tbuckley/cabot-search huggingface dataset:
Abstract 20311: MYBPC3 Mutations Causative for Hypertrophic Cardiomyopathy Result in Locus-Dependent Alterations in Cellular Localization and Contractility
Authors: Adam S Helms, Amelia Glazier, Sarah Bartolone, Vi Tang, Jaime Yob, Margaret Westfall, Santiago Schnell, Sharlene M Day
Journal: Circulation (2014)

Introduction: Mutations in MYBPC3 resulting in truncated proteins are the most common genetic cause of hypertrophic cardiomyopathy (HCM). Whether lack of sufficient MYBPC3 protein is the primary disease mechanism is controversial. We hypothesize instead that truncated MYBPC3 proteins exert dominant-negative effects on sarcomere structure and function. Methods and Results: MYBPC3 mutations resulting in short (Ile154LeuFs*5, 17 kD) or long (Asp1076Valfs*6 and Trp1098*, each ~120 kD) truncated proteins were studied. For each truncated protein, in silico analysis (I-TASSER) predicted marked deviation from the predicted wild-type (WT) structure. Immunofluorescence of adenoviral-expressed proteins in neonatal rat ventricular cardiomyocytes revealed that WT MYBPC3 was correctly localized at sarcomere A-bands. Near-complete mislocalization (predominantly nuclear) was observed for Ile154LeuFs*5 MYBPC3. Both Asp1076Valfs*6 and Trp1098*MYBPC3 mutant proteins localized imprecisely within the sarcomere, but also were diffusely present in the cytosol. Western blot of myofilament preparations confirmed no sarcomere incorporation of Ile154LeuFs*5, and reduced incorporation of Asp1076Valfs*6 and Trp1098* truncated MYBPC3 (Asp1076Valfs*6 28.1+0.4% and Trp1098* 20.3+0.2% vs. WT 72.4+0.2%, p&lt;0.001). Ile154LeuFs*5 MYBPC3 was exclusively present in the non-myofilament fraction, while Asp1076Valfs*6 and Trp1098* MYBPC3 were 3-fold enriched in this fraction (p=0.01). Analysis of sarcomere shortening (Ionoptix) in adenoviral-infected adult rat ventricular cardiomyocytes indicated reduced peak shortening for Trp1098* (5.30+0.92% vs. WT 8.35+0.49%, p&lt;0.05) and time to peak contraction (43+2 ms vs. WT 67+3 ms, p&lt;0.05). In contrast, no significant effect of Ile154LeuFs*5 MYBPC3 on cellular contractility was observed. Conclusions: Truncating MYBPC3 mutations are predicted to markedly alter protein structure. Longer truncated proteins partially incorporate into the sarcomere lattice and alter contractile function while shorter truncated proteins accumulate in other cellular compartments. These results suggest distinct mutation-specific negative effects of truncating MYBPC3 mutations on myocyte function.
Abstract MP39: Peer Comparison Feedback and Financial Incentives to Promote Employees’ Healthy Food Choices: a Randomized Controlled Trial
Authors: Anne N Thorndike, Jason Riis, Douglas E Levy
Journal: Circulation (2014)

Objective: New strategies are needed to promote healthy food choices. We conducted a 3-arm randomized controlled trial to compare the effectiveness of: 1) peer comparison feedback about food purchases (FB), 2) feedback plus financial incentives (FB+INC), or 3) no feedback (control) to promote healthy purchases by employees in a large hospital cafeteria. Methods: Subjects were 2672 employees who made ≥ 6 purchases in 2 months prior to study. All items were labeled green (healthy), yellow (less healthy), and red (unhealthy). The FB group received monthly letters from Oct-Dec 2012 reporting proportion of the individual’s purchases that were green/yellow/red in the prior month, comparing to purchases by “all” and by “healthiest” employees. The FB+INC group received a similar letter plus an incentive ($10) to increase their proportion of green in the next month. Control received no contact. We compared changes in green and red purchases from baseline (Sept) to intervention end (Dec) and to end of a 3 month wash-out (Mar 2013) using random effects models of employee-specific changes in purchases. Results: Subjects were: 73% female; 48% &gt; 40 years; 75% white. At baseline, mean proportion of green purchases was 50% for all groups. The Figure shows monthly percentage change in proportion of green purchases compared to baseline. At end of intervention compared to baseline, control had no change, FB increased 1.8% (p=0.07 vs. control), and FB+INC increased 2.2% (p=0.03 vs. control). At end of wash-out compared to baseline, control increased 1.7%, FB increased 2.6% (p=0.4 vs. control), and FB+INC increased 3.0% (p=0.2 vs. control). Red purchases decreased in both intervention groups compared to control at end of intervention (p=0.07 for both) and wash-out (p≤0.04 for both). Conclusions: Providing peer comparison feedback with small financial incentives increased healthy purchases by employees. This population-based approach for promoting healthy eating could be effective in other worksite, institutional, and retail settings.
Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice
Authors: Timothy LaVaute, Sophia Smith, Sharon Cooperman, Kazuhiro Iwai, William Land, Esther Meyron-Holtz, Steven K. Drake, Georgina Miller, Mones Abu-Asab, Maria Tsokos, Robert Switzer, Alexander Grinberg, Paul Love, Nancy Tresser, Tracey A. Rouault
Journal: Nature Genetics (2001)
Abstract A48: CD4+ T lymphocyte ablation prevents pancreatic carcinogenesis in mice
Authors: Yaqing Zhang, Wei Yan, Esha Mathew, Filip Bednar, Shanshan Wan, Meredith A. Collins, Rebecca A. Evans, Theodore H. Welling, Robert H. Vonderheide, Marina Pasca di Magliano
Journal: Cancer Research (2015)

Abstract This abstract is also being presented as a short talk in Session 6: Immunology. A full abstract is printed in the Proffered Abstracts section (PR11) of the Conference Proceedings. Citation Format: Yaqing Zhang, Wei Yan, Esha Mathew, Filip Bednar, Shanshan Wan, Meredith A. Collins, Rebecca A. Evans, Theodore H. Welling, Robert H. Vonderheide, Marina Pasca di Magliano. CD4+ T lymphocyte ablation prevents pancreatic carcinogenesis in mice. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A48.
Patients who make my practice: Known by name
Authors: F. J Dryburgh
Journal: BMJ (1998)

I had not met her before, but I have known her name for 25 years: Patricia Patterson. She had hypoparathyroidism since thyroidectomy when she was 21 years old and over the years, on treatment with vitamin D, had had episodes of hypocalcaemia and hypercalcaemia. This latest episode of hypercalcaemia was related to an uncommon conjunction of events, stopping hormone replacement therapy and continuing with vitamin D treatment at the dose prescribed for some years. We …
1020. Development and Evaluation of a Genetically-Modified Adenovirus Vector That Specifically Targets Tumors Via the Bloodstream Following Systemic Administration
Authors: Masaki Akiyama, Peter W. Roelvink, David A. Einfeld, Selva Murugesan, C. Richter King, Thomas J. Wickham
Journal: Molecular Therapy (2004)

The development of genetically modified adenovirus vectors capable of targeting tumors following systemic administration is an important goal for the treatment of disseminated cancer. Achieving this goal requires that the native adenovirus coat protein/receptor interactions are removed and replaced with new tumor-selective ligand/receptor interactions. Towards this goal, we have created vectors that are ablated for native receptor binding and that additionally contain a pseudo-receptor binding ligand or a tumor-selective peptide motif inserted into the HI loop of fiber. In vivo experiments showed that ablating both CAR and penton base binding is critical to reduce non-targeted tissue transduction. In addition, pharmacokinetic studies indicated that these tropism modified vectors efficiently enter and persist in the bloodstream following intraperitoneal (i.p.) administration. Interestingly, this sustained circulation was only observed after i.p. administration and not after intravenous administration. Furthermore, the combination of capsid modification and extended blood circulation could achieve receptor-mediated transduction on pseudo-receptor expressing subcutaneous tumor.
Traditional Risk Factors for Coronary Heart Disease
Authors: Martin Root, Fred Cobb
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 2584: Complete regression and protective immune responses obtained in B16 melanomas after treatment with LTX-315 (Oncopore®)
Authors: Ketil André Camilio, Gerd Berge, Chandra Sekhar Ravuri, Øystein Rekdal, Baldur Sveinbjørnsson
Journal: Cancer Research (2014)

Abstract Background: Malignant melanoma is the most aggressive and deadliest form of skin cancer, with a high mortality rate among late-stage melanoma patients. This calls for new and improved therapies within the field. Cationic antimicrobial peptides (CAPs) are naturally occurring molecules found in most species, in which they play a significant role in the first line of defense against pathogens, and several CAPs have shown promising anticancer activity. Structure-activity relationship studies on the CAP bovine lactoferricin has resulted in the design of a short chemically modified lytic anticancer peptide, LTX-315, which has potential as a new anticancer drug. Previous animal studies conducted with LTX-315 have demonstrated that intratumoral (i.t.) treatment of syngeneic murine A20 B-cell lymphomas and CT26WT colon carcinomas resulted in complete tumor regression. In the present study, we investigated the antitumor effects of LTX-315 against highly aggressive B16 melanomas in syngeneic mice. Methods: The cytotoxicity of LTX-315 was tested against a series of cell lines in vitro using the MTT assay. B16F1 melanoma cells (5 x 104) were intradermally inoculated into the abdomen of syngeneic C57BL/6N mice and established tumors treated i.t. with LTX-315. Tumor tissue and blood samples were taken for analysis to elaborate the mechanism of action of LTX-315 and for potential immune modulatory effects following i.t. treatment. Blood plasma was analyzed for IL 1β and IL 6 content and tumor tissue was analyzed for infiltrating immune cells and expression of pro-inflammatory cytokines using immunohistochemistry and real time qPCR, respectively. Results: LTX-315 rapidly kills B16 melanoma cells and induces the release of Danger-Associated Molecular Pattern molecules such as the High Mobility Group Box-1 protein in vitro. Intratumoral (i.t.) administration of LTX-315 resulted in tumor necrosis and the infiltration of immune cells into the tumor parenchyma followed by a complete regression of the tumor in the majority of the animals. Animals cured by LTX-315 treatment were protected against a re-challenge with live B16 tumor cells. Conclusions: Our results demonstrate that LTX-315 i.t. treatments with LTX-315 induces complete regression of solid B16F1 melanoma tumors, thus leading to local tumor control, followed by protective immune responses. Thus, LTX-315 has potential as a novel immunotherapeutic agent. Citation Format: Ketil André Camilio, Gerd Berge, Chandra Sekhar Ravuri, Øystein Rekdal, Baldur Sveinbjørnsson. Complete regression and protective immune responses obtained in B16 melanomas after treatment with LTX-315 (Oncopore®). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2584. doi:10.1158/1538-7445.AM2014-2584
HISTAMINE IN THE TREATMENT OF PEPTIC ULCER
Authors: B M BERNSTEIN
Journal: Annals of Internal Medicine (1947)

Article1 June 1947HISTAMINE IN THE TREATMENT OF PEPTIC ULCERBENJAMIN M. BERNSTEIN, M.D., F.A.C.P.BENJAMIN M. BERNSTEIN, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-26-6-852 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptCruveilhier in 1829 said "ulcer of the stomach is surrounded by profound obscurity, and one wonders why a single place in the stomach is deeply affected and all the other parts of the organ are in a state of perfect integrity." Since that date many investigations have been devoted to the study of both the etiology and treatment of ulcer, and have led to numerous arguments and conflicting opinions. The attempts to determine the etiology of peptic ulcer have failed to yield any convincing results. Others have attempted to prevent the development of experimental ulcers by psychological, endocrine or chemical...Bibliography1. PALMER WL: Peptic ulcer and gastric secretion, Arch. Surg., 1942, xliv, 452. CrossrefGoogle Scholar2. SANDWEISS D: Nocturnal gastric secretion, Jr. Am. Med. Assoc., 1946, cxxx, 260. Google Scholar3. QUIGLEY JP: Motor physiology of stomach, pylorus and duodenum with special reference to gastro-duodenal ulcer, Arch. Surg., 1942, xliv, 414. CrossrefGoogle Scholar4. BROWNDOLKART CGRE: Gastric acid during recurrences and remissions of duodenal ulcer, Arch. Int. Med., 1937, lx, 680. CrossrefGoogle Scholar5. BARFORD LJ: Statistical enquiry into etiology, symptoms, signs and results of treatment in 166 cases of gastric and duodenal ulcer, Guy's Hosp. Rep., 1928, lxxviii, 127. Google Scholar6. VALDEZ FC: Night secretion of free HCl in stomach, Illinois Med. Jr., 1942, lxxxi, 149. Google Scholar7. EUSTERMANBALFOUR GBDC: The stomach and the duodenum, W. B. Saunders Co., Philadelphia. Google Scholar8. CO TUI F: The value of protein and its components in surgical repair, Bull. New York Acad. Med., 1945, xxi, 631. Google Scholar9. HORTON BT: Discussion (Central Society for Clinical Research), Jr. Am. Med. Assoc., 1943, cxxii, 59. Google Scholar10. BRUN GC: The pathogenesis of gastric ulcer, Acta med. Scandinav., 1942, cx, 416. Google Scholar11. JACOBISRAEL AL: The treatment of ulcer pain by small doses of histamine, Presse med., 1938, xlvi, 210. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication June 1, 1946. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byGastric Surgery: A Review of the Literature 1 June 1947Volume 26, Issue 6Page: 852-857KeywordsEtiologyGastric ulcersHistaminePeptic ulcersStomachUlcers ePublished: 1 December 2008 Issue Published: 1 June 1947 PDF downloadLoading ...
"Patient knows best"---detection of common mental disorders in Santiago, Chile: cross sectional study Commentary: Clinical practice is as important as diagnosis
Authors: R. Araya
Journal: BMJ (2001)

# “Patient knows best”—detection of common mental disorders in Santiago, Chile: cross sectional study {#article-title-2}

Depression and anxiety are common in primary care but about half of patients with these disorders are not identified by primary care physicians. 1 2 Mental disorder is more likely to be diagnosed in patients who present with or attribute physical symptoms to psychological causes.2–4 We investigated how patients' ways of understanding their health problems influenced the detection of common mental disorder by primary care physicians in Santiago, Chile.

We studied 815 consecutive patients seen by 11 primary care physicians from five randomly selected clinics in northern Santiago, Chile. Patients with a chronic illness or patients aged over 50 were excluded because these patients are better known by doctors. Most doctors in Chile and in this study have less than four years' experience in primary care.

Before the patient saw the doctor, a lay interviewer asked the patient's reason for consultation and whether it was because of a physical or psychological problem. The interviewer inquired about other potential confounders: physical illness, disability, common somatic symptoms, and whether patients tended to interpret common somatic symptoms by using psychological, physical, or normalising explanations.

A psychiatrist administered the clinical interview schedule—revised, and patients scoring 12 or more were classified as having a common mental disorder.5 After the patient had seen the primary care physician, the doctor rated blindly whether the patient had a mental disorder using a five-point scale. Patients with a rating of “mild or greater” severity were considered to have a mental disorder.

The prevalence of mental disorders was 49% (396 of 802; 95% confidence interval 46% to 53%) according to the clinical interview schedule—revised and 35% …
Abstract 1693: Effect of Pitavastatin on Serum Concentrations of Endothelial Lipase and High-Density Lipoprotein Cholesterol in Humans
Authors: Li Sun, Tatsuro Ishida, Kojima Yoko, Tomoyuki Yasuda, Akira Fukuda, Fumie Kureha, Kenichi Hirata
Journal: Circulation (2008)

[Purpose] Endothelial lipase (EL) is a novel phospholipase which regulates serum high-density lipoprotein cholesterol (HDL-C) levels. In the present study, we have measured serum levels of EL in human subjects, and examined the effect of statins on serum HDL levels and EL mass. [Methods and Results] A sandwich ELISA for human EL was established using two monoclonal antibodies against amino- or carboxy-terminus of human EL. Serum EL concentrations were measured and compared with the serum lipid profile in 237 patients with cardiovascular diseases. There was no significant correlation between serum EL mass and age or gender. Serum EL levels were negatively associated with serum HDL-C levels, but not with serum LDL-C, total cholesterol, or triglyceride levels. Forty-eight patients with hypercholesterolemia were treated with pitavastatin for 6 months, and serum EL mass was evaluated before and after the pitavastatin treatment. Pitavastatin treatment significantly reduced serum EL levels by 15% and increased HDL-C levels by 12%. Complimentary cell culture experiments revealed that pitavastatin suppressed basal and cytokine-induced EL expression and phospholipase activities in endothelial cells, which is reversed by the concomitant treatment with mevalonate or geranylgeranylpyrophosphate. Also, overexpression of RhoA T19N, a dominant negative mutant of RhoA, decreased the EL expression. [Conclusion] EL is a determinant of serum HDL-C levels in humans. Pitavastatin reduced EL expression through the protein isoprenylation and inhibition of Rho activity, and raised serum HDL-C levels. Thus, EL would be a target molecule for the HDL-raising pharmaceutical interventions.
Health literacy, sunscreen and sunbed use: an uneasy association
Authors: E. Altsitsiadis, T. Undheim, E. de Vries, B. Hinrichs, E. Stockfleth, M. Trakatelli
Journal: British Journal of Dermatology (2012)

Background Skin cancer can largely be prevented by avoiding unsafe ultraviolet radiation (UVR) exposure. The evidence on potential drivers of sunscreen and sunbed use is extensive, yet in some cases, such as education, remains rather unclear. Health literacy is receiving increasing attention, but its effect on tanning decisions has not yet been explored. Objectives To explore the association between health literacy and tanning behaviour, in terms of sunscreen and sunbed use. Methods Self‐reported data were collected through a common questionnaire in eight European countries under a common protocol. A three‐item measure was used to assess health literacy; one item was collected to measure current sunscreen use and one item to measure current sunbed use. Descriptive statistics and analysis of variance tests were applied to explore the profile of sunbed and sunscreen users and health literacy among a number of variables. Univariate and multivariate logistic regressions were used to assess the relation between health literacy and sunscreen and sunbed use. Results Univariate results suggested that health literacy has opposite effects on sunscreen use vs. sunbed use. Increased health literacy was associated with the skin cancer protective practice of using sunscreen, but also with more sunbed use. In the multivariate models, health literacy had a significant effect only on sunscreen use. Conclusions The findings suggest that health literacy can be an interesting approach for influencing sunscreen use. In the case of sunbeds, based on the findings and contrary to what was expected, it can be argued that interventions targeting health literacy seem less likely to reduce sunbed use. More research is needed to elucidate the effect of health literacy on sunscreen and sunbed use in order to improve UVR prevention strategies.
Heart failure study finds more diastolic cases in older patients.
Authors: David Spurgeon
Journal: BMJ (2001)

Diastolic heart failure may be more common than systolic failure in older adults, especially women, new research suggests. A large community based US study examined almost 5000 patients aged 66 or older who had heart failure. More than half were found to have the diastolic form of the condition—only recently recognised and still poorly understood—rather than the systolic version.

The study, conducted by researchers from Wake Forest University Baptist Medical Center in …