bluuebunny/crossref_metadata_2025_split huggingface dataset:
Th1 and Th2 cytokine production is suppressed at the level of transcriptional regulation in Kawasaki disease
Authors: KIMURA J , TAKADA H , NOMURA A , OHNO T , MIZUNO Y , SAITO M , KUSUHARA K , HARA T 
Published: July 2004

SUMMARYTo clarify the functional state of T cells in Kawasaki disease, we analysed mRNA expression levels of Th1/Th2 cytokines (IFN-γ and IL-4) along with Th1/Th2-inducing transcription factors, T-bet and GATA-3, which play pivotal roles in the development of Th1 and Th2 cells, respectively. By real-time PCR, IFN-γ mRNA levels in peripheral blood mononuclear cells (PBMNC) were significantly decreased in Kawasaki disease patients compared with those with measles, and tended to be lower than those in healthy controls. T-bet mRNA levels were significantly decreased in patients with Kawasaki disease compared with healthy controls. In addition, IL-4 and GATA-3 mRNA levels were significantly decreased in Kawasaki disease compared with healthy controls. Regulatory cytokine mRNA levels (TGF-β and IL-10) were also decreased in Kawasaki disease. The mRNA levels of IFN-γ showed a significant positive correlation with those of T-bet in Kawasaki disease. These results suggest that the suppressed function of Th1 and Th2, associated with the suppression of both T-bet and GATA-3 gene expression, may be one of the immunological characteristics of Kawasaki disease.
Disruption of MAP kinase activation and nuclear factor binding to the IL-12 p40 promoter in HIV-infected myeloid cells
Authors: CHAMBERS K A , PARKS R J , ANGEL J B 
Published: July 2004

SUMMARYProgressive immunodeficiency in HIV infection is paralleled by a decrease in IL-12 production, a cytokine crucial for cellular immune function. Here we examine the molecular mechanisms by which HIV infection suppresses IL-12 p40 expression. HIV infection of THP-1 myeloid cells resulted in decreased LPS-induced nuclear factor binding to the NF-κB, AP-1, and Sp1 sites of the IL-12 p40 promoter. By site-directed mutagenesis we determined that each of these sites was necessary for transcriptional activation of the IL-12 p40 promoter. Binding of NF-κB p50, c-Rel, p65, Sp1, Sp3, c-Fos, and c-Jun proteins to their cognate nuclear factor binding sites was somewhat impaired by HV infection, although a role for other as yet unidentified factors cannot be dismissed. The cellular levels of these transcription factors were unaffected by HIV infection, with the exception of a decrease in expression of NF-κB p65, consistent with the observed decrease in its binding to the IL-12 p40 promoter following HIV infection. Analysis of regulation of upstream LPS-induced MAP kinases demonstrated impaired phosphorylation of JNK and p38 MAPK, and suppressed phosphorylation and degradation of IκBα following HIV infection. These results suggest that alterations in nuclear factor binding to numerous sites in the IL-12 p40 promoter, together may contribute to the suppression in IL-12 p40 transcription previously reported. These effects on nuclear factor binding may be a direct effect of HIV infection on the IL-12 p40 promoter, or may occur indirectly as a consequence of altered MAP kinase activation.
The ratio of n-6 to n-3 fatty acids in maternal diet influences the induction of neonatal immunological tolerance to ovalbumin
Authors: KOROTKOVA M , TELEMO E , YAMASHIRO Y , HANSON L Å , STRANDVIK B 
Published: July 2004

SUMMARYPrevalence of allergy is increasing in many countries and might be related to changed environmental factors, such as dietary fatty acids (FA). The present study investigates whether dietary ratio of n-6 to n-3 FA influences the induction of immunological tolerance to ovalbumin (OA) in neonatal rats. During late gestation and throughout lactation Sprague-Dawley rats were fed a diet containing 7% linseed oil (n-3 diet), sunflower oil (n-6 diet) or soybean oil (n-6/n-3 diet). At 10–16 days of age the rat offspring were subsequently exposed, or not, to OA via the milk. The offspring were weaned onto the same diets as the mothers and immunized with OA and the bystander antigen human serum albumin (HSA). In the offspring on the n-3 diet exposure to OA via the milk resulted in lower delayed type hypersensitivity reaction (DTH) and antibody responses against both OA and HSA, compared to those in the offspring not exposed to OA, indicating the induction of oral tolerance. In the offspring on the n-6 diet, the exposure to OA led to depressed specific immune responses against only OA, not HSA. In the offspring on the n-6/n-3 diet oral exposure to OA did not influence immune responses against OA, or HSA. The results indicate that the dietary ratio of n-6/n-3 FA is important for the induction of neonatal oral tolerance. Thus nonoptimal feeding may have effects on the development of immunological tolerance to dietary antigen ingested by the mother. The ratio of n-6/n-3 FA in the diet may be considered in the context of increased prevalence of allergy.
Rapid simultaneous measurement of multiple cytokines using 100 µl sample volumes − association with neonatal sepsis
Authors: HODGE G , HODGE S , HASLAM R , MCPHEE A , SEPULVEDA H , MORGAN E , NICHOLSON I , ZOLA H 
Published: July 2004

SUMMARY
Early diagnosis of neonatal infection has proved problematic due to the inadequacy of currently available laboratory tests. Neonatal sepsis is associated with an increase in plasma-derived cytokine levels, but an increase of a single cytokine cannot identify neonatal sepsis specifically and multiple cytokine levels are required. The time constraints and relatively large volume of plasma required to measure multiple cytokines from newborn infants by conventional enzyme-linked immunosorbent assay (ELISA) techniques is prohibitive. We therefore applied cytometric bead array (CBA) technology for simultaneous measurement of multiple cytokines from a group of 18 term neonates with infection confirmed by culture and a control group. ‘Normal’ ranges were established for each cytokine from 1–7-, 8–14- and 15–21-day-old newborns. There was no significant change in the levels of cytokines from infants in different control age groups, suggesting that basal cytokine levels are unchanged in the first 3 weeks of life. In the patient groups, however, there was a significant difference in several cytokines between the different age groups. Interleukin (IL)-6, IL-10 and IL-12 were increased significantly in the 1–7-day-old patient group compared to either the 8–14 and 15–21 age group, suggesting that infection in utero is associated with increased levels of these cytokines compared to infection acquired following birth. When individual patient cytokine levels were compared to normal control reference ranges, two patients failed to show significant elevation of any cytokine tested. All other patients showed elevated levels of between one and nine cytokines tested (mean of 4·6). There was no correlation between elevated cytokine levels and types of infective organism or patient age. In conclusion, neonatal sepsis is associated with the elevation of multiple plasma cytokines. The use of CBA kits is a rapid, easy, low sample volume and sensitive method to measure multiple plasma cytokines.
Effect of prolactin on carcinoembryonic antigen-specific cytotoxic T lymphocyte response induced by dendritic cells
Authors: MATERA L , BELTRAMO E , MARTINUZZI E , BUTTIGLIERI S 
Published: July 2004

SUMMARYThe cytokine hormone prolactin (PRL) has been shown previously to modulate native cellular responses and maturation of antigen-presenting cells. Here we have addressed its effect on the antigen-specific response of cytotoxic T lymphocytes (CTL). CTL were generated from HLA-A2 lymphocytes after three rounds of stimulation with autologous dendritic cells loaded with HLA-A2-restricted carcinoembrionic antigen (CEA) Cap-1 (YLSGANLNL) peptide. Selected cultures were expanded on cytokine-supplemented feeder-layers, enriched for CD8+ lymphocytes and analysed for PRL-receptor (PRL-R) expression and PRL responsiveness. Resting CD8+ lymphocytes were negative for PRL-R, whereas antigen-activated CD8+ lymphocytes derived from long-term cultures were highly positive. Results of a 51Cr release assay showed CTL killing of CEA-loaded, but not unloaded, T2 cell line and the CEA-positive gastric carcinoma cell line KATO, but not of the CEA-negative T leukaemia cell line Jurkat. Interferon (IFN)-γ release, evaluated in an ELISPOT assay against CEA-loaded T2, was enhanced (P &lt; 0·05) by concentrations of PRL (12–25 ng/ml) very close to the physiological levels (6–20 ng/ml), but was decreased (P &lt; 0·05) by high concentrations (200 ng/ml). Pre-incubation of the stimulators with the anti-MHC class I MoAb W6·32 induced a 40–60% decrease of the PRL-boosted IFN-γ release, thus proving the MHC restriction of the lymphocyte response. Cytotoxicity against CEA-loaded T2 and KATO cell lines was also increased by 12–25 ng (P &lt; 0·05) and decreased (P &lt; 0·05) by 200 ng PRL. Pre-incubation of CTL with an antibody specific for the PRL-R almost completely abrogated this effect.
Mycoplasma infection induces a scleroderma-like centrosome autoantibody response in mice
Authors: GAVANESCU I , PIHAN G , HALILOVIC E , SZOMOLANYI-TSUDA E , WELSH R M , DOXSEY S 
Published: July 2004

SUMMARYDevelopment of autoantibodies to intracellular molecules is a universal feature of autoimmune diseases and parallels onset of chronic inflammatory pathology. Initiating antigens of disease-specific autoantibody responses are unknown. We previously showed that the major targets of autoantibodies in scleroderma are centrosomes, organelles involved in mitotic spindle organization. Here we show that centrosome autoantibodies are induced in mice by mycoplasma infection. The centrosome-specific antibody response involves class switching of preexisting IgM to IgG isotypes, suggesting a T cell-dependent mechanism. The antibody response spreads to include additional intracellular targets, with newly recruited autoantibody specificities arising as IgM isotypes. Antibiotic treatment of mice prevents autoantibody development. Centrosome autoantibodies may provide an aetiological link between infection and human autoimmunity and suggest novel therapeutic strategies in these disorders.
The number of CD8+ T cells and NKT cells increases in the aqueous humor of patients with Behçet's uveitis
Authors: YU H G , LEE D S , SEO J M , AHN J K , YU Y S , LEE W J , CHUNG H 
Published: July 2004

SUMMARYTo determine whether there are differences in the immunopathogenesis of different endogenous uveitis syndromes, the phenotypic characteristics of immune cells were analysed among patients with endogenous uveitis. The aetiology of the uveitis included idiopathic recurrent acute anterior uveitis (18 patients), idiopathic intermediate uveitis (13 patients), Behçet's uveitis (17 patients), Vogt–Koyanagi–Harada syndrome (7 patients), and so on. Flow cytometric analysis was performed using immune cells of the aqueous humor and the peripheral blood during the active phase of intraocular inflammation, and monoclonal antibodies to CD3, CD4, CD8, CD14, CD19, CD56, TCR γδ, pan TCR αβ and Vα24. CD8+ T cells were predominant in the aqueous humor of the patients with Behçet's uveitis, whereas CD4+ T cells were mainly found in the aqueous humor of patients other than those with Behçet's uveitis. The number of NKT (CD3+CD56+) cells was significantly higher both in the aqueous humor and the peripheral blood of the patients with Behçet's uveitis compared with the other groups (P &lt; 0·05). CD8+CD56+ cells were the predominant subtype of the increased NKT cells in patients with Behçet's uveitis. In addition, intraocular infiltration of CD14+ cells significantly differed among the uveitis patients (P &lt; 0·05). These results suggest that the immunopathogenesis of endogenous uveitis can vary between syndromes, and that CD8+CD56+ NKT cells may play an important role in the immunopathogenesis of Behçet's uveitis.
Increase in Ksp37-positive peripheral blood lymphocytes in mild extrinsic asthma
Authors: KUEPPER M , KOESTER K , BRATKE K , MYRTEK D , OGAWA K , NAGATA K , VIRCHOW J C , LUTTMANN W 
Published: July 2004

SUMMARYKiller-specific secretory protein of 37 kDa (Ksp37), identified as a Th1/Tc1 specific secretory protein is expressed preferentially in cytotoxic T lymphocytes (CTL) and natural killer (NK) cells and might be involved in essential processes of CTL-mediated immunity. Although extrinsic asthma is linked currently to a Th2-dominated pathogenesis, there is increasing evidence for Th1/Tc1-mediated processes in the aetiopathology of asthma. CTL from patients with asthma have been shown to express cytokines and effector molecules which were different from healthy controls. We hypothesized that Ksp37 could indicate the involvement of CTL in the pathogenesis of extrinsic asthma. We therefore investigated Ksp37 expression in PBMC from patients with mild extrinsic asthma (n = 7) and healthy controls (n = 7). Flow cytometric analysis was used to quantify Ksp37+ cells and to investigate cellular Ksp37 expression as relative mean fluorescence intensities (MFI). We found a significantly (P = 0·016) higher percentage of Ksp37+ cells within the total lymphocyte population obtained from patients with mild extrinsic asthma compared with healthy controls. Subdifferentiation revealed a significant difference limited exclusively to the CD8+ subset (P = 0·010). In addition, Ksp37 secretion from cultured peripheral blood mononuclear cells (PBMC) and MFI of Ksp37+ lymphocytes were increased in patients with asthma compared with healthy controls. We conclude that mild extrinsic asthma appears to be associated with an increased expression of the Tc1 related protein Ksp37. The functional role of Ksp37 in the pathogenesis of asthma remains to be elucidated.
Anti-actin IgA antibodies in severe coeliac disease
Authors: GRANITO A , MURATORI P , CASSANI F , PAPPAS G , MURATORI L , AGOSTINELLI D , VERONESI L , BORTOLOTTI R , PETROLINI N , BIANCHI F B , VOLTA U 
Published: July 2004

SUMMARY
Anti-actin IgA antibodies have been found in sera of coeliacs. Our aim was to define the prevalence and clinical significance of anti-actin IgA in coeliacs before and after gluten withdrawal. One hundred and two biopsy-proven coeliacs, 95 disease controls and 50 blood donors were studied. Anti-actin IgA were evaluated by different methods: (a) antimicrofilament positivity on HEp-2 cells and on cultured fibroblasts by immunofluorescence; (b) anti-actin positivity by enzyme-linked immuosorbent assay (ELISA); and (c) presence of the tubular/glomerular pattern of anti-smooth muscle antibodies on rat kidney sections by immunofluorescence. Antimicrofilament IgA were present in 27% of coeliacs and in none of the controls. Antimicrofilament antibodies were found in 25 of 54 (46%) coeliacs with severe villous atrophy and in three of 48 (6%) with mild damage (P &lt; 0·0001). In the 20 patients tested, antimicrofilaments IgA disappeared after gluten withdrawal in accordance with histological recovery. Our study shows a significant correlation between antimicrofilament IgA and the severity of intestinal damage in untreated coeliacs. The disappearance of antimicrofilament IgA after gluten withdrawal predicts the normalization of intestinal mucosa and could be considered a useful tool in the follow-up of severe coeliac disease.
Impaired synthesis and action of antiaggregating cyclic nucleotides in platelets from obese subjects: possible role in platelet hyperactivation in obesity
Authors: Anfossi G. , Russo I. , Massucco P. , Mattiello L. , Doronzo G. , De Salve A. , Trovati M. 
Published: July 2004

AbstractBackground  Subjects with central obesity exhibit platelet hyperactivity, which is involved in the atherosclerotic process and therefore can account for the increased risk of cardiovascular morbidity and mortality. The aim of the study was to evaluate whether alterations of platelet function in obesity involve synthesis and/or action of the two antiaggregating cyclic nucleotides adenosine 3′,5′‐cyclic monophosphate (cAMP) and guanosine 3′,5′‐cyclic monophosphate (cGMP).Materials and methods  In platelets from 16 obese and 15 control subjects we investigated the influence on platelet responses to the Adenosine‐5‐diphosphate sodium salt (ADP) exerted by (i) prostacyclin analogue Iloprost (0·31–5 nmol L−1) and the cAMP analogue 8‐bromo‐cAMP (10–500 µmol L−1); and by (ii) nitric oxide (NO) donor sodium nitroprusside (SNP) (5–100 µmol L−1) and the cGMP analogue 8‐bromo‐cGMP (10–500 µmol L−1). IC50 (minimal concentration of each inhibitor necessary to reduce platelet response to ADP by half) was determined. Iloprost and SNP ability to increase cyclic nucleotides was also measured.Results  Significantly greater IC50 were observed in obese subjects than in healthy controls (1·59 ± 0·16 vs. 0·80 ± 0·08 nmol L−1, P = 0·0001 for Iloprost, and 27·6 ± 6·5 vs. 7·0 ± 1·7 µmol L−1, P = 0·006, for SNP); when data from control and obese subjects were pooled together, IC50 of Iloprost and SNP correlated with the homeostasis model assessment (HOMA IR), which is a parameter used to measure the insulin resistance (r = 0·588, P = 0·029 and r = 0·640, P = 0·006, respectively). Also the antiaggregating effect of 8‐Br‐cAMP and 8‐Br‐cGMP was smaller in the obese subjects. Finally, the ability of Iloprost to increase platelet cAMP and the ability of SNP to increase both cGMP and cAMP were reduced in obese subjects.Conclusions  Platelet resistance to the antiaggregating effects of prostacyclin and NO in obesity is attributable to impairment of cyclic nucleotide synthesis and action. As cyclic nucleotides are the main effectors of platelet antiaggregation, the resistance to them can account for platelet hyperactivity in obesity.
Cytokine gene polymorphisms and breast cancer susceptibility and prognosis*
Authors: Smith K. C. , Bateman A. C. , Fussell H. M. , Howell W. M. 
Published: July 2004

SummarySingle nucleotide polymorphisms (SNPs) in the promoter regions of cytokine genes are associated with differential levels of cytokine expression. We hypothesized that these SNPs might influence breast tumour development and progression by affecting the efficiency of the antitumour immune response and/or pathways of angiogenesis. A total of 144 female breast cancer patients and 263 cancer‐free population controls were genotyped for the interleukin (IL)‐1β−511 (T/C), IL‐6 −174 (G/C), tumour necrosis factor (TNF)‐α−308 (A/G), IL‐10 −1082 (A/G), IL‐8 −251 (A/T) and vascular endothelial growth factor (VEGF) −1154 (A/G) SNPs, using amplification refractory mutation system polymerase chain reaction (ARMS‐PCR) and TaqMan® (Applied Biosystems, Foster City, CA, USA) 5′ nuclease assays for allelic discrimination. No significant associations were seen. Patient–control comparisons revealed a non‐significant trend for association between the TNF‐α−308 GG genotype and breast cancer compared to controls (79.7 vs. 68.2%, P = 0.03, Pc = 0.54). Stratification of the patient group according to the Nottingham Prognostic Index and individual prognostic factors revealed trends for association between IL‐6 −174 GC and IL‐8 −251 AA genotypes and markers of poor prognosis (P = 0.04, Pc = 0.72 and P = 0.02, Pc = 0.36, respectively). There were also trends for associations between VEGF −1154 AG and IL‐1β−511 TC genotypes and markers of good prognosis (P = 0.02, Pc = 0.36 and P = 0.05, Pc = 0.90, respectively). These results suggest that the role of cytokine promoter SNPs in both susceptibility to and prognosis in breast cancer requires further investigation in a larger study.
High nucleotide and amino acid sequence similarities in tumour necrosis factor‐α amongst Indian buffalo (Bubalus bubalis), Indian cattle (Bos indicus) and other ruminants*
Authors: Gupta P. K. , Bind R. B. , Walunj S. S. , Saini M. 
Published: July 2004

SummaryTumour necrosis factor‐α (TNF‐α) mRNA from Indian water buffalo (Bubalus bubalis) and Indian cattle (Bos indicus) was reverse transcribed and amplified using reverse transcriptase–polymerase chain reaction (RT‐PCR). The nucleotide sequences of cDNAs were determined after cloning into pGEM‐T‐Easy vector (Promega, Madison, WI) and compared with reported nucleotide sequences of TNF‐α cDNA from other species. The nucleotide sequences of TNF‐α from Indian cattle revealed significantly high similarities at nucleotide (99.2%) and amino acid (100%) levels with those of cattle (Bos taurus; Zebu). The sequences from buffalo had 98.4% nucleotide and 99.1% amino acid similarities with Indian cattle, indicating functional cross‐reactivity. One amino acid deletion at position 63 and one substitution (A→P) at position 64 were observed in buffalo compared with Indian cattle. The amino acid deletion at position 63 was predicted due to differences in pre‐mRNA splicing.
Metapopulation structure of stream‐dwelling Dolly Varden charr inferred from patterns of occurrence in the Sorachi River basin, Hokkaido, Japan
Authors: Koizumi I. , Maekawa K. 
Published: July 2004

Summary1. We investigated the occurrence (presence or absence) of stream‐dwelling Dolly Varden (Salmonidae:Salvelinus malma) in the 78 tributaries of the Sorachi River system, Hokkaido, Japan to examine evidence for metapopulation structure.2. We hypothesised (i) that the occurrence of Dolly Varden would be less likely in small tributaries because of the higher extinction risk and (ii) that occurrence would be less likely in isolated tributaries because of reduced rates of dispersal and colonisation. In addition to these two general predictions, we hypothesised (iii) that the occurrence would be more likely in spring‐fed tributaries, because Dolly Varden prefer cold water as present in these systems.3. When all the tributaries were included in a multiple logistic regression analysis, habitat size and habitat type (spring‐fed versus non‐spring‐fed tributaries) were selected for the best model, whereas isolation was not important. However, when tributaries in the lower Sorachi basin (an area likely influenced by human activities) were excluded from the analysis, the effect of isolation became significant.4. Our results indicate there is a potential metapopulation structure of the Dolly Varden in the Sorachi River basin. Furthermore, it is possible that metapopulation dynamics follow a clinal pattern. In the upper and middle reaches of the Sorachi River basin, an equilibrium between extinction and colonisation of Dolly Varden populations is a possibility. In the lower portion of the basin, isolation appeared to be less important, and extinction rate may be driving patterns of occurrence toward systematic extinction of local populations.5. Our results illustrate the possibility of spatial variation in the processes influencing occurrence of Dolly Varden within a single river basin, and the potential influences of habitat alteration on extinction and colonisation processes.