bluuebunny/crossref_metadata_2025_split huggingface dataset:
Receptor engagement by viral interleukin-6 encoded by Kaposi sarcoma–associated herpesvirus
Authors: Aoki Yoshiyasu , Narazaki Masashi , Kishimoto Tadamitsu , Tosato Giovanna 
Published: July 2002

AbstractReceptor usage by viral interleukin-6 (vIL-6), a virokine encoded by Kaposi sarcoma– associated herpesvirus, is an issue of controversy. Recently, the crystal structure of vIL-6 identified vIL-6 sites II and III as directly binding to glycoprotein (gp)130, the common signal transducer for the IL-6 family of cytokines. Site I of vIL-6, however, comprising the outward helical face of vIL-6, where human IL-6 (hIL-6) would interact with the specific α-chain IL-6 receptor (IL-6R), is accessible and not occupied by gp130. This study examined whether this unused vIL-6 surface is available for IL-6R binding. By enzyme-linked immunosorbent assay, vIL-6 bound to soluble gp130 (sgp130) but not to soluble IL-6R (sIL-6R). Using plasmon surface resonance, vIL-6 bound to sgp130 with a dissociation constant of 2.5 μM, corresponding to 1000-fold lower affinity than that of hIL-6/sIL-6R complex for gp130. sIL-6R neither bound to vIL-6 nor affected vIL-6 binding to gp130. In bioassays, vIL-6 activity was neutralized by 4 monoclonal antibodies (mAbs) recognizing a domain within vIL-6 site I, mapped to the C-terminal part of the AB-loop and the beginning of helix B. The homologous region in hIL-6 participates in site I binding to IL-6R. In addition, binding of vIL-6 to sgp130 was interfered with specifically by the 4 neutralizing anti–vIL-6 mAbs. Based on the vIL-6 crystal structure, the vIL-6 neutralizing mAbs map outside the binding interface to gp130, suggesting that they either produce allosteric changes or block necessary conformational changes in vIL-6 preceding its binding to gp130. These results document that vIL-6 does not bind IL-6R and suggest that conformational change may be critical to vIL-6 function.
Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients
Authors: Müller Susanna M. , Ege Markus , Pottharst Annette , Schulz Ansgar S. , Schwarz Klaus , Friedrich Wilhelm 
Published: July 2002

AbstractA study in 121 infants with severe combined immunodeficiency (SCID) was performed to determine the prevalence of an engraftment by transplacentally acquired maternal T cells and to explore clinical and immunological findings related to this abnormality. Each newly diagnosed patient with SCID presenting with circulating T cells was evaluated for chimerism by performing selective HLA typing of T cells and non–T cells. In patients with engraftment, maternal T cells were characterized phenotypically and functionally, and results were correlated with clinical findings in the patients. Maternal T cells were detected in the circulation in 48 patients; these cells ranged from fewer than 100/μL in 14 cases to more than 2000/μL in 4 cases (median, 415/μL). Clinical signs of graft-versus-host disease (GVHD) were absent in 29 patients. In the other cases, manifestations of GVHD were present, involving the skin and in 14 cases also the liver. Skin GVHD was mild in 8 patients. In these patients, as well as in patients with no signs of GVHD, maternal T cells were predominantly CD8+ and, with one exception, failed to respond to mitogen stimulation. In 9 patients, manifestations of skin GVHD were prominent. T cells in these cases were predominantly CD4+ and responded, with one exception, to mitogen stimulation. In 8 of the cases with prominent skin GVHD, the underlying SCID variant was characterized by the absence of B cells. In this study, further understanding is provided of a phenomenon that is responsible for the significant heterogeneity of clinical and immunological findings in SCID.
Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies
Authors: Sanz Guillermo F. , Saavedra Silvana , Planelles Dolores , Senent Leonor , Cervera Jose , Barragán Eva , Jiménez Carmen , Larrea Luis , Martı́n Guillermo , Martı́nez Jesús , Jarque Isidro , Moscardó Federico , Plumé Gemma , Andreu Rafael , Regadera Ana I. , Garcı́a Inmaculada , Mollá Susana , Solves Pilar , de la Rubia Javier , Bolufer Pascual , Benlloch Luis , Soler Marı́a A. , Marty Marı́a L. , Sanz Miguel A. 
Published: July 2002

Abstract
The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults remains unclear. This study reports the results of UD-CBT in 22 adults with hematologic malignancies following conditioning with thiotepa, busulfan, cyclophosphamide, and antithymocyte globulin in 21, with thiotepa, fludarabine, and antithymocyte globulin in 1, and graft-versus-host disease (GVHD) prophylaxis with cyclosporine and prednisone. Median age was 29 years (range, 18-46 years), and median weight was 69.5 kg (range, 41-85 kg). HLA match was 6 of 6 in 1 case, 5 of 6 in 13 cases, and 4 of 6 in 8 cases. Median number of nucleated cells infused was 1.71 × 107/kg (range, 1.01 × 107/kg to 4.96 × 107/kg). All 20 patients surviving more than 30 days had myeloid engraftment, and only 1, who received the lowest cell dose, developed secondary graft failure. Median time to reach an absolute neutrophil count of at least 0.5 × 109/L was 22 days (range, 13-52 days). Median time to platelets numbered at least 20 × 109/L was 69 days (range, 49-153 days). Seven patients (32%) developed acute GVHD above grade II, and 9 of 10 patients at risk developed chronic GVHD, which became extensive in 4 patients. Twelve patients remained alive and disease-free 3 to 45 months after transplantation. Disease-free survival (DFS) at 1 year was 53%. Age strongly influenced DFS (P = .01). For patients aged 30 years or younger, the DFS at 1 year was 73%. These preliminary results suggest that UD-CBT should be considered a reasonable alternative in young adults with hematologic malignancy and no appropriate bone marrow donor.
Effects of PEEP on inspiratory resistance in mechanically ventilated COPD patients
Authors: Guérin C. , Fournier G. , Milic-Emili J. 
Published: July 2002

This study aimed to investigate the effect of increased lung volume with positive end-expiratory pressure (PEEP) on respiratory resistance in patients with chronic obstructive pulmonary disease (COPD).Ten patients with COPD were mechanically ventilated for acute respiratory failure. PEEP was set at 0, 5, 10 and 15 cmH2O. Using the rapid airway occlusion technique, the total inspiratory resistance of the respiratory system was partitioned into interrupter (Rint,rs) and additional effective (ΔRrs) resistances. At each level of PEEP, at constant inflation flow, the inflation volume (ΔV) was varied from 0.2–1 L, and, at constant ΔV, the inflation flow was varied from 0.2–1.2 L·s−1. The changes in end-expiratory lung volume (ΔEELV) induced by PEEP were also measured.The difference between the EELV and the relaxation volume of the respiratory system (ΔFRC) increased significantly with PEEP of 10 and 15 cmH2O as compared to a PEEP of 0, the increase being associated with a significant reduction ofRint,rs. By contrast, ΔRrswas independent of ΔFRC. At constant ΔV,Rint,rsfitted Rohrer's equation (Rint,rs=K1+K2×flow). While K2significantly declined with ΔFRC, K1did not change. At all levels of PEEP, ΔRrswas not influenced by ΔFRC.With increasing lung volume induced by positive end-expiratory pressure, the inspiratory airway resistance decreased, whereas the viscoelastic behaviour of the respiratory system, as reflected by additional effective resistance, did not change.
Influence of neonatal screening and centralized treatment on long-term clinical outcome and survival of CF patients
Authors: Mérelle M.E. , Schouten J.P. , Gerritsen J. , Dankert-Roelse J.E. 
Published: July 2002

After an experimental neonatal screening program for cystic fibrosis (CF) from 1973–1979, a follow-up study took place from 1980–1997. Patients were treated at specialized centres (C) or at local hospitals (non-C). Aims of the study were: 1) to determine whether the previously reported benefits from screening persisted with time and after adjustment for confounding variables; and 2) to investigate whether centre treatment was associated with improved prognosis of CF patients.Prognosis of patients detected by screening (S; n=24) was compared with patients detected clinically, born during (non-S; n=29) and after the screening programme (post-S; n=39). In addition, prognosis was compared between 45 C and 47 non-C patients. Multivariable regression analysis was used to compare survival and mixed-effects model regression analysis was used to compare clinical outcome between patients. The analyses included the variables screening, centre treatment, sex, meconium ileus and genotype.S patients had a significantly smaller decline in forced expiratory volume in one second (FEV1) (difference +2.74% predicted) and significantly lower immunoglobulin-G (IgG) levels (difference −473.69 mg·dL−1) than non-S patients until 12 yrs of age. At 12 yrs of age, vital capacity was significantly higher in S patients than in non-S patients (difference +362.79 mL). Survival seemed to be best for S patients compared to both non-S and post-S patients. Post-S patients were significantly heavier (difference in sd weight +0.77), had a significantly smaller decline in FEV1(difference +2.80% pred) and lower IgG levels (difference −453.04 mg·dL−1) than non-S patients until 12 yrs of age. C patients had a significantly improved survival (relative risk (RR) 0.18, 95% confidence interval 0.05–0.57) than non-C patients.Early diagnosis through neonatal screening leads to better preservation of lung function in the long term in cystic fibrosis patients. Management of cystic fibrosis patients in specialized centres improves survival.
Determinants of cough in young adults participating in the European Community Respiratory Health Survey
Authors: Janson C. , Chinn S. , Jarvis D. , Burney P. 
Published: July 2002

Cough is a common symptom that affects a large proportion of the general population. The aim of this investigation was to identify determinants of nocturnal, nonproductive and productive cough in population samples from different countries.In a cross-sectional international population survey, 18,277 subjects (20–48 yrs) from 16 countries answered an interview-led questionnaire. Total and specific immunoglobulin-;E was measured and spirometry was performed. Three types of cough were defined: nocturnal, nonproductive and productive cough. The relation of the independent variables to cough was estimated by means of logistic regression for each centre or country and combined across centre or country by random-effects meta-analysis.The median prevalence of nocturnal, nonproductive and productive cough in the different centres was 30.7%, 10.2% and 10.2%, respectively. Nocturnal and nonproductive cough were related to female sex (adjusted odds ratio (OR)=2.08 and 1.27, respectively), while nocturnal and productive cough were related to rhinitis (OR=1.46 and 1.61, respectively). All three types of cough were related to asthma, tobacco smoking, environmental tobacco smoke and obesity.Females are more likely to report nocturnal and nonproductive cough than males. Cough was related to treatable disorders, like asthma and rhinitis, as well as avoidable factors, such as tobacco smoking and environmental tobacco smoke.
Development and validation of the Adolescent Asthma Quality of Life Questionnaire (AAQOL)
Authors: Rutishauser C. , Sawyer S.M. , Bond L. , Coffey C. , Bowes G. 
Published: July 2002

Current asthma-specific quality of life questionnaires have major conceptual and methodological deficiencies for use in adolescents. The aim of this study was to develop and validate the “Adolescent Asthma Quality of Life Questionnaire (AAQOL)”, specifically developed for adolescents with asthma.One-hundred and eleven adolescents with frequent-episodic or persistent asthma aged 12–17 yrs were recruited from three tertiary paediatric asthma clinics. The standardized multi-step method consisted of: 1) item selection including semistructured interviews (n=14); 2) item reduction and validation (n=66); and 3) assessment of reproducibility (n=31). Item reduction was performed applying the clinical impact method.The 32 item AAQOL covers six domains: symptoms, medication, physical activities, emotion, social interaction and positive effects. There was high internal consistency for the six domains (α=0.70–0.90) and for the total score (α=0.93). Test-retest reliability was high for all domain scores (r=0.76–0.85) and the total score (r=0.90), indicating high reproducibility of the AAQOL. There was high correlation with the paediatric Asthma Quality of Life Questionnaire (ρ=0.81) which focuses primarily on symptoms and emotional well-being. There was weak to moderate correlation with clinical parameters of asthma severity (ρ=0.25–0.65).The 32-item Adolescent Asthma Quality of Life Questionnaire is a valid, developmentally age-appropriate and dimensionally comprehensive asthma-specific quality of life measure for use in adolescents.
Plethysmographic measurements of lung volume and airway resistance
Authors: Stocks J. , Godfrey S. , Beardsmore C. , Bar-Yishay E. , Castile R. 
Published: July 2002

Functional residual capacity (FRC) is the only static lung volume that can be measured routinely in infants. It is important for interpreting volume-dependent pulmonary mechanics such as airway resistance or forced expiratory flows, and for defining normal lung growth. Despite requiring complex equipment, the plethysmographic method for measuring FRC is very simple to apply and, unlike the gas dilution techniques, enables repeat measures of lung volume to be obtained within a few minutes. This method has the further advantage that with suitable adaptations to the equipment, simultaneous measurements of airway resistance can also be obtained.The aim of this paper is to provide recommendations pertaining to equipment requirements, study procedures and reporting of data for plethysmographic measurements in infants. Implementation of these recommendations should help to ensure that such measurements are as accurate as possible and that meaningful comparisons can be made between data collected in different centres or with different equipment. These guidelines cover numerous aspects including terminology and definitions, equipment, data acquisition and analysis and reporting of results and also highlight areas where further research is needed before consensus can be reached.
Reversing acute bronchoconstriction in asthma: the effect of bronchodilator tolerance after treatment with formoterol
Authors: Jones S.L. , Cowan J.O. , Flannery E.M. , Hancox R.J. , Herbison G.P. , Taylor D.R. 
Published: July 2002

Continuous treatment with a short-acting β2‐agonist can lead to reduced bronchodilator responsiveness during acute bronchoconstriction. This study evaluated bronchodilator tolerance to salbutamol following regular treatment with a long-acting β2‐agonist, formoterol. The modifying effect of intravenous corticosteroid was also studied.Ten asthmatic subjects (using inhaled steroids) participated in a randomised, double-blind, placebo-controlled, cross-over study. Formoterol 12 μgb.i.d.or matching placebo was given for 10–14 days with >2 weeks washout. Following each treatment, patients underwent a methacholine challenge to induce a fall in forced expired volume in one second (FEV1) of at least 20%, then salbutamol 100 μg, 100 μg, and 200 μg was inhaledviaa spacer at 5 min intervals, with a further 400 μg at 45 min. After a third single-blind formoterol treatment period, hydrocortisone 200 mg was given intravenously prior to salbutamol. Dose-response curves for change in FEV1with salbutamol were compared using analysis of covariance to take account ofmethacholine-induced changes in spirometry.Regular formoterol resulted in a significantly lower FEV1after salbutamol at each time point compared to placebo (p<0.01). The area under the curves (AUCs) for 15 (AUC0–15) and 45 (AUC0–45) min were 28.8% and 29.5% lower following formoterol treatment (p<0.001). Pretreatment with hydrocortisone had no significant modifying effect within 2 h of administration.It is concluded that significant tolerance to the bronchodilator effects of inhaled salbutamol occurs 36 h after stopping the regular administration of formoterol. This bronchodilator tolerance is evident in circumstances of acute bronchconstriction.
Allergic sensitization and diet: ecological analysis in selected European cities
Authors: Heinrich J. , Hölscher B. , Bolte G. , Winkler G. 
Published: July 2002

It has been postulated that the prevalence of atopic diseases and their increase over time are associated with regional differences in diet and trends. The results of an ecological correlation study comparing the mean daily intake of selected dietary constituents and the prevalence of allergic sensitization in adults in Europe is presented.Prevalence data from the European Community Respiratory Health Survey (ECRHS) were used. For eight out of 37 ECRHS centres (including 3,872 subjects), comparable dietary data could be obtained. The effect for each dietary constituent was modelled using logistic regression analyses with a term for over dispersion.Inverse associations between the prevalence of allergic sensitization and the energy adjusted intake of fruit were found (odds ratio (OR)=0.68, p=0.034). Furthermore OR for energy adjusted intake of vitamin A (OR=0.73, p=0.057), vitamin C (OR=0.83, p=0.338) and riboflavin (OR=0.72, p=0.077) were consistently <1, but confidence intervals were wider. Daily intake of monounsaturated fatty acids (energy adjusted) was positively associated with sensitization prevalence (OR=1.59, p=0.035).These results support the hypothesis that a high intake of monounsaturated fatty acids might promote the development of allergic sensitization.
Primary ciliary dyskinesia syndrome associated with abnormal ciliary orientation in infants
Authors: Biggart E. , Pritchard K. , Wilson R. , Bush A. 
Published: July 2002

Primary ciliary dyskinesia (PCD) syndrome associated with abnormal ciliary orientation but with normal ciliary ultrastructure has been described in adults, but there are no normal ranges for orientation in infants, despite the fact that half of all patients with PCD present in the new-born period.Nasal brush biopsies were obtained from eight infants (three males), mean age 13.1 months, range 7–23, in order to determine ciliary orientation. They had no upper or lower airway disease and normal organ arrangement and were undergoing general anaesthesia for other reasons. Two infants with typical PCD syndrome but normal ultrastructure of individual cilia also had orientation studies.In the eight normal subjects, a mean of 254 central pairs was examined, range 82–453. The mean ciliary orientation was 14.9 degrees, range 12.9–17.5. The two infants with PCD syndrome but normal ultrastructure of individual cilia had ciliary orientation of (Case 1) 44.5 degrees (range 10.6–64.5) in 218 central pairs; and on a second occasion, 28.9 degrees, (range 9.0–47.5) in 259 central pairs; for Case 2, 24.4 degrees, (range 13.1–38.4) in 196 central pairs.The normal range for ciliary orientation is similar in infants to that described in other work in adults. The two cases of phenotypic primary ciliary dyskinesia in the presence of normal ciliary ultrastructure but abnormal ciliary orientation in infants supports the contention that measurement of ciliary orientation should be part of the assessment of ciliary structure and function in cases of possible primary ciliary dyskinesia, in particular when the ultrastructure of individual cilia appear to be normal.
Long-term use of mandibular advancement splints for snoring and obstructive sleep apnoea: a questionnaire survey
Authors: McGown A.D. , Makker H.K. , Battagel J.M. , L'Estrange P.R. , Grant H.R. , Spiro S.G. 
Published: July 2002

A mandibular advancement splint (MAS) may be an alternative treatment for snoring and obstructive sleep apnoea (OSA). However, there is little subjective or objective information concerning long-term effectiveness, compliance and side effects.A retrospective questionnaire was used to survey these issues plus patient satisfaction and maintenance requirements in 166 patients who could have worn a mandibular advancement splint for over a year.One-hundred and twenty-six (76%) subjects returned the questionnaire, (84 with OSA, 42 snorers), of whom 69 (55%) reported still using the splint regularly, 47 (37%) every night. The most common reported reasons for stopping use were discomfort (29/57; 52% of nonusers), and poor perceived efficacy (12 subjects). Users reported more daytime symptoms, and they and their partners were more likely to observe improvements with splint use. Side effects were reported by 49 subjects, more commonly in nonusers. Sixty-five of 67 current users and 23 of 41 nonusers reported less snoring with splint use (p=<0.001).Long-term mandibular advancement splint usage appeared less satisfactory than previously reported, however, splints were considered effective by 97% of current users and even by over half of those who had stopped use. Reasons for stopping use included side effects, social circumstances, dental treatment, as well as lack of perceived efficacy.
Serum Clara cell protein (CC16), a marker of the integrity of the air-blood barrier in sarcoidosis
Authors: Hermans C. , Petrek M. , Kolek V. , Weynand B. , Pieters T. , Lambert M. , Bernard A. 
Published: July 2002

To test the hypothesis that sarcoidosis is associated with an intravascular leakage of lung epithelium secretory proteins, the occurrence and determinants in serum of sarcoid patients of CC16, a small size and readily diffusible lung-specific protein of 16 kDa secreted by bronchiolar Clara cells, was investigated.CC16 was measured by a sensitive latex immunoassay in the serum of 117 patients with established sarcoidosis and of 117 healthy subjects matched for age, sex and smoking status. Stepwise regression analysis was used to identify extrapulmonary variables of CC16 changes in serum. These changes were then compared with biochemical and cellular parameters in bronchoalveolar lavage fluid (BALF) as well as with the number of CC16 immunostaining cells on bronchial or pulmonary biopsy samples.CC16 concentration in serum of sarcoid patients was significantly increased, compared to their matched controls (25.9±16.2versus13.9±5.2 µg·L−1). In nonsmoking patients without significant renal impairment, CC16 in serum increased with the severity of the chest radiograph and computed tomography changes, and was on average 50–100% higher when parenchymal involvement was present. Sarcoid patients had, however, normal levels of CC16 in BALF and an unchanged number of CC16-immunopositive cells in lung biopsy samples, suggesting that an increased secretion of CC16 in the sarcoid lung is very unlikely, and that the elevation of CC16 in sarcoidosis results from an increased intravascular leakage of the protein across the air-blood barrier.The present study suggests that CC16 in serum might provide a useful tool to noninvasively evaluate the damage and increased permeability to proteins of the air-blood barrier associated with sarcoidosis.