bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different lung responses to cigarette smoke in two strains of mice sensitive to oxidants
Authors: Bartalesi B. , Cavarra E. , Fineschi S. , Lucattelli M. , Lunghi B. , Martorana P. A. , Lungarella G. 
Published: January 2005

The development of cigarette smoke-induced pulmonary changes in C57 Bl/6J and DBA/2 mice was investigated. Both strains are sensitive to oxidants and C57Bl/6J mice are moderately deficient in serum alpha1-proteinase inhibitor.Following chronic exposure to cigarette smoke, patchy emphysema was present in mice of both strains, but developed faster in DBA/2 mice. A positive reaction for mouse neutrophil elastase was seen on the septa of both strains. Additionally, the DBA/2 mice developed a uniform parenchymal dilation that was preceded by the appearance of apoptotic cells in areas with a low signal for vascular endothelial growth factor-receptor 2. Fibrotic areas scattered throughout the parenchyma, coupled with a positive immunohistochemical reaction for transforming growth factor-β was seen only in DBA/2 mice.Both DBA/2 and C57Bl/6J strains showed epithelial cell injury and areas of deciliation in their airways. However, the appearance of goblet cell metaplasia was common in C57Bl/6J mice but rare in DBA/2 mice. A positive immunohistochemical reaction for interleukin (IL)-4, IL-13 and MUC5AC was seen only in the airways of C57Bl/6J mice.Strain characteristics (alpha1-proteinase inhibitor levels, sensitivity to oxidants, and constitutive levels of vascular endothelial growth factor-receptor 2) and phenotypical responses (apoptosis and cytokine distribution) may condition parenchymal and airway changes to cigarette smoke.
Quantitative computed tomography and aerosol morphometry in COPD and α1-antitrypsin deficiency
Authors: Shaker S. B. , Maltbaek N. , Brand P. , Haeussermann S. , Dirksen A. 
Published: January 2005

Relative area of emphysema below -910 Hounsfield units (RA-910) and 15th percentile density (PD15) are quantitative computed tomography (CT) parameters used in the diagnosis of emphysema. New concepts for noninvasive diagnosis of emphysema are aerosol-derived airway morphometry, which measures effective airspace dimensions (EAD) and aerosol bolus dispersion (ABD).Quantitative CT, ABD and EAD were compared in 20 smokers with chronic obstructive pulmonary disease (COPD) and 22 patients with α1-antitrypsin deficiency (AAD) with a similar degree of airway obstruction and reduced diffusion capacity.In both groups, there was a significant correlation between RA-910 and PD15 and pulmonary function tests (PFTs). A significant correlation was also found between EAD, RA-910 and PD15 in the study population as a whole. Upon separation into two groups, the significance disappeared for the smokers with COPD and strengthened for those with AAD, where EAD correlated significantly with RA-910 and PD15. ABD was similar in the two groups and did not correlate with PFT and quantitative CT in either group.In conclusion, based on quantitative computed tomography and aerosol-derived airway morphometry, emphysema was significantly more severe in patients with α1-antitrypsin deficiency compared with patients with usual emphysema, despite similar measures of pulmonary function tests.
Respiratory muscle dysfunction in idiopathic pulmonary arterial hypertension
Authors: Meyer F. J. , Lossnitzer D. , Kristen A. V. , Schoene A. M. , Kübler W. , Katus H. A. , Borst M. M. 
Published: January 2005

Idiopathic pulmonary arterial hypertension (IPAH) is a pulmonary vasculopathy of unknown aetiology. Dyspnoea, peripheral airway obstruction and inefficient ventilation are common in IPAH. Data on respiratory muscle function are lacking.This prospective single-centre study included 26 female and 11 male patients with IPAH in World Health Organization functional classes II–IV. Mean±sdpulmonary artery pressure was 48.6±16.9 in females and 53.1±22.9 mmHg in males; cardiac output was 3.7±1.3 and 4.2±1.7 L·min−1.Maximal inspiratory pressure (PI,max) was lower in the female patients than in 20 controls (5.3±2.0versus8.2±2.0 kPa). In the male patients,PI,max was lower than in 25 controls (6.8±2.2versus10.5±3.7 kPa). Maximal expiratory pressure (PE,max) was lower in the female patients than in controls (6.2±2.6versus9.5±2.1 kPa), and in male patients as compared to controls (7.1±1.6versus10.3±3.9 kPa). There was no correlation betweenPI,max orPE,max and parameters of pulmonary haemodynamics or exercise testing. The ratio of mouth occlusion pressure within the first 0.1 s of inspiration andPI,max was higher in IPAH than in controls (females 0.067±0.066versus0.021±0.008; males 0.047±0.061versus0.023±0.016).In conclusion, this study provides the first evidence of inspiratory and expiratory muscle weakness in idiopathic pulmonary arterial hypertension. The pathomechanisms and the prognostic significance should be further investigated.
The timed walk test as a measure of severity and survival in idiopathic pulmonary fibrosis
Authors: Hallstrand T. S. , Boitano L. J. , Johnson W. C. , Spada C. A. , Hayes J. G. , Raghu G. 
Published: January 2005

Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive disease with a median survival of ∼3 yrs. Measurements of airflow and lung volumes at rest are generally used to monitor the clinical course in this disorder. This study was designed to determine if a modified version of the 6-min walk test, called the timed walk test, accurately characterises disease severity and survival in IPF.The study population consisted of 28 patients with well-characterised progressive IPF. The timed walk test and concurrent measures of disease severity were assessed at baseline. Participants were prospectively followed for ≥4 yrs to determine the relationship between parameters of the timed walk test and survival.There were strong correlations between the end-exercise saturation and walk-velocity parameters of the timed walk test and diffusing capacity, and arterial oxygen tension at rest. In univariate Cox proportional-hazards models, end-exercise saturation, change in saturation with exercise, walk distance and walk velocity were associated with survival. In unadjusted logistic regression models, odds of death at 2 yrs were associated with the same parameters.In conclusion, the timed walk test relates to disease severity and long-term outcome in progressive idiopathic pulmonary fibrosis.
Antibiotic therapy reduces nitrosative stress and programmed cell death in the rabbit foetal lung
Authors: Gras-Le Guen C. , Jarry A. , Vallette G. , Toquet C. , Colombeix C. , Laboisse C. L. , Potel G. , Roze J-C. , Bugnon D. , Debillon T. 
Published: January 2005

The correlation of clinical and epidemiological data suggests that intrauterine infection/inflammation can promote foetal lung injury.The aim of this study was: 1) to characterise the early inflammatory response elicited in infected foetal lungs, in terms of nitric oxide-derived oxidative stress and programmed cell death; and 2) to investigate the effects of antibiotic therapy on these parameters.A previously described rabbit experimental model of materno-foetal infection was used. Animals were divided into three groups: controls;Escherichia coliinfected (12 h); andE. Coliinfected (12 h) and treated (24 h gentamicin+ceftriaxone). Foetal lungs were examined in terms of histology, nitric oxide synthase (NOS) activity, immunohistochemical detection of 3-nitrotyrosine, and detection of apoptotic cells by the TUNEL assay and Hoechst staining.In the infected group, a moderate inflammatory response was observed, associated with a significant increase in inducible NOS activity, the formation of 3-nitrotyrosine residues in epithelial and immune cells, the down-regulation of constitutive NOS activity and clusters of apoptotic cells, as compared with the control group. Early antibiotic therapy, initiated at 12 h post-inoculation, elicited a significant decrease in the infection-induced nitrosative stress. Levels of 3-nitrotyrosine and of apoptotic cells were decreased in the infected-and-treated group compared with the infected group, mainly by the re-expression of constitutive NOS and of the basal level of inducible NOS.Altogether, these findings indicate that early antibiotic therapy can curb the inflammatory reaction and help avert antenatal lung injury, which is known to be involved in the onset of bronchopulmonary dysplasia.
HIV-1 Nef mediates post-translational down-regulation and redistribution of the mannose receptor
Authors: Vigerust David J , Egan Brian S , Shepherd Virginia L 
Published: January 2005

AbstractHuman immunodeficiency virus (HIV) has derived a variety of means to evade the host immune response. HIV-derived proteins, including Tat, Nef, and Env, have all been reported to decrease expression of host molecules such as CD4 and major histocompatibility complex I, which would assist in limiting viral replication. The mannose receptor (MR) on the surface of macrophages and dendritic cells (DC) has been proposed to function as an effective antigen-capture molecule, as well as a receptor for entering pathogens such as Mycobacterium tuberculosis and Pneumocystis carinii. Regulation of this receptor would therefore benefit HIV in removing an additional arm of the innate immune system. Previous work has shown that MR function is reduced in alveolar macrophages from HIV-infected patients and that surface MR levels are decreased by the HIV-derived protein Nef in DC. In addition, several laboratories have shown that CD4 is removed from the surface of T cells in a manner that might be applicable to decreased MR surface expression in macrophages. In the current study, we have investigated the role of Nef in removing MR from the cell surface. We have used a human macrophage cell line stably expressing the MR as well as human epithelial cells transiently expressing CD4 and a unique CD4/MR chimeric molecule constructed from the extracellular and transmembrane domains of CD4 and the cytoplasmic tail portion of the MR. We show that the MR is reduced on the cell surface by ∼50% in the presence of Nef and that the MR cytoplasmic tail can confer susceptibility to Nef in the CD4/MR chimera. These data suggest that the MR is a potential intracellular target of Nef and that this regulation may represent a mechanism to further cripple the host innate immune system.
Cancer Screening in Theory and in Practice
Authors: Brawley Otis W. , Kramer Barnett S. 
Published: January 2005

Improvements in technology have led to a number of tests that can be used to suggest that a patient has a cancer. Advances in cancer biology and medical imaging have led to a number of cancer screening tests. Cancer screening is commonly advocated, but its complexity is often lost in guidelines that have sound-bite quality. It is commonly viewed as of no harm, when in fact there are harms associated with every known screening test. Indeed, many screening experts believe a screening test should only be used when the potential for benefit clearly outweighs the potential for harm. Cancer screening principles are classically within the realm of the epidemiologist. As more screening tests are developed, these principles have become more relevant to the practicing clinician. What is known and what is unknown about screening is distinctly different from what is believed by the public and many practicing clinicians. Many tests have both screening and diagnostic uses, and it is only the context in which these are used that determines whether they are screening or diagnostic. A screening test is done on asymptomatic individuals who receive the test principally because they are of the age or sex at risk for the cancer. A diagnostic test is done on an individual because of clinical suspicion of disease.
Pituitary Transcription Factor-1 Induces Transient Differentiation of Adult Hepatic Stem Cells into Prolactin-Producing Cells in Vivo
Authors: Lee Eun Jig , Russell Theron , Hurley Lisa , Jameson J. Larry 
Published: January 2005

Abstract
A subset of transcription factors function as pivotal regulators of cell differentiation pathways. Pituitary transcription factor-1 (Pit-1) is a tissue-specific homeodomain protein that specifies the development of pituitary somatotropes and lactotropes. In this study, adenovirus was used to deliver rat Pit-1 to mouse liver. Pit-1 expression was detected in the majority (50–80%) of hepatocyte nuclei after tail vein injection (2 × 109 plaque forming units). Pit-1 activated hepatic expression of the endogenous prolactin (PRL), GH, and TSHβ genes along with several other markers of lactotrope progenitor cells. Focal clusters (0.2–0.5% of liver cells per tissue section) of periportal cells were positive for PRL by immunofluorescent staining. The PRL-producing cells also expressed proliferating cell nuclear antigen as well as the hepatic stem cell markers (c-Kit, Thy1, and cytokeratin 14). These data indicate that Pit-1 induces the transient differentiation of hepatic progenitor cells into PRL-producing cells, providing additional evidence that transcription factors can specify the differentiation pathway of adult stem cells.
Tetanus: the ’forgotten disease’. A rare cause of dysphagia and trismus
Authors: Tahery Jawed , Morris David P. , Birzgalis Andrew R. 
Published: January 2005

Tetanus kills approximately 500 000 people worldwide each year. Widespread immunization has ensured that it is rarely encountered in the United Kingdom. An increase in global travel may increase the likelihood of such encounters in the developed world in the future.In the non-immunized patient, death from tetanus can be avoided by early recognition and timely intervention. The potential need for airway support and sedation should not be underestimated.The authors’ case report should increase the awareness of the otolaryngologist when confronted with atypical cases of dysphagia and trismus and provides details of the recommended treatment regime.
Pseudosarcomatous fibrovascular proliferative tissue masquerading as a primary subglottic angiosarcoma
Authors: Persaud Ricardo , Vahidova Dil , Kirsch Claudia , Calaminici Maria , Ghufoor Khalid 
Published: January 2005

A unique case of pseudosarcomatous fibrovascular proliferative tissue causing biphasic stridor and simulating a primary subglottic angiosarcoma is reported.The patient presented with a wheeze and was diagnosed initially with asthma. He subsequently developed worsening biphasic stridor. Flexible nasendoscopy revealed a subglottic mass obstructing the airway. The mass was removed with a carbon dioxide laser and the patient’s condition improved dramatically. The specimen was difficult to interpret histologically and was thought at first to be a novel case of a primary subglottic angiosarcoma. However, the slides were reviewed by expert soft tissue pathologists in the UK and USA, and a final diagnosis of a pseudosarcomatous fibrovascular proliferative lesion was made.This case highlights the important principle of seeking additional opinions before making a malignant diagnosis in an atypical site. Our report also emphasizes the importance of good clinico-pathological liaison, especially in difficult cases.
Acquired Activated Protein C Resistance Associated with IgG Antibodies against β2-Glycoprotein I and Prothrombin as a Strong Risk Factor for Venous Thromboembolism
Authors: Nojima Junzo , Kuratsune Hirohiko , Suehisa Etsuji , Iwatani Yoshinori , Kanakura Yuzuru 
Published: January 2005

AbstractBackground: Venous thromboembolic events such as deep vein thrombosis and pulmonary embolism are common manifestations of antiphospholipid syndrome. Our aim was to clarify the roles of anti-phospholipid (aPL) antibodies in the pathogenesis of venous thromboembolism (VTE) in patients with systemic lupus erythematosus (SLE).Methods and Results: We examined anti-cardiolipin/β2-glycoprotein I (anti-CL/β2-GPI) antibody concentrations, anti-phosphatidylserine/prothrombin (anti-PS/PT) antibody concentrations, and lupus anticoagulant (LA) activity in 87 patients with SLE (21 with VTE and 66 without thrombosis). Both anti-CL/β2-GPI and anti-PS/PT antibodies strongly correlated with LA activity. Multivariate logistic analysis confirmed that both anti-CL/β2-GPI and anti-PS/PT antibodies were significant independent risk factors for VTE (odds ratios = 4.98 and 7.54, respectively; 95% confidence intervals, 1.51–16.4 and 2.30–24.7, respectively). We therefore studied the in vitro effects of IgG fractions containing anti-CL/β2-GPI or anti-PS/PT antibodies on the anticoagulant activity of activated protein C (APC) and found that purified IgG containing anti-CL/β2-GPI or anti-PS/PT antibodies significantly hampered the anticoagulant activity of APC. We also studied the ability of IgG fractions to impede the anticoagulant activity of APC before and after complete removal of anti-CL/β2-GPI or anti-PS/PT antibodies by adsorption. Removal of anti-CL/β2-GPI or anti-PS/PT antibodies from all positive IgG samples clearly decreased the inhibitory effect of those samples on APC anticoagulant activity.Conclusions: Anti-CL/β2-GPI and anti-PS/PT antibodies independently cause APC resistance, which may contribute to risk of VTE in patients with SLE.
Adaptive behavior in children with CHARGE syndrome
Authors: Salem‐Hartshorne Nancy , Jacob Susan 
Published: January 2005

AbstractThe “R” in the mnemonic “CHARGE” has historically stood for “Retardation of Growth and Development.” Early medical reports describing mental retardation in CHARGE syndrome have not used convincing means to assess this attribute. This article investigated the range of developmental ability in individuals with CHARGE as measured through an adaptive behavior scale, the Adaptive Behavior Evaluation Scale (ABES) [Carney (1995): The Adaptive Behavior Evaluation Scale home version technical manual‐revised. 126p.], over time. Parents of individuals with CHARGE syndrome were surveyed twice over a 4‐year time span (N = 100, 85) to obtain information about adaptive behavior and specific CHARGE characteristics. There was a significant decline in ABES scores over the 4‐year period. However, at Time two, one‐half of the children achieved a standard score above 70. Correlation and regression analyses at Time one and Time two revealed negative relationships between (a) age at walking, (b) degree of hearing impairment, (c) degree of visual impairment, and (d) medical involvement variables and the dependent variable, adaptive behavior. In both studies, age at walking was the best predictor of scores. Analysis of variance confirmed that medical involvement and degree of vision impairment were related to adaptive behavior scores because they were also related to age at walking. Age at walking and medical involvement at Time one were found to be significantly different between those who improved and declined in adaptive behavior scores over time. Adaptive behavior scores from both studies revealed a much broader and higher‐reaching range of ability for this population than has been previously reported in the literature. © 2005 Wiley‐Liss, Inc.
C‐reactive protein as a predictor of infliximab treatment outcome in patients with rheumatoid arthritis: Defining subtypes of nonresponse and subsequent response to etanercept
Authors: Buch Maya H. , Seto Yohei , Bingham Sarah J. , Bejarano Victoria , Bryer Domini , White Jo , Emery Paul 
Published: January 2005

AbstractObjectiveNonresponse to anti–tumor necrosis factor α in patients with rheumatoid arthritis (RA) is poorly understood. The aims of this study were to define nonresponse patterns using infliximab and C‐reactive protein (CRP) profiles, to assess the predictive power of a CRP response for outcome, and to correlate these findings with subsequent response to etanercept.MethodsWe studied 207 patients with resistant RA who were started on treatment with infliximab. After 12 weeks, the American College of Rheumatology 20% improvement criteria (ACR20) were used to classify patients as responders (ACR20 response or greater) or nonresponders (NRs). The NRs were further subdivided into 3 groups according to the CRP response at weeks 2, 6, and 12. Within the NR group, those with a suppressed CRP at week 12 continued taking infliximab for a further 12 weeks; those without a CRP response were switched to etanercept, and the ACR response at 12 weeks was calculated.ResultsAt week 12, 54% of patients achieved an ACR20 response, and 46% failed to achieve a response. Of the NRs, 63% demonstrated a significant reduction in the CRP level at week 12, 59% of whom achieved an ACR20 response at week 24 on continuation of infliximab. Of the patients who did not demonstrate a significant reduction in the CRP level after the first infusion, 86% failed to show a biochemical or ACR20 response by week 12. Twenty‐four percent of the NRs had a temporary reduction in the CRP level, and 13% of the NRs showed no CRP reduction. Seventy‐five percent of these NRs switched to etanercept, and 68% of this group achieved an ACR20 response at week 12 (51% achieved an ACR50 response), with a CRP response in 63%.ConclusionInfliximab NRs comprise subtypes with distinct CRP patterns. Failure to suppress the CRP at week 2 identified the majority of patients who were NRs at week 12. CRP suppression at week 12 in the NRs was associated with a late clinical improvement with infliximab treatment (24 weeks), whereas failure to suppress the CRP at week 12 was associated with a good response on switching to etanercept.
The HLA–B*5703 allele confers susceptibility to the development of spondylarthropathies in Zambian human immunodeficiency virus–infected patients with slow progression to acquired immunodeficiency syndrome
Authors: López‐Larrea C. , Njobvu P. D. , González S. , Blanco‐Gelaz M. A. , Martínez‐Borra J. , López‐Vázquez A. 
Published: January 2005

AbstractObjectiveTo analyze the HLA distribution in a population of individuals from Zambia in order to establish a possible relationship between the progression of human immunodeficiency virus (HIV) infection and the development of spondylarthropathy (SpA).MethodsA large epidemiologic analysis of rheumatology patients living in Zambia was performed in order to identify those who had SpA. We selected 64 patients with SpA and found that 54 also had HIV type 1 (HIV‐1) infection; only 10 were HIV negative. Additionally, we selected 57 HIV‐infected individuals without SpA and 43 healthy controls. Among all of the HIV‐1–infected patients, 25 SpA‐positive and 24 SpA‐negative patients were classified as slow progressors to acquired immunodeficiency syndrome (AIDS), and 8 SpA‐positive and 26 SpA‐negative patients were classified as rapid progressors. All patients were typed for HLA–B alleles.ResultsOf the 64 patients with SpA, HIV infection was observed in 54 (84%). The frequency of B*5703 was increased in patients who were SpA positive and HIV positive compared with patients who were SpA negative and HIV positive (P = 0.0002, odds ratio [OR] 8.28). Among patients who were slow progressors to AIDS, this allele was overrepresented in those with SpA compared with those without SpA (corrected P = 0.001, OR 26.25).ConclusionHLA–B*5703 seems to be a protective allele against the progression of HIV infection but could influence the increased incidence of SpA observed in this population.