tbuckley/cabot-search huggingface dataset:
Abstract 1785: Ubiquitin specific protease 3 is a regulator of histone ubiquitination required for maintenance of genomic stability.
Authors: Nidhi Sharma, Qianzheng Zhu, Qi-En Wang, Altaf A. Wani
Journal: Cancer Research (2013)

Abstract The ubiquitination of histones is crucial for the maintenance of genomic stability. Little is understood about the deubiquitinating enzymes that catalyze the removal of ubiquitin from histones in response to UV damage. In this study, we identify the ubiquitin-specific protease 3 (USP3) as a deubiquitinating enzyme which catalyzes the cleavage of ubiquitin from γH2AX and uH2A in response to UV damage. Using GFP-tagged USP3 we demonstrate that USP3 is a nuclear protein. To determine the function of USP3 in chromatin regulation we ectopically expressed USP3 in Hela cells and analyzed the ubiquitination status of histones. Our analysis demonstrated that the overexpression of the wild type USP3 (USP3wt), but not the catalytically inactive mutant (USP3C1685) resulted in a decrease in the ubiquitination of γH2AX and uH2A. This result was further supported by the functional ablation of USP3 by RNAi. The efficient reduction of the USP3 protein was accompanied by a significant increase in the levels of uH2A and the ubiquitination of γH2AX. In addition, we were also able to demonstrate that the depletion of USP3 increases the persistence of uH2A and Fk2 foci formation in response to UV damage. Together, our results implicate that USP3 is involved in the removal of ubiquitin marks from chromatin-bound proteins as a means to attenuate the damage signal. Thus, in the presence of UV damage, the functional ablation of USP3 may lead to a delay in cell cycle progression and the activation of checkpoint signals, which in turn could induce genotoxic stress. This work was supported by the PHS grant ES2388, ES12991 and CA93413. Citation Format: Nidhi Sharma, Qianzheng Zhu, Qi-En Wang, Altaf A. Wani. Ubiquitin specific protease 3 is a regulator of histone ubiquitination required for maintenance of genomic stability. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1785. doi:10.1158/1538-7445.AM2013-1785
In situ nucleic acid detection of PDC-E2, BCOADC-E2, OGDC-E2, PDC-E1?, BCOADC-E1?, OGDC-E1,and the E3 binding protein (protein X) in primary biliary cirrhosis
Authors: Kenichi Harada, Yoshiko Sudo, Naoko Kono, Satoru Ozaki, Koichi Tsuneyama, Eric M. Gershwin, Yasuni Nakanuma
Journal: Hepatology (1999)

The characteristic serological feature of primary biliary cirrhosis (PBC) is the presence of antimitochondrial antibodies (AMAs), and the major proteins recognized by AMAs are subunits of the 2-oxo acid dehydrogenase complexes (2-OADC), including the E2 components of the pyruvate dehydrogenase complex (PDC), the 2-oxo-glutarate dehydrogenase complex (OGDC), the branched-chain 2-oxoacid dehydrogenase complex (BCOADC), the E3 binding protein (E3BP or protein X) and the E1a component of mammalian PDC. Previous work has postulated that either E3BP, or a molecule cross-reactive with the PDC-E2 molecule, is uniquely expressed on the surface of biliary epithelial cells in PBC. To address this issue, we performed in situ hybridization for all of the major 2-OADC components at the mRNA level, including PDC-E2, BCOADC-E2, OGDC-E2, PDC-E1a, BCOADC-E1a, OGDC-E1, and E3BP using 13 PBC and 9 control livers using 7 mitochondrial antisense probes. In both PBC and controls, the expression of all 2-OADC component mRNA studied herein were found in hepatocytes and infiltrating mononuclear cells, without significant differences. Interestingly, however, despite published data on immunohistochemical staining, interlobular bile ducts including the injured bile ducts in PBC were generally negative or only faintly positive, with the exception of 1 bile duct in 1 of 13 cases of PBC and 1 of 9 control liver specimens. Moreover, confocal microscopic examination and image analysis revealed that the mRNA signal intensity of each of the 2-OADC components in the bile ducts of PBC was relatively lower in comparison with control liver diseases. These data suggest that continuous enhanced synthesis of the 2-OADC components is not likely to be occurring in the biliary epithelial cells in PBC, and that an increase of PDC-E2 or E3BP immunoreactivity in PBC is caused by exogenous imported or cross-reactive molecules
Judge rules that boy with brain cancer can be treated in Prague
Authors: C. Dyer
Journal: BMJ (2014)

A 5 year old boy with brain cancer whose parents were arrested and jailed after they took him from a UK hospital without telling doctors can undergo the “entirely reasonable” treatment his parents want for him in Prague, a High Court judge in London has ruled.

Brett and Naghmeh King were jailed in Spain under a European arrest warrant issued by the Crown Prosecution Service for England and Wales after a Europe-wide search.1

After considering a treatment plan agreed by the Proton Therapy Centre in Prague, clinicians at Motol University Hospital in Prague, and the doctors who treated Ashya King at Southampton General Hospital, Mr Justice Baker agreed that the boy could be taken to Prague for the proton beam …
Oral fluorescein angiography with the confocal scanning laser ophthalmoscope
Authors: Claudio R Garcia, Maria E Rivero, Dirk-Uwe Bartsch, Satoshi Ishiko, Akira Takamiya, Katsuhiro Fukui, Hiroyuki Hirokawa, Thomas Clark, Akitoshi Yoshida, William R Freeman
Journal: Ophthalmology (1999)
Controlling Research Trials
Authors: Jeffrey M. Drazen
Journal: New England Journal of Medicine (2003)

Clinical research, especially in the form of large multicenter trials, promotes changes in practice; without the accrual of new knowledge, clinical care will not advance. A deadlock between the National Heart, Lung, and Blood Institute (NHLBI) and the Office of Human Research Protections (OHRP) of the Department of Health and Human Services about the ethics of a clinical trial has the potential to bring much clinical research to a halt. The trial in question is designed to examine the ability of intravenous-fluid management directed by physiological data obtained from a pulmonary-artery catheter to influence outcomes in medical intensive care units. . . .
RELATIONSHIP OF SYMPTOM-ONSET-TO-BALLOON TIME AND LONG-TERM MORTALITY IN PATIENTS WITH PRIMARY PERCUTANEOUS CORONARY INTERVENTION FOR ACUTE MYOCARDIAL INFARCTION: INSIGHTS FROM CREDO-KYOTO AMI REGISTRY
Authors: Hiroki Shiomi, Masao Imai, Takeshi Morimoto, Yutaka Furukawa, Yoshihisa Nakagawa, Natsuhiko Ehara, Katsuhisa Ishii, Masaaki Takahashi, Satoru Suwa, Masaru Tanaka, Ryuji Nohara, Minoru Horie, Hirofumi Kambara, Masakiyo Nobuyoshi, Toru Kita, Takeshi Kimura
Journal: Journal of the American College of Cardiology (2011)
1025-42 Abciximab administration for the prevention of angiographic restenosis in small coronary arteries: Results from the randomized ISAR-SMART-2 trial
Authors: Jörg Hausleiter, Adnan Kastrati, Julinda Mehilli, Helmut Schühlen, Sonja Siebert, Franz Dotzer, Josef Dirschinger, Albert Schömig
Journal: Journal of the American College of Cardiology (2004)
Canadian media company demands right to publish direct to consumer drug advertising
Authors: R. Moynihan
Journal: BMJ (2009)

A long legal battle over advertising drugs directly to consumers is drawing to a close in Canada’s Superior Court.

The Canadian media giant Canwest is suing the federal government, claiming that the prohibition on advertising prescription drugs directly to the public is a contravention of the constitutional charter guaranteeing free speech.

In a document tendered to the court Canwest’s legal team has described the prohibitions as “paternalistic and anachronistic.” It argues that “truthful, balanced and fair statements containing information that is useful to patients cannot be curtailed” under the Canadian Charter of Rights and Freedoms.

The summary of the media company’s position, given in a 67 …
Orally Administered Activated Charcoal: Acceptance by Children
Authors: Donald G. Corby
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Activated charcoal forms complexes with a wide variety of drugs and poisonous substances, thus preventing their systemic absorption.<sup>1-3</sup>The superiority of this therapeutic agent over the so-called universal antidote has been aptly demonstrated.<sup>4</sup>For these reasons, activated charcoal has been recommended as a very useful antidote for the early management of acute poisoning by ingestion.<sup>5-9</sup> Although Holt and Holz<sup>10</sup>maintained that activated charcoal is probably the most valuable single agent currently available for the immediate treatment of ingested poison, its physical appearance could alienate its use by clinicians, nurses, and patients alike. This view is shared by Arena:<sup>11</sup> To get a 2-year-old to swallow powdered charcoal is a rare accomplishment indeed. The drawback to this compound is that it is black and many children will refuse to drink it and if spewed, it spots uniforms, clothes, walls and personnel. This study was undertaken
Modified Toxicity Probability Interval Design: A Safer and More Reliable Method Than the 3 + 3 Design for Practical Phase I Trials
Authors: Yuan Ji, Sue-Jane Wang
Journal: Journal of Clinical Oncology (2013)

The 3 + 3 design is the most common choice among clinicians for phase I dose-escalation oncology trials. In recent reviews, more than 95% of phase I trials have been based on the 3 + 3 design. Given that it is intuitive and its implementation does not require a computer program, clinicians can conduct 3 + 3 dose escalations in practice with virtually no logistic cost, and trial protocols based on the 3 + 3 design pass institutional review board and biostatistics reviews quickly. However, the performance of the 3 + 3 design has rarely been compared with model-based designs in simulation studies with matched sample sizes. In the vast majority of statistical literature, the 3 + 3 design has been shown to be inferior in identifying true maximum-tolerated doses (MTDs), although the sample size required by the 3 + 3 design is often orders-of-magnitude smaller than model-based designs. In this article, through comparative simulation studies with matched sample sizes, we demonstrate that the 3 + 3 design has higher risks of exposing patients to toxic doses above the MTD than the modified toxicity probability interval (mTPI) design, a newly developed adaptive method. In addition, compared with the mTPI design, the 3 + 3 design does not yield higher probabilities in identifying the correct MTD, even when the sample size is matched. Given that the mTPI design is equally transparent, costless to implement with free software, and more flexible in practical situations, we highly encourage its adoption in early dose-escalation studies whenever the 3 + 3 design is also considered. We provide free software to allow direct comparisons of the 3 + 3 design with other model-based designs in simulation studies with matched sample sizes.
Possible Role of the Brain Stem in Sudden Infant Death Syndrome
Authors: Nobuhisa Baba
Journal: JAMA (1983)

THE INCIDENCE of sudden infant death syndrome (SIDS) is approximately one to three per 1,000 live births. Recently, the Health Service Administration has estimated that 6,500 to 8,000 SIDS cases occur annually in the United States, accounting for almost 40% of the total infant mortality.<sup>1</sup>Sudden infant death syndrome is the single largest cause of death between the ages of 2 weeks and 1 year, with the peak incidence between 2 and 4 months of age. Clinical observations of SIDS and near-miss SIDS infants have implicated a respiratory control dysfunction. Infants observed to be apneic for 20 s or longer, possibly requiring resuscitation, are termed near-miss for SIDS.<sup>2</sup>Studies of these infants have examined such factors as periodic breathing,<sup>3</sup>prolonged apnea,<sup>4</sup>sleep states,<sup>5</sup>arousal threshold,<sup>6</sup>and ventilatory responses to hypoxia and hypercarbia.<sup>7</sup>A number of pathological investigations have demonstrated tissue alterations in the
ON THE INFLUENCE OF ACID GROUPS ON THE SEROLOGICAL SPECIFICITY OF AZOPROTEINS
Authors: K. Landsteiner, J. van der Scheer
Journal: The Journal of Experimental Medicine (1927)

The method of partial synthesis of antigens as employed in the foregoing experiments obviously cannot be substituted for the chemical study of natural antigens. But some questions of a rather general nature not easily accessible to investigations of the latter sort, may be approached by the use of artificial protein compounds. Thus the results reported indicate a peculiarity of certain chemical structures such as acid radicals. The group of immune sera obtained by injecting azoproteins made from non-acid azo components had a wide range of activity. Substituents like CH(3), OCH(3), NO(2), Cl, Br, I, in the aromatic nucleus altered the reactions to a moderate degree only, in most cases. The effects were dependent more on the position than on the nature of the substituents. Two substances were found, however, which had a pronounced effect on the specificity of the compound protein, namely acetyl-para-phenylenediamine and para-aminoacetophenone. In consideration of the above facts it is uncertain whether the antigenic changes noticed by Obermayer and Pick (7) after treating proteins with nitric acid, nitrous acid or iodine are mainly due to the substitution of hydrogen in the benzene ring by NO(2) and I, as is the general belief, or to other changes of the protein. This question had been raised already by the observation that the proteins treated with HNO(3) or HNO(2) containing respectively the nitro or the diazo group, did not differ substantially in their serological properties (8). The antigens made from acid compounds form a group with distinctive features. In the first place the presence of acid radicals destroys the reactivity with the immune sera for the non-acid substances. This influence is so marked that even the reaction with the species specific part of the protein, if such is present, appears to be diminished. Also the sera produced with the acid antigens react but feebly with the non-acid azoproteins. Accordingly it was possible to show that by hydrolysis of the ester of an aromatic acid contained in an azoprotein the serological reactions of the antigen underwent a radical change. The presence of a free carboxyl group in the antigens not only determines the characteristics mentioned but there is reason to believe that it increases markedly the degree of specificity exhibited by the antigens and the corresponding immune sera, when cross-tests are made with a number of acid azoproteins and their antisera. This is brought out by a comparison of the results of the present investigation with those described previously (3). It is of interest in this respect that the specific carbohydrates found by Avery and Heidelberger in pneumococci and pneumobacilli are mostly, if not in all cases, compounds of distinctly acid character.
Persistence of sympathetic-mediated forearm vasoconstriction after alpha-blockade in hypertensive patients.
Authors: S Taddei, A Salvetti, R Pedrinelli
Journal: Circulation (1989)

Sympathetic vasoconstriction not mediated by alpha-adrenoceptors has been identified in vitro and in animals but not in humans. We evaluated the effect of alpha-adrenoceptor blockade on either endogenous vascular sympathetic activation (obtained through the application of a nonhypotensive lower-body negative pressure, -10 mm Hg for 5 minutes) or selective postsynaptic alpha-adrenoceptor stimulation by exogenous norepinephrine (0.005 micrograms/100 ml forearm tissue/min for 3 minutes) in the presence of beta-blockade by propranolol (10 micrograms/100 ml forearm tissue/min for 15 minutes). Drugs were infused into the brachial artery at systemically ineffective rates while continuously monitoring forearm blood flow (by venous plethysmography), intra-arterial mean arterial pressure, and heart rate in patients with essential hypertension. The irreversible antagonist phenoxybenzamine was used at a rate of 20 micrograms/100 ml forearm tissue/min for 1 hour, which antagonized the local responses to norepinephrine in a range of 0.005-0.05 micrograms/100 ml forearm tissue/min. During saline administration, either lower-body negative pressure or exogenous norepinephrine decreased forearm blood flow comparably. However, after phenoxybenzamine administration, forearm vasoconstriction to norepinephrine was abolished while a residual response to lower-body negative pressure remained in each patient. To exclude insufficient alpha-adrenoceptor blockade, the same experimental protocol was repeated by doubling phenoxybenzamine concentrations. No difference from the data obtained with the lower level of antagonist was found. Further studies were performed to confirm the sympathetic origin of the residual vasoconstriction. Bretylium tosylate, a neurotransmitter blocker, infused into the brachial artery (50 micrograms/100 ml forearm tissue/min for 90 minutes) abolished the effect of endogenous sympathetic activation but did not alter the effect of exogenous norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract A53: Biomarkers of chemotherapy resistance in serous epithelial ovarian cancer identified by integrative genomic and transcriptomic analysis
Authors: Madhuri Koti, Robert J. Gooding, Paulo Nuin, Alexandria Haslehurst, Colleen Crane, Johanne Weberpals, Timothy Chids, Peter Bryson, Moyez Dharsee, Kenneth R. Evans, Harriet E. Feilotter, Paul C. Park, Jeremy A. Squire
Journal: Clinical Cancer Research (2013)

Abstract Resistance to platinum-based chemotherapy remains a major impediment in the treatment of serous epithelial ovarian cancer. The objective of this study was to use gene expression and copy number profiling to delineate major deregulated pathways and biomarker networks associated with the development of intrinsic chemotherapy resistance with exposure to standard first-line therapy for ovarian cancer. The study cohort comprised 28 high grade serous ovarian cancer patients divided into two groups based on their varying sensitivity to first-line chemotherapy using progression free survival (PFS) as a surrogate of response. Twelve patient tumors demonstrating relative resistance to platinum based chemotherapy corresponding to shorter PFS (less than 6 months) were compared to 16 tumors from platinum-sensitive patients (PFS more than 18months). Molecular profiling was performed using Affymetrix high-resolution microarray platforms to permit global comparisons of gene expression levels and copy number profiles between tumors from the resistant group with the sensitive group. Microarray data analysis using statistical methods revealed a set of 204 discriminating genes of which expression levels may be influencing differential chemotherapy response between the two groups. Pathway analysis of the differentiating genes showed IGF1 network to be significantly altered between the two groups in addition to PI3K, NFkB, distinguishing the chemotherapy resistant with the sensitive group. Copy number analysis showed differences in the chromosomal regions, 4q31.22, 5q13.2, 9p24.3, 2p23.2, 16q21, 6q14.1, 7p22.3, 12p13 and Xq. Integrative copy number and gene expression profiling will delineate the drivers of chemotherapy resistance in patients undergoing standard platinum-based treatment of ovarian cancer. Future studies to validate these markers are necessary to apply this knowledge to biomarker-based clinical trials. Citation Format: Madhuri Koti, Robert J. Gooding, Paulo Nuin, Alexandria Haslehurst, Colleen Crane, Johanne Weberpals, Timothy Chids, Peter Bryson, Moyez Dharsee, Kenneth R. Evans, Harriet E. Feilotter, Paul C. Park, Jeremy A. Squire. Biomarkers of chemotherapy resistance in serous epithelial ovarian cancer identified by integrative genomic and transcriptomic analysis. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A53.
Cortical activation of accumbens hyperpolarization-active NMDARs mediates aversion-resistant alcohol intake
Authors: Taban Seif, Shao-Ju Chang, Jeffrey A Simms, Stuart L Gibb, Jahan Dadgar, Billy T Chen, Brandon K Harvey, Dorit Ron, Robert O Messing, Antonello Bonci, F Woodward Hopf
Journal: Nature Neuroscience (2013)
Headache Quarterly: Current Treatment and Research
Authors: Gregory O. Walsh
Journal: JAMA (1992)

The new journal<i>Headache Quarterly</i>aims at "catholic coverage" of a multidisciplinary field that has seen a strong worldwide growth of interest and research output. The potential subscriber will want to know whether this publication differs in quality, content, cost, or style from other journals on the same subject such as<i>Cephalaleia</i>(Universitetsforlaget AS) or<i>Headache</i>(American Association for the Study of Headache), or from pertinent articles found in general medical, neurological, and pain journals.<i>Headache Quarterly</i>presents original contributions, review articles, case reports, a works-in-progress session, book reviews, abstracts from the literature, editorials, occasional listings of meetings, and letters to the editor. Each of the other specialty journals offers some of these features, although neither combines them all. Subject coverage among the three journals is not dissimilar, although<i>Cephalaleia</i>does have more research-oriented papers and is the only one with an occasional animal study.<i>Headache Quarterly</i>is, so far,
Enteric-Coated Potassium Supplements
Authors: Lana Gee
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Despite previous widespread publicity concerning the hazards of enteric-coated potassium supplements, these preparations are still commercially available, prescribed, and dispensed. This was shown recently in a survey that we conducted of 25 pharmacies in the San Francisco metropolitan area. The notion that enteric-coated potassium salts are safer and less irritating to the gastrointestinal tract persists, and the hazards associated with their use are not generally recognized. Repeated reports have confirmed the association of intestinal as well as gastric ulceration with the administration of enteric-coated tablets of potassium chloride alone or in combination with thiazide diuretics. In addition to their hazards, the need for these preparations has been eliminated with the introduction of potassium-sparing diuretics and the availability of potassium supplementation in liquid and effervescent tablet forms. Initial report of small bowel ulceration associated with the administration of enteric-coated potassium supplements appeared in the mid 1960s. More recent reports,