h. Electroporation without DNA was not toxic and DNase treatment of samples before transfection prevented cell death. The toxicity of DNA was concentration‐dependent and sequence independent. Synthetic, genomic and plasmid DNA all caused cell death. This sensitivity to DNA seems to be distinct from the antiviral state induced by double‐stranded RNA and may be part of an uncharacterized viral defence system.
Persistence of γ/δ T cell oligoclonality in the peripheral blood of rheumatoid arthritis patients
Authors: OLIVE COLLEEN , GATENBY PAUL A. , SERJEANTSON SUSAN W. 
Published: July 2007

SummaryThe peripheral blood of patients with rheumatoid arthritis (RA) contains oligocional γ/δ T cell populations which may contribute to the pathogenesis of the disease. To investigate whether there is persistent γ/δ T cell oligoclonality in RA peripheral blood, we screened polymerase chain reaction‐amplified T cell receptor (TCR) cDNA, derived from peripheral blood mononuclear cells (PBMC) of four RA patients, with sequence specific oligonucleotides (SSO). The SSO used were specific for TCR variable (V)δ1, Vδ2 and Vγ9 transcripts comprising V‐joining (J) junctions found over‐represented in PBMC of the same RA patients, when bled up to 3 years previously. The dominant transcripts were expressed in the new PBMC samples, although in most cases at a lower frequency than was originally detected. In one patient there was almost 100% oligoclonality of Vγ9‐(N)‐Jγ2 junctional region sequences among the Vγ9 cDNA clones. progressing from 55% oligoclonality in 15 months. These results indicate the persistence of clonally expanded γ/δ T cells in the peripheral blood of RA patients. Whether this reflects continual endogenous or exogenous antigenic stimulation remains to be investigated. The findings presented in this report may have important therapeutic implications in view of the potential for immuno‐intervention for the treatment of human autoimmune disorders, like RA.
Isolation and characterization of a neutrophil chemotactic factor from Tritrichomonas foetus organisms
Authors: OWHASHI M. , TOMIYOSHI F. , HAYASHI H. 
Published: July 2007

SummaryA neutrophil chemotactic factor (TfNCF) was isolated from the crude extract of Tritrichomonas foetus organisms by a combination of anion‐exchange chromatography on DE52 and gel filtration on Sephacryl S200. TfNCF showed homogenicity by both PAGE and SDS‐PAGE. The molecular weight of TfNCF was estimated to be 22 and 24 kDa, by Sephacryl S200 gel chromatography and by SDS‐PAGE under reducing conditions. Immunization of TfNCF caused almost complete protection against T. foetus infection in mice. Western blot analysis probed with anti‐TfNCF antibody showed that the epitopes on TfNCF were not commonly shared on the other components of T. foetus organisms nor other helminthous parasite‐derived components. Furthermore, pre‐incubation of neutrophils with antigens of other helminthous parasites or N‐formylmethionyl‐leucyl‐phenylalanine did not affect the neutrophil chemotactic activity for TfNCF. These results suggest that TfNCF is a novel NCF consisting of unique epitopes for both antigenicity and neutrophil chemotactic activity. The role of NCF in the initiation of the immune response is discussed.
The L‐selectin (Leu8) molecule is associated with the TcR/CD3 receptor; fluorescence energy transfer measurements on live cells
Authors: SZABO GABOR , PINE P. SCOTT , WEAVER JAMES L. , RAO PATRICIA E. , ASZALOS ADORJAN 
Published: July 2007

SummarySeveral accessory molecules were shown to play important roles in T cell functions and be in dose proximity to the T cell receptor (TcRyCD3). The L‐selectin molecule (Leu8, LAM 1‐1, LECAM1) also plays an important role in lymphocyte homing and proliferation. We were interested in determining the proximity of this molecule to the TcR/CD3 complex on live peripheral human T cells. Using a fluorescence energy transfer method, designed to study individual cells, we could show that L‐selectin is within 170 Å of the TcR/CD3 complex. Monoclonal antibody directed against the LAMl‐l (Leu8) epitope of the L‐selectin molecule suppressed the mitogenic activity of antibodies specific for various CD3 epitopes in vitro. Intracellular Ca2+ mobilization obtained with wt31 followed by cross‐linking antibody or with anti‐CD3 was not influenced by anti‐Leu8 antibody. Also antibody directed against the LAMl‐1 epitope did not influence the binding of the mitogenic antibodies, as shown by fluorescence‐based flow cytometry. Therefore, we suggest that binding of TcR/CD3 bound mitogenic antibodies to accessory cell Fc receptors may be hindered by antibodies bound to the close proximity L‐selectin molecules.
Internalization of the anticoagulant thrombomodulin is constitutive and does not require a signal in the cytoplasmic domain
Authors: TEASDALE M. S. , BIRD C. H. , BIRD P. 
Published: July 2007

SummaryEndocytosis of the protein C activation cofactor thrombomodulin (TM) is thought to be induced by interaction of TM with its ligand, thrombin, or by the action of inflammatory cytokines on endothelial cells. To examine the internalization of TM in the absence of thrombin or cytokines we used two assays. The first was a two‐colour indirect immunofluorescence technique to simultaneously monitor cell surface and internal pools of TM. The second involved labelling a cell surface pool of TM and following its cellular redistribution over time. Using these techniques we demonstrated that in both TM‐transfected COS cells and in endothelial cells, TM internalizes constitutively. Removal of the cytoplasmic domain, which in most receptors contains the internalization signal, did not abolish TM internalization. These results suggest that endocytosis of TM does not occur via coated pits, and that internalization probably is not a significant cause of the endothelial TM loss associated with several pathological states.
Infection of human and murine macrophages with Leishmania major is associated with early parasite heat shock protein synthesis but fails to induce a host cell stress response
Authors: KANTENGWA SALOMÉ , MÜLLER INGRID , LOUIS JACQUES , POLLA BARBARA S. 
Published: July 2007

SummaryHeat shock/stress proteins (HSP) represent the most conserved proteins expressed in prokaryotes and eukaryotes. These constitutive and inducible proteins function as molecular chaperones and are part of virulence factors. They participate in self/non‐self discrimination and may protect phagocytes from the toxic effects of the reactive oxygen species generated by these cells during bacterial phagocytosis and infection. In this study, we investigated the early stress response of host cells [either human alveolar macrophages (AM) or murine peritoneal macrophages (PM)] during infection by an obligate intracellular parasite (Leishmania major), which lives within phagolysosomes. Immunoblotting with specific antibodies demonstrated that L. major had no effect on host stress protein synthesis, but synthesized high levels of its own stress proteins within AM and PM. The lack of induction of a host cell stress response may relate to the failure of L. major to activate the respiratory burst in these cells, whereas the upshift of L. major HSP within macrophages is part of an adaptive response of the parasite to the host.