bluuebunny/crossref_metadata_2025_split huggingface dataset:
Special regulatory T cell review: The suppression problem!
Authors: Waldmann Herman 
Published: February 2008

SummaryThe concept of T‐cell mediated suppression evolved more than 30 years ago. At that time it spawned many claims that have not stood the test of time. The rediscovery of suppression phenomena and regulatory T cells over the past 15 years created schizophrenic responses amongst immunologists. Some claimed that the new proponents of suppression were, once again, bringing immunology into disrepute, whilst others have embraced the field with great enthusiasm and novel approaches to clarification. Without faithful repetition of the “old” experiments, it is difficult to establish what was right and what was wrong. Nevertheless, immunologists must now accept that a good number of the old claims were overstated, and reflected poor scientific discipline.
“I speak not to disprove what Brutus spoke, But here I am to speak what I do know”Shakespeare. Julius Caesar Act 3, Scene 2.
Special regulatory T‐cell review: regulatory T cells and the intestinal tract – patrolling the frontier
Authors: Izcue Ana , Powrie Fiona 
Published: February 2008

SummaryTolerance to self and harmless antigens is one of the central features of the immune system, and it is obtained through a combination of multiple mechanisms. Discriminating between pathogens and non‐pathogenic antigens is especially important in the intestine, which constitutes the main contact surface between the body and the outside environment. Recently, the role of Foxp3+ regulatory T cells (Treg) in the establishment and maintenance of tolerance has been the focus of numerous studies. In this review, we briefly discuss the historical background leading to the identification of Foxp3+ Treg and give an overview of their role in controlling systemic and mucosal immune responses.
Special regulatory T‐cell review: A rose by any other name: from suppressor T cells to Tregs, approbation to unbridled enthusiasm
Authors: Germain Ronald N. 
Published: February 2008

SummaryIn the early 1970s a spate of papers by research groups around the world provided evidence for a negative regulatory role of thymus‐derived lymphocytes (T cells). In 1971, Gershon and Kondo published a seminal paper in Immunology entitled ‘Infectious Immunological Tolerance’1 indicating that such negative regulation could be a dominant effect that prevented otherwise ‘helpful’ T cells from mediating their function. Over the next decade, suppressor T cells, as these negative regulatory cells became known, were intensively investigated and a complex set of interacting cells and soluble factors were described as mediators in this process of immune regulation. In the early 1980s, however, biochemical and molecular experiments raised questions about the interpretation of the earlier studies, and within a few years, the term ‘suppressor T cell’ had all but disappeared from prominence and research on this phenomenon was held in poor esteem. While this was happening, new studies appeared suggesting that a subset of T cells played a critical role in preventing autoimmunity. These T cells, eventually dubbed ‘regulatory T cells’, have become a major focus of modern cellular immunological investigation, with a predominance that perhaps eclipses even that seen in the earlier period of suppressor T cell ascendancy. This brief review summarizes the rise and fall of ‘suppressorology’ and the possibility that Tregs are a modern rediscovery of suppressor T cells made convincing by more robust models for their study and better reagents for their identification and analysis.
Special regulatory T cell review: The resurgence of the concept of contrasuppression in immunoregulation
Authors: Lehner Thomas 
Published: February 2008

SummaryThe original concept of contrasuppression (CS) is evident in many immunoregulatory mechanisms. Inhibition of suppressor activity – CS – may be critical in microbial infection and autoimmunity. The major cellular interactions involved in suppression are the CD25+ FoxP3+ CD4+ T regulatory cells, programmed death‐1 (PD‐1) : PD‐L1/L2 and cytotoxic T lymphocyte antigen‐4 (CTLA‐4) : CD80/86 pathways. These cellular functions are affected by dendritic cells (DC) and a complex array of cytokines of which interleukin (IL)‐2, IL‐10, IL‐6 and transforming growth factor‐β (TGF‐β) are especially significant. Inhibition of regulatory cells, suppressor pathways or cytokines, is consistent with CS and can be attributed to IL‐6, IL‐2, PD‐1 or PD‐L‐1 antibodies, blockade of CTLA‐4 : CD80/86 pathway, inhibition of CD40–CD40L pathways, and TGF‐β, IL‐10 antibodies. Contrasuppression may regulate innate immunity by Toll‐like receptor expressed not only in non‐cognate DC, monocytes, natural killer cells and γδ T cells but also in adaptive T cells. Furthermore, cross‐talk between innate and adaptive immunity may be facilitated by contrasuppressor activity.
‘‘What’s in a name?That which we call a rose by any other name would smell as sweet.’’ From Romeo and Juliet (II, 47–8) W. Shakespeare
The capacity ofSalmonellato survive inside dendritic cells and prevent antigen presentation to T cells is host specific
Authors: Bueno Susan M. , González Pablo A. , Carreño Leandro J. , Tobar Jaime A. , Mora Guido C. , Pereda Cristian J. , Salazar‐Onfray Flavio , Kalergis Alexis M. 
Published: February 2008

SummaryInfection withSalmonellaenterica serovar Typhimurium (S.Typhimurium) causes a severe and lethal systemic disease in mice, characterized by poor activation of the adaptive immune response againstSalmonella‐derived antigens. Recently, we and others have reported that this feature relies on the ability ofS. Typhimurium to survive within murine dendritic cells (DCs) and avoid the presentation of bacteria‐derived antigens to T cells. In contrast, here we show that infection of murine DCs with eitherS. Typhi orS. Enteritidis, two serovars adapted to different hosts, leads to an efficient T‐cell activation bothin vitroandin vivo. Accordingly,S. Typhi andS. Enteritidis failed to replicate within murine DCs and were quickly degraded, allowing T‐cell activation. In contrast, human DCs were found to be permissive for survival and proliferation ofS. Typhi, but not forS. Typhimurium orS. Enteritidis. Our data suggest thatSalmonellahost restriction is characterized by the ability of these bacteria to survive within DCs and avoid activation of the adaptive immune response in their specific hosts.
Why h2 does not always equal VA/VP?
Authors: WILSON A. J. 
Published: February 2008

AbstractOver the last decade, there has been a rapid growth in the application of quantitative genetic techniques to evolutionary studies of natural populations. Whereas this work yields enormous insight into evolutionary processes in the wild, the use of modelling techniques and strategies adopted from animal breeders means that estimates of trait heritabilities (h2) are highly vulnerable to misinterpretation. Specifically, when estimated using animal models, h2 will not generally be comparable across studies and must be interpreted as being conditioned on any fixed effects included in the model. Failure to realize the model dependency of published h2 estimates will give a very misleading, and in most cases upwardly biased, impression of the potential for trait evolution.
A Branch‐inducing Phytoplasma in Euphorbia pulcherrima is Associated with Changes in Expression of Host Genes
Authors: Nicolaisen M. , Horvath D. P. 
Published: February 2008

AbstractPhytoplasma infection causes a desirable branching phenotype in the ornamental plant Euphorbia pulcherrima by releasing apical dominance. Four E. pulcherrima genes specifically regulated during phytoplasma infection were identified using a combination of differential display of cDNA‐polymerase chain reaction (PCR) products and microarray analysis. According to BLAST searches the possible functions of identified genes included a histidine‐containing phosphotransmitter, an α‐expansin, a protein with similarity to the gibberellin‐regulated GAST‐1 and a protein with similarity to an Arabidopsis thaliana protein with unknown function.
From Gift Relationships to Quasi‐markets: An Odyssey along the Policy Paths of Altruism and Egoism
Authors: Pinker Robert 
Published: February 2008

Abstract Nearly forty years ago, the publication of ‘The Price of Blood’ (1968) and ‘The Gift Relationship’ (1970) added a new dimension of ideological conflict to the debate about the values, ends and means of social policy. The questions that Richard Titmuss posed in ‘The Gift Relationship’ are still discussed in current debates about the respective merits of unitary and pluralist models of welfare, the egoistic and altruistic motives that underpin them, and the rights and responsibilities intrinsic to the status of citizenship. The ways in which the content and focus of these debates have changed over the past forty years are here reviewed, taking Titmuss's ‘The Gift Relationship’, my own contributions in ‘Social Theory and Social Policy’ (1971) and ‘The Idea of Welfare’ (1979), and Julian Le Grand's ‘Motivation, Agency and Public Policy’ (2003) as the temporal and salient points of reference. A brief introduction describes how the academic debate became sharply polarized in the late 1960s and early 1970s, and how a key decision about the future development of this journal was taken at the same time.
Emigration from Zimbabwe: Migrant Perspectives
Authors: Bloch Alice 
Published: February 2008

Abstract This article explores migration from Zimbabwe to the UK and South Africa and the experiences of the receiving countries from the perspective of the migrants. It provides a critical examination of the impact of structural barriers in both the UK and South Africa on the economic experiences of migrants. The effects of immigration status, due to the exclusion of asylum‐seekers in the UK and the presence of undocumented migrants in the UK and South Africa, is explored in relation to employment and remittance activities. The clear evidence of the deskilling taking place among the majority of Zimbabwean migrants – and its impact on remittances and other forms of transnational support – is also examined. The article concludes that any real commitment to alleviating global poverty on the part of the world's migrant receiving countries must include a re‐examination of barriers to employment, education and the use of skills, since these barriers not only have a short‐term impact on remittances to the sending country and fiscal capacity to contribute in the receiving country, but will also impact on longer‐term development should the migrants return to their country of origin.
Anti–tumour necrosis factor‐α therapy increases body weight in patients with chronic plaque psoriasis: a retrospective cohort study
Authors: Gisondi P , Cotena C , Tessari G , Girolomoni G 
Published: February 2008

AbstractBackground  Chronic plaque psoriasis is associated with overweight or obesity. Anti–tumour necrosis factor‐α (anti‐TNF‐α) treatments are now frequently used in psoriasis management. TNF‐α is deeply involved in body weight homeostasis, which may be affected by TNF‐α–targeted therapy.Objective  To investigate whether anti‐TNF‐α treatments is associated with changes in body weight in patients with chronic plaque psoriasis.Methods  We performed a retrospective controlled analysis comparing the variations in body weight and body mass index (BMI) in three closed cohorts of psoriatic patients during a 6‐month treatment with etanercept (N = 58), infliximab (N = 40) or methotrexate (N = 43).Results  We observed a body weight increment of 1.5 ± 2.7 kg (mean ± SD; P = 0.0002) and 2.5 ± 3.3 kg (P = 0.004) in patients treated with etanercept and infliximab, respectively. In contrast, a non‐significant change (0.6 ± 1.4 kg; P = 0.4) was measured in patients treated with methotrexate. The BMI increased with 0.5 ± 0.5 (P = 0.01) and 0.8 ± 1 (P = 0.003) points in patients treated with etanercept and infliximab, respectively, whereas it did not change (< 0.2 ± 0.5; P = 0.06) in patients treated with methotrexate. About one fourth of patients experienced a 4‐ to 10‐kg weight gain. Differences in body weight variations among patients treated with anti‐TNF‐α therapies and methotrexate were statistically significant (P = 0.0005). We could not identify clinical parameters predicting this phenomenon.Conclusions  Patients with psoriasis treated with long‐term anti‐TNF‐α therapies may manifest a body weight gain. This effect should be taken into account in the global approach to patients with psoriasis.
Clinical effectiveness and safety experience with efalizumab in the treatment of patients with moderate‐to‐severe plaque psoriasis in Taiwan: results of an open‐label, single‐arm pilot study
Authors: Tsai TF , Liu MT , Liao YH , Licu D 
Published: February 2008

AbstractBackground  No clinical trial of efalizumab has been conducted in Asia.Objective  To determine the efficacy and safety of efalizumab in Taiwanese patients with psoriasis.Methods  This is an open‐label, single‐arm pilot study conducted at two centres. Patients were given 1 mg/kg efalizumab subcutaneously once a week for 12 weeks and were then followed up for a further 12 weeks.Results  A total of 49 patients participated in the study. The median improvement in Psoriasis Area and Severity Index (PASI) during the treatment period was 19.6%, and a ≥ 50% improvement in PASI was seen in 20.4%. Rebound was seen in 17.8% of patients, and anti‐efalizumab antibodies were detected in 41% of patients. The most frequent adverse events were headache (34.7%), arthralgia/arthritis (28.6%), psoriasis events (new form/exacerbation; 26.5%) and pruritus (22.4%).Conclusions  This small pilot study indicated that efalizumab was effective in improving psoriasis symptoms in Taiwanese patients, with no new safety issues identified.
Evidence‐based review of lasers, light sources and photodynamic therapy in the treatment of acne vulgaris
Authors: Hædersdal M , Togsverd‐Bo K , Wulf HC 
Published: February 2008

AbstractBackground  There is a considerable need for effective and safe treatment for acne vulgaris.Objective  In a systematic review with an evidence‐based approach to assess the effects of optical treatments for acne vulgaris.Methods  Original publications of controlled clinical trials were identified through searches in PubMed and the Cochrane Library.Results  A total of 16 randomized controlled trials (RCT) and 3 controlled trials (CT) were identified, involving a total of 587 patients. Interventions included photodynamic therapy (PDT; 5 RCTs), infrared lasers (4 RCTs), broad‐spectrum light sources (3 RCTs, 1 CT), pulsed dye lasers (PDL; 2 RCTs, 1 CT), intense pulsed light (IPL; 1 RCTs, 2 CTs), and potassium titanyl phosphate laser (1 RCT). The randomization method was mentioned in 6 of 16 RCTs, and one trial described adequate allocation concealment. Most trials were intraindividual trials (12 of 19), which applied blinded response evaluations (12 of 19) and assessed a short‐term efficacy up to 12 weeks after treatment (17 of 19). Based on the present best available evidence, we conclude that optical treatments possess the potential to improve inflammatory acne on a short‐term basis with the most consistent outcomes for PDT [up to 68% improvement, aminolevulinic acid (ALA), methyl‐aminolevulinic acid (MAL) and red light]. IPL‐assisted PDT seems to be superior to IPL alone. Only two trials compare optical vs. conventional treatments, and further studies are needed. Side‐effects from optical treatments included pain, erythema, oedema, crusting, hyperpigmentation, pustular eruptions and were more intense for treatments combined with ALA or MAL.Conclusion  Evidence from controlled clinical trials indicates a short‐term efficacy from optical treatments for acne vulgaris with the most consistent outcomes for PDT. We recommend that patients are preoperatively informed of the existing evidence, which indicates that optical treatments today are not included among first line treatments.
Maneb potentiates paraquat neurotoxicity by inducing key Bcl‐2 family members
Authors: Fei Qingyan , Ethell Douglas W. 
Published: February 2008

AbstractAn important feature of Parkinson’s disease is the degeneration of dopaminergic neurons in theSubstantia Nigra pars compacta. Paraquat (PQ) and MPTP cause the selective degeneration of these neuronsin vivo, and combining PQ with maneb exacerbates that pathology. Elucidation of the cell death mechanisms involved is important to understand how multiple environmental toxins may contribute to sporadic Parkinson’s disease. We recently reported that PQ induces neuronal apoptosis through Bak activation, in contrast to MPP+, the toxic metabolite of MPTP, which relies on Bax and p53. Here we show that individually PQ and maneb activate Bak, but together they trigger Bax‐dependent cell death. Focusing on mechanisms responsible for this synergy, we found that maneb+PQ increased the expression of three strong Bak inhibitors, Bfl‐1, Bcl‐xL and Mcl‐1, and also induced Bax activators that included Bik and Bim. Those responses favor Bax‐dependent MOMP and apoptosis. SiRNA knockdown of Bax and Bak confirmed that individually PQ and maneb induce Bak‐dependent cell death, but together they block the Bak pathway and activate apoptosis through Bax.
Effects of Aripiprazole on Subjective and Physiological Responses to Alcohol
Authors: Kranzler Henry R. , Covault Jonathan , Pierucci‐Lagha Amira , Chan Grace , Douglas Kara , Arias Albert J. , Oncken Cheryl 
Published: February 2008

Background:  Aripiprazole is an atypical antipsychotic with partial agonist activity at D2 receptors, which could reduce the reinforcing effects of alcohol. The present study examined whether aripiprazole modifies the behavioral and physiological effects of a moderate dose of alcohol in a group of social drinkers.Methods:  Eighteen healthy subjects (9 men; mean age = 27.6 years) completed a double‐blind, within‐subject study with 3 experimental sessions in a randomized sequence, during which they received no medication, aripiprazole 2.5 mg, or aripiprazole 10 mg on the day prior to the laboratory session. During the session, subjects consumed alcohol that was served as three standardized drinks (i.e., a total of 0.8 g/kg for men and 0.7 g/kg for women). Breath alcohol concentration (BrAC), heart rate, blood pressure, static ataxia, and subjective effects were measured regularly throughout the laboratory sessions.Results:  Alcohol consumption produced physiological and subjective responses that were consistent with the literature on its effects. Pre‐treatment with aripiprazole was generally well tolerated, with tiredness being the most commonly reported adverse event. The medication was associated with modest physiological effects. It also significantly and dose‐dependently increased the sedative effects of alcohol and, to a lesser degree, decreased the euphoric effects of alcohol.Conclusions:  These findings require replication in a larger subject sample that includes heavy drinkers and in a study that employs a placebo session. Based on its capacity to increase the sedative effects and decrease the euphoric effects of alcohol, aripiprazole could be of value in the treatment of heavy drinking.
Outcome Assessment in Emergency Medicine—A Beginning: Results of the Council of Emergency Medicine Residency Directors (CORD) Emergency Medicine Consensus Workgroup on Outcome Assessment
Authors: Hobgood Cherri , Promes Susan , Wang Ernest , Moriarity Risa , Goyal Deepi G. 
Published: February 2008

AbstractThis article is designed to serve as a guide for emergency medicine (EM) educators seeking to comply with the measurement and reporting requirements for Phase 3 of the Accreditation Council for Graduate Medical Education (ACGME) Outcome Project. A consensus workshop held during the 2006 Council of Emergency Medicine Residency Directors (CORD) “Best Practices” conference identified specific measures for five of the six EM competencies—interpersonal communication skills, patient care, practice‐based learning, professionalism, and systems‐based practice (medical knowledge was excluded). The suggested measures described herein should allow for ease in data collection and applicability to multiple core competencies as program directors incorporate core competency outcome measurement into their EM residency training programs.
Delta2‐Specific Opioid Receptor Agonist and Hibernating Woodchuck Plasma Fraction Provide Ischemic Neuroprotection
Authors: Govindaswami Meera , Brown Stephan A. , Yu Jin , Zhu Hong , Bishop Paul D. , Kindy Mark S. , Oeltgen Peter R. 
Published: February 2008

AbstractObjectives:  The authors present evidence that the δ opioid receptor agonist Deltorphin‐Dvariant (Delt‐Dvar) and hibernating woodchuck plasma (HWP), but not summer‐active woodchuck plasma (SAWP), can provide significant neuroprotection from focal ischemia in mice by a mechanism that relies in part on reducing nitric oxide (NO) release in ischemic tissue.Methods:  Cerebral ischemia was produced in wild‐type and NO synthase–deficient (NOS–/–) mice by transient, 1‐hour middle cerebral artery occlusion (MCAO). Behavioral deficits were determined at 22 hours and infarct volume was assessed at 24 hours after MCAO. Mice were treated with saline or Delt‐Dvar at 2.0 and 4.0 mg/kg, or 200 μL of HWP or SAWP. NOS–/– mice were treated with either saline or Delt‐Dvar at 4.0 mg/kg. NO release was determined using an N9 microglial cell line pretreated with δ‐ or μ‐specific opioids and HWP or SAWP prior to activation with lipopolysaccharide and interferon‐γ. Nitrate in the medium was measured as an indicator of NO production.Results:  Infusion of Delt‐Dvar or HWP (but not SAWP) decreased infarct volume and improved behavioral deficits following 1 hour of MCAO and 24 hours of reperfusion. In NOS–/– mice, endothelial NOS+/+ is required to provide Delt‐Dvar–induced neuroprotection. Delt‐Dvar and HWP dose‐dependently decreased NO release in cell culture, while SAWP and other δ‐ and μ‐specific opioids did not.Conclusions:  Delt‐Dvar and HWP, but not SAWP, are effective neuroprotectant agents in a mouse model of transient MCAO. In cell culture, the mechanism of this ischemic neuroprotection may rely in part on their ability to block NO release.