bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alloimmunization to red blood cell antigens after universal leucodepletion. A regional multicentre retrospective study
Authors: Schonewille Henk , Brand Anneke 
Published: March 2005

SummaryLeucodepletion has been shown to reduce human leucocyte antigen immunization, but studies on the effect of leucodepletion on red cell alloimmunization reported discordant results. We conducted a retrospective multicentre study to determine whether prestorage filter leucodepletion alters the development of clinically significant red blood cell alloimmunization against the Rhesus, Kell, Duffy, Kidd and MSs blood group systems. Two periods were investigated, 2 years before and 2 years after universal leucodepletion. Comparisons were made between the transfused patient cohorts. To control for changes not related to leucoreduction, we compared antibody incidence with antibody prevalence in the two study periods. Newly detected antibodies (n = 4770) were found in 4115 patients from 19 participating hospitals. Of these, 857 antibodies in 659 patients were because of transfusions given in the study periods. The immunization risk was 0·13% for both periods. No differences were found regarding incidence of new antibodies, nor for patients regarding age, sex, previous antibodies, multiple antibodies, additional antibodies, number of transfusions, transfusions episodes and days from transfusion to date of immunization. In conclusion, compared with buffy‐coat leucoreduction, universal prestorage filter leucodepletion did not alter the development of clinically significant red blood cell alloimmunization.
Immunomodulatory effect of human adipose tissue‐derived adult stem cells: comparison with bone marrow mesenchymal stem cells
Authors: Puissant Bénédicte , Barreau Corinne , Bourin Philippe , Clavel Cyril , Corre Jill , Bousquet Christine , Taureau Christine , Cousin Béatrice , Abbal Michel , Laharrague Patrick , Penicaud Luc , Casteilla Louis , Blancher Antoine 
Published: March 2005

SummaryLike mesenchymal stem cells from bone marrow (BM‐MSCs), adipose tissue‐derived adult stem cells (ADAS cells) can differentiate into several lineages and present therapeutical potential for repairing damaged tissues. The use of allogenic stem cells can enlarge their therapeutical interest, provided that the grafted cells could be tolerated. We investigate here, for the first time, the immunosuppressive properties of ADAS cells compared with the well‐characterized immunosuppressive properties of BM‐MSCs. ADAS cells did not provoke in vitro alloreactivity of incompatible lymphocytes and, moreover, suppressed mixed lymphocyte reaction (MLR) and lymphocyte proliferative response to mitogens. The impairment of inhibition when ADAS cells and BM‐MSCs were separated from lymphocytes by a permeable membrane suggests that cell contact is required for a full inhibitory effect. Hepatocyte growth factor is secreted by both stem cells but, similar to interleukin‐10 and transforming growth factor‐β (TGF‐β), the levels of which were undetectable in supernatants of MLR inhibited by ADAS cells or BM‐MSCs, it did not seem implicated in the stem cell suppressive effect. These findings support that ADAS cells share immunosuppressive properties with BM‐MSCs. Therefore, ADAS cell‐based reconstructive therapy could employ allogenic cells and because of their immunosuppressive properties, ADAS cells could be an alternative source to BM‐MSCs to treat allogenic conflicts.
Aberrant methylation of the negative regulators RASSFIA, SHP‐1 and SOCS‐1 in myelodysplastic syndromes and acute myeloid leukaemia
Authors: Johan M. F. , Bowen D. T. , Frew M. E. , Goodeve A. C. , Reilly J. T. 
Published: March 2005

SummaryMutations in the receptor tyrosine kinase (RTK/RAS) signalling pathway frequently provide a proliferative signal in myeloid malignancies. However, the role of RASSF1A, SHP‐1 and SOCS‐1, negative regulators of RTK/RAS signalling, has not been extensively investigated in the myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML). This study employed methylation‐specific polymerase chain reaction (MS‐PCR) to determine if aberrant promotor methylation of RASSF1A, SHP‐1 and SOCS‐1 is involved in the pathogenesis of myeloid malignancies. Patients with MDS (n = 107), AML (n = 154) and juvenile myelomonocytic leukaemia (JMML, n = 5) were investigated, together with 15 normal controls. Primers were located in the promotor region of each gene as well as within exon 2 of SOCS‐1. Methylation of RASSF1A was found in five of 55 (9%) MDS cases, but not in any of 57 AML cases studied. RASSF1A methylation was present in one case (20%) of JMML. SHP‐1 methylation was present in 13 of 121 (11%) AML cases but was not found in MDS or JMML. SOCS‐1 promoter methylation was present in eight of 74 (11%) MDS patients but was not seen in JMML or AML. Importantly, RAS mutations and RASSF1A and SOCS‐1 methylation were mutually exclusive indicating that approximately 30% of MDS cases had a defect of the RTK/RAS pathway and its negative regulation. Finally, SOCS‐1 exon 2 methylation may not be pathogenetically relevant, since it was detected in samples from normal individuals and did not correlate with promotor methylation.
Interphase FISH to detect PBX1/E2A fusion resulting from the der(19)t(1;19)(q23;p13.3) or t(1;19)(q23;p13.3) in paediatric patients with acute lymphoblastic leukaemia
Authors: Shearer Brandon M. , Flynn Heather C. , Knudson Ryan A. , Ketterling Rhett P. 
Published: March 2005

SummaryApproximately 6% of paediatric patients with precursor B‐cell acute lymphoblastic leukaemia (B‐ALL) harbour a rearrangement involving the gene regions of PBX1 (1q23) and E2A (19p13.3) which is visualized cytogenetically either as a der(19)t(1;19)(q23;p13.3) or the less common balanced t(1;19)(q23;p13.3). Unfortunately, no commercial dual‐colour, double fusion fluorescence in situ hybridization (D‐FISH) strategies are available to detect this recurrent anomaly. Therefore, we have created a D‐FISH assay to detect these translocations and monitor minimal residual disease. This probe set was created using four bacterial artificial chromosomes (BACs) corresponding to the PBX1 gene region at 1q23 and four BACs corresponding to the E2A gene region at 19p13.3. We analysed 30 negative bone marrow controls and 20 diagnostic and post‐treatment specimens from 13 paediatric B‐ALL patients with a cytogenetically defined 1;19 translocation. Once unblinded, the results demonstrated that our D‐FISH method effectively identified all diagnostic samples as abnormal and identified disease in four post‐treatment samples that were previously considered to be normal by conventional cytogenetic analysis. The development of this FISH strategy for the detection of der(19)t(1;19)(q23;p13.3) and t(1;19)(q23;p13.3) proved to be an effective technique, allowing both the detection of disease in diagnostic samples and in post‐treatment samples.
Risks factors for highly unstable response to oral anticoagulation: a case‐control study
Authors: Palareti Gualtiero , Legnani Cristina , Guazzaloca Giuliana , Lelia Valdré , Cosmi Benilde , Lunghi Barbara , Marchetti Giovanna , Poli Daniela , Pengo Vittorio ,   the ad hoc study group of the Italian Federation of Anticoagulation Clinics
Published: March 2005

SummaryThe factors associated with persistent instability of oral anticoagulant treatment (OAT) were investigated in a case‐control study. The most unstable patients from 35 Italian anticoagulation clinics were matched with stable controls, for gender, age and OAT indication. Socio‐demographic data, medical history, dietary and life habits, cytochrome P450 CYP2C9 variants, blood cell count, liver and renal functions were investigated. An ‘Abbreviated Mental Test’ (AMT) and a questionnaire to assess patient compliance to, and comprehension of, OAT indications and mechanisms were administered. An International Normalized Ratio (INR) above 4·5 was more frequently found in cases (n = 77) than controls (n = 80) (12·3% vs. 0·4%; P < 0·0001). The odds ratio for instability was significantly higher for: people who worked versus pensioners, acenocoumarol versus warfarin, and an insufficient score in the AMT and/or in the questionnaire. Cytochrome P450 CYP2C9 variants *1/*3 or *2/*3 or *3/*3 were more frequent among cases than controls (29·9% vs.15·0%; P = 0·042). No differences were observed as regards the other variables. In conclusion, we found that high intra‐individual variability in OAT control was multifactorial, but poor OAT comprehension was prevalent.
Does cryosupernatant plasma improve outcome in thrombotic thrombocytopenic purpura? No answer yet
Authors: Rock Gail , Anderson David , Clark William , Leblond Pierre , Palmer Douglas , Sternbach Marion , Sutton David , Wells George ,   members of the Canadian Apheresis Group and members of the Canadian Association of Apheresis Nurses
Published: March 2005

SummaryA randomized prospective trial compared cryosupernatant plasma (CSP) to fresh frozen plasma (FFP) for treatment of thrombotic thrombocytopenic purpura (TTP). A total of 236 patients were required: 28 patients were treated with CSP and 24 with FFP within 30 months. There were no differences in survival at 1 month. By day 9, 17 of 26 patients with CSP and 18 of 24 with FFP had a platelet count >100 × 109/l. At entry, von Willebrand factor (VWF) multimers were normal in all patients (range 1·1–3·95 IU/ml). ADAMTS‐13 levels showed large variations ranging from 10% to 100% activity. At entry, no individual had <5% VWF cleaving protease. By day 9 (end of cycle), 89% (FFP) and 67% (CSP) had levels >50% of the controls. At 6 months some patients showed inhibitors to the enzyme in spite of adequate or normal platelet counts. The data from this study do not show an apparent advantage to the use of CSP in TTP. A large number of patients will be required to determine appropriate replacement therapy. We were not able to find a statistically significant relationship between the low level of protease activity at presentation of TTP and response.
FRETS‐VWF73, a first fluorogenic substrate for ADAMTS13 assay
Authors: Kokame Koichi , Nobe Yuko , Kokubo Yoshihiro , Okayama Akira , Miyata Toshiyuki 
Published: March 2005

SummaryA plasma metalloprotease, ADAMTS13, cleaves von Willebrand factor (VWF) multimers and downregulates their activity in platelet aggregation. Functional ADAMTS13 deficiency leads to the accumulation of hyperactive large VWF multimers, inducing a life‐threatening disease, thrombotic thrombocytopenic purpura (TTP). Although measuring ADAMTS13 activity is important in TTP diagnosis, existing methods require time and skill. Here, we report a fluorescence resonance energy transfer (FRET) assay for ADAMTS13 activity. We developed a synthetic 73‐amino‐acid peptide, FRETS‐VWF73. Cleavage of this substrate between two modified residues relieves the fluorescence quenching in the intact peptide. Incubation of FRETS‐VWF73 with normal human plasma quantitatively increased fluorescence over time, while ADAMTS13‐deficient plasma had no effect. Quantitative analysis could be achieved within a 1‐h period using a 96‐well format in commercial plate readers with common filters. The FRETS‐VWF73 assay will be useful for the characterization of thrombotic microangiopathies like TTP and may clarify the importance of ADAMTS13 activity as a predictive marker for various thrombotic diseases.
Early response to induction is predictive of survival in childhood Philadelphia chromosome positive acute lymphoblastic leukaemia: results of the Medical Research Council ALL 97 trial
Authors: Roy Anindita , Bradburn Mike , Moorman Anthony V. , Burrett Julie , Love Sharon , Kinsey Sally E. , Mitchell Chris , Vora Ajay , Eden Tim , Lilleyman John S. , Hann Ian , Saha Vaskar ,   Medical Research Council Childhood Leukaemia Working Party
Published: March 2005

SummaryWe report on the outcome of children with Philadelphia positive acute lymphoblastic leukaemia (Ph+ ALL) treated on the UK Medical Research Council (MRC) trial for childhood ALL, MRC ALL 97, between January 1997 and June 2002. Forty‐two (2·3%) patients were Ph+. Nineteen (45%) had <25% blasts in bone marrow (BM) within the first 2 weeks of treatment and were defined as a good response group (GRG), the others as a poor response group (PRG). Thirty‐six (86%) achieved first complete remission (CR1) at the end of induction, of which 28 underwent BM transplantation (BMT). The median follow‐up was 42 months (range, 21–84). The 3‐year event‐free survival (EFS; 52%, 95% CI, 36–66%) was a considerable improvement on the previous MRC UKALL XI trial (27%). EFS for the GRG and PRG were 68% (43–84%) and 39% (18–59%), respectively (P = 0·03); presenting white cell count <50 × 109/l (P = 0·02) was predictive for overall survival. Changes in the MRC ALL97 trial within the study period resulted in some Ph+ ALL receiving daunorubicin and either prednisolone or dexamethasone during induction. Though the use of daunorubicin during induction was not a prospective study question, EFS was significantly better for those whose induction included this drug (P = 0·02). Steroid randomization was not stratified for Ph+ ALL patients and was not predictive for EFS. BMT in CR1 appeared to reduce the risk of a subsequent BM relapse. These results show significant improvement on previous MRC trials; future therapeutic strategies should include early intensive therapy and BMT in CR1.
Therapeutic administration of Budesonide ameliorates allergen‐induced airway remodelling
Authors: McMillan S. J. , Xanthou G. , Lloyd C. M. 
Published: March 2005

SummaryBackground
Airway inflammation and remodelling are important pathophysiologic features of chronic asthma. Although current steroid use demonstrates anti‐inflammatory activity, there are limited effects on the structural changes in the lung tissue.Objective
We have used a mouse model of prolonged allergen challenge that exhibits many of the salient features of airway remodelling in order to investigate the anti‐remodelling effects of Budesonide.Methods
Treatment was administered therapeutically, with dosing starting after the onset of established eosinophilic airway inflammation and hyper‐reactivity.Results
Budesonide administration reduced airway hyper‐reactivity and leukocyte infiltration in association with a decrease in production of the Th2 mediators, IL‐4, IL‐13 and eotaxin‐1. A reduction in peribronchiolar collagen deposition and mucus production was observed. Moreover, our data show for the first time that, Budesonide treatment regulated active transforming growth factor (TGF)‐β signalling with a reduction in the expression of pSmad 2 and the concomitant up‐regulation of Smad 7 in lung tissue sections.Conclusions
Therefore, we have determined that administration of Budesonide modulates the progression of airway remodelling following prolonged allergen challenge via regulation of inflammation and active TGF‐β signalling.
1,3‐β‐glucanases as candidates in latex–pollen–vegetable food cross‐reactivity
Authors: Palomares O. , Villalba M. , Quiralte J. , Polo F. , Rodríguez R. 
Published: March 2005

SummaryBackground
1,3‐β‐glucanases (group 2 of pathogenesis‐related proteins) are enzymes widely distributed among higher plants and have been recently proven to be significant allergens.Objective
The aim of this work was to study the potential implication of 1,3‐β‐glucanases in cross‐reactivities among latex, pollen and vegetable foods.Methods
The cDNA encoding the N‐terminal domain (NtD) of Ole e 9, a major allergenic 1,3‐β‐glucanase from olive pollen, was amplified by polymerase chain reaction and produced as a recombinant protein in Pichia pastoris (recombinant N‐terminal domain, rNtD). Circular dichroism, ELISA, immunoblotting and immunoblotting inhibition experiments were carried out. Sera from olive pollen allergic patients and a rNtD‐specific polyclonal antiserum were used.Results
The NtD of Ole e 9 has been produced at high yield in the yeast P. pastoris and possesses 1,3‐β‐glucanase activity. The expressed polypeptide conserves IgE and IgG immunodominant epitopes of the whole Ole e 9. A rNtD‐specific polyclonal antiserum and sera from olive pollen allergic patients allowed detection of IgG and IgE reactive peptidic epitopes common to 1,3‐β‐glucanase Ole e 9 in extracts from ash and birch pollen, tomato, potato, bell‐pepper, banana and latex.Conclusion
rNtD and homologous glucanases are new molecules to be used in diagnostic protocols as they could help to identify allergic pollen patients who are at risk for developing allergic symptoms to fruits, vegetables and latex.
The predictive value of specific immunoglobulin E levels in serum for the outcome of oral food challenges
Authors: Celik‐Bilgili S. , Mehl A. , Verstege A. , Staden U. , Nocon M. , Beyer K. , Niggemann B. 
Published: March 2005

SummaryBackground
Specific serum IgE is considered as one of the important diagnostic measures in the diagnostic work‐up of food allergy.Objective
To evaluate the role of specific serum IgE in predicting the outcome of oral food challenges, and to determine threshold concentrations of specific serum IgE that could render double‐blind, placebo‐controlled food challenges unnecessary.Methods
In 501 children (median age 13 months), 992 controlled oral challenges were performed with cow's milk (CM), hen's egg (HE), wheat and soy. 440/501 (88%) children suffered from atopic dermatitis. For all children, specific IgE concentrations in serum were determined. Sensitivity, specificity, positive and negative predictive values, receiver operator characteristics‐curves as well as predictive decision points were calculated.Results
Four hundred and forty‐five out of 992 oral food challenges with allergens were assessed as positive. Sensitivity of specific serum IgE was 97% for HE, 83% for CM, 69% for soy, and 79% for wheat. Specificity was 51% for HE, 53% for CM, 50% for soy, and 38% for wheat. Calculating 90%, 95% and 99% predicted probabilities using logistic regression revealed predictive decision points of 6.3, 12.6, and 59.2 kU/L for HE, respectively. Subdividing our children in those of below or above 1 year of age resulted in a markedly different predicted probability for HE. For CM, only the 90% predicted probability (88.8 kU/L) could be calculated. No decision points could be determined for CM, wheat and soy.Conclusion
In general, specific serum IgE levels showed a correlation with the outcome of positive oral food challenges for CM and HE. Meaningful predictive decision points can be calculated for HE, which may help to avoid oral food challenges in some cases. However, data need to be ascertained for each allergen separately. Furthermore, the age of the patient population under investigation must also be taken into account.
Increase in daytime symptoms is a sensitive and specific criterion for predicting corticosteroid‐treated exacerbations in a clinical asthma trial
Authors: Dennis S. M. , Altmann D. R. , Lee T. H. 
Published: March 2005

SummaryBackground
To determine which diary card variables are the most predictive for administration of additional courses of corticosteroids using the TRUST (The Regular Use of Salbutamol Trial) data set.Methods
Logistic regression models were used to identify the extent to which a change in diary card variable affected the odds ratio (OR) for administering a course of oral or increased inhaled corticosteroids. The complete TRUST diary card data were used with over 200 000 days of diary card observations from 983 mild to moderate asthmatic subjects.Results
An increase in daytime symptoms of 1–5 U over baseline was associated with an increase in the OR for starting all types of corticosteroids from two‐ to 60‐fold.Conclusions
These results indicate that an increase in daytime symptoms of two or more over baseline strongly predicts the administration of additional corticosteroids. The results have significant implications for both clinical practice and design of clinical trials in asthma.
Prenatal lipopolysaccharide‐exposure prevents allergic sensitization and airway inflammation, but not airway responsiveness in a murine model of experimental asthma
Authors: Blümer N. , Herz U. , Wegmann M. , Renz H. 
Published: March 2005

SummaryBackground
Epidemiological evidence underlines the impact of prenatal environmental factors on the development of postnatal allergies. In this regard an inverse correlation between lipopolysaccharide (LPS) exposure and development of childhood allergy has been found.Objective
To assess the impact of prenatal LPS exposure on the development of postnatal respiratory allergies in a mouse model of experimental asthma.Methods
Female BALB/c mice were exposed to LPS before conception and during pregnancy. Several weeks after birth offspring were sensitized to ovalbumin (OVA) followed by aerosol allergen challenges.Results
Prenatal, maternal LPS‐exposure enhanced neonatal IFN‐γ, but not IL‐4 and IL‐2 production. OVA sensitization of prenatally LPS‐exposed mice was accompanied by a marked suppression in anti‐OVA IgG1 and IgE as well as unchanged IgG2a antibody responses, paralleled by a significant reduction in IL‐5 and IL‐13 levels following mitogenic stimulation of splenic leucocytes. Assessment of bronchoalveolar lavage fluids following allergen challenges revealed a marked reduction in eosinophils and macrophages in these mice. Surprisingly, development of airway hyper‐responsiveness, a hallmark of bronchial asthma, was not affected.Conclusion
This study provides first experimental evidence that LPS may already operate in prenatal life in order to modulate the development of allergies in the offspring.
Glutathione protects human airway proteins and epithelial cells from isocyanates
Authors: Wisnewski A. V. , Liu Q. , Liu J. , Redlich C. A. 
Published: March 2005

SummaryBackground
Glutathione (GSH), one of the major anti‐oxidants of the lung, has been linked to the human response to isocyanate exposure. However, the ability of GSH to modulate key chemical reactions, thought to be central to the development of human isocyanate allergy, has not been directly analyzed under biologic exposure conditions.Objective
To better understand the potential role of GSH in the response to occupational isocyanate exposure, we evaluated its effects on two processes thought to be involved in the development of isocyanate allergy, isocyanate–protein conjugation and epithelial cell toxicity.Methods
The effects of GSH on (1) isocyanate conjugation with albumin, its major target in the airway fluid and (2) isocyanate‐induced toxicity to human airway epithelial cell lines, A549 and NCI‐H292, were tested using two different in vitro models. For protein conjugation studies, a newly described vapour exposure system was used to model the air/liquid interface at the surface of the epithelial fluid in the airways. Epithelial cell exposures were performed in fluid phase to mimic the in vivo exposure of airway cells covered by epithelial lining fluid.Results
Reduced GSH prevented hexamethylene diisocyanate (HDI) conjugation to albumin in a dose‐dependent manner, while oxidized GSH (GSSG) conversely increased conjugation rates. GSH levels equivalent to those found in normal human airway fluid (100 μm) provided >90% protection against HDI‐protein conjugation when albumin was exposed to HDI vapour levels 10‐fold above permissible occupational limits. Physiologic levels of GSH, but not GSSG, also reduced HDI toxicity to human airway epithelial cells in a dose‐dependent manner, when present extracellularly, however, drugs that modulate intra‐cellular GSH levels did not significantly alter isocyanate toxicity.Conclusions
Together with previously reported genetic and toxicity studies, the data suggest that airway GSH plays an important role in protection against HDI exposure and may help prevent the development of allergic sensitization and asthma.