bluuebunny/crossref_metadata_2025_split huggingface dataset:
ICL670A: a new synthetic oral chelator: evaluation in hypertransfused rats with selective radioiron probes of hepatocellular and reticuloendothelial iron stores and in iron-loaded rat heart cells in culture
Authors: Hershko Chaim , Konijn Abraham M. , Nick Hans Peter , Breuer William , Cabantchik Zvi Ioav , Link Gabriela 
Published: July 2002

Abstract
ICL670A (formerly CGP 72 670) or 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]- benzoic acid is a tridentate iron-selective synthetic chelator of the bis-hydroxyphenyl-triazole class of compounds. The present studies used selective radioiron probes of hepatocellular and reticuloendothelial (RE) iron stores in hypertransfused rats and iron-loaded heart cells to define the source of iron chelated in vivo by ICL670A and its mode of excretion, to examine its ability to remove iron directly from iron-loaded myocardial cells, and to examine its ability to interact with other chelators through a possible additive or synergistic effect. Results indicate that ICL670A given orally is 4 to 5 times more effective than parenteral deferoxamine (DFO) in promoting the excretion of chelatable iron from hepatocellular iron stores. The pattern of iron excretion produced by ICL670A is quite different from that of DFO and all iron excretion is restricted to the bile regardless of whether it is derived from RE or hepatocellular iron stores. Studies in heart cell cultures have shown a favorable interaction between DFO and ICL670A manifested in improved chelating efficiency of ICL670A, which is most probably explained by an exchange of chelated iron between ICL670A and DFO. These unique chelating properties of ICL670A may have practical implications for current efforts to design better therapeutic strategies for the management of transfusional iron overload.
Telomere length in leukocyte subpopulations of patients with aplastic anemia
Authors: Brümmendorf Tim H. , Maciejewski Jaroslaw P. , Mak Jennifer , Young Neal S. , Lansdorp Peter M. 
Published: July 2002

Abstract
In most human cells, the average length of telomere repeats at the ends of chromosomes provides indirect information about their mitotic history. To study the turnover of stem cells in patients with bone marrow failure syndromes, the telomere length in peripheral blood granulocytes and lymphocytes from patients with aplastic anemia (AA, n = 56) and hemolytic paroxysmal nocturnal hemoglobinuria (n = 6) was analyzed relative to age-matched controls by means of fluorescence in situ hybridization and flow cytometry. The telomere lengths in granulocytes from patients with AA were found to be significantly shorter than those in age-adjusted controls (P = .001). However, surprisingly, telomere length in granulocytes from AA patients who had recovered after immunosuppressive therapy did not differ significantly from controls, whereas untreated patients and nonresponders with persistent severe pancytopenia showed marked and significant telomere shortening. These results support extensive proliferation of hematopoietic stem cells in subgroups of AA patients. Because normal individuals show significant variation in telomere length, individual measurements in blood cells from AA patients may be of limited value. Whether sequential telomere length measurements can be used as a prognostic tool in this group of disorders remains to be clarified.
Effects of the Bcr/abl kinase inhibitors STI571 and adaphostin (NSC 680410) on chronic myelogenous leukemia cells in vitro
Authors: Mow Benjamin M. F. , Chandra Joya , Svingen Phyllis A. , Hallgren Christopher G. , Weisberg Ellen , Kottke Timothy J. , Narayanan Ven L. , Litzow Mark R. , Griffin James D. , Sausville Edward A. , Tefferi Ayalew , Kaufmann Scott H. 
Published: July 2002

Abstract
The adenosine triphosphate binding-site–directed agent STI571 and the tyrphostin adaphostin are undergoing evaluation as bcr/abl kinase inhibitors. The current study compared the effects of these agents on the survival of K562 cells, bcr/abl-transduced FDC-P1 cells, and myeloid progenitors from patients with chronic myelogenous leukemia (CML) compared with healthy donors. Treatment of K562 cells with 10 μM adaphostin resulted in decreased p210bcr/ablpolypeptide levels in the first 6 hours, followed by caspase activation and accumulation of apoptotic cells in less than 12 hours. By 24 hours, 90% of the cells were apoptotic and unable to form colonies. In contrast, 20 μM STI571 caused rapid inhibition of bcr/abl autophosphorylation without p210bcr/abl degradation. Although this was followed by the inhibition of Stat5 phosphorylation and the down-regulation of Bcl-xL and Mcl-1, only 7% ± 3% and 25% ± 9% of cells were apoptotic at 16 and 24 hours, respectively. Instead, the cytotoxic effects of STI571 became more pronounced with prolonged exposure, with IC90values greater than 20 μM and 1.0 ± 0.6 μM after 24 and 48 hours, respectively. Consistent with these results, 24-hour adaphostin exposure inhibited CML granulocyte colony-forming units (CFU-G) (median IC50, 12 μM) but not normal CFU-G (median IC50, greater than 20 μM), whereas 24-hour STI571 treatment had no effect on CML or normal CFU-G. Additional experiments revealed that STI571-resistant K562 cells remained sensitive to adaphostin. Moreover, the combination of STI571 + adaphostin induced more cytotoxicity in K562 cells and in CML CFU-G than either agent alone did. Collectively, these results identify adaphostin as a mechanistically distinct CML-selective agent that retains activity in STI571-resistant cell lines.
Pre- and postnatal parental smoking and wheeze in infancy: cross cultural differences
Authors: Henderson A.J. , Sherriff A. , Northstone K. , Kukla L. , Hruba D. ,   Avon Study of Parents and Children (ALSPAC) Study Team,   European Longitudinal Study of Pregnancy and Childhood (ELSPAC) Co-ordinating Centre
Published: July 2002

In longitudinal cohort studies, the relationships between prenatal and postnatal tobacco smoke exposure and infant wheezing illnesses were compared in two geographically defined populations in Avon, UK and Brno and Znojmo in the South Moravian Region of the Czech Republic.Pregnant females living in defined regions and with expected dates of delivery between defined dates were recruited. Females completed self-report questionnaires during pregnancy and when their infant was 6 months old. For this analysis, responses to questions about smoking during pregnancy, environmental tobacco smoke (ETS) exposure and reported wheezing illnesses of infants at 6 months after birth were used. Odds ratios for wheeze in relation to the smoking variables were calculated with adjustment for potential confounding effects.The prevalence of smoking during pregnancy was higher in Avon (17.5%) than the Czech Republic (7.1%). Exposure of infants to ETS during the first 6 months after birth was also reported to be higher in Avon (35.5%) than the Czech Republic (9.7%). The prevalence of reported wheezing by 6 months of age was 21.4% in Avon and 10.3% in Brno and Znojmo. In Avon, there was a significant relationship between infant wheeze and maternal smoking during pregnancy (odds ratio (95% confidence interval) 1.30 (1.09–1.56), p=0.004) but not with environmental exposure after birth (1.11 (0.98–1.25)). In contrast, in Brno and Znojmo in the Czech Republic, there was a significant relationship between infant wheeze and ETS exposure (1.66 (1.17–2.36), p=0.04) but not with maternal smoking during pregnancy (0.99 (0.64–1.55)).This study demonstrated an apparent difference in the associations between prenatal and postnatal tobacco smoke exposure and infant wheezing illnesses in two populations with different smoking prevalence. The relationships were independent of a number of potential confounding variables that have been associated with infant wheezing. Possible explanations of these observations include dose-related effects of prenatal and postnatal tobacco smoke exposure of infants.
Symptoms of asthma, bronchial responsiveness and atopy in immigrants and emigrants in Europe
Authors: Tobias A. , Soriano J.B. , Chinn S. , Anto J.M. , Sunyer J. , Burney P. 
Published: July 2002

Migration studies on asthma may provide information on its environmental causes. The European Community Respiratory Health Survey has potential advantages due to the number of countries involved, standardized collection of information, assessment of directionality of migration, and availability of physiological data on bronchial responsiveness and atopy.Prevalence rates of symptoms associated with asthma were compared for immigrants, emigrants and nonmigrants living in centres mostly in western Europe. Similar analyses were carried out for bronchial responsiveness (provocative concentration causing a 20% fall in forced expiratory volume in one second and slope) and atopy. Medication and use of health services were also explored.Overall, 1,678 (8.6%) of 19,516 participants were immigrants in the 18 countries participating in the study, of whom 581 were emigrants from one of the participating countries. Rates of asthma symptoms were higher in immigrants (odds ratio (OR): 1.21, 95% confidence interval (CI): 1.00–1.51) and emigrants (OR: 1.31, 95% CI: 0.96–1.51) compared to nonmigrants after controlling for area, sex, age and smoking status. However, bronchial responsiveness and atopy were equally distributed between immigrants, emigrants and nonmigrants. Use of health services was observed to be similar in migrants and nonmigrants with asthma.In the European Community Respiratory Health Survey, migrants reported more asthma symptoms, but had similar bronchial responsiveness, atopy, and use of health services when compared with the nonmigrant population.
Inspiratory flow limitation during sleep in pre-eclampsia: comparison with normal pregnant and nonpregnant women
Authors: Connolly G. , Razak A.R.A. , Hayanga A. , Russell A. , McKenna P. , McNicholas W.T. 
Published: July 2002

Self-reported snoring is common in pregnancy, particularly in females with pre-eclampsia. The prevalence of inspiratory flow limitation during sleep in pre-eclamptic females was objectively assessed and compared with normal pregnant and nonpregnant females.Fifteen females with pre-eclampsia were compared to 15 females from each of the three trimesters of pregnancy, as well as to 15 matched nonpregnant control females (total study population, 75 subjects). All subjects had overnight monitoring of respiration, oxygen saturation, and blood pressure (BP).No group had evidence of a clinically significant sleep apnoea syndrome, but patients with pre-eclampsia spent substantially more time (31±8.4% of sleep period time, mean±sd) with evidence of inspiratory flow limitation compared to 15.5±2.3% in third trimester subjects and <5% in the other three groups (p=0.001). In the majority of pre-eclamptics, the pattern of flow limitation was of prolonged episodes lasting several minutes without associated oxygen desaturation. As expected, systolic and diastolic BPs were significantly higher in the pre-eclamptic group (p<0.001), but all groups showed a significant fall (p≤0.05) in BP during sleep.Inspiratory flow limitation is common during sleep in patients with pre-eclampsia, which may have implications for the pathophysiology and treatment of this disorder.
Treatment of obstructive sleep apnoea with nasal continuous positive airway pressure in stroke
Authors: Wessendorf T.E. , Wang Y-;M. , Thilmann A.F. , Sorgenfrei U. , Konietzko N. , Teschler H. 
Published: July 2002

The prevalence of obstructive sleep apnoea (OSA) following stroke is high and OSA is associated with increased morbidity, mortality and poor functional outcome. Nasal continuous positive airway pressure (nCPAP) is the treatment of choice for OSA, but its effects in stroke patients are unknown.The effectiveness and acceptance of treatment with nCPAP in 105 stroke patients with OSA, admitted to rehabilitation was prospectively investigated. Subjective wellbeing was measured with a visual analogue scale in 41 patients and 24-;h blood pressure was determined in 16 patients before and after 10 days of treatment. Differences were compared between patients who did and did not accept treatment.There was an 80% reduction of respiratory events with concomitant increase in oxygen saturation and improvement in sleep architecture. No serious side-effects were noticed. Seventy-four patients (70.5%) continued treatment at home. Nonacceptance was associated with a lower functional status, as measured by the Barthel Index, and the presence of aphasia. Ten days after initiation of nCPAP, compliant users showed a clear improvement in wellbeing (differences in visual analogue scale (ΔVAS) mean±sd 26±26 mm)versusnoncompliant patients (ΔVAS 2±25 mm, p=0.021). Only the compliant group had a reduction in mean nocturnal blood pressure (ΔBP; −8±7.3 mmHgversus0.8±8.4 mmHg, p=0.037).Stroke patients with obstructive sleep apnoea can be treated effectively with nasal continuous positive airway pressure and show a similar improvement and primary acceptance to obstructive sleep apnoea patients without stroke. Continuous positive airway pressure acceptance is associated with improved wellbeing and decreased nocturnal blood pressure.
Increasing prevalence of bronchial hyperresponsiveness in three selected areas in East Germany
Authors: Frye C. , Heinrich J. , Wjst M. , Wichmann H-E. 
Published: July 2002

The prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergic rhinitis in children was lower in East Germany compared to West Germany. The reasons for this difference are still not understood. This study tested the hypothesis that prevalence of BHR increased in East German children after reunification.Two consecutive cross-sectional surveys of schoolchildren aged 8–14 yrs from three communities in East Germany were carried out in 1992–1993 and 1995–1996. A subsample of 530 and 790 children with complete lung function and cold air challenge data was analysed.The prevalence of BHR increased from 6.4% in 1992–1993 to 11.6% in 1995–1996 (odds ratio (OR): 2.0, 95% confidence interval (CI): 1.3–3.0, adjusted for age, sex, season, community and parental education). No changes were found for asthma, allergic rhinitis or allergic sensitization. In contrast, physician diagnosed bronchitis, pneumonia and frequent colds decreased significantly. The observed increase in the prevalence of BHR was reduced (OR: 1.5, 95% CI: 0.95–2.3) after adjustment for several indoor factors.In conclusion, while the prevalence of nonallergic respiratory diseases seems to decrease, the prevalence of bronchial hyperresponsiveness might be a first indicator of the suspected increase of asthma prevalence in East Germany. The present results give indirect evidence, that less respiratory infections may be associated with higher bronchial hyperresponsiveness.
Factors associated with poor pulmonary function: cross-sectional analysis of data from the ERCF
Authors: Navarro J. , Rainisio M. , Harms H.K. , Hodson M.E. , Koch C. , Mastella G. , Strandvik B. , McKenzie S.G. 
Published: July 2002

The European Epidemiologic Registry of Cystic Fibrosis began collecting longitudinal data on European cystic fibrosis patients in 1994. A cross-sectional analysis was performed to identify the factors associated with low values of % predicted forced expiratory volume in one second (FEV1) upon patient enrolment.Data from 7,010 patients aged ≥6 yrs were included. Clinical conditions, microbiological isolates and medications reported at enrolment or within the following 180 days were analysed for age-specific associations.Factors associated with FEV1that were lower by >10% of pred values were: lower weight for age percentiles, haemoptysis, pneumothorax, pulmonary symptoms at presentation,Pseudomonas aeruginosa,Burkholderia cepacia, oral corticosteroids, nonsteroid anti-inflammatory drugs, dornase alfa, oxygen and assisted ventilation and, in patients >12 yrs old only, use of airway clearance techniques, inhaled bronchodilators, oral nutritional supplements, pancreatic enzymes and insulin or oral hypoglycaemics. Slightly impaired lung function (5–10%) was associated with: diabetes (≥18-yrs-old), gastro-oesophageal reflux, allergic bronchopulmonary aspergillosis, asthma-like symptoms, portal hypertension,Aspergillusspp. andCandidaspp. Sex,Haemophilus influenzaeandStaphylococcus aureuswere not associated with impaired pulmonary status. Regular exercise (especially in older patients) and nasal polyposis were associated with slightly better FEV1.The results confirm those of previous studies and suggest selective prescribing in sicker patients.
Physiomer® reduces the chemokine interleukin-;8 production by activated human respiratory epithelial cells
Authors: Tabary O. , Muselet C. , Yvin J-;C. , Halley-Vanhove B. , Puchelle E. , Jacquot J. 
Published: July 2002

The authors have recently shown that the transcription factor nuclear factor-κB (NF-κB) is a central mediator in the NaCl-mediated interleukin (IL)-;8 production by human airway epithelial cells. In this study, it was investigated whether Physiomer®, an isotonic sea water-derived solution commercialized for cleaning the nasal mucosa, impaired the chemokine IL-;8 expression and secretion by human respiratory epithelial cells compared with that obtained with an isotonic 9% NaCl solution.Primary human bronchial gland (HBG) epithelial cells were incubated either in Physiomer® or in a NaCl 9% solution and activated either with 20 ng·mL−1tumour necrosis factor-;α, or IL-;1β, respectively. Physiomer® significantly reduced the IL-;8 protein release in basal and activated HBG cells in comparison with that obtained with the 9% NaCl solution. In contrast to the effects of Physiomer® observed on resting HBG cells, Physiomer® did not significantly reduce the level of phosphorylation of the NF-κB inhibitor protein IκBα or the steady-state IL-;8 messenger ribonucleic acid levels in activated HBG cells, suggesting that Physiomer® would have a post-transcriptional effect on IL-;8 expression in activated HBG cells.The authors conclude that Physiomer® is potentially useful in the reduction of airway mucosal inflammation.
Unaltered perception of dyspnoea during treatment with long-acting β2-agonists
Authors: van der Woude H.J. , Aalbers R. 
Published: July 2002

There is the possibility that during treatment with inhaled long-acting β2-agonists that a loss of perception of dyspnoea might occur and that the forced expiratory volume in one second (FEV1) might fall precipitously during bronchial provocation. This study investigated these possibilities during methacholine provocation, continued until there was ≥30% fall in FEV1, mimicking a moderate asthma attack.Nineteen asthmatic patients were asked to score their dyspnoea as a Borg score during provocation with methacholine. One hour prior to this provocation, the patients used the last morning dose of 14 days treatment with either formoterol (twice daily 24 µg by Turbuhaler®), salmeterol (twice daily 100 µg by DiskhalerTM) and placebo in a double-blind, randomized, double-dummy, cross-over design.The perception of dyspnoea, expressed as the Borg score divided by the change in FEV1at ≥30% fall in FEV1, was similar on the three test days at 0.067, 0.076 and 0.074%−1after formoterol, salmeterol and placebo treatment, respectively (p=0.16). The slope of the methacholine dose response curve did not differ (p=0.52).In conclusion, no suggestion was found for an abnormal perception of dyspnoea or an exaggerated fall in forced expiratory volume in one second during provocation with methacholine under long-acting β2-agonist treatment.
Computed tomography of pulmonary sarcoid-like granulomas induced by complete Freund's adjuvant in rats
Authors: Bergeron A. , Laissy J-P. , Loiseau P. , Schouman-Claeys E. , Hance A.J. , Tazi A. 
Published: July 2002

Intravenous injection of complete Freund's adjuvant (CFA) in rats has been proposed as an experimental model for pulmonary sarcoidosis, but only some animals develop granulomas. Because the detection of the presence of granulomas and evaluation of the extent of the reaction has required histological evaluation, this model has been of limited use in following the evolution of the granulomatous process.The present study evaluated the ability of lung computed tomography (CT) scanning to identifyin vivopulmonary granulomas induced by CFA in rats. Wistar rats were injected with CFA to induce pulmonary sarcoid-like granulomas, and the presence and extent of pulmonary abnormalities, as detected by spiral CT and histopathological analysis, were compared.Spiral CT had a high sensitivity and specificity for the detection of sarcoid-like granulomas in rats injected with CFA. The extent of the pulmonary granulomatous reaction as assessed by the two techniques strongly correlated (r=0.93, p<0.01). In contrast, the mean density of lungs containing granulomas was not significantly different from that of lungs with no granulomatous reaction.Thus, lung computed tomography appears to be a valuable tool for thein vivoevaluation of the pulmonary granulomatous reaction induced by complete Freund's adjuvant in rats. With the help of computed tomography, this experimental model should be suitable for the sequential study of pulmonary sarcoid-like granulomas, particularly in response to various therapeutic strategies.
The tuberculin skin test in relation to immunologicalin vitroreactions in BCG-vaccinated healthcare workers
Authors: Fjällbrant H. , Ridell M. , Larsson L.O. 
Published: July 2002

The aim was to study the tuberculin skin test in relation to immunologicalin vitroreactions in bacille Calmette-Guérin (BCG)-vaccinated healthcare workers.The present study was performed in Sweden, a country with a low incidence of tuberculosis, a high BCG vaccination efficacy and high tuberculin conversion rates. BCG-vaccinated healthcare workers (n=381) were tuberculin skin tested. From these, 11 subjects with negative tuberculin reactions (<6 mm) were matched for age and sex with 11 subjects with large positive reactions (≥15 mm). Lymphocyte transformation and the production of interferon-gamma (IFN-γ) were analysed after stimulationin vitroof peripheral blood mononuclear cells with tuberculin purified protein derivative, heat-killed tubercle bacilli and a culture filtrate from tubercle bacilli.In the tuberculin-positive group the lymphocyte transformation response was 2–3 times larger, and IFN-γ production was 7–10 times larger, than in the tuberculin-negative group (p<0.001).The present results suggest that a positive tuberculin skin test in bacille Calmette-Guérin-vaccinated subjects indicates a stronger immune response of the protective T-helper 1-type than does a negative test. In similar settings, the study supports the traditional practice of regarding the tuberculin skin test in bacille Calmette-Guérin-vaccinated subjects as an indicator of a protective immune response against tuberculosis.