tbuckley/cabot-search huggingface dataset:
Fibroblast Growth Factor Receptors Are Components of Autocrine Signaling Networks in Head and Neck Squamous Cell Carcinoma Cells
Authors: Marianne E. Marshall, Trista K. Hinz, Scott A. Kono, Katherine R. Singleton, Brady Bichon, Kathryn E. Ware, Lindsay Marek, Barbara A. Frederick, David Raben, Lynn E. Heasley
Journal: Clinical Cancer Research (2011)

We previously reported that a fibroblast growth factor (FGF) receptor (FGFR) signaling pathway drives growth of lung cancer cell lines of squamous and large cell histologies. Herein, we explored FGFR dependency in cell lines derived from the tobacco-related malignancy, head and neck squamous cell carcinoma (HNSCC).FGF and FGFR mRNA and protein expression was assessed in nine HNSCC cell lines. Dependence on secreted FGF2 for cell growth was tested with FP-1039, an FGFR1-Fc fusion protein. FGFR and epidermal growth factor receptor (EGFR) dependence was defined by sensitivity to multiple inhibitors selective for FGFRs or EGFR.FGF2 was expressed in eight of the nine HNSCC cell lines examined. Also, FGFR2 and FGFR3 were frequently expressed, whereas only two lines expressed FGFR1. FP-1039 inhibited growth of HNSCC cell lines expressing FGF2, identifying FGF2 as an autocrine growth factor. FGFR inhibitors selectively reduced in vitro growth and extracellular signal-regulated kinase signaling in three HNSCC cell lines, whereas three distinct lines exhibited responsiveness to both EGFR and FGFR inhibitors. Combinations of these drugs yielded additive growth inhibition. Finally, three cell lines were highly sensitive to EGFR tyrosine kinase inhibitors (TKI) with no contribution from FGFR pathways.FGFR signaling was dominant or codominant with EGFR in six HNSCC lines, whereas three lines exhibited little or no role for FGFRs and were highly EGFR dependent. Thus, the HNSCC cell lines can be divided into subsets defined by sensitivity to EGFR and FGFR-specific TKIs. FGFR inhibitors may represent novel therapeutics to deploy alone or in combination with EGFR inhibitors in HNSCC.
Immunomodulatory drugs reorganize cytoskeleton by modulating Rho GTPases
Authors: Yibing Xu, Jianwu Li, Gregory D. Ferguson, Frank Mercurio, Gody Khambatta, Lisa Morrison, Antonia Lopez-Girona, Laura G. Corral, David R. Webb, Brydon L. Bennett, Weilin Xie
Journal: Blood (2009)
Epidermal Growth Factor Receptor Mutation and p53 Overexpression during the Multistage Progression of Small Adenocarcinoma of the Lung
Authors: Seol Bong Yoo, Jin-Haeng Chung, Hyun Ju Lee, Choon-Taek Lee, Sanghoon Jheon, Sook Whan Sung
Journal: Journal of Thoracic Oncology (2010)
Frozen Desserts and Glycemic Response in Well-Controlled NIDDM Patients
Authors: Julie Bukar, Nicholas H E Mezitis, Vassiliki Saitas, F Xavier Pi-Sunyer
Journal: Diabetes Care (1990)

Fructose is known to elicit a lower glycemic response than sucrose, and high-fructose desserts have been recommended for a diabetic diet. We compared a cholesterol-free tofu-based frozen dessert (TFD) containing high-fructose corn syrups with a dairy-based sucrose-sweetened ice cream (IC). Six male and six female non-insulin-dependent diabetic patients (mean age 51 yr, mean ideal body weight 143%, fasting blood glucose &amp;lt;160 mg/dl) with well-controlled diabetes and managed on oral hypoglycemic agents were studied. Subjects underwent three trials. In the first trial they ingested 50 g glucose, and in the next two trials they ingested 50-g carbohydrate equivalents of either TFD or IC in random sequence. Venous blood was drawn at intervals during the 3-h trials for glucose and insulin determinations. Fasting plasma glucose was not statistically different between IC and TFD trials (130 vs. 121 mg/dl). Peak glucose responses were at 120 min in both trials (190 mg/dl for IC and 222 mg/dl for TFD), with those for TFD being significantly higher (P &amp;lt; 0.01). Mean glucose area and glycemic index for TFD were significantly greater than for IC (P &amp;lt; 0.01 and P &amp;lt; 0.03, respectively). There was no significant difference between mean insulin areas. In summary, the TFD, which contains soybean curd and high-fructose corn syrup, might have been expected to produce more satisfactory postprandial blood glucose levels than IC, which contains sucrose, yet a higher glycemic response was elicited. This is related to the substantial amount of total glucose in this “fructose” dessert. The study highlights the error of using individual components of a commercially prepared food to recommend a product for diabetic patients.
Clarithromycin Prevents Smoke-induced Emphysema in Mice
Authors: Yutaka Nakanishi, Dale Kobayashi, Yasuo Asano, Takanobu Sakurai, Masato Kashimura, Shigeru Okuyama, Yukio Yoneda, Steven D. Shapiro, Kiyoshi Takayama
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Modulating the low-grade chronic inflammation in chronic obstructive pulmonary disease remains challenging. Clarithromycin (CAM), a macrolide antibiotic, reportedly ameliorates chronic inflammation via mechanisms independent of its antibacterial activity.Objectives: The aim of this study was to examine whether CAM can prevent or reduce emphysema induced by chronic cigarette smoke exposure.Methods: Mice were exposed to cigarette smoke daily for 6 months and treated with orally administered CAM at doses of 25 to 100 mg/kg twice a day throughout the course of the experiment to test the preventive effects. The administration of CAM at 50 or 100 mg/kg was performed during the second half of a 6-month exposure period to assess the therapeutic effects. Histologic analysis was performed to evaluate the effect of CAM.Measurements and Main Results: CAM treatment for 6 months decreased airspace enlargement and the destruction of the alveolar walls and impaired the accumulation of macrophages in bronchoalveolar lavage fluid in a dose-related fashion. The administration of clarithromycin at 100 mg/kg in the therapeutic protocol reduced emphysema compared with the smoke-exposed group without treatment. An immunohistologic analysis revealed that CAM reduced the number of F4/80-positive macrophages in the lung parenchyma. In an in vitro test, CAM at 5 to 20 μM directly suppressed the activation of macrophages stimulated with tumor necrosis factor-α.Conclusions: Our data demonstrated that CAM at a clinically achievable dose prevented cigarette smoke–induced emphysema by modulating lung inflammation. This study supports the possibility that low-dose CAM treatment might provide a new therapeutic strategy for chronic obstructive pulmonary diseases.
Inducible nitric oxide synthase expression in chronic viral hepatitis. Evidence for a virus-induced gene upregulation.
Authors: P L Majano, C García-Monzón, M López-Cabrera, E Lara-Pezzi, E Fernández-Ruiz, C García-Iglesias, M J Borque, R Moreno-Otero
Journal: Journal of Clinical Investigation (1998)

Increased nitric oxide (NO) production may contribute to the pathological changes featuring in some inflammatory diseases, but the role of NO in chronic viral hepatitis is still unknown. We compared the inducible NO synthase (NOS2) expression in the liver of patients with chronic viral hepatitis with that of both nonviral liver disease and histologically normal liver. NOS2 expression was assessed by immunohistochemical and in situ hybridization studies of liver biopsy sections. An intense hepatocellular NOS2 reactivity was detected in chronic viral hepatitis, whereas it was weakly or not observed in nonviral liver disease or normal liver, respectively. In addition, we determined whether the hepatitis B virus (HBV) might regulate the synthesis of this enzyme. NOS2 mRNA and protein levels as well as enzyme activity were assessed in cytokine-stimulated HBV-transfected and untransfected hepatoma cells. Transfection with either HBV genome or HBV X gene resulted in induction of NOS2 mRNA expression, and the maximal induction of this transcript and NO production was observed in cytokine-stimulated HBV-transfected cells. These results indicate that hepatotropic viral infections are able to upregulate the NOS2 gene expression in human hepatocytes, suggesting that NO may mediate important pathogenic events in the course of chronic viral hepatitis.
Fee-for-Service Health Maintenance Organizations
Authors: Richard H. Egdahl
Journal: JAMA (1979)

COST containment is now the nation's overriding priority in the issue of health care. The continuing increase in the percentage of gross national product devoted to health care and the continued stresses on state and federal budgets combine to ensure that the demand for effective control of health care costs will persist and probably escalate.<sup>1</sup>For the first time, the appropriate national allocation of expenses for medical diagnostic and treatment procedures is being seriously weighed against other pressing economic needs. The term "rationing" is being used increasingly in discussions of health care. Physicians' orders directly or indirectly account for some 70% of health care costs<sup>2</sup>and are, therefore, a logical focus of attempts to contain costs. Traditional insurance programs have failed to engage physicians, through direct financial incentives, in the difficult but necessary process of scrutinizing the massive expenditures they initiate. Traditional insurance programs have encouraged high-cost services
Androgen Activity as a Risk Factor for Impaired Glucose Tolerance in Postmenopausal Women
Authors: Hillevi Larsson, Bo Ahrén
Journal: Diabetes Care (1996)

OBJECTIVE Low sex hormone–binding globulin (SHBG) has been proposed as a risk factor for NIDDM development in women. Our aim was to study the relationship between SHBG and androgen activity and glucose tolerance, as well as insulin sensitivity, in women with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS We studied 22 women with IGT and 46 women with normal glucose tolerance (NGT) aged 57–59 years. Free testosterone (androgen activity) was determined as the testosterone-to-SHBG ratio. A World Health Organization 75-g oral glucose tolerance test (OGTT) was performed, and insulin sensitivity was measured with a euglycemic-hyperinsulinemic clamp. RESULTS Fasting glucose (P = 0.021), 2-h blood glucose after the OGTT (P &amp;lt; 0.001), and fasting insulin (P = 0.009) were higher in the IGT group, while insulin sensitivity did not differ significantly between the two groups (P = 0.065). We found that SHBG levels were lower in the IGT group (P = 0.004), while the testosterone-to-SHBG ratio was higher in the IGT than in the NGT group (P = 0.004). Insulin sensitivity correlated negatively with testosterone-to-SHBG ratio in both groups. The correlation was higher in the IGT (r = −0.67, P = 0.001) than in the NGT group (r = −0.29, P = 0.047). In contrast, the 2-h blood glucose correlated with testosterone-to-SHBG ratio in the IGT (r = 0.66, P = 0.001) but not the NGT group (r = −0.04, NS). CONCLUSIONS Postmenopausal women with IGT have higher androgen activity than women with NGT, and the androgen activity correlates with the degree of glucose intolerance in IGT. Furthermore, in women with IGT, who have a high risk of NIDDM development, androgen activity seems to have an enhanced negative influence on insulin sensitivity. Therefore, androgen activity appears to be a risk factor for IGT.
THE HABIT OF ATTENDING MEDICAL MEETINGS
Authors: MARCUS FEINGOLD
Journal: JAMA (1925)

People in all walks of life and all kinds of occupations gather periodically for the purpose of discussing problems common to the members of these groups, to gain experience and knowledge from the experience of others and thus to improve the affairs of each participant. In a profession such as ours, whose principal and primary object is to help and benefit our fellow men, this gain in knowledge is almost incumbent on us, because it is so essential for the good of those entrusted to our care. He who attends meetings regularly, even if he does not impart his experience to others, must leave a better man, better by the knowledge he has absorbed while listening to others. How much more valuable to the community is he who imparts his knowledge and thoughts at the meeting in a discussion or in a paper. He gives to others his thoughts and
Detection and Prevalence of IUD-Associated Actinomyces Colonization and Related Morbidity
Authors: Joseph F. Valicenti
Journal: JAMA (1982)

Cervical Papanicolaou smears from 69,925 women were screened prospectively for the presence of Actinomyces israelii. The organism was not identified in non-intrauterine (contraceptive) device (IUD)-wearers. The prevalence of A israelii among IUD wearers ranged from 1.6% (general population) to 5.3% (clinic population). Protracted IUD use seemed to predispose to a higher incidence of infection. Direct immunofluorescence proved to be a more accurate and specific method of identification when compared with conventional light microscopy and anaerobic culture. Two of 112 women with direct immunofluorescence-proved A israelii had significant clinical infections. It appears that in the vast majority of cases, IUD-associated Actinomyces colonization produces only a superficial infestation. Conservative management is suggested for asymptomatic patients with cytologically detected Actinomyces to include removal of the IUD and repeated Papanicolaou smear after the next menstrual period.Cervical Papanicolaou smears from a population of 69,700 women including 6450 IUD users were prospectively analyzed for the presence of Actinomyces israelii during a 20-month period. No clinical evidence of actinomycete-like organisms was found in any non-IUD wearers. In IUD users, 212 Papanicolaou stained smears or 1.6% were found positive with actinomycetes when examined by light microscopy. The length of time of IUD insertion averaged 6.1 years, with a range from 6 months to 14 years. A 2nd study of 225 family planning clinic patients revealed a 5.3% prevalence of Actinomyces israelii among IUD users. Average length of IUD use was 6.5 years, with a range of 1-14 years. Direct immunofluorescence appeared more accurate for diagnosis than light microscopy or Pap smears. The study suggests that protracted IUD use predisposes to a higher incidence of infection. No specific type of IUD was associated with higher risk. Only 2 patients had clinically significant infection and most were asymptomatic, suggesting that the organism causes a superficial infestation of the endometrium which is shed with the menstrual period. Full diagnostic workup with appropriate therapy is required for the management of clinically proven infection, while asymptomatic women with cytological evidence of Actinomyces may require conservative management, including IUD removal and repeated Pap smears.
The case for licensing cytosine now for smoking cessation is overwhelming
Authors: J. A. Stapleton
Journal: BMJ (2013)

Prochaska and colleagues’ excellent overview of cytisine in smoking cessation fails to highlight the compelling cost-benefit evidence on why this effective, safe, and inexpensive drug should be licensed immediately worldwide.1 This case has already been made,2 and readers interested in this drug and the inflexibility of Western regulatory systems are directed to this article. …
Noninvasive ventilation improved dyspnea but did not reduce short-term mortality in acute cardiogenic pulmonary edema
Authors: Gerasimos Filippatos
Journal: Annals of Internal Medicine (2008)

ACP Journal Club16 December 2008Noninvasive ventilation improved dyspnea but did not reduce short-term mortality in acute cardiogenic pulmonary edemaGerasimos Filippatos, MD, Alexander Mebazaa, MD, Josep Masip, MDGerasimos Filippatos, MDAthens University Hospital, Athens, Greece (G.F.)Search for more papers by this author, Alexander Mebazaa, MDUniversity Paris 7, Paris, France (A.M.)Search for more papers by this author, Josep Masip, MDUniversity of Barcelona, Barcelona, Spain (J.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-149-12-200812160-02009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationGray A, Goodacre S, Newby DE, et al. Noninvasive ventilation in acute cardiogenic pulmonary edema. N Engl J Med. 2008;359:142-51. https://pubmed.ncbi.nlm.nih.gov/18614781Clinical Impact RatingsEmergency Med: Hospitalists: Cardiology: Critical Care: Pulmonology: Reference1 Masip J, Roque M, Sánchez B, et al. Noninvasive ventilation in acute cardiogenic pulmonary edema: systematic review and meta-analysis. JAMA. 2005;294:3124-30. [PMID: 16380593] Google Scholar Author, Article, and Disclosure InformationAuthors: Gerasimos Filippatos, MD; Alexander Mebazaa, MD; Josep Masip, MDAffiliations: Athens University Hospital, Athens, Greece (G.F.)University Paris 7, Paris, France (A.M.)University of Barcelona, Barcelona, Spain (J.M.) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 December 2008Volume 149, Issue 12Page: JC6-9KeywordsBlood pressureContinuous positive airway pressureCritical careDeath ratesDyspneaEdemaHospitalistsHypercapniaIntensive care unitsIntubationNoninvasive ventilationOxygenPopulation statisticsPositive pressure ventilationPulmonary medicineRespiratory failureRespiratory rateThoraxVentilators ePublished: 10 March 2020 Issue Published: 16 December 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Mast Cells Control Neutrophil Recruitment during T Cell–Mediated Delayed-Type Hypersensitivity Reactions through Tumor Necrosis Factor and Macrophage Inflammatory Protein 2
Authors: Tilo Biedermann, Manfred Kneilling, Reinhard Mailhammer, Konrad Maier, Christian A. Sander, George Kollias, Steven L. Kunkel, Lothar Hültner, Martin Röcken
Journal: The Journal of Experimental Medicine (2000)

Polymorphonuclear leukocytes (PMNs) characterize the pathology of T cell–mediated autoimmune diseases and delayed-type hypersensitivity reactions (DTHRs) in the skin, joints, and gut, but are absent in T cell–mediated autoimmune diseases of the brain or pancreas. All of these reactions are mediated by interferon γ–producing type 1 T cells and produce a similar pattern of cytokines. Thus, the cells and mediators responsible for the PMN recruitment into skin, joints, or gut during DTHRs remain unknown. Analyzing hapten-induced DTHRs of the skin, we found that mast cells determine the T cell–dependent PMN recruitment through two mediators, tumor necrosis factor (TNF) and the CXC chemokine macrophage inflammatory protein 2 (MIP-2), the functional analogue of human interleukin 8. Extractable MIP-2 protein was abundant during DTHRs in and around mast cells of wild-type (WT) mice but absent in mast cell–deficient WBB6F1-KitW/KitW-v (KitW/KitW-v) mice. T cell–dependent PMN recruitment was reduced &amp;gt;60% by anti–MIP-2 antibodies and &amp;gt;80% in mast cell–deficient KitW/KitW-v mice. Mast cells from WT mice efficiently restored DTHRs and MIP-2–dependent PMN recruitment in KitW/KitW-v mice, whereas mast cells from TNF−/− mice did not. Thus, mast cell–derived TNF and MIP-2 ultimately determine the pattern of infiltrating cells during T cell–mediated DTHRs.
The Regulation of Fat Mobilization in Man: In Vitro Studies Using Isolated Human Adipose Tissue Cells.
Authors: Thomas W. Burns
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970The Regulation of Fat Mobilization in Man: In Vitro Studies Using Isolated Human Adipose Tissue Cells.Thomas W. Burns, M.D., F.A.C.P.Thomas W. Burns, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-790_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn spite of the intensive research interest shown it, the problem of the manner in which fat mobilization is regulated remains unsolved. It would seem reasonable that one or more humeral or neurohumeral substances signal the breakdown of stored triglyceride and release of fatty acids. In an attempt to gain information relative to human lipolysis, isolated cells were prepared from human adipose tissue obtained from donors undergoing surgery. Cells were incubated with test substances, and glycerol release was used as an index of lipolysis. They were found to respond to fractions of human pituitary powder with thyroid-stimulating hormone (TSH) activity... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 790-790KeywordsAdipose tissueCellsFatsFatty acidsSurgeryThyroid-stimulating hormone Issue Published: 1 May 1970 PDF DownloadLoading ...
The Endocrine Lung in Health and Disease
Authors: Tee Lamont Guidotti
Journal: JAMA (1985)

This comprehensive and authoritative multiauthored text and reference is a sign that its topic has reached a stage of scientific maturity. It is a valuable source of information, presents a clearly defined point of view, and is generally well written and minimally repetitious. A decade ago, the usual concept of the lung and its functions included a role as an accessory endocrine organ and acknowledged certain paracrine functions comparable to those of the gut and the skin. The accessory endocrine functions of greatest visibility then were the enzymatic conversion of angiotensin I and the efficient clearance of circulating biogenic amines. This led to a falsely limited view of the lung as a passive recipient and modifier of hormones synthesized elsewhere. On the other hand, the production and action of local paracrine mediators were perceived mainly as part of the mechanistic explanation of bronchoreactivity, pulmonary vascular phenomena, and immunopathologies of the
An animal model for the chronic study of ventricular repolarisation and refractory period
Authors: B S. MANLEY, E. M. CHONG, C. WALTON, A. P ECONOMIDES, S. M COBBE
Journal: Cardiovascular Research (1989)

We have developed a simple model permitting stable, chronic measurements of ventricular repolarisation and refractory period to be made in conscious, unsedated, unrestrained animals. The model utilises the ventricular paced evoked response, recorded from permanent pacemaker electrodes implanted into the right ventricle of New Zealand White rabbits. After a "bedding in" period of 18-21 d, measured variables are stable for long periods; the stimulus to T wave interval of the evoked response remains stable up to at least 150 d after electrode insertion. The principal advantage of the model lies in the control of heart rate by pacing, eliminating the requirement for unreliable methods of correction of repolarisation data for sinus rate. Surgical techniques are straightforward. The model can also be used for studies involving recordings of the intrinsic (non-paced) intracardiac electrogram, as the quality of the signal obtained is consistently superior to standard methods of recording the electrocardiogram in animals. The stimulus-T interval of the paced evoked response has been found to correlate significantly (r = 0.96) with action potential duration measured by transmembrane microelectrode recordings in the isolated, arterially perfused interventricular septum.