bluuebunny/crossref_metadata_2025_split huggingface dataset:
A simplified statistical method for local INR using linear regression
Authors: Poller L. , Barrowcliffe T. W. , Van den Besselaar A. M. H. P. , Jespersen J. , Tripodi A. , Houghton D. 
Published: November 2003

A simplified method of International Normalized Ratio (INR) derivation using linear regression of certified INR plotted against local prothrombin time (PT) results has been compared with INR from conventional orthogonal regression. Linear regression assumes error only with the local PT results whereas orthogonal regression assumes error with both reference and local results. The reliability of local INR derivation using lyophilized plasmas has been assessed in a collaborative study. INR from conventional fresh plasma International Sensitivity Index (ISI) calibrations have been compared with INR from calibrations with two types of lyophilized plasma, artificially depleted and coumarin.Although calibration slopes differed with the two types of analysis and the different lyophilized plasmas, both gave reasonable approximations to fresh plasma ISI calibrations. With orthogonal regression the overall percentage INR deviation was 5.25% with the artificially depleted plasmas and 6.85% for the results with lyophilized coumarins. With the linear regression, deviation was 8.40% for the artificially depleted plasmas and 5.05% for coumarin‐treated patients' lyophilized plasmas. The simpler regression method appears to be worthy of further study as the present report has demonstrated that if the calibrant plasmas are accurately certified with the thromboplastin International Reference Plasma (IRP) results approximate to the conventionally determined INR using the manual PT technique. Coagulometers require further assessment.
A method for canine nasal mucosa superfusion, in vivo; evidence that pseudomonas‐induced neutrophil migration is inhibited by α2‐adrenoceptor agonist
Authors: STJÄRNE P. , AGUSTI C. , CARDELL L. O. , WAGSTAFF S. , NADEL J. A. 
Published: November 2003

SummaryMethods and Results
A method for isolating and superfusing a segment of the nasal cavity in the anaesthetized dog was developed. Introduction of Pseudomonas aeruginosa supernatant (PA), which is known to induce IL‐8 release, resulted in a marked time‐dependent exponential increase in neutrophil recruitment to the nasal chamber. When oxymetazoline (final concentration. 10‐5 M), was added to the superfusate, the PA induced‐neutrophil migration was inhibited; the addition of benzalchoniul chloride to the superfusate had no effect on the PA induced‐neutrophil migration.Conclusion
We conclude that a α2 adrenoceptor agonist profoundly inhibits neutrophil migration in response to bacterial products. Our novel method allows continuous introduction of stimuli and monitoring of responses in the nasal mucosa.
Predictability of early atopy by cord blood‐IgE and parental history
Authors: BERGMANN R. L. , EDENHARTER G. , BERGMANN K. E. , GUGGENMOOS‐HOLZMANN I. , EORSTER J. , BAUERl C. P. , WAHN V. , ZEPP F. , WAHN U. 
Published: November 2003

SummaryBackground
Atopic family history and cord blood IgE have been used as predictors of atopic disease in newborns for about 20 years, but at least for cord blood IgE the sensitivity has been shown to be very low. The objective of this paper was to evaluate whether parental history and cord blood‐IgE were more accurate predictors for the appropriate atopic phenotypes in the infants rather than for any atopy.Methods
A total of 1314 newborn infants was recruited in six German obstetric departments in 1990 and followed‐up for 2 years. Four hundred and ninty‐ninc (38%) were at high risk for atopy with at least two first degree atopic family members and/or elevated cord‐blood IgE concentrations.Results
The cumulative incidence of atopic dermatitis over the first 2 years of life (AD24) amounted to 20. 1%, and there was a significant association with AD history of the mother (OR 2.5, 95%‐Cl 1.46–4.26) and of the father (OR 3.53, 95%cC1 1.90–6.54). The cumulative incidence of recurrent wheezing in the first 2 years of life (RW24) amounted to 16.1%, and was positively associated with asthma history (OR 2.11, 95%CI 1.33–3.60) and sensitization history (OR 1.64, 95%C1 1.34–2.36) of the mother, but with neither for the father. RW24 was less prevalent in girls than in boys (OR 0.64. 95%Cl 0.47–0.89). Thirty‐one per cent of infants were sensitized (CAP test value > 0.35 kU/L) against at least one of nine food or inhalative allergens (S24) and this was signilicantly associatcd with cord blood‐IgE value (OR 2.43, 95%C1 1.69–3.49). and sensitization history of the mother (OR 1.64, 95%CI 1.18–2.41). Using multiple logistic regression analysis, the prediction of AD24 by AD of parents, of RW24 by asthma of parents, and of sensitization by cord blood IgE was of low accuracy.Conclusion
The predictive capacity of parental history and cord blood IgE is not high enough to recommend them as screening instruments for primary prevention. The majority of atopic manifestations and of sensitization occur in infants with no demonstrable risk at birth.
Allergen‐induced CD30 expression on T cells of atopic asthmatics
Authors: LEONARD C. , TORMEY V. , FAUL J. , BURKE C. M. , POULTER L. W. 
Published: November 2003

SummaryBackground
The importance of TH2‐type T cell cytokines in atopic disease is widely accepted. CD30, a member of the TNF/NGF receptor superfamily, is expressed on a proportion of activated CD45RO+ T cells and has been proposed as a marker for TH2 phenotype. CD30 ligand‐CD30 interaction has been shown to positively influence development of the TH2 phenotype, and serum levels of soluble CD30 (sCD30) have been used as prognostic markers in HIV, SLE, Epstein‐Barr Virus infection and Hodgkin's Lymphoma but not as yet in allergic disease.Objectives
To establish if serum levels of sCD30 are elevated in atopic asthma and determine whether allergen‐induced proliferation/activation of PBMCs from atopic asthmatics promotes CD30 expression on CD4+ T lymphocytes. Further, to determine if expression of CD30 and sCD30 correlate with disease severity.Methods
Eighteen atopic asthmatics were each assigned a symptomatic disease score based on symptoms and bronchodilator rescue usage. Serum sCD30 was measured in peripheral blood by ELISA. PBMCs from atopic asthmatics were analysed with flow cytometry to obtain the proportions of CD4 T cells expressing CD45RO and CD30. The cells were then cultured for 10 days with IL‐2 with or without house dust mite antigen. A proliferation index was recorded and expression of CD30 and CD45RO retested. As a control, stimulation with PHA was used. Results with patients’ PBMCs were compared with results of a parallel analysis of PBMCs from non‐atopic healthy controls.Results
Serum sCD30 was elevated in the 18 atopic asthmatics compared with a group of normal subjects but levels did not correlate with symptomatic disease activity. CD4CD45RO expression was low (14%) in atopic asthmatic peripheral blood but increased to 41% after 10 days culture with allergen. The CD4:CD8 ratio increased after Der p stimulation. A significant rise in the percentage of CD44 T cells expressing surface CD30 (29%) was seen along with increased mean fluorescence intensity. Both these results correlated with symptomatic disease severity score. Non‐specific PHA stimulation failed to significantly affect CD30 expression.Conclusions
There is a specific response to allergen in atopic asthma which causes significant increases in CD30 expression. This may correlate with disease severity.
Comparison of inflammatory cell counts in asthma: induced sputum vs bronchoalveolar lavage and bronchial biopsies
Authors: GROOTENDORST D. C. , SONT J. K. , WILLEMS L. N. A. , KLUIN‐NELEMANS J. C. , VAN KRIEKEN J. H. J. M. , VESELIC‐CHARVAT M. , STERK P. J. 
Published: November 2003

SummaryBackground
Induced sputum potentially allows monitoring of airway inflammation in patients with asthma in a non‐invasive way. However, the relationship between the cellular content in sputum and airway tissue has not been fully clarified.Objective
We compared the cellular compositions of hypertonic saline‐induced sputum, bronchoalveolar lavage fluid (BAL) and bronchial biopsies in 18 clinically stable patients with mild to moderate atopic asthma (baseline FEV1: range 61–114%pred, PC20 methacholine: 0.04–4.7 mg/mL). They were treated with inhaled short‐acting bronchodilators on demand, with (n = 8) or without (n= 10) regular inhaled steroids.Methods
Each patient underwent sputum induction and fiberoptic bronchoscopy on separate days in random order. Differential cell counts of induced sputum, bronchoalveolar lavage and bronchial wash were determined on May‐Grünwald‐Giemsa stained cytospins. Flow cytometry was performed on sputum and BAL samples. Immunohistochemical techniques were used to stain inflammatory cells in 6 μm cryostat sections of bronchial biopsies.Results
Sputum cell differentials were not different between the patients with and without inhaled steroids, and showed a median value of 19.4% squamous cells, with 1.0% eosinophils, 3.3% lymphocytes, 28.7% neutrophils, 49.4% macrophages and 6.9% cylindric epithelial cells (in percentage non‐squamous cells). The percentage eosinophils in sputum was significantly correlated with their percentage in bronchial wash(Rs= 0.52, P = 0.03) and in BAL (Rs= 0.55,P = 0.02), whilst there was a trend towards such a correlation between the number of eosinophils/mL sputum and the number of EG2+ eosinophils/mm2 lamina propria in bronchial biopsies (Rs= 0.44,P= 0.07). In addition, the percentage of CD4+ lymphocytes correlated between sputum and BAL (Rs= 0.55, P= 0.03).Conclusion
We conclude that the eosinophil counts in hypertonic saline‐induced sputum from patients with asthma are related to those in bronchial wash and BAL and, to a lesser extent, with the counts in bronchial biopsies. This suggests that induced sputum can be used to monitor the presence and severity of airway inflammation in asthma.
Clinical, parasitological and immunological features of canal cleaners hyper-exposed to Schistosoma mansoni in the Sudan
Authors: Satti M Z , Sulaiman S M , Homeida M M A , Younis S A , Ghalib H W 
Published: November 2003

SUMMARY
The present work was a longitudinal study on Schistosoma mansoni infection in occupationally hyperexposed canal cleaners in the Sudan and the influence of therapy on the parasitological and humoral immune parameters. Chronically infected canal cleaners (n=28) were more resistant to reinfection (Fisher’s exact test, P&lt;0.05) than newly recruited canal cleaners (n=17). Chronically infected canal cleaners had a significantly higher degree of Symmers' fibrosis (χ2=19.1, P&lt;0.0001), significantly larger portal vein diameter (P&lt;0.05) and enlarged spleen (χ2=4.2, P&lt;0.05) than recently infected, newly recruited canal cleaners. ELISA was used to detect IgG, IgA and IgM in response to whole worm homogenate (WWH) and cercarial homogenate (CH). Chronically infected canal cleaners had significantly higher IgG to WWH antigen than newly recruited canal cleaners and normally exposed individuals (P&lt;0.05), while both chronically infected and newly recruited canal cleaners had higher IgG levels to CH antigen than normally exposed individuals (P&lt;0.05). The newly recruited canal cleaners had a significantly higher IgM level to CH antigen than chronically infected canal cleaners (P&lt;0.05). The IgG level to WWH antigen increased significantly after treatment in newly recruited canal cleaners and normally exposed individuals (P&lt;0.05). The IgA level to CH antigen increased significantly after treatment in the chronically infected group (P&lt;0.05). Comparison of the serological parameters between the different study groups with regards to infection and treatment is discussed.
Differential spontaneous expression of mRNA for IL-4, IL-10, IL-13, IL-2 and interferon-gamma (IFN-γ) in peripheral blood mononuclear cells (PBMC) from atopic patients
Authors: Esnault S , Benbernou N , Lavaud F , Shin H C , Potron G , Guenounou M 
Published: November 2003

SUMMARY
Distinct cytokine-producing T cell subsets are well known to play a major role in IgE production and to be differentially regulated in allergic patients, although the characterization of the type 1/type 2 cytokine pattern in PBMC during allergic responses remains to be clearly defined. The aim of this study was to determine whether different cytokine profiles are observed directly in PBMC of atopic donors. We attempted to study several cytokines (IL-2, IFN-γ, IL-4, IL-10 and IL-13) using not only ELISA but also polymerase chain reaction (PCR) techniques, because the frequency of cytokine-producing cells in peripheral blood is very low. All the patients were selected during their acute symptomatologic phase. Data showed a significantly higher production of IL-4 (P=0.05) and IL-10 (P&lt;0.005) as determined by ELISA in phytohaemagglutinin (PHA)/phorbol myristate acetate (PMA)-stimulated mononuclear cells of atopic donors compared with controls, although spontaneous IL-4 production without stimulation was never detected within either atopic or control groups. The reverse-transcriptase (RT)-PCR technique appeared to be advantageous in that it allowed the detection of the spontaneous expression of cytokine mRNA in cells without stimulation. We found a clear expression of IL-4 mRNA spontaneously in all atopic patients, whereas normal donors in most cases did not show specific signals (P&lt;0.0001). Less differences between atopic subjects and controls were found in IL-10 mRNA expression. Although the technique of RT-PCR amplification used in this study is semiquantitative, a reproducible and significant (P&lt;0.001) enhancement of IL-10 mRNA expression was observed in atopic donors. A heterogeneous expression of IL-13 mRNA was observed in individuals from the two groups studied, although mean levels in atopic donors were slightly enhanced compared with controls (P=0.02). Furthermore, we did not observe any alteration in the expression of the type 1-derived cytokines such as IFN-γ and IL-2. In addition, we showed a lack of correlation between the expression of serum IgE (total or specific) and spontaneous IL-4 mRNA expression. This study showed a tendency of PBMC from atopic donors to express a type 2-like cytokine pattern, with IL-4 as the most discriminatory cytokine. Additionally, as the level of serum IgE has a low predictive value in allergic disease, and as the elevated expression of IL-4 that we found was not correlated with serum IgE, we could strongly suggest that the measurement of IL-4 in blood mononuclear cells may be of great value in the analysis of allergic responses in atopic donors.
Transforming growth factor-beta 1 (TGF-β1) down-regulates IgA Fc-receptor (CD89) expression on human monocytes
Authors: Reterink T J F , Levarht E W N , Klar-Mohamad N , Van Es L A , Daha M R 
Published: November 2003

SUMMARY
IgA is the predominant immunoglobulin in human secretions and the second most important immunoglobulin in the circulation on a quantitative basis. The clearance of IgA is dependent on the function of at least three types of receptors. One of these receptors recognizes the Fc portion of the IgA molecule, FcαR, which has been cloned recently. FcαR, also designated CD89, is found on a number of cells, including human glomerular mesangial cells, and monocytes. In this study we analysed the effect of TGF-β1, a cytokine with strong immunosuppressive function, on the expression of CD89 on freshly isolated monocytes. We found that TGF-β1 down-regulates CD89 expression on human peripheral blood monocytes in a dose-dependent fashion. Optimal down-regulation occurred at a concentration of 5 ng/ml. The down-regulation of CD89 by TGF-β1 is linear in time, with a mean down-regulation of 34 ± 13% after 24 h. Also at the mRNA level, CD89 expression was down-regulated by TGF-β1, suggesting regulation of CD89 at the transcriptional level. Monocytes pre-treated with TGF-β1 displayed a reduced response to IgA, as measured by IL-6 production by monocytes, in contrast to monocytes pre-treated with medium alone. These results suggest an important role for TGF-β1 in the regulation of CD89. This down-regulation may have direct consequences for the handling of IgA by human monocytes.
Effects of in vitro hyperthermia on proliferative responses and lymphocyte activity
Authors: Huang Y H , Haegerstrand A , Frostegård J 
Published: November 2003

SUMMARY
Fever is induced by both exogenous products like endotoxin, and endogenous cytokines, most notably IL-1 and IL-6, and tumour necrosis factor (TNF). These mediators are believed to interact with the hypothalamus, to induce enhanced body temperature. However, little is known about the biological effects of fever on the function of the immune system. We here report that a 90-min pulse of mild hyperthermia (40°C) induces enhanced proliferation of peripheral blood mononuclear cells (PBMC). This proliferative response was completely inhibited by antibodies to MHC class II, which had no effect on mitogen-induced proliferation of PBMC. The enzyme-linked immunospot (ELISPOT) assay is a sensitive method for detection of single cells secreting antibodies or cytokines. A 90-min pulse of mild hyperthermia (40°C) induced a significantly enhanced immunoglobulin production in PBMC, as determined by ELISPOT, indicating B cell activation. The T cell cytokine pattern both with and without stimulation with hyperthermia differed between individuals. Enhanced interferon-gamma (IFN-γ) secretion was noted at 39–41°C. This IFN-γ response was inhibited by antibodies to MHC class II and thus was MHC class II-restricted and dependent on antigen-presenting cells. None of the individuals tested showed IL-4 response after stimulation with hyperthermia. These findings favour the notion that fever may play an important role in immune responses, and it is possible that fever may act as a physiological adjuvant, with effects on the immune system both in infection and inflammation of other origins.
Epitope mapping of anti-glomerular basement membrane (GBM) antibodies with synthetic peptides
Authors: Hellmark T , Brunmark C , Trojnar J , Wieslander J 
Published: November 2003

Abstract
Autoantibodies to the non-collagenous (NC1) domain of the α3(IV)-chain of type IV collagen are found in sera from patients with anti-GBM nephritis. These antibodies have been shown to be pathogenic. In this study the antibody specificity has been investigated in patients with Goodpasture’s syndrome and from a patient with atypical anti-GBM antibodies, recognizing the α1(IV)-chain only. Overlapping synthetic peptides, covering the complete NC1 domains of the α1(IV)- and α3(IV)-chains were used in sandwich ELISA and competitive ELISA. None of the Goodpasture sera showed reactivity to the synthetic peptides. However, antibodies from the patient with atypical anti-GBM antibodies recognized a 20 amino acid peptide from the α1(IV)-chain. The reactive peptide was further narrowed down with glycine substitution of the different amino acids. We have localized the epitope to the four last C-terminal amino acids of the α1(IV)-chain, with the sequence 1754-MRRT. The two arginine residues were found to be essential for antibody binding. Threonine is important, while methionine is of less importance. These four amino acids are also determined to be the smallest peptide that could inhibit the binding of the autoantibodies to the native α1(IV)-chain. This study shows that overlapping peptides can be used to map linear epitopes. However, for conformational epitopes such as the Goodpasture epitope, other methods must be used. It would be prognostically important to know the fine specificity of anti-GBM antibodies, since the patient with anti-α1(IV) antibodies had a mild disease, while the Goodpasture patients with anti-α3(IV) antibodies had a rapidly progressive disease.
Elevation of plasma-soluble tumour necrosis factor receptors (TNF-R) in sarcoidosis
Authors: Nakayama T , Hashimoto S , Amemiya E , Horie T 
Published: November 2003

SUMMARY
Two types of receptor for tumour necrosis factor-alpha (TNF-R), the 55-kD receptor (TNF-RI) and the 75-kD receptor (TNF-RII), have been identified. Soluble TNF-RI (sTNF-RI) and soluble TNF-RII (sTNF-RII) can be measured in culture supernatants and biological fluids, and the role of sTNF-R has been suggested. In the present study, we measured plasma sTNF-RI and sTNF-RII levels in 19 patients with active sarcoidosis by ELISA in order to assess the state of both types of receptors in this disease. Both plasma sTNF-RI and sTNF-RII levels in patients with active sarcoidosis were significantly higher than those in normal control subjects. A longitudinal evaluation of plasma sTNF-RI and sTNF-RII levels showed that the magnitude of changes in sTNF-RII was closely related with the clinical course of sarcoidosis. These results suggest that plasma sTNF-RII levels may be useful parameters for monitoring the clinical course of sarcoidosis as well as markers for identifying disease activity.
IL-12 protects mice against pulmonary and disseminated infection caused by Cryptococcus neoformans
Authors: Kawakami K , Tohyama M , Xie Q , Saito A 
Published: November 2003

SUMMARY
We examined the role of IL-12 in host resistance to Cryptococcus neoformans using a murine model of pulmonary and disseminated infection. In this model, mice were infected intratracheally with viable yeast cells. Mice untreated with IL-12 allowed an uncontrolled multiplication of yeast cells in the lung with infiltrations of few inflammatory cells, and a cryptococcal dissemination to the brain and meningitis by 3 weeks, resulting in death of all animals within 4–6 weeks. IL-12, when administered from the day of tracheal infection for 7 days, induced a marked infiltration of inflammatory cells, consisting mostly of mononuclear cells, and significantly reduced the number of viable yeast cells in the lung. The treatment suppressed brain dissemination, as shown by a marked reduction of yeast cells in the brain and prevention of meningitis. These effects resulted in a significant increase in the survival rate of infected mice. In contrast, late administration of IL-12 commencing on day 7 after instillation of yeast cells failed to protect the mice against infection with C. neoformans. In further experiments, early administration of IL-12 markedly induced interferon-gamma (IFN-γ) mRNA in the lungs of infected mice, while no IFN-γ mRNA was detected without this treatment. Our results indicate that IL-12 is effective when administered in the early period of pulmonary cryptococcal infection.
Detection of nucleosome–IgG immune complexes in ascites from mice transplanted with anti-DNA antibody-secreting hybridomas and in plasmas from MRL-lpr/lpr mice
Authors: Fournié G J 
Published: November 2003

SUMMARY
Autoantibodies directed against chromatin components characterize lupus diseases. Immune complexes made of these autoantibodies bound to nucleosomes released from dead cells could play some pathogenic role. The aims of this study were to investigate if nucleosome–IgG complexes could contaminate IgG anti-DNA MoAb preparations, and if such complexes circulate in lupus diseases. A new method was set up using preformed nucleosome–IgG complexes. Complexes were adsorbed onto microplate through Fc binding and nucleosomal DNA was detected by internal incorporation of labelled nucleotide. Using this method, high amounts of complexes were found in ascites from mice transplanted with anti-DNA antibody-secreting hybridomas. In some ascites, nucleosome was found to be strongly associated with the MoAb, confirming that nucleosome–IgG complexes could contaminate monoclonal autoantibody preparations. In MRL-lpr/lpr mice, nucleosome–IgG complexes were detected at 16–24 weeks of age at a time when kidney lesions are rapidly worsening, raising the question of their pathogenic significance.