tbuckley/cabot-search huggingface dataset:
Integrin-mediated Ras–Extracellular Regulated Kinase (ERK) Signaling Regulates Interferon γ Production in Human Natural Killer Cells
Authors: Fabrizio Mainiero, Angela Gismondi, Alessandra Soriani, Marco Cippitelli, Gabriella Palmieri, Jordan Jacobelli, Mario Piccoli, Luigi Frati, Angela Santoni
Journal: The Journal of Experimental Medicine (1998)

Recent evidence indicates that integrin engagement results in the activation of biochemical signaling events important for regulating different cell functions, such as migration, adhesion, proliferation, differentiation, apoptosis, and specific gene expression. Here, we report that β1 integrin ligation on human natural killer (NK) cells results in the activation of Ras/mitogen-activated protein kinase pathways. Formation of Shc–growth factor receptor–bound protein 2 (Grb2) and Shc–proline-rich tyrosine kinase 2–Grb2 complexes are the receptor-proximal events accompanying the β1 integrin–mediated Ras activation. In addition, we demonstrate that ligation of β1 integrins results in the stimulation of interferon γ (IFN-γ) production, which is under the control of extracellular signal–regulated kinase 2 activation. Overall, our data indicate that β1 integrins, by delivering signals capable of triggering IFN-γ production, may function as NK-activating receptors.
Christmas Factor (IX) and Warfarin Therapy
Authors: JACK B. ALPERIN
Journal: Annals of Internal Medicine (1968)

Letters and Comments1 June 1968Christmas Factor (IX) and Warfarin TherapyJACK B. ALPERIN, M.D.JACK B. ALPERIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-6-1369_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:In the paper entitled "Quinidine-Induced Hypoprothrombinemic Hemorrhage in Patients on Chronic Warfarin Therapy" (Annals of Internal Medicine, March 1968) Dr. Jan Koch-Weser is in error when he implies that factor IX levels influence the one-stage prothrombin time. Factor IX (Christmas factor) is not measured by the prothrombin time. Those factors involved in the prothrombin time include prothrombin, V, VII, X, and fibrinogen (1)....Reference1. HARDISTYINGRAM RMGI: Bleeding Disorders. Investigation and Management, F. A. Davis Co., Philadelphia, 1965. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Internal Medicine University of Texas—Medical Branch Galveston, Tex. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1968Volume 68, Issue 6Page: 1369-1370KeywordsFibrinogenHemorrhageProthrombin time Issue Published: 1 June 1968 PDF DownloadLoading ...
Abstract 2140: Efficacy of aerosolized pioglitazone in lung carcinogenesis in A/J mice
Authors: Donna Seabloom, Art Galbraith, Beverly Wuertz, Anna Haynes, Jenny Antonides, alisha fujita, Vernon Steele, Lee Wattenberg, Frank G. Ondrey
Journal: Cancer Research (2014)

Abstract Pioglitazone is a PPAR gamma agonist commonly utilized clinically in the treatment of diabetes. There have been clinical trials with this agent in oral cancer prevention and we sought to potentially expand its use in lung cancer in a B[a]P mouse model. Directed epithelial delivery in lung cancer is an attractive treatment approach and we felt pioglitazone would be amenable to aerosol delivery. Initially, a maximum tolerated dose experiment examining standard toxicity parameters, including animal behavior characteristics, weight, general health, and increases in markers of cytotoxicity in bronchoalveolar lavage was conducted. We found no statistically significant indications of increased toxicity in the animals with administration of aerosolized pioglitazone and proceeded with the prevention protocol. We utilized 192 seven week old female A/J mice. All groups received Benzo[a]pyrene by oral gavage in 3 doses of 3mg/kg body weight over the course of 1 week. Animals were then randomized into 8 groups of 24 mice per group based on weight. Experimental diets, 0, 50, 150, and 450µg/kg body weight pioglitazone formulated into 0.6µm average diameter respiratory particles, were started 1 week or 8 weeks after last dose of B[a]P. Animals were continued on the feeding schedule, weighed weekly, and monitored for weight loss, attenuation, rough hair coat, or other signs of ill health. The study was concluded 16 weeks after administration of B[a]P. The agent was well tolerated for the duration of the experiment and there was no observable toxicity. The average number of adenomas per animal in the late treatment group was 10.69 ± 1.685 in the control, 12.27 ± 1.761 in the 50µg, 6.000 ± 0.6359 in the 150 µg, and 7.267 ± 1.071 in the 450µg groups but low control tumor counts in the early treatment group precluded analysis. The same tumor initation protocol was used with 72 mice. Animals were randomized into 3 groups of 24 animals and treated with 0, 150, or 450µg/kg body weight aerosol pioglitazone for 16 weeks starting 1 week after the last B[a]P dose. The average number of adenomas per animal was 9.217 ± 1.004 in the control, 7.957 ± 0.9440 in the in the 150 µg, and 6.304 ± 0.8653 in the 450µg groups. We conclude aerosol pioglitazone is well tolerated in the A/J mouse model and a promising chemoprevention agent in the aerodigestive tract. Citation Format: Donna Seabloom, Art Galbraith, Beverly Wuertz, Anna Haynes, Jenny Antonides, alisha fujita, Vernon Steele, Lee Wattenberg, Frank G. Ondrey. Efficacy of aerosolized pioglitazone in lung carcinogenesis in A/J mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2140. doi:10.1158/1538-7445.AM2014-2140
Malignant Adrenal Rest Tumor of the Retroperitoneum Producing Adrenocortical Steroids
Authors: Yuri Akishima-Fukasawa, Aya Yoshihara, Yukio Ishikawa, Natsuko Watanabe, Naoki Hiroi, Yoshikiyo Akasaka, Hironobu Sasano, Toshiharu Ishii, Gen Yoshino
Journal: Endocrine Pathology (2011)
TCT-346 Race and Outcomes after PCI for ACS: A Pooled Analysis of the HORIZONS-AMI and ACUITY Trials
Authors: Mahesh V. Madhavan, Giora Weisz, Michael T. Caton, Philippe Genereux, Ke Xu, Bernhard Witzenbichler, Roxana Mehran, Gregg Stone
Journal: Journal of the American College of Cardiology (2013)
Coming of age: molecular drivers of aging and therapeutic opportunities
Authors: Christopher B. Newgard, Norman E. Sharpless
Journal: Journal of Clinical Investigation (2013)

Aging is like the weather: everyone talks about it, but no one seems to do anything about it. We believe this may soon change, as an improved understanding of the molecular and genetic pathways underlying aging suggests it is possible to therapeutically target the aging process and increase health span. This Review series focuses on fundamental cellular mechanisms of aging and their relationship to human disease. These pathways include telomere dysfunction in cellular senescence and induction of the senescence-associated secretory phenotype (SASP) in systemic aging, sirtuin family regulation of metabolism and aging-associated diseases, mitochondrial metabolism in aging, the mechanistic target of rapamycin (mTOR) signaling pathway and the use of mTOR inhibitors to increase longevity, the progressive decline of the immune system with age, and aging-associated changes to pancreatic islet β cells that may contribute to diabetes. Together, these articles explore pathways affecting aging and possible interventional targets to slow or delay the onset of age-related pathologies.
INTESTINAL PARASITES IN CHILDREN
Authors: H. M. McCLANAHAN
Journal: JAMA (1918)

Every animal, including man, is an unwilling host to one or more kinds of parasites. A number of these produce serious diseases. At the present time, more than 300 kinds of animal parasites have been described for man, and the list is constantly growing. By the term parasite is understood a living organism, which, for the purpose of obtaining food, takes its abode temporarily or permanently on or within other living organisms.  There are two great general divisions, vegetable, or phytoparasites, and animal, or zooparasites. While the phytoparasites offer a rich field for research and cause many serious diseases, they will not be considered in this paper. The zooparasites invade every organ, tissue and fluid of the human body. Their significance as an etiologic factor in disease is becoming more appreciated and understood.  There are ectoparasites, which live on external surfaces of the body or in cavities easily accessible from
Acute Rejection in the Long-Term Cardiac Transplant Survivor
Authors: ANTHONY F. GRAHAM, ALAN K. RIDER, PHILIP K. CAVES, EDWARD B. STINSON, DONALD C. HARRISON, NORMAN E. SHUMWAY, JOHN S. SCHROEDER
Journal: Circulation (1974)

Thirty-two of 59 patients undergoing cardiac transplantation at Stanford University Medical Center since January, 1968, have survived longer than three months. In 19 of these long-term survivors 47 episodes of late acute rejection occurred. In the first two months post-transplantation the incidence of acute rejection is one episode per 20.5 patient days, but between four and 12 months post-transplantation decreases to one episode per 200 patient days. Late acute rejection episodes are usually clinically mild and can be detected by electrocardiographic changes, evidence of mild graft dysfunction and characteristic histologic changes in tissue obtained by transvenous endomyocardial biopsy. Out-patient treatment with increased oral prednisone has successfully reversed 70% of these late acute rejection episodes, with the other 30% requiring more aggressive therapy. Late acute rejection or complications related to its treatment have contributed to the death of three long-term survivors and has been implicated as a causative factor in the development of graft coronary atherosclerosis in six patients in the earlier part of our series. However, the occurrence of acute rejection in the long-term cardiac transplant patient does not preclude good graft function and patient survival in the majority of patients.
EGFR Amplified and Overexpressing Glioblastomas and Association With Better Response to Adjuvant Metronomic Temozolomide
Authors: Manuela Cominelli, Salvatore Grisanti, Stefania Mazzoleni, Caterina Branca, Luciano Buttolo, Daniela Furlan, Barbara Liserre, Maria Fausta Bonetti, Daniela Medicina, Vilma Pellegrini, Michela Buglione, Roberto Liserre, Serena Pellegatta, Gaetano Finocchiaro, Piero Dalerba, Fabio Facchetti, Marina Pizzi, Rossella Galli, Pietro Luigi Poliani
Journal: JNCI Journal of the National Cancer Institute (2015)

Lack of robust predictive biomarkers, other than MGMT promoter methylation, makes temozolomide responsiveness in newly diagnosed glioblastoma (GBM) patients difficult to predict. However, we identified patients with long-term survival (≥35 months) within a group of newly diagnosed GBM patients treated with standard or metronomic adjuvant temozolomide schedules. We thus investigated possible molecular profiles associated with longer survival following temozolomide treatment. We investigated the association of molecular features with progression-free (PFS) and overall survival (OS). Human-derived GBM cancer stem cells (CSCs) were used to investigate in vitro molecular mechanisms associated with temozolomide responsiveness. Surgically removed recurrences allowed investigation of molecular changes occurring during therapy in vivo. Statistical analyses included one- and two-way analysis of variance, Student’s t test, Cox proportional hazards, and the Kaplan-Meier method. All statistical tests were two-sided. No association was found between survival and gene classifiers associated with different molecular GBM subtypes in the standard-treated group, while in metronomic-treated patients robust association was found between EGFR amplification/overexpression and PFS and OS (OS, EGFR-high vs low: hazard ratiodeath = 0.22, 95% confidence interval = 0.09 to 0.55, P = .001). The result for OS remained statistically significant after Bonferroni correction (Pinteraction < .0005). Long-term survival following metronomic temozolomide was independent from MGMT and EGFRvIII status and was more pronounced in EGFR-overexpressing GBM patients with PTEN loss. In vitro findings confirmed a selective dose- and time-dependent decrease in survival of temozolomide-treated EGFR+ human-derived glioblastoma CSCs, which occurred through inhibition of NF-κB transcriptional activity. In addition, reduction in EGFR-amplified cells, along with a statistically significant decrease in NF-κB/p65 expression, were observed in specimens from recurrent metronomic-treated EGFR-overexpressing GBM patients. EGFR-amplified/overexpressing glioblastomas strongly benefit from metronomic temozolomide–based therapies.
Amitriptyline and Imipramine Poisoning in Children
Authors: K. M. Goel, R. A. Shanks
Journal: BMJ (1974)

The increasing number of children admitted to this hospital with poisoning by tricyclic antidepressants is causing concern. Of 60 children admitted between January 1966 and July 1973, half were admitted in the last 18 months. In 60% of these patients the tricyclic compounds had been prescribed for nocturnal enuresis. One child aged 2 years and 4 months died of imipramine poisoning. It is imperative that all children with poisoning by tricyclic compounds, irrespective of the dosage, are admitted to hospital for continuous cardiac monitoring. Cardiac arrhythmias induced in children by amitriptyline and imipramine are prominent and dangerous.In the earlier years of this survey the antidepressants taken by children had usually been prescribed for adults, but recently they have been increasingly prescribed as a treatment for enuresis in children themselves. Medicine for a trivial complaint is unlikely to be regarded by parents as potentially dangerous and practitioners should therefore warn them accordingly; if, indeed, the transient effect of these potentially dangerous drugs upon the average case of bed-wetting in childhood can be justified.
Development of Löffler's endocarditis in FIP1L1‐PDGFRalpha‐positive hypereosinophilic syndrome despite continuous imatinib mesylate therapy and continuous complete remission
Authors: Jan Václavík, Tomáš Szotkowski, Martin Hutyra, Jiří Kozák, Jan Lukl, Miloš Táborský
Journal: American Journal of Hematology (2010)
Glomerular Filtration of Fluid and Macromolecules: The Renal Response To Injury
Authors: D A Maddox, B M Brenner
Journal: Annual Review of Medicine (1977)

Despite significant advances in the understanding of the immunological and mor­ phological aspects of a variety of disorders involving the kidney in which the glomerular filtration of water and macromolecules is affected, there has been, until recently, relatively little information concerning the mechanisms responsible for these changes in filtration. This is due in large part to the fact that glomeruli are seldom encountered as surface structures in the mammalian kidney, and are there­ fore inaccessible to direct study in vivo. This restriction has been overcome, how­ ever, with the recent discovery of a unique strain of Wistar rats (the so-called Munich-Wistar strain) with surface glomeruli. This advantage, together with tech­ nological and methodological developments allowing the direct assessment of hy­ draulic and oncotic pressures in the glomerular and periglomerular microcirculation (1, 2), has made possible an analysis of the determinants of fluid and solute filtration in this mammalian species. This review summarizes our current understanding of the transglomerular transport of fluid and macromolecules, both in the normal state and in response to renal injury.
New appointment to drug advisory body sparks controversy
Authors: C. Dyer
Journal: BMJ (2011)

Nine new members have been appointed to the UK Advisory Council on the Misuse of Drugs after a spate of resignations sparked by a row over threats to their independence by the previous Labour government.

A raft of members of the council, an independent body that advises the Home Office on drug policy, resigned in protest after the then Labour home secretary, Alan Johnson, sacked its head, David Nutt, in November 2009 over comments he made in an academic lecture ( BMJ 2009;339:b4563, doi:10.1136/bmj.b4563). In the lecture Professor Nutt said that tobacco and alcohol were more harmful than cannabis, ecstasy, and LSD and criticised the former home secretary Jacqui Smith for reclassifying cannabis from class C to class B.

But the appointment of one …
Sublingual immunotherapy: from biological extracts to recombinant allergens
Authors: P. Moingeon
Journal: Allergy (2006)

Sublingual vaccines based on biological extracts from various natural allergen sources are effective in the treatment of respiratory allergies. These vaccines comprise a complex mixture of proteins and glycoproteins that require dedicated standardization procedures to ensure batch‐to‐batch consistency. Because of the lack of correlation between the potency of an allergen extract and the quantity of major allergen content, standardization is achieved predominantly by determining the global IgE binding capacity of the extract in vitro . New proteomic technologies can be used to further characterize the most abundant proteins present in an extract. Second‐generation sublingual vaccines based on recombinant allergens are under development. The aim is to produce molecularly defined vaccines that exhibit superior efficacy, while allowing for simplified immunization schedules. In this approach, recombinant DNA technology is used to express highly purified allergens in their native (i.e. wild‐type) conformation. The recombinant allergens are then formulated with ad hoc adjuvants and/or mucoadhesive galenic excipients so that they specifically target oral Langerhans cells and induce allergen‐specific regulatory T cells.
TWO-DOSE HEPATITIS B IMMUNISATION REGIMEN FOR INFANTS
Authors: Marcello Piazza, Ludovico Picciotto, Riccardo Villari, Vincenzo Guadagnino, Raffaele Orlando, Vincenzo Macchia, AnnaMaria Memoli, Angela Vegnente, Salvatore Guida, Concetta Fusco
Journal: The Lancet (1985)
House dust mite allergens. A major risk factor for childhood asthma in Australia.
Authors: J K Peat, E Tovey, B G Toelle, M M Haby, E J Gray, A Mahmic, A J Woolcock
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

If house dust mite allergen (Der p I) is an important cause of asthma, there should be a direct relationship between level of exposure to this allergen and asthma severity. To examine this, we studied six large random samples of children in different regions of New South Wales, Australia. We measured recent wheeze by questionnaire, airway hyperresponsiveness (AHR) by histamine inhalation test and sensitization to house dust mites by skin prick tests. Current asthma was defined as the presence of recent wheeze and AHR. We measured Der p I levels in the beds of approximately 80 children in each region. In regions where Der p I levels were high, more children were sensitized to house dust mites, and these children had significantly more AHR and recent wheeze. After adjusting for sensitization to other allergens, we found that the risk of house dust mite-sensitized children having current asthma doubled with every doubling of Der p I level. There was a modest correlation between AHR and Der p I exposure in individuals (r = 0.23, p < 0.03). These data suggest that house dust mite allergens are an important cause of childhood asthma and that reducing exposure to these allergens could have a large public health benefit in terms of asthma prevention.
The role of insulin and glucagon in the regulation of basal glucose production in the postabsorptive dog.
Authors: A D Cherrington, J L Chiasson, J E Liljenquist, A S Jennings, U Keller, W W Lacy
Journal: Journal of Clinical Investigation (1976)

The aim of the present experiments was to determine the role of insulin and glucagon in the regulation of basal glucose production in dogs fasted overnight. A deficiency of either or both pancreatic hormones was achieved by infusin somatostatin (1 mug/kg per min), a potent inhibitor of both insulin and glucagon secretion, alone or in combination with intraportal replacement infusions of either pancreatic hormone. Infusion of somatostatin alone caused the arterial levels of insulin and glucagon to drop rapidly by 72+/-6 and 81+/-8%, respectively. Intraportal infusion of insulin and glucagon at rates of 400 muU/kg per min and 1 ng/kg per min, respectively, resulted in the maintenance of the basal levels of each hormone. Glucose production was measured using tracer (primed constant infusion of [3-3H]glucose) and arteriovenous difference techniques. Isolated glucagon deficiency resulted in a 35+/-5% (P less than 0.05) rapid and sustained decrease in glucose production which was abolished upon restoration of the plasma glucagon level. Isolated insulin deficiency resulted in a 52+/-16% (P less than 0.01) increase in the rate of glucose production which was abolished when the insulin level was restored. Somatostatin had no effect on glucose production when the changes in the pancreatic hormone levels which it normally induces were prevented by simultaneous intraportal infusion of both insulin and glucagon. In conclusion, in the anesthetized dog fasted overnight; (a) basal glucagon is responsible for at least one-third of basal glucose production, (b) basal insulin prevents the increased glucose production which would result from the unrestrained action of glucagon, and (c) somatostatin has no acute effects on glucose turnover other than those it induces through perturbation of pancreatic hormone secretion. This study indicates that the opposing actions of the two pancreatic hormones are important in the regulation of basal glucose production in the postabsorptive state.
THE FINAL TRIUMPH OF SCIENTIFIC MEDICINE.
Authors: NICHOLAS SENN
Journal: JAMA (1907)

"That is to be wise to see not merely that which lies before your feet, but to foresee even those things which are in the womb of futurity."—Terentius. Nations as well as individuals have their own peculiarities, their customs and habits, their own way of thinking and acting. The most characteristic feature of the American people in the eyes of the old world is the intense concern for the present and a relative disregard for the past and little concern for the future. The typical American concentrates his energies and devotes his time to accomplish what he has undertaken in the shortest possible space of time. We are a nation of intense workers, with little time for after- or forethought. Our country is new, its resources immense and only partially developed, and the possibilities for individual and corporate efforts unlimited. This intense activity, individual, corporate and national, has made our