tbuckley/cabot-search huggingface dataset:
Reliability of Self-Reported Family History of Cancer in a Large Case–Control Study of Lymphoma
Authors: Ellen T. Chang, Karin Ekström Smedby, Henrik Hjalgrim, Bengt Glimelius, Hans-Olov Adami
Journal: JNCI Journal of the National Cancer Institute (2006)

Case-control studies of familial cancer risk traditionally rely on self-reported family history of cancer, which may bias results due to differential recall between case patients and control subjects. To evaluate the reliability of self-reported data, we analyzed questionnaire and registry-based data on familial cancer from a population-based case-control study of malignant lymphoma.All 1508 lymphoma case patients and 1229 control subjects completed a telephone interview assessing cancer in family members. Participants were linked to the Swedish Multi-Generation Register and Cancer Register to identify confirmed cancer diagnoses in first-degree relatives. The sensitivity and specificity of self-reported familial cancer were calculated among case patients and control subjects and were compared using logistic regression. All statistical tests were two-sided.Lymphoma case patients reported a family history of any cancer with statistically significantly higher sensitivity than control subjects (0.85, 95% confidence interval [CI] = 0.83 to 0.87 and 0.80, 95% CI = 0.77 to 0.82, respectively) but with marginally lower specificity (0.89, 95% CI = 0.87 to 0.91 and 0.92, 95% CI = 0.90 to 0.94, respectively). The sensitivity of self-reporting familial cancers by site ranged from less than 0.20 for rare malignancies to nearly 0.75 for more common types, whereas specificity was generally 0.98 or greater. For most sites, the reliability of self-report was similar in patients and control subjects. However, patients reported familial hematopoietic cancer with statistically significantly higher sensitivity (0.60, 95% CI = 0.57 to 0.62) than control subjects (0.38, 95% CI = 0.35 to 0.40). Odds ratios for the association between familial cancer and risk of non-Hodgkin lymphoma were consistently higher when based on self-reported, compared with registry data-based, family history of any cancer or of hematopoietic cancer.Reliability of self-reported family history of cancer varies between case patients and control subjects. Recall bias may thus produce biased results in case-control studies of familial cancer risk.
Fibroproliferation and mast cells in the acute respiratory distress syndrome
Authors: J. M Liebler, Z. Qu, B. Buckner, M. R Powers, J. T Rosenbaum
Journal: Thorax (1998)

Mast cells (MCs), which are a major source of cytokines and growth factors, have been implicated in various fibrotic disorders. To clarify the contribution of MCs to fibrogenesis, lung tissue from patients with the acute respiratory distress syndrome (ARDS) was examined during exudative through to fibroproliferative stages.Lung tissue was obtained from 17 patients with ARDS who had pathological features of the early exudative stage (n = 6) or the later reparative stages (n = 11), from four patients with idiopathic pulmonary fibrosis, and from three patients with normal lung tissue. Immunohistochemical localisation of tryptase (found in all human MCs), chymase (found in a subset of human MCs), alpha-smooth muscle actin (identifies myofibroblasts), and procollagen type I was performed.Normal lung tissue exhibited myofibroblast and procollagen type I immunolocalisation scores each of < 5 and MC scores of 1. Increased scores were defined as myofibroblast and procollagen type I scores of > 10 and MC scores of > or = 2. Eighty percent of lung tissue samples from the early exudative stage of ARDS exhibited increased numbers of myofibroblasts, 50% had increased numbers of procollagen type I producing cells, while only 17% had increased numbers of MCs compared with control samples. All samples from the later reparative stages of ARDS had increased numbers of myofibroblasts and procollagen type I producing cells. Increased numbers of MCs were seen in 55% of samples from the reparative stages. There was no significant shift in MC phenotype in the ARDS samples.Increased numbers of myofibroblasts and procollagen type I producing cells were frequently found early in the course of ARDS. MC hyperplasia was unusual during this stage, but was often a feature of the later reparative stages. MCs do not appear to initiate fibroproliferation in ARDS.
Allergic bronchopulmonary aspergillosis in cystic fibrosis
Authors: G. Mastella, M. Rainisio, H.K. Harms, M.E. Hodson, C. Koch, J. Navarro, B. Strandvik, S.G. McKenzie
Journal: European Respiratory Journal (2001)

To the Editor: 

The main criticism arising from Kastelik et al . 1 on the study of allergic bronchopulmonary aspergillosis (ABPA) based on the data of the European Registry of Cystic Fibrosis (ERCF) 2 regards the criteria adopted for the ABPA diagnosis: positive markers of hypersensitivity to Aspergillus fumigatus plus a physician's suspicion that the patient has ABPA. We agree that the clinical suspicion is subject to some diagnostic inaccuracy. However, the ERCF required that the clinical suspicion was based to some extent on “reversible bronchoconstriction, pulmonary infiltrations, elevated serum immunoglobulin (Ig)-E and/or IgG specific for A. fumigatus , peripheral eosinophilia (>1000 mL−1), recovery of A. fumigatus from sputum or hyphae present on smear, and response to steroids”.

The true problem for the ABPA diagnosis in cystic fibrosis (CF) is that …
Olopatadine Nasal Spray 0.6% is Superior to Vehicle and Non-Inferior to Azelastine Nasal Spray 0.1% When Dosed Twice-Daily for the Treatment of Seasonal Allergic Rhinitis
Authors: D MOHAR, P RATNER, S SHAH, M DRAKE, K CRENSHAW, G WALL
Journal: Journal of Allergy and Clinical Immunology (2008)
Risks for All-Cause Mortality, Cardiovascular Disease, and Diabetes Associated With the Metabolic Syndrome
Authors: Earl S. Ford
Journal: Diabetes Care (2005)

OBJECTIVE—In recent years, several major organizations have endorsed the concept of the metabolic syndrome and developed working definitions for it. How well these definitions predict the risk for adverse events in people with the metabolic syndrome is only now being learned. The purpose of this study was to summarize the estimates of relative risk for all-cause mortality, cardiovascular disease, and diabetes reported from prospective studies in samples from the general population using definitions of the metabolic syndrome developed by the National Cholesterol Education Program (NCEP) and World Health Organization (WHO). RESEARCH DESIGN AND METHODS—The author reviewed prospective studies from July 1998 through August 2004. RESULTS—For studies that used the exact NCEP definition of the metabolic syndrome, random-effects estimates of combined relative risk were 1.27 (95% CI 0.90–1.78) for all-cause mortality, 1.65 (1.38–1.99) for cardiovascular disease, and 2.99 (1.96–4.57) for diabetes. For studies that used the most exact WHO definition of the metabolic syndrome, the fixed-effects estimates of relative risk were 1.37 (1.09–1.74) for all-cause mortality and 1.93 (1.39–2.67) for cardiovascular disease; the fixed-effects estimate was 2.60 (1.55–4.38) for coronary heart disease. CONCLUSIONS—These estimates suggest that the population-attributable fraction for the metabolic syndrome, as it is currently conceived, is ∼6–7% for all-cause mortality, 12–17% for cardiovascular disease, and 30–52% for diabetes. Further research is needed to establish the use of the metabolic syndrome in predicting risk for death, cardiovascular disease, and diabetes in various population subgroups.
Clinical characteristics, airway inflammation, and adipocytokines in overweight and obese asthmatics
Authors: Masanobu Ishii, Yukari Miyamoto, Katsunori Ochiai, Saori Kirishi, Etsuko Tagaya, Kiyoshi Takeyama, Jun Tamaoki
Journal: European Respiratory Journal (2013)

Rationale: Obesity affects asthma development, severity, and treatment response. Understanding how obesity influences symptoms, QOL and asthma characteristics is thus necessary to optimize management for this phonotype.  Methods: 186 adult patients with mild-to-moderate persistent asthma were enrolled in this study, from which 25 patients whose BMI of > 25 kg/m2 and 25 normal weight patients were randomly selected. Patients completed ACT and underwent comprehensive pulmonary function testing. Blood samples were collected to measure adipocytokines including IL-6, leptin, adiponectin, PAI-1 and TNF-α. Inflammatory cell counts in induced sputum and NO contents in exhaled air were measured. We also assessed the response to 12-week treatment with FBC.  Results: Overweight patients were more likely to be women (p = 0.026), and had older age of disease onset (p = 0.022), lower ACT scores (p = 0.045) and lower serum IgE (p = 0.042). FRC and ERV were less in overweight patients than in normal weight patients (both p   Conclusion: Overweight is an important phonotypic determinant in asthma. The increased levels of leptin might play a role in eosinophilic airway inflammation, and the responses to inhaled corticosteroid are attenuated in overweight patients.
Genetic Identification of Wild and Domestic Cats (Felis silvestris) and Their Hybrids Using Bayesian Clustering Methods
Authors: E Randi, M Pierpaoli, M Beaumont, B Ragni, A Sforzi
Journal: Molecular Biology and Evolution (2001)

Crossbreeding with free-ranging domestic cats is supposed to threaten the genetic integrity of wildcat populations in Europe, although the diagnostic markers to identify “pure” or “admixed” wildcats have never been clearly defined. Here we use mitochondrial (mt) DNA sequences and allelic variation at 12 microsatellite loci to genotype 128 wild and domestic cats sampled in Italy which were preclassified into three separate groups: European wildcats (Felis silvestris silvestris), Sardinian wildcats (Felis silvestris libyca), and domestic cats (Felis silvestris catus), according to their coat color patterns, collection localities, and other phenotypical traits, independently of any genetic information. For comparison, we included some captive-reared hybrids of European wild and domestic cats. Genetic variability was significantly partitioned among the three groups (mtDNA estimate of FST = 0.36; microsatellite estimate of RST = 0.30; P < 0.001), suggesting that morphological diversity reflects the existence of distinct gene pools. Multivariate ordination of individual genotypes and clustering of interindividual genetic distances also showed evidence of distinct cat groups, partially congruent with the morphological classification. Cluster analysis, however, did not enable hybrid cats to be identified from genetic information alone, nor were all individuals assigned to their populations. In contrast, a Bayesian admixture analysis simultaneously assigned the European wildcats, the Sardinian wildcats, and the domestic cats to different clusters, independent of any prior information, and pointed out the admixed gene composition of the hybrids, which were assigned to more than one cluster. Only one putative Sardinian wildcat was assigned to the domestic cat cluster, and one presumed European wildcat showed mixed (hybrid) ancestry in the domestic cat gene pool. Mitochondrial DNA sequences indicated that three additional presumed European wildcats might have hybrid ancestry. These four cats were sampled from the same area in the northernmost edge of the European wildcat distribution in the Italian Apennines. Admixture analyses suggest that wild and domestic cats in Italy are distinct, reproductively isolated gene pools and that introgression of domestic alleles into the wild-living population is very limited and geographically localized.
A Case of Xanthoma Multiplex in a Child
Authors: T. M. Anderson
Journal: BMJ (1892)

1220 TM ftm= Il XANTHOMA MULTIPLEX.IDBC. 3 189.and far inferior to the chemical action of chloroform and other narcotic vapours.So also as an ordinary hypnotic.It is far less certain, far more troublesome, much more rarely capable of application, and much more likely to produce mischief, than opium or sulphonal, or any other of a dozen narcotics which are always at hand, are cheap, easily used, and under ordinary circumstances innocuous when properly used.As to the treatment of other diseases, I have, I believe, read all that is to be read on the subject, whether from the school of Nancy, of Paris, or of Vienna, and I have arrived at the conclusion that Professor Charcot, with his abundant d sense, his great erudition, and his vast experience, is fully justified in the conclusion at which he and his eminent pupil Richer, Babinsky, D6jerine, and others have arrived; that, for curative purposes, it is very rarely useful, generally altogether useless, and often injurious.
The Host Nonsense-Mediated mRNA Decay Pathway Restricts Mammalian RNA Virus Replication
Authors: Giuseppe Balistreri, Peter Horvath, Christoph Schweingruber, David Zünd, Gerald McInerney, Andres Merits, Oliver Mühlemann, Claus Azzalin, Ari Helenius
Journal: Cell Host & Microbe (2014)
Updated Treatment Algorithm of Pulmonary Arterial Hypertension
Authors: Nazzareno Galiè, Paul A. Corris, Adaani Frost, Reda E. Girgis, John Granton, Zhi Cheng Jing, Walter Klepetko, Michael D. McGoon, Vallerie V. McLaughlin, Ioana R. Preston, Lewis J. Rubin, Julio Sandoval, Werner Seeger, Anne Keogh
Journal: Journal of the American College of Cardiology (2013)
A Phase I Pharmacokinetic and Pharmacodynamic Study of Dalotuzumab (MK-0646), an Anti-Insulin-like Growth Factor-1 Receptor Monoclonal Antibody, in Patients with Advanced Solid Tumors
Authors: Francesco Atzori, Josep Tabernero, Andrés Cervantes, Ludmila Prudkin, Jordi Andreu, Edith Rodríguez-Braun, Amparo Domingo, Jorge Guijarro, Cristina Gamez, Jordi Rodon, Serena Di Cosimo, Holly Brown, Jason Clark, James S. Hardwick, Robert A. Beckman, William D. Hanley, Karl Hsu, Emiliano Calvo, Susana Roselló, Ronald B. Langdon, José Baselga
Journal: Clinical Cancer Research (2011)

Insulin-like growth factor-1 receptor (IGF-1R) mediates cellular processes in cancer and has been proposed as a therapeutic target. Dalotuzumab (MK-0646) is a humanized IgG1 monoclonal antibody that binds to IGF-1R preventing receptor activation. This study was designed to evaluate the safety and tolerability of dalotuzumab, determine the pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and identify a recommended phase II dose.Patients with tumors expressing IGF-1R protein were allocated to dose-escalating cohorts of three or more patients each and received intravenous dalotuzumab weekly, every 2 or 3 weeks. Plasma was collected for PK analysis. Paired baseline and on-treatment skin and tumor biopsy samples were collected for PD analyses.Eighty patients with chemotherapy-refractory solid tumors were enrolled. One dose-limiting toxicity was noted, but a maximum-tolerated dose was not identified. Grade 1 to 3 hyperglycemia, responsive to metformin, occurred in 15 (19%) patients. At dose levels or more than 5 mg/kg, dalotuzumab mean terminal half-life was 95 hours or more, mean C(min) was more than 25 μg/mL, clearance was constant, and serum exposures were approximately dose proportional. Decreases in tumor IGF-1R, downstream receptor signaling, and Ki67 expression were observed. (18)F-Fluorodeoxy-glucose positron emission tomography metabolic responses occurred in three patients. One patient with Ewing's sarcoma showed a mixed radiologic response. The recommended phase II doses were 10, 20, and 30 mg/kg for the weekly, every other week, and every third week schedules, respectively.Dalotuzumab was generally well-tolerated, exhibited dose-proportional PK, inhibited IGF-1R pathway signaling and cell proliferation in treated tumors, and showed clinical activity. The low clearance rate and long terminal half-life support more extended dosing intervals.
Interaction of Platelet Membrane Receptors with von Willebrand Factor, Ristocetin, and the Fc Region of Immunoglobulin G
Authors: Anne Moore, Gordon D. Ross, Ralph L. Nachman
Journal: Journal of Clinical Investigation (1978)

The agglutination of human platelets by ristocetin and von Willebrand factor was inhibited by aggregated immunoglobulin (Ig)G and by Fc fragments of IgG, but not by Fab, F(ab′)2 or pFc fragments of IgG. Because this inhibition occurred with formalin-fixed platelets as well as with normal platelets, a generalized aggregation of fluid membrane components by Fc fragments was not responsible for this inhibition of ristocetin and von Willebrand factor-induced agglutination. Reciprocal inhibition of platelet Fc receptors was produced by prior incubation of platelets with von Willebrand factor and ristocetin. Sucrose density gradient ultracentrifugation studies demonstrated that aggregated IgG did not form fluid-phase complexes with von Willebrand factor and ristocetin. Furthermore, passage of von Willebrand factor and ristocetin through a column of immobilized heat-aggregated IgG did not alter platelet agglutinating activity which indicates that aggregated IgG did not inactivate von Willebrand factor or ristocetin. Thus, it was likely that the IgG-mediated interference with platelet agglutination by ristocetin and von Willebrand factor did not occur in the fluid phase but at the platelet surface. These studies suggest that the platelet membrane Fc receptor may be either a part of, or sterically related to, the membrane glycoprotein I complex that interacts with von Willebrand factor, and that occupation of one of these surface components blocks the availability of the other.
IGFBP3 impedes aggressive growth of pediatric liver cancer and is epigenetically silenced in vascular invasive and metastatic tumors
Authors: Ivonne Regel, Melanie Eichenmüller, Saskia Joppien, Johanna Liebl, Beate Häberle, Josef Müller-Höcker, Angelika Vollmar, Dietrich von Schweinitz, Roland Kappler
Journal: Molecular Cancer (2012)

Abstract Background Hepatoblastoma (HB) is an embryonal liver neoplasm of early childhood with a poor prognosis for patients with distant metastases and vascular invasion. We and others have previously shown that the overexpression of insulin-like growth factor 2 ( IGF2 ), loss of imprinting at the IGF2 / H19 locus, and amplification of pleomorphic adenoma gene 1 ( PLAG1 ) are common features in HB, suggesting a critical role of the IGF axis in hepatoblastomagenesis. In this study, we investigated the role of the insulin-like growth factor binding protein 3 (IGFBP3), a known competitor of the IGF axis, in pediatric liver cancers. Results The IGFBP3 gene was highly expressed in normal pediatric livers but was heavily downregulated in four HB cell lines and the majority of HB primary tumors (26/36). Detailed methylation analysis of CpG sites in the IGFBP3 promoter region by bisulfite sequencing revealed a high degree of DNA methylation, which is causatively associated with the suppression of IGFBP3 in HB cell lines. Consequently, the treatment of HB cell lines with 5-aza-2'-deoxycytidine resulted in DNA demethylation and reactivation of the epigenetically silenced IGFBP3 expression. Interestingly, IGFBP3 promoter methylation predominantly occurred in metastatic HB with vascular invasion. Restoring IGFBP3 expression in HB cells resulted in reduced colony formation, migration, and invasion. Conclusion This study provides the first direct evidence that the reactivation of IGFBP3 decreases aggressive properties of pediatric liver cancer cells and that IGFBP3 promoter methylation might be used as an indicator for vessel-invasive tumor growth in HB patients.
Hypertension-Associated Kidney Disease
Authors: Barry I. Freedman, John R. Sedor
Journal: Journal of the American Society of Nephrology (2008)

Despite common wisdom, the role of essential hypertension in the etiopathogenesis of ESRD has been controversial. Two recently published studies demonstrated a strong association of genetic variants in the gene that encodes the molecular motor protein nonmuscle myosin 2a (MYH9) with ESRD in African American patients without diabetes. These new data demonstrate that much of the excess risk of ESRD in African American individuals is attributable to an MYH9 risk haplotype and suggest that hypertension may cause progressive kidney disease only in genetically susceptible individuals or be the result of a primary renal disease.
The U.S. Food and Drug Administration's Evidence-Based Review for Qualified Health Claims: Tomatoes, Lycopene, and Cancer
Authors: C. J. Kavanaugh, P. R. Trumbo, K. C. Ellwood
Journal: JNCI Journal of the National Cancer Institute (2007)

Several studies have reported an inverse association between tomato and/or lycopene intake and the risk of some types of cancer. In 2004, the U.S. Food and Drug Administration (FDA) received two petitions for qualified health claims regarding tomatoes, lycopene, and the risk reduction for some forms of cancer. Health claims that characterize the relationship between a food or food component and a disease or health-related condition require premarket approval by FDA to be included on the labels of conventional foods and dietary supplements. Here we describe FDA's review of the scientific data for tomato and/or lycopene intake with respect to risk reduction for certain forms of cancer. The FDA found no credible evidence to support an association between lycopene intake and a reduced risk of prostate, lung, colorectal, gastric, breast, ovarian, endometrial, or pancreatic cancer. The FDA also found no credible evidence for an assocaition between tomato consumption and a reduced risk of lung, colorectal, breast, cervical, or endometrial cancer. The FDA found very limited evidence to support an association between tomato consumption and reduced risks of prostate, ovarian, gastric, and pancreatic cancers.
Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study
Authors: P. Schlagenhauf
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective</b> To compare the tolerability of malaria chemoprophylaxis regimens in non-immune travellers. <b>Design</b> Randomised, double blind, study with placebo run-in phase. <b>Setting</b> Travel clinics in Switzerland, Germany, and Israel. <b>Main outcome measure</b> Proportion of participants in each treatment arm with subjectively moderate or severe adverse events. <b>Participants</b> 623 non-immune travellers to sub-Saharan Africa: 153 each received either doxycycline, mefloquine, or the fixed combination chloroquine and proguanil, and 164 received the fixed combination atovaquone and proguanil. <b>Results</b> A high proportion of patients reported adverse events, even in the initial placebo group. No events were serious. The chloroquine and proguanil arm had the highest proportion of mild to moderate adverse events (69/153; 45%, 95% confidence interval 37% to 53%), followed by mefloquine (64/153; 42%, 34% to 50%), doxycycline (51/153; 33%, 26% to 41%), and atovaquone and proguanil (53/164; 32%, 25% to 40%) (P = 0.048 for all). The mefloquine and combined chloroquine and proguanil arms had the highest proportion of more severe events (n = 19; 12%, 7% to 18% and n = 16; 11%, 6% to 15%, respectively), whereas the combined atovaquone and proguanil and doxycycline arms had the lowest (n = 11; 7%, 2% to 11% and n = 9; 6%, 2% to 10%, respectively: P = 0.137 for all). The mefloquine arm had the highest proportion of moderate to severe neuropsychological adverse events, particularly in women (n = 56; 37%, 29% to 44% versus chloroquine and proguanil, n = 46; 30%, 23% to 37%; doxycycline, n = 36; 24%, 17% to 30%; and atovaquone and proguanil, n = 32; 20%, 13% to 26%: P = 0.003 for all). The highest proportion of moderate or severe skin problems were reported in the chloroquine and proguanil arm (n= 12; 8%, 4% to 13% versus doxycycline, n = 5; 3%, 1% to 6%; atovaquone and proguanil, n = 4; 2%, 0% to 5%; mefloquine, n = 2; 1%, 0% to 3%: P = 0.013). <b>Conclusions</b> Combined atovaquone and proguanil and doxycyline are well tolerated antimalarial drugs. Broader experience with both agents is needed to accumulate reports of rare adverse events.