tbuckley/cabot-search huggingface dataset:
Abstract 1118: Novel Lentiviral Vectors Bearing the Cardiac-Specific Promoter of the Sodium-Calcium Exchanger (NCX1) Report Cardiogenic Differentiation in Stem Cells
Authors: Andreas S Barth, Eddy Kizana, John Terrovitis, Peihong Dong, Rachel R Smith, Jay W Schneider, Michelle K Leppo, Yiqiang Zhang, Eric N Olson, Roselle Abraham, Eduardo Marbán
Journal: Circulation (2007)

Background: Cardiosphere-derived resident cardiac stem cells (CDCs) are readily isolated from adult hearts and confer functional benefit in animal models of heart failure. To study cardiogenic differentiation in CDCs, we developed a method to genetically label and selectively enrich for cells that have differentiated down the cardiomyocyte lineage. Methods and Results: Lentiviral vectors achieved significantly higher transduction efficiency (&gt;90%) and longer-term transgene expression in human CDCs than any of the nine adeno-associated viral serotypes tested (AAV 1– 6, 2.5, 8, 9). To define the best reporter of cardiogenic differentiation, five cardiac-specific promoters (sodium-calcium exchanger [NCX1], L-type calcium channel α-subunit, α-myosin heavy chain, troponin I and myosin ventricular light chain) were subcloned upstream of GFP in lentiviral vectors. Cardiac specificity was assessed by transducing neonatal rat ventricular myocytes (NRVMs), HEK293, cardiac fibroblasts, skeletal myoblasts, endothelial and vascular smooth muscle cells with each vector and then measuring GFP fluorescence by flow cytometry. The cardiac NCX1-promoter conveyed the highest degree of cardiac specificity, with expression limited to NRVMs. At a multiplicity of infection of 35, NCX1-GFP vectors did not affect cell death or apoptosis of CDCs. Expression persisted for up to 6 months in vitro . NCX1-GFP positive CDCs subpopulations, were FACS-sorted and expanded in vitro , demonstrating enhanced expression of a variety of cardiac markers by real-time PCR. The utility of lentiviral vectors bearing the cardiac NCX1-promoter was further exemplified by treating CDCs with cardiogenic sulfonylhydrazones (SHZ). SHZ potently activated a NCX1-firefly luciferase reporter (211 ± 21% greater than control cells) and upregulated cardiac transcripts (including BNP, troponin I, α-tropomyosin, GATA-4). Conclusion: Lentiviral vectors carrying the NCX1 promoter represent a useful tool for genetically marking stem cells and their progeny that have differentiated down the cardiomyocyte lineage. The ability to selectively enrich for cardiomyocytes and their precursors has potential relevance for the development of cell-based therapies.
THE MECHANISM OF HEAT LOSS AND TEMPERATURE REGULATION
Authors: Eugene F. Du Bois
Journal: Annals of Internal Medicine (1938)

Article1 September 1938THE MECHANISM OF HEAT LOSS AND TEMPERATURE REGULATIONEUGENE F. DU BOIS, F.A.C.P.EUGENE F. DU BOIS, F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-12-3-388 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThere have been surprisingly few studies dealing with the mechanism of heat loss. Heat production has received more than its share of consideration because it is really the balance between production and loss that determines the body temperature.The Russell Sage Institute of Pathology happens to possess a respiration calorimeter which measures production and loss from the human body simultaneously but independently. This instrument, which was moved from Bellevue Hospital to New York Hospital in 1932, has been used in the study of patients with fever and many normal controls under varying atmospheric conditions. We directed our attention almost entirely... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Read before the American College of Physicians, New York, April 4, 1938.From the Russell Sage Institute of Pathology in affiliation with the New York Hospital, and the Department of Medicine, Cornell University Medical College, New York, N. Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byColossal thermo-hydro-electrochemical voltage generation for self-sustainable operation of electronicsThermodynamic Modeling of the Competition Between Cancer and Normal Cells 1 September 1938Volume 12, Issue 3Page: 338-395KeywordsFeversHospital medicineRespirationTemperature Issue Published: 1 September 1938 PDF downloadLoading ...
EPIDEMIOLOGY IN THE ARMY
Authors: James Stevens Simmons
Journal: Annals of Internal Medicine (1940)

Article1 June 1940EPIDEMIOLOGY IN THE ARMYJAMES STEVENS SIMMONS, M.D., Ph.D., S.D., D.P.H., F.A.C.P.JAMES STEVENS SIMMONS, M.D., Ph.D., S.D., D.P.H., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-13-12-2229 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptI. INTRODUCTIONThe task of safeguarding the health of the American soldier, especially during war, is a responsibility of the entire medical profession of the United States. It has always been the policy of our peace-loving nation to maintain only a small regular army, capable of rapid expansion during emergencies by the addition of civilian soldiers. Likewise, the medical care afforded the troops during each of our major wars has been provided largely by the mobilized doctors of the country; and the quality of this service has reflected the status of medical development at the time.With this responsibility in... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Medical Corps U. S. Army*Read at the Cleveland meeting of the American College of Physicians, April 1, 1940. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1940Volume 13, Issue 12Page: 2229-2234KeywordsEpidemiology ePublished: 1 December 2008 Issue Published: 1 June 1940 PDF downloadLoading ...
Long‐term safety of oral nucleos(t)ide analogs for patients with chronic hepatitis B: A cohort study of 53,500 subjects
Authors: Grace Lai‐Hung Wong, Yee‐Kit Tse, Vincent Wai‐Sun Wong, Terry Cheuk‐Fung Yip, Kelvin Kam‐Fai Tsoi, Henry Lik‐Yuen Chan
Journal: Hepatology (2015)

Widespread and long‐term use of oral nucleos(t)ide analogs (NAs) to treat chronic hepatitis B (CHB) brings about safety data in a real‐life setting. We aimed to determine the risks of renal and bone side effects in patients receiving or who have received NAs as CHB treatment. A territory‐wide cohort study using the database from Hospital Authority, the major provider of medical services in Hong Kong, was conducted. We identified CHB patients by International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes, diagnosed between 2000 and 2012. The primary events were renal (incident renal failure and renal replacement therapy [RRT]) and bone events (incident hip, vertebral, and all fractures). A 3‐year landmark analysis was used to evaluate the relative risk of primary outcome in patients with or without NA treatment. A total of 53,500 CHB patients (46,454 untreated and 7,046 treated), who were event free for 3 years, were included in the analysis. At a median follow‐up of 4.9 years, chronic renal failure, RRT, all fractures, hip fractures, and vertebral fractures occurred in 0.6%, 0.2%, 0.7%, 0.1%, and 0.1% of untreated subjects and 1.4%, 0.7%, 1.3%, 0.2%, and 0.2% of treated subjects. After propensity score weighting, NA therapy did not increase the risk of any of the events (hazard ratios [HRs] ranged from 0.79 to 1.31; P = 0.225‐0.887). Exposure to nucleotide analogues, compared with nucleoside analogs, increased the risk of hip fracture (HR = 5.69; 95% confidence interval: 1.98‐16.39; P = 0.001), but not other events (HR = 0.58‐1.44; P = 0.202‐0.823). Conclusions : NA treatment does not increase the risk of renal and bone events in general. Nucleotide analogs may increase the risk of hip fracture, but the overall event rate is low. (H epatology 2015;62:684–693)
Is genotype 3 of the hepatitis C virus the new villain?
Authors: Nicolas Goossens, Francesco Negro
Journal: Hepatology (2013)

Genotype 3 of the hepatitis C virus (HCV) has been long considered an easy-to-treat infection, with higher cure rates (˜70%) than other viral genotypes with the standard combination of pegylated interferon-α and ribavirin. However, the relative insensitivity of this genotype to most protease inhibitors and the recent unexpected data on decreased effectiveness of sofosbuvir have raised questions on how to achieve universal cure, a goal that seems reasonable for other genotypes. In addition, increasing clinical and experimental data show that HCV genotype 3 may be associated not only with severe steatosis, but also with accelerated fibrosis progression rate and increased oncogenesis. Conclusion : Currently available data suggest that we should increase our efforts to understand the virology and pathogenesis of HCV genotype 3, aiming at better and more potent, genotype-targeted treatments. (Hepatology 2014;59:2403–2412)
THE ANALYSIS OF HIGH CALORIC DIETS IN RELATION TO WEIGHT CHANGES
Authors: J. M. Strang, A. B. Cox
Journal: Annals of Internal Medicine (1933)

Article1 August 1933THE ANALYSIS OF HIGH CALORIC DIETS IN RELATION TO WEIGHT CHANGESJ. M. STRANG, M.D., A. B. COX, B.S.J. M. STRANG, M.D.Search for more papers by this author, A. B. COX, B.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-7-2-152 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptFor a period of four years, we have studied the treatment by dietary measures of patients who were underweight. The principles underlying this treatment and the clinical results have been summarized in a previous paper.6 Eighteen patients were studied on the metabolic pavilion of the Western Pennsylvania Hospital for periods varying from two to 13 weeks. On 16 subjects of this series the detailed data of the food taken in are sufficiently complete to permit analysis. The analysis of these diets with reference to the weight changes which were observed forms the subject of this present study.METHODSThe methods...Bibliography1. ATWATERBRYANT WCAP: The chemical composition of American food materials, U. S. Dept. of Agriculture, Bull. No. 28, 1906, p. 19. Google Scholar2. COLEMANDUBOIS WEF: The influence of the high calorie diet on the respiratory exchanges in typhoid fever, Arch. Int. Med., 1914, xiv, 168-209. CrossrefGoogle Scholar3. FRIEDENWALDRUHRAH JJ: Diet in health and disease, 1926, W. B. Saunders Co., Philadelphia. Google Scholar4. MITCHELLCARMAN HHGG: The composition of the gains in weight and the utilization of food energy in growing rats, Am. Jr. Physiol., 1926, lxxvi, 398-410. CrossrefGoogle Scholar5. SHERMAN HC: Food products, 1921, The Macmillan Co., New York. Google Scholar6. STRANGEVANS JMFA: Undernutrition and its treatment by adequate diet, ANN. INT. MED., 1933, vii, 45-63. Google Scholar7. STRANGMCCLUGAGEBROWNLEE JMHBMA: Nitrogen metabolism during the dietary correction of undernutrition. (In press.) Google Scholar8. WALLER DS: Nutritive value of food materials, Univ. of Mich. Hosp., 1928. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Pittsburgh, Pennsylvania*Received for publication November 11, 1932. From the Medical Service of the Western Pennsylvania Hospital. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1933Volume 7, Issue 2Page: 152-164KeywordsDietFoodMedical services ePublished: 1 December 2008 Issue Published: 1 August 1933 PDF downloadLoading ...
Abstract 11621: Fibrillin-1 Gene Mutations in Left Ventricular Non-Compaction Cardiomyopathy
Authors: John J Parent, Jeffrey A Towbin, John L Jefferies
Journal: Circulation (2014)

Introduction: Left ventricular non-compaction cardiomyopathy (LVNC) is a rare and unique cardiomyopathy. Its presentation can range from a benign phenotype to overt heart failure and sudden cardiac death. The genetics of LVNC are not completely understood and current genetic testing has a yield of about 30% in identifying a causative gene mutation. We present a series of patients with LVNC and fibrillin-1 (FBN1) gene mutations. Hypothesis: We hypothesize that FBN1 gene mutations can lead to LVNC by way of its role in the myocardial extracellular matrix during cardiac development. Methods: A retrospective review of all patients with LVNC at our institution was performed for purposes of another investigation. The process unexpectedly identified patients with LVNC and FBN1 gene mutations, as well as LVNC and Marfan syndrome. Results: Approximately 150 patients are followed in our clinic with LVNC. We screened this population and found 51 patients on medical therapy for reduced function. We retrospectively reviewed gene testing in these 51 patients, when available, and identified 5 patients (10%) with an FBN1 gene mutation. All 5 patients had a dilated LVNC phenotype and previous or current evidence of left ventricular dysfunction. Syndrome breakdown as follows: 3 with Marfan, 1 with Shprintzen-Goldberg, and 1 with no identifiable syndrome. Dilated cardiomyopathy/LVNC gene testing was performed in 3 patients; 2 had disease causing myosin heavy chain 7 gene defects and 1 had no defects. Conclusions: The role of FBN1 in the human myocardium is not completely understood but it is expressed in the developing fetal heart and is a component of the myocardial extracellular matrix. Although causation has not been proven by our report, it certainly raises interest in a mechanistic relationship between LVNC and FBN1 given the increased prevalence of Marfan syndrome and probable increased prevalence of FBN1 gene mutations in this cohort of LVNC patients in light of FBN1.
The Conquest of the Air
Authors: M. Therese Southgate
Journal: JAMA (2003)

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 806: Selective killing of cancer cells with mitochondrial respiratory dysfunction induced by activation of oncogenic Ras
Authors: Weiqin Lu, Yaying Yang, Craig Logsdon, Peng Huang
Journal: Cancer Research (2014)

Abstract Mitochondrial dysfunction is an important mechanism by which cancer cells become resistant to chemotherapeutic agents. Oncogenic Ras activation is often observed in human cancer and was reported to cause mitochondrial dysfunction by compromising mitochondrial electron transport chain. Therefore, identification of new agents capable of effectively killing mitochondrial defective cancer cells would have important therapeutic implications. Our previous work has discovered that mitochondrial respiratory dysfunction could cause increased NADPH oxidase (NOX) activity to support cell survival in the metabolic switch from mitochondrial oxidative phosphorylation to glycolysis. Mitochondrial respiratory dysfunction can also cause profound redox alteration to adapt ROS stress. Here, we report that targeted inhibition of NOX and glutathione synthesis has synergy effect in killing mitochondrial respiratory dysfunction cells, including cancer cells harboring oncogenic Ras activation. Activation of NOX and increased glutathione antioxidants are always observed in Ras activated cells. Treatment of these cancer cells with DPI and BSO to inhibit NOX activity and antioxidant adaptation function resulted in an elevated ROS stress, increased gamma-H2AX expression, leading to massive death of the cancer cells, such as Panc-1 and HCT116 cells. Antioxidant NAC and catalase attenuated the BSO and DPI induced cell death in mitochondrial respiratory dysfunction cells. The synergistic effect of BSO and DPI to kill oncogenic Ras bearing HCT116 cells was further confirmed using colony formation assay. Our results suggest that DPI, in synergy with BSO, is a promising compound capable of killing cancer cells bearing oncogenic Ras mutations through a ROS-mediated mechanism and warrants further investigations. Citation Format: Weiqin Lu, Yaying Yang, Craig Logsdon, Peng Huang. Selective killing of cancer cells with mitochondrial respiratory dysfunction induced by activation of oncogenic Ras. [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 806. doi:10.1158/1538-7445.AM2014-806
Abstract 5523: Study of the response of melanoma lines to BRAF/MEK inhibitors and combination drug treatments
Authors: Anahita Dastur, Cyril Benes
Journal: Cancer Research (2014)

Abstract The serine-threonine protein kinase, BRAF, is a frequently mutated oncogene, found in cancers of the skin, thyroid and large intestine. It is especially prevalent in malignant melanoma, where it occurs in 40-60% of the cases. The most common BRAF mutation is the valine to glutamate substitution at position 600 of the kinase (V600E). This substitution, seen in ninety percent of the BRAF cases, leads to constitutive activation of the kinase, and the downstream MEK-ERK pathway. Appropriately, several drugs have been designed to inhibit BRAF, with a broad range of outcomes in clinical trials. Unfortunately, all patients, including those showing complete responses, develop resistance to single agent therapy. Our goal is to come up with effective drug combinations that would delay, or even prevent, the cancer from becoming resistant to treatment. We used a panel of 43 melanoma lines, comprising of 28 BRAF mutants, 12 NRAS mutants and 3 lines that were wild type for these two genes. Besides BRAF and NRAS, we have the mutational status of 65 other commonly mutated cancer genes for all the lines. We assembled a set of 25 drugs targeting a wide range of proteins, including PI3K/mTOR inhibitors, the apoptosis machinery, as well as some epigenetic modulators. The melanoma lines were treated with these drugs, either (i) alone or (ii) in combination with the B-RAF inhibitor vemurafenib or (iii) in combination with the MEK inhibitor Selumetinib, for 72 hrs over a nine point, 256-fold concentration range. Viability and apoptosis were measured using cell titer glo (Promega). The results from this pilot study are discussed here. Note: This abstract was not presented at the meeting. Citation Format: Anahita Dastur, Cyril Benes. Study of the response of melanoma lines to BRAF/MEK inhibitors and combination drug treatments. [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 5523. doi:10.1158/1538-7445.AM2014-5523
Assembly of microarrays for genome-wide measurement of DNA copy number
Authors: Antoine M. Snijders, Norma Nowak, Richard Segraves, Stephanie Blackwood, Nils Brown, Jeffrey Conroy, Greg Hamilton, Anna Katherine Hindle, Bing Huey, Karen Kimura, Sindy Law, Ken Myambo, Joel Palmer, Bauke Ylstra, Jingzhu Pearl Yue, Joe W. Gray, Ajay N. Jain, Daniel Pinkel, Donna G. Albertson
Journal: Nature Genetics (2001)
Reversal of multidrug resistance by a novel third generation modulator, FG020326.
Authors: Li-Wu Fu, Yong-Ju Liang, Li-Ming Chen
Journal: Cancer Research (2006)

5413  The ABC proteins P-glycoprotein (Pgp), multidrug resistance protein-1 (MRP-1) and breast cancer resistance protein (BCRP) mediate multidrug resistance in cancer cells, and Pgp and BCRP also play important roles in drug absorption and disposition. The immunosuppressive agents cyclosporine A, sirolimus (rapamycin) and tacrolimus (FK-506) are known to inhibit drug transport mediated by Pgp, and we compared their effects on MRP-1 and BCRP, as well as Pgp. Effects of cyclosporine A, rapamycin and FK-506 on transport of mitoxantrone, a substrate for Pgp, MRP-1 and BCRP, were studied in cell lines overexpressing these proteins, including HL60/VCR (Pgp), HL60/ADR (MRP-1) and 8226/MR20 (BCRP). Cellular content of mitoxantrone was measured by flow cytometry in each cell line following 30-minute incubation with mitoxantrone in the presence and absence of each of the three immunosuppressive agents, and histograms were compared by the Kolmogorov-Smirnov statistic, generating D-values. Cyclosporine A enhanced mitoxantrone uptake in cell lines overexpressing Pgp, MRP-1 and BCRP at the clinically achievable concentration of 2.5 μM. Rapamycin also enhanced mitoxantrone uptake in all three cell lines at 2.5 μM, but this concentration exceeds that achieved with doses used in current immunosuppressive regimens. However, pre-incubation with rapamycin for at least 3 hours at the clinically achievable concentration of 0.25 μM enhanced mitoxantrone uptake in HL60/VCR, HL60/ADR and 8226/MR20 cells, without effects on Pgp, MRP-1 or BCRP expression, consistent with modulation of transport. FK-506 enhanced mitoxantrone uptake in HL60/VCR, HL60/ADR and 8226/MR20 cells at 1 μM, but had no effect at the maximum clinically achievable concentration of 24 nM. In contrast to findings with rapamycin, pre-incubation with 24 nM FK-506 for up to 6 hours did not enhance mitoxantrone uptake in any of the three cell lines. In conclusion, cyclosporine A modulates drug transport by Pgp, MRP-1 and BCRP at pharmacologically relevant concentrations, while FK-506 also modulates all three proteins, but only at concentrations exceeding those achievable in the clinical setting, and rapamycin modulates at clinically achievable concentrations, but modulation requires prolonged exposure. Thus the three immunosuppressive agents commonly used in transplantation regimens differ in their effects on multidrug resistance mediated by Pgp, MRP-1 and BCRP, and in their effects on absorption and disposition of co-administered drugs that are substrates for these ABC proteins.
Food Facts for Teenagers.
Authors: Margaret Belasis Salmon
Journal: Annals of Internal Medicine (1966)

phenobarbital or diphenylhydantoin has been spectacular. What is particularly distressing is that often, when I have suggested to an inquiring mother that her very difficult child have an EEG made, she has reported later that the child's physician had deeply resented the sug¬ gestion and had refused to have the records made. Often when they were made they showed spikes and seizure discharges. Cer¬ tainly it would seem that much greater ef¬ forts should be made in medical schools, and particularly in departments of psychiatry, to acquaint the students with the often tremen¬ dous value of EEGs, and especially the value of the magnificent work of Dr. and Mrs. Gibbs. Walter C. Alvarez, MD