bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of multiple transcripts and isoforms derived from the mouse protein tyrosine phosphatase gene Ptprr
Authors: Chirivi Renato G. S. , Dilaver Gönül , van de Vorstenbosch Rinske , Wanschers Bas , Schepens Jan , Croes Huib , Fransen Jack , Hendriks Wiljan
Published: October 2004

The use of alternative splice sites, promoters and translation start sites considerably adds to the complexity of organisms. Four mouse cDNAs (PTPBR7, PTP‐SL, PTPPBSγ+ and PTPPBSγ−) have been cloned that contain different 5′ parts but encode identical protein tyrosine phosphatase PTPRR catalytic domains. We investigated the genomic origin and coding potential of these transcripts to elucidate their interrelationship. Mouse gene Ptprr exons were identified within a 260 kbp segment on chromosome 10, revealing PTP‐SL‐ and PTPPBSγ‐specific transcription start sites within introns two and four, respectively, relative to the 14 PTPBR7 exons. Northern and RT‐PCR analyses demonstrated differential expression patterns for these promoters. Furthermore, transfection studies and AUG codon mutagenesis demonstrated that in PTP‐SL and PTPPBSγ messengers multiple translation initiation sites are being used. Resulting 72, 60, 42 and 37 kDa PTPRR protein isoforms differ not only in the length of their N‐terminal part but also in their subcellular localization, covering all major PTP subtypes; receptor‐like, membrane associated and cytosolic. In summary, mouse gene Ptprr gives rise to multiple isoforms through the use of distinct promoters, alternative splicing and differential translation starts. These results set the stage for further investigations on the physiological roles of PTPRR proteins.
DNA topoisomerase II is required for the G0‐to‐S phase transition in Drosophila Schneider cells, but not in yeast
Authors: Hossain Muktadir S. , Kurokawa Kenji , Akimitsu Nobuyoshi , Sekimizu Kazuhisa
Published: October 2004

We previously reported that DNA topoisomerase II (topo II) is required for the G0‐to‐S phase transition in mammalian cells [Hossain et al. (2002) ICRF‐193, a catalytic inhibitor of DNA topoisomerase II, inhibits re‐entry into the cell division cycle from quiescent state in mammalian cells. Genes Cells 7, 285–294]. In this study, we examined whether the requirement for topo II is evolutionarily conserved in Drosophila and yeast. ICRF‐193, a catalytic inhibitor of topo II, inhibited DNA synthesis in Drosophila Schneider cells released from the G0 (stationary) phase, whereas the drug did not inhibit DNA synthesis in Schneider cells released from the M phase. Depletion of topo II mRNA by RNA‐interference (RNAi) in G0‐phase Schneider cells resulted in significant inhibition of DNA synthesis after release from G0‐arrest. In the yeast topo II temperature‐sensitive (ts) mutant, the initial cycle of DNA synthesis occurred at a restrictive temperature after release from starvation‐induced G0 phase and doubling of the DNA content in the cells was confirmed by both flow cytometry and fluorescence spectrophotometry. DNA synthesis in yeast cells after release from the G0 phase was also observed in the presence of ICRF‐193. Doubling of the DNA content was observed during spore germination of topo II ts mutant yeast at a restrictive temperature as determined by fluorescence spectrophotometry. These results indicate that topo II is required for the G0‐to‐S phase transition in Drosophila Schneider cells, but not in yeast.
Cognitive reorganization and stigmatization among persons with HIV
Authors: Abel Elizabeth , Rew Lynn , Gortner Eva‐Maria , Delville Carol L.
Published: October 2004

Background.  A diagnosis of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is a life‐changing event, where persons must deal with a life‐threatening, debilitating disease and its associated stigma and isolation. Studies over the past decade have shown that writing and talking about stressful and traumatic experiences, such as a life‐threatening illness, causes emotions surrounding the trauma to change and to become cognitively reorganized. The result is a reduction in inhibition and change in basic cognitive and linguistic processes, which have contributed to meaningful behavioural, psychological, and physical health benefits across a variety of populations.

Aims.  To describe the construction of the Integrated Model of Health Promotion for persons with HIV/AIDS, and present initial empirical support of the model from a feasibility pilot study of women with HIV/AIDS.

Approach.  The Integrated Model of Health Promotion is described and relevant literature in the field is reviewed. The model is implemented in a feasibility pilot study utilizing the emotional writing disclosure intervention.

Results.  Participants in the experimental condition demonstrated a promising pattern of cognitive reorganization, a reduced perception of stigma, and an improvement in mental health scores compared with the control condition.

Conclusion.  Implications of these findings are discussed within the framework of the Integrated Model of Health Promotion. The model explores health and behavioural benefits associated with emotional writing in individuals with HIV/AIDS. The limited sample size of this pilot study precludes testing for significance. Further studies are required prior to the development of practice guidelines.
Deletion of the genes encoding the MtrA–MtrB two‐component system of Corynebacterium glutamicum has a strong influence on cell morphology, antibiotics susceptibility and expression of genes involved in osmoprotection
Authors: Möker Nina , Brocker Melanie , Schaffer Steffen , Krämer Reinhard , Morbach Susanne , Bott Michael
Published: October 2004

The MtrAB two‐component signal transduction system is highly conserved in sequence and genomic organization in Mycobacterium and Corynebacterium species, but its function is completely unknown. Here, the role of MtrAB was studied with C. glutamicum as model organism. In contrast to M. tuberculosis, it was possible to delete the mtrAB genes in C. glutamicum. The mutant cells showed a radically different cell morphology and were more sensitive to penicillin, vancomycin and lysozyme but more resistant to ethambutol. In order to identify the molecular basis for this pleiotropic phenotype, the mRNA profiles of mutant and wild type were compared with DNA microarrays. Three genes showed a more than threefold increased RNA level in the mutant, i.e. mepA (NCgl2411) encoding a putative secreted metalloprotease, ppmA (NCgl2737 ) encoding a putative membrane‐bound protease modulator, and lpqB encoding a putative lipoprotein of unknown function. Expression  of  plasmid‐encoded  mepA in  Escherichia  coli led to elongated cells that were hypersensitive to an osmotic downshift, supporting the idea that peptidoglycan is the target of MepA. The mRNA level of two genes was more than fivefold decreased in the mutant, i.e. betP and proP which encode transporters for the uptake of betaine and proline respectively. The microarray results were confirmed by primer extension and RNA dot blot experiments. In the latter, the transcript level of genes involved in osmoprotection was tested before and after an osmotic upshift. The mRNA level of betP, proP and lcoP was strongly reduced or undetectable in the mutant, whereas that of mscL (mechanosensitive channel) was increased. The changes in cell morphology, antibiotics susceptibility and the mRNA levels of betP, proP, lcoP, mscL and mepA could be reversed by expression of plasmid‐encoded copies of mtrAB in the ΔmtrAB mutant, confirming that these changes occurred as a consequence of the mtrAB deletion.
HopPtoN is a Pseudomonas syringae Hrp (type III secretion system) cysteine protease effector that suppresses pathogen‐induced necrosis associated with both compatible and incompatible plant interactions
Authors: López‐Solanilla Emilia , Bronstein Philip A. , Schneider Anna R. , Collmer Alan
Published: October 2004

Pseudomonas syringae pv. tomato DC3000 causes bacterial speck disease in tomato, and it elicits the hypersensitive response (HR) in non‐host plants such as Nicotiana tabacum and Nicotiana benthamiana. The compatible and incompatible interactions of DC3000 with tomato and Nicotiana spp., respectively, result in plant cell death, but the HR cell death occurs more rapidly and is associated with effective plant defense. Both interactions require the Hrp (HR and pathogenicity) type III secretion system (TTSS), which injects Hop (Hrp outer protein) effectors into plant cells. Here, we demonstrate that HopPtoN is translocated into tomato cells via the Hrp TTSS. A hopPtoN mutant produced eightfold more necrotic ‘speck’ lesions on tomato leaves than did DC3000, but the mutant and the wild‐type strain grew to the same level in infected leaves. In non‐host N. tabacum leaves, the hopPtoN mutant produced more cell death, whereas a DC3000 strain overexpressing HopPtoN produced less cell death and associated electrolyte leakage in comparison with wild‐type DC3000. Transient expression of HopPtoN via infection with a PVX viral vector enabled tomato and N. benthamiana plants to tolerate, with reduced disease lesions, challenge infections with DC3000 and P. syringae pv. tabaci 11528, respectively. HopPtoN showed cysteine protease activity in vitro, and hopPtoN mutants altered in the predicted cysteine protease catalytic triad (C172S, H283A and D299A) lost HR suppression activity. These observations reveal that HopPtoN is a TTSS effector that can suppress plant cell death events in both compatible and incompatible interactions.
Extension of a biochemical model for the generalized stoichiometry of electron transport limited C3 photosynthesis
Authors: YIN X. , VAN OIJEN M. , SCHAPENDONK A. H. C. M.
Published: October 2004

The widely used steady‐state model of Farquhar et al. (Planta 149: 78–90, 1980) for C3 photosynthesis was developed on the basis of linear whole‐chain (non‐cyclic) electron transport. In this model, calculation of the RuBP‐regeneration limited CO2‐assimilation rate depends on whether it is insufficient ATP or NADPH that causes electron transport limitation. A new, generalized equation that allows co‐limitation of NADPH and ATP on electron transport is presented herein. The model is based on the assumption that other thylakoid pathways (the Q‐cycle, cyclic photophosphorylation, and pseudocyclic electron transport) interplay with the linear chain to co‐contribute to a balanced production of NADPH and ATP as required by stromal metabolism. The original model assuming linear electron transport limited either by NADPH or by ATP, predicts quantum yields for CO2 uptake that represent the highest and the lowest values, respectively, of the range given by the new equation. The applicability of the new equation is illustrated for a number of C3 crop species, by curve fitting to gas exchange data in the literature. In comparison with the original model, the new model enables analysis of photosynthetic regulation via the electron transport pathways in response to environmental stresses.
Phytochrome modulation of blue‐light‐induced phototropism
Authors: WHIPPO C. W. , HANGARTER R. P.
Published: October 2004

Red light enhances hypocotyl phototropism toward unilateral blue light through a phytochrome‐mediated response. This study demonstrates how the phytochromes modulate blue‐light‐induced phototropism in the absence of a red light pre‐treatment. It was found that phytochromes A, B, and D have conditionally overlapping functions in the promotion of blue‐light‐induced phototropism. Under very low blue light intensities (0.01 µmol m−2 s−1) phyA activity is necessary for the progression of a normal phototropic response, whereas above 1.0 µmol m−1 s−2 phyB and phyD have functional redundancy with phyA to promote phototropism. PhyA also contributes to attenuation of phototropism under high fluence rates of unilateral blue light, which was previously shown to be dependent on the phototropins and cryptochromes. From these results, it appears that phytochromes are required to develop a robust phototropic response under low fluence rates, whereas under high irradiances where phototropism may be less important, phyA suppresses phototropism.
IgE binding to pepsin‐digested water soluble and insoluble wheat proteins
Authors: Mesa‐del‐Castillo M. , Martínez‐Cócera C. , Caballero M. L. , Vazquez L. , Moneo I.
Published: October 2004

Background:  Positive skin prick tests to wheat are a common finding among atopic patients, but only a minor fraction of these patients show immediate clinical symptoms after wheat ingestion. The aim of this study was to evaluate the allergenicity of wheat proteins after pepsin treatments.

Methods:  Six patients with positive specific IgE and/or skin prick test to soluble wheat proteins and to gluten were studied. Five of them had no symptoms after wheat ingestion and showed a negative oral challenge test. All sera were analysed with extracts obtained after pepsin hydrolysis during different time periods of water‐soluble and insoluble wheat proteins by IgE immunoblotting.

Results:  A pepsin‐sensitive allergen of around 35 kDa was recognized by the five atopic negative wheat oral challenge patients in the undigested water‐insoluble extract. A patient showing immediate urticaria after wheat ingestion detected a pepsin‐resistant allergen with similar molecular weight. Finally, an inhalation‐induced asthma patient recognized water‐soluble proteins (of around 14 kDa) that could correspond to the α‐amylase inhibitors.

Conclusions:  Our immunoblotting method shows better correlation with the clinical symptoms than skin prick test and CAP results. Pepsin resistance of the acetic acid‐soluble wheat proteins may be responsible for the immediate symptoms of the patient who presented immediate urticaria.
Cross‐reactivity to eel, eelpout and ocean pout in codfish‐allergic patients
Authors: Sten E. , Hansen T. K. , Stahl Skov P. , Andersen S. B. , Torp AM. , Bindslev‐Jensen U. , Bindslev‐Jensen C. , Poulsen L. K.
Published: October 2004

Fish allergy is one of the most common food allergies in both children and adults and patients with allergic reactions to one fish species have in many cases been given the advice to avoid all fish, without further evaluation. The possible common reactivity between different fish species is not well studied. Because of this and a possible exploitation of fish species hitherto not much used in the Scandinavian diet ocean pout, eelpout and eel were evaluated. We examined the serological and biological cross‐reactivity of these species in double‐blind challenged‐confirmed codfish‐allergic patients using CAP, Maxisorp‐radio allergosorbent test (RAST) inhibition, western blot, skin prick test (SPT) and histamine release (HR). All 18 codfish allergic patients had specific IgE to ocean pout, eelpout and eel determined by Maxisorp‐RAST. All four fish species could induce basophil HR using blood from 16 of 18 patients and all patients tested reacted in SPT. This study demonstrates that patients with a verified clinical allergy to codfish in a high frequency express biological cross‐reactivity to other fish species. By RAST inhibition this common reactivity was shown to be a true cross‐reactivity.
Randomized controlled open study of sublingual immunotherapy for respiratory allergy in real‐life: clinical efficacy and more
Authors: Marogna M. , Spadolini I. , Massolo A. , Canonica G. W. , Passalacqua G.
Published: October 2004

Background:  Some aspects of sublingual immunotherapy (SLIT) still need to be addressed: magnitude of the clinical efficacy, effect on the bronchial hyperreactivity adherence to treatment, preventive effect. We attempted to clarify these points in a randomized open, controlled, two parallel group study in a real‐life setting.

Methods:  Five hundred and eleven patients with allergic rhinitis with or without intermittent asthma were randomized to drugs only or drugs + SLIT (rate 2 : 3) for 3 years. The clinical score (symptoms + drug intake) was measured each year during the allergen exposure. Pulmonary function test, methacholine challenge and skin tests were performed at the beginning and at the end of the study. Adherence to treatment was assessed by measuring the consumed extract.

Results:  Three hundred and nineteen patients received SLIT and 192 drugs only. Dropouts were 15% in the SLIT group and 12% in the controls. There was a significant improvement of clinical scores in the SLIT group: baseline 147 ± 3.3, first year 72.9 ± 1.3, second year 68.3 ± 1.8, third year 54.7 ± 2.8 (P < 0.0001 vs baseline). Control group: baseline 138 ± 2.3, first year 124.1 ± 3.7, second year 111 ± 3.3, third year 121 ± 3.8 (P = NS). Only four patients reported systemic itching. Adherence was >80% in 72% and >60% in 18% of patients. The number of patients with a positive MCh challenge decreased significantly after 3 years only in the SLIT group. New skin sensitizations appeared in 38% of the controls and in 5.9% of the SLIT patients (P = 0.01).

Conclusion:  Sublingual immunotherapy approximately halved the clinical scores and significantly reduced the bronchial hyperreactivity. Similarly to subcutaneous immunotherapy, SLIT displayed a preventive effect on the onset of new skin sensitizations. The adherence rate was quantitatively satisfactory.
Preferential expression of IgG2b in nose draining cervical lymph nodes and its putative role in mucosal tolerance induction
Authors: Van Helvoort J. M. L. M. , Samsom J. N. , Chantry D. , Jansen W. , Schadee‐Eestermans I. , Thepen T. , Mebius R. E. , Kraal G.
Published: October 2004

Induction of intranasal tolerance prevents the body from eliciting unwanted immune responses against harmless antigens that enter the body through the nasal mucosa. To study the intrinsic capacities of the cervical, nose draining lymph nodes (CLN), which are essential for tolerance induction, genes that are differentially expressed in CLN and not in peripheral lymph nodes (PLN) were characterized. The gene that is predominantly overexpressed in CLN codes for IgG2b. This is confirmed by a higher percentage of IgG2b+ B220+ cells in CLN compared with any PLN. However, this predominance of IgG2b‐positive B cells in the CLN is not specific for the lymph node itself but rather determined by the region drained by lymph nodes at the cervical site, as transplanted PLN at these locations show a comparable predominance. It was demonstrated that IgG2b, when compared with IgG1, led to differential activation of dendritic cells (DC) through Fc receptor signalling. The results point to a unique local combination of cells and factors in the nose draining CLN leading to highly specialized immune reactivity. The results point out that predominance of a distinct IgG isotype in a lymphoid environment may lead to highly specialized immune reactivity.
Evaluation of the Asthma Life Quality test for the screening and severity assessment of asthma
Authors: Fonseca J. A. , Delgado L. , Costa‐Pereira A. , Tavares C. , Moreira A. , Morete A. , de Oliveira F. , Rodrigues J. , Vaz M.
Published: October 2004

Background:  Asthma Life Quality (ALQ) test, a 20‐question questionnaire developed by the American College of Allergy, Asthma and Immunology, has been shown to be useful for asthma diagnosis. We aimed to determine the relation between ALQ scores and (a) diagnosis of asthma; (b) physician's classification of asthma severity according to National Institutes of Health/Global Initiative for Asthma (GINA).

Methods:  Standard translation and cultural adaptation to Portuguese was performed. Patients self‐administered the ALQ in the waiting room; the attending allergist classified them, blindly for the test. The scores of nonasthmatics were compared with those of asthma patients. Asthma patients were analyzed in two severity groups: intermittent and mild persistent asthma (IMPA), and moderate and severe persistent asthma (MSPA); sensitivity, specificity, positive and negative predictive values were calculated and receiver operating characteristic curve plotted. Logistic regression analysis models were computed.

Results:  From 283 patients, 237 tests were analyzed. Non‐asthmatic patients ALQ scores (mean ± SD) were 6 ± 4 and, for asthmatics, 10 ± 5 [mean difference 4.6 (95%CI 3.3–5.9)]. The odds of positive diagnosis increased 1.27 times (95%CI 1.17–1.38) for each one‐unit increase in the test. For asthma severity ALQ scores were 9 ± 4 for IMPA, 15 ± 3 for MSPA [difference 6.0 (95%CI 4.8–7.1)]; with a sensitivity of 88% and specificity of 74% for a score of 12. The odds of MSPA increased 1.49 times (95%CI 1.28–1.74) per unit increase in ALQ.

Conclusions:  ALQ can help both to identify patients with asthma and to differentiate those more likely to have moderate/severe asthma. These are relevant characteristics for the possible use of this simple, self‐administered questionnaire in the assessment of asthma patients needing additional medical management.
Allergenicity and cross‐reactivity of Russian olive pollen (Eleagnus angustifolia)
Authors: Sastre J. , Lluch‐Bernal M. , Bustillo A. M. G. , Carnés J. , Marañón F. , Casanovas M. , Fernández‐Caldas E.
Published: October 2004

Background:  The purposes of this study were: to determine the prevalence of sensitization and immunochemical characterization of Eleagnus angustifolia pollen (Russian olive) that belongs to the family Eleagnaceae.

Methods:  A total of 134 patients with rhinoconjunctivitis and/or asthma were studied. Its allergenicity, cross‐reactivity with olive pollen and the presence of Ole e 1 and Ole e 4‐like molecules were evaluated.

Results:  Eleagnus angustifolia pollen was detected from May to June. Seventy‐three of 134 (30.5%) had positive skin test to E. angustifolia, all of them were positive to olive. There was a good correlation between specific immunoglobulin (Ig)E levels to E. angustifolia and Olea europaea (r = 0.77, P = 0.002). Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS‐PAGE) immunoblots revealed major IgE‐binding bands in the E. angustifolia extract of 43 and 63.7 kDa. The E. angustifolia extract was not able to inhibit olive, whereas O. europaea inhibited E. angustifolia up to 41%. The presence of Ole e 1‐ and Ole e 4‐like allergens in E. angustifolia extract was confirmed by enzyme‐linked immunosorbent (ELISA) inhibition assays. Nasal challenge with E. angustifolia was positive in three of six patients with positive skin test to both pollens and negative in five patients with positive skin test only to O. europaea.

Conclusions:  This study confirms that E. angustifolia is capable of sensitizing individuals in Madrid. A minimal‐to‐moderate cross‐reactivity with olive pollen was established, suggesting some cross‐reactivity but not excluding co‐sensitization.
Is secondary lymphoid‐organ chemokine (SLC/CCL21) much more than a constitutive chemokine?
Authors: Serra H. M. , Baena‐Cagnani C. E. , Eberhard Y.
Published: October 2004

Chemokines are a superfamily of small cytokines with activities ranging from leukocyte traffick to hematopoiesis, angiogenesis, and tissue organogenesis. Secondary lymphoid‐organ chemokine (SLC/CCL21) was originally reported as a chemokine constitutively expressed by stromal cells and high endothelial venules in secondary lymphoid tissues and endothelium of afferent lymphatics, directing CCR7+ cells. More recently, others and we have demonstrated that SLC/CCL21 is up‐regulated in different skin inflammatory conditions. Thereafter, this molecule is much more than a constitutive chemokine, which could play a role in effector and regulatory immune functions.
Effect of immunotherapy on asthma progression, BHR and sputum eosinophils in allergic rhinitis
Authors: Polosa R. , Li Gotti F. , Mangano G. , Paolino G. , Mastruzzo C. , Vancheri C. , Lisitano N. , Crimi N.
Published: October 2004

Background:  Bronchial hyperresponsiveness (BHR) and airway inflammation are frequently associated with allergic rhinitis, and may be important risk factors for the development of asthma. Specific immunotherapy (SIT) reduces symptom in subjects with allergic rhinitis, but the mechanisms are not clear.

Aims of the study:  To assess the effect of Parietaria‐SIT on asthma progression, rhinitic symptoms, BHR, and eosinophilic inflammation.

Methods:  Nonasthmatic subjects with seasonal rhinitis were randomly assigned to receive Parietaria pollen vaccine (n = 15) or matched placebo (n = 15). Data on symptoms and medication score, BHR to methacholine, eosinophilia in sputum were collected throughout the 3‐year study.

Results:  By the end of the study, in the placebo group, symptoms and medication scores significantly increased by a median (interquartile range) of 121% (15–280) and 263% (0–4400) respectively (P < 0.01), whereas no significant difference was observed in the SIT group. We found no significant changes in sputum eosinophils and BHR to methacholine in both groups throughout the study. Nine of 29 participants developed asthma symptoms during the study; of these, only two subjects (14%) in the SIT‐treated group (P = 0.056).

Conclusions:  Parietaria‐SIT reduces symptom and rescue medication scores, but no changes in BHR to methacholine or sputum eosinophilia were observed. Moreover, Parietaria‐SIT appears to prevent the natural progression of allergic rhinitis to asthma, suggesting that SIT should be considered earlier in the management of subjects with allergic rhinitis.
Assessment of the relation between short and intermediate term growth in children with asthma treated with inhaled glucocorticoids
Authors: Wolthers O. D. , Heuck C.
Published: October 2004

Objective:  To assess the relation between short‐term growth and intermediate term growth in children with asthma treated with inhaled glucocorticoids.

Design:  An open 12 months parallel group trial with visits to the clinic on day 1, after 2, 4, 8, 12, 20, 28, 36, 44 and 52 weeks. Setting: Outpatient clinic in a secondary referral centre. Subjects: Sixteen children with asthma aged 9 (6–13) years; 16 matched healthy subjects.

Methods:  Knemometry and stadiometry. Interventions: Dry‐powder inhaled budesonide 200 μg twice daily. Primary outcome measures: Intra‐group comparisons of mean lower leg growth rates. Secondary outcome measures: Inter‐group comparisons of mean lower leg growth rates and intra‐group comparisons of mean height‐standard deviation scores.

Results:  One year mean lower leg growth rate (0.36 mm/week) did not differ from the rates during the 2 (0.27 mm/week; P = 0.23), 4 (0.33 mm/week; P = 0.54), 8 (0.36 mm/week; P = 0.79) or 12 (0.33 mm/week; P = 0.49) weeks intervals in the asthma group. Similarly, in the healthy children 2 (0.56 mm/week; P = 0.63), 4 (0.46 mm/week; P = 0.36), 8 (0.43 mm/week; P = 0.49) and 12 (0.43 mm/week; P = 0.66) weeks mean growth rates did not vary statistically significantly from the 1 year growth rate (0.42 mm/week). Mean lower leg growth rates, however, were consistently lower during all periods in the children with asthma (P = 0.02–0.03). At completion of the study mean height‐standard deviation score in the asthma group (−0.19) was significantly suppressed as compared with the score at study entry (−0.03) (P = 0.02), whereas no statistically significant variation was detected in the control group.

Conclusions:  Short‐term lower leg growth rates are consistent with intermediate term growth rates in group studies in children with asthma treated with inhaled dry powder budesonide 400 μg/day. Short‐term group knemometry should be an integral part of growth evaluations of new inhaled glucocorticoids, doses and inhalation devices in children with asthma.
Allergy to jackfruit: a novel example of Bet v 1‐related food allergy
Authors: Bolhaar S. T. H. P. , van Ree R. , Bruijnzeel‐Koomen C. A. F. M. , Knulst A. C. , Zuidmeer L
Published: October 2004

Background:  Jackfruit allergy has been reported just once. It is unknown whether this food allergy is caused by direct sensitization or cross‐sensitization to pollen allergens.

Objective:  Establish whether jackfruit allergy is linked to birchpollen allergy.

Methods:  Two jackfruit allergic patients and five patients with birchpollen‐related apple allergy were recruited. Sensitization to pollen and plant foods was assessed by skin prick test (SPT), radio‐allergosorbent test (RAST) and immunoblot. RAST analysis was performed for Bet v 1 and Mal d 1. Cross‐reactivity was evaluated by RAST and immunoblot‐inhibition. Biological activity of immunoglobulin E (IgE) was measured by basophil histamine release. Allergy to jackfruit was evaluated by double‐blind placebo‐controlled food challenge (DBPCFC) or open challenge (OC).

Results:  In both patients DBPCFC confirmed the reported jackfruit allergy. SPT was 41 and 27 mm2 and specific IgE to jackfruit was 5.9 and 0.8 IU/ml, respectively. Immunoblot analysis revealed IgE reactivity at Mr of approximately 17 kDa. The Bet v 1‐related nature of this allergen in jackfruit was demonstrated by RAST and immunoblot inhibition. To assess whether jackfruit allergy might be common in patients with combined birchpollen‐fruit allergy, five such patients underwent an OC with jackfruit. All five had OA‐like symptoms.

Conclusions:  Jackfruit allergy can be added to the list of birchpollen‐related food allergies. Increased consumption of this fruit will result in a rise in allergic reactions.
A clinical survey on compliance in the treatment of rhinitis using nasal steroids
Authors: Loh C. Y. , Chao S. S. , Chan Y. H. , Wang D. Y.
Published: October 2004

Background:  In the treatment of persistent rhinitis, the observed efficacy with intranasal steroids in clinical practice often falls short of that reported in clinical trials. We postulate that this could be due to patient non‐compliance and thus designed this study to evaluate the impact of patient compliance on the efficacy of treatment in patients with persistent rhinitis.

Methods:  Sixty‐three consecutive adult patients with allergic and non‐allergic rhinitis, treated with intranasal triamcinolone acetonate, were included in the study. Compliance was determined both by direct questioning and by measuring the weight of medication consumed (WMC) after 30 days of therapy. Nasal symptom scores were used to determine treatment efficacy.

Results:  Forty‐nine patients (77.8%) reported a forgetfulness of using medication for a few times (1–5 times) during the treatment period. Less than 50% compliance was reported by one patient (1.6%) but detected in seven patients (11%) by WMC. There was a significant (P < 0.001) improvement in mean total symptom score before (7.45 ± 1.99) and after (3.59 ± 2.72) treatment in patients with WMC of at least 50%, but not when WMC was <50% (8.43 ± 1.72 vs 6.29 ± 2.43; P = 0.114). With >50% WMC, the positive predictive values for relief of each symptom were rhinorrhoea: 78%, nasal itch: 70%, nasal obstruction: 67% and sneezing: 65%.

Conclusion:  Patients compliance has a significant impact on treatment efficacy with intranasal steroids. There is a discrepancy between reported and actual compliance. It is thus important to establish the actual compliance when evaluating patients who fail to respond to therapy.
Neurogenic mechanisms in bronchial inflammatory diseases
Authors: Groneberg D. A. , Quarcoo D. , Frossard N. , Fischer A.
Published: October 2004

Neurogenic inflammation encompasses the release of neuropeptides from airway nerves leading to inflammatory effects. This neurogenic inflammatory response of the airways can be initiated by exogenous irritants such as cigarette smoke or gases and is characterized by a bi‐directional linkage between airway nerves and airway inflammation. The event of neurogenic inflammation may participate in the development and progression of chronic inflammatory airway diseases such as allergic asthma or chronic obstructive pulmonary disease (COPD). The molecular mechanisms underlying neurogenic inflammation are orchestrated by a large number of neuropeptides including tachykinins such as substance P and neurokinin A, or calcitonin gene‐related peptide. Also, other biologically active peptides such as neuropeptide tyrosine, vasoactive intestinal polypeptide or endogenous opioids may modulate the inflammatory response and recently, novel tachykinins such as virokinin and hemokinins were identified. Whereas the different aspects of neurogenic inflammation have been studied in detail in laboratory animal models, only little is known about the role of airway neurogenic inflammation in human diseases. However, different functional properties of airway nerves may be used as targets for future therapeutic strategies and recent clinical data indicates that novel dual receptor antagonists may be relevant new drugs for bronchial asthma or COPD.
Diagnosis of nonimmediate reactions to β‐lactam antibiotics
Authors: Romano A. , Blanca M. , Torres M. J. , Bircher A. , Aberer W. , Brockow K. , Pichler W. J. , Demoly P. ,   ENDA and the EAACI interest group on drug hypersensitivity
Published: October 2004

Nonimmediate manifestations (i.e. occurring more than 1 h after drug administration), particularly maculopapular and urticarial eruptions, are common duringβ‐lactam treatment. The mechanisms involved in most nonimmediate reactions seem to be heterogeneous and are not yet completely understood. However, clinical and immunohistological studies, as well as analysis of drug‐specific T‐cell clones obtained from the circulating blood and the skin, suggest that a type‐IV (cell‐mediated) pathogenic mechanism may be involved in some nonimmediate reactions such as maculopapular or bullous rashes and acute generalized exanthematous pustulosis. In the diagnostic work‐up, the patient's history is fundamental; patch testing is useful, together with delayed‐reading intradermal testing. The latter appears to be somewhat more sensitive than patch testing, but also less specific. In case of negative allergologic tests, consideration should be given to provocation tests, and the careful administration of the suspect agents. With regard toin vitrotests, the lymphocyte transformation test may contribute to the identification of the responsible drug.

Under the aegis of the European Academy of Allergology and Clinical Immunology (EAACI) interest group on drug hypersensitivity and the European Network for Drug Allergy (ENDA), in this review we describe the general guidelines for evaluating subjects with nonimmediate reactions toβ‐lactams.
Limit load of throughwall cracked elbows: comparison of test results with theoretical predictions
Authors: CHATTOPADHYAY J. , TOMAR A. K. S. , DUTTA B. K. , KUSHWAHA H. S.
Published: October 2004

Integrity assessment of piping components with postulated cracks is very important for safe and reliable operation of power plants. Pipe bends or elbows are among the very important piping components in any power plant. The existing equations of limit load of elbows have various shortcomings. Additionally, there is only limited test data on elbows in open literature. A comprehensive experimental and analytical programe has been undertaken at Reactor Safety Division (RSD) of Bhabha Atomic Research Centre (BARC) to conduct fracture tests on throughwall cracked elbows and to also propose new limit load equations for a throughwall cracked elbows. The prediction from these newly proposed limit load equations agreed well with the test results. The present paper describes the elbow test specimens, the test setup, the test results and provides a description of the elastic–plastic finite‐element analysis. The newly proposed collapse moment equations for throughwall circumferentially cracked elbows are presented and a comparison of test results with theoretical predictions is made to validate the equations.
Attenuation of conducted vasodilatation in rat mesenteric arteries during hypertension: role of inwardly rectifying potassium channels
Authors: Goto Kenichi , Rummery Nicole M. , Grayson T. Hilton , Hill Caryl E.
Published: October 2004

The present study was designed to elucidate whether the conduction of vasomotor responses mediated by endothelium‐derived hyperpolarizing factor (EDHF) in rat mesenteric arteries is altered during hypertension. Iontophoresed acetylcholine (ACh; 500 ms) caused EDHF‐mediated hyperpolarization and vasodilatation at the local site and these responses spread through the endothelium to remote sites in 12‐week‐old Wistar‐Kyoto rats (WKY). Conducted responses were significantly attenuated in age‐matched spontaneously hypertensive rats (SHR) although the rate of decay with distance did not change. Inhibition of inwardly rectifying potassium (Kir) channels (30 μm barium) eliminated the difference between WKY and SHR by attenuating conducted responses in WKY but not SHR. At the local site, barium (30 μm) significantly reduced the duration but not the amplitude of ACh‐induced hyperpolarization in WKY only. Barium had no effect when the iontophoretic stimulus was reduced to 350 ms. After blockade of EDHF in SHR, ACh elicited a depolarization which our indirect data suggest spreads along the vessel in the endothelium. Messenger RNA expression of Kir2.0 genes did not differ between the strains nor did the amplitude of K+‐induced hyperpolarization, which was abolished by disruption of the endothelium. Immunohistochemistry revealed a decrease in connexin (Cx)37 but not Cx40 or Cx43 protein in endothelial cells of SHR compared to WKY. Results suggest that conduction of EDHF‐mediated responses in WKY, but not in SHR, is facilitated by activation of Kir channels at the site of ACh application and not by differences in endothelial connexin expression. Lack of Kir channel involvement in hypertension may result from reduction in the duration of the hyperpolarization due to the development of ACh‐mediated depolarization, rather than to any difference in Kir subunit expression or function.
Dissociation of slow waves and fast oscillations above 200 Hz during GABA application in rat somatosensory cortex
Authors: Staba Richard J. , Bergmann Peter C. , Barth Daniel S.
Published: October 2004

Fast electrical oscillations (FOs; > 200 Hz), superimposed on vibrissa‐evoked slow potentials, may support rapid sensory integration in neocortex. Yet, while it is well established that the positive/negative (P1/N1) slow wave of the somatosensory evoked potential primarily reflects sequential activation of supragranular and infragranular pyramidal cells mediated chiefly via excitatory chemical synaptic pathways, little is known about the generation of FOs. In this study, laminar current source–density analysis and principal component analysis indicated that FOs are generated by two dipolar current sources situated in the supra‐ and infragranular layers, similar in laminar location to the two current dipoles associated with the slow wave. However, exogenous GABA application reversibly abolished the N1 slow wave, leaving the P1 intact, while the FO was unaffected by GABA. Furthermore, reductions in both supra‐ and infragranular cortical unit discharge during application of GABA suggests that FO generation is not dependent on the same intracortical synaptic circuits that are associated with the N1 slow wave. These data suggest a marked functional dissociation between neural mechanisms underlying the slow and fast components of the vibrissa‐evoked response.
Two-Phase Flow and Heat Transfer in Rectangular Micro-Channels
Authors: Qu Weilin , Yoon Seok-Mann , Mudawar Issam
Published: October 2004

Knowledge of flow pattern and flow pattern transitions is essential to the development of reliable predictive tools for pressure drop and heat transfer in two-phase micro-channel heat sinks. In the present study, experiments were conducted with adiabatic nitrogen-water two-phase flow in a rectangular micro-channel having a 0.406×2.032mm2 cross-section. Superficial velocities of nitrogen and water ranged from 0.08 to 81.92 m/s and 0.04 to 10.24 m/s, respectively. Flow patterns were first identified using high-speed video imaging, and still photos were then taken for representative patterns. Results reveal the dominant flow patterns are slug and annular, with bubbly flow occurring only occasionally; stratified and churn flow were never observed. A flow pattern map was constructed and compared with previous maps and predictions of flow pattern transition models. Features unique to two-phase micro-channel flow were identified and employed to validate key assumptions of an annular flow boiling model that was previously developed to predict pressure drop and heat transfer in two-phase micro-channel heat sinks. This earlier model was modified based on new findings from the adiabatic two-phase flow study. The modified model shows good agreement with experimental data for water-cooled heat sinks.
Compact Modeling of Fluid Flow and Heat Transfer in Pin Fin Heat Sinks
Authors: Kim Duckjong , Kim Sung Jin , Ortega Alfonso
Published: October 2004

In this work, a novel compact modeling method based on the volume-averaging technique is presented. Its application to the analysis of fluid flow and heat transfer in pin fin heat sinks are further analyzed. The pin fin heat sink is modeled as a porous medium. The volume-averaged momentum and energy equations for fluid flow and heat transfer in pin fin heat sinks are obtained by using the local volume-averaging method. The permeability, the Ergun constant, and the interstitial heat transfer coefficient required to solve these equations are determined experimentally and correlations for them are presented. To validate the compact model proposed in this paper, 20 aluminum pin fin heat sinks having a 101.43 mm×101.43 mm base size are tested with an inlet velocity ranging from 1 m/s to 5 m/s. In the experimental investigation, the heat sink is heated uniformly at the bottom. Pressure drop and heat transfer characteristics of pin fin heat sinks obtained from the porous medium approach are compared with experimental results. Upon comparison, the porous medium approach is shown to predict accurately the pressure drop and heat transfer characteristics of pin fin heat sinks. Finally, for minimal thermal resistance, the optimum surface porosities of the pin fin heat sink are obtained under constraints on pumping power and heat sink size. The optimized pin fin heat sinks are shown to be superior to the optimized straight fin heat sinks in thermal performance by about 50% under the same constraints on pumping power and heat sink size.
On the Thermal Performance Characteristics of Three-Dimensional Multichip Modules
Authors: Chen Wen-Hwa , Cheng Hsien-Chie , Lin Chih-Han
Published: October 2004

The study explores the thermal performance of three-dimensional (3-D), vertically stacked multi-chip modules (the so-called MCM-V) in natural convection through finite element (FE) modeling and experimental validation. A modified Infrared (IR) thermography-based thermal characterization (IRTTC) technique that integrates a 3-D heat conduction FE modeling and a two-phased IR thermography measurement process is proposed. In contrast to the conventional IRTTC technique (Chen et al. [1]), the technique can improve the resolution of the captured thermal images so as to attain better characterization of the chip junction temperature. The effectiveness of the proposed modified IRTTC technique is confirmed by means of the thermal test die (TTD) measurement. Furthermore, for facilitating subsequent parametric thermal design, a direct FE approach (DFEA) is also introduced. The DFEA simply incorporates existing empirical models for heat transfer (HT) coefficients to describe the surface heat transfer to the ambient through convection and radiation in the proposed heat conduction FE model. Through the modified IRTTC technique and the TTD measurement, the validity of the proposed FE modeling, including the proposed heat conduction FE model and the applied empirical models for HT coefficients, is verified. With the validated FE modeling, four different chip stacking structures of MCM-V packages, including the thick-die-attach, pyramid, cross and dummy-die types, are investigated. In addition, some essential design factors, affecting the thermal performance of the MCM-V, are also extensively explored through parametric FE study. Eventually, an extensive thermal design guideline is accordingly provided.
Analysis of the Micro-Mechanical Properties in Aged Lead-Free, Fine Pitch Flip Chip Joints
Authors: Liu Changqing , Conway Paul , Li Dezhi , Hendriksen Michael
Published: October 2004

This research seeks to characterize the micro-mechanical behavior of Sn-Ag-Cu solder bumps/joints generated by fine pitch flip chip assembly processes. The solder bumps and joints that were aged at either 80 °C or 150 °C for up to 440 hours (∼18 days); have been studied by an analysis using micro-shear testing and nano-indentation techniques. The shear test of the aged bumps showed a slight increase in shear strength after an initial period of aging (∼50 hours) as compared to the non-aged bumps, but a decrease after longer aging (e.g. 440 hours). A brittle Ag3Sn phase formed as large stick-like features in the body of bulk solder and near the interface of solder/UBM during the initial aging, and is attributed with the increase of shear strength, along with the refinement of the bump microstructure. However, as the time of aging extended, the solder bumps were softened due to grain growth and re-crystallization. It was found that the formation of brittle phases in the body of solder and along the interfaces caused localized stress concentration, which can significantly affect joint reliability. In addition, Nano-testing identified a large lamellar Au-rich structure, formed in the solder and interface of the solder/PCB in the joints after the aging process at 150 °C. These are believed to be detrimental to joint reliability.
Coherent bottom reverberation: Modeling and comparisons with at-sea measurements
Authors: Cole Bernard , Davis James , Leen William , Powers William , Hanrahan John
Published: October 2004

Shallow water bottom reverberation results collected with a hull-mounted sonar exhibit coherence effects that manifest themselves as reverberation patterns in time—analogous to the well-known Lloyd mirror effect that appears in transmission loss as a function of range for shallow sources or receivers. Moreover, the reverberation peaks and nulls arising from the coherent phasing of the propagation paths are evident both in the reverberation envelopes obtained with short pulses and in the matched filter responses for longer pulse lengths. These “coherent” properties of the reverberation deviate from the usual assumptions governing reverberation. Modified assumptions produce coherent reverberation intensity modeled results that match the coherent effects observed in measurements. Finally, the coherent peaks and nulls arising from the phenomenon are shown to produce non-Rayleigh reverberation amplitude distributions in both the measured reverberation and modeled results (increasing the probability of false alarms in this type of interference) unless the reverberation is detrended by the Lloyd mirror pattern.
Training native English speakers to perceive Japanese length contrasts in word versus sentence contexts
Authors: Hirata Yukari
Published: October 2004

This study investigated whether native speakers of American English with no knowledge of Japanese could learn to perceive Japanese vowel and consonant length distinctions through auditory training with immediate feedback. One group of participants was trained to identify the number of moras in Japanese words spoken in isolation (word training), and another group in sentences (sentence training). Trained groups’ pretest and post-test scores in the words-in-isolation context (word context) and the words-in-sentences context (sentence context) were compared to those of an untrained control group. The questions addressed were whether there was an overall effect of training, and whether there were differential effects of two types of training. Both trained groups showed similar improvement in their overall test scores. The results suggested that learning in one context generalized to the other. However, an advantage of sentence training over word training was found: at the post-test, there was a greater difference between the scores of the two contexts for the word-training group than for the sentence-training group. The results are discussed in terms of the factors that might contribute to the differences in second language learning between the word and the sentence contexts.