bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibodies against oxidized phospholipids in laboratory tests exploring lupus anti-coagulant activity
Authors: Rolla R , Vidali M , Serino R , Pergolini P , Albano E , Bellomo G 
Published: August 2010

Summary
Lupus anti-coagulants (LA) are a variety of anti-phospholipid antibodies characterized by their capacity to interfere with phospholipid-dependent coagulation assays. LA are increasingly recognized as important predictors of thrombosis. However, the antigen specificity of LA is still poorly characterized. Growing evidence indicates that oxidized phospholipids are among the targets of anti-phospholipid antibodies. This prompted us to investigate the role of IgG directed against different oxidized phospholipids in 164 subjects without clotting factor defects that were tested for the presence of LA using a LA-sensitive activate partial thromboplastin time (aPTT-FSL) and a screening/confirmation assay based on diluted Russell's viper venom test (dRVVT-PL). The response to aPTT-FSL was significantly (P &lt; 0·0005) associated with high titres of IgG against oxidized phosphatidylserine, phosphatidylethanolamine and phosphatidylinositol, whereas positivity to dRVVT-PL was associated with the elevation of IgG against oxidized phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine (P &lt; 0·0005) and phosphatidylinositol (P &lt; 0·01). No difference in reactivity against oxidized cardiolipin was evident between the different groups. Positivity to the dRVVT-PL test was also associated significantly (P &lt; 0·005) with the elevation of anti-cardiolipin and anti-β2-glycoprotein-1 IgG. However, stepwise logistic regression demonstrated that IgG recognizing oxidized phosphatidylethanolamine and oxidized phosphatidylcholine were the only independent predictors of the response to dRVVT-PL assay, while IgG recognizing oxidized phosphatidylethanolamine and oxidized phosphatidylinositol were independent predictors of the response to aPTT-FSL test. In conclusion, autoantibodies against defined oxidized phospholipids are independent predictors of LA detection by aPTT-FSL or dRVVT-PL assays and might contribute to the variability often observed in the responses to the functional tests detecting LA.
Recognition, clinical diagnosis and management of patients with primary antibody deficiencies: a systematic review
Authors: Wood P , Stanworth S , Burton J , Jones A , Peckham D G , Green T , Hyde C , Chapel H 
Published: August 2010

SummaryThe primary purpose of this systematic review was to produce an evidence-based review of the literature as a means of informing current clinical practice in the recognition, diagnosis and management of patients with suspected primary antibody deficiency. Randomized controlled trials (RCTs) were identified from a search of MEDLINE, EMBASE, The Cochrane Library, DARE (CRD website) and CINAHL by combining the search strategies with The Cochrane Collaboration's validated RCT filter. In addition, other types of studies were identified in a separate search of MEDLINE and EMBASE. Patients at any age with recurrent infections, especially in the upper and lower respiratory tracts, should be investigated for possible antibody deficiency. Replacement therapy with immunoglobulin in primary antibody deficiencies increases life expectancy and reduces infection frequency and severity. Higher doses of immunoglobulin are associated with reduced infection frequency. Late diagnosis and delayed institution of immunoglobulin replacement therapy results in increased morbidity and mortality. A wide variety of organ-specific complications can occur in primary antibody deficiency syndromes, including respiratory, gastroenterological, hepatic, haematological, neurological, rheumatological and cutaneous. There is an increased risk of malignancy. Some of these complications appear to be related to diagnostic delay and inadequate therapy. High-quality controlled trial data on the therapy of these complications is generally lacking. The present study has identified a number of key areas for further research, but RCT data, while desirable, is not always obtained easily for rare conditions. Few data from registries or large case-series have been published in the past 5 years and a greater focus on international collaboration and pooling of data is needed.
Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression
Authors: Rodrigues dos Santos R , Sartori A , Deperon Bonato V L , Coelho Castelo A A M , Vilella C A , Zollner R L , Lopes Silva C 
Published: August 2010

SummaryWe have described previously the prophylactic and therapeutic effect of a DNA vaccine encoding the Mycobacterium leprae 65 kDa heat shock protein (DNA-HSP65) in experimental murine tuberculosis. However, the high homology of this protein to the corresponding mammalian 60 kDa heat shock protein (Hsp60), together with the CpG motifs in the plasmid vector, could trigger or exacerbate the development of autoimmune diseases. The non-obese diabetic (NOD) mouse develops insulin-dependent diabetes mellitus (IDDM) spontaneously as a consequence of an autoimmune process that leads to destruction of the insulin-producing β cells of the pancreas. IDDM is characterized by increased T helper 1 (Th1) cell responses toward several autoantigens, including Hsp60, glutamic acid decarboxylase and insulin. In the present study, we evaluated the potential of DNA-HSP65 injection to modulate diabetes in NOD mice. Our results show that DNA-HSP65 or DNA empty vector had no diabetogenic effect and actually protected NOD mice against the development of severe diabetes. However, this effect was more pronounced in DNA-HSP65-injected mice. The protective effect of DNA-HSP65 injection was associated with a clear shift in the cellular infiltration pattern in the pancreas. This change included reduction of CD4+ and CD8+ T cells infiltration, appearance of CD25+ cells influx and an increased staining for interleukin (IL)-10 in the islets. These results show that DNA-HSP65 can protect NOD mice against diabetes and can therefore be considered in the development of new immunotherapeutic strategies.
The effects of interleukin-18 on rat articular chondrocytes: a study of mRNA expression and protein synthesis of proinflammatory substances
Authors: Ye X J , Tang B , Ma Z , Zhou J , Myers L K , Kang A H , Cremer M A 
Published: August 2010

SummaryInterleukin (IL)-18 is a potent stimulator of immunity and augments the severity of type II collagen-induced arthritis (CIA) in rats and mice by enhancing T helper 1 (Th1) cell activation, which increases the production of proinflammatory cytokines and arthritogenic antibodies. In this study, we show that recombinant IL-18 (rIL-18) also has a direct effect on normal rat chondrocytes maintained in vitro inducing them to produce proinflammatory factors including IL-6, regulated upon activation normal T cell expressed and secreted (RANTES), prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) in a dose- and time-dependent manner. The production of matrix metalloproteinase (MMP)-13, nitric oxide (NO), tumour necrosis factor (TNF)-α and IL-1β were also enhanced, although less intensely. Neutralizing polyclonal anti-rIL-18 antibodies effectively blocked the production of IL-6, PGE2 and RANTES, as well as mRNA expression for the same products in addition to IL-18 and TNF-α. In contrast, neutralizing antibodies to IL-1β, TNF-α and IL-6 were ineffective in suppressing any of these products. Together, these findings suggest that IL-18 may play an important, possibly direct, role in mediating cartilage injury, which might not be amenable to treatment with currently utilized anti-cytokine agents. These findings suggest further that IL-18 antagonists might prove beneficial as anti-inflammatory and chondroprotective agents in the treatment of arthritis, and that the development of such agents for human use is worth consideration.
Amelioration of lacrimal gland inflammation by oral administration of K-13182 in Sjögren's syndrome model mice
Authors: Nishiyama T , Mishima K , Obara K , Inoue H , Doi T , Kondo S , Saka M , Tabunoki Y , Hattori Y , Kodama T , Tsubota K , Saito I 
Published: August 2010

SummaryRegulation of the adhesion of mononuclear cells to endothelial cells is considered to be a critical step for the treatment of inflammatory diseases, including autoimmune diseases. K-13182 was identified as a novel inhibitor for these adhesions. K-13182 inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1, CD106) on human umbilical vein endothelial cells (HUVECs) and on mouse vascular endothelial cell line (MAECs) induced by tumour necrosis factor (TNF)-α. K-13182 also inhibited the adhesion of mononuclear cells to these HUVECs and MAECs, indicating that K-13182 suppressed these adhesions mediated by cellular adhesion molecules including VCAM-1. To evaluate the therapeutic effect in autoimmune disease model mice, K-13182 was orally administered to non-obese diabetic (NOD) mice as Sjögren's syndrome (SS) model mice. Severe destructive inflammatory lesions were observed in the lacrimal glands of vehicle-treated control mice; however, 8-week administration of K-13182 inhibited the mononuclear cell infiltration into the inflammatory lesions of the lacrimal glands. In K-13182-treated mice, the decrease in tear secretion was also prevented compared to the control mice. In addition, the apoptosis and the expression of FasL (CD178), perforin, and granzyme A was suppressed in the lacrimal glands of K-13182-treated mice. Therefore, K-13182 demonstrated the possibility of therapeutic efficacy for the inflammatory region of autoimmune disease model mice. These data reveal that VCAM-1 is a promising target molecule for the treatment of autoimmune diseases as a therapeutic strategy and that K-13182 has the potential as a new anti-inflammatory drug for SS.
The clearance kinetics of autologous RhD-positive erythrocytes coated ex vivo with novel recombinant and monoclonal anti-D antibodies
Authors: Chapman G E , Ballinger J R , Norton M J , Parry-Jones D R , Beharry N A , Cousins C , Dash C H , Peters A M 
Published: August 2010

Summary
Anti-D is given routinely to pregnant RhD-negative women to prevent haemolytic disease of the fetus and newborn. To overcome the potential drawbacks associated with plasma-derived products, monoclonal and recombinant forms of anti-D have been developed. The ability of two such antibodies, BRAD-3/5 monoclonal anti-D IgG (MAD) and rBRAD-3/5 recombinant anti-D IgG (RAD), to clear RhD-positive erythrocytes from the circulation was compared using a dual radiolabelling technique. Six RhD-positive males received autologous erythrocytes radiolabelled with 99mTc and 51Cr and coated ex vivo with MAD and RAD. Blood samples were collected up to 1 h following intravenous injection, and percentage dose of radioactivity in the samples determined. Three different levels of coating were used on three separate occasions. No significant differences between MAD and RAD were observed in the initial clearance rate constant at any dose level. The log[activity]-time clearance plots were curved, showing a reduction in the clearance rate constant with time. This reduction was more marked for RAD than for MAD. The results support a dynamic model for the clearance of antibody-coated erythrocytes that may have wider relevance for the therapeutic use of antibodies.
85-kDa cytosolic phospholipase A2 group IVα gene promoter polymorphisms in patients with severe asthma: a gene expression and case–control study
Authors: Sokolowska M , Borowiec M , Ptasinska A , Cieslak M , Shelhamer J H , Kowalski M L , Pawliczak R 
Published: August 2010

Summary
Cytosolic phospholipase A2 (cPLA2) group IVα is a critical enzyme involved in the liberation of arachidonic acid from cellular membranes. cPLA2−/− mice have reduced allergen-induced bronchoconstriction and bronchial hyperresponsiveness. The goal of this study was to investigate polymorphisms of the (CA)n and (T)n microsatellites and surrounding regions in the cPLA2α gene promoter. We analysed the cPLA2 promoter regions containing (CA)n and (T)n repeats in 87 patients with severe asthma and in 48 control subjects by bidirectional sequencing. Functional studies were performed utilizing reporter genes derived from subjects with varying numbers of these repeats, and on constructs with a series of deletions. We found that the (CA)n and (T)n regions are polymorphic and that constructs with CA or T repeats or CA and T repeats deleted revealed, respectively, a 41·8 ± 7%, 22·3 ± 5% and 100 ± 20% increase in reporter gene activity. A lower number of CA or T repeats caused higher cPLA2 promoter luciferase activity. The group of shorter alleles of the (CA)n microsatellite region (n = 12–18) (Pcor = 0·00006), and the group of shorter alleles of (T)n repeats region (n = 17–38) (Pcor = 0·0039) occurred significantly more often in patients with severe asthma. We also found novel SNPs in positions −292 C &gt; G, −185 A &gt; C, −180 T &gt; C and −165 A &gt; C. Two of them were associated with the severe asthma phenotype: −180T allele (Pcor = 0·03996) and −185 A allele (Pcor = 0·03966). These results demonstrate that (CA)n and (T)n repeats may have an influence on cPLA2 transcription which might play a role in severe asthma pathogenesis.
Gold causes genetically determined autoimmune and immunostimulatory responses in mice
Authors: Havarinasab S , Johansson U , Pollard K M , Hultman P 
Published: August 2010

SummaryNatrium aurothiomaleate (GSTM) is a useful disease-modifying anti-rheumatic drug, but causes a variety of immune-mediated adverse effects in many patients. A murine model was used to study further the interaction of GSTM with the immune system, including induction of systemic autoimmunity. Mice were given weekly intramuscular injections of GSTM and controls equimolar amounts of sodium thiomaleate. The effects of gold on lymphocyte subpopulations were determined by flow cytometry. Humoral autoimmunity was measured by indirect immunofluorescence and immunoblotting, and deposition of immunoglobulin and C3 used to assess immunopathology. Gold, in the form of GSTM, stimulated the murine immune system causing strain-dependent lymphoproliferation and autoimmunity, including a major histocompatibility complex (MHC)-restricted autoantibody response against the nucleolar protein fibrillarin. GSTM did not cause glomerular or vessel wall IgG deposits. However, it did elicit a strong B cell-stimulating effect, including both T helper 1 (Th1)- and Th2-dependent isotypes. All these effects on the immune system were dependent on the MHC genotype, emphasizing the clinical observations of a strong genetic linkage for the major adverse immune reactions seen with GSTM treatment.
WY14,643, a PPARα ligand, attenuates expression of anti-glomerular basement membrane disease
Authors: Archer D C , Frkanec J T , Cromwell J , Clopton P , Cunard R 
Published: August 2010

SummaryPeroxisome proliferator-activated receptor alpha (PPARα) ligands are medications used to treat hyperlipidaemia and atherosclerosis. Increasing evidence suggests that these agents are immunosuppressive. In the following studies we demonstrate that WY14,643, a PPARα ligand, attenuates expression of anti-glomerular basement membrane disease (AGBMD). C57BL/6 mice were fed 0·05% WY14,643 or control food and immunized with the non-collagenous domain of the α3 chain of Type IV collagen [α3(IV) NC1] in complete Freund's adjuvant (CFA). WY14,643 reduced proteinuria and greatly improved glomerular and tubulo-interstitial lesions. However, the PPARα ligand did not alter the extent of IgG-binding to the GBM. Immunohistochemical studies revealed that the prominent tubulo-interstitial infiltrates in the control-fed mice consisted predominately of F4/80+ macrophages and WY14,643-feeding decreased significantly the number of renal macrophages. The synthetic PPARα ligand also reduced significantly expression of the chemokine, monocyte chemoattractant protein (MCP)-1/CCL2. Sera from mice immunized with AGBMD were also evaluated for antigen-specific IgGs. There was a significant increase in the IgG1 : IgG2c ratio and a decline in the intrarenal and splenocyte interferon (IFN)-γ mRNA expression in the WY14,643-fed mice, suggesting that the PPARα ligand could skew the immune response to a less inflammatory T helper 2-type of response. These studies suggest that PPARα ligands may be a novel treatment for inflammatory renal disease.
Come rain or shine: the combined effects of physical stresses on physiological and protein‐level responses of an intertidal limpet in the monsoonal tropics
Authors: Williams Gray A. , De Pirro Maurizio , Cartwright Stephen , Khangura Kiki , Ng Wai‐Chuen , Leung Priscilla T.Y. , Morritt David 
Published: August 2010

Summary1. Traditional approaches to understanding species responses to environmental conditions have focused on the isolated effects of single stressors, despite the fact that in nature organisms experience a variety of conditions.2. In tropical monsoonal areas, intertidal animals can face hot desiccating conditions during emersion preceded, or followed by, intense rainfall. The combined effects of these stresses on physiological responses and protein profiles were investigated in a limpet,Cellana grata.3. With short exposure (60 min) to single stressors, heat stressed limpets had elevated heart rates and more concentrated haemolymph and mantle water osmolalities than under normal temperatures or awash. Animals under rain had reduced haemolymph and mantle water osmolalities, but similar heart rates to unstressed animals.4. After 120 min, unstressed animals did not differ in their physiological responses. Heat stressed limpets, however, had faster heart rates and more concentrated haemolymph and mantle water osmolalities, whilst those under rain had the lowest osmolalities, but similar heart rates to unstressed animals.5. Limpets under rain followed by heat stress had faster heart rates, but lower haemolymph and mantle water osmolalities compared to animals under normal temperatures or heat stress. Limpets that were heat stressed, followed by rain, had similar heart rates to animals awash, under rain or normal temperatures but lower haemolymph osmolalities than other treatments, with the exception of limpets under rain.6. There was a positive relationship between haemolymph and mantle water osmolalities, except for animals under rain, where mantle water osmolality was lower than the haemolymph, suggesting some isolation of body fluids from the external medium.7. Haemolymph protein/peptide mass spectra of heat stressed animals (either before or after rain) were similar, while all other treatments differed, suggesting differential expression and regulation of proteins.8. Heat stress invokes a more active physiological and protein level response than rain, but their combination had an interactive effect on limpets’ metabolism.9. Identifying the effects of multiple stresses at a variety of biological levels highlights the interactive effects which impact species, and provides a more complete understanding of how species may respond to environmental changes in their natural habitats.
Time to think: temporal considerations in nursing practice and research
Authors: Jones Aled R. 
Published: August 2010

Time to think: temporal considerations in nursing practice and research Aims of the study/paper. To explore the meaning of nursing time, both as it is represented in the literature and interpreted within nursing practice. To explore how nursing time may be better conceptualized through exploring non‐nursing literature and the use of theory derivation. Background/Rationale. The dynamic of time is one of the most important influences upon nursing behaviour, yet temporal issues have attracted very little attention in the literature regarding nursing practice, theory and research. Design/Method. In the course of this literature review an attempt is made, via the process of theory derivation, to clarify the meaning of ‘nursing time’, and how nursing time is valued and perceived by others. Results/Findings. The literature reveals misconceptions and a lack of value of nursing time, possibly indicative of the dominance of linear models of time (such as clock and calendar time), and the historical ascendancy of medicine and the positivistic sciences over nursing. It is proposed here that nurses exist and practice within nonlinear, complex and parallel temporal worlds; these are considered by examining research data that illustrates a moment in nursing time. Exploring this moment gives an opportunity to introduce some terms and concepts that may be useful in the future conceptualization of nursing time. Conclusions. It is recommended that attention to such factors as the complex temporal dynamics inherent within health care in general, and nursing in particular, should be considered within the domains of nursing practice and research. This may help in distinguishing the fundamental identity and nature of nursing within health care and health care professions.
Benner and Wrubel on caring in nursing
Authors: Edwards Steven D. 
Published: August 2010

Benner and Wrubel on caring in nursing Aims. To explain the distinction between intentional and ontological care; to explain the distinction, within the category of ontological care, between deep care and identity constituting care and to show how the latter form of care is of relevance to nursing theory and practice. Background. The idea of intentional care is familiar in much writing on care within nursing literature. Within Benner and Wrubel’s book The Primacy of Caring, Stress and Coping in Health and Illness the idea of ontological care is exploited. But many interpret their claims on this topic as claims concerning intentional care. The present paper tries to clarify this misunderstanding. Conclusion. The notions of intentional and ontological care are each important within nursing theory and practice. But it is also important to understand how they differ. And it is equally important to appreciate how the idea of ontological care applies to nursing practice.
Informal caring in late life: a qualitative study of the experiences of older carers
Authors: McGarry Julie , Arthur Antony 
Published: August 2010

Informal caring in late life: a qualitative study of the experiences of older carers Aim of the study. This study examined the experiences of informal carers who were aged 75 years and over. Background. It has been estimated that 13% of those aged over 65 years are providing some form of informal care. Although there is a substantial body of work reporting the experiences of informal carers, little attention has been paid to the specific situation faced by older carers. Design and methods. Potential study participants were identified during one round of annual over‐75 health checks carried out in one large general practice. Data were collected through personal interviews, which were transcribed and analysed using a thematic approach. Results. Fifty‐eight carers were identified and 14 were approached to take part in the study. Of the 14 interviewees, 13 were caring for a spouse and one was caring for a sibling. There were 10 female and four male carers in the study (age range 76–92 years). Themes to emerge from the interviews were categorized under four headings: (1) the organizational demands and structure of the caring relationship, (2) informal support networks, (3) formal services and (4) the constancy of caring and the need for the role of carer to be recognized. Conclusions. The over‐75 health check may provide a valuable tool to identify older carers who are not known to care providers. This paper concludes that nurses can take a lead role in working with this group in three ways. Firstly, in identifying older carers; secondly, in developing strategies to assist older carers in their caring role and finally, in responding swiftly to crises that can develop among this vulnerable group.