bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guidelines for the use of spiral computed tomography in screening for lung cancer
Authors: Henschke C.I. , Yankelevitz D.F. , McCauley D.I. , Libby D.M. , Pasmantier M.W. , Smith J.P. 
Published: May 2003

Screening should be considered in lung cancer, more than any other cancer. Not only is the disease highly fatal, essentially incurable, when diagnosed on the prompting of symptoms and/or clinical signs, but its occurrence is also highly concentrated in identifiably high-risk persons.The degree of usefulness of computed tomography (CT)-based screening for lung cancer must be thought of in reference to a particular, presumably optimal, regimen of pursuing early stage diagnosis. This is an algorithm that begins with the initial test (“screening CT”) and ends in either discontinuation of the diagnostic pursuit or in diagnosis of lung cancer.A carefully developed, extensively pilot tested and critically reviewed, updated protocol for CT-based screening for lung cancer is presented here. Its implementation is addressed, together with quality assurance. Finally, the associated curability rate for lung cancer is addressed in the light of what is known or can be surmised from evidence already available. However, recommendation for or against screening requires further information. Principally, the patients risk for lung cancer (in the near future) and the patients life expectancy (when spared of death from lung cancer). These two factors influence when, if ever, to begin screening, and if it is initiated, when to discontinue it. Finally, cost-effectiveness of the screening program should also be considered.
New techniques for early detection of lung cancer
Authors: Sutedja G. 
Published: May 2003

The resurgence of interest in lung cancer screening and the application of new techniques for the management of early cancer have raised various issues regarding this global epidemic. In previous randomised clinical trials, the use of conventional chest radiographs and sputum cytology examinations for screening have been shown not to reduce lung cancer mortality.The use of biomolecular markers, autofluorescence bronchoscopy, low-dose spiral and high-resolution computed tomography, endobronchial ultrasonography, optical coherence tomography, confocal micro-endoscopy, positron emission tomography in combination with video-assisted thoracic surgery and intraluminal bronchoscopic treatments may provide new modalities with which to manage lung cancer at the earliest stage possible.New hopes arise that the combined use of more accurate and minimally invasive diagnostic and treatment techniques may justify screening and reduce mortality. More individuals may also benefit, as many in the target population already suffer from poor cardiovascular and pulmonary health due to their smoking history and are considered at risk for surgical intervention. The cost-effectiveness of lung cancer screening will strongly depend on the proper selection of the target population and the optimal application of these new techniques.Despite epidemiological controversy regarding lung cancer screening, the feasibility to define more precisely who are at risk and the use of less invasive techniques may preserve quality of life and improve the survival of many lung cancer patients.
Screening
Authors: Boyle P. 
Published: May 2003

Screening for cancer is currently entering a very promising period as new technologies become available for assessment. However, this great opportunity also presents significant problems, starting with how do you select the likeliest method for evaluation? How do you do trials where the technology will be out-moded by the time the result is known? Indeed, how can all promising technologies be evaluated?There is a need for a renewal of methodological thinking on this topic at present. Randomised trials, which currently rely on death as the primary outcome, are very long and very complicated to undertake and run. There is an urgent need for biological markers, which are true surrogate end-points, to help reduce sample size and make trials more feasible, so that more trials can be done.For those screening modalities of demonstrated effectiveness, the key issue at present is how to maximise the outcome in population screening when the technology is transferred from the research setting to the public health setting. It is essential to remember that screening, per se, has never prevented a cancer nor prevented a cancer death. It is impossible to separate the issues of screening with those of adequate treatment: the best results in a screening programme will come when treatment is excellent.Screening is the first, and sometimes key, stage in a global management programme for the cancer in question. As the aim at present is to strive to maximise the effectiveness of population-based programmes, this aspect should be foremost in all thought processes.
Longitudinal evaluation of depression and anxiety in patients with clinically isolated syndrome at high risk of developing early multiple sclerosis
Authors: Di Legge S , Piattella M C , Pozzilli C , Pantano P , Caramia F , Pestalozza I F , Paolillo A , Lenzi G L 
Published: May 2003

We investigated the relationship between emotional changes, brain lesion burden and development of multiple sclerosis (MS). Thirty-seven consecutive patients with clinically isolated syndrome (C IS) were prospectively assessed with the Expanded Disability Status Scale (EDSS), the 21-item Beck Depression Inventory (BDI), the State-Trait A nxiety Inventory (STAI) and gadolinium enhanced (Gd+) MRI scans. BDI and STAI were also administered to 36 age-matched controls. C onversion to MS was defined as the occurrence of a clinical relapse. C IS patients were more likely to endorse symptoms of anxiety and depression than controls. Baseline scores for depression and anxiety did not correlate with the total lesion load (i.e., volume of Gd+, T2 and T1 lesions) and the number of Gd+ lesions during the first six months of follow-up. A positive correlation was found between severity of depressive scores and the lesion load in the right temporal region (P =0.005). After 339-6 months of the study entry, patients who had a clinical relapse were more frequently depressed (P =0.001) than those relapse free. Emotional disturbances are frequently observed in C IS patients and show a tendency towards a normalization in relapse-free patients. The increased rate of depressive symptoms observed in patients who developed MS seems to result from a combination of psychological and organic features. The lesion load in the right temporal region is confirmed as a key area for developing depressive symptoms, even in the early phase of the disease.
Multi-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Fukuoka Masahiro , Yano Seiji , Giaccone Giuseppe , Tamura Tomohide , Nakagawa Kazuhiko , Douillard Jean-Yves , Nishiwaki Yutaka , Vansteenkiste Johan , Kudoh Shinzoh , Rischin Danny , Eek Richard , Horai Takeshi , Noda Kazumasa , Takata Ichiro , Smit Egbert , Averbuch Steven , Macleod Angela , Feyereislova Andrea , Dong Rui-Ping , Baselga José 
Published: May 2003

Purpose: To evaluate the efficacy and tolerability of two doses of gefitinib (Iressa [ZD1839]; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with pretreated advanced non–small-cell lung cancer (NSCLC). Patients and Methods: This was a randomized, double-blind, parallel-group, multicenter phase II trial. Two hundred ten patients with advanced NSCLC who were previously treated with one or two chemotherapy regimens (at least one containing platinum) were randomized to receive either 250-mg or 500-mg oral doses of gefitinib once daily. Results: Efficacy was similar for the 250- and 500-mg/d groups. Objective tumor response rates were 18.4% (95% confidence interval [CI], 11.5 to 27.3) and 19.0% (95% CI, 12.1 to 27.9); among evaluable patients, symptom improvement rates were 40.3% (95% CI, 28.5 to 53.0) and 37.0% (95% CI, 26.0 to 49.1); median progression-free survival times were 2.7 and 2.8 months; and median overall survival times were 7.6 and 8.0 months, respectively. Symptom improvements were recorded for 69.2% (250 mg/d) and 85.7% (500 mg/d) of patients with a tumor response. Adverse events (AEs) at both dose levels were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent in the higher-dose group. Withdrawal due to drug-related AEs was 1.9% and 9.4% for patients receiving gefitinib 250 and 500 mg/d, respectively. Conclusion: Gefitinib showed clinically meaningful antitumor activity and provided symptom relief as second- and third-line treatment in these patients. At 250 mg/d, gefitinib had a favorable AE profile. Gefitinib 250 mg/d is an important, novel treatment option for patients with pretreated advanced NSCLC.
Inhibition of Cyclooxygenase-2 Activity Enhances Steroidogenesis and Steroidogenic Acute Regulatory Gene Expression in MA-10 Mouse Leydig Cells
Authors: Wang XingJia , Dyson Matthew T. , Jo Youngah , Stocco Douglas M. 
Published: May 2003

AbstractTo study the mechanism for the regulatory effect of arachidonic acid (AA) on steroidogenesis, the role of cyclooxygenase (COX) in steroid production and steroidogenic acute regulatory (StAR) gene expression was investigated. Although stimulation with 0.05 mm dibutyryl cAMP (Bt2cAMP) did not increase StAR protein or progesterone in MA-10 mouse Leydig cells, the addition of 1 μm of the COX inhibitor indomethacin increased StAR protein expression and progesterone production by 5.7-fold and 34.3-fold, respectively. In the presence of indomethacin, the level of Bt2cAMP required for maximal steroidogenesis was reduced from 1.0 mm to 0.25 mm. Similar results were obtained in studies on StAR promoter activity and in Northern blot analyses of StAR mRNA expression, suggesting that inhibition of COX activity enhanced StAR gene transcription. COX2 (an inducible isoform of COX) was constitutively detected in MA-10 cells. Although SC560, a selective COX1 inhibitor, did not affect steroidogenesis, the COX2 inhibitor NS398 significantly enhanced Bt2cAMP-stimulated StAR protein expression and steroid production. Overexpression of the COX2 gene in COS-1 cells significantly inhibited StAR promoter activity. The results of the present study suggest that inhibition of COX2 activity increases the sensitivity of steroidogenesis to cAMP stimulation in MA-10 Leydig cells.
17β-Estradiol Stimulates Arachidonate Release from Human Amnion-Like WISH Cells through a Rapid Mechanism Involving a Membrane Receptor
Authors: Fiorini Sara , Ferretti Maria E. , Biondi Carla , Pavan Barbara , Lunghi Laura , Paganetto Guglielmo , Abelli Luigi 
Published: May 2003

Abstract17β-Estradiol (17β-E2) greatly and dose-dependently stimulates [3H]arachidonic acid (AA) release from the human amnion-like Wistar Institute Susan Hayflick (WISH) cells. This action is abolished by the phospholipase A2 inhibitor AACOCF3, significantly reduced by the estrogen receptor (ER) antagonist ICI 182,780, and uninfluenced by cycloheximide. The estradiol-BSA conjugate E2coBSA, which binds putative membrane ERs and is unable to enter the cell, also highly stimulates [3H]AA release from WISH cells, although to a lesser extent compared with 17β-E2. The fluorescent conjugate E2coBSA-FITC specifically binds to the surface of a subset of intact WISH cells, and labeling intensity appears dose and time dependent. Cell permeabilization results in a dense intracellular staining, mainly in the peripheral cytoplasm. H-150, an antibody against the N terminus of human ERβ, also labels the plasma membrane of intact WISH cells and the cytoplasm of permeabilized cells. Almost no labeling is observed using ER-21, an antibody against the N terminus of human ERα. RT-PCR evidences the presence of mRNA for ERβ, not for ERα. Our data suggest that 17β-E2 stimulates [3H]AA release from WISH cells through an apparently nongenomic pathway and interaction with membrane binding sites. These last are, at least in part, similar if not identical to ERβ.
Phosphorylation of Insulin-Like Growth Factor (IGF) Binding Protein-3 by Breast Cancer Cell Membranes Enhances IGF-I Binding
Authors: Mishra Suresh , Murphy Liam J. 
Published: May 2003

AbstractCross-linking of nonglycosylated biotinylated IGF binding protein (IGFBP)-3 to T-47D cell membranes identifies complexes with Mr of 32, 50, 70, and 100 kDa. Nonbiotinylated glycosylated IGFBP-3 competed for binding to each of these sites. The 32-kDa band approximated the size of intact nonglycosylated IGFBP-3, but its abundance was enhanced by cross-linking, and it had a more acidic isoelectric point on isoelectric focusing, suggesting that it had undergone phosphorylation. Immobilized IGFBP-3 was phosphorylated in the presence of 32P-γATP by both T-47D cell membranes and by intact cells treated with phenylarsine oxide to inhibit internalization. MCF-7 and COS-1 cells were also able to bind and phosphorylated IGFBP-3. IGF-I inhibited both IGFBP-3 binding to membranes and phosphorylation. However, incubation of T-47D cells with IGFBP-3 enhanced binding of 125I-IGF-I to the cell monolayer indicating that membrane bound IGFBP-3 was able to bind IGF-I. Immobilized IGFBP-3 when phosphorylated by T-47D membranes bound significantly more 125I-IGF-I than nonphosphorylated IGFBP-3. Treatment with alkaline phosphatase significantly reduced 125I-IGF-I binding to phosphorylated immobilized IGFBP-3 and also reduced 125I-IGF-I to T-47D cell monolayers preincubated with IGFBP-3. Phosphorylation of IGFBP-3 by T-47D membranes was partially blocked by inhibitors of both protein kinase A and C. These data demonstrate that binding of IGFBP-3 to breast cancer membranes is accompanied by phosphorylation at the plasma membrane and that both processes are inhibited by IGF-I. However, once phosphorylated the ability of IGFBP-3 to bind IGF-I is enhanced, resulting in increased association of the IGF-I with the cell membrane.
Cardiac Lipid Accumulation Associated with Diastolic Dysfunction in Obese Mice
Authors: Christoffersen Christina , Bollano Entela , Lindegaard Marie L. S. , Bartels Emil D. , Goetze Jens P. , Andersen Claus B. , Nielsen Lars B. 
Published: May 2003

AbstractObesity may confer cardiac dysfunction due to lipid accumulation in cardiomyocytes. To test this idea, we examined whether obese ob/ob mice display heart lipid accumulation and cardiac dysfunction. Ob/ob mouse hearts had increased expression of genes mediating extracellular generation, transport across the myocyte cell membrane, intracellular transport, mitochondrial uptake, and β-oxidation of fatty acids compared with ob/+ mice. Accordingly, ob/ob mouse hearts contained more triglyceride (6.8 ± 0.4 vs. 2.3 ± 0.4 μg/mg; P &lt; 0.0005) than ob/+ mouse hearts. Histological examinations showed marked accumulation of neutral lipid droplets within cardiac myocytes but not increased deposition of collagen between myocytes in ob/ob compared with ob/+ mouse hearts. On echocardiography, the ratio of E to A transmitral flow velocities (an indicator of diastolic function) was 1.8 ± 0.1 in ob/ob mice and 2.5 ± 0.1 in ob/+ mice (P = 0.0001). In contrast, the indexes of systolic function and heart brain natriuretic peptide mRNA expression were only marginally affected and unaffected, respectively, in ob/ob compared with ob/+ mice. The results suggest that ob/ob mouse hearts have increased expression of cardiac gene products that stimulate myocyte fatty acid uptake and triglyceride storage and accumulate neutral lipids within the cardiac myocytes. The results also suggest that the cardiac lipid accumulation is paralleled by cardiac diastolic dysfunction in ob/ob mice.
Biological Activity of Activating Thyroid-Stimulating Hormone Receptor Mutants Depends on the Cellular Context
Authors: Fuhrer D. , Lewis M. D. , Alkhafaji F. , Starkey K. , Paschke R. , Wynford-Thomas D. , Eggo M. , Ludgate M. , Führer-Sakel Dagmar 
Published: May 2003

AbstractActivating TSH receptor (TSHR) mutations are a major cause of toxic thyroid adenoma and familial hyperthyroidism, and more than 37 such mutations have been described. Previously their functional activity had been assessed in terms of cAMP and inositol phosphate production and predominantly in transiently transfected COS-7 (monkey embryonic kidney cells), a model that does not reflect effects on thyrocyte proliferation and function. Here we have performed a systematic comparison of wild-type and seven gain-of-function TSHR mutants, introduced into rat FRTL-5 and human thyrocytes, using retroviral vectors. Our results show that 1) biological potency of TSHR mutants in thyroid cells does not correlate with their cAMP levels in transfected COS cells, highlighting the importance of cellular context and level of expression when assessing biological effects of oncogenic mutations; 2) dissociation between stimulation of function and growth occurs with thyrocyte differentiated functions more readily stimulated than growth; 3) TSHR mutants show a similar order of potency in FRTL-5 cells and human thyrocytes; 4) mutants inducing the highest stimulation of adenylyl cyclase may paradoxically fail to induce proliferation; and 5) biological effects of cAMP activating TSHR mutants are attenuated by complex counterregulatory mechanisms at least at the level of phosphodiesterases and cAMP regulatory element modulator isoforms.
Actin-based photo-orientation movement of chloroplasts in plant cells
Authors: Takagi Shingo 
Published: May 2003

SUMMARYIn photosynthesizing plant cells, chloroplasts change their arrangements and/or positions in response to light irradiation. These photo-orientation movements of chloroplasts are believed to play important roles in optimizing the photosynthetic activity of plant cells. We have been investigating the roles of the actin cytoskeleton in the intracellular movement and positioning of chloroplasts using the aquatic monocot Vallisneria giganteaGraebner and the terrestrial dicot Spinacia oleracea L. (spinach). In Vallisneria epidermal cells, chloroplasts accumulate on the cytoplasmic layer facing the top surface (outer periclinal layer) under dim red light, whereas they move to the cytoplasmic layer perpendicular to the outer periclinal layer (anticlinal layer) under strong blue light. Concomitant with these responses, actin filaments exhibit dramatic changes in their configurations. The possible modes of action of the actin cytoskeleton to regulate the movement and positioning of chloroplasts are briefly summarized,together with our recent analysis of the association of actin filaments with chloroplasts isolated from spinach leaves.
Diffusion, perfusion and the exclusion principles in the structural and functional organization of the living cell: reappraisal of the properties of the `ground substance'
Authors: Wheatley Denys N. 
Published: May 2003

SUMMARYThe thesis is presented that only within very small microdomains of the cell internum might diffusion operate in the sorting of molecular affinities. Much of cell metabolism is guided and controlled in rate by the speed with which molecules that have to interact encounter one another. What is clear,however, is that the cell does not have a single `modus operandi' but has the choice of many different strategies, each of which can contribute in different proportion to the rate of ongoing activity. It is probably our own desire to simplify things and use the most (or more) probable strategy that confines our appreciation of the overall robustness of the cell as a `survival machine'. The main operative process at any given time (perfusion, diffusion or whatever) has always to be considered very carefully in relation to the organisational structure of the cell, which can be transient and fickle but nevertheless has been seen as involving an extensive cytomatrix, a ground substance, within an aqueous environment in which the degree of water structuring is even more fickle.
Force–velocity relationships in actin–myosin interactions causing cytoplasmic streaming in algal cells
Authors: Sugi Haruo , Chaen Shigeru 
Published: May 2003

SUMMARYCytoplasmic streaming in giant internodal cells of green algae is caused by ATP-dependent sliding between actin cables fixed on chloroplast rows and cytoplasmic myosin molecules attached to cytoplasmic organelles. Its velocity(≥50 μm s-1) is many times larger than the maximum velocity of actin–myosin sliding in muscle. We studied kinetic properties of actin–myosin sliding causing cytoplasmic streaming in internodal cell preparations of Chara corallina, into which polystyrene beads, coated with cytoplasmic myosin molecules, were introduced. Constant centrifugal forces directed opposite to the bead movement were applied as external loads. The steady-state force–velocity(P–V) curves obtained were nearly straight, irrespective of the maximum isometric force generated by cytoplasmic myosin molecules, indicating a large duty ratio of cytoplasmic myosin head. The large velocity of cytoplasmic streaming can be accounted for, at least qualitatively, by assuming a mechanically coupled interaction between cytoplasmic myosin heads as well as a large distance of unitary actin–myosin sliding.
Actin comet tails, endosomes and endosymbionts
Authors: Fehrenbacher Kammy , Huckaba Thomas , Yang Hyeong-Cheol , Boldogh Istvan , Pon Liza 
Published: May 2003

SUMMARYThe Arp2/3 complex consists of seven highly conserved and tightly associated subunits, two of which are the actin-related proteins Arp2 and Arp3. One of the best-studied functions of the Arp2/3 complex is to stimulate actin nucleation and force production at the leading edge of motile cells. What is now clear is that Arp2/3-complex-mediated force production drives many intracellular movements, including movement of bacterial pathogens in infected host cells, internalization of extracellular materials viaphagocytosis and endocytosis, and movement of mitochondria during cell division in budding yeast. Here, we describe recent advances in the mechanisms underlying Arp2/3 complex-driven intracellular movement.