tbuckley/cabot-search huggingface dataset:
Abstract 3210: pRb, but not p107 or p130, is required for full induction of p16INK4a in human mammary epithelial cells
Authors: Alexey Bazarov, Irina Korobochkina, Moses Bosire, Curtis Hines, Rituparna Mukhopadhyay, Won Jae Lee, Agustin Chicas, Scott Lowe, Paul Yaswen
Journal: Cancer Research (2010)

Abstract Pocket family proteins pRb, p107 and p130 are important cell cycle regulators in mammalian cells. In addition to controlling G1 to S transition, they also participate in differentiation and senescence. While all three pocket proteins have similar structures and apparently overlapping functions, defects in only one, pRb, are associated with human cancers. In breast cancer, pRb loss is associated with triple negative (ER-, PR-, HER2-) tumors, which tend to be more aggressive. To explore possible functions of pRb that may be unique, we investigated relative contributions of pocket proteins to cellular senescence initiated by high levels of the cyclin-dependent kinase inhibitor p16INK4a. For this purpose, we silenced pRb, p107 and p130 expression individually with shRNA constructs and exposed MCF7 and MDA-MB-231 breast cancer cell lines to tet-inducible p16. In both malignant lines, knockdown of any single pocket protein was insufficient to prevent p16-induced senescence, indicating the likely existence of compensatory activities of the three pocket proteins in mediating p16-induced senescence. However, our finding that the introduction of HPV E7 - which inactivates all three pocket proteins, prevented p16-induced senescence, is consistent with the hypothesis that as a group, pRb, p107 and p130 constitute essential mediators of p16-induced senescence. To examine the relative contributions of the pocket proteins to cellular senescence initiated by endogenous p16, we used cultured primary human mammary epithelial cells (HMEC) from non-malignant breast tissues. These cells spontaneously induce endogenous p16 and undergo senescence. When we examined the relative contributions of pocket proteins to senescence associated with increased endogenous p16 levels in HMEC, we found that suppressing pRb alone abrogated p16-induced senescence, whereas suppressing p107 or p130 did not. Remarkably, HMEC in which pRb alone was knocked down showed reduced p16 expression and longer proliferative life spans than controls or HMEC in which p107 or p130 were knocked down. These results suggest that pRb, but not p107 or p130, is required for full induction of endogenous p16 in breast cells, and provide a possible explanation for the special tumor-suppressor role of pRb. 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 3210.
Role for tumor necrosis factor ? receptor 1 and interleukin-1 receptor in the suppression of mouse hepatocyte apoptosis by the peroxisome proliferator nafenopin
Authors: Douglas A. West, Neil H. James, Sabina C. Cosulich, Peter R. Holden, Richard Brindle, Mark Rolfe, Ruth A. Roberts
Journal: Hepatology (1999)

Peroxisome proliferators (PPs) cause rodent liver enlargement and tumors. In vitro, PPs induce rat and mouse hepatocyte DNA synthesis and suppress apoptosis, a response mimicked by exogenous tumor necrosis factor alpha (TNFalpha). Here, we determine the role of TNF receptor 1 (TNFR1), TNF receptor 2 (TNFR2), and nuclear factor kappa beta (NFkappaB) in the response of mouse hepatocytes to the PP, nafenopin. Nafenopin (50 micromol/L) induced DNA synthesis as measured by bromodeoxyuridine (BrdU) incorporation, suppressed cell death as measured by Hoechst 33258 staining, induced peroxisomal beta-oxidation as measured by cyanide insensitive palmitoyl CoA oxidation (PCO) and caused activation of nuclear factor kappa beta (NFkappaB) as determined by electrophoretic mobility gel shift assay (EMSA). The induction of DNA synthesis and the suppression of apoptosis in response to nafenopin was abrogated completely by blocking antibodies to TNFR1 but not to TNFR2. In contrast, the induction of peroxisomal beta-oxidation by nafenopin was not blocked by the anti-TNFR1 antibody. Next, we evaluated the response of hepatocytes to interleukin-1 (IL-1), another proinflammatory cytokine. IL-1alpha (2.5 ng/mL) and, to a lesser extent, IL-1beta (5 ng/mL), shared the ability of TNFalpha to induce DNA synthesis and suppress apoptosis. In addition, anti-IL-1 receptor, type 1/p80 (IL-1R) antibodies were able to abrogate the response to nafenopin. IL-1alpha was still able to perturb hepatocyte growth in the presence of the anti-TNFR1 antibody suggesting that IL-1alpha acts independently rather than by elaborating TNFalpha. In summary, these data provide additional evidence for a role for hepatic cytokines in the perturbation of hepatocyte growth by PPs such as nafenopin.
THE LIFE INSURANCE VALUE OF GRAPHIC HEART RECORDS
Authors: S. CALVIN SMITH
Journal: JAMA (1923)

Applicants for life insurance are generally free from gross, conventional physical signs of heart disease. Persons who have such signs—shortness of breath, early limitations on effort, murmurs, cardiac enlargement, etc.—are probably aware of their limitations or are already acquainted with the physical findings in their case through previous examinations. Therefore, they do not, as a rule, expose themselves to the stigma of rejection.  DETECTION OF EARLY HEART DEFECTS  There is a further reason why the applicant is not likely to present any of the customary and classic signs of heart defect. The average age of those seeking life insurance is probably around 30 years. At this period of life, the powers of resistance are at their highest and vitality is at its best. Therefore, if the heart has some defect, as yet unrevealed, which may be a heritage from the infections of childhood, the defect is usually not manifest in
Abstract 874: Mutations of aromatic amino residue to polar residue in NBDs alter the transport properties of ABCC10.
Authors: Ekaterina V. Malofeeva, Elizabeth Hopper-Borge
Journal: Cancer Research (2013)

Abstract ABCC10 is an efflux pump that confers multidrug resistance to cells by extruding a variety of natural and nucleosides analogues using energy from ATP hydrolysis. The objective of this project is to understand the detailed relationship between ATP hydrolysis and drug transport for ABCC10 and how ABCC10’s ATPase activity is regulated. For this study, we mutated aromatic residues to polar residues in the Nucleotide Binding Domains (NBDs) of ABCC10 to determine how these residues are involved in the transport of ABCC10 substrates. Prior, structural analyses of several bacterial ABC-transporters indicated that aromatic amino acid residues in NBDs are needed for ATP binding and ATP hydrolysis. In these studies, substitution of these aromatic residues completely abolished ATP-dependent transport. Prior work on ABCC1 has shown that substitutions such as W (tryptophan) to C (cytidine) or Y (tyrosine) to C (cytidine) decreased ABCC1’s affinity for ATP, and ATP-dependent LTC4 transport activities. Analogous substitutions of W (tryptophan) residues to polar residues in the NBD2 of ABCC2 eliminated estradiol glucuronide and leukotriene C4 transport. Based on these data, we hypothesize that mutating aromatic to polar residues in the NBDs of ABCC10 will modulate the biochemical and cellular transport activities of this efflux pump. At present we have generated mutant-ABCC10 constructs by site-directed mutagenesis. Specifically, we mutated the aromatic Tyr747 (NBD1), Trp607 (NBD1) and Tyr1255 (NBD2) residues to polar cysteine residues. We then examined all ABCC10-mutant, wild-type ABCC10 and empty-vector constructs using immunofluorescence, ATPase assays, sensitivity and transport assays. We observed that the mutant ABCC10 proteins localized predominantly to the membranes. Further, ABCC10-mutant cells, except for the W607C mutant clone, showed less sensitivity than empty vector-transfected cells. Using accumulation assays we also demonstrated that substitutions of aromatic to polar residues, such as W607C and Y1255C, decreased the ability of ABCC10 to transport, docetaxel and Ara-C, however transport was not completely abolished. Using our ABCC10 mutants we found that aromatic to polar residue substitutions eliminated the stimulatory effects of docetaxel and Ara-C on ATPase activity of ABCC10. Taken together, these results demonstrate that these aromatic residues are involved in the ATP binding process and mutations of these residues cause of reduction in ABCC10 transport of docetaxel and Ara-C from cells. Citation Format: Ekaterina V. Malofeeva, Elizabeth Hopper-Borge. Mutations of aromatic amino residue to polar residue in NBDs alter the transport properties of ABCC10. [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 874. doi:10.1158/1538-7445.AM2013-874
The Confounding Effects of Thoracic Gas Compression on Measurement of Acute Bronchodilator Response
Authors: Amir Sharafkhaneh, Tony G. Babb, Todd M. Officer, Nicholas A. Hanania, Hossein Sharafkhaneh, Aladin M. Boriek
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Improvement in FEV(1) is a main endpoint in clinical trials assessing the efficacy of bronchodilators. However, the effect of bronchodilators on maximal expiratory flow may be confounded by thoracic gas compression (TGC).To determine whether TGC confounds effect of albuterol on FEV(1).We evaluated the response to albuterol inhalation in 10 healthy subjects, 9 subjects with asthma, and 15 subjects with chronic obstructive pulmonary disease (COPD) with mean (SD) age in years of 38 (SD, 11), 45 (SD, 11), and 64 (SD, 8), respectively. Lung mechanics were measured at baseline and 20 minutes after inhalation of 180 micro g of albuterol. We then applied a novel method to calculate FEV(1) corrected for the effect of TGC (NFEV(1)).Prior to albuterol administration, NFEV(1) was significantly higher than FEV(1). However, post-albuterol inhalation, FEV(1) increased more than NFEV(1) because of reduced TGC. In multiple regression analysis, the changes in TGC, inspiratory lung resistance, and ratio of residual volume to total lung capacity postalbuterol predicted more than 75% of FEV(1) improvement in patients with COPD.Improvements in FEV(1) after albuterol in patients with COPD are due to reduction of lung resistance, hyperinflation, and TGC. The latter is negligible during tidal breathing. Thus, although reduction of lung resistance and hyperinflation may result in improved dyspnea with a bronchodilator, the contribution of TGC reduction to improvement of FEV(1) may not exert any meaningful clinical effect during tidal breathing. This fact has to be taken into consideration when assessing the efficacy of new bronchodilators.
Herpes simplex and temporal lobe epilepsy.
Authors: J H Millar, M Haire, K B Fraser
Journal: BMJ (1972)

hibitor and Fast Red TR salt solution in 3% aqueous dupanol as colour index.The results are summarized in the Table.Number IAbnor-Genetic Disorder Exam-mal ined Cases % i-thalassaemia trait .. 156 27 17-3 Hb A, increased (>335%) 156 25 16-0 g I thal.(Hb F > 5%) 156 2 1-3 -6-PD deficiency . . . . . . . . .
Interferon ? down-regulates cytochrome P450 3A genes in primary cultures of well-differentiated rat hepatocytes
Authors: M Tapner, C Liddle, B Goodwin, J George, G C Farrell
Journal: Hepatology (1996)

Administration of interferons of both the γ and alfa/β classes down–regulates hepatic cytochrome P450 (CYP) genes when administered to humans or rats. In male rats, interferons decrease expression of CYP3A2 at a pretranslational level, but because interferons also release other cytokines in vivo , it is unclear whether this is a direct effect on hepatocytes. We therefore examined the effects of rat recombinant interferon γ (IFN–γ) on CYP3A2, other 3A genes, and 2C11 in stable primary cultures of male rat hepatocytes. Hepatocytes were cultured on matrigel in Williams' E, and messenger RNAs (mRNAs) for 3A2, 3A1–like CYPs, and 2C11 mRNA were determined by RNase protection assays. CYP3A and 2C11 proteins were immunoquantified, and their catalytic activities were estimated by testosterone hydroxylation pathways. In control cells, 3A2 mRNA decreased initially but then recovered, and stable levels (15% of freshly isolated cells) were attained between days 3 and 7. Phenobarbital increased 3A2 mRNA to 60-120% values of freshly isolated cells, and mRNA for 3A1–like CYPs were increased 20–fold. In both control and phenobarbital–treated hepatocytes, rat recombinant IFN–γ (33 U/mL) reduced mRNA for 3A2 and 3A1–like CYPs, as well as 3A protein and testosterone 6 β–hydroxylase activity. Interferon had no effect on CYP2C11 at mRNA or protein levels in untreated cells, although a reduction in 2C11 protein was evident in phenobarbital–treated cultures. It is concluded that interferon directly alters expression of constitutive and inducible CYP3A genes in well–differentiated male rat hepatocytes in culture, but has no effect on constitutive expression of CYP2C11.
Overcoming Obstacles to Research in Residency—Reply
Authors: Michael B. Rothberg
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A Case of Early Yaws
Authors: J. Barrow, H. J. Wallace, C. S. Nicol
Journal: BMJ (1959)

TRACHEOTOMY IN INFLUENZA-~~~~~~~~~~~~~~~~~~~~Mi-,owM became almost normal.Section of this rubbery stuff showed dense mucus which appeared stratified and apparently consisted of a conglomeration of mucoid plugs from a number of bronchi.Entangled in the mucus were many necrotic cells, including some resembling epithelial cells.Culture of a laryngeal swab yielded H. influenzae, Staphylococcus aureus, and Friedlander's bacillus, but some intratracheal pus produced on culture only Staphylococcus albuis.Frequent aspirations were needed through the tracheotomy tube.The temperature remained at about 1010 F. (38.3'C.) for the next few days, but the chest remained clear and the respiration rate was not raised.X-ray examination of the chest showed no abnormality.After two days she suddenly became distressed again and all the signs of anoxia returned.The night sister succeeded, after about 15 minutes with the electric suction machine, in bringing out a large blood-stained mixture of mucus and pseudomembrane which had apparently been obstructing the trachea lower down than the end of the tracheotomy tube.After five days in hospital the temperature had settled and phonation was normal.The tracheotomy tube was removed and she remained very well.A specimen of serum was sent to the Virus Research Laboratory three days after the illness started and again after a fortnight.Complement fixation against influenza A (soluble antigen) showed a rise in titre from 12 to more than 64.Haemagglutination inhibition against influenza A/ Singapore/1957 showed a rise in titre from 40 to 240.
Married to Medicine
Authors: A. M. Horowitz
Journal: Annals of Internal Medicine (2013)

On Being a Doctor4 June 2013Married to MedicineA. M. Horowitz, MFAA. M. Horowitz, MFAFrom Edgewater, New Jersey.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-158-11-201306040-00013 Audio Reading - “Married to Medicine” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Married to Medicine," by A.M. Horowitz. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In the spring of 2010, my family prepared to move so that my husband could begin a residency program in New York City, about 250 miles from our home in Virginia. My husband was excited. He'd matched at an excellent hospital in Manhattan and was eager to begin his program.I was apprehensive. I loved where we lived in Virginia and was dreading leaving it behind. Nonetheless, on an April day, I found myself with a real estate agent, looking at places to rent just outside the city, in New Jersey. He'd found one for us, a little house, right ... Author, Article, and Disclosure InformationAffiliations: From Edgewater, New Jersey.Acknowledgment: This essay is dedicated in memory of Dr. Harry Lamparelli.Corresponding Author: A.M. Horowitz, MFA; e-mail, am.[email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Married to Medicine” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Married to Medicine," by A.M. Horowitz. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 4 June 2013Volume 158, Issue 11Page: 847KeywordsEmotionsMedical educationMemoryResidencyRiversRunning ePublished: 4 June 2013 Issue Published: 4 June 2013 Copyright & PermissionsCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL-23 inhibitor
Authors: Yumiko Wada, Rongzhen Lu, Dan Zhou, John Chu, Teresa Przewloka, Shijie Zhang, Long Li, Yaming Wu, June Qin, Vishwasenani Balasubramanyam, James Barsoum, Mitsunori Ono
Journal: Blood (2006)
Evidence for a protective role of the STAT5 transcription factor against oxidative stress in human leukemic pre-B cells
Authors: E Cholez, V Debuysscher, J Bourgeais, C Boudot, J Leprince, F Tron, B Brassart, A Regnier, E Bissac, E Pecnard, F Gouilleux, K Lassoued, V Gouilleux-Gruart
Journal: Leukemia (2012)
Cervical spine injuries in Rugby Union football.
Authors: J P Williams, B McKibbin
Journal: BMJ (1978)

Cervical spine injuries in Rugby Union footballThe BM7, in a leading article on rugby injuries to the cervical cord,' referred to the low incidence of serious neck injuries.Experience in Cardiff over the past few years, however, suggests that these lesions are becoming more common.This prompted us to review all such cases treated in the Cardiff Royal Infirmary over the past four years to assess the true extent of the problem and to analyse the mechanisms involved, thereby hoping to identify some preventive measures. Cases and lesionsAltogether nine patients were identified who had been injured in the four playing seasons since 1974.Five of them had suffered spinal cord damage.All were recalled for review and closely questioned about the circumstances of their injury.Eye witnesses were also interviewed when possible.The details of the cases are shown in the table.The predominant lesion was a dislocation or subluxation of the mid-cervical spine.Scrum injuries pre- dominated, accounting for five cases, while the remainder occurred either during or immediately after a tackle.Most of the injuries happened early in the season: only two out of the nine occurred after the relevant 1 January.There was also an association with inexperience.Four injuries occurred in schoolboy matches and one player, although aged 22, had played only 10 games in one previous season.Clinical details in nine cases of cervical spine injury occurring in rugby football
Cheaper alternative for macular degeneration is as safe as licensed drug, review finds
Authors: Z. Kmietowicz
Journal: BMJ (2014)

An anticancer drug that is used off label to treat wet age related macular degeneration causes no more side effects than the far more expensive licensed treatment, a review of trials has concluded.

The authors of the Cochrane review1 said that their findings should end disagreement over the safety of the cheaper drug, bevacizumab (marketed as Avastin), compared with ranibizumab (Lucentis). The current evidence did not support policies that backed the use of the more expensive drug for safety reasons, they said.

Ever since ranibizumab was approved in Europe in 2007 it has courted controversy. It is the drug most commonly used in the United Kingdom to treat wet age related macular degeneration and costs about £700 …
Measuring the Quality of Life: From Theory to Practice
Authors: R. Fitzpatrick
Journal: BMJ (1996)

Soren Ventegodt Forskningscentrets Forlag, £15, pp 218 ISBN 87 90190 08 4

Since the 1970s increased effort has been invested in “social indicators” research, the objectives of which are to assess levels of welfare, satisfaction, and quality of life in populations and to identify determinants of these states. This research was a logical development of the welfare state in that it attempted to provide scientific, policy oriented answers to the question of how the wellbeing of citizens was to be sustained and improved. Some of the results of such research can seem rather obvious: individuals are happier in more prosperous societies, at the top rather …
Inverse Relationship of Blood Pressure Levels to Sudden Cardiac Mortality and Benefit of the Implantable Cardioverter-Defibrillator in Patients With Ischemic Left Ventricular Dysfunction
Authors: Ilan Goldenberg, Arthur J. Moss, Scott McNitt, Wojciech Zareba, W. Jackson Hall, Mark L. Andrews
Journal: Journal of the American College of Cardiology (2007)
The Dissemination of Zymotic Disease amongst the Public by Tradespeople
Authors: C. B. Fox
Journal: BMJ (1876)

affording definite information regarding the pathological processes in different cases of Bright's disease,itwill, I think, have considerable value; and some factswhich have come under my observation, at present too few and isolated for more than mention, make me hope that ultimately it may help us better to distinguish between morbid states included under the term and at present imperfectly distinguished.
P836 ELEVATED SERUM LEVELS OF ALT ARE ASSOCIATED WITH METABOLIC SYNDROME INDEPENDENT OF FATTY LIVER DIAGNOSED BY ULTRASOUND
Authors: Y. Imamura, H. Uto, Y. Hiramine, K. Hosoyamada, S. Yoshifuku, H. Miyahara, S. Maenohara, M. Oketani, A. Ido, H. Tsubouchi
Journal: Journal of Hepatology (2014)