bluuebunny/crossref_metadata_2025_split huggingface dataset:
A distance‐learning programme in pharmacovigilance linked to educational credits is associated with improved reporting of suspected adverse drug reactions via the UK yellow card scheme
Authors: Bracchi Robert C. G. , Houghton Jane , Woods Fiona J. , Thomas Simon , Smail Simon A. , Routledge Philip A. 
Published: July 2005

AimsThe effect of a distance‐learning package linked to educational credits on the rate and quality of spontaneous adverse drug reaction (ADR) reporting by general practitioners (GPs) and pharmacists in Wales was investigated.MethodsIn April 2000, 477 GPs and 261 pharmacists enrolled in the 12 month programme.ResultsThe number and quality of yellow card reports improved compared with those of a control region in England (Northern Region).ConclusionsWe conclude that an educational initiative in drug safety linked to incentives may be associated with a significant but perhaps short‐lived improvement in the rate and quality of ADR reporting.
Impact of human leucocyte antigen mismatch on graft‐versus‐host disease and graft failure after reduced intensity conditioning allogeneic haematopoietic stem cell transplantation from related donors
Authors: Teshima Takanori , Matsuo Keitaro , Matsue Kosei , Kawano Fumio , Taniguchi Shuichi , Hara Masamichi , Hatanaka Kazuo , Tanimoto Mitsune , Harada Mine , Nakao Shinji , Abe Yasunobu , Wake Atsushi , Eto Tetsuya , Takemoto Yoshinobu , Imamura Masahiro , Takahashi Satoshi , Ishida Yoji , Kanda Yoshinobu , Kasai Masaharu , Takaue Yoichi 
Published: July 2005

SummaryThe impact of human leucocyte antigen (HLA) incompatibility between donor and recipient on graft‐versus‐host disease (GVHD) and graft failure after reduced‐intensity conditioning stem cell transplantation (RICT) remains to be elucidated. We retrospectively analysed outcome in 341 patients who underwent RICT from related donors for haematological malignancies. The overall cumulative incidence of grade II–IV acute GVHD (aGVHD) was 40% for all subjects; 39% in recipients with HLA‐matched donors, 44% in those with one‐locus‐mismatched donors, and 50% in those with two‐ to three‐loci‐mismatched donors. In a Cox regression model adjusted for potential confounders, the tendency for grade II–IV aGVHD (P = 0·01), chronic GVHD (cGVHD) (P = 0·05) and graft failure (P = 0·033) increased with HLA disparity. Use of peripheral blood grafts instead of marrow was a risk factor for cGVHD. Use of antithymocyte globulin was associated with reduced aGVHD and cGVHD. Overall survival (OS) in recipients of two‐ to three‐loci‐mismatched RICT at 2 years (18%) was significantly worse than that in patients who received one‐locus‐mismatched RICT (51%) and HLA‐matched RICT (48%) (P < 0·0001). A two‐ to three‐loci mismatch was identified as an independent risk factor for OS (P < 0·001), but there was no significant difference in OS between HLA‐matched and one‐locus‐mismatched RICT. HLA incompatibility between the donor and recipient is an important risk factor for graft failure, aGVHD, cGVHD and OS after RICT. RICT from a one‐locus‐mismatched donor may represent an effective alternative approach in patients with high‐risk malignancies who lack HLA‐matched related donors.
Immunological profile of peripheral blood lymphocytes and monocytes/macrophages in Kawasaki disease
Authors: Matsubara T , Ichiyama T , Furukawa S 
Published: July 2005

SummaryKawasaki disease (KD) is an acute illness of early childhood characterized by prolonged fever, diffuse mucosal inflammation, indurative oedema of the hands and feet, a polymorphous skin rash and nonsuppurative lymphadenopathy. The histopathological findings in KD comprise panvasculitis with endothelial necrosis, and the infiltration of mononuclear cells into small and medium-sized blood vessels. The levels of many proinflammatory cytokines, chemokines and adhesion molecules can be elevated in sera from children with KD at the acute stage. Although many immunological studies on KD involving peripheral blood have been reported, the data obtained remain controversial. This review focuses on the immune response of peripheral blood lymphocytes and monocytes/macrophages during acute KD.
Insights into the role of fibroblasts in human autoimmune diseases
Authors: Smith T J 
Published: July 2005

SummaryTraditional wisdom has considered fibroblasts as contributing to the structural integrity of tissues rather than playing a dynamic role in physiological or pathological processes. It is only recently that they have been recognized as comprising diverse populations of cells exhibiting complex patterns of biosynthetic activity. They represent determinants that react to stimuli and help define tissue remodelling through the expression of molecules imposing constraints on their cellular neighbourhood. Moreover, fibroblasts can initiate the earliest molecular events leading to inflammatory responses. Thus they must now be viewed as active participants in tissue reactivity. In this short review, I will provide an overview of contemporary thought about the contribution of fibroblasts to the pathogenesis of autoimmune processes through their expression of, and responses to, mediators of inflammation and tissue remodelling.
CXCL12 and CXCR4 expression by human gingival fibroblasts in periodontal disease
Authors: Hosokawa Y , Hosokawa I , Ozaki K , Nakae H , Murakami K , Miyake Y , Matsuo T 
Published: July 2005

Summary
CXCL12 is a CXC chemokine that is related to lymphocyte infiltration and angiogenesis in inflammatory sites such as arthritis. However, the expression and roles of CXCL12 in periodontal disease are uncertain. The aim of this study was to assess the expression of CXCL12 and its receptor, CXCR4, in periodontal tissue and to investigate the properties of CXCL12 and CXCR4 expression by human gingival fibroblasts (HGF). RT-PCR analysis revealed that CXCL12 and CXCR4 mRNA were expressed in both normal gingival tissues and periodontal diseased tissues. Immunohistochemistry disclosed that CXCL12 was expressed and CXCR4 positive cells were found in both normal and periodontal diseased gingival tissues. Our in vitro experiments elucidated that HGF constitutively produced CXCL12, and the levels were enhanced by stimulation with tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), transforming growth factor-β (TGF–β), regulated upon activation normal T cell expressed and secreted (RANTES) and macrophage inflammatory protein 3α (MIP-3α). On the other hand, heat killed Porphyromonas gingivalis (P. gingivalis) and P. gingivalis LPS reduced the CXCL12 production by HGF. Flow cytometry analysis clarified that CXCR4 was highly expressed on HGF, and CXCR4 expression was abrogated by TNF-α, IFN-γ and P. gingivalis LPS. Moreover, CXCL12 induced vascular endothelial growth factor (VEGF) production by HGF. Our results demonstrated that CXCL12 might be related to CXCR4+ cells infiltration and angiogenesis both in normal periodontal tissues and periodontal diseased tissue. P. gingivalis, a known periodontal pathogen, inhibits the production of CXCL12 and the expression of CXCR4 by HGF. This fact means that P. gingivalis may inhibit CXCR4+ cells infiltration and neovascularization in periodontal tissue and escape from the immune response.
Toxoplasma gondiiregulates recruitment and migration of human dendritic cells via different soluble secreted factors
Authors: Diana J , Vincent C , Peyron F , Picot S , Schmitt D , Persat F 
Published: July 2005

SummaryWe investigated in vitro the properties of soluble factors produced by Toxoplasma gondii on the recruitment, maturation and migration of human dendritic cells (DC) derived from CD34+ progenitor cells. We used soluble factors including excreted secreted antigens (ESA) produced under various conditions by the virulent type I RH strain (ESA-RH) and the less virulent PRU type II strain (ESA-PRU). Soluble factors of both T. gondii strains appeared to possess a chemokine-like activity that attracted immature DC. This recruitment activity required the presence of functional CCR5 molecules on the cell membrane. Incubation of DC for 24 h with ESA triggered the migration of a large percentage of these cells towards the chemokine MIP-3β; ESA-PRU was more efficient than ESA-RH. ESA produced in absence of exogenous protein and crude extract did not induce DC migration but retained recruitment activity. These data indicate that recruitment activity and migration-inducing activity are not governed by the same factors. Moreover, incubation of DC for 48 h with ESA did not modify the expression of costimulation or maturation markers (CD83, CD40, CD80, CD86 or HLA-DR), but induced a decrease in CCR6 expression associated with an increased expression of CCR7. Taken together, these results suggest that T. gondii controls recruitment and migration of immature DC by different soluble factors and may induce a dysfunction in the host-specific immune response.
CDC staging based on absolute CD4 count and CD4 percentage in an HIV-1-infected Indian population: treatment implications
Authors: Vajpayee M , Kaushik S , Sreenivas V , Wig N , Seth P 
Published: July 2005

Summary
CD4+ T-cell levels are an important criterion for categorizing HIV-related clinical conditions according to the CDC classification system and are therefore important in the management of HIV by initiating antiretroviral therapy and prophylaxis for opportunistic infections due to HIV among HIV-infected individuals. However, it has been observed that the CD4 counts are affected by the geographical location, race, ethnic origin, age, gender and changes in total and differential leucocyte counts. In the light of this knowledge, we classified 600 HIV seropositive antiretroviral treatment (ART)-naïve Indian individuals belonging to different CDC groups A, B and C on the basis of CDC criteria of both CD4% and CD4 counts and receiver operating characteristic (ROC) curves were generated. Importantly, CDC staging on the basis of CD4% indicated significant clinical implications, requiring an early implementation of effective antiretroviral treatment regimen in HIV-infected individuals deprived of treatment when classified on the basis of CD4 counts.
HUVECs from newborns with a strong family history of myocardial infarction overexpress adhesion molecules and react abnormally to stimulating agents
Authors: Paez A , Méndez-Cruz A R , Varela E , Rodriguez E , Guevara J , Flores-Romo L , Montaño L F , Massó F A 
Published: July 2005

SummaryAtherosclerosis is a complex disease involved in major fatal events such as myocardial infarction and stroke. It is the result of interactions between metabolic, dietetic and environmental risk factors acting on a genetic background that could result in endothelial susceptibility. Our aim was to determine the patterns of expression of adhesion molecules and whether phosphatidylserine is translocated to the cell surface of human umbilical vein endothelial cells (HUVECs) isolated from healthy newborns born to parents with a strong family history of myocardial infarction under TNF-α or oxLDL stimulated conditions. Compared to control HUVECs, experimental cords showed: (a) a four-fold increase in VCAM-1 expression under basal conditions, which showed no change after stimulation with the pro-atherogenic factors; (b) a two-fold increase in basal P-selectin expression that reached a 10-fold increase with any of the pro-atherogenic factors; (c) a basal ICAM-1 expression similar to P-selectin that was not modified by the pro-atherogenic molecules; (d) a similar PECAM-1 expression. Unexpectedly, phospathidylserine expression in experimental cord HUVECs was significantly increased (211 817 versus 3354 TFU) but was not associated to apoptotic death as the percentage of dead cells induced by TNF-α treatment was very low (0·55 versus 9·87% in control HUVECs). The latter result was corroborated by TUNEL staining. T cell adherence to HUVECs was highly up-regulated in the genetically predisposed samples. The analysis of nonpooled HUVECs, from newborns to family predisposed myocardial-infarction individuals, might represent a useful strategy to identify phenotypical and functional alterations, and hopefully, to take early preventive actions.
Circulating anti-actin and anti-ATP synthase antibodies identify a sub-set of patients with idiopathic nephrotic syndrome
Authors: Musante L , Candiano G , Bruschi M , Santucci L , Carnemolla B , Orecchia P , Giampuzzi M , Zennaro C , Sanna-Cherchi S , Carraro M , Oleggini R , Camussi G , Perfumo F , Ghiggeri G M 
Published: July 2005

Summary
Idiopathic nephrotic syndrome (iNS) with resistance or dependence to steroids is a common disease in children but in spite of an increasing clinical impact its pathogenesis is unknown. We screened for the presence of circulating antibodies against glomerular (podocytes, mesangium) and tubular cells (tubular epithelia) a cohort of 60 children with iNS including 8 patients with a familial trait of iNS or with proven mutation of NPHS1-NPHS2 and 12 with good sensitivity to steroids. Positive sera were found in 8 cases, all belonging to the category without familial trait/molecular defects. The targets of antibodies were characterized with Western blot and MALDI-Mass utilizing β-hexyl cell extracts separated with two-dimensional electrophoresis. In all cases antibodies of the IgM class were directed against ATP synthase β chain alone (4 cases) or in combination with actin (3 cases); one child presented IgG against aldose reductase. The clinical picture was nephrotic syndrome with steroid resistance or dependence and variable cyclosporin sensitivity; 3 patients developed end stage renal failure. The basic pathology picture was focal segmental glomerulosclerosis (FSGS) in 4 cases and mesangial proliferative glomerulonephrites with deposition of IgM in 2. Overall, patients with circulating auto-antibodies could not be readely differentiated on clinical grounds with the exception of 3 children who developed positivity for antinuclear antibodies during the follow-up. Affinity-purified IgM from one patient who underwent plasmapheresis for therapeutical pourposes (but not from a normal pool) induced proteinuria in Sprague-Dawley rats and concomitant human IgM deposition within glomeruli. This is the first report of circulating anti-actin/ATP synthase β chain antibodies in a subset of patients with iNS. Both pathological significance and clinical impact given by the presence of these antibodies and the relationship with other conditions such as lupus-erythematosus, characterized by their presence, must be defined.
Ex vivostimulation of cord blood mononuclear cells by dexamethasone and interleukin-7 results in the maturation of interferon-γ-secreting effector memory T cells
Authors: Talayev V Yu , Zaichenko I Ye , Babaykina O N , Lomunova M A , Talayeva E B , Nikonova M F 
Published: July 2005

SummaryThe effects of dexamethasone phosphate and interleukin-7 upon the proliferation of T-cells and the production of interferon-γ in the newborn's cord blood mononuclear cell cultures were studied. The capability of dexamethasone to enhance T-cell proliferation induced by anti-CD3 with interleukin-7 in some newborn cord blood mononuclear cell cultures was identified. Dexamethasone suppressed production of interferon-γ in 68-h cell cultures stimulated with anti-CD3 both in the presence of interleukin-7 and without it. However, a 68-h cultivation of newborn blood cells with dexamethasone, anti-CD3 and interleukin-7 resulted in the accumulation of T-lymphocytes capable of producing interferon-γ after restimulation. As a result of it the amount of interferon-γ producing CD7+ T-cells and the concentration of interferon-γ in cultural supernatants were maximal in the cell cultures incubated with anti-CD3, interleukin-7 and dexamethasone during the first 68 h and subsequently restimulated with phorbol 12-myristate 13-acetate and ionomycin. The stimulation of neonatal or adult blood cells by dexamethasone, anti-CD3 and interleukine-7 also causes a decrease in the number of naïve T-cells and central memory cells and an increase in the number of effector memory CD7+CD45RA+CD62L– cells in cultures. It is possible that these effects are caused by the influence of dexamethasone on IL-7 receptor expression: it is known that IL-7 receptor alpha-chain gene is a glucocorticoid-inducible gene.
Antibody to severe acute respiratory syndrome (SARS)-associated coronavirus spike protein domain 2 cross-reacts with lung epithelial cells and causes cytotoxicity
Authors: Lin Y S , Lin C F , Fang Y T , Kuo Y M , Liao P C , Yeh T M , Hwa K Y , Shieh C C K , Yen J H , Wang H J , Su I J , Lei H Y 
Published: July 2005

SummaryBoth viral effect and immune-mediated mechanism are involved in the pathogenesis of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infection. In this study, we showed that in SARS patient sera there were autoantibodies (autoAbs) that reacted with A549 cells, the type-2 pneumocytes, and that these autoAbs were mainly IgG. The autoAbs were detectable 20 days after fever onset. Tests of non-SARS-pneumonia patients did not show the same autoAb production as in SARS patients. After sera IgG bound to A549 cells, cytotoxicity was induced. Cell cytotoxicity and the anti-epithelial cell IgG level were positively correlated. Preabsorption and binding assays indicated the existence of cross-reactive epitopes on SARS-CoV spike protein domain 2 (S2). Furthermore, treatment of A549 cells with anti-S2 Abs and IFN-γ resulted in an increase in the adherence of human peripheral blood mononuclear cells to these epithelial cells. Taken together, we have demonstrated that the anti-S2 Abs in SARS patient sera cause cytotoxic injury as well as enhance immune cell adhesion to epithelial cells. The onset of autoimmune responses in SARS-CoV infection may be implicated in SARS pathogenesis.
An increased MRP8/14 expression and adhesion, but a decreased migration towards proinflammatory chemokines of type 1 diabetes monocytes
Authors: Bouma G , Coppens J M C , Lam-Tse W-K , Luini W , Sintnicolaas K , Levering W H , Sozzani S , Drexhage H A , Versnel M A 
Published: July 2005

SummaryIn the early development of type 1 diabetes macrophages and dendritic cells accumulate around the islets of Langerhans at sites of fibronectin expression. It is thought that these macrophages and dendritic cells are derived from blood monocytes. Previously, we showed an increased serum level of MRP8/14 in type 1 diabetes patients that induced healthy monocytes to adhere more strongly to fibronectin (FN). Here we show that MRP8/14 is expressed and produced at a higher level by type 1 diabetes monocytes, particularly after adhesion to FN, creating a positive feedback mechanism for a high fibronectin-adhesive capacity. Also adhesion to endothelial cells was increased in type 1 diabetes monocytes. Despite this increased adhesion the transendothelial migration of monocytes of type 1 diabetes patients was decreased towards the proinflammatory chemokines CCL2 and CCL3. Because non-obese diabetic (NOD) mouse monocytes show a similar defective proinflammatory migration, we argue that an impaired monocyte migration towards proinflammatory chemokines might be a hallmark of autoimmune diabetes. This hampered monocyte response to proinflammatory chemokines questions whether the early macrophage and dendritic cell accumulation in the diabetic pancreas originates from an inflammatory-driven influx of monocytes. We also show that the migration of type 1 diabetes monocytes towards the lymphoid tissue-related CCL19 was increased and correlated with an increased CCR7 surface expression on the monocytes. Because NOD mice show a high expression of these lymphoid tissue-related chemokines in the early pancreas it is more likely that the early macrophage and dendritic cell accumulation in the diabetic pancreas is related to an aberrant high expression of lymphoid tissue-related chemokines in the pancreas.
Sam68 is tyrosine phosphorylated and recruited to signalling in peripheral blood mononuclear cells from HIV infected patients
Authors: Najib S , Rodríguez-Baño J , Ríos M J , Muniain M A , Goberna R , Sánchez-Margalet V 
Published: July 2005

SummaryHuman immunodeficiency virus (HIV) codes for a protein, Rev, that mediates the viral RNA export from the nucleus to the cytoplasm. Recently, it has been found that Sam68, the substrate of Src associated in mitosis, is a functional homologue of Rev, and a synergistic activator of Rev activity. Thus, it has been suggested that Sam68 may play an important role in the post-transcriptional regulation of HIV. Sam68 contains an RNA binding motif named KH [homology to the nuclear ribonucleoprotein (hnRNP) K]. Tyrosine phosphorylation of Sam68 and binding to SH3 domains have been found to negatively regulate its RNA binding capacity. Besides, tyrosine phosphorylation of Sam68 allows the formation of signalling complexes with other proteins containing SH2 and SH3 domains, suggesting a role in signal transduction of different systems in human lymphocytes, such as the T cell receptor, and leptin receptor, or the insulin receptor in other cell types. In the present work, we have found that Sam68 is tyrosine phosphorylated in peripheral blood mononuclear cells (PBMC) from HIV infected subjects, leading to the formation of signalling complexes with p85 the regulatory subunit of PI3K, GAP and STAT-3, and decreasing its RNA binding capacity. In contrast, PBMC from HIV infected subjects have lower expression levels of Sam68 compared with controls. These results suggest that Sam68 may play some role in the immune function of lymphocytes in HIV infection.
Histological analysis of CD11c-DTR/GFP mice after in vivo depletion of dendritic cells
Authors: Probst H C , Tschannen K , Odermatt B , Schwendener R , Zinkernagel R M , Van Den Broek M 
Published: July 2005

Summary
To investigate the dependence of individual immunological processes on DC, a transgenic mouse system (CD11c-DTR/GFP mice) has been developed that allows conditional depletion of CD11c+ DC in vivo through administration of diphtheria toxin. We have performed careful histological analysis of CD11c-DTR/GFP mice at different time points after diphtheria toxin injection and confirmed the transient depletion of CD11c+ cells from lymph nodes and spleen. Unexpectedly, the injection of diphtheria toxin completely depleted marginal zone and metallophilic MΦ from the spleen and their sinusoidal counterparts from the lymph nodes. This finding limits the use of CD11c-DTR/GFP mice for the analysis of the role of DC to models and read outs that are proven to be independent of marginal zone and sinusoidal MΦ.