tbuckley/cabot-search huggingface dataset:
Effects of Estrogen With and Without Progestin on Urinary Incontinence
Authors: Susan L. Hendrix
Journal: JAMA (2005)

ContextMenopausal hormone therapy has long been credited with many benefits beyond the indications of relieving hot flashes, night sweats, and vaginal dryness, and it is often prescribed to treat urinary incontinence (UI).ObjectiveTo assess the effects of menopausal hormone therapy on the incidence and severity of symptoms of stress, urge, and mixed UI in healthy postmenopausal women.Design, Setting, and ParticipantsWomen’s Health Initiative multicenter double-blind, placebo-controlled, randomized clinical trials of menopausal hormone therapy in 27 347 postmenopausal women aged 50 to 79 years enrolled between 1993 and 1998, for whom UI symptoms were known in 23 296 participants at baseline and 1 year.InterventionsWomen were randomized based on hysterectomy status to active treatment or placebo in either the estrogen plus progestin (E + P) or estrogen alone trials. The E + P hormones were 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate (CEE + MPA); estrogen alone consisted of 0.625 mg/d of conjugated equine estrogen (CEE). There were 8506 participants who received CEE + MPA (8102 who received placebo) and 5310 who received CEE alone (5429 who received placebo).Main Outcome MeasuresIncident UI at 1 year among women without UI at baseline and severity of UI at 1 year among women who had UI at baseline.ResultsMenopausal hormone therapy increased the incidence of all types of UI at 1 year among women who were continent at baseline. The risk was highest for stress UI (CEE + MPA: relative risk [RR], 1.87 [95% confidence interval {CI}, 1.61-2.18]; CEE alone: RR, 2.15 [95% CI, 1.77-2.62]), followed by mixed UI (CEE + MPA: RR, 1.49 [95% CI, 1.10-2.01]; CEE alone: RR, 1.79 [95% CI, 1.26-2.53]). The combination of CEE + MPA had no significant effect on developing urge UI (RR, 1.15; 95% CI, 0.99-1.34), but CEE alone increased the risk (RR, 1.32; 95% CI, 1.10-1.58). Among women experiencing UI at baseline, frequency worsened in both trials (CEE + MPA: RR, 1.38 [95% CI, 1.28-1.49]; CEE alone: RR, 1.47 [95% CI, 1.35-1.61]). Amount of UI worsened at 1 year in both trials (CEE + MPA: RR, 1.20 [95% CI, 1.06-1.36]; CEE alone: RR, 1.59 [95% CI, 1.39-1.82]). Women receiving menopausal hormone therapy were more likely to report that UI limited their daily activities (CEE + MPA: RR, 1.18 [95% CI, 1.06-1.32]; CEE alone: RR, 1.29 [95% CI, 1.15-1.45]) and bothered or disturbed them (CEE + MPA: RR, 1.22 [95% CI, 1.13-1.32]; CEE alone: RR, 1.50 [95% CI, 1.37-1.65]) at 1 year.ConclusionsConjugated equine estrogen alone and CEE + MPA increased the risk of UI among continent women and worsened the characteristics of UI among symptomatic women after 1 year. Conjugated equine estrogen with or without progestin should not be prescribed for the prevention or relief of UI.
The Cost-Quality Relationship
Authors: Edward H. Wagner
Journal: JAMA (1994)

The relationship between cost and quality is more than an academic concern. Assumptions about the strength and direction of the association are at the heart of the current debate about the future direction of American health care. If we assume that quality and costs are positively related, then it follows that efforts to contain costs threaten quality.<sup>1</sup>If we assume a less linear or even negative relationship, then cost containment and quality improvement may even be complementary.<sup>2</sup> See also p 1903. Donabedian et al<sup>3</sup>suggest that the use of health services beyond those needed for maximum health benefit might actually have a negative effect because of complications of the unnecessary tests and treatments. Empirical studies of the cost-quality relationship have been largely confined to hospital care and show no consistency in the direction of the associations.<sup>4</sup>The article by Starfield et al<sup>5</sup>in this issue
Delineation of the distribution of beta-adrenergic receptor subtypes in canine myocardium.
Authors: S S Murphree, J E Saffitz
Journal: Circulation Research (1988)

beta 2-Receptors constitute only 10-30% of the total beta-adrenergic receptors in mammalian ventricular myocardium, but their precise tissue location cannot be determined easily by measuring physiological variables. To delineate the distribution of beta-receptor subtypes in myocytic and vascular components of the heart, we incubated transmural sections of canine left ventricle with [125Iodo]cyanopindolol and selected concentrations of the beta 1-selective antagonist betaxolol or the beta 2-selective antagonist ICI 118,551. Detailed competition binding data were best accounted for by a two-site model in which approximately 75% of total sites were beta 1- and 25% were beta 2-receptors. The relative proportions of beta-receptor subtypes in myocytic and vascular components were assessed autoradiographically by analyzing the density of binding sites in transmural sections incubated with radioligand and subtype-selective displacers. Betaxolol (10(-7) M) reduced the density of radioligand binding sites by 44% in regions composed primarily of ventricular myocytes but by less than 5% in small coronary arterioles. ICI 118,551 (10(-7) M) reduced radioligand binding-site density by 18% in myocytic regions and by 55% in small arterioles. In myocytic regions, these data indicated a subtype composition of approximately 85% beta 1- and 15% beta 2-sites. In contrast, arterioles contained almost exclusively the beta 2-subtype. The diameters of coronary vessels in which beta 2-receptors were found to be selectively increased fell within a narrow range (mean +/- SD, 35 +/- 11 microns; range, 16-55 microns). Small mural arteries and venules did not contain a significantly higher proportion of beta 2-receptors than adjacent myocytic regions.
Vaginal journey disarms newborn intestine
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

![Graphic][1] 

Intestinal epithelial cells (green) are transiently activated and produce MIP-2 (red) during vaginal birth.A trip down the vaginal tract teaches the intestinal cells of newborn mice to ignore their germy cohabitants, according to Lotz and colleagues on page 

[973][2].
Accelerated Nephropathy in Diabetic Apolipoprotein E-Knockout Mouse
Authors: Markus Lassila, Kwee K. Seah, Terri J. Allen, Vicki Thallas, Merlin C. Thomas, Riccardo Candido, Wendy C. Burns, Josephine M. Forbes, Anna C. Calkin, Mark E. Cooper, Karin A.M. Jandeleit-Dahm
Journal: Journal of the American Society of Nephrology (2004)

Hyperlipidemia not only may be relevant to cardiovascular disease in diabetes but may also play a role in the development and progression of diabetic nephropathy. Furthermore, there is increasing evidence that advanced glycation end products (AGE) play an important role in diabetic renal disease. The objectives of this study were first to characterize renal injury in diabetic apolipoprotein E knockout (apo E-KO) mice and second to explore the role of AGE in the development and progression of renal disease in this model. Diabetes was induced by injection of streptozotocin in 6-wk-old apo E-KO mice. Diabetic animals received no treatment or treatment with the inhibitor of AGE formation aminoguanidine (1 g/kg per d) or the cross-link breaker [4,5-dimethyl-3-(2-oxo2-phenylethyl)-thiazolium chloride] ALT-711, which cleaves preformed AGE (20 mg/kg per d) for 20 wk. Nondiabetic apo E-KO mice as well as nondiabetic and diabetic C57BL/6 mice served as controls. Compared with nondiabetic apo E-KO mice, induction of diabetes in apo E-KO mice resulted in accelerated renal injury characterized by albuminuria and glomerular and tubulointerstitial injury. These abnormalities were associated with increased expression of collagen type I and type IV and transforming growth factor-beta1 (TGF-beta1), increased alpha-smooth muscle actin immunostaining and macrophage infiltration, and increased serum and renal AGE. The two treatments, which attenuated renal AGE accumulation in a disparate manner, were associated with less albuminuria, structural injury, macrophage infiltration, TGF-beta1, and collagen expression. The accelerated renal injury that was observed in diabetic apo E-KO mice was attenuated by approaches that inhibit renal AGE accumulation.
Metformin decreases angiogenesis via NF-κB and Erk1/2/Erk5 pathways by increasing the antiangiogenic thrombospondin-1
Authors: Bee K. Tan, Raghu Adya, Jing Chen, Syed Farhatullah, Dennis Heutling, Dan Mitchell, Hendrik Lehnert, Harpal S. Randeva
Journal: Cardiovascular Research (2009)

AimsPolycystic ovary syndrome (PCOS) is associated with insulin resistance (IR), obesity, and cardiovascular complications. Thrombospondin-1 (TSP-1) is a novel antiangiogenic adipokine highly expressed in obese insulin-resistant subjects. We sought to assess TSP-1 levels in adipose tissue (AT) from PCOS women and matched controls. The effects of metformin treatment on circulating TSP-1 levels in PCOS subjects, the effects of serum from normal and PCOS women on in vitro migration and angiogenesis before and after metformin treatment, and ex vivo regulation of AT TSP-1 by D-glucose were also studied.
Estrogen receptors, progesterone receptors and heat-shock 27-kD protein in liver biopsy specimens from patients with hepatitis B virus infection
Authors: Daniel R. Ciocca, Arturo D. Jorge, Oliver Jorge, Carlos Milutín, Roberto Hosokawa, Marcelo Díaz Lestren, Estela Muzzio, Sergio Schulkin, Ricardo Schirbu
Journal: Hepatology (1991)

It has been proposed that in the human liver, the estrogen receptor gene may become inappropriately expressed as a consequence of HBV integration, contributing to cell transformation. This study was undertaken to examine estrogen receptor status in patients with hepatitis B virus infection and to analyze the expression of progesterone receptor and of a heat-shock 27,000-D protein (hsp27), both of which are estrogen regulated in estrogen target tissues. Receptor proteins were detected in liver biopsy specimens by immunocytochemistry using antireceptor monoclonal antibodies; a monoclonal antibody was also used to detect hsp27. Estrogen receptor and progesterone receptor were mainly seen in the nuclei of hepatocytes. The presence of hepatitis B virus infection did not always result in elevated estrogen receptor expression, but in general the expression of this receptor protein was higher in hepatitis B virus-positive patients than in patients with the same pathological findings (hepatitis, cirrhosis, hepatocarcinoma) but without hepatitis B virus. This was more clearly seen in the patients with hepatitis. Although estrogen receptor expression was moderate to high in many samples, the expression of the two biochemical markers of estrogen action at postreceptor levels (progesterone receptor and hsp27) was low or absent in most of the liver tissues examined, suggesting that in the liver the interaction of estrogen-estrogen receptor-DNA has characteristics inherent to this tissue.
POSITIVE VERSUS NEGATIVE SIGNALING BY LYMPHOCYTE ANTIGEN RECEPTORS
Authors: James I. Healy, Christopher C. Goodnow
Journal: Annual Review of Immunology (1998)

Antigen receptors on lymphocytes play a central role in immune regulation by transmitting signals that positively or negatively regulate lymphocyte survival, migration, growth, and differentiation. This review focuses on how opposing positive or negative cellular responses are brought about by antigen receptor signaling. Four types of extracellular inputs shape the response to antigen: (a) the concentration of antigen; (b) the avidity with which antigen is bound; (c) the timing and duration of antigen encounter; and (d) the association of antigen with costimuli from pathogens, the innate immune system, or other lymphocytes. Intracellular signaling by antigen receptors is not an all-or-none event, and these external variables alter both the quantity and quality of signaling. Recent findings in B lymphocytes have clearly illustrated that these external inputs affect the magnitude and duration of the intracellular calcium response, which in turn contributes to differential triggering of the transcriptional regulators NF kappa B, JNK, NFAT, and ERK. The regulation of calcium responses involves a network of tyrosine kinases (e.g. lyn, syk), tyrosine or lipid phosphatases (CD45, SHP-1, SHIP), and accessory molecules (CD21/CD19, CD22, FcR gamma 2b). Understanding the biochemistry and logic behind these integrative processes will allow development of more selective and efficient pharmaceuticals that suppress, modify, or augment immune responses in autoimmunity, transplantation, allergy, vaccines, and cancer.
An initiative offering free pneumococcal vaccination to victims of the Great East Japan earthquake
Authors: Toshio Naito
Journal: Thorax (2013)

An initiative offering free pneumococcal vaccination to victims of the Great East Japan earthquakeThe Pacific coastline of eastern Japan was severely affected by the massive tsunami that struck on 11 March 2011.The article by Daito et al, 1 published in Thorax reported a marked increase in the incidence of pneumonia during the disaster.
Oral Antibiotics for Fever in Low-Risk Neutropenic Patients With Cancer: A Double-Blind, Randomized, Multicenter Trial Comparing Single Daily Moxifloxacin With Twice Daily Ciprofloxacin Plus Amoxicillin/Clavulanic Acid Combination Therapy—EORTC Infectious Diseases Group Trial XV
Authors: Winfried V. Kern, Oscar Marchetti, Lubos Drgona, Hamdi Akan, Mickel Aoun, Murat Akova, Robrecht de Bock, Marianne Paesmans, Claudio Viscoli, Thierry Calandra
Journal: Journal of Clinical Oncology (2013)

This double-blind, multicenter trial compared the efficacy and safety of a single daily oral dose of moxifloxacin with oral combination therapy in low-risk febrile neutropenic patients with cancer.Inclusion criteria were cancer, febrile neutropenia, low risk of complications as predicted by a Multinational Association for Supportive Care in Cancer (MASCC) score > 20, ability to swallow, and ≤ one single intravenous dose of empiric antibiotic therapy before study drug treatment initiation. Early discharge was encouraged when a set of predefined criteria was met. Patients received either moxifloxacin (400 mg once daily) monotherapy or oral ciprofloxacin (750 mg twice daily) plus amoxicillin/clavulanic acid (1,000 mg twice daily). The trial was designed to show equivalence of the two drug regimens in terms of therapy success, defined as defervescence and improvement in clinical status during study drug treatment (< 10% difference).Among the 333 patients evaluated in an intention-to-treat analysis, therapy success was observed in 80% of the patients administered moxifloxacin and in 82% of the patients administered combination therapy (95% CI for the difference, -10% to 8%, consistent with equivalence). Minor differences in tolerability, safety, and reasons for failure were observed. More than 50% of the patients in the two arms were discharged on protocol therapy, with 5% readmissions among those in either arm. Survival was similar (99%) in both arms.Monotherapy with once daily oral moxifloxacin is efficacious and safe in low-risk febrile neutropenic patients identified with the help of the MASCC scoring system, discharged early, and observed as outpatients.
Differential patterns of NOTCH1-4 receptor expression are markers of glioma cell differentiation
Authors: P. Dell'Albani, M. Rodolico, R. Pellitteri, E. Tricarichi, S. A. Torrisi, S. D'Antoni, M. Zappia, V. Albanese, R. Caltabiano, N. Platania, E. Aronica, M. V. Catania
Journal: Neuro-Oncology (2013)

Notch signaling is deregulated in human gliomas and may play a role in their malignancy. However, the role of each Notch receptor in glioma cell differentiation and progression is not clear. We examined the expression pattern of Notch receptors and compared it with differentiation markers in glioma cell lines, primary human cultures, and biopsies of different grades. Furthermore, the effects of a γ-secretase inhibitor (GSI) on cell survival were assessed. Notch receptors and markers of cellular differentiation were analyzed by reverse transcriptase PCR, Western blotting, immunohistochemistry, and immunocytochemistry. GSI sensitivity was assessed in both cell lines and primary cultures grown as monolayers or tumorspheres, by MTT assay. In cell lines, Notch1 and Notch2/4 levels paralleled those of glial fibrillary acidic protein (GFAP) and vimentin, respectively. In human gliomas and primary cultures, Notch1 was moderate/strong in low-grade tumors but weak in glioblastoma multiforme (GBM). Conversely, Notch4 increased from astrocytoma grade II to GBM. Primary GBM cultures grown in serum (monolayer) showed moderate/high levels of CD133, nestin, vimentin, and Notch4 and very low levels of GFAP and Notch1, which were reduced in tumorspheres. This effect was drastic for Notch4. GSI reduced cell survival with stronger effect in serum, whilst human primary cultures showed different sensitivity. Data from cell lines and human gliomas suggest a correlation between expression of Notch receptors and cell differentiation. Namely, Notch1 and Notch4 are markers of differentiated and less differentiated glioma cells, respectively. We propose Notch receptors as markers of glioma grading and possible prognostic factors.
Preadmission antithrombotic treatment and stroke severity in patients with atrial fibrillation and acute ischaemic stroke: an observational study
Authors: Martin O'Donnell, Wes Oczkowski, Jiming Fang, Clive Kearon, Jaime Silva, Christine Bradley, Gordon Guyatt, Linda Gould, Cami D'Uva, Moira Kapral, Frank Silver
Journal: The Lancet Neurology (2006)
Thymidine Phosphorylase Participates in Platelet Signaling and Promotes Thrombosis
Authors: Wei Li, Alba Gigante, Maria-Jesus Perez-Perez, Hong Yue, Michio Hirano, Thomas M. McIntyre, Roy L. Silverstein
Journal: Circulation Research (2014)

Rationale : Platelets contain abundant thymidine phosphorylase (TYMP), which is highly expressed in diseases with high risk of thrombosis, such as atherosclerosis and type II diabetes mellitus. Objective : To test the hypothesis that TYMP participates in platelet signaling and promotes thrombosis. Methods and Results : By using a ferric chloride (FeCl 3 )–induced carotid artery injury thrombosis model, we found time to blood flow cessation was significantly prolonged in Tymp −/− and Tymp +/− mice compared with wild-type mice. Bone marrow transplantation and platelet transfusion studies demonstrated that platelet TYMP was responsible for the antithrombotic phenomenon in the TYMP-deficient mice. Collagen-, collagen-related peptide–, adenosine diphosphate-, or thrombin-induced platelet aggregation were significantly attenuated in Tymp +/− and Tymp −/− platelets, and in wild type or human platelets pretreated with TYMP inhibitor KIN59. Tymp deficiency also significantly decreased agonist-induced P-selectin expression. TYMP contains an N-terminal SH3 domain-binding proline-rich motif and forms a complex with the tyrosine kinases Lyn, Fyn, and Yes in platelets. TYMP-associated Lyn was inactive in resting platelets, and TYMP trapped and diminished active Lyn after collagen stimulation. Tymp/Lyn double haploinsufficiency diminished the antithrombotic phenotype of Tymp +/− mice. TYMP deletion or inhibition of TYMP with KIN59 dramatically increased platelet-endothelial cell adhesion molecule 1 tyrosine phosphorylation and diminished collagen-related peptide– or collagen-induced AKT phosphorylation. In vivo administration of KIN59 significantly inhibited FeCl 3 -induced carotid artery thrombosis without affecting hemostasis. Conclusions : TYMP participates in multiple platelet signaling pathways and regulates platelet activation and thrombosis. Targeting TYMP might be a novel antiplatelet and antithrombosis therapy.
A summary of the new GINA strategy: a roadmap to asthma control
Authors: Helen K. Reddel, Eric D. Bateman, Allan Becker, Louis-Philippe Boulet, Alvaro A. Cruz, Jeffrey M. Drazen, Tari Haahtela, Suzanne S. Hurd, Hiromasa Inoue, Johan C. de Jongste, Robert F. Lemanske, Mark L. Levy, Paul M. O'Byrne, Pierluigi Paggiaro, Soren E. Pedersen, Emilio Pizzichini, Manuel Soto-Quiroz, Stanley J. Szefler, Gary W.K. Wong, J. Mark FitzGerald
Journal: European Respiratory Journal (2015)

Over the past 20 years, the Global Initiative for Asthma (GINA) has regularly published and annually updated a global strategy for asthma management and prevention that has formed the basis for many national guidelines. However, uptake of existing guidelines is poor. A major revision of the GINA report was published in 2014, and updated in 2015, reflecting an evolving understanding of heterogeneous airways disease, a broader evidence base, increasing interest in targeted treatment, and evidence about effective implementation approaches. During development of the report, the clinical utility of recommendations and strategies for their practical implementation were considered in parallel with the scientific evidence. This article provides a summary of key changes in the GINA report, and their rationale. The changes include a revised asthma definition; tools for assessing symptom control and risk factors for adverse outcomes; expanded indications for inhaled corticosteroid therapy; a framework for targeted treatment based on phenotype, modifiable risk factors, patient preference, and practical issues; optimisation of medication effectiveness by addressing inhaler technique and adherence; revised recommendations about written asthma action plans; diagnosis and initial treatment of the asthma−chronic obstructive pulmonary disease overlap syndrome; diagnosis in wheezing pre-school children; and updated strategies for adaptation and implementation of GINA recommendations.
Expression of the subgenomic hepatitis C virus replicon alters iron homeostasis in Huh7 cells
Authors: Carine Fillebeen, Martina Muckenthaler, Bill Andriopoulos, Martin Bisaillon, Zineb Mounir, Matthias W. Hentze, Antonis E. Koromilas, Kostas Pantopoulos
Journal: Journal of Hepatology (2007)
Advertisement that attacked plain packaging was misleading, rules watchdog
Authors: A. O'Dowd
Journal: BMJ (2014)

The Advertising Standards Authority has ruled against a large tobacco firm over an advertisement that it ran last year about standardised packaging of tobacco products.

The authority issued a ruling1 on 30 July that an advertisement run by Gallaher, the UK trading company of Japan Tobacco International, which opposed the introduction of standardised packaging of tobacco products, was misleading and must not be published again.

Anti-tobacco campaigners and charities welcomed the ruling, saying that the advertisement in question was part of a campaign that was “one of the most blatantly dishonest in recent UK advertising history.” Gallaher, however, said that it disagreed strongly with the authority’s decision and had submitted a formal request to Hayden Phillips, the independent reviewer of the authority’s adjudications, for the decision to be reconsidered.

The company ran a series of six advertisements as part of a £2m …
Attributable causes of cancer in China
Authors: J.B. Wang, Y. Jiang, H. Liang, P. Li, H.J. Xiao, J. Ji, W. Xiang, J.F. Shi, Y.G. Fan, L. Li, D. Wang, S.S. Deng, W.Q. Chen, W.Q. Wei, Y.L. Qiao, P. Boffetta
Journal: Annals of Oncology (2012)