bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot study of evaluation of cerebral function by S100β protein and near‐infrared spectroscopy during cold and warm cardiopulmonary bypass in infants and children undergoing open‐heart surgery*
Authors: Shaaban Ali M. , Harmer M. , Elliott M. , Thomas A. Lloyd , Kirkham F. 
Published: December 2003

SummaryCerebral injury in children undergoing cardiopulmonary bypass (CPB) remains a major source of morbidity. The effect of cardiopulmonary bypass temperature on cerebral function in terms of serum S100β protein level and cerebral oxygenation monitored by near infrared spectroscopy (NIRO‐300) in children is not known. In this study, 18 children undergoing open‐heart surgery at the Hospital for Sick Children in London were equally assigned by minimisation to warm (35 ± 1 °C) or cold (25 ± 1 °C) CPB. Changes in S100β protein and cerebral oxygenation were studied in both groups. S100β protein serum level increased significantly after CPB in both groups. There was no significant difference in serum S100β protein concentrations between the two groups. However, cerebral oxygenation in terms of tissue oxygen index (TOI) was significantly impaired during rewarming from cold CPB. Five patients were desaturated (TOI < 50%) during rewarming in the cold bypass group compared to two in the warm patients. This study supports the use of warm CPB in children undergoing open‐heart surgery, although further studies recruiting more patients are warranted.
Immunopathogenic mechanisms in psoriasis
Authors: GUDJONSSON J E , JOHNSTON A , SIGMUNDSDOTTIR H , VALDIMARSSON H 
Published: December 2003

SUMMARYPsoriasis is a common autoimmune skin disease characterized by T cell-mediated hyperproliferation of keratinocytes. The disease has a strong but complex genetic background with a concordance of approximately 60% in monozygotic twins, and recent linkage and high resolution association studies indicate that HLA-Cw*0602 is itself a major susceptibility allele for psoriasis. Patients carrying this allele have been shown to have different clinical features and earlier age of disease onset, and patients homozygous for this allele have about 2·5 times higher disease risk than heterozygotes. Published data indicate that CD8+ T cells may play a major effector role in psoriasis. Epidermal infiltration of predominantly oligoclonal CD8+ T cells, and probably also of CD4+ T cells in the dermis, is a striking feature of chronic psoriasis lesions, indicating that these cells are responding to specific antigens. We argue that CD4+ T cells are essential for initiating and maintaining the pathogenic process of psoriasis but that cross-primed CD8+ T cells are the main effector cells responding to antigens in the HLA-Cw*0602 binding pocket of keratinocytes. It is further proposed that CD8+ T cells are involved in the control of the Th1 polarization, which is observed in psoriasis lesions, through a complex interplay between CD4+, CD8+ T cells and cross-presenting dendritic cells. It is also suggested that spontaneous remissions or fluctuations in disease activity may be determined by a balance within the lesions between effector and suppressor CD4+ and CD8+ T cells.
Immature anti-inflammatory response in neonates
Authors: SCHULTZ C , TEMMING P , BUCSKY P , GÖPEL W , STRUNK T , HÄRTEL C 
Published: December 2003

SUMMARYThe inflammatory response plays a major role in the induction of several neonatal diseases. We hypothesize that an imbalance between the pro- and anti-inflammatory response is crucial for the previously shown enhanced production of proinflammatory cytokines in term and preterm infants during infection. To test this hypothesis, we compared the capacity to produce the main anti-inflammatory cytokines IL-10 and TGF-β in term infants, preterm infants and adults at different levels of synthesis by quantitative real time reverse-transcribed PCR, flow cytometry, as well as enzyme-linked immunoassay. Term and preterm infants showed a profoundly diminished IL-10 mRNA-expression and IL-10 production after stimulation. In addition, the amount of TGF-β-positive lymphocytes was significantly less in neonates than adults. Furthermore, there was a considerably lower inhibition of production of IL-1α, IL-6, IL-8 and TNF-α by the use of recombinant IL-10 in term and preterm infants compared with adults. These results demonstrate not only a diminished anti-inflammatory capacity but also a reduced response to anti-inflammatory stimuli in term and preterm infants. From these data we conclude that neonates display an immature compensatory anti-inflammatory response syndrome (CARS) which may predispose preterm infants to harmful effects of proinflammatory cytokines resulting in severe organ sequelae during infection.
Epitope mapping of anti-PR3 antibodies using chimeric human/mouse PR3 recombinant proteins
Authors: SELGA D , SEGELMARK M , WIESLANDER J , GUNNARSSON L , HELLMARK T 
Published: December 2003

SUMMARYAutoantibodies against proteinase 3 (PR3) and myeloperoxidase (MPO) (ANCA = anti-neutrophil cytoplasmic antibodies) are used as diagnostic tools for patients with small vessel vasculitis. ANCA are detected by different assays, but the correlation between the results of these assays is generally poor. The overall aim of the study was to provide a framework for the future development of new assays with an increased diagnostic yield. In order to express discrete epitopes of human PR3 (hPR3), the nonantigenic molecules murine PR3 (mPR3) and human leucocyte elastase (HLE) were used as a framework. We constructed recombinant chimeric vectors and were able to produce 6 hPR3/mPR3 proteins and 3 hPR3/HLE proteins. Anti-PR3 monoclonal antibodies differed in their binding pattern to the chimeras, but no distinct binding region could be identified for any monoclonal antibody. The recombinant hPR3/mPR3 were also tested in ELISA with sera from patients with Wegener's granulomatosis with renal involvement. The results show that patients have antibodies to different constructs, indicating that the patients vary in their antibody repertoire from the beginning of the disease, and that patients may have antibodies from a broad range of clones early in the course of the disease. Recombinant hPR3/mPR3 chimeric proteins have a potential to be used as antigens in future ANCA assays.
Nicotinamide does not influence cytokines or exhaled NO in human experimental endotoxaemia
Authors: SOOP A , ALBERT J , WEITZBERG E , BENGTSSON A , NILSSON C-G , SOLLEVI A 
Published: December 2003

SUMMARYThis study examined the hypothesis that nicotinamide could attenuate endotoxin-induced inflammatory responses in humans as indicated by levels of cytokines and nitric oxide. Ten healthy male volunteers participated in a randomised, double-blind, cross-over design with regard to the effects of nicotinamide. The volunteers received orally 4 g nicotinamide or placebo at 14 h and at 2 h preceding the experiment (total dose of 8 g). Endotoxin (E. coli, 2 ng/kg), was administered intravenously. Blood samples and haemodynamic data were collected prior to and up to 6 h after the endotoxin infusion. Orally exhaled NO was measured hourly. Following endotoxin, body temperature increased from baseline 36·3 ± 0·09°C to a maximum of 38·0 ± 0·1°C for all (mean ± SEM, P &lt;0·001) and heart rate increased from 59 ± 1·9 to 87·0 ± 2·6 beats/min after 3 h (mean ± SEM, P &lt;0·001). Endotoxin challenge also markedly elevated the TNF-α, IL-6, IL-8 and IL-10 concentrations (P &lt; 0·001 versus baseline for all) during the study period. Orally exhaled NO also increased (P &lt; 0·01) compared to baseline. Nicotinamide treatment did not influence the patterns of cytokine and NO response to endotoxin.In conclusion, there was no effect on the inflammatory parameters by oral nicotinamide at a dose of 8 g, limiting the potential use of this agent for anti-inflammatory purpose in man.
Antibodies to inner ear antigens in Meniere's disease
Authors: RIENTE L , BONGIORNI F , NACCI A , MIGLIORINI P , SEGNINI G , DELLE SEDIE A , URSINO F , TOMMASI S , FATTORI B 
Published: December 2003

SUMMARYMeniere's disease (MD) is an idiopathic inner ear disorder characterized by fluctuating hearing loss, episodic vertigo and tinnitus. Its aetiology is unknown, although there is growing evidence that autoimmunity may be involved in its development. Using the Western blot immunoassay, we examined the reactivity to bovine inner ear antigens of sera from a series of MD patients who had previously been extensively studied for the presence of antibodies to collagens and membrane proteins. Reactivity to inner ear antigens of molecular weight 44 and 53 kD was found in 11/25 (44%) and 10/25 (40%) of the patients, respectively; both antigens were absent in the sera of healthy donors. It is still unclear whether the antibodies to 44 and 53 kD proteins play a role in the pathogenesis of MD or if they instead represent the result of inflammation and tissue destruction. Even if the latter is true, they may contribute to the perpetuation of the disease or play a role as a cofactor in association with other mechanisms.
Lung cell responses toM. tuberculosisin genetically susceptible and resistant mice following intratracheal challenge
Authors: ERUSLANOV E B , MAJOROV K B , ORLOVA M O , MISCHENKO V V , KONDRATIEVA T K , APT A S , LYADOVA I V 
Published: December 2003

SUMMARYOne approach to study the role of distinct cellular mechanisms in susceptibility/resistance to tuberculosis (TB) is to compare parameters of response to infection in the lungs of mouse strains exhibiting genetically determined differences in TB susceptibility/severity. Interstrain differences in antimycobacterial macrophage reactions, T cell responses & inflammation in the lungs of TB-susceptible I/St, TB-resistant A/Sn and (I/St × A/Sn)F1 mice were analysed following intratracheal inoculation of 103 CFUs of M. tuberculosis H37Rv. The antimycobacterial responses in the lungs of susceptible I/St mice were characterized by: (i) increased inflammatory infiltration by all major immune cell subsets; (ii) decreased type 1 cytokine production; (iii) impaired antimycobacterial activity of lung macrophages; (iv) unusually high proliferation of lung T lymphocytes. Differences in several parameters of anti-TB immunity between susceptible and resistant mice corresponded well to the polygenic pattern of TB control previously established in this mouse model. Importantly, lung macrophages isolated from noninfected mice were unable to respond to IFN-γ by increasing their mycobactericidal function, but between weeks 3 and 5 of the infection this capacity developed in all mice. However, by this time point susceptible but not resistant mice demonstrated a pronounced decrease in IFN-γ production by lung cells. This chain of events may explain the inability of I/St mice to control both early and chronic TB infection.
Graves’ hyperthyroidism and thyroiditis in HLA-DRB1*0301 (DR3) transgenic mice after immunization with thyrotropin receptor DNA
Authors: FLYNN J C , RAO P V , GORA M , ALSHARABI G , WEI W , GIRALDO A A , DAVID C S , BANGA J P , KONG Y M 
Published: December 2003

SUMMARYFamilial and twin studies in Caucasians have established that the MHC class II allele HLA-DRB1*0301 (DR3) is a strong susceptibility gene in Graves’ hyperthyroid disease (GD). To determine if a DR3 transgene could help establish an animal model for GD, we expressed DR3 molecules in class II-knockout NOD mice (H2Ag7–). DR3+g7– mice were given cardiotoxin prior to immunization on weeks 0, 3 and 6 with plasmid DNA encoding human thyrotropin receptor (TSHR). Two groups of mice were also coimmunized with plasmid DNA for IL-4 or GM-CSF. Serial bleeds on weeks 8, 11 and 14 showed that approximately 20% of mice produced thyroid-stimulating antibodies (Abs), and approximately 25% had elevated T4 levels. In particular, a subset displayed both signs of hyperthyroidism, resulting in approximately 30% with some aspect of GD syndrome. Additional mice had thyroid-stimulating blocking Abs and/or TSH-binding inhibitory immunoglobulins, while most mice showed strong labelling of TSHR+ cells by flow cytometry. Interestingly, lymphocytic infiltration with thyroid damage and Abs to mouse thyroglobulin were also noted. Vector controls were uniformly negative. Thus, DR3 transgenic mice can serve as a model for GD, similar to our earlier reports that this allele is permissive for the Hashimoto's thyroiditis model induced with human thyroglobulin.
NK cells modulate the cytotoxic activity generated byMycobacterium leprae-hsp65 in leprosy patients: role of IL-18 and IL-13
Authors: DE LA BARRERA S , FINIASZ M , FINK S , ILARREGUI J , ALEMÁN M , OLIVARES L , FRANCO M C , PIZZARIELLO G , DEL CARMEN SASIAIN M 
Published: December 2003

SUMMARYProtection against intracellular pathogens such as Mycobacterium leprae is critically dependent on the function of NK cells at early stages of the immune response and on Th1 cells at later stages. In the present report we evaluated the role of IL-18 and IL-13, two cytokines that can influence NK cell activity, in the generation of M. leprae-derived hsp65-cytotoxic T lymphocytes (CTL) from peripheral blood mononuclear cells (PBMC) of leprosy patients. We demonstrated that IL-18 modulates hsp65-induced CTL generation and collaborates with IL-12 for this effect. In paucibacillary (PB) patients and normal controls (N) depletion of NK cells reduces the cytolytic activity. Under these conditions, IL-12 cannot up-regulate this CTL generation, while, in contrast, IL-18 increases the cytotoxic activity both in the presence or absence of NK cells. IL-13 down-regulates the hsp65-induced CTL generation and counteracts the positive effect of IL-18. The negative effect of IL-13 is observed in the early stages of the response, suggesting that this cytokine affects IFNγ production by NK cells. mRNA coding for IFNγ is induced by IL-18 and reduced in the presence of IL-13, when PBMC from N or PB patients are stimulated with hsp65. Neutralization of IL-13 in PBMC from multibacillary (MB) leprosy patients induces the production of IFNγ protein by lymphocytes. A modulatory role on the generation of hsp65 induced CTL is demonstrated for IL-18 and IL-13 and this effect takes place through the production of IFNγ.
High-level endothelial E-selectin (CD62E) cell adhesion molecule expression by a lipopolysaccharide-deficient strain ofNeisseria meningitidisdespite poor activation of NF-κB transcription factor
Authors: DIXON G L J , HEYDERMAN R S , VAN DER LEY P , KLEIN N J 
Published: December 2003

SUMMARYBinding of host inflammatory cells to the endothelium is a critical contributor to the vascular damage characteristic of severe meningococcal disease and is regulated by endothelial cell adhesion molecules such as ICAM-1, VCAM-1 and CD62E. Intact meningococci induce far higher levels of CD62E than lipopolysaccharide (LPS) alone, whereas LPS is at least as potent as meningococci at inducing both VCAM-1 and ICAM-1 expression. This suggests that meningococci possess additional factors other than LPS present in whole bacteria that result in differential adhesion molecule expression. To investigate this possibility, we studied the capacity of an LPS-deficient isogenic strain of serogroup B Neisseria meningitidis H44/76 (lpxA-) to induce endothelial cell adhesion molecule expression and translocation of the transcription factor NF-κB, and compared it to both parent and unencapsulated strains of both B1940 and H44/76 and purified LPS. Although the LPS-deficient isogenic mutant of strain H44/76 was found to be a poor inducer of NF-κB, it induced higher levels of CD62E expression than LPS alone. These data provide evidence that intact meningococci induce a range of signals in the endothelium that are distinct from those seen with purified LPS alone and that they occur in a LPS-dependent and LPS-independent manner. These signals may explain the potent effects of N. meningitidis on CD62E expression on vascular endothelium and provide a basis for the complex endothelial dysregulation seen in meningococcal sepsis.
Mushroom plant workers experience a shift towards a T helper type 2 dominant state: contribution of innate immunity to spore antigen
Authors: SAIKAI T , TANAKA H , SATO N , ABE S , MATSUURA A 
Published: December 2003

SUMMARYContemporary mushroom factories are places where there is a substantial risk of the occurrence of respiratory allergy. The aims of this investigation were to estimate its causative agents and to evaluate the contribution of innate immune response in mushroom workers who cultivate Hypsizigus marmoreus (Bunashimeji). Cross-sectional and follow-up studies were performed in the factory. We investigated CD1b, CD3, CD4, CD8, CD14, CD45RO, CD62L and CD161 expression in peripheral blood mononuclear cells (PBMC) by flow cytometry, and serum levels of interleukin (IL-2), IL-4, granulocyte-macrophage colony stimulating factor (GM-CSF), IL-13 and interferon (IFN)-γ by enzyme-linked immunosorbent assay (ELISA). Co-culture experiments of PBMC with spore extracts were also performed. Percentages of CD1b+ monocytes, natural killer (NK), NK T and CD4+ T cells were increased in the workers compared with controls. Increases in Th2 type cells, Th2/Th1 ratio and serum IL-13 and decreased IFN-γ were detected, indicating a Th2-biased status of the workers. The follow-up study showed that monocytes and NK cells increased soon after employment while CD4+ T, Th2 and NK T cells increased gradually as employment time lengthened. Serum precipitating antibody to the mushroom antigen could be detected at a later stage. Co-cultivation of PBMC with the spore extracts induced much higher CD1b expression, and suppressed secretion of Th1 cytokine in culture supernatants. These results indicate that the mushroom antigen contains highly immunogenic substances which stimulate PBMC into a Th2-biased in vivo status, and innate immune cells might also play a critical role in developing respiratory allergy in mushroom workers.
CTLA-4 blockade inhibits induction ofHelicobacter pylori-associated gastritis in mice
Authors: WATANABE K , MURAKAMI K , SATO R , OKIMOTO T , MAEDA K , NASU M , NISHIZONO A , FUJIOKA T 
Published: December 2003

SUMMARYThe balance between Th1 and Th2 response determines the outcome of Helicobacter pylori infection. Interferon (IFN)-γ plays an inductive role in gastric inflammation, whereas interleukin (IL)-4 counterbalances Th1 response and suppresses the development of gastritis. Th cell response is regulated by co-stimulatory factors. A co-stimulatory molecule, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), plays an inhibitory role in IL-2-dependent cell growth and mediates an optimal inhibitory signal to Th1 and Th2 cells. We administered anti-CTLA-4 monoclonal antibody (MoAb), which blocks CTLA-4 signalling, to examine the relative role for this signalling during maturation of Th1 and Th2 cells in H. pylori infection in mice. Mice treated by anti-CTLA-4 MoAb within the first week of infection showed an inhibition of gastric inflammation, accompanied by an increasing ratio of H. pylori-specific IgG1/IgG2a in serum following infection. Furthermore, the treatment resulted in the higher ratio of IL-4/IFN-γ by splenocytes in response to H. pylori antigen at 6 weeks after infection, compared with untreated mice. These results suggest that the predominance of Th2 response by CTLA-4 blockade leads to an inhibition of the development of gastric inflammation. CTLA-4 signalling could contribute to the regulation of Th subsets and the development of gastric inflammation in H. pylori infection.
Evidence for autoantibody-induced CD4 depletion mediated by apoptotic and non-apoptotic mechanisms in HIV-positive long-term surviving haemophilia patients
Authors: DANIEL V , SADEGHI M , NAUJOKAT C , WEIMER R , HUTH-KÜHNE A , ZIMMERMANN R , OPELZ G 
Published: December 2003

SUMMARYIt is believed that autoimmune phenomena and apoptosis contribute to CD4 depletion. We investigated 11 long-term (&gt;20 years) HIV-infected haemophilia patients and 10 healthy controls. Using four-colour-fluorescence flow cytometry, we studied the proportions of CD3+CD4+ and CD3+CD4– blood lymphocytes that were CD95+, CD95L+, immune complex+ (IC+, consisting of IgM, IgG, C3d and/or gp120), and were viable or non-viable (propidium iodide+ = PI+). In addition, we studied viability of CD4+IgG+ patient lymphocytes using the apoptosis marker annexin and the permeability indicator 7-amino actinomycin D (7-AAD). HIV+ patients had a higher proportion of CD3+CD4+IgG+PI+ lymphocytes than healthy controls (median: 3·7%versus 0·3%; P = 0·00001). These non-viable IgG-coated lymphocytes might have been killed in vivo by ADCC or complement lysis; 9·1% of the circulating CD3+CD4+ blood lymphocytes were IgG+PI– (controls: 2·5%; P = 0·001). These viable IgG-coated lymphocytes might be targets for phagocytosis or anti-CD95 autoantibody-mediated apoptosis. Because HIV+ patients and healthy controls had similar proportions of PI+ or PI– CD3+CD4+ lymphocytes that carried CD95L on the surface, and because CD3+CD4+CD95L+ cells that were IgG+, C3d+ and/or gp120– were increased in HIV+ patients, the role of CD95L-induced apoptosis in long-term HIV-infected haemophilia patients remains unclear. The findings that HIV+ patients had higher proportions of CD3+CD4+CD95+ (PI+: 6·5%versus 1·4%; P = 0·00002; PI–: 55·8%versus 44·4%; P = 0·04) blood lymphocytes and that the proportion of CD4+IgG+Annexin+7-AAD– blood lymphocytes was associated inversely with peripheral CD4 counts (r = −0·636; P &lt; 0·05) suggest that attachment of IgG to CD4+ blood lymphocytes (anti-CD95?) induces in some lymphocytes apoptosis with subsequent depletion of these IgG-coated apoptotic CD4+ lymphocytes from the circulation. We found supporting evidence for the contention that autoantibody-induced apoptotic and non-apoptotic mechanisms contribute to CD4 depletion in long-term HIV-infected haemophilia patients.
Age-related bias in function of natural killer T cells and granulocytes after stress: reciprocal association of steroid hormones and sympathetic nerves
Authors: SAGIYAMA K , TSUCHIDA M , KAWAMURA H , WANG S , LI C , BAI X , NAGURA T , NOZOE S , ABO T 
Published: December 2003

SUMMARYStress-associated immune responses were compared between young (8 weeks of age) and old (56 weeks) mice. Since stress suppresses the conventional immune system (i.e. T and B cells) but inversely activates the primordial immune system (i.e. extrathymic T cells, NKT cells, and granulocytes), these parameters were analysed after restraint stress for 24 h. The thymus became atrophic as a function of age, and an age-related increase in the number of lymphocytes was seen in the liver. Although the number of lymphocytes in both the thymus and liver decreased as the result of stress, the magnitude was much more prominent in the thymus. To determine stress-resistant lymphocyte subsets, two-colour immunofluorescence tests were conducted in the liver and spleen. NKT cells were found to be such cells in the liver of young mice. On the other hand, an infiltration of granulocytes due to stress was more prominent in the liver of old mice than in young mice. Liver injury as a result of stress was prominent in young mice. This age-related bias in the function of NKT cells and granulocytes seemed to be associated with a difference in the responses of catecholamines (high in old mice) and corticosterone (high in young mice) after stress. Indeed, an injection of adrenaline mainly induced the infiltration of granulocytes while that of cortisol activated NKT cells. The present results suggest the existence of age-related bias in the function of NKT cells and granulocytes after stress and that such bias might be produced by different responses of sympathetic nerves and steroid hormones between young and old mice.