tbuckley/cabot-search huggingface dataset:
Fluorescent In Situ Hybridization for Human Epidermal Growth Factor Receptor 2 Assessment in Breast Cancer: Is It Applicable As a Primary Test?
Authors: Vincenzo Arena, Ilaria Pennacchia, Arnaldo Carbone, Arnaldo Capelli
Journal: Journal of Clinical Oncology (2009)

TO THE EDITOR: Recently, Sauter et al reviewing the American Society of Clinical Oncology–College of American Physicians Guidelines for determining human epidermal growth factor receptor 2 (HER2) status in breast cancer patients, suggest fluorescent in situ hybridization (FISH) as the primary HER2 assay method to select women with breast cancer candidate to targeted therapy. Undoubtedly, the paper has the merit of performing an extremely accurate analysis of all the issues relating to the immunohistochemical preanalytic and analytic critical steps which are responsible for the difficulties and the interlaboratory differences in test interpretation. However, the following points should be addressed: It is true that FISH success rate is high, compared with immunohistochemistry (IHC); however, in daily laboratory practice, FISH analysis on formalin-fixed paraffin-embedded tissues present a range of technical problems at least paralleling those met in IHC, as already stated by Peterson et al in 2004. We agree with Sauter et al’s opinion on the interlaboratory reproducibility of FISH test, nevertheless, we believe that only the combination of FISH evaluation with IHC can reduce the possibility of diagnostic pitfalls (see Dowsett et al). Sauter et al do not mention the difference in the performing time of FISH in comparison with IHC and the necessity of dedicated experienced technicians to make the analysis. We totally agree with the large spectrum analysis of the costs made by Sauter et al, but restricting the same analysis to the “pathology laboratory economy,” we are not so sure that the choice to make only FISH for HER2 determination is really sustainable. In conclusion, although we completely share the Sauter et al’s opinion about the crucial role of FISH in correct molecular characterization of breast cancers, and the article has the unquestionable merit of examining all the emergent problems about this topic, we in part disagree on the conclusions both for the points mentioned here and because we think that what Sauter et al propose is not concretely applicable on a large scale. In using FISH as the primary test for HER2 status determination, there would be an increment of the technical and medical daily workload and increased pathology laboratory costs that could not be borne by all the peripheral laboratories. Finally, we believe that both the oncologists and pathologists should not lose trust in IHC, at least as a primary assessment method of HER2 expression.
Oxidants and Antioxidants as Therapeutic Targets in Chronic Obstructive Pulmonary Disease
Authors: WILLIAM MacNEE, IRFAN RAHMAN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Section:ChooseTop of pageAbstract <<THE OXIDANT BURDEN IN SMO...OXIDANT DAMAGEEVIDENCE OF OXIDATIVE STR...EVIDENCE OF A RELATIONSHI...OXIDATIVE STRESS AND GENE...OXIDATIVE STRESS AND SUSC...THERAPEUTIC OPTIONS FOR R...ReferencesCITING ARTICLES
Creating a Unified Representation of Visual and Auditory Space in the Brain
Authors: E I Knudsen, M S Brainard
Journal: Annual Review of Neuroscience (1995)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Correlation of SRSF1 and PRMT1 expression with clinical status of pediatric acute lymphoblastic leukemia
Authors: Limin Zou, Han Zhang, Chaohao Du, Xiao Liu, Shanshan Zhu, Wei Zhang, Zhigang Li, Chao Gao, Xiaoxi Zhao, Mei Mei, Shilai Bao, Huyong Zheng
Journal: Journal of Hematology & Oncology (2012)

Abstract Background Acute lymphoblastic leukemia (ALL) is the most frequently-occurring malignant neoplasm in children, but the pathogenesis of the disease remains unclear. In a microarray assay using samples from 100 children with ALL, SFRS1 was found to be up-regulated. Serine/arginine-rich splicing factor 1 (SRSF1, also termed SF2/ASF), encoded by the SFRS1 gene, had been shown to be a pro-oncoprotein. Our previous study indicated that SRSF1 can be methylated by protein arginine methyltransferase 1 (PRMT1) in vitro; however, the biological function of SRSF1 and PRMT1 in pediatric ALL are presently unknown. Methods Matched, newly diagnosed (ND), complete remission (CR) and relapse (RE) bone marrow samples from 57 patients were collected in order to evaluate the expression patterns of SRSF1 and PRMT1. The potential oncogenic mechanism of SRSF1 and PRMT1 in leukemogenesis was also investigated. Results We identified significant up-regulation of SRSF1 and PRMT1 in the ND samples. Importantly, the expression of SRSF1 and PRMT1 returned to normal levels after CR, but rebounded in the RE samples. Our observation that SRSF1 could predict disease relapse was of particular interest, although the expression patterns of SRSF1 and PRMT1 were independent of the cytogenetic subtypes. In pre-B-cell lines, both SRSF1 and PRMT1 expression could be efficiently attenuated by the clinical chemotherapy agents arabinoside cytosine (Ara-c) or vincristine (VCR). Moreover, SRSF1 and PRMT1 were associated with each other in leukemia cells in vivo. Knock-down of SRSF1 resulted in an increase in early apoptosis, which could be further induced by chemotherapeutics. Conclusions Our results indicate that SRSF1 serves as an anti-apoptotic factor and potentially contributes to leukemogenesis in pediatric ALL patients by cooperating with PRMT1.
Pi MZ and COPD: will we ever know?
Authors: N Seersholm
Journal: Thorax (2004)

Based on the current evidence, there is no reason to believe that Pi MZ individuals have an increased risk of developing lung disease as long as they do not smoke

Is Pi MZ a risk factor for the development of chronic obstructive pulmonary disease (COPD)? That is the question many authors have tried to answer during the last decades, but the results of published studies are still conflicting.

A very high percentage of patients with COPD have been smokers, but not all smokers develop COPD. There must be other contributing factors and, with a Pi MZ prevalence of 3–5% in many Western countries, it is relevant to determine whether this genotype is an additional risk factor for COPD.1 Furthermore, if a dose-response relation exists, it is biologically plausible since plasma levels of α1-antitrypsin (AAT) are reduced to about 60% in Pi MZ subjects compared with those with the normal Pi MM genotype, and Pi Z individuals with very low levels of AAT have a significantly increased risk for emphysema.

There are a number of reasons for the discrepancy between the studies conducted on this subject. Firstly, smoking is a very significant confounder in the development of emphysema which is almost impossible to control for. Secondly, many studies have been subject to various types of bias, particularly selection bias. Thirdly, only a few studies have been sufficiently large to produce a significant result and very few studies have been population based. Finally, the phenotypic appearance of the Pi MZ genotype may be heterogenic.

In the studies of a causal relationship of a risk factor (Pi MZ genotype) and the development of a disease (COPD) there are two types of designs: case-control studies and cohort studies. Cohort studies …
Characterization of a R115777-Resistant Human Multiple Myeloma Cell Line with Cross-Resistance to PS-341
Authors: Robert Buzzeo, Steven Enkemann, Rama Nimmanapalli, Melissa Alsina, Mathias G. Lichtenheld, William S. Dalton, Darrin M. Beaupre
Journal: Clinical Cancer Research (2005)

Abstract The farnesyl transferase inhibitor R115777 has been found to have clinical activity in diverse hematopoietic tumors. Clinical efficacy, however, does not correlate with Ras mutation status or inhibition of farnesyl transferase. To further elucidate the mechanisms by which R115777 induces apoptosis and to investigate drug resistance, we have identified and characterized a R115777-resistant human myeloma cell line. 8226/R5 cells were found to be at least 50 times more resistant to R115777 compared with the parent cell line 8226/S. K-Ras remained prenylated in both resistant and sensitive cells after R115777 treatment; however, HDJ-2 farnesylation was inhibited in both lines, implying that farnesyl transferase (the drug target) has not been mutated. Whereas many 8226 lines that acquire drug resistance have elevated expression of P-glycoprotein, we found that P-glycoprotein expression is not increased in the 8226/R5 line and intracellular accumulation of R115777 was not reduced. In fact, 8226/R5 cells were insensitive to a diverse group of antitumor agents including PS-341, and multidrug resistance did not correlate with the expression of heat shock proteins. Comparison of gene expression profiles between resistant and sensitive cells revealed expression changes in several genes involved in myeloma survival and drug resistance. Future experiments will attempt to identify genes that are directly linked to the resistant phenotype. Identification of molecules associated with R115777 and PS-341 resistance is clinically relevant because both compounds are being tested in solid tumors and hematopoietic malignancies.
STAT4 activation in smokers and patients with chronic obstructive pulmonary disease
Authors: A. Di Stefano, G. Caramori, A. Capelli, I. Gnemmi, F.L. Ricciardolo, T. Oates, C.F. Donner, K.F. Chung, P.J. Barnes, I.M. Adcock
Journal: European Respiratory Journal (2004)

Activation of the transcription factor signal transducer and activator of transcription (STAT)‐4 is critical for the differentiation of T‐helper 1 cells/type‐1 cytotoxic T‐cells and the production of interferon (IFN)‐γ. Expression of STAT4, phospho‐STAT4, IFN‐γ and T‐box expressed in T‐cells (T‐bet) proteins in bronchial biopsies and bronchoalveolar lavage (BAL)‐derived lymphocytes, obtained from 12 smokers with mild/moderate chronic obstructive pulmonary disease (COPD) (forced expiratory volume in one second (FEV 1 ) 59±16% predicted), 14 smokers with normal lung function (FEV 1 106±12% pred) and 12 nonsmoking subjects (FEV 1 111±14% pred), was examined by immunohistochemistry and immunocytochemistry. In bronchial biopsies of COPD patients, the number of submucosal phospho‐STAT4+ cells was increased (240 (22–406) versus 125 (0–492) versus 29 (0–511) cells·mm −2 ) when compared with both healthy smokers and control nonsmokers, respectively. In smokers, phospho‐STAT4+ cells correlated with the degree of airflow obstruction and the number of IFN‐γ+ cells. Similar results were seen in BAL (2.8 (0.2–5.9) versus 1.03 (0.09–1.6) versus 0.69 (0–2.3) lymphocytes·mL −1 ×10 3 ). In all smokers who underwent lavage, phospho‐STAT4+ lymphocytes correlated with airflow obstruction and the number of IFNγ+ lymphocytes. T‐bet expression was not altered in bronchial biopsies and BAL‐derived lymphocytes between the three groups. In conclusion, this study suggests that stable mild/moderate chronic obstructive pulmonary disease is associated with an active T‐helper 1 cell/type‐1 cytotoxic T‐cell inflammatory process involving activation of signal transducer and activator of transcription 4 and interferon-gamma production.
OPTICAL IMAGING AND CONTROL OF GENETICALLY DESIGNATED NEURONS IN FUNCTIONING CIRCUITS
Authors: Gero Miesenböck, Ioannis G. Kevrekidis
Journal: Annual Review of Neuroscience (2005)

Proteins with engineered sensitivities to light are infiltrating the biological mechanisms by which neurons generate and detect electrochemical signals. Encoded in DNA and active only in genetically specified target cells, these proteins provide selective optical interfaces for observing and controlling signaling by defined groups of neurons in functioning circuits, in vitro and in vivo. Light-emitting sensors of neuronal activity (reporting calcium increase, neurotransmitter release, or membrane depolarization) have begun to reveal how information is represented by neuronal assemblies, and how these representations are transformed during the computations that inform behavior. Light-driven actuators control the electrical activities of central neurons in freely moving animals and establish causal connections between the activation of specific neurons and the expression of particular behaviors. Anchored within mathematical systems and control theory, the combination of finely resolved optical field sensing and finely resolved optical field actuation will open new dimensions for the analysis of the connectivity, dynamics, and plasticity of neuronal circuits, and perhaps even for replacing lost--or designing novel--functionalities.
Mitochondrial PKCε and MAPK Form Signaling Modules in the Murine Heart
Authors: Christopher P. Baines, Jun Zhang, Guang-Wu Wang, Yu-Ting Zheng, Joanne X. Xiu, Ernest M. Cardwell, Roberto Bolli, Peipei Ping
Journal: Circulation Research (2002)

Although activation of protein kinase C (PKC) ε and mitogen-activated protein kinases (MAPKs) are known to play crucial roles in the manifestation of cardioprotection, the spatial organization of PKCε signaling modules in naïve and protected myocardium remains unknown. Based on evidence that mitochondria are key mediators of the cardioprotective signal, we hypothesized that PKCε and MAPKs interact, and that they form functional signaling modules in mitochondria during cardioprotection. Both immunoblotting and immunofluorescent staining demonstrated that PKCε, ERKs, JNKs, and p38 MAPK co-localized with cardiac mitochondria. Moreover, transgenic activation of PKCε greatly increased mitochondrial PKCε expression and activity, which was concomitant with increased mitochondrial interaction of PKCε with ERKs, JNKs, and p38 as determined by co-immunoprecipitation. These complex formations appeared to be independent of PKCε activity, as the interactions were also observed in mice expressing inactive PKCε. However, although both active and inactive PKCε bound to all three MAPKs, increased phosphorylation of mitochondrial ERKs was only observed in mice expressing active PKCε but not in mice expressing inactive PKCε. Examination of potential downstream targets of mitochondrial PKCε-ERK signaling modules revealed that phosphorylation of the pro-apoptotic protein Bad was elevated in mitochondria. Together, these data show that PKCε forms subcellular-targeted signaling modules with ERKs, leading to the activation of mitochondrial ERKs. Furthermore, formation of mitochondrial PKCε-ERK modules appears to play a role in PKCε-mediated cardioprotection, in part by the phosphorylation and inactivation of Bad.
Complement receptor 2 mediates enhancement of human immunodeficiency virus 1 infection in Epstein-Barr virus-carrying B cells.
Authors: M Tremblay, S Meloche, R P Sekaly, M A Wainberg
Journal: The Journal of Experimental Medicine (1990)

Although the CD4 glycoprotein is the primary receptor for HIV-1, recent reports have suggested that other molecules might be involved in the enhancement of HIV-1 infection. We investigated the possible role of the complement receptor 2 in enhancement of HIV-1 infection in CD4+ EBV-containing B cells by infecting such cells in the presence of sera from HIV sero-positive donors, with or without added human complement. A marked increase in production of viral p24 and infectious progeny virus was observed only when infection had been carried out in the presence of human complement. The addition of mAb to the human complement receptor 2 completely inhibited this enhancement. This mechanism was CD4 dependent, suggesting a cooperative effect between these two ligands in the potentiation of viral entry.
Complement-activating rheumatoid-factor-containing complexes in patients with rheumatoid vasculitis.
Authors: C J Elson, D G Scott, D R Blake, P A Bacon, P D Holt
Journal: Annals of the Rheumatic Diseases (1983)

The role of complement and rheumatoid factor in immune complexes was examined in patients with a variety of rheumatic diseases. This was done by assessing the amount of rheumatoid factor (RF) bound from sera by F(ab)2 anti-C3 attached to a solid matrix. High levels of RF bound to C3 were detected in patients with rheumatoid arthritis complicated by vasculitis but rarely and in lower levels in patients with synovitis, ankylosing spondylitis, and systemic lupus erythematosus. The activity was bound to anti-C3 through anti-C3 antibodies because little was bound by normal F(ab)2 and was evidently complexed in the sera before in-vitro testing, since it was precipitated by 2 . 5% polyethylene glycol and sedimented with high molecular weight material on sucrose density gradient ultracentrifugation. It is considered that RF-containing complexes are present in vasculitic sera and have the potential to bind complement in vivo.
2009 Version of the Chompret Criteria for Li Fraumeni Syndrome
Authors: Julie Tinat, Gaelle Bougeard, Stéphanie Baert-Desurmont, Stéphanie Vasseur, Cosette Martin, Emilie Bouvignies, Olivier Caron, Brigitte Bressac-de Paillerets, Pascaline Berthet, Catherine Dugast, Catherine Bonaïti-Pellié, Dominique Stoppa-Lyonnet, Thierry Frébourg
Journal: Journal of Clinical Oncology (2009)

in 474FrenchfamiliessuggestiveofLFS,including232familiesfulﬁllingtheChompret criteria; obtained a mutation detection rate of 29% (67of232families);andestimatedthesensitivityandspeciﬁcityoftheChompret criteria to be 82% and 58%, respectively. We also pro-posedextendingtheChompretcriteriatocovertheclinicalpresen-tation of the 82 families in which we identiﬁed germline
Phase II Trial of Short-Course CHOP-R Followed by 90Y-ibritumomab Tiuxetan and Extended Rituximab in Previously Untreated Follicular Lymphoma
Authors: Samuel A. Jacobs, Steven H. Swerdlow, Jeffrey Kant, Kenneth A. Foon, Rachel Jankowitz, Stephanie R. Land, Nicholas DeMonaco, Judith Joyce, Jennifer L. Osborn, Terry L. Evans, Patricia M. Schaefer
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Radioimmunotherapy has been approved for relapsed follicular lymphoma (FL), including rituximab-refractory FL. This study was designed to determine the CR rate with short-course chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (CHOP-R) followed by 90-Y ibritumomab tiuxetan (RIT) with extended rituximab as first-line treatment. Experimental Design: Between March 2004 and February 2007, 60 patients with stage II to IV symptomatic or bulky FL from a single institution supported by a large community network entered this phase II trial. Patients received CHOP-R for three treatment cycles before RIT followed by four additional weekly treatments with rituximab. Response was determined using fusion [18 F] fluorodeoxyglucose-positron emission tomography (PET)-computed tomography (CT) imaging. Results: Of the 60 patients entering this trial, 55 patients completed all protocol therapy. The median follow up was 19.7 months (range, 0.26-35.9 months). For intent-to-treat analysis, the complete response (CR) rate after CHOP-R, as assessed by CT and PET imaging, was 40% and 46%, respectively. After RIT, the CR rate improved, as assessed by CT and PET imaging, to 82% and 89%, respectively. Ten patients have progressed, including eight from best response of CR. Seven of 18 patients who were PET positive after CHOP-R progressed compared with 3 of 37 patients who were PET negative (P = 0.010). Conclusions: In patients with previously untreated, symptomatic or bulky FL, short-course chemoimmunotherapy and consolidation RIT and extended rituximab resulted in a high CR rate. Failure to achieve an early PET CR after CHOP-R indicated high risk of relapse.
7, 4'-Dihydroxyflavone Isolated From Glycyrrhiza Uralensis a Constituent Of ASHMITM Prevents Dexamethasone Enhancement Of Eotaxin-1 Secretion By Human Lung Fibroblasts
Authors: Changda Liu, Nan Yang, Ryan P. Robalino, Dana Greene, Janaki Patel, Jiachen Zi, Shuwei Zhang, Joseph Goldfarb, Hugh A. Sampson, Jixun Zhan, Xiu-Min Li
Journal: Journal of Allergy and Clinical Immunology (2014)
Seizure disorders in systemic lupus erythematosus results from an international, prospective, inception cohort study
Authors: John G Hanly, Murray B Urowitz, Li Su, Caroline Gordon, Sang-Cheol Bae, Jorge Sanchez-Guerrero, Juanita Romero-Diaz, Daniel J Wallace, Ann E Clarke, EM Ginzler, Joan T Merrill, David A Isenberg, Anisur Rahman, M Petri, Paul R Fortin, DD Gladman, Ian N Bruce, Kristjan Steinsson, MA Dooley, Munther A Khamashta, Graciela S Alarcón, Barri J Fessler, Rosalind Ramsey-Goldman, Susan Manzi, Asad A Zoma, Gunnar K Sturfelt, Ola Nived, Cynthia Aranow, Meggan Mackay, Manuel Ramos-Casals, RF van Vollenhoven, Kenneth C Kalunian, Guillermo Ruiz-Irastorza, Sam Lim, Diane L Kamen, Christine A Peschken, Murat Inanc, Chris Theriault, Kara Thompson, Vernon Farewell
Journal: Annals of the Rheumatic Diseases (2012)

The aim of this study was to describe the frequency, attribution, outcome and predictors of seizures in systemic lupus erythematosus (SLE).The Systemic Lupus International Collaborating Clinics, or SLICC, performed a prospective inception cohort study. Demographic variables, global SLE disease activity (SLE Disease Activity Index 2000), cumulative organ damage (SLICC/American College of Rheumatology Damage Index (SDI)) and neuropsychiatric events were recorded at enrolment and annually. Lupus anticoagulant, anticardiolipin, anti-β(2) glycoprotein-I, antiribosomal P and anti-NR2 glutamate receptor antibodies were measured at enrolment. Physician outcomes of seizures were recorded. Patient outcomes were derived from the SF-36 (36-Item Short Form Health Survey) mental component summary and physical component summary scores. Statistical analyses included Cox and linear regressions.The cohort was 89.4% female with a mean follow-up of 3.5±2.9 years. Of 1631 patients, 75 (4.6%) had ≥1 seizure, the majority around the time of SLE diagnosis. Multivariate analysis indicated a higher risk of seizures with African race/ethnicity (HR (CI): 1.97 (1.07 to 3.63); p=0.03) and lower education status (1.97 (1.21 to 3.19); p<0.01). Higher damage scores (without neuropsychiatric variables) were associated with an increased risk of subsequent seizures (SDI=1:3.93 (1.46 to 10.55); SDI=2 or 3:1.57 (0.32 to 7.65); SDI≥4:7.86 (0.89 to 69.06); p=0.03). There was an association with disease activity but not with autoantibodies. Seizures attributed to SLE frequently resolved (59/78 (76%)) in the absence of antiseizure drugs. There was no significant impact on the mental component summary or physical component summary scores. Antimalarial drugs in the absence of immunosuppressive agents were associated with reduced seizure risk (0.07 (0.01 to 0.66); p=0.03).Seizures occurred close to SLE diagnosis, in patients with African race/ethnicity, lower educational status and cumulative organ damage. Most seizures resolved without a negative impact on health-related quality of life. Antimalarial drugs were associated with a protective effect.
Endocannabinoids and exercise
Authors: A Dietrich, W F McDaniel
Journal: British Journal of Sports Medicine (2004)

Exercise induces changes in mental status, particularly analgesia, sedation, anxiolysis, and a sense of wellbeing. The mechanisms underlying these changes remain unknown. Recent findings show that exercise increases serum concentrations of endocannabinoids, suggesting a possible explanation for a number of these changes. This article provides an overview of this emerging field.