bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mechanism of development of acute lung injury in lethal endotoxic shock using α-galactosylceramide sensitization
Authors: Tumurkhuu G , Koide N , Dagvadorj J , Morikawa A , Hassan F , Islam S , Naiki Y , Mori I , Yoshida T , Yokochi T 
Published: July 2010

SummaryThe mechanism underlying acute lung injury in lethal endotoxic shock induced by administration of lipopolysaccharide (LPS) into α-galactosylceramide (α-GalCer)-sensitized mice was studied. Sensitization with α-GalCer resulted in the increase of natural killer T (NK T) cells and the production of interferon (IFN)-γ in the lung. The IFN-γ that was produced induced expression of adhesion molecules, especially vascular cell adhesion molecule-1 (VCAM-1), on vascular endothelial cells in the lung. Anti-IFN-γ antibody inhibited significantly the VCAM-1 expression in α-GalCer-sensitized mice. Very late activating antigen-4-positive cells, as the counterpart of VCAM-1, accumulated in the lung. Anti-VCAM-1 antibody prevented LPS-mediated lethal shock in α-GalCer-sensitized mice. The administration of LPS into α-GalCer-sensitized mice caused local production of excessive proinflammatory mediators, such as tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and nitric oxide. LPS caused microvascular leakage of proteins and cells into bronchoalveolar lavage fluid. Taken together, sensitization with α-GalCer was suggested to induce the expression of VCAM-1 via IFN-γ produced by NK T cells and recruit a number of inflammatory cells into the lung. Further, LPS was suggested to lead to the production of excessive proinflammatory mediators, the elevation of pulmonary permeability and cell death. The putative mechanism of acute lung injury in LPS-mediated lethal shock using α-GalCer sensitization is discussed.
Recombinant early secreted antigen target 6 protein as a skin test antigen for the specific detection of Mycobacterium tuberculosis infection
Authors: Wu X , Zhang L , Zhang J , Zhang C , Zhu L , Shi Y 
Published: July 2010

Summary
Although the delayed-type hypersensitivity skin test reaction to tuberculin purified protein derivative (PPD) is used worldwide for tuberculosis (TB) detection, it is incapable of distinguishing Mycobacterium tuberculosis (MTB) infection from bacille Calmette–Guérin (BCG) vaccination or infection with non-tuberculous Mycobacteria. As a result, there is an urgent need for a more specific diagnostic tool for TB. This study reports the skin reactions of guinea pigs and human volunteers to recombinant early secreted antigen target 6 (rESAT6), a secretory protein found only in MTB, M. bovis and few other mycobacterial species. These volunteers had varying histories of BCG vaccination and exposure to MTB, allowing us to determine the specificity of their response to TB exposure. Our results show that 1·0 μg of the purified MTB rESAT6 antigen elicited a positive skin response in both animals and humans exposed to MTB, as well as in animals exposed to M. bovis and M. marinum, all species of Mycobacteria that contain the gene for early secreted antigen target 6 (ESAT6). ESAT6 appears to be more specific to MTB infection than PPD, as demonstrated by the fact that we saw no skin responses in the BCG-vaccinated volunteers, nor in the guinea pigs sensitized with BCG vaccine, or with Mycobacteria that do not contain the gene encoding ESAT6. We believe that this is the first report of the use of a rESAT6 protein in a skin test in human volunteers, and that these data support its use in the specific detection of MTB infection.
Mannan-binding lectinMBL2gene polymorphism in chronic hepatitis C: association with the severity of liver fibrosis and response to interferon therapy
Authors: Alves Pedroso M L , Boldt A B W , Pereira-Ferrari L , Steffensen R , Strauss E , Jensenius J C , Ioshii S O , Messias-Reason I 
Published: July 2010

SummaryHepatitis C virus (HCV) is a major cause of hepatic disease and of liver transplantation worldwide. Mannan-binding lectin (MBL), encoded by the MBL2 gene, can have an important role as an opsonin and complement activating molecule in HCV persistence and liver injury. We assessed the MBL2 polymorphism in 102 Euro–Brazilian patients with moderate and severe chronic hepatitis C, paired for gender and age with 102 HCV seronegative healthy individuals. Six common single nucleotide polymorphisms in the MBL2 gene, three in the promoter (H/L, X/Y and P/Q) and three in exon 1 (A, the wild-type, and B, C or D also known as O) were evaluated using real-time polymerase chain reaction with fluorescent hybridization probes. The concentration of MBL in plasma was measured by enzyme-linked immunosorbent assay. The frequency of the YA/YO genotype was significantly higher in the HCV patients compared with the controls (P = 0·022). On the other hand, the genotypes associated with low levels of MBL (XA/XA, XA/YO and YO/YO) were decreased significantly in the patients with severe fibrosis (stage F4), when compared with the patients with moderate fibrosis (stage F2) (P = 0·04) and to the control group (P = 0·011). Furthermore, MBL2 genotypes containing X or O mutations were found to be associated with non-responsiveness to pginterferon and ribavirin treatment (P = 0·023). MBL2 polymorphisms may therefore be associated not only with the development of chronic hepatitis C, but also with its clinical evolution and response to treatment.
Secretory immunoglobulin A (IgA) responses in IgA nephropathy patients after mucosal immunization, as part of a polymeric IgA response
Authors: Eijgenraam J W , Oortwijn B D , Kamerling S W A , De Fijter J W , Van Den Wall Bake A W L , Daha M R , Van Kooten C 
Published: July 2010

Summary
Secretory immunoglobulin A (SIgA), although generated at mucosal surfaces, is also found in low concentrations in the circulation. Recently, SIgA was demonstrated in mesangial deposits of patients with immunoglobulin A nephropathy (IgAN), suggesting a role in the pathogenesis. This finding is in line with the belief that high molecular weight (HMW) immunoglobulin A (IgA) is deposited in the kidney. However, there is little information on the size distribution of antigen-specific IgA in circulation upon mucosal challenge. In this study we measured antigen-specific IgA, including SIgA, in serum following challenge of IgAN patients and controls via intranasal vaccination with a neoantigen, cholera toxin subunit B (CTB). We size-fractionated serum and nasal washes to study the size distribution of total IgA, SIgA and CTB-specific IgA. Finally, we compared the size distribution of antigen-specific IgA after mucosal immunization with the distribution upon systemic immunization. A significant induction of antigen-specific SIgA was detectable in serum of both patients with IgAN and controls after mucosal immunization with CTB. Independent of the route of immunization, in both groups the antigen-specific IgA response was predominantly in the polymeric IgA fractions. This is in contrast to total IgA levels in serum that are predominantly monomeric. We conclude that mucosal challenge results in antigen-specific SIgA in the circulation, and that the antigen-specific IgA response in both IgAN patients and in controls is of predominantly HMW in nature. No differences between IgAN patients and controls were detected, suggesting that the size distribution of antigen-specific IgA in the circulation is not disturbed specifically in IgAN patients.
Serum levels of interleukin 6 in recently hospitalized tick-borne encephalitis patients correlate with age, but not with disease outcome
Authors: Toporkova M G , Aleshin S E , Ozherelkov S V , Nadezhdina M V , Stephenson J R , Timofeev A V 
Published: July 2010

SummaryInfection with many encephalitic viruses is associated with the induction of the proinflammatory cytokine interleukin (IL)-6. In some situations, induction of high levels of this cytokine is associated with a protective response, but in others it can be linked to tissue damage and disease. In the studies reported here, levels of serum IL-6 and virus-specific antibodies were measured on admission to hospital and correlated with clinical outcomes. Only some patients demonstrated raised levels of serum IL-6, and there was no correlation between high levels of this cytokine and either gender or the severity of clinical disease. A statistically significant association between raised IL-6 and age was observed, with all individuals below the age of 26 showing normal levels of serum IL-6, regardless of clinical presentation. Furthermore, not all patients had detectable levels of virus-specific serum immunoglobulin G (IgG) antibodies, but an inverse and statistically significant correlation between raised IL-6 levels and IgG titre was observed. Consequently, serum levels of IL-6 cannot be used as a reliable indicator of disease outcome.
Monitoring non-immediate allergic reactions to iodine contrast media
Authors: Torres M J , Mayorga C , Cornejo-Garcia J A , Lopez S , Chaves P , Rondon C , Fernandez T , Blanca M 
Published: July 2010

Summary
Non-immediate reactions to iodine contrast media (ICM) affect 2–5% of patients receiving these agents. We studied the immunological mechanisms involved in patients with a confirmed non-immediate reaction, maculopapular exanthema, after administration of ICM. The diagnosis was carried out by skin testing or drug provocation test. The immunological study was performed in sequential peripheral blood mononuclear cells taken from the onset of the reaction by flow cytometry and in skin biopsy by immunohistochemistry, with specific recognition by the lymphocyte transformation test (LTT) with different ICM. Flow cytometry showed an increase in the different activation markers [CD69, CD25 and human leucocyte antigen D-related (HLA-DR)] and the skin homing receptor [cutaneous lymphocyte-associated antigen (CLA)] in CD4 lymphocytes, whereas perforin was higher in the CD8 lymphocytes. The skin biopsy showed a perivascular mononuclear infiltrate composed of CD4 lymphocytes, expressing CD25, HLA-DR and CLA, with eosinophils. Intradermal skin tests and the LTT were positive to several ICM, including the culprit agent in four and three patients, respectively, with negative results in all 10 tolerant controls. We showed that a specific immunological mechanism was implicated in patients with non-immediate reactions to ICM. Moreover, the positive results in skin tests and lymphocyte proliferation tests indicated that an important cross-reactivity exists.
Lidocaine down-regulates nuclear factor-κB signalling and inhibits cytokine production and T cell proliferation
Authors: Lahat A , Horin S B , Lang A , Fudim E , Picard O , Chowers Y 
Published: July 2010

SummaryLidocaine is a commonly used local anaesthetic agent which has also been found to possess anti-inflammatory activity in several disorders. However, the mechanism of this effect has been little explored. The aim of this study was to investigate the effect of lidocaine on stimulated human T cells. The effect of lidocaine on Jurkat T cells was examined by enzyme-linked immunosorbent assay (ELISA) to determine secretion of interleukin (IL)-2, and by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] viability assay. Tumour necrosis factor (TNF)-α and IL-2 mRNA expression was determined by reverse transcription–polymerase chain reaction. In addition, the effect of lidocaine on the proliferation of freshly isolated peripheral blood (PB) CD3+ T cells was examined by carboxyfluorescein succinimidyl ester dilution. Apoptosis induction and cytokine production and secretion were determined by annexin V/PI assay, intracellular immunostaining and ELISA respectively. The results showed that lidocaine exerts a dose-dependent inhibition of IL-2 and TNF-α secretion by Jurkat T cells at the protein and mRNA levels. Moreover, lidocaine reduced nuclear factor-κB (NF-κB) signalling in clinically relevant concentrations. Similarly, proliferation of anti-CD3 stimulated PB T cells was abrogated significantly by lidocaine, and the percentage of interferon-γ- and TNF-α-producing T cells was diminished after culture with this agent. In both experimental systems, lidocaine's effect was not mediated by cytotoxic mechanism, as no significant apoptosis or necrosis was demonstrated following co-culture of T cells with this drug. In conclusion, lidocaine's anti-inflammatory effect may be mediated by a drug-induced abrogation of T cell proliferation and cytokine secretion independent of cell death. These effects are mediated at least partly by inhibition of NF-κB signalling.
T helper 1 (Th1)/Th2 cytokine expression shift of peripheral blood CD4+ and CD8+ T cells in patients at the post-acute phase of stroke
Authors: Theodorou G L , Marousi S , Ellul J , Mougiou A , Theodori E , Mouzaki A , Karakantza M 
Published: July 2010

SummaryLocal humoral and cellular immune responses modulate the inflammatory processes involved in the development of atherosclerotic lesions, as well as in the evolution of brain infarcts in stroke patients. The role of systemic adaptive immunity on the progression of such disease manifestations is less clear. In the current study, we evaluated the percentages of T helper 1 (Th1) [interleukin (IL)-2, interferon (IFN)-γ] and Th2 (IL-4, IL-10) cytokine-producing peripheral blood CD4+ and CD8+ T cells in 23 patients with a history of ischaemic stroke (IS) at the chronic stable phase of the disease (median post-stroke time 34·5 months). Seven stroke-free individuals matched for age and vascular risk factors (matched controls, MC) were collected for comparison. To measure cytokine values at baseline and after stimulation, we used a flow cytometry method of intracellular cytokine staining. Intrinsic Th1 and Th2 cytokine production in unstimulated T cells was negligible in all study participants. Following mitogenic stimulation with phorbol 12-myristate13-acetate/ionomycin, both the IS and the MC groups exhibited a similarly strong Th1 response; IL-2 production predominated in the CD4+ T cells and IFN-γ in the CD8+ T cells. However, when measuring the Th2 cytokine-production capacity post-stimulation, a significant increase in the percentage of IL-4-producing T cells was observed in the IS groups, compared with the MC group, resulting in a significantly lower ratio of IFN-γ-/IL-4-producing T cells. No such Th2 enhancement could be confirmed for the case of IL-10. We propose that in IS patients there is a systemic shift of the immune system towards Th2 responses at the late post-acute phase of stroke.
Clonal relationship between infiltrating immunoglobulin G4 (IgG4)-positive plasma cells in lacrimal glands and circulating IgG4-positive lymphocytes in Mikulicz's disease
Authors: Yamada K , Kawano M , Inoue R , Hamano R , Kakuchi Y , Fujii H , Matsumura M , Zen Y , Takahira M , Yachie A , Yamagishi M 
Published: July 2010

SummaryMikulicz's disease (MD) is gaining acceptance as an immunoglobulin G4 (IgG4)-related disease characterized by bilateral lacrimal and salivary gland swelling. The aetiology of MD and other IgG4-related diseases is still unclear. The present work was performed to study the clonality of infiltrating IgG4-positive plasma cells in lacrimal glands and circulating peripheral blood cells in patients with MD, and compare the clonal relationship between infiltrating and circulating IgG4 positive cells. Total cellular RNA was extracted from the lacrimal glands and peripheral blood in five MD patients. Reverse transcription polymerase chain reaction was performed with primers specific for activation-induced cytidine deaminase (AID) and for Ig VH and IgG4. Sequences of Ig VH were compared with the structure of Ig VH of the lacrimal glands and the peripheral blood cells. AID was expressed to varying degrees in lacrimal glands of all MD patients. Most IgG4-positive cells infiltrating lacrimal glands and in peripheral blood were polyclonal, although several clonally related pairs were detected. In one patient, two of the circulating IgG4 VH4-59 clones shared identical CDR3 sequences with the clones within the lacrimal glands. In conclusion, while most tissue-infiltrating and circulating IgG4-positive cells in MD are polyclonal, some clonally related IgG4 positive cells exist between lacrimal gland and peripheral blood, accounting for the clinical features of MD as an IgG4-related disease involving multiple organs.
Elevated CCR6+ CD4+ T lymphocytes in tissue compared with blood and induction of CCL20 during the asthmatic late response
Authors: Francis J N , Sabroe I , Lloyd C M , Durham S R , Till S J 
Published: July 2010

SummaryCCR6 is expressed by multiple leucocyte subsets, including peripheral blood memory T cells, and mouse models implicate a role for this receptor in diverse inflammatory responses that include allergic airway disorders, inflammatory bowel disease and autoimmune encephalitis. In order to study the role of CCR6 in humans, we have investigated the patterns of CCR6 expression and function on T cells from the peripheral blood, skin, nose and lung, in health and in allergic disease. Results show that CCR6 was expressed consistently on a higher proportion of tissue versus peripheral blood-derived CD4+ T cells (P &lt; 0·01). CCR6 was expressed predominantly on CD4+ compared with CD8+ cells in both blood- and tissue-derived T cells (P &lt; 0·001). The number of cells showing CCR6 expression was not proportionally greater in peripheral blood or nasal mucosal T cells of subjects with symptomatic allergic rhinitis. CCR6+ cells demonstrated enhanced functional responses to CCL20 and CCL20 was increased in bronchoalveolar lavage fluid of asthmatics following endobronchial allergen provocation (P &lt; 0·05). Thus, CCR6 may be important in the regulation of T cell recruitment to tissue and up-regulation of CCL20 expression may contribute to the recruitment and/or retention of effector T cells in allergic asthma.
Neutrophil surface presentation of the anti-neutrophil cytoplasmic antibody-antigen proteinase 3 depends on N-terminal processing
Authors: Von Vietinghoff S , Eulenberg C , Wellner M , Luft F C , Kettritz R 
Published: July 2010

Summary
The neutrophil serine protease proteinase 3 (PR3) is a main autoantigen in anti-neutrophil cytoplasmic antibody-associated vasculitis. PR3 surface presentation on neutrophilic granulocytes, the main effector cells, is pathogenically important. PR3 is presented by the NB1 (CD177) glycoprotein, but how the presentation develops during neutrophil differentiation is not known. An N-terminally unprocessed PR3 (proPR3) is produced early during neutrophil development and promotes myeloid cell differentiation. We therefore investigated if PR3 presentation depended on NB1 during neutrophil differentiation and if PR3 and proPR3 could both be presented by NB1. In contrast to mature neutrophils, differentiating neutrophils showed an early NB1-independent PR3 surface display that was recognized by only two of four monoclonal anti-PR3 antibodies and occurred in parallel with proPR3, but not PR3 secretion, suggesting that the NB1-independent surface PR3 was proPR3. PR3 gene expression preceeded NB1. When the NB1 receptor was detected on the surface, a mode of PR3 surface display similar to mature neutrophils developed together with the degranulation system. Ectopic expression studies showed that NB1 was a sufficient receptor for PR3 but not proPR3. ProPR3 display on the plasma membrane may influence the bone marrow microenvironment. NB1-mediated PR3 presentation depended on PR3 N-terminal processing implicating the PR3–N-terminus as NB1-binding site.
99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Psycho-neuroimmunology and the intestinal microbiota: clinical observations and basic mechanisms
Authors: Bienenstock J , Collins S 
Published: July 2010

Summary
This is a rapidly emerging field. The application of knowledge regarding the relationship between neural and immune systems in order to gain a better understanding of human conditions has been slow. In this discussion we describe how the brain and microbiota interact, and try to bring this into a context that is clinically relevant. We begin by describing established facts pertaining to the gut–brain axis and the role of gut bacteria. We then focus upon emerging data that will contribute to the generation of a new conceptual framework about the microbiota–gut–brain axis. In the final section we anticipate future directions of this field.
99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Controversial aspects of the ‘hygiene hypothesis’
Authors: Matricardi P M 
Published: July 2010

Summary
The ‘hygiene hypothesis’ proposes that the epidemic of allergic and autoimmune diseases is due to changes in the interactions between humans and the microbes of their ecosystem. This theory apparently does not explain (i) why allergic asthma is rising in ‘unhygienic’ American inner cities; (ii) why allergic diseases are less prevalent among migrants' children living in European big cities; (iii) why infections with airborne viruses do not ‘protect’ from allergic sensitization; (iv) why the inverse association between some infections (e.g. hepatitis A virus) and allergic diseases has been reproduced in some populations, but not in others; and (v) why probiotics are not effective in the prevention and therapy of allergic diseases. These challenging questions are useful starting points to improve our understanding of the hypothesis, and to identify among the infectious agents those really responsible for a protective influence against atopic and autoimmune diseases.
Texture and pH in fish muscle related to ‘cell fragility’ measurements
Authors: KELLY K. , JONES N. R. , LOVE R. M. , OLLEY J. 
Published: July 2010

SummaryThe cell fragility method relates the protein denaturation of cold‐stored fish to the optical density of a muscle homogenate. A high E1/2 cm value has been claimed to indicate a good quality frozen fish while a low one would indicate considerable cold‐storage deterioration. Three independent groups of workers have now shown that the initial optical density of a muscle homogenate may vary considerably. It appears to be correlated with the pH of the muscle, which in turn is related to the texture. It has been found that a fish with a high pH has a soft texture and gives a low cell fragility reading, while a high reading is given by fish with low pH, which have a firmer texture.At low temperatures denaturation of the muscle is slight during coldstorage, so that this pH effect may well predominate in determining the optical density of the homogenate. Thus, while the cell fragility technique is not invalidated as a research tool, it can give misleading information when used on commercial samples of unknown pH.
Systematic identification of food dyes using paper chromatographic techniques
Authors: GRIFFITHS MAUREEN H. E. 
Published: July 2010

SummarySystematic methods for the separation and identification of (a) red, (b) yellow and orange, and (c) blue, green and black water‐soluble food dyes at present in the permitted lists of the U.K. and the U.S.A. and in the E.E.C. approved list have been devised. In addition the two permitted violet food dyes have been separated and identified, and Brown FK separated from Chocolate Brown HT and Chocolate Brown FB. The dyes are separated and identified by a process of elimination using a simple paper chromatographic technique which effectively utilizes a method of ‘double‐spotting’ of the dye samples.
Thermal conductivities of muscles, fats and bones
Authors: Morley M. J. 
Published: July 2010

Summary.Summary. The thermal conductivities of the components of meat were determined by two rapid methods. Values for muscles and fats at tempera‐tures between ‐ 19°C and ± 37°C were obtained using the probe method, and for bones at OC, 19°C and 70°C using the thermal comparator method.