tbuckley/cabot-search huggingface dataset:
S133 2-adrenergic Receptor Gly16arg Polymorphism Is Not Associated With Impaired Asthma Control In Corticosteroid Treated Adult Asthmatics
Authors: B. Griffin, A. Manoharan, W. Anderson, J. Lipworth, B. Lipworth
Journal: Thorax (2014)

<h3>Introduction</h3> The Arg-16 β<sub>2</sub>-adrenergic receptor allele is associated with increased exacerbations in asthmatic children exposed to combination therapy with long-acting beta-agonists (LABA) and inhaled corticosteroids (ICS).<sup>1</sup> We evaluated whether the Gly16Arg polymorphism is associated with impaired asthma control in ICS treated adult asthmatics and whether this was influenced by concomitant LABA use. <h3>Methods</h3> In this cross-sectional study, demographics, medication and spirometry were prospectively recorded from patients attending a secondary care asthma clinic who were also genotyped and completed the Asthma Control Questionnaire (ACQ-6). <h3>Results</h3> A total of 223 patients prescribed ICS were included in the analysis. Overall mean age was 46 years, FEV<sub>1</sub> 86%, median ICS dose 800 µg/day and 73% were prescribed LABA. There were no differences in terms of spirometry and ACQ-6 between the three genotypes (Table 1). In patients who were prescribed LABA there was no difference in ACQ-6 comparing patients with no Arg copies (n = 80, ACQ-6 1.82) versus those with one or two Arg copies (n = 83, ACQ-6 1.70). Moreover salbutamol reliever use was no different. <h3>Conclusion</h3> Gly16Arg polymorphism was not associated with impaired asthma control in ICS treated adult asthmatics irrespective of LABA exposure. <h3>References</h3> Basu K, Palmer CN, Tavendale R, Lipworth BJ, Mukhopadhyay S. Adrenergic beta (2)-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol. <i>J Allergy Clin Immunol</i>. 2009 Dec;124(6):1188-94 e3
Biotech Industry Flourishes With Cancer Research Advances
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Biotech Industry Flourishes With Cancer Research Advances Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 22, 20 November 1991, Pages 1608–1611, https://doi.org/10.1093/jnci/83.22.1608 Published: 20 November 1991
SEPTAL MYECTOMY DOES NOT IMPROVE SEPTAL MYOCARDIAL EFFICIENCY IN HYPERTROPHIC CARDIOMYOPATHY
Authors: Ahmet Guclu, Paul Knaapen, Hendrik Harms, Patrick Klein, Michelle Michels, Arend Schinkel, Adriaan Lammertsma, Albert van Rossum, Tjeerd Germans, Jolanda Van Der Velden
Journal: Journal of the American College of Cardiology (2015)
Brain-Damaging Potential of Protein Hydrolysates
Authors: John W. Olney, Oi Lan Ho, Vesela Rhee
Journal: New England Journal of Medicine (1973)

Casein and fibrin hydrolysates commercially available for use in human parenteral alimentation therapy were administered subcutaneously to 90 10-day-old mice at five doses (20, 40, 60, 80 and 100 μl per gram of body weight). Casein hydrolysate at each dose tested and fibrin hydrolysate at 80 and 100 μl per gram induced acute degeneration of neurons in the developing hypothalamus. Hypothalamic lesions were identical to those occurring in various animal species after oral or parenteral administration of acidic amino acids such as glutamic, aspartic and cysteic acids. A control amino acid mixture excluding glutamic, aspartic and cysteic acids induced no brain damage in similar experiments on 30 additional mice. A relatively low combined concentration of acidic amino acids thus appears to be one of the criteria that a parenteral alimentation preparation should meet to be maximally safe as well as nutritionally effective. (N Engl J Med 289:391–395, 1973)
THU0065 Expression Profiling of Extracellular Serum Micrornas in Patients with Idiopathic Inflammatory Myopathy
Authors: M. Remáková, M. Škoda, M. Faustová, L. Pleštilová, H. Mann, J. Vencovský, P. Novota
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Idiopathic inflammatory myopathies (IIMs) are chronic autoimmune disorders characterized by skeletal muscle weakness, inflammatory immune cells in muscle tissues and frequent presence of serum autoantibodies. Besides a genetic risk located within the MHC complex, also epigenetic regulations including changes in miRNAs expression profiles have been implicated recently in many autoimmune diseases. Extracellular miRNAs circulate in the bloodstream and such miRNAs are remarkably stable. It is hypothesized that circulating miRNA may be delivered to recipient cells and regulate translation of target genes. <h3>Objectives</h3> The aim of this study was to analyze the differences in expression profiles of circulating extracellular miRNAs between patients and controls with possible selection of relevant candidate miRNA molecules involved in disease progression. <h3>Methods</h3> Expression profile of 1,347 miRNA molecules was analyzed in 47 myositis patients and 16 healthy controls. Circulating miRNAs were prepared from serum using the Trizol® reagent. The expression of miRNAs was measured using the 44K high density microarray from Agilent Company. <h3>Results</h3> The miRNA expression profiles clearly separate between healthy controls and patients with myositis. In total, 87 miRNA molecules were found to be differentially expressed in myositis patients. Analysis of the associated biological pathways regulated by the detected miRNAs revealed that 44 (50%) differentially expressed miRNAs are predicted to regulate immune response, 38 (43%) miRNAs are related to muscle activity and 40 (46%) miRNAs were predicted to be involved in cell death. <h3>Conclusions</h3> A number of miRNAs differentially expressed in patients with IIMs were identified. These molecules are potentially involved in the etiopathogenesis of the disease since all are related to important immune mechanisms or muscle function. <h3>Acknowledgements</h3> This study was supported by the Internal Grant Agency of the Ministry of Health in the Czech Republic [MZČR NT 12452-4], Institutional support of MHCR VZ (00023728) and The Charles University Grant agency (No.621812). <h3>Disclosure of Interest</h3> None Declared
LOCALIZATION OF CULPRIT ENDOTHELIAL SHEAR STRESS PATTERNS ALONG THE COURSE OF UNTREATED CORONARY LESIONS RESPONSIBLE FOR FUTURE MACE: THE PROSPECT STUDY
Authors: Marina Zaromytidou, Gregg W. Stone, Akiko Maehara, Ahmet U. Coskun, Charles C. Maynard, Gerasimos Siasos, Ioannis Andreou, Dimitris Fotiadis, Kostas Stefanou, Michail Papafaklis, Lampros Michalis, Alexandra J. Lansky, Gary S. Mintz, Patrick W. Serruys, Charles L. Feldman, Peter H. Stone
Journal: Journal of the American College of Cardiology (2016)
Genital Tumors among Men with Psoriasis Exposed to Psoralens and Ultraviolet A Radiation (PUVA) and Ultraviolet B Radiation
Authors: R S Stern
Journal: New England Journal of Medicine (1990)

Squamous-cell cancer occurs only rarely on the male genitalia. In a 12.3-year prospective study of 892 men in a cohort of patients with psoriasis who had been treated with oral methoxsalen (8-methoxypsoralen) and ultraviolet A photochemotherapy (PUVA), we identified 14 patients (1.6 percent) with 30 genital neoplasms.
P5-06-11: Quercetin-3-Methyl Ether Inhibits Lapatinib-Sensitive and Lapatinib-Resistant Breast Cancer Cell Growth by Inducing G2/M Arrest and Apoptosis.
Authors: AM Bode, J Li, F Zhu, NE Normanno, ME Ericson, RA Lubet
Journal: Cancer Research (2011)

Abstract Background: Lapatinib, an oral, small-molecule, reversible inhibitor of both EGFR and HER2, is highly active in HER2 positive breast cancer as a single agent and in combination with other therapeutics. However, resistance against lapatinib is an unresolved problem in clinical oncology. Recently, interest in the use of natural compounds to prevent or treat cancers has gained increasing interest because of presumed low toxicity. Quercetin-3-methyl ether, a naturally occurring compound present in various plants, has potent anticancer activity. Material and Methods: Quercetin-3-methyl ether was obtained from Analyticon Discovery (Potsdam, Germany). Lapatinib-resistant SK-Br-3 (SK-Br-3-Lap R) cells were isolated in the laboratory of Cell Biology and Biotherapy at the Istituto Nazionale dei Tumori, Naples, Italy. Parental SK-Br-3 and SK-Br-3-Lap R cells were cultured in monolayers at 37 °C in a 5% CO2 incubator in 10% FBS/McCoy supplemented with penicillin/streptomycin (100 units/ml; Invitrogen). SK-Br-3 Lap R cells were routinely maintained in 1 μM lapatinib. Anchorage-dependent and -independent growth and cell cycle were assessed in the presence and absence of quercetin-3-methyl ether. Results: Here, we found that quercetin-3-methyl ether caused in a significant growth inhibition of lapatinib-sensitive and -resistant breast cancer cells. Western blot data showed that quercetin-3-methyl ether had no effect on Akt or MAPKs signaling in resistant cells. However, quercetin-3-methyl ether caused a pronounced G2/M block mainly through the Chk1-Cdc25c-cyclin B1/Cdk1 pathway in lapatinib-sensitive and -resistant cells. In contrast, lapatinib produced an accumulation of cells in the G1 phase mediated through cyclin D1, but only in lapatinib-sensitive cells. Moreover, quercetin-3-methyl ether induced significant apoptosis, accompanied with an increase the levels of in cleaved caspase 3, caspase 7 and poly(ADP-ribose) polymerase (PARP) in both cell lines. Conclusion: Overall, these results suggested that quercetin-3-methyl ether might be a novel and promising therapeutic agent in lapatinib-sensitive or -resistant breast cancer patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-06-11.
Abstract 3524: Plasma pharmacokinetics and metabolism of benzaldehyde dimethane sulfonate (NSC281612, DMS612, BEN) in mice
Authors: Robert A. Parise, Julie L. Eiseman, Merrill J. Egorin, Dana M. Clausen, Joseph M. Covey, Jan H. Beumer
Journal: Cancer Research (2010)

Abstract Introduction: BEN is an alkylating agent in early clinical trials based on its in vitro and in vivo activity against renal cell carcinoma. We have previously reported that BEN is rapidly metabolized into its carboxylic acid (BA) and that BEN and BA undergo chemical conversion in vitro. In support of current clinical trials, we characterized the pharmacokinetics of BEN, BA, and their products in mice. Materials &amp; Methods: Female CD2F1 mice were dosed with 20 mg/kg BEN i.v. Twelve blood samples were obtained between 0 and 24 hrs and urine was collected at 0-6 hrs and 6-24 hrs. Formic acid was added to all samples (5%, v/v) and the sample processing was performed on ice to stop ex vivo chemical conversions. Plasma and urine concentrations of BEN, and its metabolites and conversion products were quantitated with LC-MS/MS. Plasma and urine pharmacokinetic parameters were calculated non-compartmentally. Results: BEN was rapidly converted to at least 13 different metabolites or products. The half-life (T1/2) of BEN was approximately 60 min. Half-lives of metabolites were all &amp;gt;2 h. The analytes that could be quantitated in urine represented approximately 30% of the dose administered.AnalyteCmax (µg/ml)Tmax (min)T½ (min)AUC0-inf (mg/mL*min)Vd/F (L/kg)Cl/F (mL/min/kg)% Dose 0-24 h urineBEN4.355922.974.50.96.6BA26.1531315.72.80.18.5BA-(OH)20.71107323.988.10.815.5BEN-(Cl)20.001151080.2471264481.1NDBA-(Cl)20.027580.58938534NDBEN-(OH)20.6565416.811732.9NDBA-Cl-OH 513 BA-Cl 528 BA-OH 529 BA-Gluc 1031 BA-(OH)2-Gluc 1531 BA-Cl-OH-Gluc 3049 BA-Cl-Gluc 15107 BA-OH-Gluc 1036 ND, not detectable; NQ, not quantifiable. Conclusions: BEN is rapidly metabolized to BA and chemically converted to many subsequent products, some of which are glucuronidated. Several metabolites and conversion products contain chloroethyl or methanesulphonate moieties, which would allow them to alkylate cellular targets and exhibit anti-neoplastic properties or cause toxicity. The enzymes responsible for the metabolism of BEN and BA need to be identified. Support: N01-CM07106, N01-CM52202, P30-CA47904 from the NCI. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3524.
Endoscopic resection of subtotal or completely circumferential laterally spreading colonic adenomas: technique, caveats, and outcomes
Authors: Nicholas Tutticci, Amir Klein, Rebecca Sonson, Michael Bourke
Journal: Endoscopy (2016)

Endoscopic mucosal resection (EMR) is an established treatment for large (≥ 20 mm) laterally spreading lesions (LSLs). LSLs with complete or subtotal (> 90 %) circumferential extent (C-LSLs) are generally referred for surgery. Data on technique, efficacy, and safety of EMR for these lesions are absent. The aim of this study was to describe the technique and long-term outcomes of EMR for C-LSLs.Prospective observational study of consecutive patients referred for EMR of LSL at a tertiary care center over 63 months to April 2015. Amongst 979 patients with LSL, 12 patients with C-LSL were seen.All lesions were tubulovillous adenomas with granular 0 - IIa + Is morphology. Median longitudinal extent was 95 mm (range 60 - 160), 58 % were located in the rectum, and 3 lesions (25 %) had complete circumferential involvement. EMR technical success was 100 %. There were no major adverse events. Symptomatic stricturing occurred in 2 cases (17 %) and was treated with endoscopic balloon dilation (median 4 sessions). Median follow up is 13 months. Minor residual adenoma was found in 7 (58 %) at first surveillance colonoscopy and was treated with snare excision. A total of 10 patients have completed a second surveillance colonoscopy with minor residual adenoma found in only 1 case. No patient required surgery or developed cancer in long-term follow-up.Endoscopic resection of C-LSL is feasible and safe. Minor residual adenoma is common but endoscopically treatable with long-term cure. Symptomatic stricturing amenable to balloon dilation may occur. Empiric surgical referral for C-LSL based on extensive circumferential involvement may be avoided.ClinicalTrials.gov NCT01368289.
Abstract P1-13-05: The Effect of Treatment with Denosumab or Zoledronic Acid on Health-Related Quality of Life in Patients with Metastatic Breast Cancer
Authors: L Fallowfield, D Patrick, J-J Body, A Lipton, KS Tonkin, Y Qian, Y Zhao, Q Jiang, A Braun, R Dansey, K. Chung
Journal: Cancer Research (2010)

Abstract Background: Patients with breast cancer and bone metastases often experience skeletal-related events (SREs) and pain, which may impact health-related quality of life (HRQoL). Denosumab is a fully human monoclonal antibody against RANKL shown to be superior in delaying/preventing SREs and more effective in delaying moderate or severe pain in patients with advanced breast cancer compared with zoledronic acid (ZA). Previously reported results from this study population showed that both denosumab and ZA patients showed improvement or maintenance in HRQoL relative to baseline (BL), and a greater proportion of denosumab-treated patients had a clinically meaningful improvement in HRQoL. We now describe the effect of denosumab and ZA treatment on HRQoL among patients with varying degrees of pain at BL. Methods: Enrolled patients received subcutaneous (SC) denosumab 120 mg or intravenous (IV) ZA 4 mg every 4 weeks in a double-blind, double-dummy fashion. Pain was evaluated using the Brief Pain Inventory — Short Form (BPI). Patients were divided into 2 subgroups based on the level of pain reported at BL: no/mild pain or moderate/severe pain. Patients completed the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at BL, day 8, and before each monthly visit to assess overall HRQoL. Higher scores (range 0 to 108) represent better HRQoL. Improvement, maintenance, and worsening of HRQoL were assessed through month 18, when 30% of patients had dropped out due to death, disease progression, or withdrawal of consent. A change of ≥5 points (increase or decrease) in the FACT-G total score was considered a meaningful improvement. Results: Among patients who reported no/mild pain at baseline, more denosumab-treated patients had a ≥5-point increase in their FACT-G score from month 4 onwards. Over the 18 month period, an average of 4.1% more (range: −0.6% to 9.3%) denosumab-treated patients experienced meaningful improvement in HRQoL than ZA-treated patients. There were also fewer denosumab-treated patients experiencing ≥5-point decrease in HRQoL over 18 months (average of 2.4% fewer [range:-4.4% to 6.3% fewer]). Similar patterns were also noted for patients with moderate/severe pain at baseline. An average of 3.0% more (range:-1.7% to 7.9%) denosumab-treated patients had ≥5-point increase in FACT-G scores compared with ZA-treated patients over 18 months. A lower proportion of denosumab-treated patients (3.5% fewer [range: −1.1% to 11.5% fewer]) than ZA-treated patients had a decrease ≥5-points in their FACT-G score over 18 months. Conclusion: In patients with breast cancer and bone metastases, a greater proportion treated with denosumab than ZA had a meaningful improvement in HRQoL regardless of their pain level at BL. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-13-05.
The Waterhouse-Friderichsen Syndrome
Authors: Leonard D. Weinberg, Thomas Hodge McGavack
Journal: New England Journal of Medicine (1945)

The symptom complex known as the Waterhouse-Friderichsen syndrome was first described by Voelcker1 in 1894. Early in 1944, Haas2 found 144 cases reported in the literature, to which he added 3 of his own. Rucks and Hobson3 stated that up to the beginning of 1942 there were 101 recorded cases, 26 of which had been reported in the preceding three years. Assuming that these workers did not overlook any cases up to the time of their respective communications, it appears that approximately 75 cases of the syndrome were reported between 1894 and 1939 and 75 in the five years from . . .
CS-05 * MUTATION SPECIFIC FUNCTIONS OF EGFR RESULT IN A MUTATION-SPECIFIC DOWNSTREAM PATHWAY ACTIVATION
Authors: L. Erdem-Eraslan, Y. Gao, N. Kloosterhof, Y. Atlasi, J. Demmers, A. Sacchetti, J. Kros, P. S. Smitt, J. Aerts, P. French
Journal: Neuro-Oncology (2014)

BACKGROUND: EGFR is frequently mutated in various types of cancer. Although all oncogenic mutations are considered activating, different tumor types have different mutation spectra. It is possible that functional differences underlie this tumor-type specific mutation spectrum. METHODS: We have determined whether specific mutations in EGFR (EGFR, EGFRvIII and EGFR-L858R) have differences in binding partners, differences in downstream pathway activation (gene expression and phosphoproteins), and have functional consequences on cellular growth and migration. RESULTS: Using biotin pulldown and subsequent mass spectrometry we were able to detect mutation specific binding partners for EGFR. Differential binding was confirmed using a proximilty ligation assay and/or Western Blot for the dedicator of cytokinesis 4 (DOCK4), UDP-glucose glycoprotein glucosyltransferase 1 (UGGT1), MYC binding protein 2 (MYCBP2) and Smoothelin (SMTN). We also demonstrate that each mutation induces the expression of a specific set of genes, and that each mutation is associated with specific phosphorylation patterns. Finally, we demonstrate using stably expressing cell lines that EGFRvIII and EGFL858R display reduced growth and migration compared to EGFR wildtype expressing cells. CONCLUSION: Our results indicate that there are distinct functional differences between different EGFR mutations. The functional differences between different mutations argue for the development of mutation specific targeted therapies.
AB0076 Promoter IL12B Gene Polymorphism Contributes to Rheumatoid Arthritis Development
Authors: M. Ivanova Goycheva, R. Stoilov, R. Rashkov, S. Stanilova, I. Manolova
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> <i>IL12B</i> encodes the IL-12p40 subunit of both the IL-12 and IL-23 cytokines, which play critical and unique roles in bridging the innate and adaptive immune systems. Whereas IL-12 induces development of Th1 cells, which produce IFN-gamma, IL-23 is involved in Th-17 cells that appear to play a role in the pathogenesis of rheumatoid arthritis (RA). Although the precise RA etiology is not fully understood, a strong genetic component has been established. The best-characterized genetic factor contributing to RA is the association of different <i>HLA-DRB1</i> alleles with the disease. However, other non-HLA genes also play a relevant role in RA and it is proposed that IL12B gene polymorphisms could affect the development of RA. <h3>Objectives</h3> In this regard, the aim of this study was to determine whether genetic polymorphisms of the IL-12B gene are associated with RA in Bulgarian population by genotyping for <i>IL12Bpro</i> (rs17860508), a complex polymorphism in promoter region of the <i>IL12B</i>, resulting from 4 bp microinsertion combined with AA/GC transition. <h3>Methods</h3> A total of 136 patients with RA and 125 matched healthy individuals were enrolled it the study. Genotyping for the rs17860508 was performed by allele specific-PCR. <h3>Results</h3> In logistic regression analysis the presence of <i>IL12Bpro allele 2</i> in the genotype (1.2+2.2 vs. 1.1) was associated with an increased risk of developing RA (OR=1.44) and the presence of <i>IL12Bpro allele 1</i> in the genotype (1.2+1.1 vs. 2.2) was associated with a decreased risk of developing RA (OR=0.68). However, there were no significant differences in the genotype and allele frequencies of rs17860508 polymorphism of the <i>IL12B</i> between RA patients and controls. The presence of <i>IL12Bpro</i> allele 1 in the genotype (1.2+1.1 vs. 2.2) was associated with decreased risk of early disease onset (age at onset&lt;48; OR=0.48) and the carriage of <i>IL12Bpro</i> genotype 1.1 was associated with 2-fold decreased risk of having higher disease severity (DAS28&gt;5.1; OR=0.571). These results suppose that <i>IL12Bpro</i> 1.1 genotype could be protective, whether 2.2 genotype might be predisposing to susceptibility of RA. <h3>Conclusions</h3> In conclusion, our data support the hypothesis that genetic variations in <i>IL12B</i> gene affecting inducible production of IL-12p40, contribute to the development of RA in the Bulgarian population. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2716