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‣ ANTIGENIC VARIANTS OF INFLUENZA A VIRUS (PR8 STRAIN) : V. VIRULENCE, ANTIGENIC POTENCY, AND CROSS-PROTECTION TESTS IN MICE OF THE ORIGINAL AND SECOND SERIES

Loosli, Clayton G.; Hamre, Dorothy; Gerber, Paul
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/06/1958 Português
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Two series of variants of influenza PR8-S virus have been described. While all retain the same degree of pathogenicity for mice and fertile eggs, there was a progressive loss in the ability of the variants to provoke antibody following vaccination or infection of mice and ferrets. The immunogenicity of the variants was, therefore, less than that of the original strain. Although little or no serological relationship could be demonstrated between some of the variants and the PR8-S virus a considerable degree of cross-immunity could be demonstrated in the cross-protection tests with these viruses if observations were based solely on death or survival of the mice. By employing the occurrence of lesions in the lung and the titer of virus in the lung 48 hours after challenge, the amount of cross-protection in mice could be related to the amount of serological cross-reaction. In general mice vaccinated with PR8-S virus were less resistant to infection with the variant viruses than mice vaccinated with variants and challenged with the PR8-S parent virus. The role of the immune environment of the host in the production of the variant influenza viruses with their serological differences, decreasing antigenicity, and persisting pathogenicity as well as the epidemiological implications of these findings with respect to epidemic influenza in man are discussed.

‣ An original methodology for quantitative assessment of perfusion in small animal studies using contrast-enhanced ultrasound

Mulé, Sébastien; De Cesare, Alain; Frouin, Frédérique; Lucidarme, Olivier; Herment, Alain
Fonte: IEEE Service Center Publicador: IEEE Service Center
Tipo: Artigo de Revista Científica
Publicado em //2007 Português
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The aim of this paper was to validate the combinaison of two original methods for assessing perfusion in small animal studies using Contrast-Enhanced Ultrasound. Respiratory motion was first removed using a frame selection method. This method, based on a Principal Component Analysis, enabled the definition of two subsequences, corresponding to the end-of-inspiration plane and to the end-of-expiration plane. Attenuation caused by contrast agent microbubbles was then estimated. The developed method, based on the assumption that a linear relationship holds between local attenuation and backscatter, used the time-intensity variation in a highly echogenic distal area without contrast uptake to estimate local attenuation coefficients. Ten murine renal perfusion studies were investigated after a bolus injection of SonoVue. Replenishment kinetics were acquired too and were finally modeled with an exponential function. Preliminary results were promising. Indeed, the SonoVue concentration was more faithfully represented than on native images, which allowed a better assessment of perfusion parameters in the whole field of view.

‣ Cytochrome C Maintains Mitochondrial Transmembrane Potential and Atp Generation after Outer Mitochondrial Membrane Permeabilization during the Apoptotic Process

Waterhouse, Nigel J.; Goldstein, Joshua C.; von Ahsen, Oliver; Schuler, Martin; Newmeyer, Donald D.; Green, Douglas R.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 16/04/2001 Português
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During apoptosis, cytochrome c is released into the cytosol as the outer membrane of mitochondria becomes permeable, and this acts to trigger caspase activation. The consequences of this release for mitochondrial metabolism are unclear. Using single-cell analysis, we found that when caspase activity is inhibited, mitochondrial outer membrane permeabilization causes a rapid depolarization of mitochondrial transmembrane potential, which recovers to original levels over the next 30–60 min and is then maintained. After outer membrane permeabilization, mitochondria can use cytoplasmic cytochrome c to maintain mitochondrial transmembrane potential and ATP production. Furthermore, both cytochrome c release and apoptosis proceed normally in cells in which mitochondria have been uncoupled. These studies demonstrate that cytochrome c release does not affect the integrity of the mitochondrial inner membrane and that, in the absence of caspase activation, mitochondrial functions can be maintained after the release of cytochrome c.

‣ Alternative Splicing Regulates the Subcellular Localization of a-Kinase Anchoring Protein 18 Isoforms

Trotter, Kevin W.; Fraser, Iain D.C.; Scott, Gregory K.; Stutts, M. Jackson; Scott, John D.; Milgram, Sharon L.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 27/12/1999 Português
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The cAMP-dependent protein kinase (PKA) is localized to specific subcellular compartments by association with A-kinase anchoring proteins (AKAPs). AKAPs are a family of functionally related proteins that bind the regulatory (R) subunit of PKA with high affinity and target the kinase to specific subcellular organelles. Recently, AKAP18, a low molecular weight plasma membrane AKAP that facilitates PKA-mediated phosphorylation of the L-type Ca2+ channel, was cloned. We now report the cloning of two additional isoforms of AKAP18, which we have designated AKAP18β and AKAP18γ, that arise from alternative mRNA splicing. The AKAP18 isoforms share a common R subunit binding site, but have distinct targeting domains. The original AKAP18 (renamed AKAP18α) and AKAP18β target the plasma membrane when expressed in HEK-293 cells, while AKAP18γ is cytosolic. When expressed in epithelial cells, AKAP18α is targeted to lateral membranes, whereas AKAP18β is accumulated at the apical membrane. A 23-amino acid insert, following the plasma membrane targeting domain, facilitates the association of AKAP18β with the apical membrane. The data suggest that AKAP18 isoforms are differentially targeted to modulate distinct intracellular signaling events. Furthermore...

‣ A Dendritic Cell–Specific Intercellular Adhesion Molecule 3–Grabbing Nonintegrin (Dc-Sign)–Related Protein Is Highly Expressed on Human Liver Sinusoidal Endothelial Cells and Promotes HIV-1 Infection

Bashirova, Arman A.; Geijtenbeek, Teunis B.H.; van Duijnhoven, Gerard C.F.; van Vliet, Sandra J.; Eilering, Jeroen B.G.; Martin, Maureen P.; Wu, Li; Martin, Thomas D.; Viebig, Nicola; Knolle, Percy A.; KewalRamani, Vineet N.; van Kooyk, Yvette; Carrington
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 19/03/2001 Português
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The discovery of dendritic cell (DC)-specific intercellular adhesion molecule (ICAM)-3–grabbing nonintegrin (DC-SIGN) as a DC-specific ICAM-3 binding receptor that enhances HIV-1 infection of T cells in trans has indicated a potentially important role for adhesion molecules in AIDS pathogenesis. A related molecule called DC-SIGNR exhibits 77% amino acid sequence identity with DC-SIGN. The DC-SIGN and DC-SIGNR genes map within a 30-kb region on chromosome 19p13.2-3. Their strong homology and close physical location indicate a recent duplication of the original gene. Messenger RNA and protein expression patterns demonstrate that the DC-SIGN–related molecule is highly expressed on liver sinusoidal cells and in the lymph node but not on DCs, in contrast to DC-SIGN. Therefore, we suggest that a more appropriate name for the DC-SIGN–related molecule is L-SIGN, liver/lymph node–specific ICAM-3–grabbing nonintegrin. We show that in the liver, L-SIGN is expressed by sinusoidal endothelial cells. Functional studies indicate that L-SIGN behaves similarly to DC-SIGN in that it has a high affinity for ICAM-3, captures HIV-1 through gp120 binding, and enhances HIV-1 infection of T cells in trans. We propose that L-SIGN may play an important role in the interaction between liver sinusoidal endothelium and trafficking lymphocytes...

‣ Selective Expansion of Cross-Reactive Cd8+ Memory T Cells by Viral Variants

Haanen, John B.A.G.; Wolkers, Monika C.; Kruisbeek, Ada M.; Schumacher, Ton N.M.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/11/1999 Português
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The role of memory T cells during the immune response against random antigenic variants has not been resolved. Here, we show by simultaneous staining with two tetrameric major histocompatibility complex (MHC)–peptide molecules, that the polyclonal CD8+ T cell response against a series of natural variants of the influenza A nucleoprotein epitope is completely dominated by infrequent cross-reactive T cells that expand from an original memory population. Based on both biochemical and functional criteria, these cross-reactive cytotoxic T cells productively recognize both the parental and the mutant epitope in vitro and in vivo. These results provide direct evidence that the repertoire of antigen-specific T cells used during an infection critically depends on prior antigen encounters, and indicate that polyclonal memory T cell populations can provide protection against a range of antigenic variants.

‣ The First α Helix of Interleukin (Il)-2 Folds as a Homotetramer, Acts as an Agonist of the IL-2 Receptor β Chain, and Induces Lymphokine-Activated Killer Cells

Eckenberg, Ralph; Rose, Thierry; Moreau, Jean-Louis; Weil, Robert; Gesbert, Franck; Dubois, Sigrid; Tello, Diana; Bossus, Marc; Gras, Hélène; Tartar, André; Bertoglio, Jacques; Chouaïb, Salem; Goldberg, Michel; Jacques, Yannick; Alzari, Pedro M.; Thè
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 07/02/2000 Português
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Interleukin (IL)-2 interacts with two types of functional receptors (IL-2Rαβγ and IL-2Rβγ) and acts on a broad range of target cells involved in inflammatory reactions and immune responses. For the first time, we show that a chemically synthesized fragment of the IL-2 sequence can fold into a molecule mimicking the quaternary structure of a hemopoietin. Indeed, peptide p1–30 (containing amino acids 1–30, covering the entire α helix A of IL-2) spontaneously folds into an α-helical homotetramer and stimulates the growth of T cell lines expressing human IL-2Rβ, whereas shorter versions of the peptide lack helical structure and are inactive. We also demonstrate that this neocytokine interacts with a previously undescribed dimeric form of IL-2Rβ. In agreement with its binding to IL-2Rβ, p1–30 activates Shc and p56lck but unlike IL-2, fails to activate Janus kinase (Jak)1, Jak3, and signal transducer and activator of transcription 5 (STAT5). Unexpectedly, we also show that p1–30 activates Tyk2, thus suggesting that IL-2Rβ may bind to different Jaks depending on its oligomerization. At the cellular level, p1–30 induces lymphokine-activated killer (LAK) cells and preferentially activates CD8low lymphocytes and natural killer cells...

‣ Immunoglobulin Heavy Chain Variable Region Gene Replacement as a Mechanism for Receptor Revision in Rheumatoid Arthritis Synovial Tissue B Lymphocytes

Itoh, Kenji; Meffre, Eric; Albesiano, Emilia; Farber, Andrew; Dines, David; Stein, Peter; Asnis, Stanley E.; Furie, Richard A.; Jain, Rita I.; Chiorazzi, Nicholas
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 16/10/2000 Português
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Mature B cells can alter their antibody repertoires by several mechanisms, including immunoglobulin heavy chain variable region (VH) replacement. This process changes the antigen combining site by replacing a portion of the original VH/diversity/heavy chain joining region (VHDJH) rearrangement with a corresponding portion of a new VH segment. This exchange can involve cryptic heptamer-like sequences embedded in the coding regions of VH genes.

‣ Plants as De-Worming Agents of Livestock in the Nordic Countries: Historical Perspective, Popular Beliefs and Prospects for the Future

Waller, PJ; Bernes, G; Thamsborg, SM; Sukura, A; Richter, SH; Ingebrigtsen, K; Höglund, J
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
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Preparations derived from plants were the original therapeutic interventions used by man to control diseases (including parasites), both within humans and livestock. Development of herbal products depended upon local botanical flora with the result that different remedies tended to develop in different parts of the world. Nevertheless, in some instances, the same or related plants were used over wide geographic regions, which also was the result of communication and/or the importation of plant material of high repute. Thus, the Nordic countries have an ancient, rich and diverse history of plant derived anthelmintic medications for human and animal use. Although some of the more commonly used herbal de-wormers were derived from imported plants, or their products, many are from endemic plants or those that thrive in the Scandinavian environment. With the advent of the modern chemotherapeutic era, and the discovery, development and marketing of a seemingly unlimited variety of highly efficacious, safe synthetic chemicals with very wide spectra of activities, herbal remedies virtually disappeared from the consciousness – at least in the Western world. This attitude is now rapidly changing. There is a widespread resurgence in natural product medication...

‣ Annexins V and Xii Alter the Properties of Planar Lipid Bilayers Seen by Conductance Probes

Sokolov, Yuri; Mailliard, William S.; Tranngo, Nghia; Isas, Mario; Luecke, Hartmut; Haigler, Harry T.; Hall, James E.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/05/2000 Português
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Annexins are proteins that bind lipids in the presence of calcium. Though multiple functions have been proposed for annexins, there is no general agreement on what annexins do or how they do it. We have used the well-studied conductance probes nonactin, alamethicin, and tetraphenylborate to investigate how annexins alter the functional properties of planar lipid bilayers. We found that annexin XII reduces the nonactin-induced conductance to ∼30% of its original value. Both negative lipid and ∼30 μM Ca2+ are required for the conductance reduction. The mutant annexin XIIs, E105K and E105K/K68A, do not reduce the nonactin conductance even though both bind to the membrane just as wild-type does. Thus, subtle changes in the interaction of annexins with the membrane seem to be important. Annexin V also reduces nonactin conductance in nearly the same manner as annexin XII. Pronase in the absence of annexin had no effect on the nonactin conductance. But when added to the side of the bilayer opposite that to which annexin was added, pronase increased the nonactin-induced conductance toward its pre-annexin value. Annexins also dramatically alter the conductance induced by a radically different probe...

‣ Electrical conductivity measurement: a new technique to detect iatrogenic initial pedicle perforation

Bolger, Ciaran; Kelleher, Michael O.; McEvoy, Linda; Brayda-Bruno, M.; Kaelin, A.; Lazennec, J. -Y.; Le Huec, J. -C.; Logroscino, C.; Mata, P.; Moreta, P.; Saillant, G.; Zeller, R.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
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Pedicle screw fixation has achieved significant popularity amongst spinal surgeons for both single and multi-level spinal fusion. Misplacement and pedicle cortical violation occurs in over 20% of screw placement and can result in potential complications such as dysthesia, paraparesis or paraplegia. There have been many advances in techniques available for navigating through the pedicle; however, these techniques are not without drawbacks. A new electrical conductivity-measuring device, previously evaluated on the porcine model to detect the pedicle violation, was evaluated amongst nine European Hospitals to be used in conjunction with the methods currently used in that centre. This new device is based on two original principles; the device is integrated in the drilling or screwing tool. The technology allows real-time detection of perforation through two independent parameters, impedance variation and evoked muscle contractions. Data was collected twofold. Initially, the surgeon was given the device and a comparison was made between the devices ability to detect a breech and the surgeon’s ability to detect one using his traditional methods of pedicle preparation. In the second module of the study, the surgeon was limited to using the electrical conductivity detection device as their sole guide to detect pedicle breaches. A comparison was made between the detection ability of the device and the other detection possibilities. Post-operative fine cut CT scanning was used to detect the pedicle breaches. Overall...

‣ Microwave ablation in a hepatic porcine model: correlation of CT and histopathologic findings

Awad, Michael M.; Devgan, Lara; Kamel, Ihab R.; Torbensen, Michael; Choti, Michael A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em //2007 Português
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Background. Thermal ablative techniques have gained increasing popularity in recent years as safe and effective options for patients with unresectable solid malignancies. Microwave ablation has emerged as a relatively new technique with the promise of larger and faster burns without some of the limitations of radiofrequency ablation (RFA). Here we study a new microwave ablation device in a living porcine model using gross, histologic, and radiographic analysis. Materials and methods. The size and shape of ablated lesions were assessed using six pigs in a non-survival study. Liver tissue was ablated using 2, 4, and 8 min burns, in both peripheral and central locations, with and without vascular inflow occlusion. To characterize the post-ablation appearance, three additional pigs underwent several 4 min ablations each followed by serial computed tomography (CT) imaging at 7, 14, and 28 days postoperatively. Results. The 2 and 4 min ablations resulted in lesions that were similar in size, 33.5 cm3 and 37.5 cm3, respectively. Ablations lasting 8 min produced lesions that were significantly larger, 92.0 cm3 on average. Proximity to hepatic vasculature and inflow occlusion did not significantly change lesion size or shape. In follow-up studies...

‣ Gap Junctional Coupling in Lenses from α8 Connexin Knockout Mice

Baldo, George J.; Gong, Xiaohua; Martinez-Wittinghan, Francisco J.; Kumar, Nalin M.; Gilula, Norton B.; Mathias, Richard T.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/11/2001 Português
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Lens fiber cell gap junctions contain α3 (Cx46) and α8 (Cx50) connexins. To examine the roles of the two different connexins in lens physiology, we have genetically engineered mice lacking either α3 or α8 connexin. Intracellular impedance studies of these lenses were used to measure junctional conductance and its sensitivity to intracellular pH. In Gong et al. 1998, we described results from α3 connexin knockout lenses. Here, we present original data from α8 connexin knockout lenses and a comparison with the previous results. The lens has two functionally distinct domains of fiber cell coupling. In wild-type mouse lenses, the outer shell of differentiating fibers (see 1, DF) has an average coupling conductance per area of cell–cell contact of ∼1 S/cm2, which falls to near zero when the cytoplasm is acidified. In the inner core of mature fibers (see 1, MF), the average coupling conductance is ∼0.4 S/cm2, and is insensitive to acidification of the cytoplasm. Both connexin isoforms appear to contribute about equally in the DF since the coupling conductance for either heterozygous knockout (+/−) was ∼70% of normal and 30–40% of the normal for both −/− lenses. However, their contribution to the MF was different. About 50% of the normal coupling conductance was found in the MF of α3 +/− lenses. In contrast...

‣ Open State Destabilization by Atp Occupancy Is Mechanism Speeding Burst Exit Underlying KATP Channel Inhibition by Atp

Li, Lehong; Geng, Xuehui; Drain, Peter
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/01/2002 Português
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The ATP-sensitive potassium (KATP) channel is named after its characteristic inhibition by intracellular ATP. The inhibition is a centerpiece of how the KATP channel sets electrical signaling to the energy state of the cell. In the β cell of the endocrine pancreas, for example, ATP inhibition results from high blood glucose levels and turns on electrical activity leading to insulin release. The underlying gating mechanism (ATP inhibition gating) includes ATP stabilization of closed states, but the action of ATP on the open state of the channel is disputed. The original models of ATP inhibition gating proposed that ATP directly binds the open state, whereas recent models indicate a prerequisite transition from the open to a closed state before ATP binds and inhibits activity. We tested these two classes of models by using kinetic analysis of single-channel currents from the cloned mouse pancreatic KATP channel expressed in Xenopus oocytes. In particular, we combined gating models based on fundamental rate law and burst gating kinetic considerations. The results demonstrate open-state ATP dependence as the major mechanism by which ATP speeds exit from the active burst state underlying inhibition of the KATP channel by ATP.

‣ Cross-cultural adaptation of the Norwegian version of the spinal stenosis measure

Thornes, Elisabeth; Grotle, Margreth
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
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In order to satisfy the need of a tool for assessing the treatment of patients with degenerative lumbar spinal stenosis, an evaluation was made of the reliability, construct validity, and responsiveness of the Norwegian version of Spinal Stenosis Measure (SSM, original by Stucki)). This study was a part of a prospective, cohort study. About 75 patients referred for surgery for spinal stenosis participated in the study. A subsample of 30 patients answered the questionnaire twice, test and retest, with at least one week in between. The SSM was translated according to the Guillemin criteria. Reliability was assessed by Bland and Altman’s repeatability, intraclass correlation coefficient (ICC) and the coefficient of variance (CV). Internal consistency was assessed by Cronbach’s alpha. Construct validity was analysed by correlation analyses. Responsiveness was calculated by the effect size. The reliability between test and retest scores was good for all three subscales of SSM as the ICC-values were above 0.9 and the CVs were below 15%. Cronbach’s alpha was above 0.8. The correlation analyses showed high correlation between scales that assessed the same construct, and low to moderate correlation between scales that assessed different constructs. Large effect sizes were found in all the SSM subscales with effect sizes ≥1.2.The Norwegian SSM version has added a highly useful tool for assessing the disease specific status and outcome after treatment in patients who suffer from degenerative lumbar spinal stenosis.

‣ Effectiveness of frequency shifted feedback at reducing disfluency for linguistically easy, and difficult, sections of speech (original audio recordings included)

Howell, Peter; Davis, Stephen; Bartrip, Jon; Wormald, Laura
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/09/2004 Português
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Frequency shifted feedback (FSF) induces fluency when presented to speakers who stutter. This study examined whether FSF was more effective at removing disfluencies on easy or on difficult stretches of speech (where difficulty was defined with respect to utterance and word length). There were more disfluencies on the difficult stretches than on the easy stretches. There were significantly fewer disfluencies under FSF than in normal listening conditions (indicating that FSF improved fluency). There was no interaction between difficulty of material and type of feedback when disfluency rate was used as the dependent variable, suggesting that targeting FSF on easy stretches of speech is as effective as targeting it on difficult stretches. The original audio data are provided in this report and can be used by readers to check for themselves the characteristics of voice control that alter when FSF is delivered.

‣ The significance of lobular neoplasia on needle core biopsy of the breast

Menon, S.; Porter, G. J. R.; Evans, A. J.; Ellis, I. O.; Elston, C. W.; Hodi, Z.; Lee, A. H. S.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
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The management of a core biopsy diagnosis of lobular neoplasia is controversial. Detailed radiological–pathological review of 47 patients with cores showing classical lobular neoplasia was performed (patients with pleomorphic lobular carcinoma in situ (LCIS) or associated risk lesions were considered separately). Immediate surgical excision in 25 patients showed invasive carcinoma in 7, ductal carcinoma in situ (DCIS) in 1 and pleomorphic LCIS in 1; radiological–pathological review showed that the core biopsy missed a mass in 5, missed calcification in 2 and that calcification appeared adequately sampled in 2. Nineteen patients had follow-up of at least 2 years. Four patients developed malignancy at the site of the core biopsy (invasive carcinoma in three, DCIS in one); one carcinoma was mammographically occult, one patient had dense original mammograms and two had calcifications apparently adequately sampled by the core. In conclusion, most carcinomas identified at the site of core biopsy showing lobular neoplasia were the result of the core missing the radiological lesion, emphasising the importance of multidisciplinary review and investigation of any discordance. Some carcinomas were found after apparently adequate core biopsy...

‣ Application of an original RT-PCR–ELISA multiplex assay for MDR1 and MRP, along with p53 determination in node-positive breast cancer patients

Ferrero, J M; Etienne, M C; Formento, J L; Francoual, M; Rostagno, P; Peyrottes, I; Ettore, F; Teissier, E; Leblanc-Talent, P; Namer, M; Milano, G
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
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The long-term prognostic value of tumoural MDR1 and MRP, along with p53 and other classical parameters, was analysed on 85 node-positive breast cancer patients receiving anthracycline-based adjuvant therapy. All patients underwent tumour resection plus irradiation and adjuvant chemotherapy (the majority receiving fluorouracil–epirubicin–cyclophosphamide). Median follow-up for the 54 alive patients was 7.8 years. Mean age was 53.7 years (range 28–79) and 54 patients were post-menopausal. MDR1 and MRP expression were quantified according to an original reverse transcription polymerase chain reaction multiplex assay with colourimetric enzyme-linked immunosorbent assay detection(β2-microglobulin as control). P53 protein was analysed using an immunoluminometric assay (Sangtec). MDR1 expression varied within an 11-fold range (mean 94, median 83), MRP within a 45-fold range (mean 315, median 242) and p53 protein from the limit of detection (0.002 ng mg−1) up to 35.71 ng mg−1(mean 1.18, median 0.13 ng mg−1). P53 protein was significantly higher in oestrogen receptor (ER)-negative than in ER-positive tumours (P = 0.039). The higher the p53, the lower the MDR1 expression (P = 0.015, r = –0.27). P53 was not linked to progesterone receptor (PR) status...

‣ The positive effect of posterolateral lumbar spinal fusion is preserved at long-term follow-up: a RCT with 11–13 year follow-up

Andersen, Thomas; Videbæk, Tina S.; Hansen, Ebbe S.; Bünger, Cody; Christensen, Finn B.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
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Introduction Few studies have investigated the long-term effect of posterolateral lumbar spinal fusion on functional outcome. Aim To investigate the long-term result after posterolateral lumbar spinal fusion with and without pedicle screw instrumentation. Methods Questionnaire survey of 129 patients originally randomised to posterolateral lumbar spinal fusion with or without pedicle screw instrumentation. Follow-up included Dallas Pain Questionnaire (DPQ), Oswestry Disability Index (ODI), SF-36 and a question regarding willingness to undergo the procedure again knowing the result as global outcome parameter. Results Follow-up was 83% of the original study population (107 patients). Average follow-up time was 12 years (range 11–13 years). DPQ-scores were significantly lower than preoperatively in both groups (P < 0.005) and no drift towards the preoperative level was seen. No difference between the two groups were observed (instrumented vs. non-instrumented): DPQ Daily Activity mean 37.0 versus 32.0, ODI mean 33.4 versus 30.6, SF-36 PCS mean 38.8 versus 39.8, SF-36 MCS mean 49.0 versus 53.3. About 71% in both groups were answered positively to the global outcome question. Patients who had retired due to low back pain had poorer outcome than patients retired for other reasons...

‣ Noise Susceptibility of Cochlear Implant Users: The Role of Spectral Resolution and Smearing

Fu, Qian-Jie; Nogaki, Geraldine
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
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The latest-generation cochlear implant devices provide many deaf patients with good speech recognition in quiet listening conditions. However, speech recognition deteriorates rapidly as the level of background noise increases. Previous studies have shown that, for cochlear implant users, the absence of fine spectro-temporal cues may contribute to poorer performance in noise, especially when the noise is dynamic (e.g., competing speaker or modulated noise). Here we report on sentence recognition by cochlear implant users and by normal-hearing subjects listening to an acoustic simulation of a cochlear implant, in the presence of steady or square-wave modulated speech-shaped noise. Implant users were tested using their everyday, clinically assigned speech processors. In the acoustic simulation, normal-hearing listeners were tested for different degrees of spectral resolution (16, eight, or four channels) and spectral smearing (carrier filter slopes of −24 or −6 dB/octave). For modulated noise, normal-hearing listeners experienced significant release from masking when the original, unprocessed speech was presented (which preserved the spectro-temporal fine structure), while cochlear implant users experienced no release from masking. As the spectral resolution was reduced...