tbuckley/cabot-search huggingface dataset:
IL-6–Induced Stimulation of c-<i>Myc</i> Translation in Multiple Myeloma Cells Is Mediated by Myc Internal Ribosome Entry Site Function and the RNA-Binding Protein, hnRNP A1
Authors: Yijiang Shi, Patrick J. Frost, Bao Q. Hoang, Angelica Benavides, Sanjai Sharma, Joseph F. Gera, Alan K. Lichtenstein
Journal: Cancer Research (2008)

Abstract Prior work indicates that c-myc translation is up-regulated in multiple myeloma cells. To test a role for interleukin (IL)-6 in myc translation, we studied the IL-6–responsive ANBL-6 and IL-6–autocrine U266 cell lines as well as primary patient samples. IL-6 increased c-myc translation, which was resistant to rapamycin, indicating a mechanism independent of mammalian target of rapamycin (mTOR) and cap-dependent translation. In contrast, the cytokine enhanced cap-independent translation via a stimulatory effect on the myc internal ribosome entry site (IRES). As known IRES-trans–activating factors (ITAF) were unaffected by IL-6, we used a yeast-three-hybrid screen to identify novel ITAFs and identified hnRNP A1 (A1) as a mediator of the IL-6 effect. A1 specifically interacted with the myc IRES in filter binding assays as well as EMSAs. Treatment of myeloma cells with IL-6 induced serine phosphorylation of A1 and increased its binding to the myc IRES in vivo in myeloma cells. Primary patient samples also showed binding between A1 and the IRES. RNA interference to knock down hnRNP A1 prevented an IL-6 increase in myc protein expression, myc IRES activity, and cell growth. These data point to hnRNP A1 as a critical regulator of c-myc translation and a potential therapeutic target in multiple myeloma. [Cancer Res 2008;68(24):10215–22]
Red-Cell-Membrane Polypeptide Aggregates in Glucose-6-Phosphate Dehydrogenase Mutants with Chronic Hemolytic Disease
Authors: Gerhard J Johnson, David W Allen, Shirley Cadman, Virgil F. Fairbanks, James G. White, Beatrice C. Lampkin, Manuel E. Kaplan
Journal: New England Journal of Medicine (1979)

Original Article from The New England Journal of Medicine — Red-Cell-Membrane Polypeptide Aggregates in Glucose-6-Phosphate Dehydrogenase Mutants with Chronic Hemolytic Disease — A Clue to the Mechanism of Hemolysis
Potential of probiotics, prebiotics and synbiotics for management of colorectal cancer
Authors: Maya Raman, Padma Ambalam, Kanthi Kiran Kondepudi, Sheetal Pithva, Charmy Kothari, Arti T. Patel, Ravi Kiran Purama, J.M. Dave, B.R.M. Vyas
Journal: Gut Microbes (2013)

Colorectal Cancer (CRC) is the second leading cause of cancer-related mortality and is the fourth most common malignant neoplasm in USA. Escaping apoptosis and cell mutation are the prime hallmarks of cancer. It is apparent that balancing the network between DNA damage and DNA repair is critical in preventing carcinogenesis. One-third of cancers might be prevented by nutritious healthy diet, maintaining healthy weight and physical activity. In this review, an attempt is made to abridge the role of carcinogen in colorectal cancer establishment and prognosis, where special attention has been paid to food-borne mutagens and functional role of beneficial human gut microbiome in evading cancer. Further the significance of tailor-made prebiotics, probiotics and synbiotics in cancer management by bio-antimutagenic and desmutagenic activity has been elaborated. Probiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host. Prebiotics are a selectively fermentable non-digestible oligosaccharide or ingredient that brings specific changes, both in the composition and/or activity of the gastrointestinal microflora, conferring health benefits. Synbiotics are a combination of probiotic bacteria and the growth promoting prebiotic ingredients that purport "synergism."
A DEVICE FOR THE RELIEF OF WRITERS' CRAMP
Authors: Reginald H. Sayre
Journal: JAMA (1924)

For years, various mechanical devices have been tried for the prevention of writers' cramp in those who have to write constantly. In one of the New York Sunday papers there recently appeared a picture of Paul Vosburg, a German inventor, using what was described as "blocks of wood" for this purpose. I have seen molds of dental wax used, but their weight is a serious objection. Miss Keenly, the clerk in my clinic at the University and Bellevue Hospital Medical College, was very much troubled with pain in her right arm and hand whenever she had much writing to do, and after experimenting with various methods to relieve her hand from cramp, had the apparatus made that is shown herewith. It has afforded relief to her. Miss Keenly made the original model by holding a wet plaster-of-Paris bandage in her hand, thus getting an accurate mold of her palm and
Oral Contraceptives and Thrombosis
Authors: J. Scorey
Journal: BMJ (1965)

we can at least cope with our N.H.S. patients under the present scheme, but the thought of some of our private insurance patients, having paid their annual fee and out to get their pound of flesh, is terrifying.None of us can feel completely satisfied with Dr. Jones's insistence that there should be no reconsideration even of some minor form of item-of-service charge.Insurance companies will have the last word, of course, but they are not usually so inflexible as to be unable to provide some compromise to overcome what appears to be a major defect in the scheme.The ludicrous part of the Meeting came, however, when, having got away without much difficulty from this " item-of-service " issue, the conference fell overboard in insist- ing on .theinclusion of it in the Charter.As a convinced " item-of-service " general practi- tioner, I was amazed to see, the chance
Importance of cytolytic activity and dietary iodine in the pathogenesis of postpartum thyroiditis
Authors: K. Bech
Journal: Allergy (1989)

The incidence of lymphocytic thyroiditis (LT) has increased since the introduction of iodine prophylaxis, and LT is claimed to represent an adverse reaction to iodine. This theory is supported by animal studies as well as experimental studies in humans. In pregnancy iodine turnover is increased. During the immunological rebound period occurring postpartum the thyroid autoantibodies increase, and may lead to postpartum thyroiditis (PPT). The iodine content within the gland may be important for this reaction. In vitro it has been shown that iodine inhibits the cAMP‐dependent events of the thyroid cell function, but iodine may also stimulate the intrathyroidal immuno‐competent cells leading to cytokine synthesis. Cytokines have been shown to interfer with the thyroid cell function. Iodine may thus trigger the autoreactive attack and enhance the local autoantibody production, which plays a primary pathogenic role for development of PPT.
Care of the Dying — Kidneys for Transplant — Topics of Common Concern
Authors: John Lister
Journal: New England Journal of Medicine (1973)

THERE is no doubt that the care of the dying patient demands not only special skills but also considerable thought and planning, and it is interesting that the subject has recently been much debated on both sides of the Atlantic. Apart from the direct care of the patient there are many aspects to the problem, some of which reflect changing public attitudes. For instance, the advances in many fields of medicine have been so impressive that the layman tends to believe, at any rate subconsciously, that all disease must be curable, and the discovery that it is not may come . . .
Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy
Authors: I. Berlin, G. Grange, N. Jacob, M.-L. Tanguy
Journal: BMJ (2014)

<b>Objective</b> To determine the efficacy of 16 hour nicotine patches among pregnant smokers, with the dose individually adjusted according to saliva cotinine levels (potential range 10-30 mg/day). <b>Design</b> Randomised, double blind, placebo controlled, parallel group, multicentre trial (Study of Nicotine Patch in Pregnancy, SNIPP) between October 2007 and January 2013. <b>Setting</b> 23 maternity wards in France. <b>Participants</b> 476 pregnant smokers aged more than 18 years and between 12 and 20 weeks’ gestation, who smoked at least five cigarettes a day. After exclusions, 402 women were randomised: 203 to nicotine patches and 199 to placebo patches. Data were available on 192 live births in each group. <b>Interventions</b> Nicotine and identical placebo patches were administered from quit day up to the time of delivery. Doses were adjusted to saliva cotinine levels when smoking to yield a substitution rate of 100%. Participants were assessed monthly and received behavioural smoking cessation support. <b>Main outcome measures</b> The primary outcomes were complete abstinence (self report confirmed by carbon monoxide level in expired air ≤8 ppm) from quit date to delivery, and birth weight. The secondary outcomes were point prevalence of abstinence, time to lapse (a few puffs) or relapse, and delivery and birth characteristics. All data were analysed on an intention to treat basis. <b>Results</b> Complete abstinence was achieved by 5.5% (n=11) of women in the nicotine patch group and 5.1% (n=10) in the placebo patch group (odds ratio 1.08, 95% confidence interval 0.45 to 2.60). The median time to the first cigarette smoked after target quit day was 15 days in both groups (interquartile range 13-18 in the nicotine patch group, 13-20 in the placebo patch group). The point prevalence abstinence ranged from 8% to 12.5% in the nicotine patch group and 8% to 9.5% in the placebo patch group without statistically significant differences. The nicotine substitution rate did not differ from 100%, and the self reported median compliance rate was 85% (interquartile range 56-99%) in the nicotine patch group and 83% (56-95%) in the placebo patch group, assessed at 1016 visits. The mean birth weight was 3065 g (SE 44 g) in the nicotine patch group and 3015 g (SE 44 g) in the placebo patch group (P=0.41). Diastolic blood pressure was significantly higher in the nicotine patch group than in the placebo patch group. The frequency of serious adverse events was similar between the groups, although more non-serious adverse reactions, mainly of skin, occurred in the nicotine patch group. <b>Conclusion</b> The nicotine patch did not increase either smoking cessation rates or birth weights despite adjustment of nicotine dose to match levels attained when smoking, and higher than usual doses. <b>Trial registration</b> ClinicalTrials.gov NCT00507975.
Abstract P5-05-03: The 5p12 breast cancer susceptibility locus is associated with MRPS30 expression in estrogen receptor - positive tumors
Authors: DA Quigley, P Van Loo, GG Alnæs, J Tost, D Zelenika, A Balmain, A-L Børresen-Dale, VN Kristensen
Journal: Cancer Research (2012)

Abstract Genome-wide association studies (GWAS) have identified numerous loci linked to breast cancer susceptibility, but few of these loci have been convincingly linked to causal variants. We identified genes whose mRNA expression is linked to germline variation in normal mammary tissue and breast tumors by performing a genome-wide expression Quantitative Trait Locus (eQTL) analysis in 97 samples of normal mammary tissue and 286 breast adenocarcinomas. In the tumors we found 164 cis-acting loci, which affect expression of nearby genes. Twenty nine of these loci are previously unreported in other eQTL studies, including a cis-acting locus at 5p12 affecting expression of the mitochondrial ribosomal 28S subunit protein MRPS30 in estrogen receptor-positive but not estrogen receptor-negative tumors. This locus has been associated with susceptibility to estrogen receptor-positive breast cancer in several GWAS, with MRPS30 being the suggested candidate gene. One of these studies found that the rs771660 variant was most significantly associated with breast cancer in the 5p12 region, and we found that rs771660 was most strongly associated with MRPS30 gene expression. We provide the first evidence that this breast cancer susceptibility locus affects MRPS30 expression specifically in estrogen receptor-positive tumors and suggest a mechanism for estrogen activation of MRPS30 via proteins in the AP-1 complex. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-05-03.
Interpretation of bronchodilator response in patients with obstructive airways disease. The Dutch Chronic Non-Specific Lung Disease (CNSLD) Study Group.
Authors: P L Brand, P H Quanjer, D S Postma, H A Kerstjens, G H Koeter, P N Dekhuijzen, H J Sluiter
Journal: Thorax (1992)

BACKGROUND: There is no agreement on how a bronchodilator response should be expressed. Ideally, the index used should be able to distinguish asthma from chronic obstructive lung disease and be independent of initial FEV1. METHODS: Two hundred and seventy four adults (aged 18-60 years) outpatients with obstructive airways disease were studied. Patients were divided into syndrome groups on the basis of a standardised history: asthma (n = 99), asthmatic bronchitis (n = 88), and chronic obstructive lung disease (n = 51); 36 subjects could not be attributed to any subgroup. FEV1 was measured before and 20 minutes after inhalation of 1000 micrograms terbutaline. Different expressions of bronchodilator response (delta FEV1) were compared with respect to their dependence on initial FEV1 and their efficacy in separating subjects with asthma from those with chronic obstructive lung disease. delta FEV1 was expressed as a percentage of initial FEV1 (delta FEV1%init), absolute value (delta FEV1[1]), percentage of predicted FEV1 (delta FEV1%pred), standardised residual (delta SR-FEV1), and percentage of maximal possible increase (delta FEV1%[pred-init]). RESULTS: delta FEV1%init was more dependent on initial FEV1 (p = -0.405) than delta FEV1[1] (r = -0.145), delta FEV1%pred (r = -0.166), and delta SR-FEV1 (r = -0.127). delta FEV1%[pred-init] reached infinity when initial FEV1 approached predicted levels. delta FEV1%pred had a higher likelihood ratio (1.71) for separating patients with asthma from those with chronic obstructive lung disease than other expressions of bronchodilator response. Asthmatic patients had larger mean bronchodilator responses than patients in other subgroups; this difference was largest for delta SR-FEV1 (F = 9.19) and delta FEV1%pred (F = 9.03); it was much smaller for delta FEV1%init (F = 5.89). Despite significant differences in mean response, there was a large overlap of individual responses between diagnostic subgroups. The bronchodilator response was continuously and unimodally distributed for all expressions. CONCLUSIONS: delta FEV1%pred appears to be the most useful method of expressing bronchodilator response, both for clinical and for research purposes. Reversibility of airways obstruction in response to a bronchodilator is a continuous variable and not a dichotomous triat. Any cut off level of a "positive" bronchodilator response is therefore arbitrary.
Soft-tissue Uptake of Technetium-99m MDP in Multiple Myeloma
Authors: TADASHI KANOH, HARUTO UCHINO, ITSUO YAMAMOTO, KANJI TORIZUKA
Journal: Clinical Nuclear Medicine (1986)

Abnormal accumulation of Tc-99m MDP in the lungs and stomach was observed in a patient with multiple myeloma and refractory hypercalcemia. There was no roentgenographic evidence of calcification. At postmortem examination, the presence of amyloid deposits was confirmed in both organs, while the corresponding metastatic calcification was demonstrated only in the gastric mucosa. It seems likely that, in our case, softtissue localization of bone-seeking agent was attributable to the presence of amyloid deposits rather than metastatic calcification. No cases showing the combined occurrence of amyloid deposition and metastatic calcification in soft-tissues have previously been demonstrated to concentrate bone-seeking agent.
Enhanced production of leukotrienes by peripheral leukocytes and specific IgE antibodies in patients with chronic obstructive pulmonary disease
Authors: Fumihiro Mitsunobu, Takashi Mifune, Yasuhiro Hosaki, Kozo Ashida, Hirofumi Tsugeno, Makoto Okamoto, Shingo Takata, Yoshiro Tanizaki
Journal: Journal of Allergy and Clinical Immunology (2001)
Phase I Safety, Pharmacokinetic and Pharmacodynamic Evaluation of the Vascular Disrupting Agent Ombrabulin (AVE8062) in Patients with Advanced Solid Tumors
Authors: Cristiana Sessa, Patricia Lorusso, Anthony Tolcher, Françoise Farace, Nathalie Lassau, Angelo Delmonte, Antonio Braghetti, Rastislav Bahleda, Patrick Cohen, Marie Hospitel, Christine Veyrat-Follet, Jean-Charles Soria
Journal: Clinical Cancer Research (2013)

The vascular disrupting agent ombrabulin rapidly reduces tumor blood flow and causes necrosis in vivo. A phase I dose-escalation study was designed to determine the recommended phase II dose (RP2D) of single-agent ombrabulin administered once every three weeks in patients with advanced solid malignancies.Ombrabulin (30-minute infusion) was escalated from 6 to 60 mg/m2, with RP2D cohort expansion. Safety, tumor response, pharmacokinetics, and pharmacodynamic biomarkers were evaluated.Eleven dose levels were evaluated in 105 patients. Two patients had dose-limiting toxicities in cycle 1 during escalation: grade 3 abdominal pain at 50 mg/m2, grade 3 tumor pain/grade 3 hypertension at 60 mg/m2, and the RP2D was 50 mg/m2 (39 patients). Common toxicities were headache, asthenia, abdominal pain, nausea, diarrhea, transient hypertension, anemia, and lymphopenia. No clinically significant QTc prolongations or left ventricular ejection fraction (LVEF) decreases occurred. Ombrabulin was rapidly converted to its active metabolite RPR258063 (half-life 17 minutes and 8.7 hours, respectively), both having dose-proportional exposure. Weak inhibition of CYP2C19-mediated metabolism occurred at the clinical doses used and there was no effect on CYP1A2 and CYP3A4. A patient with rectal cancer had a partial response and eight patients had stable disease lasting four months or more. Circulating endothelial cells (CEC), VEGF, and matrix metalloproteinase (MMP)-9 levels increased significantly six to 10 hours postinfusion in a subset of patients.The recommended schedule for single-agent ombrabulin is 50 mg/m2 every 3 weeks. CECs, VEGF, and MMP-9 are potential biomarkers of ombrabulin activity.
What neuron doctrines might never explain
Authors: Keith Gunderson
Journal: Behavioral and Brain Sciences (1999)

My focus is on the inability of neuron doctrines to provide an explanatory context for aspects of consciousness that give rise to the mind–body and other minds problem(s). Neuroscience and related psychological sciences may be viewed as richly contributing to our taxonomic understanding of the mind and conditions underlying consciousness, without illuminating mind–body and other minds perplexities.
Campaigners press for legislation to make researchers publish full data with trial results
Authors: R. Watson
Journal: BMJ (2012)

The European Commission will table proposals early next month to update existing legislation on clinical trials, but it is unclear whether it will demand that researchers publish the full background data from clinical trials. 

Stefano Soro, a senior commission official, last week acknowledged that present European legislation contained failings and confirmed that its successor would deal with the issue of transparency. “We want to move away from the situation where everything is forbidden unless explicitly authorised,” he said.

He emphasised that the new proposal would also focus on patients’ safety, data protection, and individual …
An update on treatment of hepatitis C virus genotype 1 infection and viral load assessments
Authors: Bryan Cobb, Regis A. Vilchez
Journal: Hepatology (2011)

We read with interest the article by Ghany et al. 1 that describes an update to the treatment of hepatitis C virus (HCV) genotype 1 infection after the approval of the NS3/4A serine protease inhibitors boceprevir and telaprevir. The trials for both drugs relied on HCV RNA results to make decisions about shortening or extending treatment (response-guided therapy [RGT]). In the article, the term “undetectable” was referred to “as defined in the package insert as <10-15 IU/mL.” However, physicians need to know that quantitative polymerase chain reaction (PCR) viral load assays have a lower limit of quantification (LLOQ). HCV RNA detectable below the LLOQ is described as detected but, by definition, cannot be quantified. Thus, PCR results beneath the LLOQ can reported as <LLOQ, detected or <LLOQ, undetected. A result <LLOQ, undetected should be referred as target not detected (TND), which means that no PCR amplification or detection can be achieved, indicating absence of HCV RNA. The limit of sensitivity for detection of HCV RNA that cannot be quantified is the limit of detection (LOD) that is established as HCV RNA detected at a rate of ≥95%. 2 Based on this, HCV RNA would be undetected 5% of the time. The boceprevir and telaprevir phase 3 trials measured HCV RNA with the COBAS® TaqMan® HCV Test, v2.0 for use with the High Pure System (Roche Molecular Systems Inc., Branchburg, NJ). This assay has an overall LOD across multiple samples and genotypes of 20 IU/mL and an LLOQ of 25 IU/mL. 3 The genotype 1 LOD differs by plasma or serum and can range between 10 and 15 IU/mL. Therefore, any result between 1 and 24 will be reported as “<25 IU/mL, detected.” Similarly, if the HCV RNA is <10-15 IU/mL but detected, the result will also be reported as “<25 IU/mL, detected.” Only a TND result will be reported if no virus is detectable. The prescribing information for both antivirals states that for assessing RGT, an “undetectable” HCV RNA result is required and a “detectable but below limit of quantification” HCV RNA result should not be considered equivalent to an “undetectable HCV RNA result.” 4, 5 Given that an “undetectable” result is required for RGT with boceprevir or telaprevir and should not be considered equivalent to a result of “<25 IU/mL, detected,” the term “undetectable” should therefore be defined as a result that is TND rather than the assay LOD, or <10-15 IU/mL. Bryan Cobb Ph.D.*, Regis A. Vilchez M.D., Ph.D.*, * Roche Molecular Systems, Inc., Pleasanton, CA.
Effects of Beer on Breast-fed Infants
Authors: Julie A. Mennella
Journal: JAMA (1993)

<h3>To the Editor.</h3> —In response to a query in<i>JAMA</i>about the value of beer consumption to the breast-feeding mother,<sup>1</sup>it was concluded that there was a scientific basis for the folklore that beer is a galactagogue.<sup>2</sup>Beer, unlike other alcoholic beverages, increases serum prolactin levels.<sup>3</sup>The subjects in these studies were normal men and nonlactating women, however. To our knowledge, no investigation in this area focused on the lactating women and, perhaps more importantly, determined whether milk intake by breast-fed infants is enhanced when their mothers drink beer. Recently, we demonstrated that breast-fed infants consumed significantly less milk during the 3-hour testing session in which their mothers drank a small dose of ethanol in orange juice than when the mothers drank orange juice alone.<sup>4</sup>Using similar methods, we now report similar effects following alcoholic beer consumption. Each of 11 nursing mothers and their infants was
Impaired Delayed Hypersensitivity
Authors: Louis Tuft
Journal: JAMA (1968)

To the Editor:—  I was very much interested in the report of Waldorf et al (203:831, 1968) concerning the impairment in skin reactivity of older individuals after the induction of delayed skin test reactions by the application of patch tests of 2, 4-dinitrochlorobenzene (DNCB). While these studies involved delayed skin test reactions, I wondered whether any of these individuals also had been tested with allergens producing immediate-type skin test reactions and if so, whether such reactions also were reduced in intensity. I am interested because in July 1955 my associates and I1reported the results of studies designed to show the influence of age upon skin reactivity as applied to direct skin test reactions. To determine this, we did intradermal skin tests upon nonallergic individuals in all the age decades from infancy on, with histamine solution diluted 1:1,000, 1:10,000, 1:100,000, and 1:million, using 100 individuals for each decade