tbuckley/cabot-search huggingface dataset:
The H syndrome: A genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestations
Authors: Vered Molho-Pessach, Ziad Agha, Suhail Aamar, Benjamin Glaser, Victoria Doviner, Nurith Hiller, David Haim Zangen, Annick Raas-Rothschild, Ziva Ben-Neriah, Shaher Shweiki, Orly Elpeleg, Abraham Zlotogorski
Journal: Journal of the American Academy of Dermatology (2008)
Incidence of acute decreases in peak expiratory flow following the use of metered-dose inhalers in asthmatic patients
Authors: MZ Shaheen, JG Ayres, C Benincasa
Journal: European Respiratory Journal (1994)

This study aimed to investigate and compare the incidence of metered-dose inhaler (MDI)-associated bronchoconstriction in an asthmatic population, following the use of three different MDIs. Two different placebo metered-dose inhaler preparations containing the same chlorofluorocarbons but differing in dispersant chemicals, one containing oleic acid (MDI-OA) and the other lecithin NF (MDI-L), were compared with a MDI containing salmeterol xinafoate (25 micrograms) and lecithin NF (MDI-S). The study population comprised 11,850 asthmatic patients, who were assigned to receive two puffs from one of the three inhalers: MDI-S (n = 3,948); MDI-L (n = 3,942); or MDI-OA (n = 3,960). Peak expiratory flow (PEF) was measured before and 5 min after inhalation. A 20% fall in PEF was defined as a clinically significant bronchoconstriction. Overall 180 (1.5%) patients demonstrated bronchoconstriction, 43 (1.1%) in the MDI-S group, 67 (1.7%) in the MDI-L group and 70 (1.8%) in the MDI-OA. A significantly lower incidence of bronchoconstriction was seen with the salmeterol xinafoate MDI compared to either of the other two preparations. The risk of acute bronchoconstriction was also shown to increase with age and with decreasing pretreatment PEF. The study has shown that acute bronchoconstriction is an uncommon adverse reaction following the use of metered-dose inhalers. In addition, the study suggests that one of the inert constituents currently within metered-dose inhalers is the likely source of the irritant leading to bronchoconstriction.
Cannabis Induces a Clinical Response in Patients With Crohn's Disease: A Prospective Placebo-Controlled Study
Authors: Timna Naftali, Lihi Bar-Lev Schleider, Iris Dotan, Ephraim Philip Lansky, Fabiana Sklerovsky Benjaminov, Fred Meir Konikoff
Journal: Clinical Gastroenterology and Hepatology (2013)
Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex
Authors: Ying Huang, Zhiping Wu, Meliana Riwanto, Shengqiang Gao, Bruce S. Levison, Xiaodong Gu, Xiaoming Fu, Matthew A. Wagner, Christian Besler, Gary Gerstenecker, Renliang Zhang, Xin-Min Li, Anthony J. DiDonato, Valentin Gogonea, W.H. Wilson Tang, Jonathan D. Smith, Edward F. Plow, Paul L. Fox, Diana M. Shih, Aldons J. Lusis, Edward A. Fisher, Joseph A. DiDonato, Ulf Landmesser, Stanley L. Hazen
Journal: Journal of Clinical Investigation (2013)

Myeloperoxidase (MPO) and paraoxonase 1 (PON1) are high-density lipoprotein-associated (HDL-associated) proteins mechanistically linked to inflammation, oxidant stress, and atherosclerosis. MPO is a source of ROS during inflammation and can oxidize apolipoprotein A1 (APOA1) of HDL, impairing its atheroprotective functions. In contrast, PON1 fosters systemic antioxidant effects and promotes some of the atheroprotective properties attributed to HDL. Here, we demonstrate that MPO, PON1, and HDL bind to one another, forming a ternary complex, wherein PON1 partially inhibits MPO activity, while MPO inactivates PON1. MPO oxidizes PON1 on tyrosine 71 (Tyr71), a modified residue found in human atheroma that is critical for HDL binding and PON1 function. Acute inflammation model studies with transgenic and knockout mice for either PON1 or MPO confirmed that MPO and PON1 reciprocally modulate each other's function in vivo. Further structure and function studies identified critical contact sites between APOA1 within HDL, PON1, and MPO, and proteomics studies of HDL recovered from acute coronary syndrome (ACS) subjects revealed enhanced chlorotyrosine content, site-specific PON1 methionine oxidation, and reduced PON1 activity. HDL thus serves as a scaffold upon which MPO and PON1 interact during inflammation, whereupon PON1 binding partially inhibits MPO activity, and MPO promotes site-specific oxidative modification and impairment of PON1 and APOA1 function.
Overexpression of Thioredoxin-1 in Transgenic Mice Attenuates Adriamycin-Induced Cardiotoxicity
Authors: Keisuke Shioji, Chiharu Kishimoto, Hajime Nakamura, Hiroshi Masutani, Zuyi Yuan, Shin-ichi Oka, Junji Yodoi
Journal: Circulation (2002)

Background— Adriamycin (ADR) is an anticancer drug known to cause severe cardiac toxicity by generating free radicals. We investigated the role of a redox-regulating molecule, thioredoxin-1 (TRX1), in ADR-induced cardiotoxicity. Methods and Results— The in vitro study showed that TRX1 was dose-dependently increased concomitant with the formation of hydroxyl radicals in ADR-treated neonatal rat cardiomyocytes. Lactate dehydrogenase–releasing assay showed that treatment with recombinant human TRX1 suppressed cardiomyocyte injury in ADR-treated cardiomyocytes. To examine the biological significance of TRX1 in vivo, we used transgenic mice expressing increased levels of human TRX1 (TRX1-TG mice). Electron microscopy revealed that mitochondria, myofibrils, and other cellular details were much better maintained in ADR-treated TRX1-TG mice than in ADR-treated nontransgenic (WT) mice. The increase in the protein carbonyl content, a marker of cellular protein oxidation, was suppressed in ADR-treated TRX1-TG mice compared with ADR-treated WT mice. The formation of hydroxyl radicals in ADR-treated heart homogenates of TRX1-TG mice was decreased compared with WT mice. For the survival study, all WT mice treated with ADR died within 6 weeks, but 5 of 6 TRX1-TG mice treated with ADR survived &gt;8 weeks. Conclusions— TRX1 is upregulated by intracellular oxidative stress generated by ADR. TRX1 has a protective role against ADR-induced cardiotoxicity by reducing oxidative stress.
Extra-Pancreatic Manifestations in Diabetes Secondary to Mitochondrial DNA Point Mutation Within the tRNALeu(UUR) Gene
Authors: Bernard Vialettes, Véronique Paquis-Fluckinger, Pascale Silvestre-Aillaud, David Ben Dahan, Jean-François Pelissier, Frédérique Etchary-Bouyx, Denis Raccah, Henri Gin, Pierre Jean Guillausseau, Danielle Vanuxen, Frederic Orsini, Jean Pouget, Patrick Cozzone, Claude Desnuelle
Journal: Diabetes Care (1995)

A point mutation in the mitochondrial genome has been identified as a cause of diabetes and deafness. We report two pedigrees with and A-to-G transition at nucleotide 3243 of mtDNA within the tRNALeu(UUR) gene and focus our investigations on other localizations of the anomaly, particularly muscle and retina.Muscular localization has been studied in probands by invasive and noninvasive methods, including muscle biopsy (evaluation of the proportion of mutated mtDNA in comparison to blood cells, measurement of respiratory chain complex activities and histological and histochemical aspects) and 31P-nuclear magnetic resonance (NMR) spectroscopy. Ophthalmic and angiographic examination of retina, electroretinography, and visual evoked potentials were performed in five subjects.This mutation, previously described in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), was expressed more abundantly in muscle than in nucleated blood cells. This low expression in blood cells could hamper the diagnosis for some patients. In addition, despite poor clinical expression, muscle was found to be highly affected. Ragged red fibers and dystrophic mitochondria were observed in muscle biopsy. Histochemical assays showed decreased activity of respiratory chain complexes, and 31P-NMR in vivo data further confirmed the defect of muscle oxidative processes. Exercise-induced lactate production was increased. Finally, in both families, an atypical "salt and pepper" pigmentary retinopathy was observed without consequences on visual acuity.In diabetes secondary to 3243 mtDNA mutation, infraclinical muscular and ocular lesions are frequent. These two locations of the disease, which are easily investigated by simple methods, can help in the diagnosis of this new type of diabetes.
Development and Independent Validation of a Prognostic Assay for Stage II Colon Cancer Using Formalin-Fixed Paraffin-Embedded Tissue
Authors: Richard D. Kennedy, Max Bylesjo, Peter Kerr, Timothy Davison, Julie M. Black, Elaine W. Kay, Robert J. Holt, Vitali Proutski, Miika Ahdesmaki, Vadim Farztdinov, Nicolas Goffard, Peter Hey, Fionnuala McDyer, Karl Mulligan, Julie Mussen, Eamonn O'Brien, Gavin Oliver, Steven M. Walker, Jude M. Mulligan, Claire Wilson, Andreas Winter, Diarmuid O'Donoghue, Hugh Mulcahy, Jacintha O'Sullivan, Kieran Sheahan, John Hyland, Rajiv Dhir, Oliver F. Bathe, Ola Winqvist, Upender Manne, Chandrakumar Shanmugam, Sridhar Ramaswamy, Eduardo J. Leon, William I. Smith, Ultan McDermott, Richard H. Wilson, Daniel Longley, John Marshall, Robert Cummins, Daniel J. Sargent, Patrick G. Johnston, D. Paul Harkin
Journal: Journal of Clinical Oncology (2011)

Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray-based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples.A gene signature was developed from a balanced set of 73 patients with recurrent disease (high risk) and 142 patients with no recurrence (low risk) within 5 years of surgery.The 634-probe set signature identified high-risk patients with a hazard ratio (HR) of 2.62 (P < .001) during cross validation of the training set. In an independent validation set of 144 samples, the signature identified high-risk patients with an HR of 2.53 (P < .001) for recurrence and an HR of 2.21 (P = .0084) for cancer-related death. Additionally, the signature was shown to perform independently from known prognostic factors (P < .001).This gene signature represents a novel prognostic biomarker for patients with stage II colon cancer that can be applied to FFPE tumor samples.
Effects of Combined Ezetimibe and Simvastatin Therapy as Compared With Simvastatin Alone in Patients With Type 2 Diabetes
Authors: Piero Ruggenenti, Dario Cattaneo, Stefano Rota, Ilian Iliev, Aneliya Parvanova, Olimpia Diadei, Bogdan Ene-Iordache, Silvia Ferrari, Antonio C. Bossi, Roberto Trevisan, Antonio Belviso, Giuseppe Remuzzi
Journal: Diabetes Care (2010)

OBJECTIVE To assess the effects of inhibited gastrointestinal cholesterol absorption in statin-treated dyslipidemic patients. RESEARCH DESIGN AND METHODS In a multicenter prospective randomized double-blind placebo-controlled trial, we primarily compared by ANCOVA the effect of 2-month ezetimibe (10 mg/day) or placebo therapy on LDL cholesterol serum levels in 108 type 2 diabetic patients with albuminuria &amp;lt;200 μg/min and total cholesterol concentrations &amp;gt;135 mg/dl despite simvastatin treatment (40 mg/day). RESULTS Unlike placebo, ezetimibe decreased LDL cholesterol from 99 ± 31 to 66 ± 22 mg/dl, total cholesterol from 162 ± 36 to 124 ± 30 mg/dl, and apolipoprotein B from 83 ± 22 to 64 ± 18 mg/dl (P &amp;lt; 0.0001 for all changes versus placebo). A total of 72 and 17% of patients on ezetimibe or placebo achieved LDL levels &amp;lt;70 mg/dl, respectively (P &amp;lt; 0.0001). Treatment was well tolerated. CONCLUSIONS Adding ezetimibe to simvastatin therapy helps to improve the pro-atherogenic lipoprotein profile in type 2 diabetic patients who fail to reach recommended lipid targets with statin therapy alone.
A Novel Method for Viral Gene Delivery in Solid Tumors
Authors: Yong Wang, Shanling Liu, Chuan-Yuan Li, Fan Yuan
Journal: Cancer Research (2005)

Abstract Intratumoral infusion is the most commonly used method for viral gene delivery in clinical trials for cancer treatment. However, a potential problem in this approach is that viral vectors may disseminate from tumor to normal tissues during and after the infusion. To reduce the dissemination, we developed a novel method based on a biocompatible polymer, poloxamer 407, which could significantly increase the viscosity of virus suspension when the temperature was changed from 4°C to 37°C. With this method, we could significantly increase transgene expression in solid tumors and reduce virus dissemination by 2 orders of magnitude after intratumoral infusion of adenoviral vectors. The mechanism of reduction was likely to be that the viscous poloxamer solution blocked convection of viral vectors in the interstitial space and the lumen of microvessels in the vicinity of the infusion site. This method has a potential to be used in the clinic for enhancing efficacy and reducing toxicity in viral gene therapy.
Abnormal angiogenesis in diabetes mellitus
Authors: Alexandra Martin, Michael R. Komada, David C. Sane
Journal: Medicinal Research Reviews (2002)

The adverse long-term effects of diabetes mellitus have been well described and involve many organ systems. While diabetes management has largely focused on control of hyperglycemia, the presence of abnormalities of angiogenesis may cause or contribute to many of the clinical manifestations of diabetes. When compared with non-diabetic subjects, diabetics demonstrate vascular abnormalities of the retina, kidneys, and fetus. Diabetics have impaired wound healing, increased risk of rejection of transplanted organs, and impaired formation of coronary collaterals. In each of these conditions, and possibly in diabetic neuropathy as well, abnormalities of angiogenesis can be implicated in the pathogenesis. A perplexing feature of the aberrant angiogenesis is that excessive and insufficient angiogenesis can occur in different organs in the same individual. In this review, the clinical features, molecular mechanisms, and potential therapeutic options of abnormal angiogenesis in diabetes will be reviewed.
Bile Acids and Metabolic Regulation
Authors: Bart Staels, Vivian A. Fonseca
Journal: Diabetes Care (2009)

Bile acids have long been known to facilitate digestion and absorption of lipids in the small intestine as well as regulate cholesterol homeostasis (1,2). Over the last decade, however, it has become clear that bile acids are not simply digestive detergents and the primary route governing cholesterol catabolism. Bile acids are now recognized as hormones involved in the regulation of various metabolic processes (3). Through activation of various signaling pathways, bile acids regulate not only their own synthesis and enterohepatic circulation, but also triglyceride, cholesterol, glucose, and energy homeostasis (2).

Manipulation of bile acid enterohepatic circulation by bile acid sequestration with nonsystemically absorbed resins can modulate the processes regulated by bile acids. Whereas bile acid sequestrants (BASs) have been used for over 40 years in the treatment of dyslipidemia (1), more recent data have emerged that have expanded their role in the treatment of dysglycemia in type 2 diabetes (4–9). The initial data suggesting such an effect were derived from post hoc analysis of a clinical trial for dyslipidemia that determined that BASs lowered glucose, particularly when compared with other lipid-lowering drugs (4). This concept was subsequently proven in several studies showing that BASs, such as colesevelam, lower glucose (5–8).

This review examines recent data exploring possible mechanisms involved in regulation of glucose metabolism by bile acids and the potential impact of disruption of their enterohepatic circulation on diabetes. We will also summarize the available clinical trial data that supported the regulatory approval of colesevelam for the treatment of hyperglycemia in type 2 diabetes.

Bile acids are potent “digestive surfactants” that promote absorption of lipids (including fat-soluble vitamins), acting as emulsifiers (1,2).

Bile acids represent the primary pathway for cholesterol catabolism and account for ∼50% of the daily turnover …
Delay in Surgical Treatment and Survival After Breast Cancer Diagnosis in Young Women by Race/Ethnicity
Authors: Erlyn C. Smith, Argyrios Ziogas, Hoda Anton-Culver
Journal: JAMA Surgery (2013)

Importance: Breast cancer in women between the ages of 15 and 39 years (adolescents and young adults [AYAs]) constitutes 5% to 6% of all breast cancer cases in the United States.Breast cancer in AYA women has a worse prognosis than in older women.Five-year survival rates are lowest for AYA women, and only a few studies have examined the impact of delay in treatment, race/ ethnicity, and other socioeconomic factors on survival in AYA women.Objective: To examine the impact of treatment delay time (TDT), race/ethnicity, socioeconomic status, insurance status, cancer stage, and age on the survival from breast cancer among AYA women.Design, Setting, and Participants: This is a retrospective case-only study of 8860 AYA breast cancer cases diagnosed from 1997 to 2006 using the California Cancer Registry database.Exposure: Treatment delay time was defined as the number of weeks between the date of diagnosis and date of definitive treatment.Kaplan-Meier estimation was used to generate survival curves, and a multivariate Cox proportional hazards regression model was performed to assess the association of TDT with survival while accounting for covariates (age, race/ethnicity, socioeconomic status, insurance status, cancer stage [American Joint Committee on Cancer], tumor markers, and treatment).Main Outcomes and Measures: Five-year survival rates for breast cancer as influenced by host factors, tumor factors, and TDT.Results: Treatment delay time more than 6 weeks after diagnosis was significantly different (PϽ.001) between racial/ethnic groups (Hispanic, 15.3% and African American, 15.3% compared with non-Hispanic white, 8.1%).Women with public or no insurance (17.8%) compared with those with private insurance (9.5%) and women with low socioeconomic status (17.5%) compared with those with high socioeconomic status (7.7%) were shown to have TDT more than 6 weeks.The 5-year survival in women who were treated by surgery and had TDT more than 6 weeks was 80% compared with 90% (P=.005) in those with TDT less than 2 weeks.In multivariate analysis, longer TDT, estrogen receptor negative status, having public or no insurance, and late cancer stage were significant risk factors for shorter survival. Conclusions and Relevance:Young women with breast cancer with a longer TDT have significantly decreased survival time compared with those with a shorter TDT.This adverse impact on survival was more pronounced in African American women, those with public or no insurance, and those with low SES.
Angiotensin converting enzyme in bronchoalveolar lavage fluid in pulmonary sarcoidosis.
Authors: M Perrin-Fayolle, Y Pacheco, R Harf, B Montagnon, N Biot
Journal: Thorax (1981)

Alveolar angiotensin converting enzyme (ACE) and serum ACE were measured simultaneously in 16 patients with histologically confirmed sarcoidosis and in 16 control subjects. Although alveolar ACE was abnormally elevated in all 15 cases of active sarcoidosis, serum ACE was not. No correlations were found between radiographic staging of pulmonary sarcoidosis and the levels of these enzymes. There was a clear correlation, however, between the levels of alveolar ACE and counts made on bronchoalveolar lavage fluid. This correlation was closer than that existing between serum ACE and bronchoalveolar lavaged lymphocytes. It is suggested that alveolar ACE is an additional biological marker of pulmonary sarcoidosis which is possibly more sensitive than serum ACE.
Epidemiological changes of patients with lung cancer over Years
Authors: Yavuz Havlucu, Pinar Celik, Feride Durmaz, Aysin Sakar Coskun, Tugba Goktalay, Arzu Yorgancioglu
Journal: European Respiratory Journal (2013)

Aim of the sudy was to investigate the epidemiological changes of patients with lung cancer over the years.

721 lung cancer cases diagnosed between January 2000 and January 2013 years were included.The patient were categorized in three group according to thier diagnosis time as 2000-2005,2006-2010,and 2011-2013.

79,2% of patients were male and mean age was 60,4±7,9 years.The percentage of squamous cell carcinoma (SCC),adenocarcinoma, other non small cell lung carcinoma (NSCLC), and small cell lung carcinoma (SCLC) were 35.4%, 26.7%, 8.4%, and 29.5% respectively.The percentage of stage IIIB and IV of NSCLC were 49,3% and 29,1 respectively.Between 2000-2005 years, 90,6% of patients were male and mean age was 69,7±11,9 years.The percentage of SCC,adenocarcinoma,other NSCLC, and SCLC were 45,7%, 6,9%, 17,2%, and 30,2% respectively.The percentage of stage IIIB and IV of NSCLC were 45,9% and 41,8% respectively.Between 2006-2010 years, 80,72% of patients were male and mean age was 61,8±5,4 years.The percentage of SCC,adenocarcinoma,other NSCLC, and SCLC were 37,3%, 23,5%, 9,7%, and 29,5% respectively.The percentage of stage IIIB and IV of NSCLC were 50,5% and 31,2% respectively.Between 2011-2013 years, 71,3% of patients were male and mean age was 54,1±10,8 years.The percentage of SCC,adenocarcinoma,other NSCLC, and SCLC were 26,2%, 39,4%, 6,9%, and 27,5% respectively.The percentage of stage IIIB and IV of NSCLC were 51,3% and 22,4% respectively.

According to years, the mean age year of lung cancer diagnosis was decreased and teh percentage of female and adenocarcinoma lung cancer were increased.Although the new and advanced diagnostic tools and methods most of the patients stage were advanced stage at the time of diagnosis.
Gene-culture coevolution between cattle milk protein genes and human lactase genes
Authors: Albano Beja-Pereira, Gordon Luikart, Phillip R England, Daniel G Bradley, Oliver C Jann, Giorgio Bertorelle, Andrew T Chamberlain, Telmo P Nunes, Stoitcho Metodiev, Nuno Ferrand, Georg Erhardt
Journal: Nature Genetics (2003)
Series on education: Teaching the teachers: ways of improving teaching and identifying areas for development
Authors: L Millard
Journal: Annals of the Rheumatic Diseases (2000)

What does "teaching the teachers" mean?The term refers to ways of enabling teachers to develop their ability to help students to learn.It can denote a range of activities and have a variety of outcomes.Boxes 1 and 2 outline some of these activities and outcomes.When considering how teaching ability may be developed, it is helpful to bear in mind the breadth of opportunities available and also the varied outcomes which may be sought.Well motivated teachers convey their enthusiasm to their students and this encourages them to learn. 1 Teachers can be helped to maintain their motivation by knowing that they are doing a good job: that they are helping stu-dents to learn eVectively.By enhancing teachers' understanding and abilities, teaching the teachers activities can help to nurture enthusiasm for teaching in the face of competing pressures from clinical and other demands.