tbuckley/cabot-search huggingface dataset:
Asbestos related pleuropulmonary lesions and the erythrocyte sedimentation rate.
Authors: G Hillerdal
Journal: Thorax (1984)

Asbestos related lesions of the lung parenchyma and the pleura can be divided into three main types: parietal pleural plaques, diffuse interstitial fibrosis ("classical asbestosis"), and a third type of reaction affecting both the pleura and the lung parenchyma. The last type includes such lesions as acute pleurisy, diffuse pleural thickening, and rounded atelectasis. Among 1344 patients with asbestos related pleural lesions, 1190 had pleural plaques, 29 of whom also had pulmonary fibrosis (asbestosis); 83 had unilateral sequelae of pleurisy, of whom nine had asbestosis; and 71 had bilateral sequelae of pleurisy, of whom 23 also suffered from asbestosis. The erythrocyte sedimentation rate (ESR) was measured in 184 patients--79 with pleural plaques, 44 with unilateral sequelae of pleurisy, and 61 with bilateral sequelae. In patients with pleural plaques with or without asbestosis the ESR was usually normal, the mean being 9.6 mm in one hour. Among patients with sequelae of pleurisy, however, many had a raised ESR. The mean ESR was 25.7 mm in one hour in those with bilateral changes and 13.2 in those with unilateral changes. Statistical analysis showed that in this group of subjects the presence of sequelae of pleurisy was a highly significant determining factor for the ESR (p less than 0.0001). Asbestosis alone was not a significant determining factor but there was a low grade of significance for the combined effect of asbestosis and sequelae of pleurisy (p less than 0.05). These findings suggest that the pathogenesis of the various changes is different.
Molecular profiling of malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1, based on large-scale real-time RT-PCR.
Authors: Pascale Lévy, Dominique Vidaud, Karen Leroy, Ingrid Laurendeau, Janine Wechsler, Giulia Bolasco, Béatrice Parfait, Pierre Wolkenstein, Michel Vidaud, Ivan Bièche
Journal: Molecular Cancer (2004)

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a complex range of clinical symptoms. The hallmark of NF1 is the onset of heterogeneous (dermal or plexiform) benign neurofibromas. Plexiform neurofibromas can give rise to malignant peripheral nerve sheath tumors (MPNSTs), and the underlying molecular mechanisms are largely unknown. To obtain further insight into the molecular pathogenesis of MPNSTs, we used real-time quantitative RT-PCR to quantify the mRNA expression of 489 selected genes in MPNSTs, in comparison with plexiform neurofibromas. The expression of 28 (5.7%) of the 489 genes was significantly different between MPNSTs and plexiform neurofibromas; 16 genes were upregulated and 12 were downregulated in MPNSTs. The altered genes were mainly involved in cell proliferation (MKI67, TOP2A, CCNE2), senescence (TERT, TERC), apoptosis (BIRC5/Survivin, TP73) and extracellular matrix remodeling (MMP13, MMP9, TIMP4, ITGB4). More interestingly, other genes were involved in the Ras signaling pathway (RASSF2, HMMR/RHAMM) and the Hedgehog-Gli signaling pathway (DHH, PTCH2). Several of the down-regulated genes were Schwann cell-specific (L1CAM, MPZ, S100B, SOX10, ERBB3) or mast cell-specific (CMA1, TPSB), pointing to a depletion and/or dedifferentiation of Schwann cells and mast cells during malignant transformation of plexiform neurofibromas. These data suggest that a limited number of signaling pathways, and particularly the Hedgehog-Gli signaling pathway, may be involved in malignant transformation of plexiform neurofibromas. Some of the relevant genes or their products warrant further investigation as potential therapeutic targets in NF1.
Nutritional deficit as a negative prognostic factor in patients with miliary tuberculosis
Authors: D. K. Kim, H. J. Kim, S-Y. Kwon, H-I. Yoon, C-T. Lee, Y. W. Kim, H. S. Chung, S. K. Han, Y-S. Shim, J-H. Lee
Journal: European Respiratory Journal (2008)

The effects of malnutrition on outcomes in miliary tuberculosis (MTB) are not well described. The aim of the present study was to find predictors for the development of acute respiratory failure (ARF) and survival in MTB patients, focusing on parameters reflecting nutritional condition. Out of the patients from three hospitals who had microbiologically or histopathologically confirmed tuberculosis, 56 patients presenting with typical disseminated pulmonary nodules on radiographs were retrospectively enrolled. A four-point nutritional risk score (NRS) was defined according to the presence of four nutritional factors: low body mass index (BMI; <18.5 kg x m(-2)), hypoalbuminaemia (<30.0 g x L(-1)), hypocholesterolaemia (<2.33 mmol x L(-1)) and severe lymphocytopenia (<7 x 10(5) cells x L(-1)). The male to female ratio was 1:3. ARF developed in 25% of patients (14 out of 56), with a 50% fatality rate. A high NRS (> or =3 points) was an independent risk factor for the development of ARF and fatality. In 90-day survival analysis, ARF, severe lymphocytopenia, hypocholesterolaemia, low BMI and higher NRS were risk factors for poor outcome. In multivariate analysis, only high NRS was an independent risk factor for 90-day survival rate in patients with MTB. A high nutritional risk score was a good predictor of poor outcome in miliary tuberculosis patients. Additional approaches to recover the nutritional deficits may become a focus in future management of miliary tuberculosis.
Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases
Authors: Véronique Gelsi-Boyer, Mandy Brecqueville, Raynier Devillier, Anne Murati, Marie-Joelle Mozziconacci, Daniel Birnbaum
Journal: Journal of Hematology & Oncology (2012)

The ASXL1 gene is one of the most frequently mutated genes in malignant myeloid diseases. The ASXL1 protein belongs to protein complexes involved in the epigenetic regulation of gene expression. ASXL1 mutations are found in myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). They are generally associated with signs of aggressiveness and poor clinical outcome. Because of this, a systematic determination of ASXL1 mutational status in myeloid malignancies should help in prognosis assessment.
Role of Endoscopic Ultrasound in the Diagnosis of Intraductal Papillary Mucinous Neoplasms: Correlation With Surgical Histopathology
Authors: Shireen A. Pais, Siriboon Attasaranya, Julia K. Leblanc, Stuart Sherman, C. Max Schmidt, John DeWitt
Journal: Clinical Gastroenterology and Hepatology (2007)
BASP1 Promotes Apoptosis in Diabetic Nephropathy
Authors: Maria Dolores Sanchez-Niño, Ana Belen Sanz, Corina Lorz, Andrea Gnirke, Maria Pia Rastaldi, Viji Nair, Jesus Egido, Marta Ruiz-Ortega, Matthias Kretzler, Alberto Ortiz
Journal: Journal of the American Society of Nephrology (2010)

Apoptosis contributes to the development of diabetic nephropathy (DN), but the mechanisms that lead to diabetes-induced cell death are not fully understood. Here, we combined a functional genomics screen for cDNAs that induce apoptosis in vitro with transcriptional profiling of renal biopsies from patients with DN. Twelve of the 138 full-length cDNAs that induced cell death in human embryonic kidney cells matched upregulated mRNA transcripts in tissue from human DN. Confirmatory screens identified induction of BASP1 in tubular cross sections of human DN tissue. In vitro, apoptosis-inducing conditions such as serum deprivation, high concentrations of glucose, and proinflammatory cytokines increased BASP1 mRNA and protein in human tubular epithelial cells. In normal cells, BASP1 localized to the cytoplasm, but in apoptotic cells, it colocalized with actin in the periphery. Overexpression of BASP1 induced cell death with features of apoptosis; conversely, small interfering RNA (siRNA)-mediated knockdown of BASP1 protected tubular cells from apoptosis. Supporting possible involvement of BASP1 in renal disease other than DN, we also observed significant upregulation of renal BASP1 in spontaneously hypertensive rats and a trend toward increased tubulointerstitial BASP1 mRNA in human hypertensive nephropathy. In summary, a combined functional genomics approach identified BASP1 as a proapoptotic factor in DN and possibly also in hypertensive nephropathy.
Human C4-binding protein. II. Role in proteolysis of C4b by C3b-inactivator.
Authors: T Fujita, I Gigli, V Nussenzweig
Journal: The Journal of Experimental Medicine (1978)

We recently described the isolation from human serum of a high molecular weight protein with specific binding affinity for fluid-phase activated C4. We show here that the C4-binding protein (C4-Bp) functions as an essential cofactor in the proteolysis of C4b in the presence of C3b-inactivator (C3bINA). C4-bp, together with C3bINA, cleave the alpha'-chain of C4b into three fragments called alpha2, alpha3, and alpha4, with mol wt of 47,000, 25,000, and 17,000 daltons, respectively. The alpha2 fragment was dissociated from C4b without reduction, whereas the alpha3 and alpha4 fragments were disulfide bonded the other chains of C4b. The reaction did not occur when either C4-bp or C3bINA were omitted, nor in the presence of either protein in combination with beta1H. Native C4 was not affected by C3bINA aand C4-bp. C4b was not cleaved when incubated in serum of a patient with genetic deficiency of C3bINA. However, when purified C3bINA was added, the alpha'-chain of C4b was cleaved and fragments with the same molecular weight as alpha2, alpha3, and alpha4 were generated.
Intraplatelet Tetrahydrobiopterin Plays an Important Role in Regulating Canine Coronary Arterial Thrombosis by Modulating Intraplatelet Nitric Oxide and Superoxide Generation
Authors: Seiji Kanaya, Hisao Ikeda, Nobuya Haramaki, Toyoaki Murohara, Tsutomu Imaizumi
Journal: Circulation (2001)

Background Platelet-derived nitric oxide inhibits platelet aggregation via constitutive NO synthase (NOS). Tetrahydrobiopterin (BH 4 ), a cofactor of NOS, augments NO formation, whereas its deficiency decreases NO bioactivity and increases superoxide generation by NOS. The roles of intraplatelet BH 4 in platelet aggregation and thrombus formation, however, are unknown. Accordingly, we investigated whether intraplatelet BH 4 is involved in regulating cyclic flow variations (CFVs) and platelet aggregation in a canine model with stenosed and endothelium-injured coronary arteries that mimics acute coronary syndromes in humans. Methods and Results After developing CFVs, dogs received saline or BH 4 (10 or 30 mg/kg) intravenously. Intraplatelet BH 4 and cGMP levels were decreased and intraplatelet nitrotyrosine production was increased during CFVs. ADP- and U46619-induced ex vivo platelet aggregation and platelet P-selectin expression were augmented during CFVs. BH 4 administration restored intraplatelet BH 4 and cGMP levels and decreased intraplatelet nitrotyrosine production, resulting in reduced CFVs and inhibited ex vivo platelet aggregation and platelet P-selectin expression. CFVs again developed after N G -monomethyl- l -arginine, an inhibitor of NOS, in BH 4 -treated dogs. Ex vivo platelet NOS activity at baseline, during CFVs, and after BH 4 administration did not differ. Conclusions Intraplatelet BH 4 may play an important role in regulating thrombus formation by modulating platelet-derived nitric oxide and superoxide generation by platelet NOS.
Phase I and Pharmacologic Study of OSI-774, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Advanced Solid Malignancies
Authors: Manuel Hidalgo, Lillian L. Siu, John Nemunaitis, Jinee Rizzo, Lisa A. Hammond, Chris Takimoto, S. Gail Eckhardt, Anthony Tolcher, Carolyn D. Britten, Louis Denis, Karen Ferrante, Daniel D. Von Hoff, Sandra Silberman, Eric K. Rowinsky
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To assess the feasibility of administering OSI-774, to recommend a dose on a protracted, continuous daily schedule, to characterize its pharmacokinetic behavior, and to acquire preliminary evidence of anticancer activity. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of OSI-774 in three study parts (A to C) to evaluate progressively longer treatment intervals. Part A patients received OSI-774 25 to 100 mg once daily, for 3 days each week, for 3 weeks every 4 weeks. Part B patients received OSI-774 doses ranging from 50 to 200 mg given once daily for 3 weeks every 4 weeks to establish the maximum tolerated dose (MTD). In part C, patients received this MTD on a continuous, uninterrupted schedule. The pharmacokinetics of OSI-774 and its O-demethylated metabolite, OSI-420, were characterized. RESULTS: Forty patients received a total of 123 28-day courses of OSI-774. No severe toxicities precluded dose escalation of OSI-774 from 25 to 100 mg/d in part A. In part B, the incidence of severe diarrhea and/or cutaneous toxicity was unacceptably high at OSI-774 doses exceeding 150 mg/d. Uninterrupted, daily administration of OSI-774 150 mg/d represented the MTD on a protracted daily schedule. The pharmacokinetics of OSI-774 were dose independent; repetitive daily treatment did not result in drug accumulation (at 150 mg/d [average]: minimum steady-state plasma concentration, 1.20 ± 0.62 μg/mL; clearance rate, 6.33 ± 6.41 L/h; elimination half-life, 24.4 ± 14.6 hours; volume of distribution, 136. 4 ± 93.1 L; area under the plasma concentration-time curve for OSI-420 relative to OSI-774, 0.12 ± 0.12 μg/h/mL). CONCLUSION: The recommended dose for disease-directed studies of OSI-774 administered orally on a daily, continuous, uninterrupted schedule is 150 mg/d. OSI-774 was well tolerated, and several patients with epidermoid malignancies demonstrated either antitumor activity or relatively long periods of stable disease. The precise contribution of OSI-774 to these effects is not known.
Customizing Cisplatin Based on Quantitative Excision Repair Cross-Complementing 1 mRNA Expression: A Phase III Trial in Non–Small-Cell Lung Cancer
Authors: Manuel Cobo, Dolores Isla, Bartomeu Massuti, Ana Montes, Jose Miguel Sanchez, Mariano Provencio, Nuria Viñolas, Luis Paz-Ares, Guillermo Lopez-Vivanco, Miguel Angel Muñoz, Enriqueta Felip, Vicente Alberola, Carlos Camps, Manuel Domine, Jose Javier Sanchez, Maria Sanchez-Ronco, Kathleen Danenberg, Miquel Taron, David Gandara, Rafael Rosell
Journal: Journal of Clinical Oncology (2007)

Purpose Although current treatment options for metastatic non–small-cell lung cancer (NSCLC) rely on cisplatin-based chemotherapy, individualized approaches to therapy may improve response or reduce unnecessary toxicity. Excision repair cross-complementing 1 (ERCC1) has been associated with cisplatin resistance. We hypothesized that assigning cisplatin based on pretreatment ERCC1 mRNA levels would improve response. Patients and Methods From August 2001 to October 2005, 444 stage IV NSCLC patients were enrolled. RNA was isolated from pretreatment biopsies, and quantitative real-time reverse transcriptase PCR assays were performed to determine ERCC1 mRNA expression. Patients were randomly assigned in a 1:2 ratio to either the control or genotypic arm before ERCC1 assessment. Patients in the control arm received docetaxel plus cisplatin. In the genotypic arm, patients with low ERCC1 levels received docetaxel plus cisplatin, and those with high levels received docetaxel plus gemcitabine. The primary end point was the overall objective response rate. Results Of 444 patients enrolled, 78 (17.6%) went off study before receiving one cycle of chemotherapy, mainly due to insufficient tumor tissue for ERCC1 mRNA assessment. Of the remaining 346 patients assessable for response, objective response was attained by 53 patients (39.3%) in the control arm and 107 patients (50.7%) in the genotypic arm (P = .02). Conclusion Assessment of ERCC1 mRNA expression in patient tumor tissue is feasible in the clinical setting and predicts response to docetaxel and cisplatin. Additional studies are warranted to optimize methodologies for ERCC1 analysis in small tumor samples and to refine a multibiomarker profile predictive of patient outcome.
The epidemiology of chronic hepatitis C infection in survivors of childhood cancer: an update of the St Jude Children's Research Hospital hepatitis C seropositive cohort
Authors: Sharon Castellino, Shelly Lensing, Caroline Riely, Shesh N. Rai, Rene Davila, Randall T. Hayden, Jackie Fleckenstein, Mark Levstik, Shari Taylor, Patrick J. Dean, Sarah Kippenbrock, Jennifer Pope, Jeanne Carr, Donald K. Strickland, Melissa M. Hudson
Journal: Blood (2003)
MicroRNA Gene Expression Deregulation in Human Breast Cancer
Authors: Marilena V. Iorio, Manuela Ferracin, Chang-Gong Liu, Angelo Veronese, Riccardo Spizzo, Silvia Sabbioni, Eros Magri, Massimo Pedriali, Muller Fabbri, Manuela Campiglio, Sylvie Ménard, Juan P. Palazzo, Anne Rosenberg, Piero Musiani, Stefano Volinia, Italo Nenci, George A. Calin, Patrizia Querzoli, Massimo Negrini, Carlo M. Croce
Journal: Cancer Research (2005)

Abstract MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. Indeed, miRNA aberrant expression has been previously found in human chronic lymphocytic leukemias, where miRNA signatures were associated with specific clinicobiological features. Here, we show that, compared with normal breast tissue, miRNAs are also aberrantly expressed in human breast cancer. The overall miRNA expression could clearly separate normal versus cancer tissues, with the most significantly deregulated miRNAs being mir-125b, mir-145, mir-21, and mir-155. Results were confirmed by microarray and Northern blot analyses. We could identify miRNAs whose expression was correlated with specific breast cancer biopathologic features, such as estrogen and progesterone receptor expression, tumor stage, vascular invasion, or proliferation index.
Human Cardiac Stem Cell Differentiation Is Regulated by a Mircrine Mechanism
Authors: Toru Hosoda, Hanqiao Zheng, Mauricio Cabral-da-Silva, Fumihiro Sanada, Noriko Ide-Iwata, Barbara Ogórek, João Ferreira-Martins, Christian Arranto, Domenico D'Amario, Federica del Monte, Konrad Urbanek, David A. D'Alessandro, Robert E. Michler, Piero Anversa, Marcello Rota, Jan Kajstura, Annarosa Leri
Journal: Circulation (2011)

RETRACTION This article has been retracted: Circulation . 2019;139:e1. DOI: 10.1161/CIR.0000000000000644
Short- and long-term efficacy of prednisolone for first acute rhinovirus-induced wheezing episode
Authors: Tuomas Jartti, Riitta Nieminen, Tytti Vuorinen, Pasi Lehtinen, Tero Vahlberg, James Gern, Carlos A. Camargo, Olli Ruuskanen
Journal: Journal of Allergy and Clinical Immunology (2014)

Rhinovirus-induced wheezing is an important risk factor for recurrent wheezing. There are no randomized controlled trials on the effect of systemic corticosteroids in patients with this disease.We sought to study the short- and long-term effects of prednisolone treatment of the first acute, moderate-to-severe, rhinovirus-induced wheezing episode in young children.After confirming rhinovirus from nasopharyngeal aspirate by using PCR, 79 children with a first wheezing episode at age 3 to 23 months were randomized to receive oral prednisolone (first dose of 2 mg/kg, followed by 2 mg/kg/d in 2 divided doses for 3 days) or placebo. The trial was double blind throughout the 12-month follow-up. The primary outcomes were long term: new physician-confirmed wheezing episode within 2 months, number of physician-confirmed wheezing episodes within 12 months, and initiation of regular controller medication for asthma symptoms within 12 months. The primary interaction analysis examined rhinovirus load.Seventy-four patients completed the study (mean age, 13 months; 28% atopic). Long-term outcomes did not differ between groups (all P ≥ .30). For short-term outcomes, the prednisolone group had less cough, rhinitis, noisy breathing, severe breathing difficulties, and nocturnal respiratory symptoms at home within 2 weeks (all P < .05). The 25 children with greater than 7000 rhinovirus copies/mL (most sensitive cutoff) benefitted from prednisolone in terms of less risk of physician-confirmed recurrence within 2 and 12 months compared with placebo (both P < .05).Prednisolone cannot be routinely recommended for all young children experiencing their first acute, moderate-to-severe, rhinovirus-induced wheezing episode. Prednisolone might be beneficial in a subgroup of children with high viral loads.
Primary Central Nervous System Lymphoma: The Memorial Sloan-Kettering Cancer Center Prognostic Model
Authors: Lauren E. Abrey, Leah Ben-Porat, Katherine S. Panageas, Joachim Yahalom, Brian Berkey, Walter Curran, Christopher Schultz, Steven Leibel, Diana Nelson, Minesh Mehta, Lisa M. DeAngelis
Journal: Journal of Clinical Oncology (2006)

The purpose of this study was to analyze prognostic factors for patients with newly diagnosed primary CNS lymphoma (PCNSL) in order to establish a predictive model that could be applied to the care of patients and the design of prospective clinical trials.Three hundred thirty-eight consecutive patients with newly diagnosed PCNSL seen at Memorial Sloan-Kettering Cancer Center (MSKCC; New York, NY) between 1983 and 2003 were analyzed. Standard univariate and multivariate analyses were performed. In addition, a formal cut point analysis was used to determine the most statistically significant cut point for age. Recursive partitioning analysis (RPA) was used to create independent prognostic classes. An external validation set obtained from three prospective Radiation Therapy Oncology Group (RTOG) PCNSL clinical trials was used to test the RPA classification.Age and performance status were the only variables identified on standard multivariate analysis. Cut point analysis of age determined that patients age < or = 50 years had significantly improved outcome compared with older patients. RPA of 282 patients identified three distinct prognostic classes: class 1 (patients < 50 years), class 2 (patients > or =50; Karnofsky performance score [KPS] > or = 70) and class 3 (patients > or = 50; KPS < 70). These three classes significantly distinguished outcome with regard to both overall and failure-free survival. Analysis of the RTOG data set confirmed the validity of this classification. CONCLUSION The MSKCC prognostic score is a simple, statistically powerful model with universal applicability to patients with newly diagnosed PCNSL. We recommend that it be adopted for the management of newly diagnosed patients and incorporated into the design of prospective clinical trials.