bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic and functional characteristics of CD28+ and CD28− cells from chagasic patients: distinct repertoire and cytokine expression
Authors: MENEZES C A S , ROCHA M O C , SOUZA P E A , CHAVES A C L , GOLLOB K J , DUTRA W O 
Published: June 2004

SUMMARYChronic human Chagas’ disease ranges from an asymptomatic to a severe cardiac clinical form. The involvement of the host's immune response in the development and maintenance of chagasic pathology has been demonstrated by several groups. We have shown that activated T-cells lacking CD28 expression are increased in the peripheral blood of chagasic patients (CP), suggesting a relationship between these cells and disease. In order to better characterize this cell population, determining their possible role in immunoregulation of human Chagas’ disease, we evaluated the expression of TCR-Vbeta regions 2, 3·1, 5, 8 and 17, as well as the expression of IFN-γ, TNF-α, IL-4 and IL-10 by CD28+ and CD28− cells from polarized indeterminate and cardiac CP. Flow cytometric analysis demonstrated equivalent TCR-Vbeta usage between CD4+CD28+ and CD4+CD28− cells from all groups (chagasic and healthy controls). However, there was a predominance of Vbeta5 expression in the CD28+ and CD28− populations in the CP groups (indeterminate and cardiac). Interestingly, CD8+CD28− cells from CP, but not from nonchagasic individuals, displayed a reduced frequency of most analysed Vbetas when compared with the CD8+CD28+ subpopulation. Comparison of V-beta expression in CD28+ or CD28− cell populations among individuals from different groups also showed several interesting differences. Functionally, cardiac CP displayed a higher frequency of IFN-γ, TNF-α and IL-4 producing lymphocytes than indeterminate CP. Correlation analysis between the frequency of cytokine expressing cells, and the frequency of CD4+ T-cells with differential expression of CD28 demonstrated that CD4+CD28− T-cells were positively correlated with TNF-α in cardiac and with IL-10 in indeterminate CP, suggesting that these cells might have an important regulatory role in human Chagas’ disease.
Systemic complement activation following human acute ischaemic stroke
Authors: PEDERSEN E D , WAJE-ANDREASSEN U , VEDELER C A , AAMODT G , MOLLNES T E 
Published: June 2004

SUMMARY
The brain tissue damage after stroke is mediated partly by inflammation induced by ischaemia–reperfusion injury where the complement system plays a pivotal role. In the present study we investigated systemic complement activation and its relation to C-reactive protein (CRP), a known complement activator, and other inflammatory mediators after acute ischaemic stroke. Sequential plasma samples from 11 acute stroke patients were obtained from the time of admittance to hospital and for a follow-up period of 12 months. Nine healthy gender- and age-matched subjects served as controls. The terminal SC5b-9 complement complex (TCC), CRP, soluble adhesion molecules (L-, E- and P- selectin, ICAM, VCAM) and cytokines [tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8] were analysed. All parameters were within normal values and similar to the controls the first hours after stroke. Terminal complement complex (TCC) increased significantly from 0·54 to 0·74 AU/ml at 72 h (P = 0·032), reached maximum at 7 days (0·90 AU/ml, P &lt; 0·001), was still significantly increased at 12 days (0·70 AU/ml, P = 0·009) and thereafter normalized. CRP increased significantly from 1·02 to 2·11 mg/l at 24 h (P = 0·023), remained significantly increased for 1 week (2·53–2·94 mg/l, P = 0·012–0·017) and thereafter normalized. TCC and C-reactive protein (CRP) correlated significantly (r = 0·36, P &lt; 0·001). The increase in TCC and CRP correlated to the size of infarction (r = 0·80 and P = 0·017 for TCC; r = 0·72 and P = 0·043 for CRP). No significant changes were seen for adhesion molecules and cytokines. In conclusion, transitory systemic complement activation takes place after stroke. The early rise in CRP and the following TCC increase suggest a possible role for CRP in complement activation, which may contribute to inflammation after stroke.
Screening of a HUAEC cDNA library identifies actin as a candidate autoantigen associated with carotid atherosclerosis
Authors: MARGUTTI P , DELUNARDO F , SORICE M , VALESINI G , ALESSANDRI C , CAPOANO R , PROFUMO E , SIRACUSANO A , SALVATI B , RIGANÒ R , ORTONA E 
Published: June 2004

SUMMARY
The humoral immune response to endothelium has a pivotal role in the development of atherosclerosis. Using a molecular method, we sought to identify endothelial autoantigens in carotid atherosclerosis. Immunoscreening of a HUAEC expression library with IgG from a pool of two sera from patients with carotid atherosclerosis identified a clone specific to actin. We evaluated actin-specific IgG reactivity in patients with carotid atherosclerosis and compared responses with those in patients with systemic lupus erythematosus and type 1 diabetes mellitus and in healthy subjects. Enzyme-linked immunoassay detected actin-specific IgG in a significantly higher percentage of sera from patients with atherosclerosis and systemic lupus erythematosus than from healthy subjects (16/61, 26% and 13/33, 39%versus 2/41, 5%, P = 0·012 and P &lt; 10−4, by χ2 test). Mean optical density values were significantly higher in patients than in healthy subjects (P &lt; 10−4 by Student's t-test). Patients with atherosclerosis and uncomplicated plaques had significantly higher serum anti-actin IgG reactivity than those with complicated plaques (P = 0·048 by Student's t-test). Our findings suggest that actin is an autoantigenic molecule of potential clinical interest in carotid atherosclerosis.
The impact of an early truncating founder ATM mutation on immunoglobulins, specific antibodies and lymphocyte populations in ataxia-telangiectasia patients and their parents
Authors: STRAY-PEDERSEN A , JÓNSSON T , HEIBERG A , LINDMAN C R , WIDING E , AABERGE I S , BORRESEN-DALE A L , ABRAHAMSEN T G 
Published: June 2004

SUMMARY
Eleven Norwegian patients (aged 2–33 years, seven males and four females) with Ataxia-telangiectasia (A-T) and their parents were investigated. Five of the patients were homozygous for the same ATM mutation, 3245delATCinsTGAT, a Norwegian founder mutation. They had the lowest IgG2 levels; mean (95% confidence interval) 0·23 (0·05–0·41) g/l versus 0·91 (0·58–1·26) g/l in the other patients (P = 0·002). Among the 11 A-T patients, six had IgG2 deficiency, six had IgA deficiency (three in combination with IgG2 deficiency) and seven had low/undetectable IgE values. All patients had very low levels of antibodies to Streptococcus pneumoniae 0·9 (0·4–1·4) U/ml, while normal levels were found in their parents 11·1 (8·7–13·4) U/ml (P &lt; 0·001). A positive linear relationship between pneumococcal antibodies and IgG2 (r = 0·85, P = 0·001) was found in the patients. Six of 11 had diphtheria antibodies and 7 of 11 tetanus antibodies after childhood vaccinations, while 4 of 7 Hemophilus influenzae type b (Hib) vaccinated patients had protective antibodies. Ten patients had low B cell (CD19+) counts, while six had low T cell (CD3+) counts. Of the T cell subpopulations, 11 had low CD4+ cell counts, six had reduced CD8+ cell counts, and four had an increased portion of double negative (CD3+/CD4-/CD8-) gamma delta T cells. Of the 22 parents (aged 23–64 years) 12 were heterozygous for the ATM founder mutation. Abnormalities in immunoglobulin levels and/or lymphocyte subpopulations were also observed in these carriers, with no correlation to a special ATM genotype.
The tetraspanin CD9 is preferentially expressed on the human CD4+CD45RA+ naive T cell population and is involved in T cell activation
Authors: KOBAYASHI H , HOSONO O , IWATA S , KAWASAKI H , KUWANA M , TANAKA H , DANG N H , MORIMOTO C 
Published: June 2004

SUMMARYHuman CD4+ T cells can be divided into reciprocal memory and naive T cell subsets based on their expression of CD45 isoforms and CD29/integrin beta1 subunit. To identify unique cell surface molecules on human T cells, we developed a new monoclonal antibody termed anti5H9. Binding of anti5H9 triggers a co-stimulatory response in human peripheral blood T cells. Retrovirus-mediated expression cloning has revealed that the antigen recognized by anti5H9 is identical to the tetraspanin CD9. We now show that human CD9 is preferentially expressed on the CD4+CD45RA+ naive T cell subset, and that CD9+CD45RA+ T cells respond preferentially to the recombinant beta2-glycoprotein I, compared to CD9–CD45RA+ T cells. Furthermore, anti5H9 inhibits both the recombinant beta2-glycoprotein I- and the recall antigen tetanus toxoid-specific T cell proliferation. These results suggest that the tetraspanin CD9 plays an important role in T cell activation.
Effect of maternal anti-HPA-1a antibodies and polyclonal IVIG on the activation status of vascular endothelial cells
Authors: RADDER C M , BEEKHUIZEN H , KANHAI H H H , BRAND A 
Published: June 2004

SUMMARYMaternal anti-HPA-1a antibodies can cause severe fetal and neonatal alloimmune thrombocytopenia (FNAIT), complicated by intracranial haemorrhage (ICH). Antenatal treatment with maternal intravenous immunoglobulin (IVIG) seems to protect against ICH even when thrombocytopenia persists. The aim of this study was to investigate if anti-HPA-1a antibodies and IVIG potentially affect vascular endothelial cells (ECs) in order to identify susceptibility for ICH. Human umbilical cord endothelial cells (HUVEC) were incubated with anti-HPA-1a antibodies with or without polyclonal IVIG and evaluated for EC activation. Maternal sera with anti-HPA-1a antibodies affected neither the EC expression of intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and tissue factor (TF) nor the release of van Willebrand factor (vWF) or interleukin (IL)-8 nor the integrity of ECs. Maternal sera obtained after IVIG treatment and polyclonal IVIG decrease constitutive and cytokine-induced ICAM-1 and VCAM-1 expression on ECs. The results show that maternal anti-HPA-1a antibodies cause no activation or damage of ECs in this model. The clinical relevance of the de-activating properties of IVIG on EC activation with respect to ICH deserves further investigation.
Adjuvant oil induces waves of arthritogenic lymph node cells prior to arthritis onset
Authors: HOLM B C , LORENTZEN J C , BUCHT A 
Published: June 2004

SUMMARY
A single intradermal injection of the adjuvant-oil squalene induces T cell mediated arthritis in DA rats. The chain of events leading from nonspecific provocation of the immune system to arthritis is largely unknown. Previous studies have demonstrated that lymph node (LN) cells are of pathogenic importance, i.e. cells from LNs draining the injection site can transfer arthritis to naïve DA rats. Recently we have demonstrated cellular uptake of adjuvant oil in draining lymph nodes but also that nondraining LNs become hyperplastic and harbour arthritogenic cells. Here, we aimed to determine from which time-point prior to arthritis onset arthritogenic cells appear in draining inguinal and nondraining axillary/brachial LNs, respectively. We demonstrated that the ability to transfer arthritis was strongly dependent on the time-point after adjuvant-injection with clear-cut differences between draining and nondraining LN cells. Cells harvested at day 5 postinjection (p.i) were not able to transfer arthritis, while at day 8 p.i, a first wave of arthritogenic cells appeared in draining LNs. The ability to transfer arthritis was associated with a pro-inflammatory cytokine profile as indicated by the IL-1β and IFNγ expression in cells from draining LNs. Subsequently, at day 11 p.i., just before arthritis onset, arthritogenic cells appeared also in nondraining LNs. These results shed new light on the induction of arthritic diseases, implicating a two step mechanism for the development of pathogenic cells. Firstly, a pro-inflammatory burst in responding lymphoid organs leading to a local pool of arthritogenic cells and, secondly, a transmission of arthritogenecity to other LNs and precipitation of disease in peripheral joints.
Joint cytokine quantification in two rodent arthritis models: kinetics of expression, correlation of mRNA and protein levels and response to prednisolone treatment
Authors: RIOJA I , BUSH K A , BUCKTON J B , DICKSON M C , LIFE P F 
Published: June 2004

SUMMARYBiomarker quantification in disease tissues from animal models of rheumatoid arthritis (RA) can help to provide insights into the mechanisms of action of novel therapeutic agents. In this study we validated the kinetics of IL-1β, TNF-α and IL-6 mRNA and protein expression levels in joints from DBA/1OlaHsd murine collagen-induced arthritis (CIA) and Lewis rat Streptococcal cell wall (SCW)-induced arthritis by real-time polymerase chain reaction (PCR) TaqMan® and Enzyme-linked immunosorbent assay (ELISA). Prednisolone was used as a reference to investigate any correlation between clinical response and cytokine levels at selected time-points. To our knowledge this is the first report showing a close pattern of expression between mRNA and protein for IL-1β and IL-6, but not for TNF-α, in these two models of RA. The kinetics of expression for these biomarkers suggested that the optimal sampling time-points to study the effect of compounds on both inflammation and cytokine levels were day 4 postonset in CIA and day 3 after i.v challenge in SCW-induced arthritis. Prednisolone reduced joint swelling through a mechanism associated with a reduction in IL-1β and IL-6 protein and mRNA expression levels. At the investigated time points, protein levels for TNF-α in arthritic joints were lower than the lower limit of detection of the ELISA, whereas mRNA levels for this cytokine were reliably detected. These observations suggest that RT-PCR TaqMan® is a sensitive technique that can be successfully applied to the quantification of mRNA levels in rodent joints from experimental arthritis models providing insights into mechanisms of action of novel anti-inflammatory drugs.
Increased Fas-mediated apoptosis in polymorphonuclear cells from HIV-infected patients
Authors: SALMEN S , TERÁN G , BORGES L , GONCALVES L , ALBARRÁN B , URDANETA H , MONTES H , BERRUETA L 
Published: June 2004

SUMMARYNeutrophils represent an important line of innate host defence against invading microorganisms and their functional detriment during HIV infection, including accelerated spontaneous cell death, has been shown to contribute to AIDS development. Neutrophils are susceptible to apoptosis via Fas and an interaction between Fas and FasL was suggested originally as a mechanism to explain constitutive neutrophil apoptosis. We have explored some intracellular pathways leading to PMN apoptosis from 28 HIV-infected patients and 24 healthy volunteers. As previously reported, accelerated spontaneous apoptosis was observed in HIV+ patients, but this did not correlate with viral load. Furthermore, an increase in the level of spontaneous apoptosis was detected in neutrophils from HIV-infected patients following inhibition of ERK, suggesting an impairment of this kinase pathway during the early stages of infection which may contribute to PMN dysfunction. An elevated susceptibility to undergo apoptosis was observed following cross-linking of Fas, which correlated both with viral load and co-expression of Fas/FasL surface molecules. Different mechanisms for spontaneous and Fas-induced apoptosis are proposed which together contribute to the neutropenia and secondary infections observed during the progression to AIDS.
Decreased interferon-gamma response in respiratory syncytial virus compared to other respiratory viral infections in infants
Authors: ABERLE J H , ABERLE S W , REBHANDL W , PRACHER E , KUNDI M , POPOW-KRAUPP T 
Published: June 2004

SUMMARY
An inappropriate interferon-gamma response has been implicated in the pathogenesis of severe respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI). To assess whether this is unique for RSV primary LRTI compared to a first non-RSV LRTI, intracellular interferon-gamma was determined by flow cytometry in peripheral blood mononuclear cells from 32 infants with a primary RSV infection, 28 with a first non-RSV LRTI due to adenoviral, parainfluenzaviral and rhinoviral infection and 13 healthy infants. Interferon-γ responses were increased significantly during adenoviral, parainfluenzaviral and the majority of the rhinoviral infections, but remained low during RSV and severe rhinoviral infection. Low interferon-γ responses were associated with a more severe clinical course of LRTI. This indicates that depending on the nature of the viral pathogen, respiratory virus infections in infants differ significantly with regard to the quantity of the interferon-γ production and that this may contribute to the clinical course of the disease.
Rotavirus-specific T-cell responses in young prospectively followed-up children
Authors: MÄKELÄ M , MARTTILA J , SIMELL O , ILONEN J 
Published: June 2004

SUMMARY
Rotavirus is a major cause of gastroenteritis in young children. Antibodies seem to protect against rotavirus infection but cell-mediated immune responses are probably also important for protection. We evaluated the development of T-cell responses to rotavirus in follow-up samples from 20 healthy children with an increased genetic risk for type 1 diabetes. Blood samples from 16 healthy adults were also available for the study. T-cell proliferation was analysed at 3–6 month intervals from the age of 3 months to the age of 4–5 years using the Wa strain of human rotavirus and the NCDV strain of bovine rotavirus as antigens. IgG and IgA antibodies to rotavirus were studied from simultaneously drawn plasma samples with EIA method using NCDV as an antigen. A total of 24 infections were revealed by antibody analysis. Sixteen children showed diagnostic increases in both IgG and IgA antibodies to rotavirus, while 5 children showed increases in IgA antibodies only and 3 in IgG only. Antibody rises were accompanied by T-cell responses to rotavirus (SI &gt; 3) in 9 of the 24 cases. T-cell responses to purified or lysed human rotavirus were stronger after a rise in rotavirus antibodies than the responses before infection (P = 0·017 and 0·027, respectively). There was a correlation between T-cell responses to purified and lysed human rotavirus and NCDV. Strong T-cell responses to rotavirus were transient and the ability to respond usually disappeared in one year, but in all adults T-cell responses to rotavirus were strong implicating that several infections are needed to develop consistent, strong T-cell responsiveness.
Differential regulation of mast cell cytokines by both dexamethasone and the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580
Authors: KORANTENG R D , SWINDLE E J , DAVIS B J , DEARMAN R J , KIMBER I , FLANAGAN B F , COLEMAN J W 
Published: June 2004

SUMMARYActivated mast cells generate multiple cytokines but it is not known if these can be differentially regulated by pharmacological agents. We report here that the glucocorticoid dexamethasone (DEX) preferentially inhibited Ag-induced expression of IL-4 and IL-6 mRNA relative to TNF-α mRNA in RBL-2H3 cells. Likewise, the drug more readily inhibited release of IL-4 than TNF-α protein. SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK), enhanced Ag-induced TNF-α mRNA expression without affecting IL-4 or IL-6 mRNA. At the protein level, SB203580 exerted little effect on TNF-α release but inhibited IL-4 release; notably, the ratio of TNF-α : IL-4 increased markedly with the concentration of SB203580, confirming the differential regulation of these cytokines. PD98059, an inhibitor of MAPK kinase (MEK), a component of the p44/42 MAPK pathway, partially inhibited Ag-induced expression of mRNA for all three cytokines while cyclosporin A inhibited Ag-induced IL-4 and IL-6 mRNA more readily than TNF-α mRNA. Ag activation of the cells led to phosphorylation of p38 and p44/42 MAPK but this was not influenced by DEX. In conclusion, mast cell cytokines can be differentially regulated pre- and post-translationally by DEX and SB203580 but there does not appear to be a direct mechanistic link between the actions of these two drugs.
Polyreactive antigen-binding B (PAB+) cells are widely distributed and the PAB+ population consists of both B-1+ and B-1– phenotypes
Authors: ZHOU Z-H , NOTKINS A L 
Published: June 2004

SUMMARYB cells that make polyreactive antibodies (PAB+ cells) express polyreactive Ig receptors on their surface and can bind a variety of different antigens. The present study shows that PAB+ cells are widely distributed, are present in varying numbers in different lymphoid organs and that their phenotype varies depending on the organs from which they are isolated. Up to 10 times more cells in PAB+ enriched populations bind antigens as compared to PAB– populations. Comparison of PAB+ with B-1+ cells showed that a high percentage of PAB+ cells are B-1+, but that many PAB+ cells do not express B-1 cell surface markers and, in fact, are B-1–. It is concluded that the B cell population consists of PAB+/B-1+, PAB+/B-1–, PAB–/B-1+, and PAB–/B-1– cells. The presence of PAB+ cells in the thymus points to the possibility that PAB+ cells may carry endogenous host antigens from peripheral tissues to the thymus where they may contribute to immunological tolerance.
Iron down-regulates macrophage anti-tumour activity by blocking nitric oxide production
Authors: HARHAJI L , VUCKOVIC O , MILJKOVIC D , STOSIC-GRUJICIC S , TRAJKOVIC V 
Published: June 2004

SUMMARYAlthough the inhibitory effect of iron on macrophage production of tumoricidal free radical nitric oxide (NO) has been reported, its possible influence on macrophage anti-tumour activity has not been established. In the present study, FeSO4 markedly reduced IFN-γ + LPS-induced NO synthesis in mouse and rat macrophages. The effect of iron coincided with the loss of macrophage cytotoxic activity against NO-sensitive C6 rat astrocytoma and L929 mouse fibrosarcoma cell lines, as measured by MTT assay for cellular respiration and the crystal violet test for cell viability. Tumour cell survival did not improve further in the presence of FeSO4 if macrophage NO release and cytotoxicity were already blocked by aminoguanidine. In accordance with the results obtained with exogenous iron, cell membrane permeable iron chelator o-phenanthroline enhanced both macrophage NO release and anti-tumour activity. Iron also down-regulated NO production and increased the viability of L929 fibrosarcoma cells stimulated with IFN-γ + LPS in the absence of macrophages. However, neither NO release nor cell viability was affected by iron addition to cultures of the C6 astrocytoma cell line. Iron was unable to prevent L929 and C6 cell death induced by the NO releasing chemicals SNP and SIN-1, indicating that iron-mediated inhibition of NO synthesis, rather than interference with its cytotoxic action, was responsible for the protection of tumour cells. Collectively, these results indicate that iron might protect tumour cells by reducing both macrophage and tumour cell-derived NO release.