bluuebunny/crossref_metadata_2025_split huggingface dataset:
4‐1BB and OX40 stimulation enhance CD8 and CD4 T‐cell responses to a DNA prime, poxvirus boost vaccine
Authors: Munks Michael W. , Mourich Dan V. , Mittler Robert S. , Weinberg Andrew D. , Hill Ann B. 
Published: December 2004

Summary4‐1BB (CD137) is a tumour necrosis factor receptor (TNFR) family member, expressed primarily on CD8 T cells after activation. Signalling through 4‐1BB has been reported to enhance CD8 T‐cell expansion and to protect activated CD8 T cells from death, resulting in an enlarged memory population. Although stimulating 4‐1BB has been shown to significantly improve the immune response to weak immunogens such as tumours, little is known about its effect on the CD8 T‐cell response to a powerful viral vector such as vaccinia. To test 4‐1BB's ability to improve the murine CD8 T cell response to a DNA prime, poxvirus boost vaccine, similar to those used for human immunodeficiency virus and simian immunodeficiency virus vaccines, we administered 4‐1BB agonist antibody at the time of the poxvirus boost. 4‐1BB stimulation increased the number of functional memory CD8 T cells by two‐ to fourfold. However, we saw a similar enhancement at the peak of the response and in the memory phase, thus we found no evidence in the context of virus infection that 4‐1BB stimulation could increase the percentage of CD8 T cells that survive the acute activation phase to become memory cells. OX40 (CD134) is an analogous TNFR family member expressed primarily on activated CD4 T cells. OX40 stimulation increased the number of antigen‐specific CD4 T cells approximately threefold. Stimulating both 4‐1BB and OX40 enhanced the CD8 T‐cell response more than 4‐1BB alone. Thus stimulating these receptors can improve the response to a powerful virus vector, and may be useful in vaccine development.
Deficiency of BLNK hampers PLC‐γ2 phosphorylation and Ca2+ influx induced by the pre‐B‐cell receptor in human pre‐B cells
Authors: Taguchi Tomoko , Kiyokawa Nobutaka , Takenouch Hisami , Matsui Jun , Tang Wei‐Ran , Nakajima Hideki , Suzuki Kyoko , Shiozawa Yusuke , Saito Masahiro , Katagiri Yohko U. , Takahashi Takao , Karasuyama Hajime , Matsuo Yoshinobu , Okita Hajime , Fujimoto Junichiro 
Published: December 2004

SummaryB‐cell linker protein (BLNK) is a component of the B‐cell receptor (BCR) as well as of the pre‐BCR signalling pathway, and BLNK–/– mice have a block in B lymphopoiesis at the pro‐B/pre‐B cell stage. A recent report described the complete loss or drastic reduction of BLNK expression in approximately 50% of human childhood pre‐B acute lymphoblastic leukaemias (ALL), therefore we investigated BLNK expression in human pre‐B ALL cell lines. One of the four cell lines tested, HPB‐NULL cells, was found to lack BLNK expression, and we used these human pre‐B ALL cell lines that express and do not express BLNK to investigate the intracellular signalling events following pre‐BCR cross‐linking. When pre‐BCR was cross‐linked with anti‐μ heavy‐chain antibodies, significant phosphorylation of intracellular molecules, including Syk, Shc, ERK MAP kinase, and AKT, and an activation of Ras were observed without regard to deficiency of BLNK expression, suggesting that BLNK is not required for pre‐BCR‐mediated activation of MAP kinase and phosphatidyl‐inositol 3 (PI3) kinase signalling. By contrast, phospholipase C‐γ2 (PLC‐γ2) phosphorylation and an increase in intracellular Ca2+ level mediated by pre‐BCR cross‐linking were observed only in the BLNK‐expressing cells, indicating that BLNK is essential for PLC‐γ2‐induced Ca2+ influx. Human pre‐B cell lines expressing and not expressing BLNK should provide an in vitro model for investigation of the role of BLNK in the pre‐BCR‐mediated signalling mechanism.
The use of membrane translocating peptides to identify sites of interaction between the C5a receptor and downstream effector proteins
Authors: Auger Graham A. , Smith Brenda M. , Pease James E. , Barker Michael D. 
Published: December 2004

SummaryThe complement fragment C5a is a potent leucocyte chemoattractant and activator, mediating its effects through a G‐protein‐coupled receptor. Whilst the C‐terminal domain of this receptor has been shown to be essential for receptor desensitization and internalization, it is not known which domains couple to the receptor's heterotrimeric G proteins. In this report we have used a membrane translocating sequence (MTS) to examine the effects of the four intracellular domains of the human C5a receptor (C5aR) on the receptor's signalling via Gαi family heterotrimeric G proteins in intact RBL‐2H3 cells. The results indicate that all of the intracellular domains couple to downstream signalling, with the proximal region of the C terminus being a major binding site and intracellular loop 3 playing a role in G protein activation or receptor desensitization.
Differential production of interleukin‐10 and interleukin‐12 in mononuclear cells from leprosy patients with a Toll‐like receptor 2 mutation
Authors: Kang Tae Jin , Yeum Chung Eun , Kim Byoung Chul , You Eun‐Young , Chae Gue‐Tae 
Published: December 2004

SummaryToll‐like receptor 2 (TLR2) is a key mediator of the immune response to mycobacterial infections, and mutations in TLR2 have been shown to confer susceptibility to infection with mycobacteria. This study investigated the profiles of cytokines, such as interferon (IFN)‐γ, interleukin (IL)‐10, IL‐12 and tumour necrosis factor (TNF)‐α in response to Mycobacterium leprae in peripheral blood mononuclear cells (PBMC) with the TLR2 mutation Arg677Trp, a recently reported polymorphism that is associated with lepromatous leprosy. In leprosy patients with the TLR2 mutation, production of IL‐2, IL‐12, IFN‐γ, and TNF‐α by M. leprae‐stimulated PBMC were significantly decreased compared with that in groups with wild‐type TLR2. However, the cells from patients with the TLR2 mutation showed significantly increased production of IL‐10. There was no significant difference in IL‐4 production between the mutant and wild‐type during stimulation. Thus, these results suggest that the TLR2 signal pathway plays a critical role in the alteration of cytokine profiles in PBMC from leprosy patients and the TLR2 mutation Arg677Trp provides a mechanism for the poor cellular immune response associated with lepromatous leprosy.
The potential for Toll‐like receptors to collaborate with other innate immune receptors
Authors: Mukhopadhyay Subhankar , Herre Jurgen , Brown Gordon D. , Gordon Siamon 
Published: December 2004

SummaryCells of the innate immune system express a large repertoire of germ‐line encoded cell‐surface glycoprotein receptors including Toll‐like receptors (TLRs). TLRs recognize conserved motifs on microbes and induce inflammatory signals. Evidence suggests that individual members of the TLR family or other non‐TLR surface antigens either physically or functionally interact with each other and cumulative effects of these interactions instruct the nature and outcome of the immune response to a particular pathogen.
Nest predators affect spatial dynamics of breeding red‐backed shrikes (Lanius collurio)
Authors: Roos Staffan , Pärt Tomas 
Published: December 2004

SummaryPredation may be a strong selective factor affecting individual behaviour and life histories. However, few studies have investigated whether predators affect breeding habitat selection of prey species.We tested whether breeding habitat selection and reproduction of a tropical migrant, the red‐backed shrike (Lanius collurioL.), was related to the presence of breeding pairs of its potential nest predators, magpie (Pica picaL.), hooded crow (Corvus corone cornixL.) and jackdaw (C. monedulaL.).Only magpie and hooded crow territories were associated with an elevated risk of predation based on an artificial nest experiment with nests mimicking red‐backed shrike nests. Predation risk on real red‐backed shrike nests was also higher close to nests of hooded crow and magpie than elsewhere in the landscape.Occupation frequency of known red‐backed shrike territory sites during 3 years of study increased with increasing mean distance to the nearest magpie nest.Changes in spatial distribution of corvids affected the spatial distribution of red‐backed shrikes. Vacant red‐backed shrike territory sites were more likely to become occupied in the next year when magpie and hooded crows had moved away from the site, while occupied sites were more likely to be abandoned in the next year when at least hooded crows had moved closer.Our results suggest that breeding territories of nest predators may affect breeding habitat selection of prey species. Thus, a large part of an observed spatial dynamics of prey species may be caused by a corresponding spatial dynamics of predators. Because sink territories are occupied more irregularly than source territories, we suggest that the dynamics in predator sinks may be the driving force of the spatial dynamics of prey species.
Large‐scale spatial dynamics of vole populations in Finland revealed by the breeding success of vole‐eating avian predators
Authors: Sundell Janne , Huitu Otso , Henttonen Heikki , Kaikusalo Asko , Korpimäki Erkki , Pietiäinen Hannu , Saurola Pertti , Hanski Ilkka 
Published: December 2004

Summary

Voles in northern Europe have been shown to exhibit cyclic population dynamics, with a latitudinal gradient in cycle length, amplitude and interspecific synchrony.
Previous studies have been based on a relatively sparse network of sampling sites. In the absence of spatially comprehensive long‐term records of vole dynamics, we analysed a proxy of vole density, bird‐ringing data on vole‐eating avian predators, Tengmalm's owl (Aegolius funereus L.), the Ural owl (Strix uralensis Pall.), the long‐eared owl (Asio otus L.) and the rough‐legged buzzard (Buteo lagopus Pontoppidan) to study spatial population dynamics of voles.
We demonstrate that the breeding success of the avian predators is highly dependent on the abundance of voles, which is also reflected in the numbers of nestlings ringed in a particular area in each year.
Our results show the expected increase in cycle length from south to north in Finland, but also from west to east, and in contrast to previous studies, increasing irregularity of the cyclic dynamics towards the north.
Fluctuations of vole populations have been synchronous over large distances, up to several hundred kilometres. Such large‐scale synchrony is more likely to be caused by movements of vole‐eating predators and/or by climatic perturbations than by dispersal of voles.
We could not conclusively verify the recent suggestion that vole population dynamics have become less regular across Finland, although certain long‐term changes are apparent.
Process evaluation of two environmental nutrition programmes and an educational nutrition programme conducted at supermarkets and worksite cafeterias in the Netherlands
Authors: Steenhuis I. , van Assema P. , Reubsaet A. , Kok G. 
Published: December 2004

AbstractIntroduction  This article describes the process evaluation of two environmental programmes and an educational nutrition programme, implemented at supermarkets and worksite cafeterias. Studies conducted earlier, indicated that the programmes had no effect on consumers’ eating behaviour. Consequently, the more specific purpose of the present study was to identify explanations for the ineffectiveness of the programmes and to formulate recommendations for future programmes.Materials and methods  The environmental programmes included labelling of healthy products and increasing the range of healthy foods on offer. The education programme consisted of several elements, such as brochures and a self‐help guide. Semi‐structured interviews were conducted with 21 managers of supermarkets and worksite cafeterias where the programmes were implemented.Results  Although materials were not always entirely compatible with the different supermarkets and worksite cafeterias, the degree of implementation was satisfactory. According to the managers, the programmes were not striking enough, the labelling would have been more effective if it had discriminated between different brands of a product, and the number of new products was too small compared with the total range of foods on offer.Conclusions  The findings suggest that programmes should be promoted intensively. Furthermore, the relevant manufacturers and wholesalers supplying worksite cafeterias should be encouraged to increase their range of suitable low‐fat products. Finally, the feasibility and possible effects of brand‐specific labelling should be investigated further.
Quality of lipid‐lowering therapy in patients with ischaemic heart disease: a register‐based study in 3477 patients
Authors: Kanstrup H. , Lassen J. F. , Heickendorff L. , Lauritzen T. , Larsen M. L. 
Published: December 2004

Abstract.Objective.  To develop a method to evaluate routine management practices concerning lipid‐lowering treatment in patients with ischaemic heart disease (IHD) in a large geographic area.Design.  A register‐based study linking information on IHD with cholesterol levels and prescriptions on lipid‐lowering medications by personal registration number. Plasma cholesterol levels were collected from the electronic laboratory information system (LIS), and information on IHD from the Danish National Hospital Register (LPR). The extent of treatment was evaluated by information on prescriptions on lipid‐lowering medications from the Danish National Health Service.Setting.  Evaluates treatment in both hospitals and primary care.Subjects.  Patients with IHD.Results.  In total 3477 patients <75 years were identified, and 43.7% had claimed prescriptions on lipid‐lowering medications (01.01.2000–31.07.2000). In the whole population, 42% reached the goal for total cholesterol lower than 5 mmol L−1 set by European guidelines. In the 1521 patients treated with lipid‐lowering medications 55% reached the goal.Conclusion.  By use of registers it was possible to develop a method to evaluate and monitor current treatment practice for dyslipidaemia in a large geographic area. The method makes it possible to evaluate the impact of guidelines, changes in treatment procedures and to provide feedback to physicians. The study revealed that lipid‐lowering treatment is still not sufficiently implemented in clinical practice even in patients with known IHD, and the used doses of statins are lower than those used in randomized clinical trials.
Amphoterin as an extracellular regulator of cell motility: from discovery to disease
Authors: Huttunen H. J. , Rauvala H. 
Published: December 2004

Abstract.Amphoterin is a ubiquitous and highly conserved protein previously considered solely as a chromatin‐associated, nuclear molecule. Amphoterin is released into the extracellular space by various cell types, and plays an important role in the regulation of cell migration, differentiation, tumorigenesis and inflammation. This paper reviews recent research on the mechanistic background underlying the biology of secreted amphoterin, with an emphasis on the role of amphoterin as an autocrine/paracrine regulator of cell migration.
HMGB1 is a potent trigger of arthritis
Authors: Andersson U. , Erlandsson‐Harris H. 
Published: December 2004

Abstract.Rheumatoid arthritis is a chronic inflammatory disease characterized by synovial inflammation and structural damage of joints. Although the cause of rheumatoid arthritis (RA) remains unknown, the excessive production of proinflammatory cytokines such as tumour necrosis factor (TNF) and interleukin‐1 (IL‐1) by intra‐articular macrophages occupies a critical pathogenic role in the development and progression of the disease. High mobility group box chromosomal protein 1 (HMGB1) is a recently identified mediator of interest in human and experimental arthritides. HMGB1 can either be actively secreted from macrophages or passively released from necrotic cells of all kinds. Activated macrophages and unprogrammed cell death caused by ischaemia or activated complement are all prominent features of chronic arthritis, contributing to the persistent synovial inflammation. HMGB1 is cytoplasmically and extracellularly overexpressed in inflammatory synovial tissue in human RA as well as experimental collagen‐induced arthritis. Elevated levels of HMGB1 are also present in synovial fluid samples from RA patients. Synovial tissue from rats with experimental arthritis exhibits aberrant deposition of HMGB1 preceding the onset of clinical signs of arthritis, and the expression becomes prominent after the onset of clinical disease. The synovial levels of HMGB1 are comparable with those of TNF and IL‐1β at the peak of manifest disease. HMGB1‐targeted intervention with either neutralizing antibodies or the antagonistic A box domain of HMGB1 ameliorates collagen‐induced arthritis both in mice and rats, and inhibits the local overexpression of IL‐1β in the joints. It is thus conceivable that therapeutic HMGB1 blockade may contribute to future treatment of human chronic arthritis.
Prognostic impact of different regional referral practices for interventional investigation and coronary treatment after exercise testing: a population‐based 5‐year follow‐up study
Authors: Niemann T. , Labouriau R. , Sørensen H. Toft , Thorsgaard N. , Nielsen T. Toftegaard 
Published: December 2004

Abstract.Objective. To examine the association among different centres’ referral practices for coronary angiography (CAG) after exercise testing, with 1‐ and 5‐year outcomes.Design. Observational population‐based cohort study.Setting. All 10 hospitals and six private practising consultants in Aarhus and Ringkjoebing counties (900 000 inhabitants), Denmark.Subjects. All patients who in 1996 had an abnormal bicycle exercise test (n = 736).Measurements. Referral for CAG, coronary intervention, cardiovascular and all‐cause mortality, and myocardial infarction (MI).Results. As an immediate consequence of the exercise test, 60.7% of subjects were referred for CAG. Based on the centres’ fraction of patients referred for CAG, three categories of centres were defined: low (<33%), intermediate (33–66%) and high (>66%). A low compared with a high referral fraction was associated with a similar 5‐year mortality and MI ratio [all‐cause/cardiovascular mortality rate ratio (RR) = 1.33, 95% confidence interval (CI): 0.45–3.92/RR = 0.62, 95% CI: 0.25–1.57; and MI RR = 0.92, 95% CI: 0.45–1.86]. The same was found for an intermediate compared with a high fraction (all‐cause/cardiovascular mortality RR = 0.92, 95% CI: 0.49–1.72/RR = 0.74, 95% CI: 0.42–1.33; and MI RR = 1.07, 95% CI: 0.68–1.70). Estimates were about the same after 1 year of follow‐up with no major differences among centres in mortality or MI.Conclusions. Centres’ different referral practices for interventional investigation and treatment were not associated significantly with short‐term or long‐term mortality or MI among patients with an abnormal exercise test.
The 21‐year follow‐up of the Cardiovascular Risk in Young Finns Study: risk factor levels, secular trends and east–west difference
Authors: Juonala M. , Viikari J. S. A. , Hutri‐Kähönen N. , Pietikäinen M. , Jokinen E. , Taittonen L. , Marniemi J. , Rönnemaa T. , Raitakari O. T. 
Published: December 2004

Abstract.Objectives.  The Cardiovascular Risk in Young Finns Study is an on‐going multicentre study of atherosclerosis precursors in Finnish children and young adults. We have collected risk factor data in the 21‐year follow‐up performed in 2001. The aims of this analysis were to examine the levels, secular trends and east–west difference in risk factors amongst young adults.Design.  Population based follow‐up study.Subjects.  A total of 2283 participants aged 24–39 years in 2001 (63.5% of the original cohort).Main outcome measures.  Levels of serum lipids, apolipoproteins, blood pressure and smoking.Results.  The mean serum total cholesterol, low density lipoprotein cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride concentrations in 24–39‐year‐old adults were 5.16, 3.27, 1.29 and 1.34 mmol L−1, respectively. Total cholesterol (5.21 vs. 5.12 mmol L−1, P = 0.046), HDL cholesterol (1.31 vs. 1.28 mmol L−1, P = 0.027), systolic blood pressure (118 vs. 115 mmHg, P < 0.0001) and diastolic blood pressure (72 vs. 70 mmHg, P < 0.0001) were higher in subjects originating from eastern Finland compared with those from western Finland. Significant secular trends between 1986 and 2001 in 24‐year‐old subjects (n = 783) included an increase in serum triglycerides and body mass index (BMI), a decrease in blood pressure and HDL cholesterol and a modest 5% decrease in total cholesterol levels.Conclusions.  During the past 15 years, BMI and triglyceride levels have increased in young adults in Finland. At the same time, the reduction in cholesterol concentration has been slow. Consistent with persistent regional differences in cardiovascular morbidity within Finland, our data demonstrate significant differences in the levels of cardiovascular risk factors between subjects originating from eastern and western Finland.
Orthostatic hypotension and the risk of myocardial infarction in the home‐dwelling elderly
Authors: Luukinen H. , Koski K. , Laippala P. , Airaksinen K. E. J. 
Published: December 2004

Abstract.Objectives.  We investigated the prognostic significance of orthostatic hypotension on the risk of myocardial infarction (MI) amongst the elderly.Design.  Prospective population‐based study. Setting.  Home‐dwelling population.Subjects.  Orthostatic testing was performed between 8 a.m. and 2 p.m., irrespective of having had meals, on 792 persons, representing 82% of all home‐dwelling persons aged ≥70 years living in five municipalities around the city of Oulu.Main outcome measures.  Occurrence of cases of MI were recorded during mean 3.58 (SD 1.09) years follow‐up period, from national mortality statistics and local hospital discharge registers.Results.  Ninety cases of MI, of which 40 were fatal after initial hospitalization, occurred during the follow‐up period. Orthostatic diastolic blood pressure (BP) drop 1 min after standing up was associated with subsequent MI, but systolic BP reactions had no predictive value. According to the Cox regression model, the strongest predictor of the occurrence of subsequent MI was found in regard to ≥8 mmHg drop in diastolic BP 1 min after standing up; adjusted for history of MI, diabetes mellitus, chest pain, use of calcium antagonist, β‐blocker, nitrate and diuretic medication, hazard ratio of MI being 2.00 (1.11–3.59).Conclusions.  Orthostatic testing offers a novel means to assess the risk of MI amongst elderly persons. Diastolic BP drop immediately after standing up identifies elderly subjects at a high risk of subsequent MI.
Depot‐specific differences in perilipin mRNA but not protein expression in obesity
Authors: Arvidsson E. , Blomqvist L. , Rydén M. 
Published: December 2004

Abstract.Background.  Perilipin (PLIN) is a lipid droplet‐associated protein, which regulates lipolysis in rodent adipocytes by modulating the access of hormone‐sensitive lipase to the lipid surface. Little is known regarding the expression and function of PLIN in man. Subcutaneous (s.c.) and omental fat tissue display marked differences in both basal and stimulated lipolysis.Objective and subjects.  In order to assess whether this can be caused by differences in PLIN expression, we investigated the expression of PLIN mRNA and protein in s.c. and omental fat tissue samples from 16 obese women (n = 8) and men (n = 8).Methods.  For mRNA detection a quantitative real‐time PCR was used. Protein was analysed by Western blot.Results.  PLIN mRNA was significantly reduced in omental versus s.c. tissue (P = 0.022). In contrast, although PLIN protein levels were highly variable between the two depots when related to the reference protein β‐actin, no significant difference in PLIN protein expression was observed between the fat depots (P = 0.61). There were no gender‐specific differences in PLIN mRNA or protein.Conclusion.  Our results suggest that post‐transcriptional mechanisms may influence PLIN protein expression and that PLIN expression per se is probably not a major factor in determining the lipolytic differences between the s.c. and omental fat depots.