bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of murine thyroiditis by a non dominant Ek‐restricted peptide of human thyroglobulin
Authors: Karras Evangelos , Carayanniotis George , Lymberi Peggy
Published: December 2004

We have previously shown that the human thyroglobulin (hTg) 20‐mer peptide p2340 (aa 2340–2359) contains an epitope recognized by Tg‐reactive B cells in patients with Graves' disease. The presence of several Ek‐binding motifs within p2340 prompted us to examine whether this peptide can stimulate a T‐cell response and elicit experimental autoimmune thyroiditis (EAT) in AKR/J (H‐2k) mice. The peptide was found to be immunogenic at the T‐cell level since it induced specific proliferative responses as well as interleukin‐2 and interferon‐γ secretion in secondary cultures of peptide‐primed lymph node cells (LNC). The p2340‐specific proliferation was blocked almost completely by an Ek‐specific monoclonal antibody (mAb) but was unaffected by a control Ak‐specific mAb. Peptide‐primed LNC did not respond to intact hTg and conversely, LNC primed in vivo with hTg did not respond to p2340 in culture, suggesting that p2340 contains non‐dominant T‐cell epitope(s). Direct subcutanaeous challenge of AKR/J mice (n = 9) with p2340 in adjuvant, elicited mild to moderate EAT (infiltration index of 1–2) and strong p2340‐specific immunoglobulin G responses in all mice tested. These data delineate a new thyroiditogenic sequence within the carboxyl terminal region of hTg.
Evidence of CXC, CC and C chemokine production by lymphatic endothelial cells
Authors: Mancardi Sabrina , Vecile Elena , Dusetti Nelson , Calvo Ezequiel , Stanta Giorgio , Burrone Oscar R. , Dobrina Aldo
Published: December 2004

Although production of chemokines by vascular endothelial cells has been documented, there is only limited information regarding the expression of chemokines by the lymphatic endothelium. Here we used lymphatic endothelial cells (LEC) derived from experimentally induced murine lymphangiomas to investigate the pattern of chemokine expression by these cells. Histological analysis of the lymphatic hyperplasia revealed the presence of leucocytes in the tissues surrounding the lesions, suggesting the presence of chemoattractant activity. A functional chemotactic assay on human polymorphonuclear cells and on purified subpopulations of murine leucocytes using culture supernatants from LEC primary cultures confirmed the presence of chemoattractant activity. The identity of different cytokines of the CXC, CC and C subfamilies was investigated by reverse trancriptase–polymerase chain reaction on total endothelial cell RNA. Amplified fragments corresponding to KC, IP10, Mig‐1, BCL, MIP‐2, SLC, RANTES, MCP‐1, C10, and Lptn were obtained, and confirmed by Southern blot and sequencing. In contrast, MIP‐1α, MIP‐1β, and MIP‐1γ were not detected. Higher levels of expression were revealed by Northern blot analysis for Mig‐1, MCP‐1 and C10. The lymphatic endothelium‐restricted production of these chemokines was also confirmed by in situ hybridization. The presence of high C10 mRNA expression levels in LEC was particularly unexpected, because the production of this molecule has been previously identified only in cells of the haematopoietic lineage. These observations represent the first detailed analysis of chemokine production by lymphatic endothelial cells and may account, in part, for the mechanism of leucocyte recruitment into the lymphatics, and of lymphocyte recirculation within the lymphatic system.
Anti‐inflammatory effects in the skin of thymosin‐β4 splice‐variants
Authors: Girardi Michael , Sherling Michael A. , Filler Renata B. , Shires John , Theodoridis Efstathios , Hayday Adrian C. , Tigelaar Robert E.
Published: December 2004

The intraepithelial lymphocyte (IEL) network of T‐cell receptor γδ+ (Vγ5+) dendritic epidermal T cells (DETC) in murine skin down‐regulates cutaneous inflammation, although the mechanism is unknown. Thymosin‐β4 (Tβ4), identified by serial analysis of gene expression as a predominant transcript in gut IEL, encodes both a ubiquitous actin‐binding protein (UTβ4) with demonstrated capacity to inhibit neutrophilic infiltration, and a splice‐variant limited to lymphoid tissue (LTβ4) with unknown bioactivity. Freshly isolated Vγ5+ DETCs expressed both forms, while only LTβ4 was preferentially up‐regulated after cellular activation in vitro. To compare the anti‐inflammatory properties of LTβ4 and UTβ4 in the skin in vivo, the biological activities of synthesized polypeptides were assessed using three different strategies: neutrophil infiltration by footpad λ‐carrageenan injection; irritant contact dermatitis to 12‐O‐tetradecanoylphorbol 13‐acetate; and allergic contact dermatitis to 2,4‐dinitrofluorobenzene. These studies clearly showed that the anti‐inflammatory activities of LTβ4 were broader and most often stronger than those of UTβ4. Thus, the activation‐responsive expression of the lymph‐specific form of Tβ4 may be one mechanism by which DETC, and possibly other IELs, down‐regulate local inflammation.
Receptor/ligand avidity determines the capacity of Ly49 inhibitory receptors to interfere with T‐cell receptor‐mediated activation
Authors: Chalifour Anick , Roger Joanne , Lemieux Suzanne , Duplay Pascale
Published: December 2004

The specificity and the relative affinity of many Ly49 receptors for major histocompatibility complex class I ligands have been studied in detail in various adhesion and binding assays. However, how the level of cell surface expression of a given Ly49 receptor and its ligand affinity influence the strength of the inhibition signal is not well documented. To address this issue, we developed a series of human Jurkat T‐cell transfectants expressing the whole range of Ly49A and Ly49C levels found in vivo on natural killer and T cells and evaluated their capacity to alter superantigen‐induced NF‐AT activation and interleukin‐2 production. We show that the strength of the inhibition induced by Ly49A/H‐2Dd interaction correlates with Ly49A density up to a certain level after which increasing expression does not further inhibit significantly the T‐cell receptor‐induced activation. This system also represents a valuable tool for the determination of the relative strength of the inhibitory signals of Ly49 receptors following their interactions with different ligands. Even at high levels of expression there was no evidence that engagement of Ly49A with H‐2b class I molecules provided an inhibitory signal. Moreover, we showed that functional inhibitory interactions of Ly49C with H‐2b class I molecules were only the result of H‐2Kb and that H‐2d represent lower affinity ligands for Ly49C than H‐2b. Therefore, depending on the relative affinity of Ly49 receptors for their ligands, the modulation of their expression level will be determinant for the functional outcome of activated T cells.
Signalling events involved in interferon‐γ‐inducible macrophage nitric oxide generation
Authors: Blanchette Julie , Jaramillo Maritza , Olivier Martin
Published: December 2004

Nitric oxide (NO) produced by macrophages (Mφ) in response to interferon‐γ (IFN‐γ) plays a pivotal role in the control of intracellular pathogens. Current knowledge of the specific biochemical cascades involved in this IFN‐γ‐inducible Mφ function is still limited. In the present study, we evaluated the participation of various second messengers – Janus kinase 2 (JAK2), signal transducer and activator of transcription (STAT) 1α, MAP kinase kinase (MEK1/2), extracellular signal‐regulated kinases 1 and 2 (Erk1/Erk2) and nuclear factor kappa B (NF‐κB) – in the regulation of NO production by IFN‐γ‐stimulated J774 murine Mφ. The use of specific signalling inhibitors permitted us to establish that JAK2/STAT1α‐ and Erk1/Erk2‐dependent pathways are the main players in IFN‐γ‐inducible Mφ NO generation. To determine whether the inhibitory effect was taking place at the pre‐ and/or post‐transcriptional level, we evaluated the effect of each antagonist on inducible nitric oxide synthase (iNOS) gene and protein expression, and on the capacity of IFN‐γ to induce JAK2, Erk1/Erk2 and STAT1α phosphorylation. All downregulatory effects occurred at the pretranscriptional level, except for NF‐κB, which seems to exert its role in NO production through an iNOS‐independent event. In addition, electrophoretic mobility shift assay (EMSA) analysis revealed that STAT1α is essential for IFN‐γ‐inducible iNOS expression and NO production, whereas the contribution of NF‐κB to this cellular regulation seems to be minimal. Moreover, our data suggest that Erk1/Erk2 are responsible for STAT1α Ser727 residue phosphorylation in IFN‐γ‐stimulated Mφ, thus contributing to the full activation of STAT1α. Taken together, our results indicate that JAK2, MEK1/2, Erk1/Erk2 and STAT1α are key players in the IFN‐γ‐inducible generation of NO by Mφ.
Induction of apoptosis in monocytes by Mycobacterium leprae in vitro: a possible role for tumour necrosis factor‐α
Authors: Hernandez M. O. , Neves I. , Sales J. S. , Carvalho D. S. , Sarno E. N. , Sampaio E. P.
Published: December 2004

A diverse range of infectious organisms, including mycobacteria, have been reported to induce cell death in vivo and in vitro. Although morphological features of apoptosis have been identified in leprosy lesions, it has not yet been determined whether Mycobacterium leprae modulates programmed cell death. For that purpose, peripheral blood mononuclear cells obtained from leprosy patients were stimulated with different concentrations of this pathogen. Following analysis by flow cytometry on 7AAD/CD14+ cells, it was observed that M. leprae induced apoptosis of monocyte‐derived macrophages in a dose‐dependent manner in both leprosy patients and healthy individuals, but still with lower efficiency as compared to M. tuberculosis. Expression of tumour necrosis factor‐α (TNF‐α), Bax‐α, Bak mRNA and TNF‐α protein was also detected in these cultures; in addition, an enhancement in the rate of apoptotic cells (and of TNF‐α release) was noted when interferon‐γ was added to the wells. On the other hand, incubation of the cells with pentoxifylline impaired mycobacterium‐induced cell death, the secretion of TNF‐α, and gene expression in vitro. In addition, diminished bacterial entry decreased both TNF‐α levels and the death of CD14+ cells, albeit to a different extent. When investigating leprosy reactions, an enhanced rate of spontaneous apoptosis was detected as compared to the unreactive lepromatous patients. The results demonstrated that M. leprae can lead to apoptosis of macrophages through a mechanism that could be at least partially related to the expression of pro‐apoptotic members of the Bcl‐2 protein family and of TNF‐α. Moreover, while phagocytosis may be necessary, it seems not to be crucial to the induction of cell death by the mycobacteria.
A potent adjuvant effect of CD40 antibody attached to antigen
Authors: Barr Tom A. , Mccormick Adele L. , Carlring Jennifer , Heath Andrew W.
Published: December 2004

There is great potential for novel vaccines based on recombinant proteins and synthetic peptides. Unfortunately these antigens often lack the immunogenicity of whole, killed pathogens used in traditional vaccines. Thus there is strong interest in the identification of immunological adjuvants with low reactogenicity, but high potency, to enhance immune responses and realize the potential of these new vaccine strategies. CD40 antibodies have been shown to have adjuvant effects when administered at very high doses. These large doses are impractical and induce a cascade of cytokine release giving rise to septic shock‐like symptoms, as well as splenomegaly and polyclonal antibody production. We show here that a very small amount of CD40 antibody can exhibit potent adjuvant effects when attached to soluble antigen. The lack of detectable systemic effects indicates that this method may be a powerful and practical means of enhancing the efficacy of recombinant vaccines.
Mycophenolic acid is a potent inhibitor of the expression of tumour necrosis factor‐ and tumour necrosis factor‐receptor superfamily costimulatory molecules
Authors: Van Rijen Miranda M. L. , Metselaar Herold J. , Hommes Martijn , Ijzermans Jan N. M. , Tilanus Hugo W. , Kwekkeboom Jaap
Published: December 2004

The tumour necrosis factor (TNF) ligands CD154, CD70 and TNF receptors CD134 and CD137 are all involved in allograft rejection. Because these molecules are not present on resting T cells, we investigated whether immunosuppressive drugs could inhibit their induction. Expression was induced in vitro on T cells by phorbol 12‐myristate 13‐acetate and ionomycin or by allogeneic dendritic cells in the presence or absence of cyclosporin A (CsA), tacrolimus (TAC), rapamycin derivative (SDZ RAD), or mycophenolic acid (MPA), and determined by flow cytometry. To study the effect of in vivo exposure to immunosuppressive drugs on these molecules, immunohistochemistry was performed on human lymph nodes from patients treated with TAC or TAC and MMF. The calcineurin inhibitors (CI) CsA and TAC strongly suppressed the induction of CD70, CD137 and CD154, but not of CD134, upon pharmacological stimulation of T cells in vitro. In allogeneic stimulations only CD137 and CD154 were inhibited by CI. SDZ RAD did not inhibit pharmacological induction, but in allogeneic stimulations all the investigated molecules were partially suppressed. Both in pharmacological and in allogeneic stimulations, MPA inhibited induction of all tested molecules on T cells nearly completely at 4 µg/ml. However, in lymph nodes obtained from patients chronically treated with MMF and TAC no reduction of the expression of these molecules was observed. This was possibly caused by trough levels which were in vivo lower (mean: 2·3 µg/ml) than the concentration giving complete inhibition in vitro. In conclusion, in contrast to CsA, TAC and SDZ RAD, MPA is a potent inhibitor of the induction of TNF‐ and TNF‐receptor superfamily molecules on T cells. To obtain long‐term suppression of these molecules in vivo, a plasma trough level of 4 µg/ml is indicated.
Peptide‐based analysis of the amino acid sequence important to the immunoregulatory function of Trypanosoma cruzi Tc52 virulence factor
Authors: Borges Margarida , Da Silva Anabela Cordeiro , Sereno Denis , Ouaissi Ali
Published: December 2004

The intracellular protozoan parasite Trypanosoma cruzi is the aetiological agent of Chagas' disease. We have previously identified a T. cruzi‐released protein called Tc52, which is crucial for parasite survival and virulence. In the present study, we attempted to define the Tc52 epitope(s) responsible for its immunoregulatory function. A naturally occurring major peptide fragment of molecular mass 28 kDa (Tc28k) was identified, which was localized in the C‐terminal portion of Tc52 and was inhibitory for T‐cell activation. Synthetic peptides corresponding to amino acid sequences in Tc52 were evaluated for their ability to modulate T‐cell proliferation and cytokine production. Results obtained using five peptides spanning the N‐terminal or C‐terminal domain of the Tc52 protein indicated that the activity mapped to Tc52 residues 432–445. Moreover, it was found that the peptide, when coupled to a carrier protein (ovalbumin), exhibited increased inhibitory activity on T‐lymphocyte activation. Incubation with 8 nm ovalbumin‐coupled peptide 432–445 resulted in approximately the same levels (>75%) of inhibition of T‐cell proliferation as 5 µg/ml Tc28k. Furthermore, we showed that the coupled peptide significantly down‐regulated the secretion of interferon‐γ (IFN‐γ) and interleukin‐2 (IL‐2). Likewise, in immunized mice, the coupled peptide 432–445 was a very poor B‐ and T‐cell antigen compared with the other Tc52‐derived peptides. These results suggest that the immunomodulatory portion of the T. cruzi Tc52 virulent factor may reside, at least in part, in a conserved sequence within its C‐terminal domain, which could minimize its antigenicity.
A differential requirement for phosphoinositide 3‐kinase reveals two pathways for inducible upregulation of major histocompatibility complex class II molecules and CD86 expression by murine B lymphocytes
Authors: Marshall‐Clarke Stuart , Tasker Lynn , Heaton Mark P. , Parkhouse R. Michael E.
Published: December 2004

Constitutive expression of major histocompatibility complex class II molecules (MHC II) is restricted to dendritic cells, cells of the macrophage lineage and B lymphocytes. In all three lineages, peptide fragments of captured antigen are loaded into newly synthesized MHC II molecules. In B‐lineage cells, MHC II synthesis is dramatically increased on encounter with antigen, by T‐cell‐derived signals and by microbial products. We have previously shown that immature B cells fail to hyperexpress MHC II after antigen receptor [B‐cell receptor (BCR)] ligation, but are responsive to other stimuli. Expression of the costimulatory molecule, CD86, was similarly regulated. This suggested the existence of two pathways regulating expression of these important molecules. Here we present data supporting this hypothesis. We show that activity of the enzyme phosphatidylinositol 3‐kinase is critical for MHC II hyperexpression and induction of CD86 in response to ligation of the BCR or CD38, but not for responses to other stimuli including interleukin‐4, lipopolysaccharide and CD40 ligation.
Telomere length measurement and determination of immunosenescence‐related markers (CD28, CD45RO, CD45RA, interferon‐γ and interleukin‐4) in skin‐homing T cells expressing the cutaneous lymphocyte antigen: indication of a non‐ageing T‐cell subset
Authors: Neuber Karsten , Schmidt Saskia , Mensch Andrea
Published: December 2004

The purpose of this study was to investigate the immunosenescence of skin‐homing T cells expressing the cutaneous lymphocyte antigen (CLA). Peripheral blood lymphocytes from 72 healthy individuals (33 male and 39 female; median age 54 years; age‐range: 18–94 years) were investigated. The expression of CD28, CD45RA and CD45RO, as well as intracellular interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4) formation of CLA+ ‘skin homing’ T cells, was analysed. In addition, T cells were detected immunohistologically in skin specimens from 15 young and 15 old, healthy individuals. The relative telomere length (RTL) was measured by fluorescence in situ hybridization using flow cytometry (flow FISH). The total number of CLA+ T cells was found to remain constant with increasing age. In contrast to peripheral blood T cells (CD3+ CLA−), which showed significantly decreased CD28 and CD45RA expression in donors > 60 years of age, no age‐related alterations of either CD28+ CLA+ T cells or CD45RA+ CLA+ T cells were observed. In the group of donors > 60 years of age, the proportion of intracellular IFN‐γ‐producing CD3+ CLA− cells showed a significant increase, whereas the number of IFN‐γ‐ and IL‐4‐producing CLA+ T cells was not affected by age. After stimulation with phytohaemagglutinin (PHA) or staphylococcal enterotoxin B (SEB), CLA+ T cells from old donors did not show a reduced response compared with CLA+ T cells from young donors. Additionally, the counts of T cells in healthy skin from young and old adults were statistically not different. Furthermore, the RTL was significantly shortened in enriched CD45RO+ CLA− T cells from healthy old individuals, but not in aged CLA+ T cells. The present data suggest that CLA+ T cells might be a T‐cell subpopulation which does not undergo immunosenescence. This may explain why the intensity of inflammatory skin reactions (e.g. psoriasis or eczema) seems to be independent of the patients' age.
Year‐dependent sex‐biased mortality in supplementary‐fed Tengmalm's owl nestlings
Authors: Hipkiss Tim , Hörnfeldt Birger , Eklund Ulf , Berlin Sofia
Published: December 2004

In sexually size‐dimorphic birds, the larger sex requires more energy during growth, and often suffers from a higher mortality risk during growth than the smaller one when food is limited.

Sex‐specific growth and mortality were examined in Tengmalm's owl Aegolius funereus (L.) nestlings, a species in which adult females are slightly larger than males. Nestlings were unambiguously sexed using molecular techniques. Nestling mortality in broods provided with supplemental food was compared with that in controls in an experiment carried out during two breeding seasons, 1998 and 1999.

The natural food supply during the two years of the experiment differed. Although the spring vole abundance was similar for the two years, 1998 was characterized by a less severe decline in vole abundance during the previous winter, and also a greater increase in vole abundance during the summer than 1999. It was consequently inferred that the owls’ natural food supply was more limited in 1999.

In 1998, female nestlings attained a 5% higher asymptotic mass than males, and fed nestlings were heavier than controls. No difference in rate of mass gain or wing growth was detected.

Overall mortality was lower in fed broods than controls in 1999 only. Unexpectedly, female nestling mortality was unaffected by supplemental feeding during both years. However, in 1999, when natural food supply was more limited, male nestling mortality was reduced in supplementary‐fed broods.

It is suggested that the females’ larger size gives them a competitive advantage against their male siblings when fighting over food items, and that when food is limited, males rather than females suffer increased mortality owing to lack of food.

This study illustrates the importance of repeating food supplementation experiments to account for annual variation in natural food supply.
The functional response in three species of herbivorous Anatidae: effects of sward height, body mass and bill size
Authors: Durant Daphné , Fritz Hervé , Blais Sandra , Duncan Patrick
Published: December 2004

The functional response, i.e. the quantity of food consumed per unit of time as a function of food availability, is a central process in foraging ecology. The application of this concept to foraging by mammalian herbivores has led to major insights into the process of resource acquisition, but it has so far been little used to understand foraging in avian herbivores.

In this study, we describe the functional responses of three grazing Anatidae, the wigeon Anas penelope L. (mean body mass in this study 620 g), the barnacle goose Branta leucopsis B. (2000 g), and the greylag goose Anser anser L. (3500 g). We measured instantaneous intake rates on eight grass heights from 1 cm to 12 cm, as well as pecking rates and peck sizes, and used the Spalinger–Hobbs model developed for mammalian herbivores to explore the mechanisms limiting intake in these three species.

Greylag geese increased their intake rate with increasing food availability (a Type II response), wigeon showed a weak quadratic (Type IV) response, and intake rate by barnacle geese did not vary significantly across the range of variability we offered the birds.

Intake rates differed markedly between individuals, especially in greylag geese, where body mass explained much of the variation. For individuals in all three species, peck sizes strongly influenced instantaneous intake rates, and the size of the bill (width in particular) appeared to be an important determinant of peck size.

Peck sizes increased with sward height (although only very weakly in wigeon), but so did cropping time for wigeon and barnacle geese, which led to a significant decline of intake rates on the tallest grass, at least in the small wigeon. For these very selective small herbivores, the time to crop a mouthful was therefore a significant limiting factor for the birds’ instantaneous intake rate (in addition to peck size and swallowing time). This differs markedly from the situation in mammalian herbivores where bite size (through chewing time) is the principal controlling process in food concentrated patches, a result that we found in greylag geese. We discuss the differences in foraging between the three species in relation to their principal food resources, body mass and bill morphology.
Phenotypic correlates of post‐fledging dispersal in a population of greater flamingos: the importance of body condition
Authors: Barbraud Christophe , Johnson Alan R. , Bertault Guillaume
Published: December 2004

Factors influencing post‐fledging movements before the first breeding attempt were studied in individually marked greater flamingos (Phoenicopterus ruber roseus) born in the Camargue, southern France, between their natal area and their principal wintering grounds (Spain, Sardinia, Tunisia and France) from 1995 to 1999.

We tested whether post‐fledging dispersal was affected by sex, age, year, body condition, body mass and tarsus length using a multistate capture–recapture modelling approach. We focused particularly on the hypothesis that increased movement probabilities were associated with good and poor body condition. Because long‐distance dispersal is energetically expensive and may involve a high risk of mortality, the acquisition of a robust physical condition prior to dispersal probably plays a critical role in determining the extent to which animals disperse. At the other extreme, birds in poor condition either leave their natal area or starve, which should result in relatively high dispersal rates.

Movement probabilities were not sex‐dependent, but were age‐dependent with high movement probabilities during the first year of life (above 0·6) and low probabilities after the first year (0·055). Movement probabilities also differed between years and localities.

Movement probability from the natal area was related to the body condition (and body mass) of the fledglings, with a high movement probability (0·873) when juveniles were in good body condition, and a relatively lower probability (from 0·629 to 0·724) when juveniles were in poorer condition. The proportion of variability in dispersal explained by body condition and body mass were 90·9% and 63·5%, respectively.

Results support the hypothesis that condition affects dispersal patterns from the natal area. They also suggest that body condition and local environmental conditions during the early growth play a role in dispersal.
Manipulation of offspring number and size: benefits of large body size at birth depend upon the rearing environment
Authors: Oksanen Tuula A. , Jokinen Ilmari , Koskela Esa , Mappes Tapio , Vilpas Heli
Published: December 2004

Allocation of reproductive effort between the number and size of offspring determines the immediate rearing environment for the growing young. As the number of offspring increases, the amount of parental investment per individual offspring decreases, and the quality of the rearing environment is expected to decrease. This may result in a lower quality of offspring reared in such conditions.

We studied the effects of the rearing environment on the quality of juvenile bank voles, Clethrionomys glareolus, with different initial body sizes at birth in a 2 × 2 factorial experiment. The rearing environment was manipulated by enlarging both the litter size by two extra pups, and mean offspring body size at birth by replacing the original litter with heavier pups from smaller litters. Offspring quality was estimated from body size measurements, parasitic infection with Eimeria spp. and the level of immune response to a novel antigen.

The analyses revealed that large body size at birth was an advantage in ‘normal’ rearing environments, but a disadvantage in poor ones. The initially normal sized offspring grown in enlarged litters had a relatively good capacity for growth and high immune function confirming that a poor rearing environment alone does not reduce their quality.

Our findings that the benefits of large body size depend on the rearing environment suggest that offspring body size is adjusted in relation to litter size, and thus the evolution of these two traits is combined.
Rodents, cowpox virus and islands: densities, numbers and thresholds
Authors: Begon Michael , Hazel Sarah M. , Telfer Sandra , Bown Kevin , Carslake David , Cavanagh Rachel , Chantrey Julian , Jones Trevor , Bennett Malcolm
Published: December 2004

The population dynamics of bank voles and wood mice, and of cowpox virus infection in these two species, was studied over a 2‐year period in a mainland population and in 14 nearby island populations of varying sizes.

For both species, there was no intrinsic variation in the pattern of host dynamics with island size: small island populations behaved as though they were small subsamples of a larger population, displaying no more than the expected random variation from the general pattern.

None the less, the relative numbers of bank voles to wood mice increased markedly with decreasing island size; and bank vole densities tended to be higher on smaller islands.

Only 22 animals were discovered to have moved either between islands or between the mainland and the islands, out of 1883 captured in all. None the less, it was apparent that males were more likely to move than females.

Overall patterns of cowpox virus dynamics were similar in all cases. However, on all islands there were extended periods when cowpox virus infection was apparently absent, and on the small islands the numbers of infected individuals were mostly very low and in many cases infection was never found.

For both host species, there was no evidence for a threshold population size for cowpox virus (critical community size) in terms of density, but clear evidence for one in terms of the numerical size of populations. This suggests little support for density‐dependent transmission, despite this having been the usual default assumption for non‐sexually transmitted infections.

There was also evidence for a separate invasion threshold (between ecological and epidemiological invasion) and persistence threshold (between epidemiological invasion and persistence). This is contrary to the output of the most‐quoted (deterministic) models – persistence and invasion threshold one and the same – highlighting the fact that little attention has been paid in the past to the practical meaning of the theoretical concept of a threshold.

In the case of the wood mice, a superficial similarity to the bank vole thresholds was potentially misleading. Wood mouse thresholds were influenced at least as much by the bank vole thresholds as they were by the dynamics within the wood mouse populations themselves.
Population consequences of mutual attraction between settling and adult barnacles
Authors: Kent Adam , Hawkins Stephen J. , Doncaster C. Patrick
Published: December 2004

Spatial patterns of recruitment were compared between populations of the rocky shore barnacles (Crustacea: Cirripedia) Semibalanus balanoides, an obligate cross‐fertilizer, and Chthamalus montagui, which can self‐fertilize. We tested the hypothesis that recruitment depends on a behaviourally mediated interaction at settlement between the effects of adult background density and adult spacing, which limit free space for settlement and mating opportunities, respectively. Recruitment to patches of cleared rock (10‐ or 30‐cm diameter) was compared between replicate shores with background densities of adult barnacles classed as low (≤20 per 25 cm2) and high (>4× low). Replicate patches were cleared of all barnacles surrounding a remnant cluster, comprising 0, 1, 2, 4, 8, 16 or 32 adults.

For S. balanoides, settlement and subsequent recruitment over 5 months varied in direct proportion to remnant cluster size, except on the shore with the highest background density where recruitment was inversely proportional to cluster size. We interpret this inversion to indicate attraction to potential mates at low adult densities (positive density dependence, an Allee effect) switching to attraction to free space at high density (negative density dependence). The strengths and slopes of the regressions increased from shores with the lowest to the highest overall recruitment of barnacles, but retained significance over a five‐fold range in recruitment. Positive effects of cluster size on recruitment were consistent between consecutive years, despite considerable variation in recruitment densities. In contrast, recruitment of C. montagui was generally more weakly proportional to cluster size, except for a strong positive correlation at the shore with the highest recruitment.

Dispersion of recruits within treatment patches was accurately modelled by a computer simulation that allowed each barnacle to settle at random between fixed minimum and maximum distances from the nearest other settled barnacle. The model estimated threshold distances by maximum likelihood fit to observed recruitment into concentric annuli around the central adult cluster. Upper thresholds of separation corresponded to penis length for 65% of S. balanoides and 42% of C. montagui patches. Lower thresholds were ∼2× cyprid length for 75% of S. balanoides patches, but were larger than this for C. montagui patches.
On the relation between temporal variability and persistence time in animal populations
Authors: Inchausti Pablo , Halley John
Published: December 2004

The relationship between temporal variability, spectral redness and population persistence for a large number of long‐term time series was investigated. Although both intuition and theory suggest that more variability in population abundance would mean greater probability of extinction, previous empirical support for this view has not been conclusive. Possible reasons are the shortage of long‐term data and the difficulties of adequately characterizing temporal variability, two issues that are explicitly addressed in this paper.

We examined the relationship between population variability and quasi‐extinction time (measured as the time required to observe a 90% decline of population abundance) for a large set of data comprising 554 populations for 123 species that were censused for more than 30 years. Two aspects of temporal variability were considered in relation with the quasi‐extinction time: a baseline value (coefficient of variation over a fixed, 30‐year, time scale), and a measure of the rate of increase of the population variability over time (spectral exponent).

The results show that the quasi‐extinction time was shorter for populations having higher temporal variability and redder dynamics. The relation between persistence time and population variability was compared for different taxa, trophic levels, habitat type (aquatic and terrestrial) and body sizes and compared with theoretical expectations.
Moving forward in a role as a researcher: the effect of a research method course on nurses' research activity
Authors: Adamsen Lis , Larsen Kristian , Bjerregaard Lene , Madsen Jan K.
Published: December 2004

• The aim of this study was to investigate whether a 1‐year research course in basic research methodology, designed for clinical nurses, had a positive effect on the nurses' own research activity and their commitment to research in general.

• The research method applied was use of semistructured interviews. Seventy‐nine clinical nurses participated in the study. Students of the research course (n = 37), i.e. the study group, were compared with a group of clinical nurses who did not participate in the course (n = 42), i.e. the reference group.

• A statistically significant difference was found in several variables between the two groups. Eighty‐nine per cent of the study group members were active in planning their own research projects compared with 35.7% in the reference group. The study group also showed a higher level of interest and commitment to research results of others and read English language articles. A total of 13.9% of the study group experienced being unable to find time during working hours to participate in research projects, while this was true for 50% of nurses in the reference group.

• Experiences from the research course in basic methodology show that educational programmes designed for clinical nurses may facilitate and support their own research efforts as well as enhance their commitment to research in general. The course reinforced nurses' self‐confidence in research‐based practice. Clinical nurses require personal initiative, perseverance and competence in research methodology as well as sensitization towards a research culture in order to move away from the salaried work of a practitioner and into the role of a researcher.
Using patient stories to inspire quality improvement within the NHS Modernization Agency collaborative programmes
Authors: Wilcock Peter Michael , Stewart Brown Geraint Ceri , Bateson John , Carver Jonathon , Machin Sheelagh
Published: December 2004

• The importance of obtaining the opinions of service users has long been recognized and, traditionally, most contact has focused on measuring their satisfaction with the services they receive. However, there is little evidence that this has had much impact on improving care.

• The Discovery Interview Process, a technique for listening to patients and carers and using their narratives to improve care, is discussed in this article. This approach has been used in the pilot phases of the UK Coronary Heart Disease Collaborative and Critical Care Collaborative.

• These narratives develop understanding grounded in experience. Those delivering care can interpret the narratives using their own clinical and professional knowledge and experience to create better or new ways of meeting patients' and carers' needs. Using their own expert knowledge they can identify needs within the narratives, including those that patients and carers did not know they had.

• The principal techniques for gathering these narratives are outlined, and ways of using such data to inform patient‐focused service improvements are discussed. Various locally sensitive methods for presenting the narratives to expert interprofessional teams are also described along with emerging experience of this feedback.

• We consider the Discovery Interview technique for gathering patient and carer narratives to be a potentially powerful method for informing quality improvements, discovering what really matters to patients and their carers. This pragmatic approach could prove manageable within local quality improvement projects.
Leg ulcers: a review of their impact on daily life
Authors: Persoon Anke , Heinen Maud M. , Van Der Vleuten Carien J.M. , De Rooij Michette J. , Van De Kerkhof Peter C.M. , Van Achterberg Theo
Published: December 2004

Background.  Current nursing care for leg ulcer patients often focuses on wound care and providing compression therapy. Nurses perceive leg ulcer patients as ‘under‐served’ with regard to problems patients experience in daily life. An overview of patient problems is a first and essential step in the development of comprehensive nursing care.

Aims and objectives.  To gather information about the impact of leg ulcers on patient's daily life as described in quantitative and qualitative studies.

Design.  Systematic literature review.

Methods.  Medline and Cinahl databases were searched for venous leg ulcer studies, up to 2002; this was followed by the ‘snowball method’. Studies were selected in accordance with preset criteria.

Results.  A total of 37 studies was included. All studies report that leg ulcers pose a threat to physical functioning. Furthermore, a negative impact on psychological functioning is reported and, to a lesser degree, on social functioning. Major limitations are pain and immobility, followed by sleep disturbance, lack of energy, limitations in work and leisure activities, worries and frustrations and a lack of self‐esteem. Patients have a significantly poorer quality of life compared with healthy people. Finally, patients report problems with regard to follow‐up treatment.

Conclusions.  Having a leg ulcer has a major impact on a patient's life. There are indications of under‐treatment of pain.

Relevance to clinical practice.  Keeping in mind that leg ulceration is notorious for its chronic character, the negative impact on patient's life implies that many patients suffer over longer periods of time. This emphasizes the need to focus on quality of life aspects in patient care. There is much to gain, especially concerning pain and mobility. The development of comprehensive care programmes is essential.
ICU nurses' knowledge of, and attitudes towards, the APACHE II scoring system
Authors: Chen Shiu‐Lien , Wei Ien‐Lan , Sang Yiing‐Yiing , Tang Fu‐In
Published: December 2004

Aims and objectives.  This study was undertaken to determine whether intensive care unit nurses possess adequate knowledge to implement the Acute Physiological and Chronic Health Evaluation (APACHE) II scoring system and to understand nurses’ attitudes towards this scoring system.

Design.  A questionnaire, which contained 20 multiple‐choice questions to test knowledge of the scoring system and 27 statements with a five‐points Likert type scale to assess attitude, was developed by researchers for this study.

Methods.  The participants consisted of 102 intensive care unit nurses working in adult, emergency, or coronary intensive care units in a large teaching hospital (Veterans General Hospital) in Taiwan, where the APACHE II scoring system is used routinely by nurses.

Results.  On the knowledge section of the questionnaire, 76% of the questions were answered correctly. However, more than 50% of the nurses were uncertain about how to score a patient's chronic history status, only 44.1% of the nurses knew that APACHE II total scores range from 0 to 71, and only 37.3% understood that the value for bicarbonate in venous samples could replace the arterial pH value. The results of the attitude questionnaire revealed that nurses believed APACHE II was useful mainly for statistical purposes by the administration rather than for patient care, but acknowledged that the scores could provide a reference for more aggressive treatment.

Conclusions.  The questionnaire answers indicated that greater knowledge concerning the APACHE II is needed.

Relevance to clinical practice.  Information and training concerning the proper use and purpose of APACHE II needs to be provided, especially for those intensive care unit nurses using this evaluation tool to score patients’ conditions routinely.
Rheumatology: a study of patient satisfaction with follow‐up monitoring care
Authors: Arthur Valerie , Clifford Collette
Published: December 2004

Background.  This paper reports the findings of a quantitative study to determine the satisfaction of rheumatology patients receiving follow‐up monitoring care within primary and secondary locations.

Aims and objectives.  The aim of the study was to compare and contrast the satisfaction of patients with rheumatoid arthritis following two different routes of care. The objective was to explore the dimensions of care identified in an earlier qualitative study.

Design.  A convenience sample of 80 participants was used; 40 from each care location.

Methods.  Data were collected using the Leeds Satisfaction Questionnaire, which explores the dimensions of satisfaction previously identified as being important to this group of patients.

Results.  The secondary care group showed significantly higher levels of satisfaction in respect of general satisfaction, provision of information and continuity of care and a significant difference in relation to empathy, technical ability and attitude to the patient.

Conclusions.  While patients from both locations were satisfied with the care they received, those receiving specialist nursing care in the secondary location were more satisfied.

Relevance to clinical practice.  Increased emphasis on care in the community and the evolution of nurse specialist roles indicate the need for further qualitative work to inform the future planning of care provision for rheumatology patients in this area.
Decision‐making during hospitalization: parents’ and children's involvement
Authors: Hallström Inger , Elander Gunnel
Published: December 2004

Background.  Ethical duties of health professionals include the obligation to enhance their patients’ competence and ability to participate.

Aims and objectives.  To explore what kind of decisions and how these decisions were made during a child's hospitalization.

Design.  During a 9‐week period 24 children and their parents were followed during the course of events at the hospital. In total 135 hours of observations were made and analysed in two steps.

Results.  In most of the situations one or both parents were present with the child. Most decisions were of a medical nature, and commonly decisions were made in consultation with those affected by the decision. Although one or more persons protested in 83 of the 218 described situations, decisions were seldom reconsidered.

Conclusions.  The children and their parents were usually involved in the decision‐making process. Children and parents made few decisions themselves and even if they disagreed with the decision made, few decisions were reconsidered.

Relevance to clinical practice.  Having a voice in decision‐making helps the child to develop a sense of himself as a person and gives the parents a feeling that they are part of a team giving their child optimal care during hospitalization. Promoting children's rights is one of the most important roles for the children's nurse.
Venous leg ulcer patients: a review of the literature on lifestyle and pain‐related interventions
Authors: Heinen Maud M. , Achterberg Theo van , Reimer Wilma Scholte op , Kerkhof Peter C.M. van de , Laat Erik de
Published: December 2004

Background.  Having a leg ulcer has a major impact on daily life. Lifestyle is mentioned in most leg ulcer guidelines but mostly without much emphasis on the subject.

Aims and objectives.  Evidence for the effect of nutrition, leg elevation and exercise on the healing of leg ulcers was reconsidered. Furthermore, the evidence for effective pain‐related interventions was investigated.

Design.  Systematic literature review.

Methods.  Medline, Cinahl, Psychinfo and Cochrane were searched for studies on pain related interventions, and the effectiveness of leg elevation, leg exercise and nutritional interventions in patients with venous leg ulceration.

Results.  Some evidence was found to support a positive effect of leg exercises on the endurance and power of the calf muscle and on the haemodynamic status of the limb. There is also evidence for a positive effect of leg elevation during bed rest without compression. No hard evidence was found concerning the effect of enriched or altered nutrition on wound healing. However, there is some evidence of nutritional deficits in this patient group. The use of eutectic mixture of local anaesthetic cream is effective for reducing pain in wound debridement, but pain relief in daily life is insufficiently treated.

Conclusion.  There is no real evidence of effectiveness of the investigated lifestyle interventions but there are indications that lifestyle interventions might contribute to healing or prevention of venous leg ulceration.

Relevance to clinical practice.  Although there is no hard evidence, it can be expected that interventions such as nutritional monitoring, guided exercise and leg elevation will have a substantial impact on wound healing in patients with venous leg ulceration. The use of eutectic mixture of local anaesthetic cream can be advised for pain relief with wound debridement. The current lack of effective pain treatment with venous leg ulceration emphasizes the need for effective pain treatment.