bluuebunny/crossref_metadata_2025 huggingface dataset:
Softening Competition by Inducing Switching in Credit Markets
Authors: Bouckaert Jan , Degryse Hans
Published: March 2004

We show that competing banks relax overall competition by inducing borrowers to switch lenders. We illustrate our findings in a two‐period model with adverse selection where banks strategically commit to disclosing borrower information. By doing this, they invite rivals to poach their first‐period market. Disclosure of borrower information increases the rival's second‐period profits. This dampens competition for serving the first‐period market.
Optimal Regulation of Cooperative R&D Under Incomplete Information
Authors: Brocas Isabelle
Published: March 2004

A regulator offers a cooperation contract to two firms to develop a research project. The contract provides incentives to encourage skill‐sharing and coordinate subsequent efforts. Innovators must get informational rents to disclose their privately known skills, which results in distorting R&D efforts with respect to the first‐best level. When efforts are strategic complements, both efforts are distorted downwards. By contrast, when efforts are strategic substitutes, the effort of the firm with most valuable skills is distorted downwards (to decrease rents) and the effort of the other firm is distorted upwards (to compensate the previous efficiency loss).
Market Power and Joint Dominance in U.K. Brewing
Authors: Slade Margaret E.
Published: March 2004

Market power and joint dominance are examined in U.K. brewing. I assess unilateral and coordinated effects, where the latter is equated with joint dominance, and show how one can distinguish between the two econometrically. The application makes use of two demand equations: the nested logit of McFadden [1978a] and the distance‐metric of Pinkse, Slade, and Brett [2002]. The two equations yield very different predictions concerning elasticities and markups. Nevertheless, although there is evidence of market power using either demand model, that power is due entirely to unilateral effects. In other words, neither model uncovers evidence of coordinated effects (tacit collusion).
CD40 is Necessary for Activation of Naïve T Cells by a Dendritic Cell Line In Vivo but not In Vitro
Authors: Haase C. , Michelsen B. K. , Jørgensen T. N.
Published: March 2004

The importance of CD40–CD40L interactions during CD4+ T‐cell activation has been extensively investigated over the years; however, it still remains questionable whether the interaction is a prerequisite for dendritic cell (DC)‐mediated antigen‐specific priming in vivo. Naïve CD4+ T cells require two signals for proper activation and induction of differentiation: signal 1 is provided by peptide antigens in the context of the major histocompatibility complex (MHC) class II, while signal 2 is delivered by costimulatory molecules such as CD80 or CD86 present on the antigen‐presenting cell (APC). It is well known that the expression of CD80/CD86 is upregulated after interaction between CD40 on APCs and CD40L expressed by at least partly activated T cells. We used a DC line, JawsII, to compare the importance of CD40 expression and downstream signalling in vitro and in vivo. JawsII cells represent pre‐immature bone marrow‐derived DCs expressing low levels of MHC molecules, low levels of B7 molecules and no CD40. We have previously shown that JawsII cells, despite the lack of CD40 expression, are capable of priming naïve allogeneic T cells in vitro. In correlation with the current literature, we present data showing that constitutive expression of CD40 significantly increases the priming capacity of JawsII cells in vitro. In addition, we show that CD40 expression is required for JawsII cell‐dependent T‐cell priming in vivo.
A Recombinant Vaccinia Virus Encoding the Interferon‐Inducible T‐Cell Alpha Chemoattractant is Attenuated In Vivo
Authors: Hamilton N. H. R. , Mahalingam S. , Banyer J. L. , Ramshaw I. A. , Thomson S. A.
Published: March 2004

Murine interferon‐inducible T‐cell alpha chemoattractant (I‐TAC) is a potent non‐ELR CXC chemokine that predominantly attracts activated T lymphocytes, binds to the receptor CXCR3 and is induced by interferon‐γ (IFN‐γ). We analysed I‐TAC expression by reverse transcriptase‐polymerase chain reaction during three different virus‐infection models in mice, respiratory syncytial virus (RSV), influenza A and vaccinia virus western reserve (VV‐WR). In the lungs from mice infected with RSV or influenza A viruses, peak expression of I‐TAC coincided with peak viraemia. Surprisingly, there was no expression in the lungs of mice infected with vaccinia, unlike the elevated expression shown previously for other interferon‐regulated chemokines, such as Crg2 and Mig. To further investigate the importance of this difference during vaccinia infection in mice, a recombinant virus encoding I‐TAC (rVV I‐TAC) was generated. Studies in C57BL/6 and Swiss nude mice showed that I‐TAC expression caused increased mononuclear cell infiltration and significantly attenuated the VV. Infection of the footpads of naïve or already immune (with VV‐WR) mice with either rVV I‐TAC or VV‐WR demonstrated that I‐TAC expression reduced overall inflammation during infection and that this reduction was more pronounced in already immune mice. The data presented here show that I‐TAC can have an important role during virus infections and that vaccinia has evolved ways to avoid inducing I‐TAC expression.
Regulation of Mast Cell Migration by TH1 and TH2 Cytokines: Identification of Tumour Necrosis Factor‐α and Interleukin‐4 as Mast Cell Chemotaxins
Authors: Olsson N. , Taub D. D. , Nilsson G.
Published: March 2004

Mast cells act as central effector and regulatory cells in many inflammatory disorders, including T helper 1 (TH1)‐mediated inflammations such as autoimmunity and TH2‐mediated inflammations such as allergy and parasite infections. One characteristic for mast cell‐mediated inflammations is the accumulation of mast cells in the inflamed tissue. The factors regulating mast cell recruitment in these inflammations are still not fully characterized. We have investigated the potency of TH1‐ and TH2‐secreted cytokines to mediate mast cell migration. Supernatants from six different TH1 and TH2 clones were tested for mast cell‐chemotactic activity using the human mast cell line (HMC‐1) as a responder cell. All six clones produced factors that induced mast cell migration. Using blocking antibodies to a broad range of cytokines, we found that anti‐tumour necrosis factor‐α (anti‐TNF‐α) reduced the migration of mast cells to supernatants from TH1 clones. In contrast, the main mast cell chemoattractants secreted by TH2 clones were found to be interleukin‐4 (IL‐4) and IL‐8. The potency of these cytokines to act as mast cell chemoattractants was confirmed by using recombinant IL‐4, IL‐8 and TNF‐α. Our results suggest that TNF‐α can be involved in the recruitment of mast cells in TH1‐mediated inflammations, whereas IL‐4 and IL‐8 might play a similar role in TH2‐mediated inflammations.
Antibodies to GAD65 Epitopes at Diagnosis and Over the First 10 years of Clinical Type 1 Diabetes Mellitus
Authors: Ronkainen M. S. , Savola K. , Knip M.
Published: March 2004

Antibodies to glutamate decarboxylase (GAD65Ab) may persist, and their titres even increase after the clinical onset of type 1 diabetes. To characterize this phenomenon in detail, we analysed sequentially antibodies to GAD65 epitope clusters in a radio‐binding assay in patients with type 1 diabetes. Serum samples were taken at diagnosis and 2, 5 and 10 years later from 50 young patients who had tested positive for GAD65Ab at least once during observation. The levels of GAD65Ab peaked in 21 patients after diagnosis. Antibodies to the middle region of GAD65 (GAD65‐M‐Ab, 88%) were more common at diagnosis than antibodies to the C‐terminal (GAD65‐C‐Ab, 68%, P < 0.05) or N‐terminal region (4%, P < 0.001). Antibodies to middle and especially to C‐terminal epitopes decreased in those with decreasing levels of GAD65Ab (P < 0.001), whereas the frequencies of GAD65‐M‐Ab and GAD65‐C‐Ab remained quite stable among the subjects with increasing levels. Lower exogenous insulin dose and HbA1 levels and stronger humoral immune response to islet cells were observed in those with increasing levels of GAD65‐M‐Ab than in those with decreasing levels (P < 0.05). The present observation supports the view that the middle region of GAD65 comprises immunodominant epitopes. An enhanced humoral immune response to GAD65 after diagnosis is related to persistent immune reactivity to the middle and C‐terminal regions.
Severe Hypercholesterolaemia Leads to Strong Th2 Responses to an Exogenous Antigen
Authors: Robertson A.‐K. L. , Zhou X. , Strandvik B. , Hansson G. K.
Published: March 2004

Severe hypercholesterolaemia is associated with decreased levels of immunoglobulin G2a (IgG2a) antibodies [T‐helper 1 (Th1) response] to modified malondialdehyde‐modified low‐density lipoprotein (MDA‐LDL) and increased levels of Th2‐dependent IgG1 antibodies in apolipoprotein E‐deficient (apoE–/–) mice. To investigate whether this reflects a general pattern of metabolic regulation of the humoral immune response, apoE–/– mice were fed diets resulting in different degrees of hypercholesterolaemia and immunized with keyhole limpet haemocyanin (KLH) in aluminium hydroxide. Cholesterol levels for different treatment groups ranged from 14 to 77 mmol/l in serum and from 10 to 39 mmol/g in liver. Mice with severe hypercholesterolaemia had increased IgG1 antibodies to MDA‐LDL and decreased IgG2a anti‐MDA‐LDL. Importantly, titres of IgG2a antibodies to KLH were also decreased, while IgE anti‐KLH was increased, with a corresponding induction of interleukin‐4 (IL‐4) and IL‐10 and a decrease in interferon‐γ (IFN‐γ) in KLH‐stimulated spleen cells in vitro. Thus, hypercholesterolaemia clearly affects antibody production both to the autoantigen MDA‐LDL and to the exogenous antigen KLH, favouring antibody isotypes (IgG1 and IgE) that are dependent on Th2 help to B cells. Nuclear receptors ligated by oxidized lipid derivatives modulate T‐cell responses, and it is speculated that this mechanism may cause the switch to Th2 in severe hypercholesterolaemia.
The limitations of using statutory child protection data for research into child maltreatment
Authors: Bromfield Leah M , Higgins Daryl J
Published: March 2004

Child protection legislation has undergone a number of changes since its inception, changes that have redefined the population of children in need of protection. However, child protection data on notifications and substantiations remain the most common source of data for statistics on the rate of maltreatment and the breakdown of specific maltreatment types. In the present study, three factors are identified that have compromised the accuracy of child protection data reporting the incidence of child abuse and neglect: (i) the legislative changes that mandate child protection services to protect children from harm rather than from identifiable adult actions; (ii) the shift from the Harm Standard to the Endangerment Standard; and (iii) the assignment of responsibility solely to parents. The examples in this paper are drawn from Australian legislation, however, the legislative changes that have created these issues are evident internationally, rendering child protection data an unreliable and invalid source for statutory or research data on the rates of child maltreatment.
The systematic abrogation of practice standards in foster care
Authors: Gilbertson Robyn , Barber James G
Published: March 2004

Over the past decade, a number of reviews of the alternative care system in South Australia identified various shortcomings in the system. An extensive restructure and outsourcing of alternative care services in the mid 1990s was reported to have done little to rectify the problems. Between 1998 and 2001 the statutory agency, Family and Youth Services, conducted three internal surveys to measure social workers' compliance with a range of practice standards for children and young people in foster care. The authors of this paper obtained the survey reports and, using data extracted from the reports, constructed a picture of the type of social work service provided to children and young people in care. Where variables were directly comparable, the authors conducted secondary data analysis to identify changes in compliance on a number of practice standards over time. It was found that many young people under state protection may not be receiving adequate levels of care. Of particular concern was the high number of cases in which statutory obligations with respect to health, case review and involvement of young people in decision‐making were not being met.
Powerful partnerships in social work: group work with parents of children in care
Authors: Thomson Jane , Thorpe Ros
Published: March 2004

In this paper we describe and promote a model of group work with parents of children in care in operation in Townsville, a regional city in northern Australia, since 1989. We begin from the premise that parents have frequently been ‘left out of the loop’ as key players in child protection. This is despite the fact that it is parents' ability to afford protection that is at issue. The paper proceeds to discuss what is meant by empowerment in the context of a social work group work approach with parents. A model of group work is then presented. The paper concludes with discussion of the implications that this approach has for social work in child protection practice.
Mother blaming: a covert practice in therapeutic intervention
Authors: Allan Julaine
Published: March 2004

In this article I will discuss the continuing discursive support for idealised motherhood, describe some ways mother blaming is practiced within therapeutic intervention and discuss the implications of this for social work practice. The article is based on a qualitative study of professionals who provide therapeutic intervention for sexually violent children and their families. The case examples discussed come from this study and describe the roles attributed to mothers in causing and maintaining their children's sexual violence.
Exposure to continuous bromodeoxyuridine (BrdU) differentially affects cell cycle progression of human breast and bladder cancer cell lines
Authors: Diermeier S. , Schmidt‐Bruecken E. , Kubbies M. , Kunz‐Schughart L. A. , Brockhoff G.
Published: March 2004

Abstract.   Incorporation of bromodeoxyuridine (BrdU) during DNA replication is frequently used for cell cycle analysis. The flow cytometric BrdU/Hoechst quenching technique is conducive to high‐resolution assessment of cell cycle kinetics, but requires continuous BrdU treatment, which may have cytostatic or cytotoxic effects. Here, we have examined the impact of BrdU on the proliferation of BT474 and SK‐BR‐3 breast cancer cell lines and compared the observed effects with cell proliferation of RT4 and J82 bladder carcinoma cells, previously described to be sensitive and insensitive to BrdU, respectively. Both uni‐ and bi‐parametric DNA measurements were performed to identify BrdU‐induced alterations in the S‐phase fraction and in cell cycle progression. An annexinV/propidium iodide (PI) assay was used to identify potential induction of apoptosis by BrdU. Proliferative activity in BT474, SK‐BR‐3, and RT4 cultures was reduced in different cell cycle phases due to continuous treatment with 60, 5.0, and 3.5 µm BrdU. This effect, which was not found in J82 cultures, was dependent on exposure time (96 versus 48 h) and was also dose‐dependent for RT4 and SK‐BR‐3. BrdU application does not induce apoptosis or necrosis as revealed with the annexin V/PI assay. We concluded that continuous BrdU treatment did not affect cell viability, but essentially alters cell cycle progression in three out of four cell lines tested. Cell‐type specific validation of the feasibility of the powerful BrdU/Hoechst quenching technique is required and recommended.
Cell cycle‐related variation in subcellular localization of eIF3e/INT6 in human fibroblasts
Authors: Watkins S. J. , Norbury C. J.
Published: March 2004

Abstract.  The Int‐6 gene is a site of mouse mammary tumour virus (MMTV) integration in murine tumours and INT6 protein has been identified independently as a subunit (eIF3e) of the eukaryotic translation initiation factor eIF3. In addition, the protein can interact with two other multi‐subunit complexes: the COP9 signalosome (CSN) and the proteasome. The role of INT6 in tumourigenesis is nonetheless currently unclear. Here, using immunofluorescence microscopy, we show that eIF3e/INT6 is localized in part to the nucleus, while other eIF3 components are cytoplasmic. Primary human fibroblasts, but not their transformed counterparts, showed reduced nuclear INT6 staining in some cells, and this reduction was maximal in early S phase. This variation in eIF3e/INT6 may indicate regulated shuttling between cellular compartments and would be consistent with the presence of a nuclear export signal as well as a nuclear localization signal in the protein sequence. Loss of regulation of eIF3e/INT6 redistribution may therefore be a significant feature of malignancy in human cells.
Blocking lymphotoxin-βreceptor activation diminishes inflammation via reduced mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression and leucocyte margination in chronic DSS-induced colitis
Authors: Stopfer P , Obermeier F , Dunger N , Falk W , Farkas S , Janotta M , Möller A , Männel D N , Hehlgans T
Published: March 2004

The lymphotoxin-β receptor (LTβR) pathway is critical for maintenance of organized lymphoid structures and is involved in the development of colitis. To investigate the mechanisms by which LTβR activation contributes to the pathology of chronic inflammation we used a soluble LTβR-Ig fusion protein as a competitive inhibitor of LTβR activation in the mouse model of chronic colitis induced by oral administration of dextran sulphate sodium. Strong expression of LTβ which constitutes part of the LTα1β2 ligand complex was detected in colonic tissue of mice with chronic colitis. Treatment with LTβR-Ig significantly attenuated the development and histological manifestations of the chronic inflammation and reduced the production of inflammatory cytokines such as TNF, IL-1β, and IL-6. Moreover, LTβR-Ig treatment significantly down-regulated mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression, leading to reduced leucocyte rolling and sticking in postcapillary and collecting venules and reduced extravasation into the intestinal mucosa as quantified by in vivo fluorescence microscopy. Thus, LTβR pathway inhibition ameliorates DSS-induced experimental chronic colitis in mice by MAdCAM-1 down-regulation entailing reduced lymphocyte margination and extravasation into the inflamed mucosa. Therefore, a combined treatment with reagents blocking T cell-mediated perpetuation of chronic inflammation such as LTβR-Ig together with direct anti-inflammatory reagents such as TNF inhibitors could constitute a promising treatment strategy for chronic colitis.
Maternal immunity to insulin does not affect diabetes risk in progeny of non obese diabetic mice
Authors: KOCZWARA K , ZIEGLER A-G , BONIFACIO E
Published: March 2004

It has been suggested that maternal environment, in particular maternal autoantibodies, modify the risk of developing autoimmune diabetes in offspring. The aim of this study was to determine whether modification of maternal environment and maternal diabetes risk through immunization affects autoimmune diabetes risk in the progeny. The risk of developing insulin antibodies and of developing diabetes was determined in 113 female progeny of non obese diabetic (NOD) dams that were immunized with insulin, control antigen or vehicle before or during pregnancy. Although NOD dams immunized with insulin were rendered diabetes resistant (40% diabetes by age 36 weeks versus 100% in control dams), diabetes development in their female offspring (72%, 26/36) was similar to that in female offspring of dams immunized with glucagon (82%, 22/27) or vehicle (76%, 19/25). Furthermore, no significant differences in diabetes development or insulin autoantibody titres were observed between female progeny of insulin autoantibody positive NOD dams (82% diabetes by age 36 weeks, 18/22), insulin autoantibody negative NOD dams (75%, 41/55), and NOD dams that had antibodies against exogneous insulin (71%, 22/31). The findings suggest that modification of the maternal risk for autoimmune diabetes via antigen-specific immunization is not transferred to progeny and that fetal exposure to insulin autoantibodies does not increase the risk for diabetes development.
Binding capacity and pathophysiological effects of IgA1 from patients with IgA nephropathy on human glomerular mesangial cells
Authors: Wang Y , Zhao M-H , Zhang Y-K , Li X-M , Wang H-Y
Published: March 2004

IgA deposition in glomerular mesangium and the interaction with mesangial cells may well be the final common pathway to IgA nephropathy (IgAN). Altered hinge-region O-glycosylation of IgA1 from patients with IgAN may predispose to mesangial deposition and activation of the mesangial cell (MC) by IgA1, via a novel IgA1 receptor, and may be a key event in the pathogensis of IgAN. The aim of this study was to investigate the binding capacity and biological effects of IgA1, from both patients with IgAN and healthy controls, on human mesangial cells (HMC). Serum IgA1 was isolated with jacalin affinity chromatography, heated to aggregated form (aIgA1) and labelled with 125I. Binding capacity of aIgA1 in vitro to cultured primary HMC was evaluated by a radioligand binding assay and the specificity of binding was determined by a competitive inhibition assay. Intracellular calcium release was studied by confocal analysis and phosphorylation of extracellular signal-regulated kinase (ERK) was determined by Western blot analysis. Change of cell cycles was demonstrated by flow cytometry and HMC proliferation was evaluated by direct cell count. Expression of TGF-β mRNA and production of supernatant fibronectin were tested by RT-PCR and indirect competitive ELISA, respectively. aIgA1 from both the patients with IgAN and normal controls bound to HMC in a dose-dependent, saturable manner, and was saturated at approximately 500 pmoles per 0·5 ml of aIgA1. aIgA1 from patients with IgAN, however, bound to HMC at a higher speed and Scatchard analysis revealed a Kd of (8·89 ± 2·1) × 10−8mversus (4·3 ± 1·2) × 10−7m for aIgA1 from healthy controls (P = 0·026). The binding was specific because it was only inhibited by unlabelled Mono-IgA1 (mIgA1) and not by serum albumin or IgG. aIgA1 from patients with IgAN could induce release of intracellular calcium, phosphorylation of ERK, DNA synthesis, proliferation of HMC, expression of TGF-βmRNA and secretion of fibronectin in HMC in a similar time-dependent manner as aIgA1 from healthy controls, but the effects were much stronger and the durations were much longer (P < 0·05, respectively). We conclude that aIgA1 from patients with IgAN has a higher binding capacity to HMC and stronger biological effects than aIgA1 from healthy controls. This suggests that direct interaction between IgA1 and HMC and subsequential pathophysiological responses may play an important role in the pathogenesis for IgAN.
Increased risk of adverse events when changing intravenous immunoglobulin preparations
Authors: AMERATUNGA R , SINCLAIR J , KOLBE J
Published: March 2004

Intravenous immunoglobulin (IVIG) therapy has represented a major advance in the treatment of patients with primary immune deficiency disorders. In September 2000 a new IVIG formulation, Intragam P, was introduced into clinical use. Intragam P is prepared by delipidation of pooled plasma followed by an ion exchange chromatography step to eliminate immunoglobulin aggregates. It is then pasteurized for 10 h at 60°C for viral inactivation before storage at pH 4·25 in 10% maltose. We report initial clinical experience with this new preparation. The details of adverse reactions of patients who received the new preparation were gathered shortly after it became apparent there was a change in IVIG formulation. Seven of 49 patients receiving Intragam P spontaneously reported adverse effects, which were temporally related to infusions. Subsequently, all seven patients have been able to tolerate the product with prophylactic use of antihistamines and paracetamol. This case series indicates that long-term tolerance of an older IVIG product does not necessarily equate to tolerance to a newer product, even if technically superior. Caution should be exercised when changing IVIG products, as they are not biologically equivalent.
Serum granulysin is a marker for Th1 type immunity in pre-eclampsia
Authors: Sakai M , Ogawa K , Shiozaki A , Yoneda S , Sasaki Y , Nagata K , Saito S
Published: March 2004

Recent studies suggest that pre-eclampsia is associated with a Th1 predominant state and may be considered a failure of tolerance. Granulysin is a cytotoxic granule protein of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Recently, we developed an enzyme-linked immunosorbent assay (ELISA) system for detecting serum granulysin, and reported that serum granulysin is a useful marker to evaluate the cell-mediated immunity. In this study, we show that the serum levels of granulysin were significantly elevated in pre-eclamptic patients compared with those in normal pregnancy subjects. In addition, the serum granulysin levels in pre-eclamptic patients were well associated with mean blood pressure, percentage of peripheral blood Th1 cells and Th1/Th2 ratios. The present results suggest that the serum granulysin levels would be a useful and novel serum marker to evaluate the Th1/Th2 balance, especially Th1 type immunity in pre-eclampsia.
Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome
Authors: WONG C K , LAM C W K , WU A K L , IP W K , LEE N L S , CHAN I H S , LIT L C W , HUI D S C , CHAN M H M , CHUNG S S C , SUNG J J Y
Published: March 2004

Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel coronavirus, but its immunopathological mechanisms have not yet been fully elucidated. We investigated changes in plasma T helper (Th) cell cytokines, inflammatory cytokines and chemokines in 20 patients diagnosed with SARS. Cytokine profile of SARS patients showed marked elevation of Th1 cytokine interferon (IFN)-γ, inflammatory cytokines interleukin (IL)-1, IL-6 and IL-12 for at least 2 weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumour necrosis factor (TNF)-α, anti-inflammatory cytokine IL-10, Th1 cytokine IL-2 and Th2 cytokine IL-4. The chemokine profile demonstrated significant elevation of neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-γ-inducible protein-10 (IP-10). Corticosteroid reduced significantly IL-8, MCP-1 and IP-10 concentrations from 5 to 8 days after treatment (all P < 0·001). Together, the elevation of Th1 cytokine IFN-γ, inflammatory cytokines IL-1, IL-6 and IL-12 and chemokines IL-8, MCP-1 and IP-10 confirmed the activation of Th1 cell-mediated immunity and hyperinnate inflammatory response in SARS through the accumulation of monocytes/macrophages and neutrophils.
GAD65 antibody isotypes and epitope recognition during the prediabetic process in siblings of children with type I diabetes
Authors:   THE CHILDHOOD DIABETES IN FINLAND STUDY GROUP, HOPPU S , RONKAINEN M S , KULMALA P , ÅKerblom H K , KNIP M
Published: March 2004

We observed 42 initially non-diabetic siblings of affected children to characterize the humoral immune response to the 65 kDa isoform of glutamic acid decarboxylase (GAD65) in preclinical type I diabetes. During the observation period with a mean duration of 9·6 years 21 siblings progressed to type I diabetes. The humoral immune response to GAD65 was observed initially as a simultaneous response to the middle (M) and carboxy (C)-terminal regions of the GAD65 molecule in most cases, and if the response was restricted initially to the middle region, it spread rapidly to the C-terminal domain and in a few cases later to the amino (N)-terminal domain. There was some heterogeneity in the GAD65 isotype response, but it was composed mainly of antibodies of immunoglobulin (Ig) G1 subclass. Responses of IgG2-, IgG4-, IgM- and IgA-GAD65Ab were observed frequently, whereas IgE- and IgG3-GAD65Ab responses were seen more rarely. Initially, the non-progressors tended more often to have IgG2- and IgG4-GAD65Ab than the progressors. As a sign of a dynamic process a significant isotype spreading was seen for IgG2-GAD65Ab (P < 0·05) and close to significant for IgM (P = 0·06) among progressors and for IgM-GAD65Ab (P < 0·05) among non-progressors during the observation period. This study failed to identify any GAD65 epitope- or isotype-specific antibody reactivity that could be used as a marker for progression to disease, as such progression was not associated with any specific changes in reactivity over time. Our findings indicate that epitope- and isotype-specific GAD65 antibodies are hardly capable of separating progressors from non-progressors among GAD65Ab-positive first-degree relatives of children with type I diabetes.
Interleukin-6 production and secretion by human parathyroids
Authors: SAFLEY S A , VILLINGER F , JACKSON E H , TUCKER-BURDEN C , COHEN C , WEBER C J
Published: March 2004

Parathyroid hormone (PTH) stimulates osteoblasts to produce the proinflammatory cytokine interleukin-6 (IL-6), causing bone resorption. In patients with primary hyperparathyroidism, elevated serum levels of IL-6 normalize after resection of parathyroid tumours. Because IL-6 is also expressed in normal parathyroids and in other endocrine cells (adrenal and islet), we hypothesized that parathyroid tumours might contribute directly to the elevated serum IL-6 levels in patients with hyperparathyroidism. Immunohistochemistry identified IL-6, PTH, and chromogranin-A (an endocrine and neuroendocrine tumour marker) in normal, adenomatous and hyperplastic parathyroids. Using immunofluorescence and confocal microscopy, IL-6 co-localized with PTH and with chromogranin-A in parathyroid cells. All cultured parathyroid tumours secreted IL-6 at levels markedly higher than optimally stimulated peripheral blood mononuclear cells. Supernates from cultured parathyroids stimulated proliferation of an IL-6-dependent cell line, and anti-IL-6 MoAb abolished this stimulatory effect. IL-6 mRNA was documented in cultured parathyroid tumours, cultured normal parathyroids, fresh operative parathyroid tumours and fresh operative normal specimens. In conclusion, these data show that parathyroid tumours and normal parathyroids contain, produce and secrete IL-6. Our findings present a novel pathway by which human parathyroids may contribute markedly to IL-6 production and elevation of serum IL-6 levels in patients with hyperparathyroidism. The physiological relevance of IL-6 production by human parathyroids remains to be determined, but IL-6 secretion by parathyroid tumours may contribute to bone loss and to other multi-system complaints observed in these patients.
Cathepsin D is up-regulated in inflammatory bowel disease macrophages
Authors: HAUSMANN M , OBERMEIER F , SCHREITER K , SPOTTL T , FALK W , SCHÖLMERICH J , HERFARTH H , SAFTIG P , ROGLER G
Published: March 2004

Down-regulation of receptors involved in the recognition or transmission of inflammatory signals and a reduced responsiveness support the concept that macrophages are ‘desensitized’ during their differentiation in the intestinal mucosa. During inflammatory bowel disease (IBD) intestinal macrophages (IMACs) change to a reactive or ‘aggressive’ type. After having established a method of isolation and purification of IMACs, message for cathepsin D was one of the mRNAs we found to be up-regulated in a subtractive hybridization of Crohn's disease (CD) macrophages versus IMACs from control mucosa. The expression of cathepsin D in intestinal mucosa was analysed by immunohistochemistry in biopsies from IBD and control patients and in a mouse model of dextran sulphate sodium (DSS)-induced acute and chronic colitis. IMACs were isolated and purified from normal and inflamed mucosa by immunomagnetic beads armed with a CD33 antibody. RT-PCR was performed for cathepsin D mRNA. Results were confirmed by Northern blot and flow cytometrical analysis. Immunohistochemistry revealed a significant increase in the cathepsin D protein expression in inflamed intestinal mucosa from IBD patients compared to non-inflamed mucosa. No cathepsin D polymerase chain reaction (PCR) product could be obtained with mRNA from CD33-positive IMACs from normal mucosa. Reverse transcription (RT)-PCR showed an induction of mRNA for cathepsin D in purified IMACs from IBD patients. Northern blot and flow cytometry analysis confirmed these results. Cathepsin D protein was also found in intestinal mucosa in acute and chronic DSS-colitis but was absent in normal mucosa. This study shows that expression of cathepsin D is induced in inflammation-associated IMACs. The presence of cathepsin D might contribute to the mucosal damage in IBD.
Patients with comorbidities: perceptions of acute care services
Authors: Williams Allison
Published: March 2004

Background.  Advances in medical science and improved lifestyles have reduced mortality rates in Australia and most Western countries. As a result, there is an ageing population with a concomitant growth in the number of people living with chronic illnesses. Indeed, a significant number of people will experience multiple chronic illnesses (comorbidities) and may require admission to hospital for acute care that is superimposed on their chronic illnesses.

Aim.  The aim of this study was to investigate perceptions of quality of care by patients experiencing comorbidities who required an acute hospital stay.

Method.  A qualitative descriptive design was adopted, informed by Colaizzi's phenomenological method. Single semi‐structured interviews were conducted with 12 patients within 14 days of being discharged home after an acute illness episode.

Findings.  Data analysis revealed three themes: poor continuity of care for comorbidities, the inevitability of something going wrong during acute care and chronic conditions persisting after discharge. Combinations of chronic illnesses and treatments affected these patients’ experiences of acute care and recovery postdischarge. Medicalized conceptualizations of comorbidity failed to capture the underlying health care needs of these patients.

Limitations.  No generalizations can be drawn because the findings and conclusions were derived from a purposive sample of patients who agreed to participate.

Conclusion.  These findings have implications for a comprehensive and co‐ordinated approach to this group of patients, and inform the body of nursing knowledge about how patients with comorbidities experience nursing care.
Socio‐cultural influences on Chinese women's attendance for cervical screening
Authors: Holroyd Eleanor , Twinn Sheila , Adab Peymane
Published: March 2004

Background.  Compared with other countries, Hong Kong has a relatively high rate of cervical cancer. Much of this morbidity should be avoidable with cervical screening, but uptake rates for screening in Hong Kong are low. In programmes to promote cervical screening attendance, it is essential that aspects of the socio‐cultural system be taken into account to provide appropriate preventive health strategies.

Aim.  This paper outlines an investigation of the cultural and social factors contributing to Chinese women's attendance for cervical screening.

Method.  A mixed methods design was employed, combining and comparing two data sets. The initial data set was drawn from 10 focus groups involving both screened and unscreened Chinese women (n = 54). The second data set was drawn from a total population of Hong Kong doctors, and involved face‐to‐face semi‐structured interviews (n = 28).

Results.  Thematic analysis of the data from women indicated that the social factors of cost, educational base, knowledge of risk, the social value of early detection and cultural issues such as modesty and embarrassment contributed to screening attendance. The doctors perceived a cultural tendency towards fatalism, as well as seeing the gender, interpersonal and interprofessional skills of the practitioner to be important in influencing levels of Chinese women's shyness and discomfort, and hence affecting attendance. The lay and practitioner data sets varied in the perceptions of women's pain, embarrassment and risk factors.

Conclusion.  Programmes providing services for Chinese women need to ensure that the philosophy of the staff and the approach and materials used are culturally relevant. Recommendations are that nurses equipped with relevant social and cultural knowledge of population groups should have a central role in health promotion and screening services.
Reported pain after day surgery: a critical literature review
Authors: Coll Anne Marie , Ameen Jamal R.M. , Moseley Laurence G.
Published: March 2004

Background.  Despite technological advancements in anaesthesia and analgesia, reported pain levels after day surgery remains high. Whilst it is unrealistic to expect no pain, the level that constitutes ‘acceptable’ pain remains unclear because of inconsistencies in reporting. These inconsistencies have resulted from different interpretations of what pain is and the use of different measurement tools.

Aim.  The aim of this paper is to report a study investigating any disparity in reported levels of pain following day surgery, within different specialities and in relation to specific operative procedures.

Method.  Nursing and health care papers published since 1983 were sought using the keywords: postoperative pain, postoperative complications, pain after day surgery, day surgery, ambulatory surgery, nursing, operation types, operative procedures, surgical procedures, descriptors of pain, pain intensity, verbal descriptor scale, numerical rating scale, visual analogue scale, validity, reliability, design, sample size, data collection methods and their various combinations. Databases searched were Medline, CINAHL, Nursing Collection, Embase, Healthstar, BMJ and several on‐line Internet journals, specifically Ambulatory Surgery. The search was restricted to publications in the English language.

Findings.  Twenty‐four papers were identified. Inconsistencies in the reported intensity of pain are highlighted, in relation to different operative procedures and specialities. Data in the papers are based on different descriptors, measurement tools and data collection methods. In many cases, sample size, and validity and reliability can also be questioned.

Conclusions.  There is a disparity in reported levels of pain after day surgery. It is important that a unified day surgery pain measurement strategy is established, so that patients can be informed about the intensity of pain that they are likely to experience following specific procedures.
Primary mental health workers in child and adolescent mental health services
Authors: Macdonald Wendy , Bradley Sally , Bower Peter , Kramer Tami , Sibbald Bonnie , Garralda Elena , Harrington Richard
Published: March 2004

Background.  The interface between primary care and specialist services is increasingly seen as crucial in the effective management of child and adolescent mental health (CAMH) problems. In the United Kingdom, a new role of primary mental health worker (PMHW), has been established in order to achieve effective collaboration across the interface through the provision of clinical care in primary care settings and by improving the skills and confidence of primary care staff. However, little is known about the development of this innovative role in service contexts. Issues raised during the early stages of implementation may have important implications for the preparation and development of professionals who undertake the role.

Aims.  The aim of this paper is to report on a study that examined key issues in implementation of the PMHW role in six health authorities in England.

Methods.  Case study evaluation was conducted, using thematic analysis of 75 qualitative interviews with key stakeholders from different professions (e.g. PMHWs, general practitioners, health visitors, psychiatrists and service managers) and representing different sectors (primary care, specialist services and community child health services).

Findings.  The study identified three models of organization (outreach, primary care‐based and teams). Each was associated with different advantages and disadvantages in its effects on referral rates to specialist services and the development of effective working relationships with primary care providers. Problems associated with accommodation and effective integration of PMHWs with specialist services, and tensions caused by the two different roles that PMHWs could undertake (direct clinical care vs. consultation‐liaison) were common across all sites.

Conclusions.  The PMHW role is an important development that may go some way towards realizing the potential of primary care services in CAMH. The implementation of new roles and models of working in primary care is complex, but may be facilitated by effective planning with primary care providers, clear goals for staff, and a long‐term perspective on service development.
A community survey of loneliness
Authors: Lauder William , Sharkey Siobhan , Mummery Kerry
Published: March 2004

Background.  Loneliness is associated with an increased incidence of a wide range of physical and mental health problems. The detection, prevention and amelioration of loneliness is an important public health issue for nurses.

Methods.  This study reports findings from the 2002 Central Queensland Social Survey. The aims of the study were to (i) establish the extent of loneliness in a community sample; and (ii) to identify the factors that are predictors of loneliness. A random sample of 1241 subjects were interviewed by Computer‐Assisted Telephone Interviewing. This interview included the Loneliness Scale formulated by De Jong Gierveld and Kamphuis.

Findings.  Loneliness is a common phenomenon and risk factors include experience of domestic violence in current relationship, not having recent paid employment, not being married/partnered, and the number of children under 18 years in a household. Loneliness is not associated with higher rates of health care professional consultations.

Conclusion.  Loneliness is a very common problem and should be seen as a major public health issue. Nurses, through a community capacity building framework, have a major role to play in the prevention of loneliness.
Pemphigus: current therapy
Authors: Rosenkrantz Wayne S.
Published: March 2004

Abstract Pemphigus is an autoimmune skin disease that can present in a variety of forms and can be a challenging disease to manage and treat. An overview of the different forms of pemphigus and diagnostics are discussed including pemphigus foliaceus (PF), pemphigus erythematosus (PE), panepidermal pustular pemphigus (PPP), pemphigus vulgaris (PV) and paraneoplastic pemphigus (PNP). Emphasis on therapy is presented. Included are the most current commonly used therapeutics (glucocorticoids, azathioprine, chlorambucil and tetracycline and niacinamide); current alternative therapeutics (cyclosporin and tacrolimus and mycophenolate mofetil) and additional alternative therapeutics (cyclophosphamide, chrysotherapy, dapsone, sulfasalazine and intravenous immunoglobulin (IVIG) therapy).
Immunomodulation and immunodeficiency
Authors: Foster Aiden P.
Published: March 2004

Abstract This article briefly reviews the concepts of immunodeficiency and immunomodulation as they relate to selected skin diseases in the dog and cat. Immunodeficiency states are uncommon and may be associated with a subnormal or down‐regulated immune system, including humoral deficiencies, such as IgA, and abnormal lymphocyte or neutrophil function. Establishing a causal relationship between a skin disease and presumed immunodeficient state has been difficult due to the rarity of such conditions, and the limited nature of the techniques used to characterise the immune system response. Severe combined immunodeficiency in dogs is a well characterised primary immunodeficiency state involving lymphocytes; retrovirus infection in cats may lead to an acquired immunodeficient state with some association with certain dermatological conditions although it remains unclear that infection is causally linked with disease. Immunomodulation usually implies stimulating the immune system along a beneficial pathway. Such a therapeutic approach may involve a wide variety of agents, for example intravenous immunoglobulin. There are few randomised controlled trials with veterinary patients that unequivocally demonstrate beneficial responses to immunomodulatory agents. Interferons are cytokines of major interest in human and veterinary medicine for their antiviral, anti‐tumour and immunomodulatory effects. The advent of veterinary‐licensed products containing recombinant interferon may enable demonstration of the efficacy of interferons for conditions such as canine papillomatosis and feline eosinophilic granuloma complex. Canine pyoderma has been treated with a number of presumed immunomodulatory agents with limited success. With more detailed knowledge of the pathogenesis of pyoderma it may be possible to develop efficacious immunomodulators.
Ear cleaning: the UK and US perspective
Authors: Nuttall Tim , Cole Lynette K.
Published: March 2004

Abstract Ear cleaning helps maintain the normal otic environment and is important in the treatment of otitis. Over cleaning, however, may trigger otitis through maceration of the epidermal lining. Simple manual cleaning is useful for routine cleansing but doesn’t remove tightly adherent debris. Bulb syringes are more vigorous but may damage the ear in inexperienced hands. Devices using mains water pressure or dental machines are also available. Thorough cleaning of the ear canals and middle ear cavity can only be achieved by retrograde flushing using specially adapted catheters, feeding tubes or video otoscopes under anaesthesia. Myringotomy, inspection and cleaning of the middle should be performed if the tympanic membrane appears abnormal. There are a wide variety of cleaning fluids available. Ceruminolytics soften and dissolve cerumen to facilitate cleaning. Surfactants emulsify debris, breaking it up and keeping it in solution. Astringents dry the ear canal surface, preventing maceration. Maintaining a low pH and incorporating antimicrobial agents can inhibit microbial proliferation and glucocorticoids can be used to reduce inflammation. Adverse effects and contraindications following ear cleaning can include maceration, contact reactions, otitis media, ear canal avulsion, vestibular syndrome, Horner's syndrome, facial nerve paralysis and deafness. Care should be exercised in selecting cleaning fluids if the tympanic membranes are ruptured.