bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effect of CD28 versus B7 blockade on direct pathway of allorecognition and self-restricted responses
Authors: Haspot Fabienne , Villemain Florence , Laflamme Geneviève , Coulon Flora , Olive Daniel , Tiollier Jérôme , Soulillou Jean-Paul , Vanhove Bernard 
Published: October 2002

AbstractImmunosuppression with B7 antagonists might have 2 opposite effects: reducing T-cell costimulation through CD28 but also preventing CTLA-4 from transmitting its negative regulatory signal. We therefore hypothesized that a selective blockade of CD28 might be qualitatively different from blocking B7. It was previously reported that CD28 modulation prolongs allograft survival in the rat and reverses induction of experimental autoimmune encephalomyelitis in mice. However, whether CD28 or B7 blockade results in similar immunosuppression on alloimmune and self-restricted responses to soluble antigens has not yet been investigated. Here, we addressed this issue in vitro with antagonist anti-CD28 Fab fragments and in vivo using the modulating anti-rat JJ319 monoclonal antibody. As in the inhibition of B7 with CTLA4 immunoglobulin, anti-CD28 Fab fragments inhibited allogenic T-cell proliferation in mixed cultures. In vivo modulation of CD28 blocked the expansion of alloreactive T cells and promoted their apoptosis. In contrast, selective blockade of CD28 did not modify T-cell proliferative responses and antibody production to soluble antigens, whereas blocking B7 with CTLA4 immunoglobulin did. Our data show that blocking CD28, while leaving CTLA4-B7 interactions undisturbed, inhibits alloreactive CD4+ T-cell expansion but does not modify the response to nominal antigens presented in the context of a self-major histocompatibility complex. That B7 engagement is needed for self-restricted responses whereas engagement of CD28 is not essential adds to the suggestion that another unidentified ligand of B7 might deliver a costimulatory signal in the absence of CD28.
Addition of a second, different allogeneic graft accelerates white cell and platelet engraftment after T-cell–depleted bone marrow transplantation
Authors: Chen Benny J. , Cui Xiuyu , Chao Nelson J. 
Published: October 2002

AbstractSignificant delays in engraftment and lymphoid recovery are the 2 major challenges in cord blood transplantation. The cause for this delay is presumed to be the low numbers of hematopoietic precursors found in one unit of cord blood. One approach to increase the stem cell doses could be to combine cord blood units from different donors differing at the major histocompatibility complex (MHC). As a first step toward this goal, the kinetics of hematologic engraftment and immune reconstitution were compared between 1 unit (2.5 × 106 cells) of T-cell–depleted bone marrow cells from a single donor (C57BL/6 [H2b] or SJL/J [H2s]) and 2 units from different donors (C57BL/6 + SJL/J) after transplantation into lethally irradiated (8.5 Gy) BALB/c recipients (H2d). Addition of T-cell–depleted bone marrow from an MHC-mismatched allogeneic donor doubled the white blood counts compared with recipients of one single unit on days +10 and +14. Similar effects were also observed on platelets. The beneficial effect of additional cells on peripheral T-cell counts were first observed on day +14. Cells both from donors (C57BL/6 and/or SJL/J) and recipients (BALB/c) contributed to myeloid and lymphoid reconstitution. The chimeras containing cells from 3 strains of mice were able to mount a recall immune response. Our data suggest that combining stem cells from MHC-mismatched allogeneic donors is feasible, that it has beneficial effects on myeloid engraftment and T-cell phenotypic recovery, and that the long-term stable mixed chimeras are immunologically normal following T-cell–depleted bone marrow transplantation.
Combined treatment with temozolomide and poly(ADP-ribose) polymerase inhibitor enhances survival of mice bearing hematologic malignancy at the central nervous system site
Authors: Tentori Lucio , Leonetti Carlo , Scarsella Marco , d'Amati Giulia , Portarena Ilaria , Zupi Gabriella , Bonmassar Enzo , Graziani Grazia 
Published: October 2002

AbstractTemozolomide (TZM) is a DNA-methylating agent that has recently been introduced into various clinical trials for treatment of solid or hematologic neoplasias, including brain lymphomas. In the current study, we have investigated whether the antitumor activity of TZM could be selectively enhanced at the central nervous system (CNS) site by intracerebral injection of a poly(ADP-ribose) polymerase (PARP) inhibitor. Mice were injected intracranially with lymphoma cells. The PARP inhibitor NU1025 (1 mg/animal) was delivered intracerebrally, whereas TZM was given as a single or a fractionated dose of 200 mg/kg by intraperitoneal administration. Results indicated that this drug combination significantly enhanced the survival of tumor-bearing mice and that this fractionated modality of treatment was the most effective schedule. Increased survival time was related to a marked reduction of tumor growth, as evidenced by histologic studies. Treatment with TZM alone was ineffective. This is the first report exploring in vivo the combination of TZM with PARP inhibitor for intracerebral neoplasias.
Histone deacetylase inhibitor FR901228 enhances adenovirus infection of hematopoietic cells
Authors: Kitazono Masaki , Rao Vemulkonda Koneti , Robey Rob , Aikou Takashi , Bates Susan , Fojo Tito , Goldsmith Merrill E. 
Published: October 2002

AbstractAdenovirus infection of hematopoietic cells frequently requires high virus concentrations and long incubation times to obtain moderate infection levels because these cells have low levels of Coxsackie and adenovirus receptor (CAR) and αv integrin. The effect of treatment with FR901228 (depsipeptide), a histone deacetylase inhibitor in phase 2 clinical trials, was studied in K562 cells, granulocyte–colony-stimulating factor–mobilized peripheral blood mononuclear cells (PBMCs), and CD34+ peripheral blood stem cells (PBSCs). FR901228 increased CAR and αvintegrin RNA levels and histone H3 acetylation. FR901228 treatment before adenovirus infection was associated with at least a 10-fold increase in transgene expression from a β-galactosidase–expressing adenoviral vector. More than 80% of the PBMCs or CD34+ PBSCs from 7 different donors were β-galactosidase–positive after adenovirus infection with a multiplicity of infection of 10 for 60 minutes. Increased CAR, αv integrin, and acetylated histone H3 levels were observed in PBMCs from a patient treated with FR901228. These studies suggest that FR901228 can increase the efficiency of adenoviral infection in hematopoietic cells.
Prognostic significance of cellular vascular endothelial growth factor expression in chronic phase chronic myeloid leukemia
Authors: Verstovsek Srdan , Kantarjian Hagop , Manshouri Taghi , Cortes Jorge , Giles Francis J. , Rogers Anna , Albitar Maher 
Published: October 2002

Abstract
The impact of elevated vascular endothelial growth factor (VEGF) expression on the course of chronic myeloid leukemia (CML) is unknown. By radioimmunoassay, we measured pretreatment cellular VEGF protein in bone marrow samples from 184 (148 chronic and 36 accelerated/blastic phases) CML patients and found the levels to be 1.6-fold higher than in 31 normal control bone marrow samples (P = .000 01). No significant differences were found in VEGF levels by different phases of CML (P = .1). VEGF levels correlated with older age (P = .01) and higher platelet count (P = .0003), but also with smaller spleen size (P = .004), lower white blood cell count (P = .0006), and lower percentage of peripheral blasts (P = .04). With the use of Cox proportional hazard model and VEGF levels as a continuous variable, high VEGF levels correlated with shorter survival of patients in chronic CML (P = .008). Multivariate analysis showed that VEGF was not independent of the synthesis stage (P = .09). These data suggest that VEGF plays a role in the biology of CML and that VEGF inhibitors should be investigated in CML.
Relationship of carbon dioxide tension in arterial blood to pulmonary wedge pressure in heart failure
Authors: Lorenzi-Filho G. , Azevedo E.R. , Parker J.D. , Bradley T.D. 
Published: October 2002

Hypocapnia contributes to the genesis of Cheyne-Stokes respiration and central sleep apnoea in patients with congestive heart failure (CHF) and is associated with increased mortality. However, the cause of hypocapnia in patients with chronic stable CHF is unknown. Since pulmonary congestion can induce hyperventilationviastimulation of pulmonary vagal afferents, the present study tested the hypothesis that in patients with CHF (carbon dioxide tension in arterial blood (Pa,CO2)) is inversely related to pulmonary capillary wedge pressure (PCWP), and that alterations in PCWP would cause inverse changes inPa,CO2.In 11 CHF patients undergoing diagnostic cardiac catheterization, haemodynamic variables and arterial blood gas tensions were measured simultaneously at baseline. In three patients, these measurements were repeated after coronary angiographic dye infusion and nitroglycerine infusion.At baseline,Pa,CO2correlated inversely with PCWP (r=−0.80, p=0.003). In the three patients in whom multiple measurements were made, acute alterations in PCWP caused inversely proportional changes inPa,CO2.The present study concludes that in patients with congestive heart failure, pulmonary capillary wedge pressure is an important determinant of carbon dioxide tension in arterial blood. These findings imply that hypocapnia in patients with chronic stable congestive heart failure is a respiratory manifestation of elevated left ventricular filling pressures.
BAX and p16INK4Aare independent positive prognostic markers for advanced tumour stage of nonsmall cell lung cancer
Authors: Gessner C. , Liebers U. , Kuhn H. , Stiehl P. , Witt C. , Schauer J. , Wolff G. 
Published: October 2002

Clinical studies suggest prognostic relevance of p16INK4Ain nonsmall cell lung cancer (NSCLC) while conflicting results for p53 have been published. However, the importance of the apoptosis regulating gene BAX, a downstream regulator of p53, on the prognosis of NSCLC is unknown. The present study investigated the prognostic relevance of BAX with respect to the status of p53 and p16INK4Ain 61 patients with advanced NSCLC.Protein expression of BAX, p53 and p16INK4Awas investigated retrospectively by immunohistochemistry. Tumour deoxyribonucleic acid (DNA) was screened for p53 mutations by single strand-conformation polymorphism polymerase chain reaction (PCR) and BAX frameshift mutations by fragment length analysis.Patients with positive BAX protein expression had a significantly longer median survival (14 months) than those patients without BAX expression (6 months, p=0.0004). In contrast, p53 status did not influence prognosis. Patients with p16INK4Anegative tumours had a significantly shorter survival (4 months) than those with p16INK4Aprotein expression (15 months, p=0.0001). Furthermore, the loss of p16INK4Aprotein expression correlated strongly with the pressure of distant and advanced lymph-node metastases. The best survival was seen in a subgroup of 20 patients with positive p16INK4Aexpression and intact BAX (p=0.0002).The results of the present study suggest that the loss of BAX and p16INK4Aexpression are independent markers for poor prognosis in nonsmall cell lung cancer. The study suggests that multimarker analysis of genes involved in apoptosis may be useful for determining individual therapy and for identifying targets for gene-replacement therapy. This should be assessed in a prospective study with a larger cohort of patients.
High postoperative risk after pneumonectomy in elderly patients with right-sided lung cancer
Authors: van Meerbeeck J.P. , Damhuis R.A.M. , Vos de Wael M.L. 
Published: October 2002

The present study investigated postoperative mortality (POM), its predictors and relationship with long-term survival in patients who underwent surgery for lung cancer.The 30-day mortality after thoracotomy in 1,830 patients from the Flemish multicentre hospital-based lung cancer registry was analysed according to patient, tumour, treatment and hospital characteristics and compared with 5-yr survival figures for the same patients.Overall POM was 4.4%. In univariate analysis age, extent of surgery and low hospital volume were associated with a higher POM. In multiple regression analysis age, extent of surgery and side of the pneumonectomy proved to be independent predictors of POM. In patients aged >70 yrs who underwent right-sided pneumonectomy POM was 17.8%.Overall, mortality was comparable to published series from referral centres. Age and extent of resection are the main predictors of postoperative mortality in lung-cancer patients. In the operable elderly patient, age alone does not justify denying the survival benefit experienced by resection of lung cancer. The high mortality after right-sided pneumonectomy in elderly patients warrants caution, as the treatment benefit may become marginal.
The SleepStripTM: an apnoea screener for the early detection of sleep apnoea syndrome
Authors: Shochat T. , Hadas N. , Kerkhofs M. , Herchuelz A. , Penzel T. , Peter J.H. , Lavie P. 
Published: October 2002

Sleep apnoea syndrome (SAS) is a largely undiagnosed and prevalent disorder. It is associated with cardiovascular morbidity as well as excessive daytime sleepiness and poor quality of life. In the present study the SleepStripTM, a novel screening device is introduced, which is low cost and easy to use and is aimed for widespread use.The results of three independent validation studies, which compared the SleepStripTMscore (Sscore) against “gold standard” polysomnographically-determined apnoea/hypopnoea index (AHI), are reported both separately and combined. Four hundred and two patients suspected of SAS underwent full polysomnography recordings concomitantly with the use of the SleepStripTM.For all samples combined, the correlation between AHI and Sscore was r=0.73, sensitivity and specificity values ranged from 80–86% and 57–86% respectively, and the area under the curve derived from receiver-operating characteristic curves ranged from 0.81–0.92 at varying AHI thresholds.Though not intended as a substitute for polysomnography, the SleepStripTMmay provide initial screening information, which may be useful in both clinical and experimental settings.
Costs of asthma are correlated with severity: a 1-yr prospective study
Authors: Godard P. , Chanez P. , Siraudin L. , Nicoloyannis N. , Duru G. 
Published: October 2002

Asthma prevalence is increasing and asthma-related costs are likely to increase, but few studies have analysed the relationship of asthma costs and severity. The impact of severity on costs was quantified in a cohort of 318 asthmatic patients followed up prospectively for 1 yr.Patients presenting with a broad range of severity of the disease (intermittent, mild persistent, moderate persistent, severe persistent) were recruited by chest physicians throughout France and treated for 1 yr according to customary clinical practice and following international guidelines. Severity, direct and indirect costs, and quality of life (QoL) were assessed. A multivariate analysis was conducted to relate factors contributing to the costs measured.Mean direct costs for goods and services excluding hospitalization, numbers of consultations, supplementary examinations, and the use and cost of bronchodilators and corticosteroids, indirect costs of days lost from work, and adverse QoL parameters all increased significantly with increasing severity. This also applied to mean age, body weight, asthma duration, depression of forced expiratory volume in one second, and inhaled corticosteroid posology in the 234 patients completing the study. There was a significant relationship (r=0.614, p<0.001) between direct costs (hospitalization and cures were excluded) and three domains of the QoL questionnaire (mobility, pain and energy).Overall costs of asthma (including individual direct costs, indirect costs, and intangible quality of life costs) are clearly related to severity. This is the first study in asthma to combine rigorous independent classification of grades of severity in statistically valid numbers of patients of grades receiving “real-world” treatment and followed-up prospectively for 1 yr. It allowed severity to be accurately related to direct, indirect and intangible costs of asthma. Quality of life explained a significant part of these costs.
Adjustment to chronic obstructive pulmonary disease: the importance of psychological factors
Authors: McCathie H.C.F. , Spence S.H. , Tate R.L. 
Published: October 2002

Research has indicated a weak relationship between the degree of physical problems and quality of life in patients with chronic obstructive pulmonary disease (COPD). The importance of adaptive psychological functioning to maintain optimum quality of life has long been recognized, but there is a lack of empirical evidence concerning the nature of psychological factors involved in adjustment to COPD.Ninety-two males completed questionnaires to determine their coping strategies, levels of self-efficacy of symptom management and social support. Adjustment was measured in terms of depression, anxiety and quality of life. Symptom severity, socioeconomic status, duration of disease and age, which have been demonstrated to be of consequence in COPD, were used as control variables in hierarchical multiple regression analyses.Higher levels of catastrophic withdrawal coping strategies and lower levels of self-efficacy of symptom management were associated with higher levels of depression, anxiety and a reduced quality of life. Higher levels of positive social support were linked to lower levels of depression and anxiety, while higher levels of negative social support were linked to higher levels of depression and anxiety.To maximize quality of life in patients with chronic obstructive pulmonary disease, psychological factors need to be carefully assessed and addressed.
Exhaled carbon monoxide is not elevated in patients with asthma or cystic fibrosis
Authors: Zetterquist W. , Marteus H. , Johannesson M. , Nordvall S.L. , Ihre E. , Lundberg J.O.N. , Alving K. 
Published: October 2002

Increased levels of exhaled carbon monoxide (fractional concentration of CO in expired gas (FE,CO)), measured with an electrochemical sensor, have been reported in patients with inflammatory airway disorders, such as asthma, rhinitis and cystic fibrosis. This study aimed to evaluate these findings by using a fast-response nondisperse infrared (NDIR) analyser, and to compare these measurements with the fractional concentration of nitric oxide in exhaled air (FE,NO).Thirty-two steroid-naïve asthmatics, 24 steroid-treated asthmatics (16 patients with allergic rhinitis, nine patients with cystic fibrosis), and 30 nonsmoking healthy controls were included. CO measurements with the NDIR analyser were performed simultaneously with nitric oxide (NO) analysis (chemiluminescence technique). After 15 s of breath-hold, single-breath exhalations over 10 s were performed at two flow rates and end-tidal plateau concentrations were registered. An electrochemical CO sensor was used independently with an exhalation to residual volume, after a 15 s breath-hold.None of the two CO analysers gave a significant increase inFE,COin the groups of patients with inflammatory airway disorders compared to controls.FE,NOwas significantly elevated in steroid-naïve asthmatics and subjects with allergic rhinitis, but not in steroid-treated asthmatics and subjects with cystic fibrosis. Reducing exhalation flow rate by 50% gave a two-fold increase inFE,NO, whileFE,COwas unaffected. A significant increase was seen inFE,CO, but not inFE,NO, when comparing with and without a 10 s breath-hold.In conclusion, the fractional concentration of carbon monoxide in expired gas was not increased in any of the patient groups, while the fractional concentration of nitric oxide in expired gas was significantly elevated in patients with steroid-naïve asthma and allergic rhinitis. Moreover, carbon monoxide was unaffected by flow rate but increased with breath-hold, suggesting an origin in the alveoli rather than the conducting airways.
Rhinovirus infection in nonasthmatic subjects: effects on intrapulmonary airways
Authors: de Kluijver J. , Grünberg K. , Sont J.K. , Hoogeveen M. , van Schadewijk W.A.A.M. , de Klerk E.P.A. , Dick C.R. , van Krieken J.H.J.M. , Sterk P.J. 
Published: October 2002

The common cold is a highly prevalent, uncomplicated upper airway disease. However, rhinovirus (RV) infection can lead to exacerbation of asthma, with worsening in airway hyperresponsiveness and bronchial inflammation. The current authors questioned whether such involvement of the intrapulmonary airways is disease specific.Twelve nonatopic, healthy subjects (forced expiratory volume in one second (FEV1) >80% predicted, provocation concentration causing a 20% fall in FEV1(PC20) >8 mg·mL−1) were experimentally infected with RV16. Next to PC20and the maximal response to methacholine (MFEV1and MV′40p), the numbers of mucosal inflammatory cells and epithelial intercellular adhesion molecule (ICAM)‐1 expression in bronchial biopsies were assessed before and 6 days after RV16 inoculation.RV16 infection induced a small but consistent increase in maximal airway narrowing, without a change in PC20. There was a significant increase in bronchial epithelial ICAM‐1 expression after RV16, whereas inflammatory cell counts did not change. Nevertheless, the change in the number of submucosal CD3+ cells was correlated with the change in MV′40p.In conclusion, rhinovirus infection in normal subjects induces a limited, but significant increase in maximal airway narrowing, which is associated with changes in bronchial T‐cell numbers. Together with the upregulation of bronchial epithelial intercellular adhesion molecule‐1, these findings indicate that, even in healthy subjects, rhinovirus infection affects the intrapulmonary airways.
The bidirectional capacity of bacterial antigens to modulate allergy and asthma
Authors: Renz H. , Herz U. 
Published: October 2002

In recent decades, the prevalence of allergic diseases including bronchial asthma, hay fever and atopic dermatitis, has risen steadily in high-income countries. The underlying mechanisms for this phenomenon remain largely unknown. Since the natural mutation rate is low, altered environmental and lifestyle conditions are thought to play an important role.Epidemiological and clinical studies have provided indirect evidence that infections may prevent the development of atopy and atopic disease. This is referred to as the “hygiene hypothesis”. According to the hygiene hypothesis, viral and/or bacterial infections could inhibit the T-helper (Th)-2 immune response associated with atopic reactions by stimulating a Th-1 response involved in defence of bacterial infections and delayed-type hypersensitivity reactions.In particular, the prenatal period and early childhood are considered to be critical for the establishment and maintenance of a normal Th-1/Th-2 balance. On the other hand, several studies suggested that infections exacerbate established allergic diseases,e.g.bronchial asthma, airway hyperresponsiveness and atopic dermatitis. Therefore, viral and/or microbial infections and/or their products may have bidirectional effects on the development of allergy and asthma.This review will focus on recent findings related to the interaction between allergic disorders and infectious diseases, with the main emphasis on bacterial infections.