tbuckley/cabot-search huggingface dataset:
1α,25(OH)2-Vitamin D3 Increases Dysferlin Expression in vitro and in a Human Clinical Trial
Authors: Noemi De Luna, Jordi Díaz-Manera, Carmen Paradas, Cristina Iturriaga, Ricardo Rojas-García, Josefa Araque, Mireia Genebriera, Ignasi Gich, Isabel Illa, Eduard Gallardo
Journal: Molecular Therapy (2012)

Dysferlinopathies are a heterogenous group of autosomal recessive inherited muscular dystrophies caused by mutations in DYSF gene. Dysferlin is expressed mainly in skeletal muscle and in monocytes and patients display a severe reduction or absence of protein in both tissues. Vitamin D3 promotes differentiation of the promyelocytic leukemia HL60 cells. We analyzed the effect of vitamin D3 on dysferlin expression in vitro using HL60 cells, monocytes and myotubes from controls and carriers of a single mutation in DYSF. We also performed an observational study with oral vitamin D3 in a cohort of 21 carriers. Fifteen subjects were treated for 1 year and dysferlin expression in monocytes was analysed before and after treatment. Treatment with vitamin D3 increased expression of dysferlin in vitro. The effect of vitamin D3 was mediated by both a nongenomic pathway through MEK/ERK and a genomic pathway involving binding of vitamin D3 receptor to the dysferlin promoter. Carriers treated with vitamin D3 had significantly increased expression of dysferlin in monocytes compared with nontreated carriers (P < 0.05). These findings will have important therapeutic implications since a combination of different molecular strategies together with vitamin D3 uptake could increase dysferlin expression to nonpathological protein levels.
Chronic Liver Disease: Differences in Autoimmune Serological Reactions between Australians and Asians
Authors: S. Whittingham, I. R. Mackay, R. S. Thanabalasundrum, H. K. Chuttani, R. Manjuran, C. S. Seah, M. Yu, V. Viranuvatti
Journal: BMJ (1973)

A total of 164 patients from Australia, Ceylon, India, Singapore, and Thailand were studied for the prevalence of autoantibodies associated with "idiopathic" chronic liver disease-namely, antinuclear antibody, smooth muscle antibody, and mitochondrial antibody. The prevalence of these autoantibodies was high among patients from Australia (55%), but was low among patients from Ceylon (14%), India (11%), Singapore (0%), and Thailand (8%). There are variations in types of hepatitis and cirrhosis between races, and this applies particularly to the type associated with autoimmune markers. This may be related to genetic differences that have evolved between peoples of European and Asian descent.
Sports utility vehicles and older pedestrians
Authors: Ciaran Simms, Desmond O'Neill
Journal: BMJ (2005)

A damaging collision 

T wo independent trends in the developed world are likely to reverse some of the hard won improvements that have been made in road safety. One is the ageing of the population; the other the increase in the use of sports utility vehicles (SUVs, high performance four wheel drive cars capable of off-road driving). The first trend produces a growing number of vulnerable road users; the second produces a likelihood of more severe injuries when vehicles and pedestrians collide. Public health professionals will need to work with transportation and road safety agencies to avoid the inevitable consequences of more vulnerable road users and more lethal vehicles.

Among road users, pedestrians are already a group at high risk, and elderly pedestrians are particularly at risk. People over 60 are more than four times as likely to die if injured by a car than younger people1: in a pattern repeated around the developed world, older people in Ireland account for 30% of pedestrian deaths but only 11% of the population.2 The World Health Organization has recognised protection of older pedestrians as a key safety measure for this age group.3 Pedestrian protection is an even more pressing problem in the developing world. Pedestrian injuries …
Primary sclerosing cholangitis, the biliary tree, and ulcerative colitis.
Authors: M E Thorpe, P J Scheuer, S Sherlock
Journal: Gut (1967)

EDITORIAL COMMENT It is well known that ulcerative colitis may be associated with a number of different diseases of the liver.This paper records sclerosing cholangitis as one possible mechanism of intrahepatic cholestasis.Sclerosing cholangitis is a general disease of the biliary system involving intra-and extrahepatic ducts and also the gall bladder.The diagnosis can only be made by laparotomy.The prognosis seems to be better that was originally thought.
PEG-derivatized embelin as a nanomicellar carrier for delivery of paclitaxel to breast and prostate cancers
Authors: Jianqin Lu, Yixian Huang, Wenchen Zhao, Rebecca T. Marquez, Xiaojie Meng, Jiang Li, Xiang Gao, Raman Venkataramanan, Zhou Wang, Song Li
Journal: Biomaterials (2012)
Drug management of ulcerative colitis.
Authors: M. A. Kamm, A. Senapati
Journal: BMJ (1992)

Ulcerative colitis is a common disease affecting about 1 in 1000 of the population in the United Kingdom.' Recent therapeutic advances have improved our management of this condition, even though the aetiology remains unknown.Effective treatment of ulcerative colitis depends on making a precise diagnosis and determining the extent and severity of the disease.Crohn's disease, enteric infections, irradiation, and ischaemic colitis should all be excluded.This review covers drug treatment but other factors such as nutrition, psychological factors, risk of cancer in those with longstanding disease, and surgical options all form part of the management. Pharmacology CORTICOSTEROIDSPractice points * Corticosteroids work in acute colitis but should not be used to maintain remission * 5-Aminosalicylic acid compounds prevent relapses and are effective in mild and moderate episodes ofcolitis * Azathioprine is valuable in patients with severe disease
Comparison of alendronate and sodium fluoride effects on cancellous and cortical bone in minipigs. A one-year study.
Authors: M H Lafage, R Balena, M A Battle, M Shea, J G Seedor, H Klein, W C Hayes, G A Rodan
Journal: Journal of Clinical Investigation (1995)

Fluoride stimulates trabecular bone formation, whereas bisphosphonates reduce bone resorption and turnover. Fracture prevention has not been convincingly demonstrated for either treatment so far. We compared the effects of 1-yr treatment of 9-mo-old minipigs with sodium fluoride (NaF, 2 mg/kg/d p.o.) or alendronate (ALN, 4 amino-1-hydroxybutylidene bisphosphonate monosodium, 1 mg/kg/d p.o.) on the biomechanical and histomorphometric properties of pig bones. As expected, NaF increased and ALN decreased bone turnover, but in these normal animals neither changed mean bone volume. NaF reduced the strength of cancellous bone from the L4 vertebra, relative to control animals, and the stiffness (resistance to deformation) of the femora, relative to the ALN group. In the ALN-treated animals, there was a strong positive correlation between bone strength and L5 cancellous bone volume, but no such correlation was observed in the NaF group. Furthermore, the modulus (resistance to deformation of the tissue) was inversely related to NaF content and there was a relative decrease in bone strength above 0.25 mg NaF/g bone. Moreover, within the range of changes measured in this study, there was an inverse correlation between bone turnover, estimated as the percentage of osteoid surface, and modulus. These findings have relevant implications regarding the use of these agents for osteoporosis therapy.
Latulippe--a case study of a one hundred and sixty kilometre runner--. Part II--Environmental conditions.
Authors: L. A. Kuehn
Journal: British Journal of Sports Medicine (1977)

The physiological and biochemical data concerning the hundred and sixty kilometre run performed by this 55 year old athlete in 20 hours was described by O'Hara et al earlier this year, 1977.The environmental con- ditions and other biophysical measurements were not included in this earlier paper, and may be of interest to readers in regards to the environmental stress ex- perienced by this remarkable individual.
Government launches campaign to give MMR vaccine to a million children in England
Authors: G. Iacobucci
Journal: BMJ (2013)

The UK government has launched a national measles, mumps, and rubella (MMR) vaccination catch-up programme for children and teenagers in England in response to the recent surge in measles cases.

The programme will aim to reach as many unvaccinated and partly vaccinated 10-16 year olds as possible by September (the start of the next school year), by using local intelligence such as general practice case registers to identify and vaccinate around a million young people in practices and schools.

The campaign, coordinated by Public Health England, NHS England, and the Department of Health, is aimed at preventing outbreaks similar to the current epidemic in Wales, which has seen 886 confirmed cases since November 2012 after an outbreak in Swansea.1

New figures show 587 confirmed measles cases in England in the first three months of 2013,2 twice …
Perceived prevalence of peanut allergy in Great Britain and its association with other atopic conditions and with peanut allergy in other household members
Authors: SE Emmett, FJ Angus, JS Fry, PN Lee
Journal: Allergy (1999)

Background: Despite increasing awareness of peanut allergy, little is known of its prevalence. We report on a two‐stage interview survey conducted in Great Britain. Methods: A total of 16 434 adults (aged 15+ years) reported their own allergies and atopies and named cohabitants with peanut allergy (stage 1). Follow‐up interviews were conducted with identified sufferers from peanut allergy (stage 2). Results: At stage 1, peanut allergy was reported in 58 respondents and 205 other household members. When we accounted for cases where peanut allergy was unconfirmed or newly reported at stage 2, the prevalence, based on 124 confirmed sufferers, was estimated as 0.48% (95% confidence interval 0.40%–0.55%). The prevalence in children (0.61%, 0.41%–0.82%) was slightly higher than in adults; age‐of‐onset was strikingly earlier. Prevalence was strongly associated with other atopies, particularly tree‐nut allergy. Cases tended significantly to cluster in households. Half of cases had never consulted a doctor. Exactly 7.4% reported being hospitalized after a reaction. Conclusions: Peanut allergy is reported by 1 in 200 of the population and is commoner in those reporting other atopies. The fact of similar rates in children and adults argues against a recent marked rise in prevalence. The frequency and potential lethality of this disorder emphasize the need for sufferers to receive correct medical advice on management.
Phosphatidylinositol 3-kinase-δ inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals
Authors: Sarah E. M. Herman, Amber L. Gordon, Amy J. Wagner, Nyla A. Heerema, Weiqiang Zhao, Joseph M. Flynn, Jeffrey Jones, Leslie Andritsos, Kamal D. Puri, Brian J. Lannutti, Neill A. Giese, Xiaoli Zhang, Lai Wei, John C. Byrd, Amy J. Johnson
Journal: Blood (2010)
Effect of alpha-blocking drugs in asthma.
Authors: E S Assem, S Paterson
Journal: BMJ (1974)

serotonin in the striatum.In the light of these findings and our present clinical finding it seems reasonable to conclude that mid- brain tremor is most probably due to combined interruption of the cerebellofugal pathway, the rubrospinal tract, and the ascending monoaminergic nervous pathways.-Weare, etc.,
Impact of prior acute GVHD on chronic GVHD outcomes: a chronic graft versus host disease consortium study
Authors: M Arora, J Pidala, C S Cutler, X Chai, B Kurland, D A Jacobsohn, S Z Pavletic, J Palmer, G Vogelsang, M Jagasia, K Schultz, S J Lee
Journal: Leukemia (2012)
An Electronic Health Records Study of Long-Term Weight Gain Following Antidepressant Use
Authors: Sarah R. Blumenthal, Victor M. Castro, Caitlin C. Clements, Hannah R. Rosenfield, Shawn N. Murphy, Maurizio Fava, Jeffrey B. Weilburg, Jane L. Erb, Susanne E. Churchill, Isaac S. Kohane, Jordan W. Smoller, Roy H. Perlis
Journal: JAMA Psychiatry (2014)

Short-term studies suggest antidepressants are associated with modest weight gain but little is known about longer-term effects and differences between individual medications in general clinical populations.To estimate weight gain associated with specific antidepressants over the 12 months following initial prescription in a large and diverse clinical population.We identified 22,610 adult patients who began receiving a medication of interest with available weight data in a large New England health care system, including 2 academic medical centers and affiliated outpatient primary and specialty care clinics. We used electronic health records to extract prescribing data and recorded weights for any patient with an index antidepressant prescription including amitriptyline hydrochloride, bupropion hydrochloride, citalopram hydrobromide, duloxetine hydrochloride, escitalopram oxalate, fluoxetine hydrochloride, mirtazapine, nortriptyline hydrochloride, paroxetine hydrochloride, venlafaxine hydrochloride, and sertraline hydrochloride. As measures of assay sensitivity, additional index prescriptions examined included the antiasthma medication albuterol sulfate and the antiobesity medications orlistat, phentermine hydrochloride, and sibutramine hydrochloride. Mixed-effects models were used to estimate rate of weight change over 12 months in comparison with the reference antidepressant, citalopram.Clinician-recorded weight at 3-month intervals up to 12 months.Compared with citalopram, in models adjusted for sociodemographic and clinical features, significantly decreased rate of weight gain was observed among individuals treated with bupropion (β [SE]: -0.063 [0.027]; P = .02), amitriptyline (β [SE]: -0.081 [0.025]; P = .001), and nortriptyline (β [SE]: -0.147 [0.034]; P < .001). As anticipated, differences were less pronounced among individuals discontinuing treatment prior to 12 months.Antidepressants differ modestly in their propensity to contribute to weight gain. Short-term investigations may be insufficient to characterize and differentiate this risk.
Sudden cardiac death in heart failure. The role of abnormal repolarization.
Authors: G F Tomaselli, D J Beuckelmann, H G Calkins, R D Berger, P D Kessler, J H Lawrence, D Kass, A M Feldman, E Marban
Journal: Circulation (1994)

Congestive heart failure is a common, highly lethal cardiovascular disorder claiming over 200,000 lives a year in the United States alone. Some 50% of the deaths in heart failure patients are sudden, and most of these are probably the result of ventricular tachyarrhythmias. Methods designed to identify patients at risk have been remarkably unrewarding, as have attempts to intervene and prevent sudden death in these patients. The failure to impact favorably on the incidence of sudden death in heart failure patients stems largely from a lack of understanding of the underlying mechanisms of arrhythmogenesis. This article explores the role of abnormalities of ventricular repolarization in heart failure patients. We will examine evidence for the hypothesis that alteration of repolarizing K+ channel expression in failing myocardium predisposes to abnormalities in repolarization that are arrhythmogenic. The possible utility of novel electrophysiological and ECG measures of altered ventricular repolarization will be explored. Understanding the mechanism of sudden death in heart failure may lead to effective therapy and more accurate identification of patients at greatest risk.
Reduction of norepinephrine levels with biventricular pacing but recurrence of arrhythmic events in patients with biventricular-ICD and cardiomyopathy
Authors: Domenico Spaziani, Massimo Pagani, Gianfranco del Rosso, Stefano De Servi, Guido Grassi, Gluseppe Mancia
Journal: Journal of the American College of Cardiology (2002)
Eosinophil activation by eotaxin – eotaxin primes the production of reactive oxygen species from eosinophils
Authors: K. Honda, J. Chihara
Journal: Allergy (1999)

Background: The CC chemokine eotaxin has been shown to possess selective chemotactic activity for eosinophils, the major effector cells in allergic inflammation. Reactive oxygen species (ROS) from eosinophils may damage cells or tissue, such as the mucosal epithelium. In this study, we examined the effect of eotaxin on ROS from eosinophils and compared its activity with RANTES and interleukin (IL)‐5. Moreover, we examined the signal transduction of eotaxin and the effect of dexamethasone on ROS from eosinophils. Methods: Eosinophils were isolated by modified CD16‐negative selection. ROS in luminol‐dependent or lucigenin‐dependent chemiluminescence reaction were examined. Calcium ionophore A23187 was added to the mixture of eosinophils with luminol or lucigenin, and then ROS were determined. Results: Eotaxin primed the production of ROS in a dose‐dependent manner. ROS from untreated eosinophils evoked with calcium ionophore A23187 in luminol‐dependent chemiluminescence gave a maximal value of 4957±1035 intensity counts (IC) (mean±SE, n =7) and an integral value of 15.75±3.14 IC (×10 −4 ), while eosinophils that were treated with eotaxin gave maximal values of 11 142±2300 IC (10 nM) and 29 165±3718 IC (100 nM) and integral values of 41.07±5.44 IC (×10 −4 ) (10 nM) and 152.90±22.38 IC (×10 −4 ) (100 nM). Moreover, eotaxin was less effective as a priming agent with lucigenin‐sensitive pathways than luminol‐sensitive pathways. Among several kinds of eosinophils activating cytokines and chemokines, the priming effect of eotaxin on ROS was the most potent. Eotaxin‐primed ROS were inhibited by pertussis toxin, which ADP‐ribolysates G proteins; wortmannin, a phosphatidylinositol‐3‐kinase inhibitor; and genistein, a tyrosine kinase inhibitor, suggesting the involvement of pertussis toxin‐sensitive G proteins, phosphatidylinositol‐3‐kinase, and tyrosine kinase in the signal transduction of eotaxin. Moreover, dexamethasone inhibited ROS from not only untreated eosinophils but also eosinophils treated with eotaxin. Conclusions: Eotaxin may play an important role in the pathogenesis of allergic inflammation through eosinophil activation by priming of eosinophil oxidative metabolism, as well as by involvement in selective eosinophil chemotaxis.
A potent and specific morpholino antisense inhibitor of hepatitis C translation in mice
Authors: Anton P. McCaffrey, Leonard Meuse, Mobin Karimi, Christopher H. Contag, Mark A. Kay
Journal: Hepatology (2003)

Hepatitis C virus (HCV) is an RNA virus infecting one in every 40 people worldwide. Current treatments are ineffective and HCV is the leading cause of liver failure leading to transplantation in the United States and Europe. Translational control of HCV is a prime therapeutic target. We assessed the inhibitory potential of morpholino phosphoramidate antisense oligonucleotides (morpholinos) on HCV translation by codelivering them with reporter plasmids expressing firefly luciferase under the translational control of the HCV internal ribosome entry site (IRES) into the livers of mice. Real–time imaging of HCV IRES luciferase reporter messenger RNA (mRNA) translation in living mice showed that a 20–mer complementary to nucleotides 345–365 of the IRES inhibited translation by greater than 95% for at least 6 days and showed mismatch specificity. No significant nonspecific inhibition of a cap–dependent luciferase or encephalomyocarditis virus (EMCV) IRES luciferase reporter translation was observed. Inhibition by the 20–mer morpholino was dose dependent, with 1 nmol/mouse giving the highest inhibition. In conclusion, morpholino antisense oligonucleotides are potent inhibitors of HCV IRES translation in a preclinical mouse model; morpholinos have potential as molecular therapeutics for treating HCV and other viral infections. The in vivo model described is a broadly applicable, straightforward, and rapid readout for inhibitor efficacy. As such, it will greatly facilitate the development of novel therapeutic strategies for viral hepatitis. Notably, the level of antisense inhibition observed in this in vivo model is similar to the maximal inhibition we have obtained previously with RNA interference in mice.
Continuing education should no longer be funded by drug industry, says <i>CMAJ</i>
Authors: David Spurgeon
Journal: BMJ (2008)

The current system of continuing health education—sponsored largely by an industry with a vested interest in promoting its products—is unacceptable to self regulated health professionals, says the journal of the Canadian Medical Association. 

The CMAJ editorial says that health professionals should take over medical education and base it on their needs and those of their patients (doi: 10.1503/cmaj.080317).

“It is time to stop the pharma-driven ‘free lunch’ approach and place our continuing medical education system firmly in the hands of unbiased and qualified people, not corporations whose …
Biomarker Analysis of WJOG4107 (A Randomized Phase II Trial of Adjuvant Chemotherapy with S-1 vs CDDP + S-1 in NSCLC)
Authors: M. Takeda, T. Mitsudomi, K. Nishio, Y. Iwamoto, T. Yamanaka, H. Yoshioka, S. Tsukamoto, T. Koike, K. Nakagawa, Y. Nakanishi
Journal: Annals of Oncology (2013)
Abstract 1762: Highly potent anti-cancer ‘salan’ Titanium(IV) complexes: Structure - function relationship
Authors: Sigalit Meker, Ori Braitbard, Cesar Manna, Esther Weiss, Edit Tshuva, Jacob Hochman
Journal: Cancer Research (2012)

Abstract Cisplatin is a widely used platinum-based metallo-chemotherapeutic drug that is considered an efficient treatment mainly for testicular and ovarian cancers. However, its narrow activity range and severe side effects trigger studies of other potent transition metal complexes. Two titanium(IV) anti-cancer agents that have been previously studied extensively as cisplatin alternatives are titanocene dichloride and budotitane. Despite their high activity, these complexes failed clinical trials mainly due to their poor water stability and formation of unidentified aggregates in water solutions. Our research group focuses on development of new, better-suited families of anti-tumor Ti(IV) complexes lacking Cp or diketonato ligands, and their investigation as anti-tumor agents. We recently reported the synthesis, characterization, and cytotoxicity of “salan” type Ti(IV) complexes [1]. The well defined hydrolytic behaviour, high stability, and high cytotoxicity of these compounds are strongly correlated to their particular structure. This enables fine tuning of complex properties by structural modifications. Herein we elaborate on the investigation of these salan titanium(IV) compounds. The correlation between the complex properties: structure, hydrolytic stability and cytotoxicity will be discussed, revealing insights on the biological mechanism of their cytotoxicity, suggesting an apoptotic cell death pathway.Additionally, further biological evaluation is presented, evincing that these compounds are markedly more active than cisplatin towards human and murine cancer-derived cell lines, including colon, ovarian, lung, cervix, pancreas, leukaemia, skin and breast, with activity also against cisplatin-resistant and multi-drug-resistant cells, and with minor effect on primary murine cells. In vivo experiments are now under way to determine both safety, as well as the anti-cancer activity of these complexes. [1] D. Peri, S. Meker, C. M. Manna, E. Y. Tshuva, Inorg. Chem., 2011, 50, 1030. 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 1762. doi:1538-7445.AM2012-1762