bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular drug sensitivity in MLL‐rearranged childhood acute leukaemia is correlated to partner genes and cell lineage
Authors: Palle J. , Frost B. M. , Forestier E. , Gustafsson G. , Nygren P. , Hellebostad M. , Jonsson O. G. , Kanerva J. , Schmiegelow K. , Larsson R. , Lönnerholm G. ,   on behalf of the Nordic Society for Paediatric Haematology and Oncology
Published: April 2005

SummaryRearrangements in the 11q23 region, the site of the mixed lineage leukaemia (MLL) gene, are found in both childhood acute myeloid (AML) and lymphoblastic (ALL) leukaemia. We studied the in vitro drug resistance by the fluorometric microculture cytotoxicity assay (FMCA) in 132 children with AML and 178 children with ALL (aged 0–17 years). In AML, children with t(9;11) (n = 10) were significantly more sensitive to cytarabine (P < 0·001) and doxorubicin (P = 0·005) than non‐11q23 rearranged patients (n = 108). Children with other 11q23 rearrangements (n = 14) differed less from non‐rearranged children. The ‘AML‐profile’ common to all three groups included relative resistance to glucocorticoids and vincristine. In ALL, children with 11q23 rearrangement (n = 22) were significantly more sensitive to cytarabine (P = 0·026) than children without 11q23 rearrangement (n = 156), also after stratification for white blood cell count. In conclusion, the findings indicate that the cellular drug resistance is correlated to both the cell lineage and the type of 11q23 rearrangement. High cellular sensitivity to cytarabine and doxorubicin might explain the excellent treatment results in children with AML and t(9;11). The present study supports the strategy of contemporary protocols to include high‐dose cytarabine in the treatment of 11q23‐positive patients both in AML and ALL.
Anti‐prothrombin IgG from patients with anti‐phospholipid antibodies inhibits the inactivation of factor Va by activated protein C
Authors: Galli Monica , Willems George M. , Rosing Jan , Janssen Rita M. , Govers‐Riemslag José W. P. , Comfurius Paul , Barbui Tiziano , Zwaal Robert F. A. , Bevers Edouard M. 
Published: April 2005

SummaryInterference of anti‐phospholipid antibodies with the protein C pathway has been suggested to play a role in the development of thrombosis in the anti‐phospholipid syndrome. We studied the effect of IgG preparations containing anti‐prothrombin antibodies of 17 lupus anticoagulant‐positive patients and 12 controls on the inactivation of factor Va (FVa) by activated protein C (APC) in a system with purified coagulation factors. Test IgG was incubated with human prothrombin, phospholipid vesicles and CaCl2. Protein S, FVa and APC were added and the APC‐dependent loss of FVa activity was monitored over time. The residual amount of FVa remaining after 10 min was 14 ± 4% (mean ± SD) when 1·5 mg/ml normal IgG was present and ranged between 17% and 82% with 1·5 mg/ml patient IgG. Twelve patients IgG gave values of residual FVa >22% (i.e. 2 SD above the mean of controls), indicating that APC‐mediated inactivation of FVa was significantly inhibited. The inhibition was strictly dependent on the presence of prothrombin, proportional to the concentration of IgG and strongly diminished at a 20‐fold higher phospholipid concentration. Most, although not all, IgG containing anti‐prothrombin antibodies inhibit the APC‐catalysed FVa inactivation, which may contribute to the increased risk of thrombosis in patients with the anti‐phospholipid syndrome.
Bone marrow endothelial cells in multiple myeloma secrete CXC‐chemokines that mediate interactions with plasma cells
Authors: Pellegrino Antonio , Ria Roberto , Pietro Giulia Di , Cirulli Teresa , Surico Giammarco , Pennisi Angela , Morabito Fortunato , Ribatti Domenico , Vacca Angelo 
Published: April 2005

SummaryBone marrow endothelial cells (EC) from patients with multiple myeloma (MM) were found to express and secrete higher amounts of the CXC‐chemokines CXCL8/interleukin (IL)‐8, CXCL11/interferon‐inducible T‐cell alpha chemoattractant (I‐TAC), CXCL12/stromal cell‐derived factor (SDF)‐1α, and CCL2/monocyte chemotactic protein(MCP)‐1 than EC from human umbilical vein (HUVEC), considered as a healthy counterpart. Paired plasma cells and several MM cell lines expressed cognate receptors of each chemokine to a variable extent. When cells were exposed to chemokines, CXCL8/IL‐8 and CXCL12/SDF‐1α stimulated their proliferation and all chemokines stimulated cell chemotaxis. It is suggested that angiogenesis also favours MM progression through the release of CXC‐chemokines.
Nicotinic acetylcholine receptor‐mediated stimulation of endothelial cells results in the arrest of haematopoietic progenitor cells on endothelium
Authors: Serobyan Naira , Schraufstatter Ingrid U. , Strongin Alex , Khaldoyanidi Sophia K. 
Published: April 2005

SummaryThe function of endothelial cells that contribute to the regulation of haematopoietic stem/progenitor cells (HSPC) migration from peripheral blood into bone marrow can be influenced by extrinsic factors including nicotine. Therefore, the effect of nicotine on HSPC extravasation was studied. Using a parallel laminar flow chamber, we demonstrated an increase in the number of HSPC adhering to the nicotine‐exposed endothelium under conditions of physiological shear stress in vitro. Nicotine‐induced adhesion of HSPC was inhibited by mecamylamine, a non‐selective nicotinic acetylcholine receptor (nAchR) antagonist. The enhanced adhesive interactions of HSPC with nicotine‐exposed endothelial monolayers coincided with the nicotine‐induced activation of endothelial cells. Nicotine induced fast cytoskeletal reorganization and formation of filopodia in endothelial cells through interaction with the non‐neuronal nAchR expressed by these cells. In addition, nicotine treatment stimulated rapid phosphorylation of Erk1/2 and p‐38 in endothelial cells. Finally, nicotine inhibited the stroma derived factor‐1‐mediated transendothelial migration of HSPC. Decreased migration of HSPC correlated with diminished matrix metalloproteinase‐9 activity secreted by bone marrow cells and decreased expression of CD44 on the surface of endothelial cells. Overall, our data suggest that exposure to nicotine causes endothelial cell dysfunction and leads to the pathological arrest of HSPC on endothelium, interfering with their proper migration process.
Quantitative analysis of IgE antibodies to food and inhalant allergens in 4‐year‐old children reflects their likelihood of allergic disease
Authors: Wickman M. , Lilja G. , Söderström L. , Hamsten M. v. H. , Ahlstedt S. 
Published: April 2005

Background:  It is well established that early diagnosis of allergic disease is warranted.Methods:  In a prospective birth cohort study (BAMSE) 3743 children at 4 years of age were included. Children were classified as having any allergic disease, e.g. asthma, suspected allergic rhinitis (suspAR), eczema or oro‐gastro‐intestinal symptoms with questionnaire. Blood was obtained from 2612 of these children and analysed for IgE antibodies (ab) towards 14 common food and airborne allergens.Results:  Positive IgE ab results were found in 38% of the children with any allergic disease, whereas such IgE ab results were found in 17% among those without any allergic disease. Furthermore, among children with any allergic disease the median summated IgE ab levels were 10.7 kUA/l compared with 1.5 kUA/l among those without such symptoms. The highest IgE ab levels were found to birch, peanut, cat and horse. When the sum of the IgE‐ab levels towards the selected allergens was at least 34 kUA/l, or, alternatively, more than four allergen tests were positive, there was a 75% likelihood of identifying the individual with any allergic disease. To identify those with asthma, as well as those with suspAR, a significant interaction was found for the combination of the sum of IgE‐ab levels and number of allergens positive at test. For eczema only, the number of positive allergens at test was associated to the likelihood of such disease.Conclusions:  In children, 4 years of age, allergic disease was frequently not associated with the presence of single positive IgE antibody results, whereas increased IgE ab levels were significantly more prevalent among those with allergic disease. Thus, testing a certain profile of airborne and food allergens, and utilizing the sum of the IgE‐ab levels in combination with the number of allergens positive at tests, may represent a more efficient diagnostic tool then to use just single positive IgE‐ab results.
The inverse association of salmonellosis in infancy with allergic rhinoconjunctivitis and asthma at school‐age: a longitudinal study
Authors: Pelosi U. , Porcedda G. , Tiddia F. , Tripodi S. , Tozzi A. E. , Panetta V. , Pintor C. , Matricardi P. M. 
Published: April 2005

Background:  Respiratory allergies are inversely related to early acquisition of food‐borne and fecal‐oral infections, consumption of unpasteurized milk, early exposure to stables and high endotoxin concentrations in a farming environment. We tested therefore if infection by Salmonella in early life can protect from development of respiratory allergies later in life.Methods:  During 2003, we studied two groups of Sardinian children (age 6–18 years) who had been hospitalized before 4 years of age (during 1989–2001) with non‐typhoid salmonellosis (n = 148) or acute enteritis of nonbacterial etiology (NB‐enteritis) (n = 167). Allergic rhinoconjunctivitis (AR) and asthma were evaluated by telephonic interview with a ISAAC questionnaire; participants reporting AR and/or asthma were further examined through a complete diagnostic work‐up to objectively confirm or exclude current disease. Kaplan–Meier curves and Cox proportional hazard models were used to analyze the role of different types of enteritis on the risk of developing allergic rhinoconjunctivitis or asthma over time.Results:  Children who had been hospitalized with salmonellosis had a lower prevalence of allergic rhinoconjunctivitis (eight of 148, 5.4%vs 23 of 167, 13.8%; P = 0.019) or asthma (five of 148, 3.4%vs 21 of 167, 12.6%; P = 0.006) than those who had been hospitalized with NB‐enteritis. The proportional hazard of salmonellosis for asthma was 0.23 (95% CI: 0.08–0.67; P < 0.01) and for allergic rhinoconjunctivitis was 0.40 (95% CI: 0.17–0.95; P = 0.04), after adjusting for confounders.Discussion:  The strength of the observed associations suggests that Salmonella may contribute to shape the natural history of respiratory allergies. However, further studies are needed to test in other settings the association observed in Sardinian children. We speculate that clinical or subclinical infection by Salmonella may contribute to the atopy protective influence of a traditional farming environment or of areas endemic for food‐borne and fecal‐oral infections. Food hygiene and prevention of salmonellosis must remain however a public health priority.
Nonimmediate reactions to systemic corticosteroids suggest an immunological mechanism
Authors: Padial A. , Posadas S. , Alvarez J. , Torres M.‐J. , Alvarez J. A. , Mayorga C. , Blanca M. 
Published: April 2005

Background:  Administration of corticosteroids (CS) by different routes may cause varying types of allergic reactions, thereby hampering their further use in affected patients. In order to verify an immunological involvement we evaluated a group of patients with symptoms compatible with nonimmediate allergic reactions to CS.Methods:  Studies included patch and intradermal tests, immunohistochemical studies and controlled administration to reproduce the response. The cytokines interleukin (IL)‐4, interferon (IFN)‐γ and tumor necrosis factor (TNF)‐α were quantified in peripheral blood during the response.Results:  Of 32 subjects evaluated presenting nonimmediate urticaria or exanthema, 21 were finally considered positive after re‐exposure. The drugs most frequently involved were betamethasone and dexamethasone. Fewer than half the patients responded to prednisolone whilst some responded to three or more CS. Hydrocortisone and deflazacort were well tolerated by all the patients. Subjects with a positive intradermal or patch test had a perivascular mononuclear cell infiltrate with the presence of CD4 and CD8 lymphocytes positive for CD45RO+ (memory) and CD69 (activation marker) cells. Monitoring peripheral blood during the acute response showed expression of IFN‐γ and TNF‐α, with downregulation of IL‐4.Conclusion:  Adverse systemic responses to different CS are suggestive of a nonimmediate reaction. The symptoms elicited together with the immunlogical studies suggest a T‐cell mediated response. The response to closely related CS was especially marked between betamethasone and dexamethasone, whereas hydrocortisone and deflazacort were well tolerated.
A differing pattern of association between dietary fish and allergen‐specific subgroups of atopy
Authors: Andreasyan K. , Ponsonby A.‐L. , Dwyer T. , Kemp A. , Dear K. , Cochrane J. , Carmichael A. 
Published: April 2005

Background:  We examined the role of fish intake in the development of atopic disease with particular reference to the possibility of differential effects on allergen‐specific subgroups of sensitization.Methods:  The exposure of interest was parental report of fish intake by children aged 8 years at the 1997 Childhood Allergy and Respiratory Health Study (n = 499). The outcomes of interest were subgroups of atopy: house dust mite (HDM)‐pure sensitization [a positive skin‐prick test (SPT) ≥2 mm to Der p or Der f only], ryegrass‐pure sensitization (a positive SPT ≥2 mm to ryegrass only); asthma and hay fever by allergen‐specific sensitization.Results:  A significant association between fish intake and ryegrass‐pure [adjusted odds ratio (AOR) 0.37 (0.15–0.90)] but not HDM‐pure sensitization [AOR 0.87 (0.36–2.13)] was found. Fish consumption significantly decreased the risk for ryegrass‐pure sensitization in comparison with HDM‐pure sensitization [AOR 0.20 (0.05–0.79)].Conclusions:  We have demonstrated a differential effect of fish intake for sensitization to different aeroallergens. This may be due to the different timing of allergen exposure during early life. Further investigation of the causes of atopic disease should take into account allergen‐specific subgroups.
Monophosphoryl lipid A (MPL®)* promotes allergen‐induced immune deviation in favour of Th1 responses
Authors: Puggioni F. , Durham S. R. , Francis J. N. 
Published: April 2005

Background:  Monophosphoryl lipid A (MPL®) is a nontoxic derivative of the lipopolysaccharide (LPS) of Salmonella minnesota R595. MPL has been used as an adjuvant in grass and tree pollen vaccines for the treatment of seasonal allergic rhinitis. Little is known about the influence of MPL on cellular responses to allergens in man. We therefore studied the effects of MPL in vitro on peripheral blood mononuclear cells (PBMC) obtained from patients with grass pollen hay fever.Methods:  The PBMCs from 13 subjects were cultured with grass pollen Phleum pratense extract (0, 2 and 20 μg/ml) and MPL (0 and 10 μg/ml; defined as an optimal concentration in preliminary studies) and after 6 days proliferative responses were measured by thymidine incorporation and cytokine production by enzyme‐linked immunosorbent assay (ELISA).Results:  Proliferative responses were unaffected by the presence of MPL whereas MPL induced a significant increase in allergen‐induced interferon (IFN)‐γ production [allergen alone, 645 ± 466 pg/ml (mean ± SE) vs allergen + MPL, 3232 ± 818 pg/ml; P < 0.001]. In addition, there was a significant decrease in interleukin (IL)‐5 production (4307 ± 1030 pg/ml vs 2997 ± 826 pg/ml; P < 0.01). Although MPL alone could induce modest increases in IL‐10 production, MPL did not influence the production of this cytokine in allergen‐stimulated cultures. Addition of neutralizing antibody against IL‐12 resulted in 95% inhibition of MPL‐induced IFN‐γ production. Depletion of monocytes from the culture system abrogated the effects of MPL on elevated cytokine production.Conclusions:  In summary, use of MPL with grass pollen extract results in immune deviation of allergen‐induced peripheral Th2‐cell responses in favour of ‘protective’ Th1 responses in an IL‐12 and monocyte‐dependent fashion.
Peanut‐ and cow's milk‐specific IgE, Th2 cells and local anaphylactic reaction are induced in Balb/c mice orally sensitized with cholera toxin
Authors: Adel‐Patient K. , Bernard H. , Ah‐Leung S. , Créminon C. , Wal J.‐M. 
Published: April 2005

Background:  The development of animal models developing specific immunoglobulin (Ig)E presenting the same specificity as human IgE and similar clinical symptoms as those observed in allergic patients are of great interest for the understanding of mechanisms involved in the induction and regulation of food allergy.Methods:  Balb/c female mice were sensitized with whole peanut protein extract (WPPE) by means of intraperitoneal (i.p.) injections with alum or gavages with cholera toxin (CT). The WPPE specific IgE, IgG1 and IgG2a were monitored. Th2 cells activation was analysed assaying interleukin (IL)‐4 and IL‐5 vs IFNγ on reactivated splenocytes. Local anaphylactic reaction was evaluated by assaying histamine in faecal samples. The oral sensitization protocol was further extended to cow's milk proteins (CMP).Results:  Balb/c mice developed high peanut‐specific IgE and IgG1 responses either after i.p. or oral sensitizations. In both cases, antibodies were specific to polymer of glycinin fragments, containing polypeptides from Ara h3/4, and to a lesser extent to Ara h1 and Ara h2. Interleukin‐4 and IL‐5 production were evidenced. Balb/c mice could also be sensitized to CMP, as demonstrated by CMP‐specific IL‐4 and IL‐5 secretions and induction of IgE specific for whole caseins, β‐lactoglobulin, serum bovine albumin and lactoferrin. Of interest was the occurrence of a local anaphylactic reaction in the peanut and CM models.Conclusions:  In contrast with previous authors, Balb/c mice were sensitized and evidenced an allergic reaction after oral administrations of peanut or CMP plus CT, providing an interesting model for further studies on immunopathogenic mechanisms.
Possible circadian variation of serum mast cell tryptase concentration
Authors: Dugas‐Breit S. , Przybilla B. , Schöpf P. , Ruëff F. 
Published: April 2005

Background:  A temporarily elevated level of serum mast cell tryptase (ST) indicates mast cell activation and occurs in systemic anaphylactic reactions (SAR). We measured ST following a sting challenge in vespid venom‐allergic patients treated with venom immunotherapy (VIT) and in healthy controls, respectively.Aim of the study:  To assess changes of ST over time in vespid venom‐allergic patients at the occasion of a re‐sting and in healthy controls.Methods:  A sting challenge was performed in 20 patients on vespid VIT to monitor efficacy of VIT. ST was measured between 9.00 and 10.00 a.m. (baseline). Sting challenge was performed at 2.00 p.m., and ST was determined again 20 min, 90 min and 18 h later. Measurements at corresponding times of the day were done in nine healthy controls.Results:  One patient developed a mild SAR to the sting challenge which was associated with a temporary increase of ST. In the other 19 patients who tolerated the sting challenge without SAR ST decreased significantly by 18.0% (median, range 8.3–36.7%). Twenty minutes after the sting when compared with baseline levels (P < 0.001), a significant decrease of ST was still present after 90 min (median 13.7%) (P < 0.001), but not after 18 h (P = 0.57). A comparably significant temporary decline was found in controls.Conclusions:  The temporary decline of ST in patients and in controls suggests a circadian variation of ST concentration. A normal diurnal pattern of ST concentration after sting challenge is associated with successful treatment.
Early effects of Asthma Prevention Program on asthma diagnosis and hospitalization in urban population of Poland
Authors: Stelmach W. , Majak P. , Jerzynska J. , Stelmach I. 
Published: April 2005

Background:  Asthma is one of the commonest public health problems in Poland and the commonest chronic disorder in children. Lodz Regional Health Insurance Fund was a sponsor of the Prevention Asthma Program in 2000–03, directed at increasing early detection and providing optimal treatment of allergies by specialists in children.Methods:  All funds were divided between 127 primary and 12 specialized care centres participated in the programme. Primary care centre goals were: anamnestic information, mapping of allergy‐causing factors, repeated auscultation of the lungs, bronchial dilation test, peak expiratory flow (PEF) measurement at the clinic and at home for 2 weeks. After preliminary diagnosis patients have been send to specialized centres. Specialized care centre goals were as follows: skin testing, spirometry, repeated bronchial dilation test, determination of eosinophilic white blood cells and eosinophil cationic protein (ECP) in blood.Results:  Increasing trend of new asthma diagnosis, expressed per 1000 inhabitants, was observed from 0.99 in 2000 to 2.19 in 2003. In the first year of Asthma Prevention Program, we observed more hospital episodes because of asthma exacerbation in comparison with year 1999 but from the second year of programme we showed systematically decreasing number of hospital episodes as a result of asthma exacerbation from 1.48 in 2000 to 0.84 in 2003. We found significantly decreasing trend in duration of hospitalization due to asthma exacerbation (P = 0.001).Conclusions:  Effects of this programmes are: early identification of allergic diseases, mainly asthma, reduced number and shorter duration of hospitalization because of asthma exacerbation and establishing new Asthma Schools Education.
Anti‐IL‐5 recombinant humanized monoclonal antibody (Mepolizumab) for the treatment of atopic dermatitis
Authors: Oldhoff J. M. , Darsow U. , Werfel T. , Katzer K. , Wulf A. , Laifaoui J. , Hijnen D. J. , Plötz S. , Knol E. F. , Kapp A. , Bruijnzeel‐Koomen C. A. F. M. , Ring J. , de Bruin‐Weller M. S. 
Published: April 2005

Background:  Eosinophils may play an important role in the pathogenesis of atopic dermatitis (AD). Interleukin‐5 is essential for eosinophil growth, differentiation and migration. A monoclonal antibody to human interleukin‐5 (mepolizumab) was developed for atopic diseases. This study was designed to study the effect of mepolizumab in AD.Methods:  Two single doses of 750 mg mepolizumab, given 1 week apart, were studied in patients with moderate to severe AD using a randomized, placebo‐controlled parallel group design. The primary endpoint of ‘success’ to treatment was defined as the percentage of patients with at least ‘marked improvement’ after 2 weeks as assessed by the Physician's Global Assessment of Improvement (PGA). Furthermore, SCORing AD (SCORAD), pruritus scoring, number of blood eosinophils and serum thymus and activation‐regulated chemokine (TARC) values served as secondary endpoints. Fluticason propionate cream 0.05%, once daily could be used as rescue medication from day 16 if no improvement was recorded.Results:  Eighteen patients received mepolizumab and 22 placebo treatment. Peripheral blood eosinophil numbers were significantly reduced in the treatment group compared with placebo (P < 0.05). No clinical success was reached by PGA assessment (P = 0.115), SCORAD (P = 0.293), pruritus scoring and TARC values in the mepolizumab‐treated group compared with placebo. However, modest improvement (<50% improvement) assessed by PGA was scored significantly more in the mepolizumab‐treated group compared with placebo (P < 0.05).Conclusion:  Two single doses of 750 mg mepolizumab did not result in clinical success in patients with AD, despite a significant decrease in peripheral blood eosinophils.