bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen-dependent E2a/Pbx1 myeloid cell lines exhibit conditional differentiation that can be arrested by other leukemic oncoproteins
Authors: Sykes David B. , Kamps Mark P. 
Published: July 2002

AbstractThe molecular pathways of normal myeloid differentiation, as well as the mechanisms by which oncogenes disrupt this process, remain poorly understood. A major limitation in approaching this problem has been the lack of suitable cell lines that exhibit normal, terminal, and synchronous differentiation in the absence of endogenous oncoproteins and in response to physiologic cytokines, and whose differentiation can be arrested by ectopically expressed human oncoproteins. This report describes clonal, granulocyte-macrophage colony-stimulating factor-dependent myeloid cell lines that exhibit these properties. The cell lines were established by conditional immortalization of primary murine marrow progenitors with an estrogen-regulated E2a/Pbx1-estrogen receptor fusion protein. Clones were identified that proliferated as immortalized blasts in the presence of estrogen, and that exhibited granulocytic, monocytic, or bipotential (granulocytic and monocytic) differentiation on estrogen withdrawal. Differentiation was normal and terminal as evidenced by morphology, cell surface markers, gene expression, and functional assays. The differentiation of the cells could be arrested by heterologous oncoproteins including AML1/ETO, PML/RARα, PLZF/RARα, Nup98/HoxA9, and other Hox proteins. Furthermore, the study examined the effects of cooperating oncoproteins such as Ras or Bcr/Abl, which allowed for both factor-independent proliferation and differentiation, or Bcl-2, which permitted factor-independent survival but not proliferation. These myeloid cell lines provide tools for examining the biochemical and genetic pathways that accompany normal differentiation as well as a system in which to dissect how other leukemic oncoproteins interfere with these pathways.
Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow
Authors: Campagnoli Cesare , Roberts Irene A. G. , Kumar Sailesh , Bennett Phillip R. , Bellantuono Ilaria , Fisk Nicholas M. 
Published: July 2002

AbstractHuman mesenchymal stem/progenitor cells (MSCs) have been identified in adult bone marrow, but little is known about their presence during fetal life. MSCs were isolated and characterized in first-trimester fetal blood, liver, and bone marrow. When 106 fetal blood nucleated cells (median gestational age, 10+2 weeks [10 weeks, 2 days]) were cultured in 10% fetal bovine serum, the mean number (± SEM) of adherent fibroblastlike colonies was 8.2 ± 0.6/106 nucleated cells (69.6 ± 10/μL fetal blood). Frequency declined with advancing gestation. Fetal blood MSCs could be expanded for at least 20 passages with a mean cumulative population doubling of 50.3 ± 4.5. In their undifferentiated state, fetal blood MSCs were CD29+, CD44+, SH2+, SH3+, and SH4+; produced prolyl-4-hydroxylase, α-smooth muscle actin, fibronectin, laminin, and vimentin; and were CD45−, CD34−, CD14−, CD68−, vWF−, and HLA-DR−. Fetal blood MSCs cultured in adipogenic, osteogenic, or chondrogenic media differentiated, respectively, into adipocytes, osteocytes, and chondrocytes. Fetal blood MSCs supported the proliferation and differentiation of cord blood CD34+cells in long-term culture. MSCs were also detected in first-trimester fetal liver (11.3 ± 2.0/106 nucleated cells) and bone marrow (12.6 ± 3.6/106 nucleated cells). Their morphology, growth kinetics, and immunophenotype were comparable to those of fetal blood-derived MSCs and similarly differentiated along adipogenic, osteogenic, and chondrogenic lineages, even after sorting and expansion of a single mesenchymal cell. MSCs similar to those derived from adult bone marrow, fetal liver, and fetal bone marrow circulate in first-trimester human blood and may provide novel targets for in utero cellular and gene therapy.
Selective inhibitor of Janus tyrosine kinase 3, PNU156804, prolongs allograft survival and acts synergistically with cyclosporine but additively with rapamycin
Authors: Stepkowski Stanislaw M. , Erwin-Cohen Rebecca A. , Behbod Fariba , Wang Mou-Er , Qu Xienui , Tejpal Neelam , Nagy Zsuzsanna S. , Kahan Barry D. , Kirken Robert A. 
Published: July 2002

AbstractJanus kinase 3 (Jak3) is a cytoplasmic tyrosine (Tyr) kinase associated with the interleukin-2 (IL-2) receptor common gamma chain (γc) that is activated by multiple T-cell growth factors (TCGFs) such as IL-2, -4, and -7. Using human T cells, it was found that a recently discovered variant of the undecylprodigiosin family of antibiotics, PNU156804, previously shown to inhibit IL-2–induced cell proliferation, also blocks IL-2–mediated Jak3 auto-tyrosine phosphorylation, activation of Jak3 substrates signal transducers and activators of transcription (Stat) 5a and Stat5b, and extracellular regulated kinase 1 (Erk1) and Erk2 (p44/p42). Although PNU156804 displayed similar efficacy in blocking Jak3-dependent T-cell proliferation by IL-2, -4, -7, or -15, it was more than 2-fold less effective in blocking Jak2-mediated cell growth, its most homologous Jak family member. A 14-day alternate-day oral gavage with 40 to 120 mg/kg PNU156804 extended the survival of heart allografts in a dose-dependent fashion. In vivo, PNU156804 acted synergistically with the signal 1 inhibitor cyclosporine A (CsA) and additively with the signal 3 inhibitor rapamycin to block allograft rejection. It is concluded that inhibition of signal 3 alone by targeting Jak3 in combination with a signal 1 inhibitor provides a unique strategy to achieve potent immunosuppression.
P2X7 receptor expression in evolutive and indolent forms of chronic B lymphocytic leukemia
Authors: Adinolfi Elena , Melchiorri Loredana , Falzoni Simonetta , Chiozzi Paola , Morelli Anna , Tieghi Alessia , Cuneo Antonio , Castoldi Gianluigi , Di Virgilio Francesco , Baricordi Olavio R. 
Published: July 2002

AbstractHuman leukocytes express a receptor for extracellular nucleotides, named P2X7R, that in lymphocytes can either mediate cell death or proliferation, depending on the level of activation. The authors have investigated P2X7R expression and function in 21 patients affected by B-cell chronic lymphocytic leukemia, 13 with an evolutive and 8 with an indolent variant of the disease. Resting cytoplasmic Ca++ concentration was significantly higher in lymphocytes from patients with the evolutive compared with indolent variant. Furthermore, in the former, P2X7R stimulation triggered a Ca++ influx significantly larger. Higher Ca++ influx correlated with an increased P2X7R expression in the lymphocytes from patients with the evolutive form. Finally, incubation in the presence of extracellular adenosine triphosphate decreased spontaneous proliferation of lymphocytes from patients affected with the evolutive variant but had no effects on lymphocytes from patients with the indolent form. These results suggest that expression and function of P2X7R may correlate with the severity of B-cell chronic lymphocytic leukemia.
Inhaled fluticasone decreases bronchial but not alveolar nitric oxide output in asthma
Authors: Lehtimäki L. , Kankaanranta H. , Saarelainen S. , Turjanmaa V. , Moilanen E. 
Published: July 2002

Exhaled nitric oxide (NO) concentration is a noninvasive measure of airway inflammation and is increased in asthma. Inhaled glucocorticoids decrease exhaled NO concentration, but the relative contributions of alveolar and bronchial levels to the decrease in exhaled NO concentration are unknown. Alveolar NO concentration and bronchial NO flux can be separately approximated by measuring exhaled NO at several exhalation flow rates. The effect of steroid treatment on alveolar and bronchial NO output in asthma was studied.Alveolar NO concentration and bronchial NO flux were assessed in 16 patients with asthma before and during treatment with inhaled fluticasone for 8 weeks and in 16 healthy controls.Before the treatment, asthmatics had increased bronchial NO flux (mean±sem: 3.6±0.4versus0.7±0.1 nL·s−1, p<0.001) but normal alveolar NO concentration (1.2±0.5versus1.0±0.2 parts per billion (ppb), p>0.05) compared with controls. Inhaled fluticasone decreased bronchial NO flux from 3.6±0.4 to 0.7±0.1 nL·s−1(p<0.01) but had no effect on alveolar NO concentration (before: 1.2±0.5; after: 1.2±0.1 ppb, p>0.05). The forced expiratory volume in one second improved, whereas asthma symptom score and serum levels of eosinophil cationic protein and eosinophil protein X decreased during the treatment.In conclusion, inhaled fluticasone decreases bronchial but not alveolar nitric oxide output simultaneously with clinical improvement in patients with asthma.
Comparison of resistance measured by the interrupter technique and by passive mechanics in sedated infants
Authors: Chavasse R.J. , Bastian-Lee Y. , Seddon P. 
Published: July 2002

Airways resistance measured by the interrupter technique (Rint) requires little patient cooperation and has been successfully used in young children, but little studied in infants. The authors aimed to evaluate the measurement ofRintin infants, using a commercially available device (the MicroRint), by comparing it with an established technique to measure respiratory resistance: the single breath occlusion technique (SBT); and a measure of airflow obstruction during forced expiration.Infants <18 months old with a history of wheeze, sedated with triclofos for pulmonary function testing, had measurements taken and compared toRint(using the MicroRint), respiratory system resistance (Rrs) by SBT, and to maximal flow at functional residual capacity (V′maxFRC).Paired data from 25 of 37 infants studied was obtained. There was a significant difference betweenRint(mean 2.94±0.68) andRrs(4.02±0.87), but the two measures were strongly correlated (r=0.7).Rintwas negatively correlated withV′maxFRC(r=−0.63). Smaller infants failed to trigger the MicroRint.Interrupter resistance values in infants are significantly lower than values of respiratory system resistance obtained by passive mechanics. However, there is a strong correlation between the two measurements, as well as between resistance measured using the interrupter technique and maximal flow at functional residual capacity, which indicates that resistance measured using the interrupter technique may be a useful marker of airway obstruction in infants. There remain a number of theoretical and technical problems which require further exploration.
Nasal continuous positive airway pressure in stroke patients with sleep apnoea: a randomized treatment study
Authors: Sandberg O. , Franklin K.A. , Bucht G. , Eriksson S. , Gustafson Y. 
Published: July 2002

The authors have investigated whether treatment of sleep apnoea with nasal continuous positive airway pressure (nCPAP) improves depressive symptoms, personal activities of daily living (ADL), cognitive functioning and delirium in patients that have suffered a stroke.Sixty-three patients consecutively admitted to a stroke rehabilitation unit 2–4 weeks after a stroke, with an apnoea/hypopnoea index ≥15, were randomized to either nCPAP treatment (n=33) or a control group (n=30). Four patients dropped out after randomization. Both groups were assessed at baseline and after 7 and 28 nights using the Montgomery-Åsberg Depression Rating Scale (MADRS), Barthel-ADL index, and the Mini-Mental State Examination (MMSE) scale.Compared to the control group, depressive symptoms (MADRS total score) improved in patients randomized to nCPAP treatment (p=0.004). No significant treatment effect was found with regard to delirium, MMSE or Barthel-ADL index. Delirium and low cognitive level (MMSE score) explained poor compliance with nCPAP.Depressive symptoms are reduced through nasal continuous positive airway pressure treatment in patients with severe stroke and sleep apnoea. Compliance with nasal continuous positive airway pressure treatment is a problem in stroke patients, especially when delirium and severe cognitive impairment occur.
Guidelines of tuberculosis preventive therapy for HIV-infected persons: a prospective, multicentre study
Authors: Antonucci G. , Girardi E. , Raviglione M. , Vanacore P. , Angarano G. , Chirianni A. , Pagano G. , Suter F. , Lauria F.N. , Ippolito G. ,   GISTA (Gruppo Italiano di Studio Tubercolosi e AIDS)
Published: July 2002

The aim of this study was to assess the degree of implementation of national guidelines for isoniazid preventive therapy (IPT) among human immunodeficiency virus (HIV)-infected individuals and factors affecting the impact of the programme.Twenty-eight infectious disease hospital units in Italy participated in this observational, multicentre, prospective cohort study. A number of HIV-infected subjects, (n=1,705) seen for the first time as outpatients, were included in this analysis.Of the subjects considered, 1,215 out of the 1,705 completed purified protein derivative (PPD) screening. Variables independently associated with offering and completion of PPD screening included having acquired immune deficiency syndrome (AIDS), higher educational levels and currently receiving therapy. Overall, 103 subjects were identified as candidates for IPT. Of these subjects, five had tuberculosis and 15 had contraindications to IPT. Forty subjects agreed to start IPT, and 29 completed a full-course regimen. The incidence of tuberculosis among IPT candidates who either did not begin or discontinued IPT was 6.1 per 100 person-yrs, while no cases of tuberculosis were observed in subjects completing IPT.Several factors may limit the implementation of an isoniazid preventive therapy programme for human immunodeficiency virus-infected persons. Physicians fail to offer purified protein derivative screening to patients with high degrees of immunodeficiency, and those with a more intense workload seem to pay less attention to this test. The high number of contraindications among patients and their low level of acceptance further affects the impact of isoniazid preventive therapy.
The effect of exposure to sulphuric acid on the early asthmatic response to inhaled grass pollen allergen
Authors: Tunnicliffe W.S. , Evans D.E. , Mark D. , Harrison R.M. , Ayres J.G. 
Published: July 2002

Particulate sulphates, including sulphuric acid (H2SO4), are important components of the ambient aerosol in some areas and are regarded as air pollutants with potentially important human health effects. Challenge studies suggest little or no effect of H2SO4exposure on lung function in asthmatic adults, although some epidemiological studies demonstrate an effect of acid species on symptoms in subjects with asthma. To date, the effect of H2SO4on allergen responsiveness has not been studied.The effect of exposure to particulate H2SO4on the early asthmatic response to grass pollen allergen has been investigated in 13 adults with mild asthma. After establishment of the provocative dose of allergen producing a 15% fall in forced expiratory volume in one second (FEV1) (PD15) for each subject, they were exposed to air, 100 µg·m−3or 1,000 g·m−3H2SO4for 1 h, double-blind in random order ≥2 weeks apart, through a head dome delivery system 14 h after each exposure subject underwent a fixed-dose allergen challenge (PD15).Ten subjects completed the study. The mean early asthmatic responses (maximum percentage change in FEV1during the first 2 h after challenge) following air, 100 µg·m−3H2SO4, and 1,000 µg·m−3H2SO4, were −14.1%, −16.7%, and −18.4%, respectively. The difference between 1,000 µg·m−3H2SO4and air was significant (mean difference: −4.3%, 95% confidence interval (CI: −1.2–−7.4%, p=0.013). The difference between air and 100 µg·m−3H2SO4approached significance (mean difference: −2.6%, 95% CI: 0.0–−5.3%, p=0.051).These results suggest that, at least at high mass concentration, sulphuric acid can potentiate the early asthmatic response of mild asthmatic subjects to grass pollen allergen, although the effect is limited.
Major histocompatibility locus genetic markers of beryllium sensitization and disease
Authors: Saltini C. , Richeldi L. , Losi M. , Amicosante M. , Voorter C. , van den Berg-Loonen E. , Dweik R.A. , Wiedemann H.P. , Deubner D.C. , Tinelli C. 
Published: July 2002

Hypersensitivity to beryllium (Be) is found in 1–16% of exposed workers undergoing immunological screening for beryllium disease using the beryllium lymphocyte proliferation test (BeLPT). However, only ∼50% of BeLPT-positive workers present with lung granulomas (i.e.berylliosis). As berylliosis is associated with the human leukocyte antigen (HLA)-DP supratypic marker DPGlu69, the authors asked whether this marker is differentially associated with disease presentation.A population of 639 workers from a beryllium factory undergoing BeLPT screening was evaluated in a nested case-control study for the prevalence of HLA-DPGlu69, the HLA-DPB1, HLA-DQ and HLA-DR alleles and of the biallelic tumour necrosis factor (TNF)-;α polymorphism TNF-;α-;308 in 23 individuals presenting as “sensitized” (i.e.BeLPT-positive without lung granulomas) and in 22 presenting as “diseased” (i.e.BeLPT-positive with granulomas in the lung biopsy).The HLA-DPGlu69 marker was associated with “disease” (odds ratio (OR) 3.7, p=0.016, 95% confidence interval (CI) 1.4–10.0), whilst the high TNF-;α production-related TNF-;α-;308*2 marker was associated with both a positive BeLPT (OR 7.8, corrected p<0.0001, 95% CI 3.2–19.1) with no difference between “sensitization” and “disease”. Furthermore, the HLA-DRArg74 marker was associated with “sensitization” without disease (OR 3.96, p=0.005, 95% CI 1.5–10.1).The data indicate that tumour necrosis factor-;α, human leukocyte antigen-DR and human leukocyte antigen-DP markers play different roles in beryllium sensitization and granuloma formation in beryllium-exposed workers.
International approaches to the prescription of long-term oxygen therapy
Authors: Wijkstra P.J. , Guyatt G.H. , Ambrosino N. , Celli B.R. , Güell R. , Muir J.F. , Préfaut C. , Mendes E.S. , Ferreira I. , Austin P. , Weaver B. , Goldstein R.S. 
Published: July 2002

While there is broad agreement about who should receive long-term oxygen therapy (LTOT), there is little information available on how clinicians should decide on the oxygen prescription itself, at rest, during sleep and during exercise. The authors describe the results of an international survey that was undertaken to compare how respirologists prescribed oxygen.A questionnaire was sent to 100 respirologists in each of seven countries. The questionnaire identified whether resting flow rates were derived in a standard manner or by individualized patient testing. Test targets were ascertained for rest, exercise and sleep, as was the percentage of time that each test target had to reach for the test to be accepted.The majority of respondents individualized the oxygen prescription at rest (81%). Resting arterial oxygen saturation (Sa,O2) was most commonly targeted at 90–91%. The approach to night prescription varied (p<0.001). Respirologists in Canada and the USA increased the restingSa,O2by 1–2 L·min−1during sleep, while those in Spain used the resting (awake) flow for the night prescription (62%). Respirologists in the Netherlands, France, and Italy individualized the night prescription more frequently. Although oxygen during exercise was individualized in most countries (74%), significant differences remained among countries (p<0.001). The majority of respirologists (62%) aimed to achieve anSa,O2of 90–91% during exercise, while 70% of all respirologists tried to achieve the desiredSa,O2for 90% of the test.There were substantial differences among countries as to how the oxygen prescription was written. This survey highlights the need for multicentre studies that improve the effectiveness of long-term oxygen therapy utilization.
A prospective comparison of nursing home acquired pneumonia with community acquired pneumonia
Authors: Lim W.S. , Macfarlane J.T. 
Published: July 2002

Nursing home acquired pneumonia (NHAP) is thought to be clinically distinct from community acquired pneumonia (CAP). This observation, based on studies conducted mainly in North America, may not be relevant in countries with a different healthcare system.The authors describe an 18-month prospective cohort study of 437 patients admitted to hospital with CAP, 40 (9%) of whom came from nursing homes. Detailed microbiological tests were performed in a subset of patients over 12 months.Patients with NHAP were less likely to have a productive cough (odds ratio (OR) 0.4, p=0.02) or pleuritic pain (OR 0.1, p=0.03), but they were more likely to be confused (OR 2.6, p<0.001). They had poorer functional status (p<0.001) and more severe disease (p=0.03). Mortality was higher compared to CAP (53%versus13%), but this was mainly explained by prior functional status (OR 0.5, after adjustment for functional status). Pathogens were identified in 68% of 22 NHAP and 80% of 44 matched CAP patients.Streptococcus pneumoniaewas the most common (55% NHAP, 43% CAP). Atypical pathogens, enteric Gram negative bacilli andStaphylococcus aureuswere uncommon.In conclusion, differences in functional status accounted for the increased mortality in nursing home acquired pneumonia compared to community acquired pneumonia. The pathogens implicated were similar. No grounds for a difference in choice of empirical antibiotics were apparent.
Controlled, prospective trial of psychosocial function before and after continuous positive airway pressure therapy
Authors: McFadyen T.A. , Espie C.A. , McArdle N. , Douglas N.J. , Engleman H.M. 
Published: July 2002

The aim of the study was to investigate psychosocial function before and after continuous positive airway pressure (CPAP) therapy, and establish the determinants and consequences of objective CPAP use.In a prospective, parallel-group study, changes in psychosocial scores were compared with conservative management or CPAP therapy for the sleep apnoea/hypopnoea syndrome (SAHS). Patient/partner couples from the top (CPAP treated, n=44) or bottom (conservatively treated, n=25) of a CPAP waiting list rated marital satisfaction (evaluation and nurturing relationship issues, communication and happiness (ENRICH), behavioural questionnaire), health/functional status (Short-Form-36 Health Survey, functional outcomes of sleep questionnaire) and sleepiness (Epworth sleepiness scale). Both groups' ratings at baseline were completed while on conservative therapy.Baseline variables did not differ between groups. At follow-up, all seven summary psychosocial scores were statistically better in CPAP-treated patients, effect sizes (ES) ranging from moderate (0.5 sd: marital satisfaction) to very large (>1.0 sd: patients health, functional status and sleepiness scores). Scores in conservatively-treated patients deteriorated to a small or moderate degree (ES −0.2– −0.7 sd), while those in the CPAP-treated group improved to a larger degree (0.3–1.3 sd). Baseline polysomnographical and psychosocial scores, including marital satisfaction, did not predict objective CPAP use (r<0.3). CPAP use was modestly correlated (r=0.3–0.6) with improvement in all psychosocial areas.Continuous positive airway pressure produced statistically and clinically significant psychosocial improvements, some of large magnitude, in psychosocial function. Determinants of usage were not identified, but benefits and usage were positively correlated.