tbuckley/cabot-search huggingface dataset:
Activation of Vascular Bone Morphogenetic Protein Signaling in Diabetes Mellitus
Authors: Kristina I. Boström, Medet Jumabay, Aleksey Matveyenko, Susanne B. Nicholas, Yucheng Yao
Journal: Circulation Research (2010)

Rationale: Diabetes mellitus is frequently complicated by cardiovascular disease, such as vascular calcification and endothelial dysfunction, which have been associated with bone morphogenetic proteins (BMPs). Objective: To determine whether hyperglycemia in vitro and diabetes in vivo promote vascular BMP activity and correlate with vascular calcification. Methods and Results: Increased glucose augmented expression of BMP-2 and BMP-4; the BMP inhibitors matrix Gla protein (MGP) and Noggin; activin-like kinase receptor (ALK)1, -2, -3 and -6; the BMP type 2 receptor; and the vascular endothelial growth factor in human aortic endothelial cells (HAECs). Diabetes induced expression of the same factors in the aortic wall of 3 animal models of diabetes, Ins2 Akita/+ mice, db/db mice, and HIP rats (rats transgenic for human islet amyloid polypeptide), representative of types 1 and 2 diabetes. Conditioned media from glucose-treated HAECs increased angiogenesis in bovine aortic endothelial cells, as mediated by BMP-4, and osteogenesis in calcifying vascular cells, as mediated by BMP-2. BMP-4, MGP, ALK1, and ALK2 were predominantly expressed on the endothelial side of the aorta, and small interfering RNA experiments showed that these genes were regulated as a group. Diabetic mice and rats showed a dramatic increase in aortic BMP activity, as demonstrated by SMAD1/5/8 phosphorylation. This was associated with increased osteogenesis and calcium accumulation. These changes were prevented in the Ins2 Akita/+ mice by breeding them with MGP transgenic mice, which increased aortic BMP inhibition. Conclusions: Hyperglycemia and diabetes activate vascular BMP activity, which is instrumental in promoting vascular calcification and may be limited by increasing BMP inhibition.
Teenage pregnancy and risk of adverse perinatal outcomes associated with first and second births: population based retrospective cohort study
Authors: G. C S Smith, J. P Pell
Journal: BMJ (2001)

To determine whether first and second births among teenagers are associated with increased risk of adverse perinatal outcomes after confounding variables have been taken into account.Population based retrospective cohort study using routine discharge data for 1992-8.Scotland.Stillbirth, preterm delivery, emergency caesarean section, and small for gestational age baby among non-smoking mothers aged 15-19 and 20-29.The 110 233 eligible deliveries were stratified into first and second births. Among first births, the only significant difference in adverse outcomes by age group was for emergency caesarean section, which was less likely among younger mothers (odds ratio 0.5, 95% confidence interval 0.5 to 0.6). Second births in women aged 15-19 were associated with an increased risk of moderate (1.6, 1.2 to 2.1) and extreme prematurity (2.5, 1.5 to 4.3) and stillbirth (2.6, 1.3 to 5.3) but a reduced risk of emergency caesarean section (0.7, 0.5 to 1.0).First teenage births are not independently associated with an increased risk of adverse pregnancy outcome and are at decreased risk of delivery by emergency caesarean section. However, second teenage births are associated with an almost threefold risk of preterm delivery and stillbirth.
Biological effects of short-term, high-concentration exposure to methyl isocyanate. I. Study objectives and inhalation exposure design.
Authors: D E Dodd, F R Frank, E H Fowler, C M Troup, R M Milton
Journal: Environmental Health Perspectives (1987)

Early reports from India indicated that humans were dying within minutes to a few hours from exposure to methyl isocyanate (MIC). Attempts to explain the cause(s) of these rapid mortalities is where Union Carbide Corporation concentrated its post-Bhopal toxicologic investigations. The MIC studies involving rats and guinea pigs focused primarily on the consequences of acute pulmonary damage. All MIC inhalation exposures were acute, of short duration (mainly 15 min), and high in concentration (ranging from 25-3506 ppm). MIC vapors were statically generated in a double chamber exposure design. Precautionary measures taken during exposures are discussed. Guinea pigs were more susceptible than rats to MIC exposure-related early mortality. A greater than one order of magnitude difference was observed between an MIC concentration that caused no early mortality in rats (3506 ppm) and an MIC concentration that caused partial (6%) early mortality in guinea pigs (225 ppm) for exposures of 10 to 15 min duration. For both species, the most noteworthy clinical signs during exposure were lacrimation, blepharospasm, and mouth breathing. Fifteen minute LC50 tests with 14-day postexposure follow-up were conducted, and the LC50 (95% confidence limit) values were 171 (114-256) ppm for rats and 112 (61-204) ppm for guinea pigs. Target exposure concentrations for the toxicologic investigations of MIC-induced early mortality were established. A short summary of pertinent results of Union Carbide Corporation's post-Bhopal toxicologic investigations is presented.
Same-sex rape of nonincarcerated men
Authors: Peter F. Goyer, Henry C. Eddleman
Journal: American Journal of Psychiatry (1984)

Psychiatric evaluations of nonincarcerated adult male victims of same-sex rape have been reported infrequently in the literature. In their work with a population of military men, the authors reviewed the psychiatric evaluations of 13 such victims, ages 18 to 31, over a 2-year period. Most of the men reported mood disturbances (e.g., fear, depression, anger), somatic disturbances (e.g., in sleep, appetite, digestion), and difficulties in peer relationships following the assault, and almost half of these victims reported that they had experienced subsequent sexual problems.
The diastolic dilemma.
Authors: D Short
Journal: BMJ (1976)

There is hopeless confusion in the English-speaking world about the determination of the diastolic blood pressure by sphygmo manometry. In Britain generations of students have been taught that the point of muffling of the Korotkow sounds (often referred to as the fourth phase) should be taken as the index of diastolic pressure, and until recently all the major British studies on hypertension have been based on this practice. Workers in the United States, however, have long favoured the point of disappearance of the Korotkow sounds (the fifth phase) as the index of diastolic pressure. This disagreement was evident in the joint report of the Cardiac Society of Great Britain and Ireland and the American Heart Association (AHA)' published in 1939 and became explicit in the recommendations of the Scientific Council of the AHA2 in 1951. Many important American studies on the epidemiology and treatment of hypertension used fifth phase recordings-notably the Build and Blood Pressure Study of the Society of Actuaries of Chicago3 and the Veterans Administration Co-operative study on antihypertensive agents.4 The Framingham study,5 on the other hand, used fourth phase recording. In 1967 agreement seemed to have been reached when a subcommittee of the Postgraduate Education Committee of the AHA concluded that the fourth phase should be regarded as the best index of diastolic pressure. But in 1972, or possibly earlier, the Hypertension Detection and Follow-up Programme Collaborative Group in the USA decided to use the fifth phase,7 and it has recently been intimated8 that the fifth phase is to be used in the British Medical Research Council's mild hypertension treatment trial. So now the confusion is worse than ever. Two questions arise: Firstly, Is the issue important ? Secondly, What can be done about it ?
Fatal Aplastic Anemia with Piperacetazine Therapy
Authors: Kai-Yiu Yeung, Milton Corn
Journal: Annals of Internal Medicine (1974)

Letters1 September 1974Fatal Aplastic Anemia with Piperacetazine TherapyKAI-YIU YEUNG, M.D., F.R.C.P. (C), MILTON CORN, M.D., F.A.C.P.KAI-YIU YEUNG, M.D., F.R.C.P. (C)Search for more papers by this author, MILTON CORN, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-81-3-411 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Piperacetazine, a piperidine derivative of phenothiazine introduced in 1961 for treatment of schizophrenia, has been shown to be an effective tranquilizer, safe for short- and long-term therapy. Reported hematologic complications have been infrequent and restricted to mild transient decrease in hemoglobin (one case) (1); and reversible leukopenia and thrombocytopenia (2). Recently, we saw a patient who developed fatal aplastic anemia receiving piperacetazine, and no other medication, for 17 months. Review of the English journal literature and personal communication with Dow Chemical Company*uncovered no previous report of this association. We, therefore, report this case to...References1. GALLANTBISHOP DM: Quide vs. Mellaril In chronic schizophrenic patients. Curr Ther Res 14:10-16, 1972 MedlineGoogle Scholar2. : Evaluation of a new antipsychotic agent, piperacetazine (Quide). Jama 215:783-784, 1971 CrossrefMedlineGoogle Scholar3. SHELDONKINGSTONMCRAE JWC: Aplastic anemia and agranulocytosis following chlorpromazine therapy. Aust Med J 1:130-131, 1960 CrossrefGoogle Scholar4. BHASKARANSUBRAHMANYANNAND KPD: Fatal bone marrow aplasia complicating prochlorperazine therapy. Am J Psychiatry 119:373-374, 1962 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: KAI-YIU YEUNG, M.D., F.R.C.P. (C); MILTON CORN, M.D., F.A.C.P.Affiliations: *Personal communication from D. B. Johns, Medical Director, Dow Chemical Co., Zionsville, Indiana. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1974Volume 81, Issue 3Page: 411-411KeywordsAplastic anemiaHemoglobinPhenothiazineSchizophrenia ePublished: 1 December 2008 Issue Published: 1 September 1974 PDF downloadLoading ...
Relationship to Blood Pressure of Combinations of Dietary Macronutrients
Authors: Jeremiah Stamler, Arlene Caggiula, Greg A. Grandits, Marcus Kjelsberg, Jeffrey A. Cutler
Journal: Circulation (1996)

Background Elevated blood pressure remains a widespread major impediment to health. Obesity and specific dietary factors such as high salt and alcohol intake and low potassium intake adversely affect blood pressure. It is a reasonable hypothesis that additional dietary constituents, particularly macronutrients, may also influence blood pressure. Methods and Results Participants were 11 342 middle-aged men from the Multiple Risk Factor Intervention Trial (MRFIT). Data from repeat 24-hour dietary recalls (four to five per person) and blood pressure measurements at six annual visits were used to assess relationships, singly and in combination, of dietary macronutrients to blood pressure, adjusted for multiple possible confounders (demographic, dietary, and biomedical). Multiple linear regression was used to assess diet–blood pressure relations in two MRFIT treatment groups (special intervention and usual care), with adjustment for confounders, pooling of coefficients from the two groups (weighted by inverse of variance), and correction of coefficients for regression-dilution bias. In multivariate regression models, dietary cholesterol (milligrams per 1000 kilocalories), saturated fatty acids (percent of kilocalories), and starch (percent of kilocalories) were positively related to blood pressure; protein and the ratio of dietary polyunsaturated to saturated fatty acids were inversely related to blood pressure. These macronutrient–blood pressure findings were obtained in analyses that controlled for body mass, dietary sodium and ratio of sodium to potassium, and alcohol intake, each positively related to blood pressure, and intake of potassium and caffeine, both inversely related to blood pressure. Conclusions These data support the concept that multiple dietary factors influence blood pressure; hence, broad improvements in nutrition can be important in preventing and controlling high-normal and high blood pressure.
New movie monsters from the medical world
Authors: L. S. King
Journal: JAMA (1972)

Movies fall into many different categories: historical extravaganzas, mysteries, adaptations of literary classics, slapstick comedy, drawing room (or bedroom) farces, Westerns, the pornies, science fiction, horror stories, gangster films, and many others. For a great many movie goers the horror stories make a particularly strong appeal. There is a vast chasm between the science fiction and the horror films. Even though some of the props may be comparable, with the same kind of complicated apparatus, the same kind of scientist, whether austere or jovial, mad or sane, the physiological effects on the spectator are different. Science fiction movies produce impulses which tend to ripple across the cerebral cortex, skipping lightly from one Brodmann area to another, occasionally burrowing down as deep as the second or third cell layer, and even sending an occasional hit-and-run impulse into the thalamus. But the horror movies set up reverberations through the gut, tie knots
Heterogeneity of 5′-Nucleotidase Activity in Lymphocytes in Chronic Lymphocytic Leukemia
Authors: John Lopes, Dorothea Zucker-Franklin, Robert Silber
Journal: Journal of Clinical Investigation (1973)

The specific activity of 5'-nucleotidase was determined in lymphocyte plasma membranes from 14 normal subjects and 10 patients with chronic lymphocytic leukemia (CLL). Whereas the enzyme was present in the preparation from normal lymphocytes, in 7 out of 10 CLL patients the membranes had markedly decreased or no detectable 5'-nucleotidase activity. The lack of this activity from the lymphocytes of most patients with CLL constitutes an alteration in a plasma membrane enzyme from the normal cell. The presence of the enzyme in the lymphocytes of some patients with CLL and its decrease in others provide further evidence for biochemical heterogeneity among patients with this disorder.
Abstract 5131: Modeling of EMT/MET transitions in breast cancer stem cells.
Authors: Mary E. Sehl, Miki Shimada, Kenneth Lange, Max S. Wicha
Journal: Cancer Research (2013)

Abstract Background: Recent studies suggest that breast cancer stem-like cells (BCSCs) exist in two freely interconvertible states: an EMT- and an MET-like state, and that conversion between these two states is regulated by both intracellular and microenvironmental signaling (Liu et al. 2012, Korkaya et al. 2012). Using a mathematical model, we quantify rates of transition between the EMT and MET-like states. We further explore BCSC behavior in response to alterations in microenvironmental signaling and examine key regulators of BCSC population dynamics. Methods: We employ a continuous-time Markov chain model to quantify rates of transition between the EMT and MET-like state for BCSCs. Our data-based modeling approach employs parameter estimates derived from mouse xenograft experiments from the Wicha laboratory (Liu et al. 2012) to estimate the equilibrium EMT- and MET-like state distributions. We expand our model to simulate BCSC population counts and EMT and MET state transitions in response to alterations in the complex regulatory network involving IL-6, HER2, miRNA, NF-κB, and TGF-β signaling. Results: We estimate the rate of BCSC transition from an EMT- to MET-like state to be 0.08 per cell per day, and the rate of transition from an MET- to EMT-like state to be 0.013 per cell per day. Simulation studies examining the effects of abrogating microenvironmental signals individually and in combinations revealed that slowing both self-renewal rate and the rate of transition from an MET- to EMT-like state is essential to eradicating the total BCSC population. The fastest decline in the BCSC population was observed when IL-6 is inhibited and the activation of NF-κB via HER2 signaling and IL-6 feedback was blocked. Conclusions: Rates of transition between EMT- and MET-like states are estimated to occur frequently and these events are much more likely than dedifferentiation. Predictions from our mathematical model match experimental data (Korkaya et al. 2012) showing the efficacy of combined HER2 and IL-6 blockade in reducing the BCSC population. Citation Format: Mary E. Sehl, Miki Shimada, Kenneth Lange, Max S. Wicha. Modeling of EMT/MET transitions in breast cancer stem cells. [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 5131. doi:10.1158/1538-7445.AM2013-5131
Role of the epithelial cell rests of <scp>M</scp>alassez in the development, maintenance and regeneration of periodontal ligament tissues
Authors: Jimin Xiong, Stan Gronthos, P. Mark Bartold
Journal: Periodontology 2000 (2013)

Abstract Periodontitis is a highly prevalent inflammatory disease that results in damage to the tooth‐supporting tissues, potentially leading to tooth loss. Periodontal tissue regeneration is a complex process that involves the collaboration of two hard tissues (cementum and alveolar bone) and two soft tissues (gingiva and periodontal ligament). To date, no periodontal‐regenerative procedures provide predictable clinical outcomes. To understand the rational basis of regenerative procedures, a better understanding of the events associated with the formation of periodontal components will help to establish reliable strategies for clinical practice. An important aspect of this is the role of the Hertwig's epithelial root sheath in periodontal development and that of its descendants, the epithelial cell rests of M alassez, in the maintenance of the periodontium. An important structure during tooth root development, the Hertwig's epithelial root sheath is not only a barrier between the dental follicle and dental papilla cells but is also involved in determining the shape, size and number of roots and in the development of dentin and cementum, and may act as a source of mesenchymal progenitor cells for cementoblasts. In adulthood, the epithelial cell rests of M alassez are the only odontogenic epithelial population in the periodontal ligament. Although there is no general agreement on the functions of the epithelial cell rests of M alassez, accumulating evidence suggests that the putative roles of the epithelial cell rests of M alassez in adult periodontal ligament include maintaining periodontal ligament homeostasis to prevent ankylosis and maintain periodontal ligament space, to prevent root resorption, to serve as a target during periodontal ligament innervation and to contribute to cementum repair. Recently, ovine epithelial cell rests of M alassez cells have been shown to harbor clonogenic epithelial stem‐cell populations that demonstrate similar properties to mesenchymal stromal/stem cells, both functionally and phenotypically. Therefore, the epithelial cell rests of M alassez, rather than being ‘cell rests’, as indicated by their name, are an important source of stem cells that might play a pivotal role in periodontal regeneration.
Abstract 2915: Discovery and characterization of OSI-296, a dual inhibitor of cMET and RON kinases
Authors: Arno G. Steinig, An-Hu Li, Jing Wang, Andrew Kleinberg, Hanqing Dong, Ti Wang, Kathryn M. Stolz Gavagan, Meizhong Jin, Paula Tavares-Greco, Yue Peng, Jen Kahler, Linda Castaldo, Siobhan McCormack, Julie Kan, Mark Albertella, Andy Cooke, Roy Turton, Mark Bittner, Maryland Franklin, Darla Landfair, Prafulla Gokhale, Robert Wild, Jonathan Pachter, David Epstein, Mark J. Mulvihill
Journal: Cancer Research (2012)

Abstract cMET and RON are receptor tyrosine kinases of the MET proto-oncogene family that are activated by their respective ligands HGF and MSP. Signaling through the cMET/HGF system can be deregulated in cancer by HGF-dependent autocrine activation, gene amplification, and/or the presence of activating mutations, among others, while for RON, constitutively active variants generated by alternative splicing or methylation-dependent promoter usage [short-form RON (sfRON)] have been identified. Approaches to abrogate aberrant cMET and RON signaling that have led to agents in clinical trials include inhibiting their kinase function with small molecules. We report here the discovery and characterization of OSI-296, a dual inhibitor of cMET and RON. The compound exhibited selectivity in a panel of 96 kinases with potent activity against cMET, including common Y1230 mutants, and RON. OSI-296 blocked cMET autophosphorylation in MKN45 cells, resulting in dose-dependent inhibition of downstream ERK, AKT, and STAT3 phosphorylation. It also showed potent cellular activity in ELISA-format sfRON and caRON cell mechanistic assays that we developed, resulting in dose-dependent inhibition of downstream ERK and AKT phosphorylation. OSI-296 showed a PK profile in rodents suitable for oral dosing with &amp;gt;70% bioavailability. In multiple xenografts models (cMET: MKN45, SNU-5, U87MG; RON: caRON), significant tumor growth inhibition was observed upon oral dosing with regression at higher doses. OSI-296 was very well tolerated with little body weight loss and no adverse effects even at the highest tested dose of 300 mg/kg p.o. qdx14. Solid PK/PD/TGI correlations have been established wherein &amp;gt;90% inhibition of cMET or RON phosphorylation sustained over 24 h by OSI-296 translated to 100% TGI. In summary, OSI-296 was shown to be a well tolerated, dual inhibitor of cMET and RON with in vivo activity in mouse xenografts models for both targets upon oral dosing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2915. doi:1538-7445.AM2012-2915
Therapeutic effect of loratadine on pruritus in patients with atopic dermatitis
Authors: T. Langeland, H. E. Fagertun, S. Larsen
Journal: Allergy (1994)

The aim of the study was to assess the therapeutic efficacy of loratadine on pruritus in patients with atopic dermatitis, considering the patients’ sensation of itch. Sixteen patients, mean age 24.8 years, with moderate or severe atopic dermatitis were included in a double‐blind and placebo‐controlled study with a six‐period, multi‐crossover design. The patients were given 10 mg loratadine or placebo every day, alternating between loratadine and placebo every 2 weeks. The degree of pruritus during the day and during the night was recorded by the patients every morning and every evening, respectively, on a 10‐cm visual analog scale. The study detected a significant effect of loratadine, as compared with placebo, on pruritus during the day, pruritus during the night, and severity of rash. At least nine of the 16 patients included were classified as responders and only one as a nonresponder to loratadine treatment. It is concluded that loratadine may be tried as an adjuvant therapy in the management of severe and moderate atopic dermatitis, in patients complaining of pruritus.
Cytokine Profile In Nasal Lavage Fluid And The Clinical Alterations In Children With Allergic Rhinitis After Treatment With Montelukast, Mometasone And Desloratadine.
Authors: G.R.S. Segundo, F.A. Gomes, K.P. Fernandes, R. Alves, D.A.O. Silva, E.A. Taketomi
Journal: Journal of Allergy and Clinical Immunology (2009)
PREDICTORS OF LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 MASS AND ACTIVITY LEVELS AMONG PATIENTS WITH STABLE AND ACUTE CORONARY SYNDROMES: A CREDO BIOMARKER SUBSTUDY
Authors: Herbert D. Aronow, W. H. Wilson Tang, Steven Steinhubl, Danielle Brennan, Robert Wilensky, Steven Marso, Peter Berger, Michael Wegner, Eric Topol
Journal: Journal of the American College of Cardiology (2010)