bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-dose radioimmunotherapy versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin lymphoma: a multivariable cohort analysis
Authors: Gopal Ajay K. , Gooley Theodore A. , Maloney David G. , Petersdorf Stephen H. , Eary Janet F. , Rajendran Joseph G. , Bush Sharon A. , Durack Lawrence D. , Golden Jane , Martin Paul J. , Matthews Dana C. , Appelbaum Frederick R. , Bernstein Irwin D. , Press Oliver W. 
Published: May 2003

Abstract
We performed a multivariable comparison of 125 consecutive patients with follicular lymphoma (FL) treated at our centers with either high-dose radioimmunotherapy (HD-RIT) using 131I-anti-CD20 (n = 27) or conventional high-dose therapy (C-HDT) (n = 98) and autologous hematopoietic stem cell transplantation. The groups were similar, although more patients treated with HD-RIT had an elevated pretransplantation level of lactate dehydrogenase (41% versus 20%, P = .03) and elevated international prognostic score (41% versus 19%, P = .02). Patients treated with HD-RIT received individualized therapeutic doses of 131I-tositumomab (median, 19.7 GBq [531 mCi]) to deliver 17 to 31 Gy (median, 27 Gy) to critical organs. Patients treated with C-HDT received total body irradiation plus chemotherapy (70%) or chemotherapy alone (30%). Patients treated with HD-RIT experienced improved overall survival (OS) (unadjusted hazard ratio [HR] for death = 0.4 [95% confidence interval (95% CI), 0.2-0.9], P = .02; adjusted HR, 0.3, P = .004) and progression-free survival (PFS) (unadjusted HR = .6 [95% C.I., 0.3-1.0], P = .06; adjusted HR, 0.5, P = .03) versus patients treated with C-HDT. The estimated 5-year OS and PFS were 67% and 48%, respectively, for HD-RIT and 53% and 29%, respectively, for C-HDT. One hundred-day treatment-related mortality was 3.7% in the HD-RIT group and 11% in the C-HDT group. The probability of secondary myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) was estimated to be .076 at 8 years in the HD-RIT group and .086 at 7 years in the C-HDT group. HD-RIT may improve outcomes versus C-HDT in patients with relapsed FL. (Blood. 2003;102:2351-2357)
Disease-associated dendritic cells respond to disease-specific antigens through the common heat shock protein receptor
Authors: Stebbing Justin , Gazzard Brian , Portsmouth Simon , Gotch Frances , Kim Louise , Bower Mark , Mandalia Sundhiya , Binder Robert , Srivastava Pramod , Patterson Steve 
Published: May 2003

AbstractThe most abundant intracellular proteins, heat shock proteins (HSPs), serve as molecular chaperones for regulatory and maturation pathways. Diverse families of HSPs have been shown to bind antigenic peptides and to play major roles in innate and adaptive immune responses through the common HSP receptor, CD91. HIV-1+ patients with Kaposi sarcoma (KS) were matched for CD4 count and HIV-1 RNA viral load to HIV-1+ patients without Kaposi sarcoma (and negative for Kaposisarcoma–associated herpesvirus). We then investigated the pathways used by tumor lysates, viral lysates, and viral particles in their activation. In particular, we observed immune responses after HSP depletion using antitumor antibiotics and blockade of the common HSP receptor, CD91. Despite the impaired functional capacity of dendritic cells (DCs) derived from patients with KS, DCs retain the ability to prime the adaptive arm of the immune system through the common HSP receptor, leading to phenotypic activation and stimulation of tetramer-positive CD8+ cytotoxic T cells. We also show that interferon-producing plasmacytoid DCs are selectively depleted in KS-positive compared with matched KS-negative HIV-1–infected patients. Functionally impaired DCs can effectively cross-present immune responses through the common HSP receptor. These results have important implications for the etiopathogenesis of KS and for the development and design of any compounds, including vaccines, derived from cellular lysates.
ALK activation by the CLTC-ALK fusion is a recurrent event in large B-cell lymphoma
Authors: De Paepe Pascale , Baens Mathijs , van Krieken Han , Verhasselt Bruno , Stul Michel , Simons Annet , Poppe Bruce , Laureys Geneviève , Brons Paul , Vandenberghe Peter , Speleman Frank , Praet Marleen , De Wolf-Peeters Chris , Marynen Peter , Wlodarska Iwona 
Published: May 2003

AbstractWe present 3 cases of large B-cell lymphoma (LBCL) with a granular cytoplasmic staining for anaplastic lymphoma kinase (ALK). All of the cases showed striking similarities in morphology and immunohistochemical profile characterized by a massive monomorphic proliferation of CD20-/CD138+ plasmablast-like cells. In one of the cases, initially diagnosed as a null-type anaplastic large cell lymphoma (ALCL), the B-cell phenotype became evident only at recurrence. Fluorescent in situ hybridization (FISH) and molecular studies led to the detection of a CLTC-ALK rearrangement in all 3 cases, without any evidence of full-length ALK receptor expression. The associated t(2;17)(p23;q23) was demonstrated in the karyotype of 2 cases. Although a similar CLTC-ALK aberration was previously identified in ALK-positive T-/null cell ALCL and inflammatory myofibroblastic tumor, its association with ALK-positive LBCL seems to be specific and intriguing. (Blood. 2003;102:2638-2641)
Signaling through JAM-1 and αvβ3 is required for the angiogenic action of bFGF: dissociation of the JAM-1 and αvβ3 complex
Authors: Naik Meghna U. , Mousa Shaker A. , Parkos Charles A. , Naik Ulhas P. 
Published: May 2003

AbstractGrowth factor–induced neovascularization has received a great deal of attention because it is fundamental to the growth and metastasis of solid tumors. This multistep process requires extensive signaling through growth factor receptors and integrins. Among the integrins involved in this process, integrin αvβ3 is specific to basic fibroblast growth factor (bFGF)–induced angiogenesis. Here we show that junctional adhesion molecule 1/A (JAM-1/A) and αvβ3 form a complex in the absence of bFGF. JAM-1, which is normally localized at the cell-cell junctions of quiescent endothelial cells, redistributes to the cell surface on bFGF treatment. Blockage of the extracellular domain of JAM-1 inhibits bFGF-induced endothelial cell morphology, proliferation, and angiogenesis. Additionally, mutation in the JAM-1 cytoplasmic domain blocks bFGF-induced mitogen-activated protein (MAP) kinase activation and ablates its ability to induce endothelial cell tube formation, suggesting that signaling through JAM-1 is key to bFGF-induced signaling. Immunoprecipitation analysis suggests that bFGF signaling dissociates the JAM-1/ αvβ3 complex, allowing for signaling through JAM-1 and αvβ3. In addition, blockage of either JAM-1 or αvβ3 inhibits bFGF-induced MAP kinase activation. Thus, our results suggest that signaling through JAM-1 and αvβ3 is necessary for bFGF-induced angiogenesis.
Fcγ receptor transmembrane domains: role in cell surface expression, γ chain interaction, and phagocytosis
Authors: Kim Moo-Kyung , Huang Zhen-Yu , Hwang Pyoung-Han , Jones Brian A. , Sato Norihito , Hunter Sharon , Kim-Han Tai-Hee , Worth Randall G. , Indik Zena K. , Schreiber Alan D. 
Published: May 2003

AbstractWe constructed chimeric receptors to dissect the role of the transmembrane (TM) domain in cell surface expression of and phagocytosis by the γ chain–dependent Fcγ receptors FcγRIIIA and FcγRI. FcγR chimeras containing the TM and cytoplasmic (CY) domains of the γ chain were expressed on the cell surface and mediated an efficient phagocytic signal. In contrast, chimeras containing the FcγRIIIA TM were poorly expressed. Receptors containing the FcγRI TM and the γ chain CY but lacking the γ chain TM also were expressed efficiently and mediated phagocytosis, suggesting that a γ chain dimer induced by the γ chain TM is not required for efficient phagocytosis. Cotransfection of FcγRI or FcγRIIIA with the chimera CD8-γ-γ (EC-TM-CY) resulted in FcγR cell surface expression and phagocytosis, whereas CD8-CD8-γ, whose TM does not associate with FcγR, allowed cell surface expression of (but not phagocytosis by) FcγRI. CD8-CD8-γ also did not allow surface expression of FcγRIIIA. Exchanging FcγRI and CD8 TMs indicated that the C-terminal 11 amino acids of the FcγRI TM are essential for association of FcγRI with the γ chain and phagocytosis. The data indicate that specific sequences in the FcγRIIIA and FcγRI TMs govern their different interactions with the γ chain in cell surface expression and phagocytosis and that γ chain TM sequences are not required for γ chain–mediated phagocytosis. The data identify a specific region of the FcγRI TM and its asparagine as important for FcγRI cell surface expression in the absence of the γ chain and for distinguishing the FcγRI and FcγRIIIA phenotypes.
Translating research into practice: how are guidelines implemented?
Authors: Partridge M.R. 
Published: May 2003

Numerous guidelines have now been produced both nationally and internationally for the management of respiratory and nonrespiratory disease. They should be regarded as useful tools designed to aid the busy clinician, but their method of production, their value and especially their applicability to primary care and to low income countries need to be assessed critically.The production of guidelines needs to be carefully incorporated into a planned dissemination and implementation programme. This is likely to be most successful when use is made of interactive educational methods associated with intraconsultation prompting and use of reminders. Updating and life-long learning is necessary and guideline revisions need to be closely incorporated into continuing medical education programmes. National campaigns, the use of media and the “training” of patients to make them more effective partners in healthcare can all enhance a beneficial change in health professional behaviour.Recent research has enhanced the knowledge of a wide range of respiratory conditions and very effective therapies now exist for many conditions. However, too little attention is often given to the ways in which care is organised and to the important aspects of management that are nonpharmacological. When dealing with long-term conditions, long-term supervision and the teaching of self-management skills are as important as the prescription.In many parts of the world the ideals, as laid out in guidelines, remain dreams and will continue to be dreams until there is some global redistribution of wealth. Only then will research be translated into practice everywhere.
Early detection of lung cancer: role of biomarkers
Authors: Brambilla C. , Fievet F. , Jeanmart M. , de Fraipont F. , Lantuejoul S. , Frappat V. , Ferretti G. , Brichon P.Y. , Moro-Sibilot D. 
Published: May 2003

Early detection of lung cancer requires none or few invasive techniques. Distal lung cancer (40% of the cases in most European countries) can be sensitively detected by spiral computed tomography. Theoretically, in 60% of cases, the proximal lesions (main to segmental bronchi, accessible by bronchoscopy) should be able to be detected by sputum cytology. Unfortunately, this very specific technique has a low sensitivity and is time consuming. Fluorescent bronchoscopy increases the detection rate of early or micro-invasive lesions and may be proposed in highly selected populations, but not as a screening test. Biomarkers in blood and sputum have not yet been clinically validated. However, the amount of data generated from studies first on resected tumours, then on early bronchial lesions and more recently on blood and sputum offer a wide field for investigation.Lung carcinogenesis is a multistep process characterised by the accumulation of successive molecular genetic and epigenetic abnormalities, resulting in selection of clonal cells with uncontrolled growth capacities throughout the whole respiratory tract (field cancerisation). Molecular lesions far precede morphological transformation of preneoplastic bronchial lesions (dysplasia) or alveolar lesions (atypical alveolar hyperplasia). Genetic and epigenetic abnormalities in the genes involved in cell cycle, senescence, apoptosis, repair, differentiation and cell migration control may be detected on bronchial biopsies, on respiratory cells from the sputum and even in the circulating deoxyribonucleic acid (DNA). The key genes involved include those in the P53- retinoblastoma (Rb) pathways.The balance between cyclin-dependent kinases and their inhibitors regulates the level of Rb phosphorylation and its function at G1-S transition; P53 plays at least two functions (cell cycle and apoptosis control). The balance of bax-bcl2 is important in the control of apoptosis as well as loss of fragile histidine triad expression. O(6)-methylguanine-DNA methyltransferase seems to be important in DNA repair control, the RARβ receptor in differentiation, and cadherin H and E and different metalloproteases genes in cell migration.The demonstration of hyperexpression or silencing of these genes needs different validated techniques: immunohistochemistry on biopsies or cytological preparations, molecular biology techniques for mutations, loss of heterozygosity and aberrant methylation abnormalities. Automation and miniaturisation of these techniques will allow early detection and may be widely applied once clinically validated.
Detection of asthma and chronic obstructive pulmonary disease in primary care
Authors: van Schayck C.P. , Chavannes N.H. 
Published: May 2003

Chronic obstructive pulmonary disease (COPD) and asthma are major health problems, the number of patients with these diseases is still rising and only 25–50% of these patients are known to their doctors.Lung function gradually decreases in COPD and asthmatic patients during their lives. Due to adaptation of the patients or due to the doctor being unaware of the symptoms, COPD is often diagnosed late in its course and when finally diagnosed, lung function is often relatively poor. Underdiagnosis and consequently undertreatment might play an important role in the increase in morbidity and mortality as a result of COPD and asthma. Early detection and treatment might improve the long-term prognosis of these patients and this secondary prevention may also prevent irreversible loss of function.The identification of patients is useless if no effective preventive measures are available. In asthma, inhaled corticosteroids have been shown to have distinct effects on the progression of the disease. However, in COPD inhaled corticosteroids have only been shown to have some effects and the long-term effects on lung function have been disappointing. At present, the most effective treatment available for COPD is the cessation of smoking. It appears that a smoker at risk of developing COPD is more motivated to stop smoking than someone who is not at risk and this may help a physician in encouraging an attempt to quit.General practitioners appear to be already using this knowledge, as they seem more likely to advise smokers to quit smoking if they perceive their problems to be smoking related.
Surgery for nonsmall cell lung cancer: can improvements be made?
Authors: Spiro S.G. 
Published: May 2003

Low-dose spiral computed tomography (CT) for the earlier detection of lung cancer is at the stage of producing hypothesis-generating studies. These studies have shown that more cancers are found at a favourable stage (IA) in prevalence screening but that the fewer numbers found in incidence screening tend to have a slightly worse stage. Randomised controlled trials will be necessary to resolve the place of spiral CT screening.The role of neo-adjuvant chemotherapy before surgery in nonsmall cell lung cancer looks less promising than suggested by earlier studies and the place of adjuvant chemotherapy following surgery appears to be unhelpful, although results of some large, randomised international studies are still awaited.Radical radiotherapy is a poor alternative to surgery in resectable patients who refuse or are unfit for surgery and postoperative radiotherapy is detrimental. Positron emission tomography scanning offers a genuine opportunity to identify occult disease and improve staging prior to surgery and therefore save futile thoracotomies in ∼20% of patients otherwise apparently suitable for resection.
Airway inflammation in COPD: physiological outcome measures and induced sputum
Authors: Crapo R.O. , Jensen R.L. , Hargreave F.E. 
Published: May 2003

Chronic obstructive pulmonary disease (COPD) is a result of airway inflammation, and the best predictor of COPD is the early detection of airflow limitation by spirometry. The Global Initiative for Obstructive Lung Disease Workshop Report defines airflow limitation using simple spirometric indices. Available guidelines categorise the severity of COPD using forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), with symptoms playing a minor role in the assessment.Current standards define COPD by progressive loss of FEV1, and thus longitudinal decline in FEV1will be the primary outcome variable for intervention studies aimed at preventing or reducing the loss of pulmonary function. There is evidence, however, that the variable FEV1/FVC and FEV1are often not measured properly in all settings.This article will discuss the roles of physiological measurements in diagnosing COPD and physiological outcome measures for COPD. It does not formally compare physiological measures with other outcome measures, such as symptoms or quality of life. Additionally, improved treatment of established disease requires a better understanding of the inflammatory process and its clinical effects and treatment.The inflammatory process, and how drugs affect it, can be studied noninvasively or relatively noninvasively by using refined methods of examining spontaneous or induced sputum. Enhanced understanding of the use of induced sputum will assist in predicting patients' responses to short- and long-term inhaled corticosteroid treatment, and the methods of sputum examination need to be simplified so that they can be applied more easily to clinical practice.
COPD exacerbations: definitions and classifications
Authors: Burge S. , Wedzicha J.A. 
Published: May 2003

Chronic obstructive pulmonary disease (COPD) is defined independently of exacerbations, which are largely a feature of moderate-to-severe disease. This article is the result of a workshop that tried to define exacerbations of COPD for use in clinical, pharmacological and epidemiological studies. The conclusions represent the consensus of those present.This review describes definitions, ascertainment, severity assessments, duration and frequency, using varying sources of data including direct patient interview, healthcare databases and symptom diaries kept by patients in studies.The best general definition of a COPD exacerbation is the following: an exacerbation of COPD is a sustained worsening of the patient's condition, from the stable state and beyond normal day-to-day variations that is acute in onset and may warrant additional treatment in a patient with underlying COPD.A more specific definition for studies where a bacteriological cause of exacerbation is being studied is included, as well as simpler definitions for retrospective identification from database sources. Prospective diary card assessments are best recorded as changes from an agreed baseline, rather than absolute symptom severities. Diary cards identify many unreported exacerbations, which on average have similar severities to reported exacerbations. A scale for exacerbation severity is proposed that incorporates in- and outpatient assessments. Exacerbation duration, which also relates to severity, is defined from diary card reports. Healthcare utilisation is not an adequate substitute for severity, depending on many unrelated social and comorbidity factors. It is an outcome in its own right.
The assessment of health status among patients with COPD
Authors: Curtis J.R. , Patrick D.L. 
Published: May 2003

Survival and physiological measures alone do not represent the full experiences of patients with chronic obstructive pulmonary disease. Reducing the personal and social burden of disease by improving patients' symptoms, functional status and quality of life are also important goals.There has been a substantial increase in the use of newly developed tools that measure health status and it is important for clinicians and researchers to understand these instruments' strengths and weaknesses in providing insight into a patient's condition and experience.Relying only on mortality and physiological outcomes could blind a clinician to significant benefits patients may receive from a treatment. A growing body of research utilises end-points assessed directly by patients whose self-reported health status includes health-related quality of life and functional status.This article reviews major concepts and methods in health-status assessments for patients with chronic obstructive pulmonary disease, which will have an important role in assessing the efficacy and effectiveness of new treatments.
The burden of illness and economic evaluation for COPD
Authors: Ramsey S.D. , Sullivan S.D. 
Published: May 2003

In today's cost-conscious environment, understanding the economic implications associated with disease processes and their treatments is as important as understanding their clinical impact.Medical expenditures for treating chronic obstructive pulmonary disease (COPD) and the indirect costs of morbidity can represent a substantial economic and social burden. Very little economic information concerning COPD is available, however, particularly outside of a few very well-developed Western nations.This article will provide an approach for conducting high-quality studies aimed at estimating the economic burden of chronic obstructive pulmonary disease and for making economic evaluations of healthcare interventions aimed at preventing and treating this disease.
Similarities and differences between asthma and chronic obstructive pulmonary disease: treatment and early outcomes
Authors: Buist A.S. 
Published: May 2003

There are now many guidelines that provide direction for the diagnosis and management of asthma and chronic obstructive pulmonary disease (COPD). However, both diseases are still underdiagnosed (or misdiagnosed) and undertreated.There is considerable evidence that treatment with anti-inflammatory drugs reduces morbidity and mortality in asthma. The evidence is growing regarding their effect on slowing the remodelling that occurs in subsets of asthmatics. COPD is more challenging. There are no disease-modifying drugs available yet that will change the natural history of COPD.However, there is overwhelming evidence that smoking cessation will slow the progression of disease. Until better drugs are available for the treatment of COPD, emphasis must be placed on primary and secondary prevention by reducing exposure to noxious agents (cigarette smoke in particular).Inhaled corticosteroids appear to have a place in the management of severe chronic obstructive pulmonary disease, perhaps by decreasing the frequency of exacerbations.