bluuebunny/crossref_metadata_2025 huggingface dataset:
Skin delivery of a hybrid liposome/ISCOM vaccine implicates a role for adjuvants in rapid modulation of inflammatory cells involved in innate immunity before the enhancement of adaptive immune responses
Authors: Chin James , Gil Ferdinand San
Published: March 2003

There is now compelling evidence that intradermal vaccination with an efficacious adjuvanted antigen triggers a series of coordinated responses characterized initially by the rapid mobilization and recruitment of granulocytes to the lung. Activation of effector cells of the innate immune system is intended to provide surveillance and temporary protective cover at vulnerable mucosal sites while both T and B cell precursors, as well as haematopoietic progenitor cells, are undergoing dramatic reductions in numbers during the first 2–4 days post‐vaccination. Some of these events recapitulate those seen after infection with a pathogen. Initial decreases in cell numbers in the thymus and bone marrow (BM) are followed by rapid increases in cellular proliferation in these organs, probably in response to peripheral signals. Vaccine‐induced cell death (by apoptosis) in the thymus may provide one of many stimuli needed to up‐regulate BM production of progenitor cells, and cells of the B, myeloid and monocytic lineages so that depleted peripheral compartments are replenished. Reconstitution of the latter cell population is critical in ensuring sufficient numbers of APC are generated to deal with extraneous antigen resulting from either vaccination or proliferation of a pathogen. Ultimately, these APC, as effector cells of the innate immune system, must provide pattern recognition of dangerous pathogens and serve to activate appropriate T cell responses. Vaccination not only educates both the innate and adaptive arms of the immune response but also more interestingly, appears to regulate subsequent innate immune responses following exposure to a lethal challenge dose of bacteria. Under these conditions, the rate of loss of BM precursors is greatly attenuated in mice previously vaccinated with adjuvanted antigen compared to unvaccinated controls or mice that had received only antigen. Mice intradermally vaccinated with adjuvanted antigen also displayed increased rates of granulocyte and monocyte recruitment in the lung and spleen. These events occurred very rapidly within 12–36 h of challenge and may be crucial in providing complete protection in vaccinated mice against a challenge dose that was otherwise lethal for unvaccinated controls. Therefore, an important characteristic of an efficacious intradermal vaccine may be the ability to deplete T and B precursors in the thymus and BM lymphoid compartments followed by increased rates of haematopoiesis to re‐supply peripheral requirements for granulocytes/monocytes, and T and B cells. Adaptive immunity elicited by intradermal vaccination is, therefore, dependent upon prior activation of the innate immune system.
FGF signal transduction in PC12 cells: Comparison of the responses induced by endogenous and chimeric receptors
Authors: Foehr Erik D , Raffioni Simona , Fuji Ritsuko , Bradshaw Ralph A
Published: March 2003

Rat phaeochromocytoma (PC12) cells respond to many growth factors and produce different phenotypes, including neurite outgrowth. Receptor tyrosine kinases (RTK), which activate multiple signalling pathways in response to ligand binding, initiate many of these. One such family of receptors, the fibroblast growth factor receptor (FGFR), has four different members and expresses at least three of these in PC12 cells. A chimeric tyrosine kinase receptor, consisting of the extracellular domain of human plasma‐derived growth factor receptor‐β (hPDGFR‐β) and the transmembrane and intracellular region of FGFR1 (designated PFR1), was constructed and was stably transfected into cloned PC12 cell lines. This chimera, which can be activated without stimulating endogenous RTK including other FGFR, induces neurite outgrowth in a PDGF‐dependent manner. By altering the protocol for preparing the retroviral vectors, cells with a wide range of expression levels can be obtained. The amount of these chimeric receptors seems to correlate with the time and the intensity of response as observed in neurite outgrowth assays. Analysis of proteins implicated in FGFR1 signalling indicates that upon stimulation, a tyrosine phosphorylated protein designated FRS2 associates with SOS, Grb2 and the receptor. The chimeric receptor appears entirely similar to that observed for the stimulation of native PC12 cells with FGF2. These results support the view that FRS2 is the dominant FGFR1 signalling entity in PC12 cells.
Accessible xenografts of human synovium in the subcutaneous tissues of the ears of SCID mice
Authors: Proudman Susanna M , Cleland Leslie G , Fusco Michael , Mayrhofer Graham
Published: March 2003

This work was undertaken to examine whether human synovium could be engrafted into subcutaneous pouches in the ears of severe combined immunodeficient (SCID) mice. Synovium was transplanted into surgically constructed ear pouches. The grafts were examined by histological and immunohistochemical methods after varying periods after engraftment, or after percutaneous injection of TNF‐α. Normal, osteo‐arthritic and rheumatoid synovium was engrafted successfully in subcutaneous ear pouches. The general morphology and cellular compositions of xenografts were retained including human endothelial cells. In rheumatoid xenografts, macrophages, fibroblasts and lymphocytes persisted for at least 4 weeks. Vascular expression of intercellular adhesion molecule‐1 (ICAM‐1) was maintained but expression of vascular adhesion molecule‐1 (VCAM‐1), E‐selectin and MHC class II diminished with time. Percutaneous injection of TNF‐α induced up‐regulation of VCAM‐1. Human synovium can be engrafted into subcutaneous ear pouches in SCID mice. The xenografts are accessible and respond to injection of a pro‐inflammatory cytokine.
Cholera toxin‐induced alteration of the phenotype and behaviour of an ovarian carcinoma cell line, SR8
Authors: Han Xin , Papadopoulos Andreas J , Jones Tanya , Devaja Omer , Raju Kankipati S
Published: March 2003

Cholera toxin (CT) has been reported to cause a variety of effects on several different cell types. Recently, CT has been shown to increase the susceptibility of ovarian carcinoma cells to cytotoxicity mediated by a variety of effector cells (natural killer, lymphokine‐activated killer cells and tumour‐associated lymphocytes derived from ascites of ovarian cancer patients) of both autologous and allogenic background. In the present study, CT demonstrated several effects on a newly established ovarian carcinoma line (SR8)1 when added to the culture medium at a concentration of 12.5 ng/mL for 2 days. Cholera toxin altered SR8 morphology to a uniform polygonal cellular shape, with less cell dispersion than the non‐CT treated cells. Cholera toxin prolonged the population doubling time by approximately 10 h. The CT‐treated SR8 cells exhibited reduced epidermal growth factor receptor expression (39 versus 50%), and increased carbohydrate antigen 125 expression (45 versus 2%) in both immunocytochemical and quantitative flow cytometric analyses. These changes in morphology and tumour marker expression were reversible when CT was removed from the culture. The CT‐treated SR8 cells showed reduced capacity to generate tumours in female nude mice in comparison with non‐CT treated cells, which produce both subcutaneous and intraperitoneal xenografts with local invasion in an animal model. Cytogenetic analysis of the cell line SR8 before and during treatment with CT showed no new clonal rearrangements. The possible mechanisms involved and the influence of CT on the biological behviour of ovarian tumour cells are discussed.
Monocyte‐derived dendritic cells as a model for the study of HIV‐1 infection: Productive infection and phenotypic changes during culture in human serum
Authors: Mallon Dominic FJ , Buck Andrew , Reece Jeanette C , Crowe Suzanne M , Cameron Paul U
Published: March 2003

Dendritic cells (DC) have been implicated in the initial selection for macrophage‐tropic HIV‐1 during transmission and in the generation of high‐level virus replication during interactions with CD4 T cells. The role of DC as viral reservoirs and the extent of productive infection is unclear, but the ability to generate large numbers of DC from blood monocytes has produced a tractable model for study of DC–HIV‐1 interactions. When cultured in granulocyte–macrophage colony stimulating factor and IL‐4, sorted CD14+ monocytes rapidly lost phagocytic function for both 93 nm and 977 nm latex particles and developed the surface markers and function of DC. After 7 days, when returned to medium containing human serum without cytokines, some monocyte‐derived dendritic cells (MDDC) became adherent, but retained the costimulatory markers CD80 and CD86 and continued to express CD83 and CD40. The MDDC stimulated allogeneic CD4 T cells, did not express new macrophage markers and remained non‐phagocytic. With or without TNF‐α, MDDC generated in cytokines were infected by macrophage and T cell‐tropic virus and produced higher reverse transcriptase levels than did the autologous monocyte‐derived macrophages (MDM). When added to T cells, the infected MDDC were able to infect T cells with a wider range of viral isolates than were MDM.
Carboxyfluorescein diacetate succinimidyl ester and the virgin lymphocyte: A marriage made in heaven
Authors: De St Groth Barbara Fazekas , Smith Adrian L , Koh Woon‐Puay , Girgis Laila , Cook Matthew C , Bertolino Patrick
Published: March 2003

Carboxyfluorescein diacetate succinimidyl ester (CFSE) labelling of naïve lymphocyte populations provides unique insights into the immune response. The clonal nature of immune responses, necessitating clonal expansion to achieve a sufficiently large number of Ag‐reactive effector cells, combined with the dependence of lymphocyte differentiation on cell division, underlie the usefulness of CFSE in understanding the factors that regulate responses both in vitro and in vivo. We have combined CFSE labelling with Ag receptor transgenic models, using seven channel flow cytometry to track the correlation between cell division and a number of other parameters, such as surface expression of activation markers, cytokine receptors and homing receptors, cytokine production, cytotoxic activity and indicators of apoptosis. Our data have allowed us to classify and understand immune responses in novel ways, suggesting many further avenues of enquiry and indicating previously unrecognized relationships between cell division and eventual cell fate.
KC production in the cornea in response to Pseudomonas aeruginosa challenge
Authors: Cole Nerida , Bao Shisan , Thakur Archana , Willcox Mark , Husband Alan J
Published: March 2003

Pseudomonas aeruginosa can cause ulcerative bacterial keratitis. A feature of keratitis is the rapid infiltration of the avascular corneal stroma by neutrophils. KC is a potent neutrophil chemokine. The present study used a mouse model of ocular infection to assess the relationship between KC and inflammation in the cornea in response to challenge with a strain of P. aeruginosa causing keratitis. Low levels of KC mRNA and protein were detected by in situ hybridization and ELISA, respectively, in unchallenged corneas. Dramatically increased numbers of KC mRNA+ cells were present in P. aeruginosa strain 6294‐challenged corneas. Expression of KC mRNA was found to be up‐regulated in the corneal epithelium in response to wounding alone. The KC mRNA+ cells were located in the epithelium and corresponding to infiltrating neutrophils cells in the stroma. Quantification of KC protein at different time points showed peak levels at 8 h of bacterial challenge. These results suggest that KC may be involved with the regulation of leucocyte infiltration early during bacterial keratitis.
Therapeutic immunization against Helicobacter pylori infection in the absence of antibodies
Authors: Sutton Philip , Wilson John , Kosaka Tadashi , Wolowczuk Isabelle , Lee Adrian
Published: March 2003

Helicobacter pylori is an important human pathogen. Prophylactic immunization with bacterial antigen plus an adjuvant protects mice against challenge with live H. pylori. Surprisingly, it was found that immunizations of mice already infected with Helicobacter also influenced bacterial colonization. This concept of therapeutic immunization is a novel phenomenon. Because H. pylori lives in the lumen of the stomach, it was initially hypothesized that the protective mechanism would involve induction of secretory IgA. However, work with knockout mice has demonstrated that prophylactic immunization is equally effective in mice deficient in IgA and even in μMT mice lacking B lymphocytes. Currently nothing is known about therapeutic vaccination and the effect of immunizing a host with an ongoing ineffective immune response. To address this, we infected B‐cell deficient, μMT mice with H. pylori and therapeutically immunized them four times in 3 weeks with bacterial sonicate and cholera toxin adjuvant. These immunizations significantly reduced colonization by H. pylori. The antibody‐ negative status of the μMT mice was confirmed by ELISA. Thus, therapeutic immunization stimulates an immune response, which reduces H. pylori infection via a mechanism that is antibody independent. How this is achieved remains to be determined, but may well involve a novel immune mechanism.
Bioactive molecules in milk and their role in health and disease: The role of transforming growth factor‐β
Authors: Donnet‐Hughes A , Duc N , Serrant P , Vidal K , Schiffrin Ej
Published: March 2003

Human breast milk is rich in nutrients, hormones, growth factors and immunoactive molecules, which influence the growth, development and immune status of the newborn infant. Although several of these factors are also present in bovine milk, the greater susceptibility of the formula‐fed infant to infection and disease and the development of allergy is often attributed to the reduced level of protective factors in milk formulas. Nevertheless, modifying manufacturing processes may preserve the biological activity of some bioactive molecules in end products. Transforming growth factor (TGF)‐β is one such molecule. TGF‐β is a polypeptide, which has been described in both human and bovine milk. It is implicated in many processes, including epithelial cell growth and differentiation, development, carcinogenesis and immune regulation. The present article discusses the biological activity of TGF‐β2 that has been preserved and activated in a cow's milk‐based product. More specifically, it addresses possible mechanisms of action in the intestinal lumen and speculates on how milk products containing naturally occurring TGF‐β2 could be exploited in functional foods for the infant or as therapies for specific intestinal diseases.
Characterization of the ovalbumin‐specific TCR transgenic line OT‐I: MHC elements for positive and negative selection
Authors: Clarke Sally RMcK , Barnden Megan , Kurts Christian , Carbone Francis R , Miller Jacques Fap , Heath William R
Published: March 2003

The present report provides the first extensive characterization of the OT‐I TCR transgenic line, which produces MHC class I‐restricted, ovalbumin‐specific, CD8+ T cells (OT‐I cells). These cells are shown to be positively selected in vivo in H‐2b C57BL/6 mice and in bm5 mice, which express the Kbm5 mutant molecule. In contrast, OT‐I cells were not selected by mutant Kb molecules in bm1, bm3, bm8, bm10, bm11 or bm23 mice. Interestingly, however, when positive selection was examined in vitro in foetal thymic organ culture (FTOC), bm1 and bm8 were still poorly selective, but the bm3 haplotype now selected as efficiently as B6. The ability to select in vitro correlated with the capacity to present the ovalbumin (OVA) peptide to OT‐I cells, as measured by induction of an OVA‐specific proliferative response. These results suggest that a lower affinity TCR:MHC interaction may be necessary for positive selection in FTOC compared with selection in situ.
Improved FACS analysis confirms generation of immature dendritic cells in long‐term stromal‐dependent spleen cultures
Authors: Ni Keping , O’Neill Helen C
Published: March 2003

Cells produced in spleen stroma‐dependent long‐term cultures (LTC) have now been clearly defined as dendritic cells (DC). Characterization of cells by antibody staining and FACS analysis has only been possible using a procedure to quench the high autofluorescence of DC produced in LTC (LTC‐DC). The population of large cells produced by the established LTC‐X1 culture are homogeneously positive for a number of cell‐surface markers expressed by DC. These include CD11c, CD11b, Dec‐205, Fc receptor and CD86. They also express markers detectable with the F4/80 and 33D1 antibodies. Cells produced in LTC do not uniformly express the MHC II marker, consistent with an immature DC phenotype. Most cells are weakly positive for MHC II with a small subset of highly positive cells. The quenching method involves staining cells with crystal violet dye, which is taken up within the cell. The importance of optimizimg fluorescent antibody staining assays for delineating DC subsets is indicated and the LTC system is established as a valuable and continuous source of DC precursors.
Studies on the IgA‐independent immunological responses in mice to influenza virus challenge after oral vaccination with irradiated whole virus and an erythrocyte complex
Authors: Lidbury Brett A , Grissell Terrence V , Sizer Philip J , Clancy Robert , Cripps Allan W
Published: March 2003

Previous studies have described an oral influenza vaccine comprising whole irradiated virus and an erythrocyte complex (IV‐EC), which gave broad‐based protection against influenza virus challenge in mice. The present study examined the immune responses generated after live virus challenge of vaccinated mice, particularly to determine whether mice vaccinated with IV‐EC had enhanced CTL activity to compensate for the previously reported diminution in lung IgA response. Oral vaccine groups examined were IV‐EC, live virus alone (LV) or live virus‐erythrocyte complex (LV‐EC), compared with irradiated virus and erythrocyte alone controls. The antibody responses of IV‐EC and LV‐EC vaccinated mice showed significantly elevated lung and serum IgG2a levels post live virus challenge, with no comparable increases in IgG1 levels compared to controls. Spleen cells from IV‐EC mice showed an enhanced post‐challenge proliferative response to antigen compared with mice that had received live oral vaccines, indicating enhanced cellular activity post IV‐EC immunization. However, CTL activity was not enhanced for IV‐EC mice, and live virus‐vaccinated mice had reduced CTL activity compared with controls, indicating that CTL were not important for post‐vaccine protection. Cytokine analysis revealed a predominant IFN‐γ response in spleen cells from orally vaccinated mice, whereas IL‐4 was not detected in any lung or spleen culture analysed. The results suggest, therefore, that protection from live influenza challenge after IV‐EC or LV‐EC vaccination was due to an IFN‐mediated IgG2a response. Definitive confirmation of the role of these factors in post‐vaccine protection can now be tested in IgG2a‐depleted or IFN‐γ gene knockout mouse models.
Associations between HLA‐DQB1 high‐risk alleles and type I diabetes do not depend on cytomegalovirus antibody status at onset: A case‐parent study conducted in Chile
Authors: Santos Jl , Pérez‐Bravo F , Carrasco E , Petri R , Calvillán M , Albala C
Published: March 2003

The purpose of the present study is to ascertain whether the associations between HLA‐DQB1∗0201 and DQB1∗0302 alleles and childhood diabetes depend on the presence of antibodies to human cytomegalovirus (CMV). A study of incident type I diabetes cases and parents was conducted in Santiago, Chile. HLA‐DQB1 polymorphisms were determined in 85 case‐parent trios (255 subjects), while the detection of CMV was carried out only in the incident cases. As expected, HLA‐DQB1 polymorphisms are strongly associated with type I diabetes, with crude odds ratios of 3.7 (95% confidence interval (CI) 1.8–7.7) for the DQB1∗0201 allele and 10.3 (95% CI 5.0–21.4) for the DQB1∗0302 allele. In the subset of families with CMV+ cases, the odds ratios were estimated as 3.7 (95% CI 1.6–8.6) for the DQB1∗0201 allele and 11.1 (95% CI 4.8–25.8) for the DQB1∗0302 allele. In families with patients who tested negative for CMV antibodies, the odds ratios were calculated as 3.5 (95% CI 0.7–16.8) for the DQB1∗0201 allele, and 8.0 (95% CI 1.8–34.7) for the DQB1∗0302 allele. There was no evidence of statistical interaction between CMV antibodies and the DQB1∗0201 allele (P value = 0.9) or the DQB1∗0302 allele (P value = 0.7). In conclusion, alleles DQB1∗0302 and DQB1∗0201 do not display distinct associations with type I diabetes depending on the presence of antibodies for CMV.
Interleukin‐2‐producing helper T lymphocyte precursor frequency and rejection: A longitudinal cellular study after cardiac transplantation
Authors: Weston Lyanne E , Sullivan John S , Keogh Anne M , Geczy Andrew F
Published: March 2003

Interleukin‐2‐producing helper T lymphocyte precursors (HTLp) in the recipient recognize donor alloantigen expressed by the transplanted organ. The frequency of these reactive cells in the peripheral blood was determined and correlated with rejection episodes. Endomyocardial biopsy is generally used to quantify cardiac allograft rejection and guide immunotherapy. While non‐invasive techniques have been investigated, none of these has demonstrated sufficient sensitivity or specificity to replace myocardial biopsy. Twelve cardiac transplant recipients were assessed over a 1 year period using limiting dilution analysis, to determine the frequency of HTLp in response to cadaver donor splenocytes. The IL‐2‐dependent mouse cell line CTLL‐2 was used to measure the IL‐2 present and the precursor frequency was calculated using maximum likelihood estimation. In the months immediately post transplantation, six of the 12 recipients displayed an association with increases in HTLp frequency, which preceded histologically detectable rejection. The second six recipients had fewer rejection episodes and achieved ‘acceptance’ of their graft sooner. Once ‘acceptance’ was achieved, the association between IL‐2 HTLp frequency and rejection was no longer apparent. The ability to identify two groups of patients on the basis of IL‐2 HTLp frequency clearly highlights the heterogenous nature of the response to the graft and this emphasizes the need to monitor other cytokines, which may influence the functioning of effector T cells.
Recirculating and marginal zone B cell populations can be established and maintained independently of primary and secondary follicles
Authors: Körner Heinrich , Winkler Thomas H , Sedgwick Jonathon D , Röllinghoff Martin , Basten Antony , Cook Matthew C
Published: March 2003

In normal spleen, most recirculating naïve IgM+IgDhi B cells are located within primary follicles and mantle zones of secondary follicles. By contrast, the marginal zone contains a heterogeneous population of IgMhiIgDlo/‐ B cells that are mostly non‐recirculating. Although these are dynamic populations they are maintained at a constant size, the fundamental homeostatic mechanisms remain uncertain. One possibility is that the presence and turnover of each of the B cell populations is dependent on their location within discrete splenic compartments. To investigate this, we have characterized immature, non‐recirculating, mature recirculating, marginal zone and B‐1 cell populations in TNF−/− and TNF/lymphotoxin(LT)‐α−/− mice that have disorganized splenic architecture. Labelling with 5‐bromo‐2′‐deoxyuridine revealed that turnover of B cells in TNF−/− mice is normal, but is diminished in TNF/LT‐α−/− mice. The recirculating B cell populations in both mutant strains are normal in proportion and phenotype. Marginal zone B cells are not seen in TNF/LT‐α−/− mice, but this population appears normal in TNF−/− mice, even though they lack germinal centres. These findings indicate that peripheral B cell subsets can be established and maintained independently of normal follicular architecture.
Macrophages and nitric oxide as the possible cellular and molecular basis for strain and gender differences in susceptibility to autoimmune central nervous system inflammation
Authors: Staykova Maria A , Cowden William B , Willenborg David O
Published: March 2003

PVG rats are resistant to actively induced experimental autoimmune encephalomyelitis (EAE) and this appears to be directly related to high and sustained systemic levels of reactive nitrogen intermediates (RNI) following sensitization for EAE when compared to the highly susceptable Lewis rat. An apparent cellular basis for the different EAE susceptibility between the two rat strains is described. Spleens of PVG rats have increased monocyte/macrophage numbers (NO producing cells) and lower erythrocyte (NO scavengers) to nucleated spleen cell ratios compared with Lewis rats. Splenectomy demonstrated the pivotal role of the spleen in resistance to EAE as splenectomized PVG rats were rendered completely susceptible to disease induction. It was further demonstrated that EAE resistance in PVG rats is limited only to females and that only female PVG rats have increased splenic macrophage and an enhanced NO production following immunization. The males are fully susceptible to EAE and their spleen cell populations are similar to those of Lewis rats of either gender. Despite being resistant to active disease induction, immunized female PVG rats can generate EAE effector cells that are capable of passively transferring disease. Furthermore, female PVG rats are fully susceptible to passively transferred EAE. Thus, there appears to be no defect in the female PVG target tissue or in the processing or presentation of antigen, but a block at the level of effector cell expansion and/or recirculation and transmigration into the target tissue in actively induced EAE.
IL‐1β transcript stability in monocytes is linked to cytoskeletal reorganization and the availability of mRNA degradation factors
Authors: Sirenko Oksana , Böcker Ulrich , Morris John S , Haskill J Stephen , Watson Joanna M
Published: March 2003

Monocyte extravasation initiates reorganization of the cytoskeleton (CSK) and adhesion‐dependent cytokine gene transcription. The actin CSK is thought to be crucial for compartmentalization and translation of mRNA, many of which contain AU‐rich (ARE) instability motifs in the 3′ untranslated region. We investigated regulation of adhesion‐induced IL‐1β expression by the monocyte CSK. In serum‐free adherent monocytes, the induced IL‐1β mRNA was stable and did not coextract with actin filaments. In contrast, in cells adherent in autologous serum, IL‐1β transcripts were unstable, coextracted with actin filaments and were associated with only transient activation of the mitogen‐activated protein kinases (MAPK). Under both conditions of adherence, the ARE‐binding protein AUF1/hnRNP D was readily extracted in the cytosolic fraction. Electro‐injection with AUF1/hnRNP D modified the actin CSK and, surprisingly, stabilized IL‐1β transcripts. These data suggest that the control of mRNA degradation is linked with changes in the CSK. Mitogen‐activated protein kinase activation or alterations in the availability of mRNA degradation factors may mediate these effects.
Mucosal immunity in the brushtail possum (Trichosurus vulpecula): Detection of antibody in serum and at female reproductive sites after intranasal immunization
Authors: Doolin Elizabeth E , Wedlock D Neil , Buddle Bryce M , Skinner Margot A
Published: March 2003

Vaccination strategies for the brushtail possum, which rely upon stimulation of mucosal immunity, are being developed for biocontrol purposes. As little is known about how to stimulate possum immune responses via a mucosal site, groups of possums were immunized intranasally with keyhole limpet haemocyanin (KLH) alone or in combination with known or novel mucosal adjuvants. Antigen‐specific antibody titres in female reproductive secretions were measured by ELISA and compared with antibody titres in the serum. Antigen‐induced lymphocyte proliferative responses were measured as an indicator of cell‐mediated responses. Intranasal immunization with KLH alone stimulated a weak serum antibody response that was significantly increased when KLH was given with cholera toxin subunit B (CTB), recombinant possum tumour necrosis factor α (TNFα) or live Mycobacterium bovis bacillus Calmette Guerin (BCG). Antibody titres in secretions from ovarian follicles and the uterus were very low in animals administered KLH alone. Significantly higher antibody titres to KLH were present in the reproductive secretions of possums immunized with KLH plus CTB, BCG or heat‐killed Mycobacterium vaccae. Antibody titres were lower in mucosal secretions than in the serum, but there was a significant correlation between the two. In addition, coadministration of live BCG with KLH produced a strong antigen‐specific cell‐mediated response to KLH. This study has shown that an immune response to a protein antigen can be stimulated in possums by intranasal immunization and that antigen‐specific antibodies can be detected in secretions from the female reproductive tract.
The role of CD4+CD25+ immunoregulatory T cells in the induction of autoimmune gastritis
Authors: Laurie Karen L , Van Driel Ian R , Gleeson Paul A
Published: March 2003

A number of experimental models of organ‐specific autoimmunity involve a period of peripheral lymphopenia prior to disease onset. There is now considerable evidence that the development of autoimmune disease in these models is due to the absence of CD4+CD25+ regulatory T cells. However, the role of CD4+CD25+ regulatory T cells in the prevention of autoimmune disease in normal individuals has not been defined. Here we have assessed the affect of depletion of CD4+CD25+ regulatory T cells in BALB/c mice on the induction of autoimmune gastritis. The CD4+CD25+ T cell population was reduced to 95% of the original population in adult thymectomized mice by treatment with anti‐CD25 mAb. By 48 days after the anti‐CD25 treatment, the CD4+CD25+ regulatory T cell population had returned to a normal level. Treatment of thymectomized adult mice for up to 4 weeks with anti‐CD25 mAb did not result in the development of autoimmune gastritis. Furthermore, we have demonstrated that depletion of CD4+CD25+ regulatory T cells, together with transient CD4+ T lymphopenia, also did not result in the development of autoimmune gastritis, indicating that peripheral expansion of the CD4+ T cell population, per se, does not result in autoimmunity in adult mice. On the other hand, depletion of CD4+CD25+ T cells in 10‐day‐old euthymic mice resulted in a 30% incidence of autoimmune gastritis. These data suggest that CD4+CD25+ regulatory T cells may be important in protection against autoimmunity while the immune system is being established in young animals, but subsequently other factors are required to initiate autoimmunity.
The good, the bad and the relative, part one: Conceptions of goodness in qualitative research
Authors: Emden Carolyn , Sandelowski Margarete
Published: March 2003

The good, the bad and the relative, part one: Conceptions of goodness in qualitative research

This (part one) paper traces efforts to define ‘goodness’ in qualitative research within various fields, including nursing. At first closely aligned with the traditional tenets of quantitative research (reliability and validity), over time these are found to be increasingly problematic to uphold within a qualitative context. As alternative criteria more appropriate to qualitative approaches are developed, in many instances these also are wanting in that they continue to reflect a search for order and certainty that permeates the quantitative domain. In reviewing various sets of criteria of goodness, the concepts of reliability and validity in relation to qualitative research are conceived as being championed, translated, exiled, redeemed and surpassed. Part two of the paper addresses the topic of goodness of qualitative research within the philosophical ‘problem of the criterion’. Discussion extends to how researchers might usefully juxtapose the rationality of a modern world with a mounting postmodern sensibility.
Patient satisfaction with nursing care in a colorectal surgical population
Authors: Lumby J. , England K.
Published: March 2003

This paper describes one arm of a much larger, multi‐site study whose hypothesis was that evidence‐based nursing practice is more effective than routine nursing care in improving patient outcomes and health gain. This arm of the study investigated patient satisfaction as an outcome measure for those patients undergoing colorectal surgery. The study’s relevance for nurses is in the potential feedback for reviewing nursing practice and health care delivery. Patient satisfaction with nursing care was measured through a validated questionnaire, the SERVQUAL, followed by interviews with a percentage of the study population. The results of this arm of the study confirm the importance of measuring patient satisfaction through a triangulated method which investigates thoroughly, providing feedback for continuous quality improvement. The in‐depth interviews provided greater insight into the results of the questionnaire, enabling clear feedback to nursing staff at the different sites of the study. Results of the questionnaire revealed age, sex and education levels of patients as major influences on individual perceptions of nursing care. Patients whose surgery resulted in stomas were also less satisfied with health‐care delivery.
Registered nurse management of urinary catheters in a rehabilitation and long‐term care hospital
Authors: Gnc A Andrew Fleming Rn , Rn Jenny Day , Mn Linda Glanfield Rn Grad Dip(hlthSc)
Published: March 2003

Nurses are the primary managers of all the routine care and problem solving associated with patients who have indwelling urinary catheters. Despite the key role nurses have, there is a lack of uniformity in the nature of documentation provided to guide practice. This paper discusses the findings from a research project that identified knowledge levels and management practices in a rehabilitation and long‐term care hospital. A convenience sample of 39 registered nurses completed a questionnaire examining knowledge levels and identifying current practices. The results revealed knowledge deficits in catheter‐related knowledge, and variation in client education and documentation. The results also demonstrated the continued use of traditional knowledge as well as unclear application of fundamental nursing principles. There is a clear need for increased use of evidence‐based practice and development of suitable post‐registration education.
Women's experience of myocardial infarction
Authors: E Holliday Julie , M Lowe Julia , Outram Sue
Published: March 2003

Background: Heart disease is a major cause of mortality in women. Women have a poorer prognosis than men after myocardial infarction (MI) and research to date has failed to find a definitive explanation. Women have been identified as late presenters for emergency care after acute myocardial infarction. The aim of this study was to discover the underlying processes that effect women's decisions to seek medical help for symptoms of MI.

Methods: Qualitative analysis, of semistructured face‐to‐face interviews with 16 women aged between 48 and 82 years, admitted to a major teaching hospital with MI.

Results: The women delayed presentation from 1 h to 168 h (median 6.25 h). The decision to seek help was influenced by beliefs about personal susceptibility to MI and beliefs about the way MI presents. Symptoms were diverse and were rarely as described in current health promotion literature.

Conclusion: The pivotal factor for early presentation is that women, and their significant others, recognise the variety of signs and symptoms of MI and their personal susceptibility. A theoretical model, adapted from the Self Regulation Model of Illness Cognition of Leventhal et al. is proposed to explain the women's response and also areas of intervention.
Falls risk factors in the hospital setting: A systematic review
Authors: Evans David , Hodgkinson Brent , Lambert Leonnie , Wood Jacquelin
Published: March 2003

The objective of this systematic review was to summarize the best available evidence on the factors that increase the risk of patients falling during hospitalization. Studies included in the review were those that involved adult patients in hospital, that attempted to identify risk factors for falling, and used a cohort or case‐control research design. The search strategy covered all major databases and including MEDLINE, CINAHL, Current Contents, Psyclit, Embase and the Cochrane Library. Results were summarized by a narrative discussion, identifying risk factors that were commonly identified in a range of practice settings. Eighteen papers met the review inclusion criteria and are reported in this paper. Factors associated with an increased risk of falling include impaired mental status, special toileting needs, impaired mobility, and a history of falling. While findings are contradictory, it appears that both medications and advanced age will also influence a patient's risk of falling.
Approaches used to implement research findings into nursing practice: Report of a study tour to Australia and New Zealand
Authors: Kitson Alison L
Published: March 2003

The focus of the study tour to several research and nursing units in Australia and New Zealand (NZ) was to investigate what has influenced the way nurses implement research into practice. The key areas examined were strategic policy influences, activities within leading academic units and responses in practice areas. The main themes to emerge were that the strategies developed by health policy makers in Australia and New Zealand have been profoundly influenced by the global clinical effectiveness and evidence‐based practice movements. Nursing needs to position itself firmly in the centre of such developments and leading nursing initiatives need to be mainstreamed into the wider evidence‐based movement. While activity around clinical/practice guideline development moves on, more work needs to be done to understand how best to actually implement research in practice. Issues of organizational context, ownership, practice, culture and identifying local champions are emerging as key challenges for the next stage of implementation. Much can be learnt from ongoing dialogue.
Influence of self‐efficacy and other factors on dietary behaviours in Japanese haemodialysis patients
Authors: Oka Michiyo , Chaboyer Wendy
Published: March 2003

In Japan, haemodialysis patients are required to adhere to a fairly rigid dietary regimen. Guided by Bandura’s theory of self‐efficacy, this study tested a prediction model of dietary behaviour. A total of 325 individuals completed a self‐administered survey containing nine scales, which were used to measure the six constructs in the model. Using multiple regression analysis, 24% of the variance on the Dietary Behaviour Scale could be accounted for by three predictor scales, Dietary Management Self‐efficacy, Support from Family, and Self‐Repressive Behaviour Patterns. Multiple regression analysis identified that four scales, Character Image of Dialysis Staff, Support from Family, Dialysis Acceptance, and Somatic Symptoms, contributed to 13% of the variance of the Dietary Management Self‐efficacy Scale. These results might provide direction to those who are involved in the support and care of haemodialysis patients, some of whom require life‐long treatment, as is common in Japan.
Rb–Sr isochron ages of the Cretaceous granitoids in the Ryoke belt, Kinki district, Southwest Japan
Authors: Morioka Kozaburo , Tainosho Yoshiaki , Kagami Hiroo
Published: March 2003

Abstract Granitoids are widely distributed in the Ryoke belt and have been divided into four main igneous stages based on their field setting. In this paper, we present Rb–Sr isochron ages for the younger Ryoke granitoids (second stage to fourth stage) in the Kinki district. The Yagyu granite (second stage) gave a Rb–Sr whole‐rock isochron age of 74.6 ± 10.9 Ma with an initial 87Sr/86Sr ratio of 0.70938 ± 0.00016, and a Rb–Sr mineral isochron age of 71.8 ± 0.1 Ma. The Narukawa granite (second stage) yielded a Rb–Sr mineral isochron age of 79.5 ± 0.4 Ma. A Rb–Sr whole‐rock isochron age of 78.3 ± 3.0 Ma with an initial 87Sr/86Sr ratio of 0.70764 ± 0.00014 was obtained for the Takijiri adamellite (third stage). The Katsuragi quartzdiorite (fourth stage) gave a Rb–Sr whole‐rock isochron age of 85.1 ± 18.3 Ma (initial 87Sr/86Sr ratio of 0.70728 ± 0.00006), and mineral isochron ages of 76.9 ± 0.5 Ma and 74.8 ± 0.5 Ma. The Minamikawachi granite (fourth stage) gave a Rb–Sr whole‐rock isochron age of 72.8 ± 2.0 Ma with an initial 87Sr/86Sr ratio of 0.70891 ± 0.00021. These age data indicate that the igneous activity in younger Ryoke granitoids of Kinki district occurred between 80 and 70 Ma, except for the Katsuragi quartz diorite. The isotopic data on the various igneous stages in Kinki district correspond with the relative timing from field observations. Based on the initial 87Sr/86Sr ratios, the granitoids of the Ryoke belt in Kinki district are spatially divided into two groups. One is granitoids with initial 87Sr/86Sr ratio of 0.707–0.708, distributed in the southern part of the Ryoke belt. The other is granitoids with initial 87Sr/86Sr ratio of 0.708–0.710 distributed in the northern part of the Ryoke belt. The initial 87Sr/86Sr ratios of granitoids increase with decreasing (becoming younger) Rb–Sr whole‐rock isochron ages.
Predictive factors for success of neo‐adjuvant therapy in upper gastrointestinal cancer
Authors: WALSH THOMAS N , GRANNELL MARK , MANSOOR SHABAZ
Published: March 2003

Background:

Predicting response to treatment has long been the Holy Grail of clinicians treating patients with upper gastrointestinal malignancy. The widespread use of neoadjuvant therapy for esophageal cancer has provided an added urgency to the issue and at the same time brought success a step closer because accurate response can be determined from analysis of the resected specimen.

Methods:

A search was undertaken of the Medline database for text references to neoadjuvant therapy, esophagus, stomach and predicting response. The references of these publications were further scanned for appropriate references in the text and reference lists.

Results:

Publications describing predictive markers to neoadjuvant therapy for esophageal cancer, which were most likely to be of clinical significance, were selected for inclusion in this report.

Conclusions:

The most reliable tissue markers of response based on analysis of pretreatment biopsy specimens include P53, Ki‐67, EGFR and the most impressive serum marker for monitoring response are CYFRA 21–1 and CEA. The results, however, are inconsistent, and the markers of relatively low sensitivity and none reliably identifies individual patients who will respond.
Surgery for hepatocellular carcinoma
Authors: TAN KC
Published: March 2003

Abstract  Today there is an array of therapeutic modalities available for the patients with hepatocellular carcinoma (HCC). However, surgery, be it resection or transplantation, offers the only hope of long‐term disease‐free survival. Unfortunately, because the majority of HCC in Asia is associated with cirrhosis, surgical resection is restricted to only a small proportion of these patients. However, in selected candidates resection may offer a 5‐year survival of up to 70%. With the clinical application of adult‐to‐adult living donor liver transplantation, an increasing number of patients with small HCC and decompensating cirrhosis are undergoing transplantation.

© 2002 Blackwell Publishing Asia Pty Ltd
Prevention of human hepatocellular carcinoma with natural lymphoblastoid alpha interferon
Authors: OON CHONG JIN
Published: March 2003

Abstract  Hepatitis B surface antigen (HBsAg) positive hepatocellular carcinoma (HCC) patients have a high risk of recurrence within 5 years of hepatic resection and suitable long‐term maintenance therapy is required. An open‐ended controlled trial on 30 HBsAg positive Child Pugh's grade A cirrhotic patients was started in September 1986 using Wellferon (natural lymphoblastoid alpha interferon). Ten patients had standard adriamycin and mitomycin C monthly for 6 months, then discontinued when the course was completed. Twenty other patients had this regime, plus the addition of Wellferon given at 3 MU i.m. daily for 10 days. No HCC recurrence was observed in the interferon group. Followed to 14 years, 11 of the interferon‐treated patients are still well and HCC free, whereas none of the chemotherapy patients are alive. High incidence of recurrence occurred in those who discontinued interferon (IFN), reduced the dose, or took the scheduled dose, but at longer intervals of more than 3 months. Wellferon, a natural α‐IFN has potent inhibitory effects and reduces the risk of HCC development. It is a suitable agent for long‐term maintenance prophylactic therapy for high‐risk resected HBsAg positive HCC patients.

© 2002 Blackwell Publishing Asia Pty Ltd
Sodium butyrate induces alkaline phosphatase gene expression in human hepatoma cells
Authors: Khan Khaleque , Tsutsumi Takuya , Nakata Keisuke , Kato Yuji
Published: March 2003

Background and Aims: Butyrate, a natural product of colonic bacterial flora, has been reported to increase the activities of a number of enzymes, including alkaline phosphatase, (ALP) in several cancer cell lines. However, butyrate‐induced ALP gene expression in human hepatoma cells has not been previously demonstrated. In the present study, the effects of sodium butyrate on cell growth and proliferation, cellular activity and expression of ALP gene in human hepatoblastoma‐derived HepG2 cells were investigated.

Methods: The HepG2 cells were treated with sodium butyrate (0–1 mmol/L) and the number of viable cells were counted at 24, 48 and 72 h after treatment. A [3H]‐thymidine incorporation study was performed at different concentrations of sodium butyrate for 48 h. The cellular activity of ALP in HepG2 cells by sodium butyrate was measured by a substrate‐specific enzymatic assay. To elucidate the effects of sodium butyrate on ALP gene expression, a northern blotting experiment employing hybridization with mouse placental ALP cDNA was performed.

Results: Cell growth and proliferation were dose‐dependently inhibited by sodium butyrate. Cellular ALP activity was significantly increased in HepG2 cells in a time‐ and dose‐dependent fashion by treatment with sodium butyrate and a maximum activity was observed at 48 h. These effects were reversible when sodium butyrate was removed from the culture medium. By northern blot analysis, the level of ALP messenger RNA was dose‐dependently elevated by sodium butyrate.

Conclusion: Butyrate, at a concentration relevant to the normal physiology of the liver, causes augmented expression of ALP mRNA in HepG2 cells. We assume that increased ALP synthesis in HepG2 cells by sodium butyrate results from an enhanced rate of transcription rather than translation of mRNA.