tbuckley/cabot-search huggingface dataset:
A monoclonal antibody that recognizes B cells and B cell precursors in mice.
Authors: R L Coffman, I L Weissman
Journal: The Journal of Experimental Medicine (1981)

The monoclonal antibody, RA3-2C2, appears to be specific for cells within the B cell lineage. This antibody does not recognize thymocytes, peripheral T cells, or nonlymphoid hematopoietic cells in the spleen or bone marrow. Nor does it recognize the pluripotent hematopoietic stem cells, the spleen colony-forming unit, All sIg+ B cells and most plasma cells are RA3-2C2+. In addition, approximately 20% of nucleated bone marrow cells are RA3-2C2+ but sIg-. This population contains B cell precursors that can give rise to sIg+ cells within 2 d in vitro.
Prediction of Muscle-invasive Bladder Cancer Using Urinary Proteomics
Authors: Eric Schiffer, Antonia Vlahou, Andreas Petrolekas, Konstantinos Stravodimos, Robert Tauber, Jürgen E. Geschwend, Jochen Neuhaus, Jens-Uwe Stolzenburg, Mark R. Conaway, Harald Mischak, Dan Theodorescu
Journal: Clinical Cancer Research (2009)

Minimally invasive methods of predicting the risk of muscle-invasive urothelial bladder carcinoma may expedite appropriate therapy and reduce morbidity and cost.Here, capillary electrophoresis coupled mass spectrometry was used to identify urinary polypeptide bladder cancer biomarkers in 127 patients. These markers were used to construct a panel discriminating muscle-invasive from noninvasive disease, which was refined in 297 additional samples from healthy volunteers, patients with malignant and nonmalignant genitourinary conditions. Sequencing of panel polypeptides was then done. Finally, the ability of the panel to predict muscle-invasive disease was evaluated prospectively in 130 bladder carcinoma patients. Four sequenced polypeptides formed a panel predictive of muscle-invasive disease.Prospective evaluation of this panel revealed a sensitivity of 81% [95% confidence interval (CI), 69-90] and specificity of 57% (95% CI, 45-69) for muscle-invasive disease. Multivariate analysis revealed the panel (P < 0.0001) and tumor grade (P = 0.0001), but not urine cytology, predict muscle invasion. A model including grade and panel polypeptide levels improved sensitivity [92% (95% CI, 82-97)] and specificity [68% (95% CI, 55-79)] for muscle-invasive disease. A model score of >0.88 provided a negative predictive value of 77% and positive predictive value of 90% for muscle invasion.Use of urinary peptides seems promising in estimating the probability a patient harbors muscle-invasive urothelial bladder cancer. These peptides may also shed novel insights into the biology of bladder tumor progression not obtainable by other methods. Clinical trials seem warranted to evaluate the effect of this approach on practice.
Why I am not a pretentious pseudo-intellectual
Authors: G. O'Neill
Journal: BMJ (2000)

EDITOR—As Chapman's anti-Christian diatribe contains no discernible connection to the practice of medicine I have to wonder why it was published in a medical journal.1 Chapman may think his article daring, but it represents only the latest in an ever increasing tide of abuse to which Christianity is subjected daily. It deserves to be challenged.

Chapman brings out the old chestnut about “the horrors wrought in the name of religion.” The great …
Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis
Authors: Elio Novembre, Elena Galli, Fabiola Landi, Carlo Caffarelli, Massimo Pifferi, Emanuela De Marco, Samuele E. Burastero, Giliola Calori, Luca Benetti, Paolo Bonazza
Journal: Journal of Allergy and Clinical Immunology (2004)
Do mental magnitudes form part of the foundation for natural number concepts? Don't count them out yet
Authors: Hilary Barth
Journal: Behavioral and Brain Sciences (2008)

Abstract The current consensus among most researchers is that natural number is not built solely upon a foundation of mental magnitudes. On their way to the conclusion that magnitudes do not form any part of that foundation, Rips et al. pass rather quickly by theories suggesting that mental magnitudes might play some role. These theories deserve a closer look.
Deletions in the COL4A5 collagen gene in X-linked Alport syndrome. Characterization of the pathological transcripts in nonrenal cells and correlation with disease expression.
Authors: C Antignac, B Knebelmann, L Drouot, F Gros, G Deschênes, M C Hors-Cayla, J Zhou, K Tryggvason, J P Grünfeld, M Broyer
Journal: Journal of Clinical Investigation (1994)

The type IV collagen alpha 5 chain (COL4A5) gene of 88 unrelated male patients with X-linked Alport syndrome was tested for major gene rearrangements by Southern blot analysis, using COL4A5 cDNA probes. 14 different deletions were detected, providing a 16% deletion rate in the COL4A5 gene in the patient population. The deletions are dispersed all over the gene with different sizes, ranging from 1 kb to the complete absence of the gene (> 250 kb) in one patient. In four patients with intragenic deletions, absence of the alpha 3 (IV) chain in the glomerular basement membrane was demonstrated by immunohistochemical studies. This finding supports the hypothesis that abnormalities in the alpha 5 (IV) chain may prevent normal incorporation of the alpha 3 (IV) chain into the glomerular basement membrane. Direct sequencing of cDNA amplified from lymphoblast mRNA of four patients with internal gene deletions, using appropriate combinations of primers amplifying across the predicted boundaries of the deletions, allowed us to determine the effect of the genomic rearrangements on the transcripts and, by inference, on the alpha 5 (IV) chain. Regardless of the extent of deletion and of the putative protein product, the 14 deletions occur in patients with juvenile-type Alport syndrome.
Health‐based selection for asthma, but not for chronic bronchitis, in pig farmers: an evidence‐based hypothesis
Authors: P.F.J. Vogelzang, J.W.J. van der Gulden, M.J.m Tielen, H. Folgering, C.P. van Schayck
Journal: European Respiratory Journal (1999)

In cross-sectional surveys among pig farmers an elevated prevalence of chronic bronchitis is usually reported, but not of asthma, despite many factors promoting the manifestation of asthma. To investigate this apparent contradiction a postal questionnaire survey was performed among 239 pig farmers and 311 rural controls. Pig farmers reported an elevated prevalence of symptoms of chronic bronchitis (20.2 versus 7.7%, p&lt;0.001), but not of asthma (5.9 versus 5.5% for chest tightness). Among pig farmers the use of disinfectants (prevalence odds ratio (POR) 9.4, 95% confidence interval (CI) 1.6-57.2 for quaternary ammonium compounds) and aspects of the disinfecting procedure were associated with the prevalence of asthma symptoms. Compared with controls, pig farmers reported fewer allergies to common allergens (4.6 versus 14.6%, p&lt;0.001 for pollen) and fewer symptoms of atopy in childhood (9.9 versus 17.2, p&lt;0.05 for one or more of four symptoms). Atopy in childhood was strongly associated with the prevalence of asthma symptoms (POR 4.1, 95% CI 2.2-7.7), but not with chronic bronchitis. Health-based selection of nonasthmatics for pig farming, which tends to mask a work-related hazard for asthma, is offered as an explanation for these results.
Evidence against the "early protection-delayed death" hypothesis of superoxide dismutase therapy in experimental myocardial infarction. Polyethylene glycol-superoxide dismutase plus catalase does not limit myocardial infarct size in dogs.
Authors: M Tanaka, R C Stoler, G P FitzHarris, R B Jennings, K A Reimer
Journal: Circulation Research (1990)

We previously found that superoxide dismutase (SOD) did not limit myocardial infarct size after 40 or 90 minutes of ischemia and 4 days of reperfusion in dogs. Because some other studies have shown limitation of infarct size after shorter periods of reperfusion, we postulated that our negative results might be due to late reperfusion injury mediated by superoxide anions produced after excretion of SOD. To test this "early protection-delayed death" hypothesis, we have examined whether SOD, conjugated to polyethylene glycol (PEG-SOD) to prolong its circulating half-life, limited myocardial infarct size. The circumflex artery was occluded for 90 minutes followed by 4 days of reperfusion. PEG-SOD (total dose, 10,000 units/kg) and catalase (55,000 units/kg) were given during the 30 minutes before reperfusion. Plasma SOD levels in the treated group were 330 +/- 20 units/ml at the onset of reperfusion and 140 +/- 10 units/ml on day 4 (circulating half-life, 75 +/- 5 hours) versus 5 +/- 1 units/ml in controls. Histological infarct size was 37.1 +/- 4.2% of the area at risk in the treated group (n = 11) versus 44.5 +/- 6.2% in controls (n = 10) (p = NS). Infarct size and collateral blood flow were inversely related in controls; PEG-SOD and catalase did not shift this regression (p = NS by analysis of covariance). Thus, infarct size was not limited when measured after 4 days of reperfusion, even though plasma SOD exceeded 100 units/ml throughout this reperfusion period.(ABSTRACT TRUNCATED AT 250 WORDS)
Infection control measures to limit the spread of Clostridium difficile
Authors: R.-P. Vonberg, E.J. Kuijper, M.H. Wilcox, F. Barbut, P. Tüll, P. Gastmeier, P.J. van den Broek, A. Colville, B. Coignard, T. Daha, S. Debast, B.I. Duerden, S. van den Hof, T. van der Kooi, H.J.H. Maarleveld, E. Nagy, D.W. Notermans, J. O'Driscoll, B. Patel, S. Stone, C. Wiuff
Journal: Clinical Microbiology and Infection (2008)
Transcriptome analysis of Sinorhizobium melilotiduring symbiosis
Authors: Frederic Ampe, Ernö Kiss, Frédérique Sabourdy, Jacques Batut
Journal: Genome biology (2003)

Rhizobia induce the formation on specific legumes of new organs, the root nodules, as a result of an elaborated developmental program involving the two partners. In order to contribute to a more global view of the genetics underlying this plant-microbe symbiosis, we have mined the recently determined Sinorhizobium meliloti genome sequence for genes potentially relevant to symbiosis. We describe here the construction and use of dedicated nylon macroarrays to study simultaneously the expression of 200 of these genes in a variety of environmental conditions, pertinent to symbiosis.The expression of 214 S. meliloti genes was monitored under ten environmental conditions, including free-living aerobic and microaerobic conditions, addition of the plant symbiotic elicitor luteolin, and a variety of symbiotic conditions. Five new genes induced by luteolin have been identified as well as nine new genes induced in mature nitrogen-fixing bacteroids. A bacterial and a plant symbiotic mutant affected in nodule development have been found of particular interest to decipher gene expression at the intermediate stage of the symbiotic interaction. S. meliloti gene expression in the cultivated legume Medicago sativa (alfalfa) and the model plant M. truncatula were compared and a small number of differences was found.In addition to exploring conditions for a genome-wide transcriptome analysis of the model rhizobium S. meliloti, the present work has highlighted the differential expression of several classes of genes during symbiosis. These genes are related to invasion, oxidative stress protection, iron mobilization, and signaling, thus emphasizing possible common mechanisms between symbiosis and pathogenesis.
Alterations of Choline Phospholipid Metabolism in Ovarian Tumor Progression
Authors: Egidio Iorio, Delia Mezzanzanica, Paola Alberti, Francesca Spadaro, Carlo Ramoni, Sandra D'Ascenzo, Danilo Millimaggi, Antonio Pavan, Vincenza Dolo, Silvana Canevari, Franca Podo
Journal: Cancer Research (2005)

Recent characterization of abnormal phosphatidylcholine metabolism in tumor cells by nuclear magnetic resonance (NMR) has identified novel fingerprints of tumor progression that are potentially useful as clinical diagnostic indicators. In the present study, we analyzed the concentrations of phosphatidylcholine metabolites, activities of phosphocholine-producing enzymes, and uptake of [methyl-14C]choline in human epithelial ovarian carcinoma cell lines (EOC) compared with normal or immortalized ovary epithelial cells (EONT). Quantification of phosphatidylcholine metabolites contributing to the 1H NMR total choline resonance (3.20-3.24 ppm) revealed intracellular [phosphocholine] and [total choline] of 2.3 +/- 0.9 and 5.2 +/- 2.4 nmol/10(6) cells, respectively, with a glycerophosphocholine/phosphocholine ratio of 0.95 +/- 0.93 in EONT cells; average [phosphocholine] was 3- to 8-fold higher in EOC cells (P < 0.0001), becoming the predominant phosphatidylcholine metabolite, whereas average glycerophosphocholine/phosphocholine values decreased significantly to < or =0.2. Two-dimensional (phosphocholine/total choline, [total choline]) and (glycerophosphocholine/total choline, [total choline]) maps allowed separate clustering of EOC from EONT cells (P < 0.0001, 95% confidence limits). Rates of choline kinase activity in EOC cells were 12- to 24-fold higher (P < 0.03) than those in EONT cells (basal rate, 0.5 +/- 0.1 nmol/10(6) cells/h), accounting for a consistently elevated (5- to 15-fold) [methyl-14C]choline uptake after 1-hour incubation (P < 0.0001). The overall activity of phosphatidylcholine-specific phospholipase C and phospholipase D was also higher ( approximately 5-fold) in EOC cells, suggesting that both biosynthetic and catabolic pathways of the phosphatidylcholine cycle likely contribute to phosphocholine accumulation. Evidence of abnormal phosphatidylcholine metabolism might have implications in EOC biology and might provide an avenue to the development of noninvasive clinical tools for EOC diagnosis and treatment follow-up.
Quantification of Adaptive Evolution of Genes Expressed in Avian Brain and the Population Size Effect on the Efficacy of Selection
Authors: E. Axelsson, H. Ellegren
Journal: Molecular Biology and Evolution (2009)

Whether protein evolution is mainly due to fixation of beneficial alleles by positive selection or to random genetic drift has remained a contentious issue over the years. Here, we use two genomewide polymorphism data sets collected from chicken populations, together with divergence data from >5,000 chicken–zebra finch gene orthologs expressed in brain, to assess the amount of adaptive evolution in protein-coding genes of birds. First, we show that estimates of the fixation index (FI, the ratio of fixed nonsynonymous-to-synonymous changes over the ratio of the corresponding polymorphisms) are highly dependent on the character of the underlying data sets. Second, by using polymorphism data from high-frequency alleles, to avoid the confounding effect of slightly deleterious mutations segregating at low frequency, we estimate that about 20% of amino acid changes have been brought to fixation through positive selection during avian evolution. This estimate is intermediate to that obtained in humans (lower) and flies as well as bacteria (higher), and is consistent with population genetics theory that stipulates a positive relationship between the efficiency of selection and the effective population size. Further, by comparing the FIs for common and all alleles, we estimate that ≈20% of nonsynonymous variation segregating in chicken populations represent slightly deleterious mutations, which is less than in Drosophila. Overall, these results highlight the link between the effective population size and positive as well as negative selection.
Phase II Trial of a Toll-Like Receptor 9–Activating Oligonucleotide in Patients With Metastatic Melanoma
Authors: Mikhail Pashenkov, Gerda Goëss, Christine Wagner, Markus Hörmann, Tamara Jandl, Anna Moser, Cedrik M. Britten, Josef Smolle, Silvia Koller, Cornelia Mauch, Iliana Tantcheva-Poor, Stephan Grabbe, Carmen Loquai, Stefan Esser, Tom Franckson, Achim Schneeberger, Cäcilia Haarmann, Arthur M. Krieg, Georg Stingl, Stephan N. Wagner
Journal: Journal of Clinical Oncology (2006)

The recent identification of toll-like receptors (TLRs) and respective ligands allows the evaluation of novel dendritic cell (DC) -activating strategies. Stimulation of TLR9 directly activates human plasmacytoid DCs (PDCs) and indirectly induces potent innate immune responses in preclinical tumor models. We performed an open-label, multicenter, single-arm, phase II pilot trial with a TLR9-stimulating oligodeoxynucleotide in melanoma patients.Patients with unresectable stage IIIb/c or stage IV melanoma received 6 mg PF-3512676 weekly by subcutaneous injection for 24 weeks or until disease progression to evaluate safety as well as clinical and immunologic activity. Clinical and laboratory safety assessments were performed weekly; blood samples for immunological measurements were taken every 8 weeks. Tumor measurements were performed according to Response Evaluation Criteria in Solid Tumors.Twenty patients received PF-3512676 for a mean of 10.9 weeks with a mean of 10.7 injections. Laboratory and nonlaboratory adverse events were limited, transient, and did not result in any withdrawals. Two patients experienced a confirmed partial response; one response is ongoing for 140+ weeks. Three patients experienced stable disease. Immunologic measurements revealed induction of an activated phenotype of PDC, elevation of serum levels of 2',5'-oligoadenylate, a surrogate marker of type I interferon production, and significant stimulation of natural killer cell cytotoxicity (the latter was associated with clinical benefit).These results indicate that TLR9-targeted therapy can stimulate innate immune responses in cancer patients, identify biomarkers that may be associated with TLR9-induced tumor regression, and encourage the design of follow-up studies to evaluate the ability of this therapeutic approach to target human cancer.
Effectiveness of Tyrosine Kinase Inhibitors on “Uncommon” Epidermal Growth Factor Receptor Mutations of Unknown Clinical Significance in Non–Small Cell Lung Cancer
Authors: Jenn-Yu Wu, Chong-Jen Yu, Yeun-Chung Chang, Chih-Hsin Yang, Jin-Yuan Shih, Pan-Chyr Yang
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Clinical features of epidermal growth factor receptor (EGFR) mutations, L858R, deletions in exon 19, T790M, and insertions in exon 20, in non–small cell lung cancer (NSCLC) are well known. The clinical significance of other uncommon EGFR mutations, such as their association with the effectiveness of EGFR tyrosine kinase inhibitors (TKI), is not well understood. This study aimed to improve the understanding of these uncommon EGFR mutations of unknown clinical significance. Patients and Methods: Specimens from 1,261 patients were tested for EGFR mutations. We surveyed the clinical data and the effectiveness of gefitinib and erlotinib in NSCLC patients with uncommon EGFR mutations. Results: Of the 1,261 patients, 627 (49.8%) had EGFR mutations. This included 258 patients with deletions in exon 19, 260 patients with L858R, 25 patients with insertions or duplications in exon 20, 6 patients with de novo T790M, and 78 (12.4%) patients with uncommon mutations. Of the 78 patients, 62 received either gefitinib or erlotinib treatment. The response rate of TKIs treatment was 48.4%, and the median progression-free survival (PFS) was 5.0 months. Mutations on G719 and L861 composed a major part (28 of 62) of uncommon mutations, and were associated with a favorable effectiveness of EGFR TKIs (response rate, 57.1%; median PFS, 6.0 months). Mutations other than G719 and L861 led to a worse response to EGFR TKIs (response rate, 20.0%; median PFS, 1.6 months). Conclusions: Uncommon EGFR mutations constituted a distinct part of the whole group of EGFR mutations. Their composition was heterogeneous, and their associations with EGFR TKIs differed. Clin Cancer Res; 17(11); 3812–21. ©2011 AACR.
Annual Report to the Nation on the Status of Cancer, 1975–2009, Featuring the Burden and Trends in Human Papillomavirus (HPV)–Associated Cancers and HPV Vaccination Coverage Levels
Authors: Ahmedin Jemal, Edgar P. Simard, Christina Dorell, Anne-Michelle Noone, Lauri E. Markowitz, Betsy Kohler, Christie Eheman, Mona Saraiya, Priti Bandi, Debbie Saslow, Kathleen A. Cronin, Meg Watson, Mark Schiffman, S. Jane Henley, Maria J. Schymura, Robert N. Anderson, David Yankey, Brenda K. Edwards
Journal: JNCI Journal of the National Cancer Institute (2013)

BackgroundThe American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updates on cancer incidence and death rates and trends in these outcomes for the United States. This year's report includes incidence trends for human papillomavirus (HPV)–associated cancers and HPV vaccination (recommended for adolescents aged 11–12 years).
Matrix-Specific Protein Kinase A Signaling Regulates p21-Activated Kinase Activation by Flow in Endothelial Cells
Authors: Steven Daniel Funk, Arif Yurdagul, Jonette M. Green, Krishna A. Jhaveri, Martin Alexander Schwartz, A. Wayne Orr
Journal: Circulation Research (2010)

Rationale : Atherosclerosis is initiated by blood flow patterns that activate inflammatory pathways in endothelial cells. Activation of inflammatory signaling by fluid shear stress is highly dependent on the composition of the subendothelial extracellular matrix. The basement membrane proteins laminin and collagen found in normal vessels suppress flow-induced p21 activated kinase (PAK) and nuclear factor (NF)-κB activation. By contrast, the provisional matrix proteins fibronectin and fibrinogen found in wounded or inflamed vessels support flow-induced PAK and NF-κB activation. PAK mediates both flow-induced permeability and matrix-specific activation of NF-κB. Objective : To elucidate the mechanisms regulating matrix-specific PAK activation. Methods and Results : We now show that matrix composition does not affect the upstream pathway by which flow activates PAK (integrin activation, Rac). Instead, basement membrane proteins enhance flow-induced protein kinase (PK)A activation, which suppresses PAK. Inhibiting PKA restored flow-induced PAK and NF-κB activation in cells on basement membrane proteins, whereas stimulating PKA inhibited flow-induced activation of inflammatory signaling in cells on fibronectin. PKA suppressed inflammatory signaling through PAK inhibition. Activating PKA by injection of the prostacyclin analog iloprost reduced PAK activation and inflammatory gene expression at sites of disturbed flow in vivo, whereas inhibiting PKA by PKA inhibitor (PKI) injection enhanced PAK activation and inflammatory gene expression. Inhibiting PAK prevented the enhancement of inflammatory gene expression by PKI. Conclusions : Basement membrane proteins inhibit inflammatory signaling in endothelial cells via PKA-dependent inhibition of PAK.