tbuckley/cabot-search huggingface dataset:
Raised arterial pressure in parents of proteinuric insulin dependent diabetics.
Authors: G C Viberti, H Keen, M J Wiseman
Journal: BMJ (1987)

Arterial pressure is raised early in the subset of insulin dependent diabetics at risk of later development of progressive renal failure, suggesting that liability to arterial hypertension may play a part in the aetiology of diabetic kidney disease. Evidence for a genetic basis was therefore sought by measuring the blood pressures of the 26 surviving parents of 17 insulin dependent diabetic patients with proteinuria and comparing them with those of the parents of 17 matched insulin dependent diabetic patients without proteinuria selected from the same cohort. Systolic and diastolic pressures were significantly higher in parents of the proteinuric (mean (SD) 161 (27)/94 (14) mm Hg) than in parents of the non-proteinuric patients (146 (21)/86 (11) mm Hg). The difference between the sample mean blood pressures was 15 mm Hg (95% confidence interval 3.3 to 26.7 mm Hg) for systolic pressure and 8 mm Hg (95% confidence interval 0.8 to 15.2 mm Hg) for diastolic pressure. These differences were independent of age, sex, and adiposity. There was a significant correlation between the mean arterial pressures in the proteinuric patients and the higher mean blood pressure in their parents. High blood pressure in non-diabetic parents may be a marker of susceptibility to clinical nephropathy in their insulin dependent diabetic offspring.
The PKCα-D294G Mutant Found in Pituitary and Thyroid Tumors Fails to Transduce Extracellular Signals
Authors: Yimin Zhu, Qihan Dong, Bee Jen Tan, Wee Guan Lim, Shufeng Zhou, Wei Duan
Journal: Cancer Research (2005)

Abstract Protein kinase C (PKC) is a key regulator of cell proliferation, differentiation, and apoptosis and is one of the drug targets of anticancer therapy. Recently, a single point mutation (D294G) in PKCα has been found in pituitary and thyroid tumors with more invasive phenotype. Although the PKCα-D294G mutant is implicated in the progression of endocrine tumors, no apparent biochemical/cell biological abnormalities underlying tumorigenesis with this mutant have been found. We report here that the PKCα-D294G mutant is unable to bind to cellular membranes tightly despite the fact that it translocates to the membrane as efficiently as the wild-type PKCα upon treatment of phorbol ester. The impaired membrane binding is associated with this mutant's inability to transduce several antitumorigenic signals as it fails to mediate phorbol ester–stimulated translocation of myristoylated alanine–rich protein kinase C substrate (MARCKS), to activate mitogen-activated protein kinase and to augment melatonin-stimulated neurite outgrowth. Thus, the PKCα-D294G is a loss-of-function mutation. We propose that the wild-type PKCα may play important antitumorigenic roles in the progression of endocrine tumors. Therefore, developing selective activators instead of inhibitors of PKCα might provide effective pharmacological interventions for the treatment of certain endocrine tumors.
135 HEPATOCYTE SPECIFIC IKK2 DELETION CAUSES IMBALANCED NF-κB ACTIVATION AFTER PARTIAL HEPATECTOMY AND LEADS TO AN EARLIER RESOLUTION OF LIVER DAMAGE
Authors: Y. Malato, N. Beraza, L.E. Sander, M. Almasaoudi, C. Liedtke, C. Trautwein
Journal: Journal of Hepatology (2008)
New tool to aid detection of child sexual exploitation
Authors: K. Rogstad, J. Ashby, D. Wilkinson
Journal: BMJ (2014)

Thomas and Humphery highlighted the challenges inherent in safeguarding young people against child sexual exploitation (CSE).1 Consultations with young people within sexual health services routinely entail detailed exploration of risk and vulnerability, placing sexual health as key services to identify those at risk of CSE.

In response to emerging understanding about the prevalence and nature of CSE,2 the …
Roentgenographic Findings in PEEP Therapy
Authors: Adele R. Altman
Journal: JAMA (1979)

We reviewed serial chest roentgenograms of 82 patients treated with positive end-expiratory pressure (PEEP) therapy for morbid pulmonary failure. No change was identified in the appearance of the chest roentgenograms in 49 patients. Thirty-three patients showed pulmonary hyperinflation, varying degrees of apparent clearing of alveolar or interstitial disease, and resorption of interstitial and pleural fluid. Lung hyperinflation and interstitial gas generally preceded pneumomediastinum and pneumothorax. These pulmonary complications were identified roentgenographically, often before they became clinically apparent. No consistent correlation was observed between these roentgenographic changes and the ventilatory pressures employed. The radiologist should be informed that a patient is receiving PEEP therapy, as the earliest signs of alveolar rupture—interstitial emphysema—are frequently subtle. (<i>JAMA</i>242:727-730, 1979)
Effect of norepinephrine and heart rate on intracellular sodium activity and membrane potential in beating guinea pig ventricular muscle.
Authors: A A Wilde, A G Kléber
Journal: Circulation Research (1991)

The effect of 3 microM norepinephrine (NE) on intracellular sodium activity (aiNa) and resting membrane potential was studied by continuous intracellular recordings with a conventional and an ion-selective microelectrode. The electrodes were impaled simultaneously in small (diameter, 0.3 mm) superfused trabeculae of the beating guinea pig ventricle at 37 degrees C. In the absence of NE, changes of the beating rate produced an increase of aiNa by 1.5 +/- 0.17 mM (from 0 to 1 Hz) and 1.9 +/- 0.47 mM (from 0 to 2 Hz). In the presence of NE, there was a very small significant increase of aiNa during constant stimulation (1 Hz) and at at [K+]o of 4.7 and 11.5 mM. After 7 minutes of exposure, aiNa increased by 0.5 +/- 0.19 mM (mean +/- SEM, n = 4) at [K+]o of 4.7 mM and by 0.5 +/- 0.22 (n = 6) at [K+]o of 11.5 mM. Resting membrane potential became more positive by 1 mV at both levels of [K+]o. The effect of NE became also clearly manifest from the configurational changes of action potentials (profound increase in plateau height and duration). Stimulation of the Na(+)-K+ pump by NE became manifest from the changes of resting membrane potential and aiNa after abrupt cessation of stimulation. The magnitude and the rate of the decrease in aiNa and the initial rate of hyperpolarization were significantly greater in the presence of NE than in its absence.(ABSTRACT TRUNCATED AT 250 WORDS)
Scientists are urged to oppose new US legislation that will put studies behind a pay wall
Authors: K. Epstein
Journal: BMJ (2012)

The US government could end guarantees of free access to publicly funded medical research under legislation introduced in Congress on 16 December that has backing from the publishing industry. 

The Research Works Act, although only 370 words in length, is the latest attempt by the Association of American Publishers, which represents scholarly and professional publications, to undo a 2008 policy adopted by the National Institutes of Health. That policy made it mandatory for articles arising from government financed research to be made free to view on the electronic archives of the National Library of Medicine’s website PubMed Central ( BMJ 2007;335:906, doi:10.1136/bmj.39384.638241.DB). A similar policy is being adopted in the United Kingdom, the coalition government noted in a December 2011 report on innovation (http://bit.ly/wiKOaK).

In the US the threat of a reinstated pay wall has triggered a backlash from researchers, doctors, patients, peer reviewers, librarians, teachers, and other advocates of open access, who argue that the intellectual work of research …
G-CSF Induced Bone Marrow Hyperplasia: Characteristic Appearance on Total Body Blood Pool and Delayed Tc-99m MDP Bone Scan
Authors: HANI H. ABU-JUDEH, SLEIMAN Y. NADDAF, HOSSAM A. EL-ZEFTAWY, HUSSEIN M. ABDEL-DAYEM
Journal: Clinical Nuclear Medicine (1998)

Total body blood pool and delayed bone scans are presented as an example of bone marrow hyperplasia in patient with AIDS with a CD4 count of <50, who was receiving high doses of granulocyte-colony stimulating factor (G-CSF).
Drug combination adds fuel to US abortion debate
Authors: T. L Rutter
Journal: BMJ (1995)

A recent study in the US showed that abortion was achieved in 171/178 women aged 18 to 47 with pregnancies of 63 days or less duration through the administration of an intramuscular injection of methotrexate (a drug used to treat cancer) followed five to seven days later with a dose of misoprostol (used to treat ulcers). The report of this study prompted the founder of the anti-abortion group Operation Rescue to threaten the report's author with being "hunted down and tried for genocide" should abortion ever be made illegal. While the National Abortion Rights Action League urged that the procedure be judged on medical not political terms, a spokesperson for the National Right to Life Committee expressed concern for the reproductive and psychological health of women undergoing medical abortions. The Population Council is currently completing clinical trials of the regimen which employs RU-486 to achieve medical abortion and expects to file a new drug application with the US Food and Drug Administration (FDA) in 1996. The methotrexate/misoprostol combination would be much less expensive than RU-486 (approximately $10 compared to $250 at current prices), and a pharmaceutical company is currently attempting to raise the six million dollars necessary to fund the large-scale clinical trials which must precede FDA approval. While the availability of medical abortions would make the procedure much more accessible and private for women, proper counseling must be given to the women to avoid unwanted side effects and so that the women know what to expect.
RESPECTIVE AND COMBINED CONTRIBUTIONS OF MITRAL VALVE LEAFLET LENGTH AND SEPTAL THICKNESS TO LEFT VENTRICULAR OUTFLOW OBSTRUCTION IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY: A CARDIAC MAGNETIC RESONANCE IMAGING STUDY
Authors: Kareem Andre Morant, David McCarty, John Stirrat, David Scholl, Maria Drangova, Terry Thompson, Gerald Wisenberg, James White
Journal: Journal of the American College of Cardiology (2012)
Human herpesvirus 8 acute infection of endothelial cells induces monocyte chemoattractant protein 1–dependent capillary-like structure formation: role of the IKK/NF-κB pathway
Authors: Elisabetta Caselli, Simona Fiorentini, Carla Amici, Dario Di Luca, Arnaldo Caruso, M. Gabriella Santoro
Journal: Blood (2006)
Abstract 2073: Parthenolide-mediated redox modification of Keap1 leads to differential effects on radiosensitivities of prostate cancer and normal cells
Authors: Yong Xu, Fang Fang, Daret K. St. Clair, Yulan Sun, William H. St. Clair
Journal: Cancer Research (2012)

Abstract Elevated oxidative stress is more frequently observed in cancer cells than in normal cells. Thus, further exposure to exogenous reactive oxygen species (ROS) is expected to push cancer to cell death, whereas normal cells may maintain redox homeostasis through ROS mediated adaptive responses. We previously demonstrated that parthenolide selectively enhances radiosensitivity of prostate cancer cells through activation of a NADPH oxidase-dependent redox signaling pathway. Our present study identifies the status of the redox sensitive Kelch-like ECH-associated protein-1 (Keap1) as a central regulator responsible for the parthenolide-mediated differential redox modification. This results in both a radiosensitization effect in prostate cancer cells and a radioresistance effect in normal prostate epithelial cells. Mechanistically, parthenolide increases the reduced state of Keap1 in prostate cancer cells in a thioredoxin-dependent manner but causes oxidation of Keap1 in normal prostate epithelial cells. Selective knock-down of thioredoxin leads to Keap1 oxidation and subsequent activation of the NF-E2-related factor 2 (Nrf2). These results suggest that redox modification of Keap1 is a major mechanism for the parthenolide effect on radiation therapy in cancer and normal cells. Consistent with the differential effect of parthenolide in cancer and normal cells, the levels of superoxide, hydrogen peroxide and peroxynitrite were selectively increased in parthenolide treated prostate cancer cells but not in normal prostate epithelial cells, indicating the selective increase of ROS in cancer cells. Parthenolide reduces the levels of Nrf2 targets, antioxidant proteins including manganese superoxide dismutase and heme oxygenase in prostate cancer cells, but increases the levels of these proteins in normal cells. This suggests that an antioxidant response is critical for the protection of normal cells against ROS generated from parthenolide. 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 2073. doi:1538-7445.AM2012-2073
975. TLR9 Activation Is Involved in the Immune Response to Helper Dependent Adenoviral Vectors
Authors: Vincenzo Cerullo, Michael P. Seiler, Nicola Brunetti-Pierri, Viraje Mane, Christopher Clarcke, Brendan Lee
Journal: Molecular Therapy (2006)

Toll-like Receptors (TLRs) are innate receptors that sense microbial products and trigger dendritic cell (DCs) maturation and cytokine production, thus effectively bridging innate and adaptive immunity. Members of the Toll-like receptor 9 (TLR9) subfamily are evolutionarily related and sense viral and bacterial infection at the endosomal subcellular compartment. Whereas TLR9 directly recognizes viral and bacterial CpG-DNA motifs, murine TLR7 and human TLR8 sense viral single stranded RNA motifs. Upon ligand- driven activation, members of the TLR9 subfamily bridge innate and adaptive immunity by activating immature antigen-presenting DCs into professional antigen-presenting cells in a T helper cell- independent fashion. In this study we evaluated whether TLR9 contributes to the acute immunopathology typically seen after systemic administration of a Helper-dependent adenoviral vector (HD-Ad) in the pΔ28E4 Backbone. To address this question we investigated the degree of activation of the innate immune response following systemic injection of Helper-dependent adenoviral vector (HD-Ad) in mice expressing a structurally aberrant TLR9 receptor). In contrast to wild type mice, we found that TLR9CpG1/CpG1 mice showed a reduced activation of the innate immune response following i.v. injection of high doses of HD-Ad, as shown by reduced increase in IL-6 and IL-12. Next we tested whether pharmacologically blocking TLR9 signaling in wild type mice could attenuate the innate immune response to HD-Ad. In agreement with the TLR9 CpG1/CpG1 model, we found a similar reduction in innate immune response after TLR9 blockade. In the present study we showed for the first time that TLRs are involved in the innate immune response following systemic administration of adenoviral vectors and we showed that selectively blocking TLRs can be potentially used to reduce the toxicity of Ad-mediated gene therapy.
Laser microdissection for the assessment of the clonal relationship between chronic lymphocytic leukemia/small lymphocytic lymphoma and proliferating B cells within lymph node pseudofollicles
Authors: M L Vandewoestyne, V C Pede, K Y Lambein, M F Dhaenens, F C Offner, M M Praet, J J Philippé, T J Kipps, D L Deforce
Journal: Leukemia (2011)
Response to Comment on: Wheeler et al. Macronutrients, Food Groups, and Eating Patterns in the Management of Diabetes: A Systematic Review of the Literature, 2010. Diabetes Care 2012;35:434–445
Authors: Madelyn L. Wheeler, Stephanie A. Dunbar, Lindsay M. Jaacks, Wahida Karmally, Elizabeth J. Mayer-Davis, Judith Wylie-Rosett, William S. Yancy
Journal: Diabetes Care (2012)

We appreciate the comments from Drs. Esposito and Giugliano (1) concerning our systematic review (2). Each issue will be addressed as outlined in their letter.

Wrong statement about results of published articles (reference 104): We acknowledge that the results were misquoted in the systematic review and appreciate the identification of the error. The correct data have been substituted in the online version of the article.

Reporting of one triplicate study (references 105–107): The three publications include different patients from the same hospital, different meals consumed, and, to some extent, different methodology used. The authors …
Drug development: Innovation or imitation deficit?
Authors: S. G. Morgan, C. M. Cunningham, M. R. Law
Journal: BMJ (2012)

Light and Lexchin argue that the pharmaceutical innovation crisis is a myth.1 Although they correctly diagnose the issue, the drug approval data provided tell only half of the story. To shed more light on drug development trends, we classified US Food and Drug Administration approvals of new drugs (therapeutic new molecular entities) into one of three mutually exclusive categories: first-of-kind drugs to be approved within chemical or …
Antibodies to thyroglobulin and thyroid peroxidase in rheumatoid arthritis: environmental and genetic associations
Authors: Peter J Charles, Darren Plant, Muslima Chowdhury, Jane Worthington, Patrick Venables
Journal: Annals of the Rheumatic Diseases (2011)

Recent years have seen the emergence and establishment of antibodies to citrullinated antigens as the primary diagnostic marker for rheumatoid arthritis (RA). Recent work has established the close link between genetic factors, environmental factors and the presence of these antibodies. The authors have therefore examined these relationships in another serological subgroup with RA. Autoimmune thyroid disease (AITD) is reported in up to 30% of patients with RA. Like RA, AITD has also been associated with a combination of genetic and environmental influences. The authors have examined the incidence of antithyroid antibodies (ATA) and anti-CCP by ELISA in a well-characterised cohort collected by the Arthritis Research Epidemiology Unit, University of Manchester. This cohort (n=754) was genotyped for shared epitope and <i>PTPN22</i> and smoking history was recorded as never smoked; past smoker or current smoker. Antibodies to thyroid peroxidase or thyroglobulin were detected in 16% and 9% of patients, respectively. The overall frequency of ATA in this cohort was 19%. Anti-CCP was detected in 58% of patients. There was no association between the presence of ATA and anti-CCP. There was no association between the shared epitope expression, or shared epitope copy number, and the presence of ATA. However the presence of <i>PTPN22 R620W</i> was significantly associated with the presence of ATA (p=0.034). The presence of the <i>R620W</i> allele increased the risk of ATA by 44%. This association was shown to be independent of any association between <i>PTPN22</i> and anti-CCP. There was a negative association of ATA and smoking. ATA frequencies were higher in patients who had never smoked. A differential risk was observed between those patients who were still smoking (p=0.001; OR 0.360 (0.198–0.654)) and those who had stopped smoking in the past (p=0.013; OR 0.558 (0.352-0.885)) compared to those who had never smoked. This is in keeping with the recent reports of a protective effect of smoking in primary AITD. The presence of ATA in patients with RA is associated with the expression of the <i>PTPN22 R620W</i> allele, independent of any association with RA or anti-CCP. Smoking, in contrast to its role as a risk factor for the development of RA, appears to have a protective effect for the presence of ATA in RA patients.
THE EPIDEMIOLOGY OF CONTACT DERMATITIS IN POLAND
Authors: EDWARD RUDZKI, DANUTA KLENIEWSKA
Journal: British Journal of Dermatology (1970)

Journal Article THE EPIDEMIOLOGY OF CONTACT DERMATITIS IN POLAND Get access EDWARD RUDZKI, EDWARD RUDZKI Department of Dermatology, School of Medicine, Warsaw Search for other works by this author on: Oxford Academic Google Scholar DANUTA KLENIEWSKA DANUTA KLENIEWSKA Department of Dermatology, School of Medicine, Warsaw Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 83, Issue 5, 1 November 1970, Pages 543–545, https://doi.org/10.1111/j.1365-2133.1970.tb15738.x Published: 01 November 1970 Article history Accepted: 29 January 1970 Published: 01 November 1970
Time of Exposure and Type of Diabetes May Determine Treatment Outcome of Group Clinics
Authors: David Edelman
Journal: Annals of Internal Medicine (2010)

Letters5 October 2010Time of Exposure and Type of Diabetes May Determine Treatment Outcome of Group ClinicsDavid Edelman, MDDavid Edelman, MDFrom Durham Veterans Affairs Medical Center, Durham, NC 27705.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-7-201010050-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We appreciate the thoughtful response from Drs. Porta and Trento. We considered the possibility that hemoglobin A1c levels might be more slowly reactive to interventions than blood pressure and that this could explain why our group medical clinic intervention, compared with usual care, reduced systolic blood pressure but not hemoglobin A1c level. Because we did not follow patients for more than 1 year, we cannot exclude Drs. Porta and Trento's hypothesis that significant differences may have occurred between study groups had we continued the intervention longer. However, our leading hypothesis was that there was more available support, and ...References1. Trento M, Gamba S, Gentile L, Grassi G, Miselli V, Morone G, et al; ROMEO Investigators. Rethink Organization to iMprove Education and Outcomes (ROMEO): a multicenter randomized trial of lifestyle intervention by group care to manage type 2 diabetes. Diabetes Care. 2010;33:745-7. [PMID: 20103547] CrossrefMedlineGoogle Scholar2. Trento M, Passera P, Borgo E, Tomalino M, Bajardi M, Cavallo F, et al. A 5-year randomized controlled study of learning, problem solving ability, and quality of life modifications in people with type 2 diabetes managed by group care. Diabetes Care. 2004;27:670-5. [PMID: 14988283] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Durham Veterans Affairs Medical Center, Durham, NC 27705.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMedical Clinics Versus Usual Care for Patients With Both Diabetes and Hypertension David Edelman , Sonja K. Fredrickson , Stephanie D. Melnyk , Cynthia J. Coffman , Amy S. Jeffreys , Santanu Datta , George L. Jackson , Amy C. Harris , Natia S. Hamilton , Helen Stewart , Jeannette Stein , and Morris Weinberger Time of Exposure and Type of Diabetes May Determine Treatment Outcome of Group Clinics Massimo Porta and Marina Trento Metrics 5 October 2010Volume 153, Issue 7Page: 483KeywordsBlood pressureConflicts of interestGlucoseHemoglobinPatientsSystolic pressure ePublished: 5 October 2010 Issue Published: 5 October 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...