tbuckley/cabot-search huggingface dataset:
Abstract 5269: Divergent roles of Akt isoforms in insulin-like growth factor-mediated lung tumorigenesis.
Authors: Sarah Elizabeth Franks, Roger A. Moorehead
Journal: Cancer Research (2013)

Abstract Lung cancer is the leading cause of cancer related mortalities worldwide. Akt is an important kinase in the PI3K pathway of growth factor signaling, and increased Akt activation in lung cancer is associated with poor prognosis. Akt regulates cell growth, proliferation, survival, metabolism and migration making it an attractive target for molecular therapies. Akt exists as three isoforms (Akt1-3) and while it was previously thought they were largely redundant in activity, evidence of differing roles is emerging. Our lab has generated a doxycycline-inducible, tissue-specific transgenic mouse model of lung cancer. Using a surfactant protein C (SPC) promoter, the type I insulin-like growth factor receptor (IGF-IR) is overexpressed in type II alveolar cells which initiates the development of tumors in the lungs. Following nine months of treatment with doxycycline, macroscopic tumors are present on 100% of transgenic mice. These lung adenomas typically present as one or more discrete nodules on the surface of the lung. In this model, cells expressing high levels of IGF-IR also had higher levels of activated Akt. To investigate the role of specific Akt isoforms in lung tumorigenesis, these SPC-IGFIR transgenic mice were crossed with Akt1 null or Akt2 null mice to generate SPC-IGFIR-Akt1-/- and SPC-IGFIR-Akt2-/- mice. The Akt1 null SPC-IGFIR mice have reduced tumor burden compared to their Akt wild-type counterparts. In contrast, the absence of Akt2 accelerates tumor growth in SPC-IGFIR mice. Tumors formed in Akt1 null mice maintain the phenotype of distinct nodules. However, in the advanced tumor progression seen in Akt2 null mice the tumor tissue appears to permeate the lungs rather than form large nodules. These tumors are currently being characterized through evaluation of intracellular signaling as well as rates of proliferation and apoptosis. Initial results indicate opposing roles of Akt1 and Akt2 in the development and progression of lung cancer. While pan-Akt inhibitors are currently in clinical trials, our data suggests targeting Akt1 may be a more effective therapeutic strategy for lung cancer. However, further understanding of the function of each Akt isoform in lung cancer is needed. Citation Format: Sarah Elizabeth Franks, Roger A. Moorehead. Divergent roles of Akt isoforms in insulin-like growth factor-mediated lung tumorigenesis. [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 5269. doi:10.1158/1538-7445.AM2013-5269
Coexistence of passive and carrier-mediated processes in drug transport
Authors: Kiyohiko Sugano, Manfred Kansy, Per Artursson, Alex Avdeef, Stefanie Bendels, Li Di, Gerhard F. Ecker, Bernard Faller, Holger Fischer, Grégori Gerebtzoff, Hans Lennernaes, Frank Senner
Journal: Nature Reviews Drug Discovery (2010)
Reconstructing the Evolutionary History of Polyploids from Multilabeled Trees
Authors: Katharina T. Huber, Bengt Oxelman, Martin Lott, Vincent Moulton
Journal: Molecular Biology and Evolution (2006)

In recent studies, phylogenetic networks have been derived from so-called multilabeled trees in order to understand the origins of certain polyploids. Although the trees used in these studies were constructed using sophisticated techniques in phylogenetic analysis, the presented networks were inferred using ad hoc arguments that cannot be easily extended to larger, more complicated examples. In this paper, we present a general method for constructing such networks, which takes as input a multilabeled phylogenetic tree and outputs a phylogenetic network with certain desirable properties. To illustrate the applicability of our method, we discuss its use in reconstructing the evolutionary history of plant allopolyploids. We conclude with a discussion concerning possible future directions. The network construction method has been implemented and is freely available for use from http://www.uea.ac.uk/∼a043878/padre.html.
A NEW ANTIHISTAMINE HC 20‐511* COMPARED WITH DIMETINDEN (FENISTIL RETARD®) IN THE TREATMENT OF CHRONIC URTICARIA AND OTHER PRURITIC DERMATOSES
Authors: KIRSTI KCOKKANEN
Journal: Allergy (1975)

The new antihistamine, HC20-511 (Sandoz), was compared with Dimetinden (Fenistil retard) in a single-blind comparative study in 42 patients with dermatoses, 28 of whom suffered from chronic urticaria. HC20-511 had a better effect, especially in chronic urticaria, where pruritus, erythema and papules quickly disappeared. The effect appeared somewhat faster than and lasted as long as that of Dimetinden, although HC20-511 is not a retard-preparation unlike the Dimetinden preparation used for comparison. HC20-511 also caused less side effects.
PSILOSIS (?) MUCOSÆ INTESTINI.
Authors: C. M. FENN
Journal: JAMA (1884)

In a brief article which you copy from the<i>Practitioner</i>, Sept., 1883, I discover that Dr. Thin has anticipated me somewhat in the description of a lesion of the mucous membranes, which I have been studying with much interest, as often as such cases came under my observation. Having met with but few instances stances of it, and most of these<i>in transitu</i>(nonresident), I hesitated to announce my impressions until after further investigation. However, by contributing a few paragraphs now, I may at least assist in calling the attention of others to this peculiar disease. The name “ psilosis (loss of hair by depilation) mucosæ intestini,” with which the new malady has been christened, would seem to be somewhat forced in its application to epithelial (intestinal) desquamation, but, perhaps, does not do great violence to our usual nomenclature of diseases. Though I have not yet been able to recognize
EXPERIENCES IN TEACHING COMMUNITY PSYCHIATRY TO RESIDENTS
Authors: LUCY D. OZARIN
Journal: American Journal of Psychiatry (1963)

Fifty-one psychiatric residents attended two workshops on Community Psychiatry and Public Health—Mental Health. Their reaction to and evaluation of these workshops is presented. These experiences suggest that residents are presently receiving only limited information about and experience in community psychiatry. It should be possible to incorporate training in community psychiatry into existing programs by faculty awareness and use of appropriate approaches and by ongoing seminars, utilizing outside lecturers as needed.
Human <i>In vivo</i> Dose-Response to Controlled, Low-Dose Low Linear Energy Transfer Ionizing Radiation Exposure
Authors: Zelanna Goldberg, David M. Rocke, Chad Schwietert, Susanne R. Berglund, Alison Santana, Angela Jones, Jörg Lehmann, Robin Stern, Ruixiao Lu, Christine Hartmann Siantar
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The effect of low doses of low–linear energy transfer (photon) ionizing radiation (LDIR, &amp;lt;10 cGy) on human tissue when exposure is under normal physiologic conditions is of significant interest to the medical and scientific community in therapeutic and other contexts. Although, to date, there has been no direct assessment of the response of human tissue to LDIR when exposure is under normal physiologic conditions of intact three-dimensional architecture, vasculature, and cell-cell contacts (between epithelial cells and between epithelial and stromal cells). Experimental Design: In this article, we present the first data on the response of human tissue exposed in vivo to LDIR with precisely controlled and calibrated doses. We evaluated transcriptomic responses to a single exposure of LDIR in the normal skin of men undergoing therapeutic radiation for prostate cancer (research protocol, Health Insurance Portability and Accountability Act–compliant, Institutional Review Board–approved). Using newly developed biostatistical tools that account for individual splice variants and the expected variability of temporal response between humans even when the outcome is measured at a single time, we show a dose-response pattern in gene expression in a number of pathways and gene groups that are biologically plausible responses to LDIR. Results: Examining genes and pathways identified as radiation-responsive in cell culture models, we found seven gene groups and five pathways that were altered in men in this experiment. These included the Akt/phosphoinositide-3-kinase pathway, the growth factor pathway, the stress/apoptosis pathway, and the pathway initiated by transforming growth factor-β signaling, whereas gene groups with altered expression included the keratins, the zinc finger proteins and signaling molecules in the mitogen-activated protein kinase gene group. We show that there is considerable individual variability in radiation response that makes the detection of effects difficult, but still feasible when analyzed according to gene group and pathway. Conclusions: These results show for the first time that low doses of radiation have an identifiable biosignature in human tissue, irradiated in vivo with normal intact three-dimensional architecture, vascular supply, and innervation. The genes and pathways show that the tissue (a) does detect the injury, (b) initiates a stress/inflammatory response, (c) undergoes DNA remodeling, as suggested by the significant increase in zinc finger protein gene expression, and (d) initiates a “pro-survival” response. The ability to detect a distinct radiation response pattern following LDIR exposure has important implications for risk assessment in both therapeutic and national defense contexts.
Effect of exposure route, regimen, and duration on benzene-induced genotoxic and cytotoxic bone marrow damage in mice.
Authors: R R Tice, C A Luke, R T Drew
Journal: Environmental Health Perspectives (1989)

Mice were exposed to benzene for 13 to 14 weeks by inhalation for either 3 or 5 consecutive days per week or by gavage for 5 consecutive days per week. A weekly evaluation of peripheral blood smears for micronucleated (MN) erythrocyte frequencies and for the percentage of polychromatic erythrocytes (PCE) indicated that the induction of MN-PCE by benzene depended on the sex and strain of mice and on the route of exposure, but not on the inhalation regimen or on the exposure duration. The frequency of MN normochromatic erythrocytes (NCE) not only depended on the sex and strain of mice and on the route of exposure, but directly depended on the inhalation regimen and on the exposure duration. Similarly, the extent of erythropoietic depression in benzene-exposed mice was dependent on sex, mouse strain, exposure duration, and route. However, in contrast to the MN-NCE data, the 3 day/week exposure regimen induced a more persistent depression in erythropoiesis than the 5 day/week exposure regimen. Exposure to benzene also induced in mice a significant depression in packed cell volume (PCV) and bone marrow cellularity, the magnitude of which depended on the sex and strain of mice and on the regimen and route of exposure.
Control of Secondary Hyperparathyroidism During Long-Term Hemodialysis.
Authors: W. J. Johnson
Journal: Annals of Internal Medicine (1971)

Meeting Abstracts1 May 1971Control of Secondary Hyperparathyroidism During Long-Term Hemodialysis.W. J. Johnson, M.D., F.A.C.P., R. S. Goldsmith, M.D., C. D. Arnaud, M.D., J. Jowsey, P. J. Kelly, M.D.W. J. Johnson, M.D., F.A.C.P.Search for more papers by this author, R. S. Goldsmith, M.D.Search for more papers by this author, C. D. Arnaud, M.D.Search for more papers by this author, J. JowseySearch for more papers by this author, P. J. Kelly, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-5-831_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOur studies of parathyroid function in patients with end-stage renal disease maintained by hemodialysis showed that plasma parathyroid hormone concentrations (PTH) were higher in patients with severe symptomatic bone disease and correlated significantly with dialysate calcium concentration (negative) and plasma phosphate (positive). The increased sensitivity of our assay demonstrated, however, that, contrary to some reports, PTH failed to decrease to normal during 8-hr calcium infusions and increased progressively during conventional long-term hemodialysis. To determine the cause of the latter observation, calcium fluxes across the artificial kidney were measured hourly using45Ca and differing dialysate calcium concentrations. Net calcium transfer was... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Rochester, Minn. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1971Volume 74, Issue 5Page: 831-831KeywordsAttentionBlood plasmaBoneCalciumHyperparathyroidismKidneysParathyroidParathyroid hormonePhosphatesRenal failure Issue Published: 1 May 1971 PDF DownloadLoading ...
Inhibition of Hydroxymethylglutaryl-Coenzyme A Reductase Reduces Th1 Development and Promotes Th2 Development
Authors: Rie Hakamada-Taguchi, Yoshio Uehara, Kagemasa Kuribayashi, Atsushi Numabe, Kanako Saito, Hideyuki Negoro, Toshiro Fujita, Teruhiko Toyo-oka, Takuma Kato
Journal: Circulation Research (2003)

Several prospective clinical studies have indicated that hydroxymethylglutaryl-coenzyme A reductase inhibitors, statins, prevent cardiovascular events in part through their antiinflammatory properties. Because inflammation is positively and negatively regulated by T helper (Th) 1 cells and Th2 cells, respectively, we examined the effects of statins on the Th polarization in vitro and in vivo. Here we demonstrated that the statins tested, ie, cerivastatin, simvastatin, lovastatin, and atorvastatin, promoted Th2 polarization through both inhibition of Th1 development and augmentation of Th2 development of CD4 + T cells primed in vitro with anti-CD3 antibody and splenic antigen-presenting cells. Cerivastatin exerted most potent effect on modulation of Th1/Th2 development, and the effect was completely abrogated by an addition of mevalonate. Consistent with in vitro experiments, cerivastatin treatment decreased IFN-γ production of lymph node cells from mice immunized with ovalbumin emulsified in complete Freund’s adjuvant, indicating that Th1 development is also suppressed in an in vivo proinflammatory environment. In this murine model, cerivastatin significantly reduced mesangial matrix expansion of glomeruli in the kidney and attenuated proteinuria. The decrease of glomerular sclerosis by cerivastatin treatment was positively related to the suppression of interferon (IFN)-γ–producing Th1 response in draining lymph node cells. Hence, these findings strongly suggest that statins’ inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase regulates Th1/Th2 polarization in vivo and such a mechanism possibly plays a pathophysiological role in immune-related glomerular injury.
Supreme Court Case, Federal `Initiative' Put Focus on Alcoholism
Authors: Timothy F. Kirn
Journal: JAMA (1987)

ON THE SENATE floor, a vitriolic Strom Thurmond (SC) was shaking a tiny stuffed dog by the neck, a facsimile of Spuds MacKenzie, Anheuser-Busch's bull-terrier mascot, suggesting that it was a ploy that encourages alcohol use by the people who usually own such dolls (read: children). Though the company denies any such intention, Thurmond said, alcohol advertising campaigns geared toward young people are unnecessary, inadvisable, and against the public interest.  Across town, two groups of about 500 conventioneers were at the same Washington, DC, hotel, attending either the annual meeting of the Association for Medical Education and Research in Substance Abuse and/or the first National Conference on Alcohol Abuse and Alcoholism. At the  conference, Secretary of Health and Human Services Otis Bowen, MD, announced a national initiative, pledging to make alcohol problems a department priority.  The war against the country's alcohol problems goes on. A recent report (see LEADS
Neonatal Subclinical Adrenal Insufficiency
Authors: Luiz A. Grajwer
Journal: JAMA (1977)

STEROID-INDUCED diabetes and greatly reduced urinary estriol levels developed in a pregnant woman with pseudotumor cerebri. The infant was born with subclinical adrenal insufficiency. <h3>Report of a Case</h3> A 19-year-old woman was examined at 10 weeks of gestation, with headaches, vomiting, and photophobia. Physical examination showed a 77 kg, 1.70 m normotensive woman. Eye findings included papilledema, slightly constricted visual fields, and enlarged blind spots bilaterally. A lumbar puncture showed an opening pressure greater than 590 mm of water. Skull roentgenogram, electroencephalogram, and echoencephalogram results were normal. Corticoid levels, measured by a modified fluorometric determination, were 25 μg/dl at 8:00 AM and 12 μg/dl at 4:00 PM. Diagnosis of benign intracranial hypertension was made and glycerol therapy was started. Symptoms abated, only to reappear a week later. After the results of her glucose tolerance test (GTT) were found to be normal, she was treated with dexamethasone, 4 mg every 6
57 TENOFOVIR DISOPROXIL FUMARATE (TDF) FOR THE TREATMENT OF HBEAG-NEGATIVE CHRONIC HEPATITIS B: WEEK 72 TDF DATA AND WEEK 24 ADEFOVIR DIPIVOXIL SWITCH DATA (STUDY 102)
Authors: P. Marcellin, I. Jacobson, F. Habersetzer, H. Senturk, P. Andreone, C. Moyes, A. Horban, G. Teuber, J. Sorbel, J. Anderson, E. Mondou, J. Quinn, F. Rousseau
Journal: Journal of Hepatology (2008)
IT-35 * cGMP MANUFACTURING OF EX VIVO EXPANDED TUMOR-SPECIFIC T CELLS AND AMPLIFIED TUMOR RNA-PULSED DC VACCINES TARGETING GLIOBLASTOMA AND MEDULLOBLASTOMA
Authors: O. Yegorov, A. Dechkovskaia, J. Drake, B. D. Cleaver, N. Clement, J. Huang, D. A. Mitchell
Journal: Neuro-Oncology (2014)

BACKGROUND: Adoptive cellular therapy using transfer of tumor-specific lymphocytes has emerged as a potent strategy for treatment of advanced and refractory malignancies. We have employed the use of total tumor RNA (TTRNA)-pulsed DCs in the ex vivo expansion of tumor-specific lymphocytes for use in adoptive cellular therapy targeting pediatric and adult malignant brain tumors. METHODS: Total tumor RNA was extracted and amplified from resected brain tumor specimens using previously published methods. Efforts to improve recovery, fidelity of amplification, and integrity of RNA included comparative analysis of free extraction methods, SMART TM-based cDNA synthesis, and PCR primer modifications. DC generation and T cell expansion under varying culture conditions and cytokine milieus were evaluated to improve functional yields of autologous cellular products. Validation runs of multi-site collection of tumor cells and leukapheresis products for DC and T cell generation under GLP and GMP conditions were performed using standardized operating procedures. RESULTS AND CONCLUSIONS: We have optimized high quality (RNA integrity, RIN ≥ 8) TTRNA amplification from resected brain tumor specimens using as little as 1 ng of input TTRNA through incorporation of solid-phase paramagnetic bead technology for cDNA synthesis and optimized PCR conditions. We founded that TTRNA transfection up-regulates the expression of CD80, CD83, CD86, HLA-DR in mature DCs. The feasibility of external site collection and delivery of tumor cells and leukapheresis products for tumor RNA amplification, DC generation, and T cell expansion has been validated by our laboratory. We have recently demonstrated the safety and feasibility of this adoptive cellular therapy platform in a phase I trial of pediatric patients with relapsed medulloblastoma and PNETs in a single institutional setting. A multi-institutional phase 2 clinical trial is underway (Re-MATCH trial: FDA IND BB-14058, UF IRB 128-2013).
Vaccination and Breast-feeding
Authors: R. Kim-Farley, E. Brink, W. Orenstein, K. Bart
Journal: JAMA (1982)

<h3>To the Editor.—</h3> A recent book for physicians, nurses, and other medical personnel correctly states that diphtheria, tetanus, pertussis (DTP), rubella, mumps, and measles vaccines should be given at the regularly scheduled times to infants who are breast-fed.<sup>1</sup>However, the recommendations regarding oral polio vaccine (OPV) are not supported by the two major immunization advisory bodies in the United States, the Advisory Committee on Immunization Practices (ACIP) and the Committee on Infectious Diseases of the American Academy of Pediatrics (Red Book Committee). The author recommends that breast-feeding be postponed for at least 30 minutes after the administration of an OPV and that booster doses should be given as soon as the infant is weaned and one year after weaning. We believe that the author's recommendations have caused unnecessary confusion and are not supported by the available scientific literature. We have received several inquiries from physicians for clarification. Because of
Ototoxicity Induced by Furosemide
Authors: Gabriel H. Schwartz, David S. David, Robert R. Riggio, Kurt H. Stenzel, Albert L. Rubin
Journal: New England Journal of Medicine (1970)

FUROSEMIDE is a diuretic that has achieved wide use because of its great potency as a saluretic agent and its low order of toxicity. We describe here transient ototoxic effects of high-dose furosemide therapy in five patients with diminished renal function.Case ReportsA 37-year-old woman with marked renal impairment due to radiation nephritis and with normal hearing received a cadaveric renal transplant. A total of 3600 mg of furosemide was given intravenously in divided doses in the 1st 18 hours after transplantation. Sixty hours after transplantation the urine output fell from 80 to 20 ml per hour. A 1600-mg . . .
E-cigarettes as good as patches in helping to reduce smoking, study concludes
Authors: J. Wise
Journal: BMJ (2013)

A randomised controlled trial that compared electronic cigarettes with nicotine patches found that the methods were roughly equivalent in helping smokers to quit. 

The New Zealand study, published in the Lancet , randomised 657 smokers to nicotine e-cigarettes, nicotine patches, or placebo e-cigarettes.1 At six months follow-up the verified abstinence rate was 7.3% of participants (21 of 289) in …
A SIMPLE AND RAPID METHOD FOR THE SELECTION OF SUITABLE DONORS FOR TRANSFUSION BY THE DETERMINATION OF BLOOD GROUPS
Authors: R. I. Lee
Journal: BMJ (1917)

Position of the Patient and Dontor.The-left hand of donor' grasps the arm of tlle patient just above the elbow, biinging tlle-donor's radial artery in close proximity to tlhe patient's median basilic veinl.THE OPERATION.An incision about 2 in. in length is made in thle patient's
92 SAFETY, TOLERABILITY AND ANTIVIRAL ACTIVITY OF VCH-916, A NOVEL NON-NUCLEOSIDE HCV POLYMERASE INHIBITOR IN PATIENTS WITH CHRONIC HCV GENOTYPE-1 INFECTION
Authors: E. Lawitz, C. Cooper, M. Rodriguez-Torres, R. Ghalib, R. Lalonde, A. Sheikh, B. Bourgault, N. Chauret, L. Proulx, J. McHutchison
Journal: Journal of Hepatology (2009)
Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus
Authors: Jian-Wen Han, Hou-Feng Zheng, Yong Cui, Liang-Dan Sun, Dong-Qing Ye, Zhi Hu, Jin-Hua Xu, Zhi-Ming Cai, Wei Huang, Guo-Ping Zhao, Hong-Fu Xie, Hong Fang, Qian-Jin Lu, Jian-Hua Xu, Xiang-Pei Li, Yun-Feng Pan, Dan-Qi Deng, Fan-Qin Zeng, Zhi-Zhong Ye, Xiao-Yan Zhang, Qing-Wen Wang, Fei Hao, Li Ma, Xian-Bo Zuo, Fu-Sheng Zhou, Wen-Hui Du, Yi-Lin Cheng, Jian-Qiang Yang, Song-Ke Shen, Jian Li, Yu-Jun Sheng, Xiao-Xia Zuo, Wei-Fang Zhu, Fei Gao, Pei-Lian Zhang, Qing Guo, Bo Li, Min Gao, Feng-Li Xiao, Cheng Quan, Chi Zhang, Zheng Zhang, Kun-Ju Zhu, Yang Li, Da-Yan Hu, Wen-Sheng Lu, Jian-Lin Huang, Sheng-Xiu Liu, Hui Li, Yun-Qing Ren, Zai-Xing Wang, Chun-Jun Yang, Pei-Guang Wang, Wen-Ming Zhou, Yong-Mei Lv, An-Ping Zhang, Sheng-Quan Zhang, Da Lin, Yi Li, Hui Qi Low, Min Shen, Zhi-Fang Zhai, Ying Wang, Feng-Yu Zhang, Sen Yang, Jian-Jun Liu, Xue-Jun Zhang
Journal: Nature Genetics (2009)