bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding diseases by mouse click: the promise and potential of computational approaches in Systems Biology
Authors: Klauschen F , Angermann B R , Meier-Schellersheim M 
Published: August 2010

SummaryComputational modelling approaches can nowadays build large-scale simulations of cellular behaviour based on data describing detailed molecular level interactions, thus performing the space- and time-scale integrations that would be impossible just by intuition. Recent progress in the development of both experimental methods and computational tools has provided the means to generate the necessary quantitative data and has made computational methods accessible even to non-theorists, thereby removing a major hurdle that has in the past made many experimentalists hesitate to invest serious effort in formulating quantitative models. We describe how computational biology differs from classical bioinformatics, how it emerged from mathematical biology and elucidate the role it plays for the integration of traditionally separated areas of biomedical research within the larger framework of Systems Biology.
Dynamic changes in CD4+ CD25+ high T cell apoptosis after the diagnosis of type 1 diabetes
Authors: Glisic-Milosavljevic S , Wang T , Koppen M , Kramer J , Ehlenbach S , Waukau J , Jailwala P , Jana S , Alemzadeh R , Ghosh S 
Published: August 2010

Summary
Because type 1 diabetes (T1D) is a chronic, autoimmune, T cell-mediated disease, interventions affecting T cells are expected to modulate the immune cascade and lead to disease remission. We propose that increased CD4+ CD25+high T cell apoptosis, a trait we discovered in recent-onset T1D subjects, reflects T1D partial remission within the first 6 months after diagnosis. Apoptosis of forkhead box P3 (FoxP3)+ CD4+ CD25+high T cells, in addition to total daily doses of insulin (TDD), blood glucose, HbA1c and age, were measured in 45 subjects with T1D at various times after diagnosis. Sixteen healthy control subjects were also recruited to the study. Higher CD4+ CD25+high T cell apoptosis levels were detected within the first 6 months of diagnosis (odds ratio = 1·39, P = 0·009), after adjustment for age, TDD and HbA1c. A proportional hazards model confirmed that the decline of apoptosis after diagnosis of T1D was related significantly to survival time (hazards ratio = 1·08, P = 0·014), with TDD and age also contributing to survival. During this time there was an inverse relationship between CD4+ CD25+high T cell apoptosis with TDD (r = −0·39, P = 0·008). The CD4+ CD25+high T cell apoptosis levels decline significantly after the first 6 months from diagnosis of T1D and may help in the close monitoring of autoimmunity. In parallel, there is an increase in TDD during this time. We also propose that CD4+ CD25+high T cell apoptosis assay can be used to gauge the efficacy of the several immune tolerance induction protocols, now under way.
Conditional regulation of cyclooxygenase-2 in tracheobronchial epithelial cells modulates pulmonary immunity
Authors: Park G Y , Hu N , Wang X , Sadikot R T , Yull F E , Joo M , Stokes Peebles R , Blackwell T S , Christman J W 
Published: August 2010

Summary
Cyclooxygenase-2 (COX-2) gene expression in the lung is induced in pathological conditions such as asthma and pneumonia; however, the exact impact of COX-2 gene expression in the airway in regulating inflammatory and immunological response in the lung is not understood. To define a physiological role of inducible COX-2 in airway epithelial cells, we developed a novel line of transgenic mice, referred to as CycloOxygenase-2 TransActivated (COTA) mice, that overexpress a COX-2 transgene in the distribution of the CC-10 promoter in response to doxycycline. In response to doxycycline treatment, COX-2 expression was increased in airway epithelium of COTA mice and whole lung tissue contained a three- to sevenfold increase in prostaglandin E2 (PGE2), prostaglandin D2 (PGD2) thromboxane B2 (TXB2) and 6-Keto prostaglandin F2α (PGF2α) compared to wild-type and untreated COTA mice. Interestingly, primary mouse tracheal epithelial cells from COTA mice produced only PGE2 by doxycycline-induced COX-2 activation, providing an indication of cellular specificity in terms of mediator production. In the ovalbumin model, in which doxycycline was given at the sensitization stage, there was an increase in interleukin (IL)-4 level in lung tissue from COTA mice compared to untreated COTA and wild-type mice. In addition, COTA mice that were treated with doxycycline had impaired clearance of Pseudomonas aeruginosa pneumonia compared to wild-type mice. COX-2 gene expression in airway epithelial cells has an important role in determining immunological response to infectious and allergic agents.
Low mannose-binding lectin (MBL) levels in neonates with pneumonia and sepsis
Authors: Frakking F N J , Brouwer N , Van Eijkelenburg N K A , Merkus M P , Kuijpers T W , Offringa M , Dolman K M 
Published: August 2010

SummaryWe investigated whether deficiency of mannose-binding lectin (MBL), a component of innate immunity, is associated with neonatal pneumonia and sepsis during the first 72 h, i.e. early onset, and during the first month after birth. In 88 neonatal intensive care patients (71 premature), MBL2 genotype and MBL plasma levels at birth were determined prospectively by Taqman analysis and enzyme-linked immunosorbent assay, respectively. Thirty-five neonates (40%) had low, i.e. ≤ 0·7 µg/ml, MBL plasma levels at birth. Median (interquartile range) MBL plasma levels in 32 no early-onset sepsis (EOS) cases, 44 possible EOS cases and 11 EOS cases were 1·57 (0·57–2·67) µg/ml, 1·05 (0·41–1·70) µg/ml and 0·20 (0·10–0·77) µg/ml, respectively (P &lt; 0·01). During the first month, 28 neonates (32%) had no infection, 49 (55%) had suspected infection, five (6%) had pneumonia and six (7%) had culture-proven sepsis. Low MBL levels at birth were associated both with an increased risk of developing pneumonia (OR: 12·0; 95% CI: 1·1–126·1; P = 0·04) and culture-proven sepsis (OR: 15·0; 95% CI: 1·5–151·3; P = 0·02). These results were confirmed by genetic analysis of MBL deficiency. Low MBL levels at birth are associated with an increased risk of early-onset sepsis, culture-proven sepsis and pneumonia during the first month of life.
Indoleamine 2,3-dioxygenase activity is increased in patients with systemic lupus erythematosus and predicts disease activation in the sunny season
Authors: Pertovaara M , Hasan T , Raitala A , Oja S S , Yli-Kerttula U , Korpela M , Hurme M 
Published: August 2010

Summary
Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme which suppresses T lymphocyte activity. IDO activity can be determined by relating kynurenine, the main metabolite of tryptophan, to tryptophan (kyn/trp). We have demonstrated recently that systemic lupus erythematosus (SLE) is activated during the sunny season as measured by the European Consensus Lupus Activity Measurement Index (ECLAM) activity score. Our aim here was to establish whether IDO-dependent mechanisms are involved in the activation process of SLE. Kyn/trp was measured by reverse-phase high-performance liquid chromatography (HPLC) in 33 (30 female, three male) SLE patients in winter, spring and summer and in 309 healthy control subjects. At the same time-points the SLE patients were examined by a rheumatologist and a dermatologist and the activity of SLE assessed by the ECLAM score. IDO activity was higher in SLE patients than in healthy subjects. There was no seasonal variation in IDO activity in SLE patients and it did not correlate with the ECLAM activity score in winter. However, there was a significant correlation between IDO activity and the ECLAM score both in spring and in summer. High IDO activity in winter predicted subsequent activation of SLE in spring and summer. Our results indicate that IDO-dependent immunosuppressive mechanisms are activated in SLE patients. Exposure to sunlight or another factor causing seasonal variation in SLE activity leads to insufficiency of this suppression in a subgroup of patients, causing activation of SLE. High IDO activity in winter predicts activation of SLE in the sunny season.
Serum levels of interferon-γ, tumour necrosis factor-α, soluble interleukin-6R and soluble cell activation markers for monitoring response to treatment of leprosy reactions
Authors: Iyer A , Hatta M , Usman R , Luiten S , Oskam L , Faber W , Geluk A , Das P 
Published: August 2010

SummaryIdentifying pathogen and host-related laboratory parameters are essential for the early diagnosis of leprosy reactions. The present study aimed to clarify the validity of measuring the profiles of serum cytokines [interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-γ and tumour necrosis factor (TNF)-α], the soluble IL-6 receptor (sIL-6R), soluble T cell (sCD27) and macrophage (neopterin) activation markers and Mycobacterium leprae-specific anti-PGL-I IgM antibodies in relation to the leprosy spectrum and reactions. Serum samples from 131 Indonesian leprosy patients (82 non-reactional leprosy patients and 49 reactional) and 112 healthy controls (HC) from the same endemic region were investigated. Forty-four (89·8%) of the reactional patients had erythema nodosum leprosum (ENL) while only five (10·2%) had reversal reaction (RR). Follow-up serum samples after corticosteroid treatment were also obtained from 17 of the patients with ENL and one with RR. A wide variability in cytokine levels was observed in the patient groups. However, IFN-γ and sIL-6R were elevated significantly in ENL compared to non-ENL patients. Levels of IFN-γ, TNF-α and sIL-6R declined significantly upon corticosteroid treatment of ENL. Thus, although the present study suggests limited applicability of serial measurement of IFN-γ, TNF-α and sIL-6R in monitoring treatment efficacy of ENL, reactions it recommends a search for a wider panel of more disease-specific markers in future studies.
Leptin improves pulmonary bacterial clearance and survival inob/obmice during pneumococcal pneumonia
Authors: Hsu A , Aronoff D M , Phipps J , Goel D , Mancuso P 
Published: August 2010

SummaryThe adipocyte-derived hormone leptin is an important regulator of appetite and energy expenditure and is now appreciated for its ability to control innate and adaptive immune responses. We have reported previously that the leptin-deficient ob/ob mouse exhibited increased susceptibility to the Gram-negative bacterium Klebsiella pneumoniae. In this report we assessed the impact of chronic leptin deficiency, using ob/ob mice, on pneumococcal pneumonia and examined whether restoring circulating leptin to physiological levels in vivo could improve host defences against this pathogen. We observed that ob/ob mice, compared with wild-type (WT) animals, exhibited enhanced lethality and reduced pulmonary bacterial clearance following Streptococcus pneumoniae challenge. These impairments in host defence in ob/ob mice were associated with elevated levels of lung tumour necrosis factor (TNF)-α, macrophage inflammatory peptide (MIP)-2 [correction added after online publication 28 September 2007: definition of MIP corrected], prostaglandin E2 (PGE2), lung neutrophil polymorphonuclear leukocyte (PMN) counts, defective alveolar macrophage (AM) phagocytosis and PMN killing of S. pneumoniae in vitro. Exogenous leptin administration to ob/ob mice in vivo improved survival and greatly improved pulmonary bacterial clearance, reduced bacteraemia, reconstituted AM phagocytosis and PMN H2O2 production and killing of S. pneumoniae in vitro. Our results demonstrate, for the first time, that leptin improves pulmonary bacterial clearance and survival in ob/ob mice during pneumococcal pneumonia. Further investigations are warranted to determine whether there is a potential therapeutic role for this adipokine in immunocompromised patients.
Generation of functionally distinct B lymphocytes from common myeloid progenitors
Authors: Yang G-X , Lian Z-X , Chuang Y-H , Shu S-A , Moritoki Y , Lan R , Wakabayashi K , Ansari A A , Dorshkind K , Ikehara S , Gershwin M E 
Published: August 2010

Summary
Current models of adult haematopoiesis propose that haematopoietic stem cells (HSCs) differentiate into common lymphoid (CLP) and common myeloid (CMP) progenitors and establish an early separation between myeloid and lymphoid lineages. Nevertheless, the developmental potential of CMP-associated B cells suggests the existence of alternate pathways for B lymphopoesis. The aim of this study was to compare the developmental and functional properties of CMP- and CLP-derived B cells. While both populations matured through pro-B cell and transitional B cell intermediates in the bone marrow and spleen, respectively, following transfer into irradiated mice, mature CMP- and CLP-derived B cells exhibit distinct functional responses. Specifically, CMP-derived B cells did not respond to mitogenic stimulation to the same degree as their CLP-derived counterparts and secrete lower levels of IgM and the inflammatory cytokines such as interleukin (IL)-6 and IL-10. Together, these data suggest the existence of multiple pathways for generating functionally distinct B cells from bone marrow precursors.
Translocation of bacterial DNA from Gram-positive microorganisms is associated with a species-specific inflammatory response in serum and ascitic fluid of patients with cirrhosis
Authors: Francés R , González-Navajas J M , Zapater P , Muñoz C , Caño R , Pascual S , Santana F , Márquez D , Pérez-Mateo M , Such J 
Published: August 2010

SummaryTranslocation of bacterial-DNA in patients with cirrhosis and ascites triggers an innate immune response. Identification of characteristics to which this response is sensitive is relevant from a clinical standpoint. The aim of this study has been to determine if the proinflammatory immune response established in vivo in cirrhotic patients with ascites as a consequence of bacterial-DNA translocation is related to the identified bacterial species and their frequency of cytosine-guanosine content in serum and ascitic fluid. Patients with advanced cirrhosis and ascites were included in the study and distributed into groups I and II according to the absence or presence of bacterial-DNA translocation, respectively. Serum and ascitic fluid levels of proinflammatory cytokines after normalization of bacterial-DNA concentration and the activated form of nuclear factor-kappa B in ascitic fluid pellets were measured by enzyme-linked immunosorbent assay techniques. Translocation of bacterial-DNA with higher cytosine-guanosine content induced the highest cytokine response, which was higher than that in patients without bacterial-DNA translocation. The activated form of nuclear factor-kappa B in ascitic fluid pellets of patients with bacterial-DNA translocation was greater in patients with higher bacterial-DNA cytosine-guanosine content, whereas the amount of total nuclear factor-kappa B remained unaltered. Bacterial-DNA translocation induces a marked immune reaction in vivo in patients with advanced cirrhosis and ascites which is related, among other factors, to the bacterial-DNA cytosine-guanosine content. Therefore, the host's immune response to bacterial-DNA translocation constitutes a species-specific phenomenon.
An impossible dream? Images of nursing held by pre‐registration students and their effect on sustaining motivation to become nurses
Authors: Spouse Jenny 
Published: August 2010

An impossible dream? Images of nursing held by pre‐registration students and their effect on sustaining motivation to become nurses Each year approximately 13 000 people enter higher education programmes leading to nurse registration in England. Evidence suggests that students enter nursing with strong images about how they will practice. This paper explores the nature of such images and how they are used to inform students’ approaches to nursing practice. Findings come from a longitudinal study designed to investigate how students develop their professional knowledge whilst working in clinical settings. Eight pre‐registration degree‐course nursing students participated in the study. A multi‐method approach to data collection was used over their 4‐year programme. One involved in‐depth interviews taking place during each of students’ clinical placements. Data were analysed manually and subjected to a constant comparative method of analysis. From this material individual case studies of the five completing students were constructed, with participants checking their own case study to ensure that it reflected their intended meaning. A second phase followed where cross‐case comparison addressed each of the original research questions. The question relevant to this paper was: What were students’ conceptions of nursing on entry, and how do these influence their development? Findings indicate that participating students’ preconceptions of nursing had a profound influence on their decision whether to continue with their course, sometimes despite social and academic set‐backs, or to leave nursing. An important contribution to realizing their aims was their supernumerary status and effective support from knowledgeable and experienced practitioners. These findings indicate that with better understanding of the relationship between this form of personal knowing and practice, educators would have more information with which to select students and to design professional curricula.
Language, research and nursing practice
Authors: Björnsdottir Kristin 
Published: August 2010

Language, research and nursing practiceAim of the paper. This paper highlights the centrality of language in constructing knowledge. It aims at making us sensitive to the political nature of knowledge production and the complex power relationships that may emerge as a result of our efforts to create new knowledge.Background: Science, as understood here, is a linguistic construction, rather than a mirror reflection of reality. A number of examples are presented, demonstrating the complex ways in which language is central in shaping all our attempts to know, science included, and nursing practice.Conclusion: Based on the analysis presented in this paper an argument is made for a substantial re‐thinking of nursing research and its relationship to nursing practice. Research needs to be an integral part of everyday nursing practice, a way of posing questions and reflecting on answers. Further, nurses need to be aware of the potentially coercive nature of knowledge as well as its liberating effect.
Are people with learning disabilities able to contribute to focus groups on health promotion?
Authors: Fraser Mary , Fraser Anne 
Published: August 2010

Are people with learning disabilities able to contribute to focus groups on health promotion? Aim. This paper shows the differences between the success of three focus groups in promoting group discussion on health promotion and also the detailed effects of individual members with speech and language difficulties in participating. Background. Conducting focus groups with people with learning disabilities can promote their social inclusion. Conclusions. We conclude that focus groups are an effective method of conducting exploratory research with adults with learning disabilities in the community, however, ability to participate with other members may be a limiting factor. Furthermore, special arrangements may need to be made for groups to be successful, including the use of an interpreter. The preparation of the moderator is also an important factor in group success.
Ambulatory orthopaedic surgery patients’ knowledge expectations and perceptions of received knowledge
Authors: Heikkinen Katja , Leino‐Kilpi Helena , Hiltunen Ari , Johansson Kirsi , Kaljonen Anne , Rankinen Sirkku , Virtanen Heli , Salanterä Sanna 
Published: August 2010

AbstractTitle.  Ambulatory orthopaedic surgery patients’ knowledge expectations and perceptions of received knowledge Aim.  This paper is a report of a study to compare orthopaedic ambulatory surgery patients’ knowledge expectations before admission and their perceptions of received knowledge 2 weeks after discharge.Background.  Advances in technology and population ageing are driving up the number of ambulatory orthopaedic surgical procedures. Shorter hospital stays present a major challenge for patient education.Methods.  A descriptive comparative cross‐sectional study (pre‐ and post‐test) design was adopted. The data were collected from 120 consecutive patients in 2004, using the Hospital Patient’s Knowledge Expectations Scale and Hospital Patient’s Received Knowledge Scale. All patients participated in a preoperative education session given by a nurse.Results.  Patients expected more knowledge than they actually perceived that they received on all dimensions except the bio‐physiological. They perceived that they received least knowledge about experiential, ethical, social and financial dimensions of knowledge. Knowledge expectations correlated with age and professional education. Perceptions of received knowledge correlated with earlier ambulatory surgery, and both expected knowledge and perceptions of received knowledge were related to the level of basic education.Conclusion.  Patients’ knowledge expectations are greater than the knowledge they perceived that they receive, and they cannot become empowered if they lack important knowledge. Further research is needed to learn about meeting patients’ knowledge expectations.
The complex nature of informal care in home‐based heart failure management
Authors: Clark Alexander M. , Reid Margaret E. , Morrison Caroline E. , Capewell Simon , Murdoch David L. , McMurray John J. 
Published: August 2010

AbstractTitle. The complex nature of informal care in home‐based heart failure management.Aim. This paper is a report of a study to examine the complexities of informal caregiving for people with chronic heart failure.Background. Little is known of the activities involved and underlying informal care. Heart failure is a common and burdensome condition in which carers play an important management role.Method. Semi‐structured interviews were carried out with 30 informal carers nominated by patients with mild‐to‐moderate heart failure (24 spouses, four children, one sibling and one neighbour). Interviews examined knowledge of heart failure, its effects, reported management practices and concerns, decision making and support. The data were collected in 2001.Findings. The management of heart failure was a shared and ongoing responsibility between the carer and patient. Carers’ clinical knowledge of the condition and management was often limited, but they developed extensive knowledge of its personal effects on the patient. Invisible care activities included monitoring signs of symptom exacerbation and energy boundaries against perceived current and future demands and priorities. Visible care activities included medication management, dressing, bathing and help‐seeking. Carers responded to patients’ capacities, and adopted philosophies that sought to foster independence while facilitating as normal a life for the patient as was possible and safe.Conclusion. Interventions for informal carers around effective chronic heart failure management should address both visible and invisible informal caring. Future research is needed to develop interventions with carers to improve quality of care, reduce costs and improve patient quality of life. More research is needed to explore the complexities of lay caregiving and to explore the invisible dimensions of informal care further.