bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination use of immune complexes and a Ca2+ channel blocker azelnidipine enhances interleukin-12 p40 secretion without T helper type 17 cytokine secretion in human monocyte-derived dendritic cells
Authors: Abe T , Fuse I , Narita M , Takahashi M , Aizawa Y 
Published: February 2009

SummaryImmune complexes (ICs) improve the capacity of priming specific CD8+ cytotoxic T cell responses of dendritic cells (DCs). ICs induce phosphorylation of mitogen-activated protein kinases (MAPK) and calcium influx, although the precise regulating mechanism still remains unclear. In the present study, we investigated the effect of a Ca2+ channel blocker on the phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK) in immature monocyte-derived DCs stimulated with lipopolysaccharide (LPS) or LPS-ICs, and the production of interleukin (IL)-12 family members (p40, p70, IL-23), T helper type 17 (Th17) cytokines (IL-6 and IL-23), tumour necrosis factor (TNF)-α and IL-10 were also investigated. In comparison with LPS stimulation, LPS-ICs stimulation enhanced p38 MAPK phosphorylation significantly, which was associated with an increase in IL-12 p40 monomer/homodimer secretion. LPS-ICs also enhanced TNF-α and IL-6 secretion, but suppressed IL-23 secretion. The use of azelnidipine (Aze), a long-acting L-type Ca2+ channel blocker with a high lipid solubility, suppressed p38 MAPK phosphorylation stimulated with LPS or LPS-ICs, but surprisingly enhanced IL-12 p40 monomer/homodimer secretion stimulated with LPS-ICs. This IL-12 p40 secretion-enhancing effect was not accompanied by IL-10 or IL-23 production, but was associated with ERK phosphorylation. The use of Aze did not affect IL-12 p70 production. These results suggest that the use of Aze enhances ICs-mediated IL-12 p40 secretion without additional IL-23 secretion. Therefore, the use of Aze and ICs could be a new therapeutic approach to immunomolecular therapy, as it does not cause Th17 differentiation which induces autoimmunity or reduces anti-tumour immunity.
Cancer immunotherapy: co-stimulatory agonists and co-inhibitory antagonists
Authors: Peggs K S , Quezada S A , Allison J P 
Published: February 2009

SummaryThe generation and maintenance of immune responses are controlled by both co-stimulatory and co-inhibitory signalling through T cell co-receptors, many of which belong to the immunoglobulin-like superfamily or the tumour necrosis factor receptor superfamily. Agonistic or antagonistic monoclonal antibodies targeting these co-receptors have the potential to enhance immunity. Furthermore, their activity on the immunosuppressive regulatory T cell populations which are prevalent within many tumours provides an additional rationale for their use as anti-cancer therapies. This review summarizes the interactions between cancer and the immune system, highlighting the ways in which these new classes of immunostimulatory antibodies might enhance anti-tumour immunity and summarizing early clinical experience with their use.
Human gingival fibroblasts express functional chemokine receptor CXCR6
Authors: Hosokawa Y , Hosokawa I , Ozaki K , Nakae H , Matsuo T 
Published: February 2009

Summary
We have reported that CXCL16, a recently discovered transmembrane chemokine, is expressed in human gingival fibroblasts (HGF). However, it is not known whether HGF express CXCR6, the receptor for CXCL16, or CXCL16 affects HGF biology. We have shown that HGF expressed CXCR6 by reverse transcription–polymerase chain reaction and flow cytometric analysis. Moreover, we elucidated that tumour necrosis factor (TNF)-α and cytosine-guanine dinucleotide (CpG) DNA (Toll-like receptor-9 ligand) treatment enhanced CXCR6 expression by HGF. Interleukin (IL)-4, IL-13 and CpG DNA up-regulated CXCR6 expression by TNF-α-stimulated HGF. On the other hand, IL-1β and interferon-γ inhibited CXCR6 expression on TNF-α-treated HGF. CXCL16 treatment induced HGF proliferation and phosphorylation of extracellular regulated kinase (ERK) and protein kinase B (AKT) in HGF. In conclusion, HGF expressed CXCR6 functionally, because CXCL16 induced HGF proliferation and ERK and AKT phosphorylation in HGF. These results indicate that CXCL16 may play an important role in the pathogenesis and remodelling in periodontally diseased tissues.
Lower bone mineral density is associated with higher coronary calcification and coronary plaque burdens by multidetector row coronary computed tomography in pre‐ and postmenopausal women
Authors: Choi Sung Hee , An Jee Hyun , Lim Soo , Koo Bo Kyung , Park Se Eun , Chang Hyuck Jae , Choi Sang Il , Park Young Joo , Park Kyong Soo , Jang Hak Chul , Shin Chan Soo 
Published: February 2009

SummaryObjectives  There is growing evidence for the association between bone mineral density (BMD) and vascular calcification, which is related to cardiovascular disease. Coronary multidetector row computed tomography (MDCT) is a noninvasive tool developed to evaluate coronary status precisely. We used MDCT to evaluate this association.Design and patients  Eight hundred and fifteen subjects received routine checkups. After excluding subjects with factors affecting bone metabolism and cardiovascular disease, 467 subjects were analysed.Measurements  Coronary calcification was measured with MDCT and BMD was measured with dual X‐ray absorptiometry (DXA).Results  The BMD of the femur and the lumbar spine (L‐spine) were negatively associated with the coronary calcium score (CCS) after adjusting for age in women but not in men. This inverse correlation was stronger in women with a longer time since menopause (r = −0·35 at femur, postmenopausal women vs. r = −0·10 at femur, premenopausal women, P < 0·05), and it was stronger at the femur than in the L‐spine (r = −0·35 at femur vs. r = −0·16 at L‐spine, P < 0·01). The relationship was also stronger in postmenopausal women with osteoporosis and osteopaenia than in women with normal BMD. The lower BMD was associated with higher coronary plaque burdens and multidiseased coronary vessels in both men and women (P < 0·01).Conclusions  Increased CCS and subclinical atherosclerosis of plaque burdens as revealed by MDCT was associated with a low BMD in all women, independent of cardiovascular risk factors and age.
How do you approach the problem of TSH elevation in a patient on high‐dose thyroid hormone replacement?
Authors: Morris John C. 
Published: February 2009

SummaryPersistent elevation of TSH levels in patients under treatment for hypothyroidism is a relatively common clinical problem in endocrinology practice. The most common cause for this phenomenon is poor patient compliance with their thyroid hormone tablets. In the compliant patient, however, multiple aetiologies are possible and a methodological and stepwise approach to the patient's problem will uniformly identify a cause, or at least a resolution.
Age and sex as predictors of biochemical activity in acromegaly: analysis of 1485 patients from the German Acromegaly Register
Authors: Petersenn S. , Buchfelder M. , Gerbert B. , Franz H. , Quabbe H. J. , Schulte H. M. , Grussendorf M. , Reincke M. ,   for the Participants of the German Acromegaly Register
Published: February 2009

SummaryObjective We evaluated the German Acromegaly Register for clinical variables associated with the initial biochemical activity of patients with acromegaly.Design Retrospective analysis of data in the registry.Patients A total of 1485 patients with acromegaly (males 45·6%, females 54·4%) were treated in 42 German endocrine centres until November 2005. Linear regression models were used to estimate the influence of various parameters on biochemical activity.Results Male patients with acromegaly were significantly younger at the time of diagnosis than female patients (41vs.47 years,P < 0·0001) and had significantly higher random GH levels than females (21vs.14 ng/ml,P < 0·005) and IGF‐1 levels (773vs.679 ng/ml,P < 0·0001), respectively. Age at initial presentation turned out to be the most important independent risk factor associated with random GH levels, oral glucose tolerance test‐suppressed GH levels, IGF‐1 levels, body mass index (BMI), tumour size and prevalence of hypopituitarism. Sex was an independent risk factor for IGF‐1 levels, BMI and prevalence of hypopituitarism. Tumour size was an independent risk factor for both GH and IGF‐1 levels.Conclusions In summary, initial biochemical activity of acromegaly is influenced by patient’s age and to a lesser degree by patient’s sex. Male patients are on an average 6 years younger than females.
Vitamin D and mortality in older men and women
Authors: Pilz Stefan , Dobnig Harald , Nijpels Giel , Heine Robert J. , Stehouwer Coen D. A. , Snijder Marieke B. , Van Dam Rob M. , Dekker Jacqueline M. 
Published: February 2009

SummaryObjective  Vitamin D deficiency is common among the elderly and may contribute to cardiovascular disease. The aim of our study was to elucidate whether low serum levels of 25‐hydroxyvitamin D [25(OH)D] are associated with an increased risk of all‐cause and cardiovascular mortality.Design and patients  The Hoorn Study is a prospective population‐based study among older men and women.Measurements  Fasting serum 25(OH)D was determined in 614 study participants at the follow‐up visit in 2000–2001, the baseline for the present analysis. To account for sex differences and seasonal variations of 25(OH)D levels we formed sex‐specific quartiles, which were calculated from the 25(OH)D values of each season.Results  After a mean follow‐up period of 6·2 years, 51 study participants died including 20 deaths due to cardiovascular causes. Unadjusted Cox proportional hazard ratios (HRs; with 95% confidence intervals) for all‐cause and cardiovascular mortality in the first when compared with the upper three 25(OH)D quartiles were 2·24 (1·28–3·92; P = 0·005) and 4·78 (1·95–11·69; P = 0·001), respectively. After adjustment for age, sex, diabetes mellitus, smoking status, arterial hypertension, high‐density lipoprotein‐cholesterol, glomerular filtration rate and waist‐to‐hip ratio, the HRs remained significant for all‐cause [1·97 (1·08–3·58; P = 0·027)] and for cardiovascular mortality [5·38 (2·02–14·34; P = 0·001)].Conclusions  Low 25(OH)D levels are associated with all‐cause mortality and even more pronounced with cardiovascular mortality, but it remains unclear whether vitamin D deficiency is a cause or a consequence of a poor health status. Therefore, intervention studies are warranted to evaluate whether vitamin D supplementation reduces mortality and cardiovascular diseases.
Insulin‐like factor 3 as a marker of testicular function in obese men
Authors: Foresta Carlo , Di Mambro Antonella , Pagano Claudio , Garolla Andrea , Vettor Roberto , Ferlin Alberto 
Published: February 2009

SummaryObjectives  Testicular function declines with obesity as a result of central and peripheral mechanisms, including a primary dysfunction of the Leydig cells. The levels of insulin‐like factor 3 (INSL3), a sensitive marker of Leydig cell impairment, have never been evaluated in obese men. To better evaluate the hormonal function of the testis in obese men, we analysed their INSL3 plasma levels and compared them with the obesity status and the other reproductive hormones.Design  Cross‐sectional study.Patients  Thirty‐one obese men [body mass index (BMI) >30 kg/m2) aged 22–49 years and 64 age‐matched nonobese men.Measurements  Plasma concentrations of INSL3, testosterone (T), sex hormone‐binding globulin (SHBG), oestradiol (E2), LH, FSH. Free testosterone (FT) levels were calculated.Results  Obese men had significantly lower plasma concentrations of total T, SHBG, FT and INSL3, and higher levels of E2 with respect to nonobese men. LH and FSH values were not different from controls. In obese men, we found a significant negative correlation between BMI and INSL3, and a positive correlation between INSL3 and T. Only one (1/31, 3·2%) obese man had subnormal T levels. On the contrary, 10/31 (32·3%) obese men had low INSL3 values.Conclusions  This study showed for the first time that INSL3 levels decrease with obesity, probably as a result of a primary dysfunction of the Leydig cells. INSL3 is a reliable marker of Leydig cell general impairment, whereas T mainly reflects the steroidogenic activity of these cells.
Likelihood of persistent GH deficiency into late adolescence: relationship to the presence of an ectopic or normally sited posterior pituitary gland
Authors: Murray P.G. , Hague C. , Fafoula O. , Gleeson H. , Patel L. , Banerjee I. , Raabe A.L. , Hall C.M. , Wright N.B. , Amin R. , Clayton P.E. 
Published: February 2009

SummaryObjectives  The presence of an ectopic posterior pituitary gland (EPP) in childhood is associated with isolated GH deficiency (IGHD) and multiple pituitary hormone deficiency. GHD in late adolescence has been defined as a peak GH level <5 μg/l. The aim of this study was to identify the likelihood of persistent GHD in late adolescence in patients with an EPP compared with those with a normally sited posterior pituitary (NPP).Methods  In 18 patients with an EPP and 15 patients with an NPP, clinical, biochemical and radiographic data were collected.Results  In the EPP vs. the NPP group, the change in peak GH levels at the end of growth was less (+0·4[95% confidence interval (CI) ‐ 0·8 to 2·7] vs. +4·1[95%CI + 0·4 to +10·5] μg/l, P‐value for ancova = 0·03, after adjustment for age and sex). Using a peak GH level of <5 μg/l as a cut‐off for GHD, 66% of EPP subjects compared with 40% of NPP subjects had GHD (P = 0·3). Hundred per cent of EPP subjects had a peak GH level on retesting <10 μg/l, compared with 40% of NPP subjects (P < 0·001).Conclusion  It is important to document GH status at the end of growth, even if there is a structural abnormality of the hypothalamic–pituitary axis. The presence of an EPP compared to an NPP increases the likelihood of persistent GHD by 26%. As all EPP patients had a peak GH level of <10 μg/l, the cut‐off for persistent GHD in late adolescence may need to be revised.
Prevalence of mental disorders in acromegaly: a cross‐sectional study in 81 acromegalic patients
Authors: Sievers Caroline , Dimopoulou Christina , Pfister Hildegard , Lieb Roselind , Steffin Birgit , Roemmler Josefine , Schopohl Jochen , Mueller Marion , Schneider Harald Jörn , Ising Marcus , Wittchen Hans Ulrich , Stalla Guenter Karl 
Published: February 2009

SummaryObjective  Emotional and behavioural alterations have been described in acromegalic patients. However, the nature and psychopathological value of these changes remained unclear.We examined whether acromegalic patients have an increased prevalence of comorbid DSM‐IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Version) mental disorders in comparison to subjects with or without chronic somatic disorders.Design/patients  A cross‐sectional study was conducted at the Max‐Planck Institute of Psychiatry and the Ludwig‐Maximilians‐University Munich. Eighty‐one acromegalic patients were enrolled. Control subjects with (n = 3281) and without chronic somatic (n = 430) disorders were drawn from a representative sample of the German adult general population as part of the Mental Health Supplement of the German Health Interview and Examination Survey. Lifetime and 12‐month prevalences of DSM‐IV mental disorders were assessed with face‐to‐face interviews using the standardized German computer‐assisted version of the Composite International Diagnostic Interview.Results  Acromegalic patients had increased lifetime rates of affective disorders of 34·6% compared to 21·4% in the group with chronic somatic disorders (OR = 2·0, 95% CI 1·2–3·2) and to 11·1% in the group without chronic somatic disorders (OR = 4·4, 95% CI 2·3–8·7). Affective disorders that occurred significantly more often than in the control groups began during the putative period of already present GH excess. Higher rates of DSM‐IV mental disorders were reported in those patients with additional treatment after surgery.Conclusion  Acromegaly is associated with an increased prevalence and a specific pattern of affective disorders. Greater emphasis on diagnosing and treatment of mental disorders in acromegalic patients might improve the disease management.
Site prioritisation for the protection of rare subterranean species – the cases of two ostracods from south‐western France
Authors: DANIELOPOL DAN L. , ARTHEAU MALVINA , MARMONIER PIERRE 
Published: February 2009

Summary1. Delineation of protected areas for rare subterranean species is a key problem for groundwater biodiversity conservation, because of practical difficulties in implementation. Criteria for site selection are presented that are derived from studies on two remarkable Ostracoda, Dolekiella europaea Gidó, Artheau, Colin, Danielopol & Marmonier (Limnocytheridae) and Vestalenula carveli Artheau (Darwinulidae) discovered in south‐western France.2. Arguments for natural heritage value and protection of subterranean species are proposed and illustrated by using information on these two ostracod species. The proposed criteria are: (i) local and/or regional endemism; (ii) known occurrence of the species at a few localities only; (iii) representativeness for ancient phylogenetic lineages with wider geographical distributions in the past; and (iv) suitability for scientific study because of unique morphological or biological traits.3. It is also proposed to prioritise the protection of subsurface sites using the following criteria: (i) type locality for newly described species; (ii) presence of other rare stygobiotic taxa; and (iii) high population densities of the primary target species.4. Development and implementation of protection strategies at local scale are likely to benefit from collaboration between scientists, policy makers and stakeholders. The measures taken should complement existing national and/or international attempts at large‐scale protection of groundwater biodiversity.
Substantial differences in littoral fish community structure and dynamics in subtropical and temperate shallow lakes
Authors: TEIXEIRA‐de MELLO FRANCO , MEERHOFF MARIANA , PEKCAN‐HEKIM ZEYNEP , JEPPESEN ERIK 
Published: February 2009

Summary1. Fish play a key role in the functioning of temperate shallow lakes by affecting nutrient exchange among habitats as well as lake trophic structure and dynamics. These processes are, in turn, strongly influenced by the abundance of submerged macrophytes, because piscivorous fish are often abundant at high macrophyte density. Whether this applies to warmer climates as well is virtually unknown.2. To compare fish community structure and dynamics in plant beds between subtropical and temperate shallow lakes we conducted experiments with artificial submerged and free‐floating plant beds in a set of 10 shallow lakes in Uruguay (30°–35°S) and Denmark (55°–57°N), paired along a gradient of limnological characteristics.3. The differences between regions were more pronounced than differences attributable to trophic state. The subtropical littoral fish communities were characterised by higher species richness, higher densities, higher biomass, higher trophic diversity (with predominance of omnivores and lack of true piscivores) and smaller body size than in the comparable temperate lakes. On average, fish densities were 93 ind. m−2 (±10 SE) in the subtropical and 10 ind. m−2 (±2 SE) in the temperate lakes. We found a twofold higher total fish biomass per unit of total phosphorus in the subtropical than in the temperate lakes, and as fish size is smaller in the former, the implication is that more energy reaches the littoral zone fish community of the warmer lakes.4. Plant architecture affected the spatial distribution of fish within each climate zone. Thus, in the temperate zone fish exhibited higher densities among the artificial free‐floating plants while subtropical fish were denser in the artificial submerged plant beds. These patterns appeared in most lakes, regardless of water turbidity or trophic state.5. The subtropical littoral fish communities resembled the fish communities typically occurring in temperate eutrophic and hypertrophic lakes. Our results add to the growing evidence that climate warming may lead to more complex and omnivory‐dominated food webs and higher density and dominance of smaller‐sized fish. This type of community structure may lead to a weakening of the trophic cascading effects commonly observed in temperate shallow lakes and a higher risk of eutrophication.
Patient acuity: a concept analysis
Authors: Brennan Caitlin W. , Daly Barbara J. 
Published: February 2009

AbstractTitle. Patient acuity: a concept analysis.Aim. This paper is a report of a concept analysis of patient acuity.Background. Patient acuity is a widely‐used term in the health sciences literature, but often without specification of its exact meaning. Concept clarification is therefore needed to delineate the meaning of patient acuity.Data sources. A review of the Pubmed, CINAHL, MEDLINE and PsychInfo databases for the keyword ‘acuity’ in the title or abstract of papers in English language journals, as well as searches for the term ‘acuity’ and ‘acute’ in the Merriam‐Webster and Oxford English Dictionaries were the data sources for this concept analysis. Papers were excluded if ‘acuity’ was not present in the title or abstract. Publication dates of the literature included in the review ranged from 1974 to 2008.Findings. The attributes of acuity are severity, intensity and the pairing of acuity measurements with another concept. These attributes were organized according to Holzemer’s Outcomes Model for Health Care Research as patient‐, provider‐ or system‐related. The sub‐categories of attributes identified were physical, psychological, nursing care needs, workload, complexity, case‐mix, patient classification systems, urgency/triage scales and other uses.Conclusion. Researchers are encouraged to specify which attribute of acuity they are studying and to develop measurement tools specific to that attribute, in order to move the science towards standardization of the concept of acuity and its measurement.
Task‐oriented training in rehabilitation after stroke: systematic review
Authors: Rensink Marijke , Schuurmans Marieke , Lindeman Eline , Hafsteinsdóttir Thóra 
Published: February 2009

AbstractTitle. Task‐oriented training in rehabilitation after stroke: systematic review.Aim. This paper is a report of a review conducted to provide an overview of the evidence in the literature on task‐oriented training of stroke survivors and its relevance in daily nursing practice.Background. Stroke is the second leading cause of death and one of the leading causes of adult disability in the Western world. The use of neurodevelopmental treatment in the daily nursing care of stroke survivors does not improve clinical outcomes. Nurses are therefore exploring other forms of rehabilitation intervention, including task‐oriented rehabilitation. Despite the growing number of studies showing evidence on task‐oriented interventions, recommendations for daily nursing practice are lacking.Data Sources. A range of databases was searched to identify papers addressing task‐oriented training in stroke rehabilitation, including Medline, CINAHL, Embase and the Cochrane Library of systematic reviews. Papers published in English between January 1996 and September 2007 were included. There were 42 papers in the final dataset, including nine systematic reviews.Review methods. The selected randomized controlled trials and systematic reviews were assessed for quality. Important characteristics and outcomes were extracted and summarized.Results. Studies of task‐related training showed benefits for functional outcome compared with traditional therapies. Active use of task‐oriented training with stroke survivors will lead to improvements in functional outcomes and overall health‐related quality of life.Conclusion. Generally, task‐oriented rehabilitation proved to be more effective. Many interventions are feasible for nurses and can be performed in a ward or at home. Nurses can and should play an important role in creating opportunities to practise meaningful functional tasks outside of regular therapy sessions.