bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities
Authors: Gonzalez-Quintela A , Alende R , Gude F , Campos J , Rey J , Meijide L M , Fernandez-Merino C , Vidal C 
Published: July 2010

SummaryThe present study investigated serum immunoglobulin (Ig) concentrations in relation to demographic factors, common habits (alcohol consumption and smoking) and metabolic abnormalities in an adult population-based survey including 460 individuals. Serum levels of interleukin (IL)-6, a marker of inflammation, were also determined. After adjusting for confounders, male sex was associated positively with IgA levels and negatively with IgM levels. Age was associated positively with IgA and IgG levels. Smoking was associated negatively with IgG levels. Heavy drinking was associated positively with IgA levels. Metabolic abnormalities (obesity and metabolic syndrome) were associated positively with IgA levels. Abdominal obesity and hypertriglyceridaemia were the components of metabolic syndrome associated most strongly with serum IgA. Heavy drinkers with metabolic syndrome showed particularly high serum IgA levels. Serum IL-6 levels were correlated positively with IgA and IgG concentrations. It is concluded that sex, age, alcohol consumption, smoking and common metabolic abnormalities should be taken into account when interpreting serum levels of IgA, IgG and IgM.
Persistent of respiratory syncytial virus in human dendritic cells and influence of nitric oxide
Authors: Hobson L , Everard M L 
Published: July 2010

Summary
The annual epidemics of respiratory syncytial virus (RSV) infection are probably explained by poor herd immunity and the existence of a dormant reservoir of virus that is activated by an unknown trigger. The virus causes particular problems in infants, the elderly and patients with chronic obstructive airways disease (COPD). During two consecutive winters, human monocyte-derived dendritic cells (DCs) were exposed on a single occasion to one of two forms of RSV labelled with a fluorescent expresser genes (rgRSV or rrRSV) during the epidemic season. The cultures were maintained for many months, with fresh DCs being added at monthly intervals. The cultures were variously exposed to 600 parts per billion (ppb) nitric oxide for 15 min, nitric oxide (NO) donors and NO inhibitors outside the RSV epidemic season. The pattern of productive infection of DCs in vitro appeared to parallel the natural epidemics, in that DCs exhibited evidence of viral replication and productive infection only as manifested by intracellular fluorescence and infection of HeLa cells during the RSV epidemic season. When the long-term cultures were exposed to the above agents outside the RSV epidemic season there was again evidence of vigorous replication and productive infection, as shown by the reappearance of fluorescence and productive infection of HeLa cells. The results indicate that RSV may remain dormant in dendritic cells for prolonged periods and that replication appears to be activated by suppression of endogenous NO production. These observations may be key to our understanding of the mechanisms contributing to the annual epidemics of RSV infection.
Imatinib mesylate, a new kid on the block for the treatment of anti-neutrophil cytoplasmic autoantibodies-associated vasculitis?
Authors: Kälsch A-I , Soboletzki M , Schmitt W H , van der Woude F J , Hochhaus A , Yard B A , Birck R 
Published: July 2010

Summary
Persistent T cell activation is a common finding in anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitis (AAV) patients. Because imatinib, a selective inhibitor of the ABL, ARG, PDGFR and c-KIT tyrosine kinases, inhibits T cell activation, this study was conducted to evaluate the potential use of imatinib for the treatment AAV patients refractory to conventional therapy. In particular, we investigated the inhibition of T cell activation by this drug and its efficacy on activated T cells from anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitides (AASV) patients. T cell stimulation has been induced by anti-CD3/anti-CD28 antibodies or by phorbol myristate acetate (PMA)/ionomycin. T cell proliferation was analysed by tritiumthymidine incorporation. Cell cycle progression was determined by propidium iodide staining using fluorescence activated cell sorter (FACS) analysis and by RNAse protection assay (RPA). Cytokine levels were assessed by enzyme-linked immunosorbent assay. T cell proliferation was inhibited significantly by imatinib, due most probably to cell cycle arrest in the G1-phase. This was paralleled by inhibition in the expression of cyclin-dependent kinases 1 and 2 mRNA. The expression of CD25 in naive and memory T cells was decreased significantly by imatinib in activated T cells. Similarly, conversion from naive to memory T cells after T cell activation was impaired by imatinib. Imatinib did not influence interleukin-2 and tumour necrosis factor-α production but increased interferon-γ production. These observed effects of imatinib were similar in T cells from AASV patients and from healthy individuals. Imatinib might be an alternative therapeutical option for AASV patients refractory to conventional therapy.
Factors associated with CD4 lymphocyte counts in HIV-negative Senegalese individuals
Authors: Mair C , Hawes S E , Agne H D , Sow P S , N'doye I , Manhart L E , Fu P L , Gottlieb G S , Kiviat N B 
Published: July 2010

Summary
CD4+ lymphocytes are a primary target of the human immunodeficiency virus (HIV), and CD4 counts are one of the factors used to measure disease progression in HIV-positive individuals. CD4 counts vary in uninfected individuals and across populations due to a variety of demographic, environmental, immunological and genetic factors that probably persist throughout the course of HIV infection. This study sought to determine reference levels and identify factors that influence lymphocyte counts in 681 HIV-uninfected adults in Senegal, where residents are exposed to a variety of infectious diseases and other conditions that may affect CD4 counts. Lymphocyte counts were assessed in commercial sex workers, symptomatic men and women presenting to the University of Dakar infectious disease clinic for out-patient care and women seeking family planning services. CD4 and CD3 lymphocyte counts differed between the four study groups (P &lt; 0·01). Men had the lowest mean CD4 count (711·6 cells/μl), while commercial sex workers had the highest levels (966·0 cells/μl). After adjustment for age and other behavioural and clinical factors, the difference in CD4 counts between the three groups of women did not remain. However, both gender and smoking were associated independently with CD4 counts, as men maintained lower mean CD4 counts (β = −156·4 cells/μl, P &lt; 0·01) and smokers had higher mean CD4 counts (β = 124·0 cells/μl, P &lt; 0·01) than non-smokers in multivariable analyses. This study is the first to explore factors that may influence CD4 levels in Senegal and to estimate baseline CD4 levels among HIV-negatives, information that may guide clinicians in interpreting CD4 counts.
The Wistar Bonn Kobori rat, a unique animal model for autoimmune pancreatitis with extrapancreatic exocrinopathy
Authors: Sakaguchi Y , Inaba M , Tsuda M , Quan G K , Omae M , Ando Y , Uchida K , Okazaki K , Ikehara S 
Published: July 2010

Summary
The male Wistar Bonn/Kobori (WBN/Kob) rat is known to be a unique animal model for chronic pancreatitis with widely distributed fibrosis and degeneration of parenchyma because of the infiltration of lymphocytes. In this report, we show that female (but not male) rats develop dacryoadenitis at 3 months of age, and that both male and female WBN/Kob rats develop sialoadenitis, thyroiditis, sclerotic cholangitis and tubulointerstitial nephritis over 18 months of age. The infiltration of CD8+ cells and the deposits of tissue-specific IgG2b were observed in the injured pancreas and lachrymal glands. Furthermore, the number of regulatory T cells (defined as CD4+ Forkhead box P3+ cells) decreased in the periphery of both male and female WBN/Kob rats, suggesting that the onset of these diseases is attributable, at least, to the failure in the maintenance of peripheral immune tolerance. These features show clearly that WBN/Kob rats are a useful animal model for autoimmune pancreatitis and Sjøgren-like syndrome or multi-focal fibrosclerosis in humans. We also show that these autoimmune diseases can be prevented by a newly devised strategy of bone marrow transplantation (BMT) in which bone marrow cells are injected directly into the bone marrow cavity: intrabone marrow–BMT.
Effect of taurine on oxidative stress and apoptosis-related protein expression in trinitrobenzene sulphonic acid-induced colitis
Authors: Giriş M , Depboylu B , Doğru-Abbasoğlu S , Erbil Y , Olgaç V , Alış H , Aykaç-Toker G , Uysal M 
Published: July 2010

Summary
Ulcerative colitis (UC) is a multi-factorial inflammatory disease of the colon and rectum. The present study was undertaken to investigate the effect of taurine, an anti-oxidant amino acid, on oxidative stress and the expression of apoptosis-related proteins, pro-apoptotic Bax and anti-apoptotic B cell lymphoma-2 (Bcl-2) in colon tissue in rats with 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. Rats received taurine (1·5% w/v) in drinking water for 15 days before and 15 days after administration of TNBS solution. Then, colonic myeloperoxidase (MPO) activity, malondialdehyde (MDA) and glutathione (GSH) levels, and Bax and Bcl-2 expression were measured. TNBS-induced colitis caused significantly increased MPO activity and MDA levels and decreased GSH levels in colon tissue compared to controls. Increase in Bax expression and decrease in Bcl-2 expression were detected in colon of rats with TNBS-induced colitis. Taurine treatment was associated with amelioration in macroscopic and microscopic colitis scores, decreased colonic MPO activity and MDA levels and increased GSH levels in TNBS-induced colitis. In addition, taurine reduced the expression of Bax and prevented the loss of Bcl-2 proteins in colon tissue of rats with TNBS-induced colitis. The results of this study show that taurine administration may exert beneficial effects in UC by decreasing inflammatory reactions, oxidative stress and apoptosis.
Common studied polymorphisms do not affect plasma cytokine levels upon endotoxin exposure in humans
Authors: Taudorf S , Krabbe K S , Berg R M G , Møller K , Pedersen B K , Bruunsgaard H 
Published: July 2010

SummaryThe aim of this study was to investigate to what extent single nucleotide polymorphisms (SNPs) in promoter regions of genes of Toll-like receptor (TLR)-4, tumour necrosis factor (TNF)-α, interleukin (IL)-18, interferon (IFN)-γ, IL-6 and IL-10 affect the cytokine response during a controlled low-grade inflammatory response in vivo. Two hundred healthy young male volunteers were genotyped, and cytokine levels were measured in response to a low-dose intravenous bolus of Escherichia coli endotoxin. No association was detected between SNPs (TLR-4299, TLR-4399, TNF-308, IL-18-137, IL-18-607, IFN-γ+874, IL-6-174, IL-10-592 and IL-10-1082) and endotoxin-induced changes in plasma levels of TNF-α, IL-6 and IL-10. IL-18 levels were unaffected by endotoxin. In conclusion, the investigated SNPs did not affect endotoxin-induced low-grade cytokine production of TNF-α, IL-6, IL-18 or IL-10 in healthy young men. Previous reports of a major heritability factor in the inflammatory response may be due to other target genes or effects in older age groups or women.
Innate lymphocyte and dendritic cell cross-talk: a key factor in the regulation of the immune response
Authors: Reschner A , Hubert P , Delvenne P , Boniver J , Jacobs N 
Published: July 2010

Summary
Dendritic cells (DC) are specialized in the presentation of antigens and the initiation of specific immune responses. They have been involved recently in supporting innate immunity by interacting with various innate lymphocytes, such as natural killer (NK), NK T or T cell receptor (TCR)-γδ cells. The functional links between innate lymphocytes and DC have been investigated widely and different studies demonstrated that reciprocal activations follow on from NK/DC interactions. The cross-talk between innate cells and DC which leads to innate lymphocyte activation and DC maturation was found to be multi-directional, involving not only cell–cell contacts but also soluble factors. The final outcome of these cellular interactions may have a dramatic impact on the quality and strength of the down-stream immune responses, mainly in the context of early responses to tumour cells and infectious agents. Interestingly, DC, NK and TCR-γδ cells also share similar functions, such as antigen uptake and presentation, as well as cytotoxic and tumoricidal activity. In addition, NK and NK T cells have the ability to kill DC. This review will focus upon the different aspects of the cross-talk between DC and innate lymphocytes and its key role in all the steps of the immune response. These cellular interactions may be particularly critical in situations where immune surveillance requires efficient early innate responses.
The tumour suppressor gene p53 modulates the severity of antigen-induced arthritis and the systemic immune response
Authors: Leech M , Xue J R , Dacumos A , Hall P , Santos L , Yang Y , Li M , Kitching A R , Morand E F 
Published: July 2010

Summary
p53 is a transcription factor with a well-described role in the induction of apoptosis and cell cycle arrest as part of a protective response to a variety of stressful stimuli. Expansion of inflamed tissue in rheumatoid arthritis has been related to the loss of functioning p53, and the severity of collagen-induced arthritis is increased in p53–/– mice. Our objective was to assess the role of p53 in a model of adaptive immunity, antigen-induced arthritis (AIA). AIA was induced in p53–/– and wild-type mice by priming with methylated bovine serum albumin followed by intra-articular challenge. Severity of arthritis was assessed using a standardized scoring system and synovial apoptosis was detected by TdT-mediated biotin-dUTP nick-end labelling. Splenocyte proliferation was measured by [H3] incorporation and interferon (IFN)-γ release. Splenocyte viability was assessed using Titreglow. Splenic T cell activation status was assessed by flow cytometry. Serum cytokines were measured using enzyme-linked immunosorbent assay. Increased severity of AIA in p53–/– mice was associated with decreased synovial apoptosis and with increased delayed-type hypersensitivity response, increased mitogen and antigen-induced splenocyte proliferation and increased IFN-γ release in p53–/– mice compared with wild-type mice. Antigen-specific immunoglobulin responses were equivalent in both groups. Splenocyte viability was increased in p53–/– mice but T cell apoptosis was equivalent. T cell activation markers were increased in p53–/– mice compared with wild-type mice. Lipopolysaccharide-induced tumour necrosis factor release was increased in p53–/– mice with a trend to increased interleukin-6 in p53–/– mice compared with littermates. p53 is involved in the modulation of adaptive and innate immune responses relevant to arthritis models and is also involved in the modulation of severity of AIA by both cell-cycle dependent and cell-cycle-independent mechanisms.
Possible role of natural killer cells in pemphigus vulgaris − preliminary observations
Authors: Stern J N H , Keskin D B , Barteneva N , Zuniga J , Yunis E J , Ahmed A R 
Published: July 2010

SummaryPemphigus vulgaris (PV) is an autoimmune blistering disease that affects the skin and multiple mucous membranes, and is caused by antibodies to desmoglein (Dsg) 1 and 3. Natural killer (NK) cells have a role in autoimmunity, but their role in PV is not known. NK cells in the peripheral blood leucocytes (PBL) of 15 untreated Caucasian patients with active PV were studied and compared with healthy controls for the expression of major histocompatibility complex (MHC) class II and co-stimulatory molecules. CD56+ CD16- CD3- NK or CD56+ CD16+ CD3- NK cells from the PBL of PV patients co-express MHC class II and co-stimulatory molecule B7-H3 without exogenous stimulation. CD4+ T cells from the PBL and perilesional skin of PV patients were co-cultured with CD56+ CD3- NK cells from the PBL of the same patients; in the presence of Dsg3 peptides underwent statistically significant proliferation, indicating that NK cells functioned as antigen-presenting cells. Supernatants from these co-cultures and serum of the same patients with active PV had statistically significantly elevated levels of interleukin (IL)-6, IL-8 and interferon-γ, compared with controls indicating that the NK cells stimulated CD4+ T cells to produce proinflammatory cytokines. In these experiments, we present preliminary evidence that NK cells may play a role in the pathobiology of PV.
Clinical Immunology Review Series: An approach to the patient with recurrent superficial abscesses
Authors: Johnston S L 
Published: July 2010

Summary
Patients may be referred to the immunology clinic for investigation of recurrent superficial abscess formation. In the majority of adult patients this clinical presentation does not equate with an underlying primary immune deficiency. Nevertheless, recurrent mucocutaneous abscesses can be associated with significant morbidity and long-term complications, including scarring and fistula formation, and may be associated with underlying immune-mediated disease. This review sets out an approach to the patient with recurrent superficial abscesses, focusing on the differential diagnoses, investigation and management of both the common causes and those associated with specific immune deficiency.
Adrenomedullin suppresses tumour necrosis factor alpha-induced CXC chemokine ligand 10 production by human gingival fibroblasts
Authors: Hosokawa I , Hosokawa Y , Ozaki K , Nakae H , Matsuo T 
Published: July 2010

SummaryPeriodontal disease is an inflammatory disorder characterized by the involvement of chemokines that are important for the recruitment of leucocytes. Several cytokines, including tumour necrosis factor alpha (TNF-α), are involved in regulating levels of chemokines in periodontal disease. CXC chemokine ligand 10 (CXCL10) is a chemokine related to the migration of T helper 1 cells. In this study, we examined CXCL10 expression in human gingival fibroblasts (HGFs). Moreover, we investigated the effects of adrenomedullin (AM), which is a multi-functional regulatory peptide, on the production of CXCL10 by HGFs. We revealed that TNF-α stimulation induced CXCL10 production by HGFs. HGFs expressed AM and AM receptors, calcitonin-receptor-like receptor (CRLR) and receptor-activity-modifying protein (RAMP) 2, mRNAs constitutively. AM treatment supressed CXCL10 production by TNF-α-stimulated HGFs. Moreover, we elucidated that AM produced by HGFs inhibited CXCL10 production by HGFs, because AM antagonist enhanced CXCL10 production by HGFs. TNF-α treatment enhanced CRLR and RAMP2 mRNA expression in HGFs. Furthermore, AM is expressed in human periodontal tissues, including both inflamed and clinically healthy tissues. These results suggest that the CXCL10 produced by HGFs may be involved in the migration of leucocytes into inflamed tissues and related to exacerbation of periodontal disease. AM might be a therapeutic target of periodontal disease, because AM can inhibit CXCL10 production by HGFs.
99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Darwinian medicine and the ‘hygiene’ or ‘old friends’ hypothesis
Authors: Rook G A W 
Published: July 2010

Summary
The current synthesis of the ‘hygiene hypothesis’ suggests that the recent increase in chronic inflammatory disorders is at least partly attributable to immunodysregulation resulting from lack of exposure to microorganisms that have evolved an essential role in the establishment of the immune system. This document provides a background for discussion of the following propositions. The essential role of these organisms is an example of ‘evolved dependence’.The most relevant organisms are those that co-evolved with mammals, and already accompanied early hominids in the Paleolithic.More recently evolved ‘childhood infections’ are not likely to have evolved this role, and recent epidemiology supports this contention.This mechanism is interacting with other modern environmental changes that also lead to enhanced inflammatory responses [inappropriate diet, obesity, psychological stress, vitamin D deficiency, pollution (dioxins), etc.].The range of chronic inflammatory disorders that is affected is potentially larger than usually assumed [allergies, autoimmunity, inflammatory bowel disease, but also vascular disease, some cancers, depression/anxiety (when accompanied by raised inflammatory cytokines), and perhaps neurodegenerative disorders and type 2 diabetes].
99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Innate immune responses in plants
Authors: Schulze-Lefert P 
Published: July 2010

Summary
Plants rely exclusively upon mechanisms of innate immunity. Current concepts of the plant innate immune system are based largely on two forms of immunity that engage distinct classes of immune receptors. These receptors enable the recognition of non-self structures that are either conserved between members of a microbial class or specific to individual strains of a microbe. One type of receptor comprises membrane-resident pattern recognition receptors (PRRs) that detect widely conserved microbe-associated molecular patterns (MAMPs) on the cell surface. A second type of mainly intracellular immune sensors, designated resistance (R) proteins, recognizes either the structure or function of strain-specific pathogen effectors that are delivered inside host cells. Phytopathogenic microorganisms have evolved a repertoire of effectors, some of which are delivered into plant cells to sabotage MAMP-triggered immune responses. Plants appear to have also evolved receptors that sense cellular injury by the release and perception of endogenous damage-associated molecular patterns (DAMPs). It is possible that the integration of MAMP and DAMP responses is critical to mount robust MAMP-triggered immunity. This signal integration might help to explain why plants are colonized in nature by remarkably diverse and seemingly asymptomatic microbial communities.
99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Neonatal immune function and vaccine responses in children born in low-incomeversushigh-income countries
Authors: Van Den Biggelaar A H J , Holt P G 
Published: July 2010

SummaryThere is increasing evidence that the functional state of the immune system at birth is predictive of the kinetics of immune maturation in early infancy. Moreover, this maturation process can have a major impact on early vaccine responses and can be a key determinant of risk for communicable and non-communicable diseases in later life. We hypothesize that environmental and genetic factors that are often typical for poor-resource countries may have an important impact on prenatal immune development and predispose populations in low-income settings to different vaccine responses and disease risks, compared to those living in high-income countries. In this paper we aimed to summarize the major differences between neonatal and adult immune function and describe what is known so far about discrepancies in immune function between newborns in high- and low-income settings. Further, we discuss the need to test the immunological feasibility of accelerated vaccination schedules in high-risk populations and the potential of variation in disease specific and non-specific vaccine effects.