tbuckley/cabot-search huggingface dataset:
Two novel mutations of the nicastrin gene in Chinese patients with acne inversa
Authors: C.-R. Li, M.-J. Jiang, D.-B. Shen, H.-X. Xu, H.-S. Wang, X. Yao, Y. Zhang, W.-Q. Zhou, B. Wang
Journal: British Journal of Dermatology (2011)

Acne inversa (AI, OMIM 142690), also called hidradenitis suppurativa, is a chronic, inflammatory, recurrent and debilitating skin follicular disease that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly the axilla, inguinal and anogenital regions.(1) The prevalence of AI has been estimated at 1 in 100 to 1 in 600.(2) Of patients with AI, 35-40% have a positive family history.(3) The pattern of transmission is consistent with autosomal dominant inheritance.(4) In 2006, Gao et al.(5) mapped the AI gene at chromosome 1p21.1-1q25.3. In 2010, Wang et al.(6) were the first to identify mutations of γ-secretase genes responsible for AI among six Chinese families. γ-Secretase is a transmembrane protease composed of four essential protein subunits: one catalytic presenilin (PSEN1) subunit and three cofactor subunits [presenilin enhancer 2 (PSENEN), nicastrin (NCSTN) and anterior pharynx defective 1 (APH1)]. Two, one and three mutations were found in PSENEN, PSEN1 and NCSTN, respectively. Here, we report a heterozygous nonsense c.1695T>G mutation and a heterozygous missense c.632C>G mutation of the NCSTN gene in two Chinese AI families.
The mouse pudgy mutation disrupts Delta homologue Dll3 and initiation of early somite boundaries
Authors: Kenro Kusumi, Eileen Sun, Anne W. Kerrebrock, Roderick T. Bronson, Dow-Chung Chi, Monique Bulotsky, Jessica B. Spencer, Bruce W. Birren, Wayne N. Frankel, Eric S. Lander
Journal: Nature Genetics (1998)
Abstract 13454: Development of Functional Tissue-engineered Artificial Cardiac Construct using Human Induced Pluripotent Stem Cells; Optimizing the Cell Components to Mimic Cardiac Tissue
Authors: Hiroko Iseoka, Shigeru Miyagawa, Satsuki Fukushima, Shigeo Masuda, Noriko Mochizuki-Oda, Atsuhiro Saito, Emiko Ito, Tsuyoshi Ishikawa, Jong-Kook Lee, Yoshiki Sawa
Journal: Circulation (2014)

Background: Tissue-engineered artificial cardiac constructs (ACCs) derived from human induced pluripotent stem cells (hiPSCs) are promising for myocardial regenerative medicine and drug discovery. However, the appropriate ratio of cardiomyocytes (CMs) and non-CMs, which would substantially impact on functionality of the ACC, is poorly understood. We herein developed the well-functioning ACCs derived from hiPSCs, mimicking native cardiac tissue.

Methods: Cardiomyogenic differentiation was induced in hiPSCs to produce a mixed cell preparation including iPSC-CMs and non-CMs. The cell preparation was separated based on expression of the iPSC-CM specific marker, CD172, using a magnetic-activated cell sorting system to produce cell preparations with different ratios (25, 50, 70, and 90%) of iPSC-CMs, which were then prepared as scaffold-free constructs using thermoresponsive culture dishes.

Results: The CD172-sorted iPSC-CMs showed >90% positivity for cardiac troponin T, whereas the CD172-negative iPSC-non-CMs included CD31-, α-smooth muscle actin- or vimentin-positive cells. The ACC showed synchronized spontaneous beating when CMs constituted 50% or more of the total cells in the ACC. The electrical conduction velocity, assessed by a multi-electrode array, was positively related to the CM ratio in the ACCs and was 3.5±1.8, 8.6±2.8, and 16±5.0 cm/sec for CM ratios of 50, 70, and 90%, respectively. However, the ACC including 90% CMs failed to form a stable structure. Collagen type I and III were more abundantly expressed in the ACC including 25% and 50% CMs, whereas laminin alpha 2 and 4, major extra cellular matrix components of cardiac tissue, were more abundantly expressed in the ACC including 70% CMs, as assessed by quantitative PCR. In addition, the gene expression ratio of myosin light chain (MLC) 2v and MLC2a, an indicative ratio of myocyte maturation, was the highest in the ACC including 70% CMs. Moreover, expression of angiogenic factors, such as vascular endothelial growth factor, was highest in the ACC including 70% CMs.

Counclusions: The ACC composed of 70% CMs displayed greater stability and functionality compared to those of other ratios, indicating a possibility of optimal ACCs as a bio-cardiac support device or a tool for drug discovery.
Present Results and Outlook of Diabetic Treatment
Authors: Frederick M. Allen
Journal: Annals of Internal Medicine (1928)

Article1 August 1928Present Results and Outlook of Diabetic TreatmentFREDERICK M. ALLEN, M. D.FREDERICK M. ALLEN, M. D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-2-2-203 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDiabetes is a subject of perennial interest. The topic selected for me is in the nature of a review, which is timely, because at present we have reached a point where some old questions are apparently decided and new ones are just beginning to be opened up by research.DIETThe first part of diabetic treatment is necessarily diet. This is the most important and fundamental part, and the only one which must be employed in every case. The components of the diet requiring consideration are protein, carbohydrate, fat, and finally total calories and body weight.Protein has been the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Pyschiatric Institute Morristown, New Jersey*Read before the American College of Physicians, New Orleans Clinical Week, March 8, 1928. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCurrent Judgments on Metabolic Control and Complications in DiabetesThe Management of the Acute Complications of Diabetes Mellitus 1 August 1928Volume 2, Issue 2Page: 203-214KeywordsBody weightCarbohydratesDietFatsProteins ePublished: 1 December 2008 Issue Published: 1 August 1928 PDF downloadLoading ...
Abstract B89: Polyisoprenylated cysteinyl amide inhibitors of PMPMEase inhibit pancreatic cancer cell viability and migration: Implications for pancreatic cancer therapy
Authors: Augustine T. Nkembo, Byron J. aguilar, Randolph Duverna, Felix Amissah, Nazarius S. Lamango
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains one of the most deadly neoplasms due to lack of effective targeted therapies. This vacuum stems from the fact that over 90% of pancreatic cancer cases harbor the K-Ras mutation which has been very challenging to drug. The numerous efforts to drug oncogenic Ras have involved inhibiting the post-translational modifications that are essential to its proliferative activity. These drug discovery efforts have largely ignored a critical step in the metabolism of Ras and related proteins involving polyisoprenylated methylated protein methyl esterase (PMPMEase). The objectives of these studies were to test the hypothesis that PMPMEase hyperactivity promotes pancreatic cancer progression. The potential for polyisoprenylated cysteinyl amide inhibitors (PCAIs) of PMPMEase as potential anticancer agents was evaluated against PDAC cell lines MIAPaCa-2 with K-Ras mutation and BxPC-3 with wild type K-Ras for their effects on cell viability, migration, and cytoskeletal organization. The PCAIs inhibited the viability of MIAPaCa-2 and BxPC-3 cells with 48 h EC50 values as low as 1.9 and 3.2 µM, respectively. Erlotinib and Salirasib (FTS) were ineffective at concentrations in excess of 20 µM. The PCAIs also inhibited MIAPaCa-2 cell migration by up to 50% at 0.5 µM and disrupted F-actin organization at 5 µM. Further investigations showed that at the EC50 concentrations the PCAIs caused the pancreatic cancer cells to die by apoptosis. The cell cycle analysis for MIAPaCa-2 cells showed that the PCAIs block the cells growth at G0/G1 phase. The results showed that the PCAIs are over 10-fold more effective than Salirasib and Erlotinib against PDAC cell viability. Furthermore, their effects against cell migration and actin filament organization suggest their potential for treating tumor growth and metastasis in not only PDAC but other cancers with oncogenic Ras. Citation Format: Augustine T. Nkembo, Byron J. aguilar, Randolph Duverna, Felix Amissah, Nazarius S. Lamango. Polyisoprenylated cysteinyl amide inhibitors of PMPMEase inhibit pancreatic cancer cell viability and migration: Implications for pancreatic cancer therapy. [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 B89.
Abstract 20500: Trx1 Promotes Trans-Nitrosylation of Cellular Proteins to Stimulate Autophagy and Cell Survival
Authors: Narayani Nagarajan, Sebastiano Sciarretta, Junichi Sadoshima
Journal: Circulation (2014)

Thioredoxin-1 (Trx1) is cardioprotective during oxidative stress, mainly through its antioxidant activity. Trx1 is also S-nitrosylated and, in turn, trans-nitrosylates other proteins. However, the role of Trx1-dependent S-nitrosylation in cardiomyocytes (CMs) is unknown. Here, we investigated the role of Trx1-mediated protein S-nitrosylation in the regulation of CM survival during stress in vitro. Using biotin-switch assays, we found that wild-type Trx1 (Trx1WT) is S-nitrosylated at baseline, but the extent of S-nitrosylation was attenuated in Trx1C73S, suggesting that Trx1 is S-nitrosylated at Cys73. Trx1WT and Trx1C73S do not differ in their redox activity, as determined by Amplex Red assays. Cellular protein S-nitrosylation levels were increased after 4 hours of glucose deprivation (GD), an energy stress condition (1.64±0.27 fold, p&lt;0.05), as determined by biotin switch assays. Overexpression of Trx1WT increased (3.94-fold), whereas knockdown of Trx1 (0.66±0.01 fold, p&lt;0.01) or overexpression of Trx1C73S (0.77±0.02 fold, p&lt;0.01) decreased, total protein S-nitrosylation in response to GD. These results suggest that Trx1C73 regulates protein S-nitrosylation in CMs during GD. Overexpression of Trx1 increased CM survival after 24 hours of GD (1.42±0.08 fold vs LacZ, p&lt;0.05), as evaluated with propidium iodide assays. Conversely, shTrx1 (2.13±0.05 fold vs control, p&lt;0.01) or Trx1C73S (1.73±0.034 fold vs LacZ, p&lt;0.01) increased cell death during GD. Either knockdown of Trx1 (LC3-II/Tubulin: 0.55 fold vs control) or overexpression of Trx1C73S (vs LacZ: LC3-II/Tubulin, 0.60 fold; autophagosomes, 0.83±0.16-fold, p&lt;0.005; autolysosomes, 0.62±0.13-fold, p&lt;0.005) significantly decreased autophagy during GD. Mechanistically, Trx1 co-immunoprecipitates with Atg7, an E1-like protein which plays a critical role in mediating autophagy. Using mass spectroscopy analyses, we found that SNO-Trx1 can trans-nitrosylate Atg7 in vitro. These results suggest that Trx1 trans-nitrosylates Atg7 during GD. Taken all together, our results indicate that Trx1 promotes trans-nitrosylation of cellular proteins, including Atg7, and autophagy, thereby promoting cell survival during energy stress in CMs.
Punishment for Intoxication
Authors: M. Therese Southgate
Journal: JAMA (2001)

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 20724: Matrix-Promoted Efficient Cardiac Differentiation of Human iPS and ES Cells
Authors: Jianhua Zhang, Kunil K Raval, Xiaojun Lian, Amanda M Herman, Gisela F Wilson, Matthew R Barron, Junying Yu, Sean P Palecek, James A Thomson, Timothy J Kamp
Journal: Circulation (2010)

Efficient and reproducible approaches for differentiating human iPS and ES cells to cardiomyocytes (CMs) are needed for research and potential clinical applications. The purpose of this study was t...
Abstract 11901: Elevated Blood Glucose Levels and Type 2 Diabetes Are Related to the Risk of Sudden Cardiac Death
Authors: Jari Laukkanen, Timo Mäkikallio, Sudhir Kurl
Journal: Circulation (2011)

Background:  The reduction of mortality from sudden cardiac arrest remains a major challenge among patients with impaired glucose levels. It is not well documented whether impaired fasting blood glucose and type 2 diabetes may be risk factors for sudden cardiac death.   Methods:  This population study was based on 2641 men 42 to 60 years of age. Elevated fasting blood glucose level was defined according the International Diabetes Federation and type 2 diabetes was defined with either dietary, oral or insulin treatment or high fasting blood glucose (>6.1 mmol/L).   Results:  During the 17-year follow-up, there were 167 SCDs. As a continuous variable, one mmol/L (18 mg/dL) increment in blood glucose was related an increase of 10 % in the risk of SCD (adjusted risk 1.10, 95 % CI 1.02 to 1.19, p=0.009). The risk for SCD was 2.44-fold (95 % CI 1.42 to 4.16, p=0.001) among non-diabetic men with slightly elevated fasting glucose (> 5.6 mmol/L, 100 mg/dL) and 2.16-fold (95 % CI 1.28 to 3.64, p=0.0038) in diabetic men, when adjusted for age, body mass index, systolic blood pressure, serum low density lipoprotein cholesterol, smoking, C-reactive protein, energy expenditure of physical activity and a history of myocardial infarction. The Harrell C-index for the total model discrimination was 0.764, while blood glucose provides modest improvement (from 0.758 to 0.764) in the risk prediction when added with other risk factors. The net reclassification index (NRI) was significantly improved (NRI= 0.056, p=0.002) and the integrated discrimination improvement (IDI) was 0.014 (p=0.0001, relative IDI=0.22).   Conclusions:  Elevated fasting glucose level in addition to type 2 diabetes is a risk predictor for SCD. There was an improvement in the level of discrimination and the NRI while using impaired fasting blood glucose with conventional risk factors in the prediction of SCD.
Abstract MP04: 25 year Physical Activity Trajectories and Development of Subclinical Coronary Artery Disease as Measured by Coronary Artery Calcium: the CARDIA Study
Authors: Jamal S Rana, Rosenda Murillo, Charles P Quesenberry, Michael E Sorel, Barbara Sternfeld, Kelley P Gabriel, Mercedes R Carnethon, Kiang Liu, Jared P Reis, Norrina B Allen, Donald Lloyd-Jones, J. Jeffrey Carr, Stephen Sidney
Journal: Circulation (2015)

Background: Physical activity (PA) has been shown to be protective against the development of clinical cardiovascular disease. There is paucity of data regarding the association of long term PA patterns and development of subclinical atherosclerosis, as measured by coronary artery calcium (CAC). Studies so far are limited by evaluation of PA only at baseline. The goal of this study was to identify 25 year patterns of PA from young to middle age and its association with development of CAC. Methods: CARDIA is a prospective longitudinal study of black and white men and women, ages 18-30 years at baseline in 1985-86, with up to 7 follow-up exams over 25 years of follow-up. PA was determined at each exam by a questionnaire that assessed typical PA during the past 12 months for 13 types of activities. Men and women who had at least 3 measures of PA during the 25 years of follow up and CAC assessment at the Year 25 exam were included (N= 3178). CARDIA Physical Activity Score &gt; 300 units is approximately equivalent to &gt;150 min/week of moderate or vigorous physical activity and was considered as meeting PA guidelines (MPAG). Latent class modeling was used to identify unique trajectories of PA. Odds ratios for CAC were estimated from a multivariable logistic model controlling for age, sex, ethnicity, hypertension, diabetes, BMI, smoking status and education. Results: Our analyses showed 5 unique PA trajectories (figure). 1. Maintaining-not MPAG (46.5%); 2. maintaining-MPAG (35.6%); 3 increasing-MPAG (8.5%); 4. decreasing-MPAG (6.5%), and 5. maintaining- &gt; 3 fold MPAG (2.4%). Compared with the maintaining-not MPAG, the multivariable adjusted odds ratio for presence of CAC (non-zero CAC score) was 1.02 (95% CI, 0.84-1.24) for maintaining-MPAG, 1.07 (95% CI, 0.78-1.44) for increasing-MPAG , 1.01(95% CI, 0.72- 1.41) for decreasing-MPAG , and 1.37 (95% CI, 0.82-2.27) for maintaining- &gt; 3 fold MPAG. Conclusion: Long-term trajectories for levels of PA through young adulthood are not associated with development of subclinical atherosclerosis by middle age.
Long-Term Outcomes After Transcatheter Aortic Valve Implantation in High-Risk Patients With Severe Aortic Stenosis
Authors: Neil E. Moat, Peter Ludman, Mark A. de Belder, Ben Bridgewater, Andrew D. Cunningham, Christopher P. Young, Martyn Thomas, Jan Kovac, Tom Spyt, Philip A. MacCarthy, Olaf Wendler, David Hildick-Smith, Simon W. Davies, Uday Trivedi, Daniel J. Blackman, Richard D. Levy, Stephen J.D. Brecker, Andreas Baumbach, Tim Daniel, Huon Gray, Michael J. Mullen
Journal: Journal of the American College of Cardiology (2011)

The objective was to define the characteristics of a real-world patient population treated with transcatheter aortic valve implantation (TAVI), regardless of technology or access route, and to evaluate their clinical outcome over the mid to long term. Although a substantial body of data exists in relation to early clinical outcomes after TAVI, there are few data on outcomes beyond 1 year in any notable number of patients. The U.K. TAVI (United Kingdom Transcatheter Aortic Valve Implantation) Registry was established to report outcomes of all TAVI procedures performed within the United Kingdom. Data were collected prospectively on 870 patients undergoing 877 TAVI procedures up until December 31, 2009. Mortality tracking was achieved in 100% of patients with mortality status reported as of December 2010. Survival at 30 days was 92.9%, and it was 78.6% and 73.7% at 1 year and 2 years, respectively. There was a marked attrition in survival between 30 days and 1 year. In a univariate model, survival was significantly adversely affected by renal dysfunction, the presence of coronary artery disease, and a nontransfemoral approach; whereas left ventricular function (ejection fraction <30%), the presence of moderate/severe aortic regurgitation, and chronic obstructive pulmonary disease remained the only independent predictors of mortality in the multivariate model. Midterm to long-term survival after TAVI was encouraging in this high-risk patient population, although a substantial proportion of patients died within the first year.
High versus Low Blood-Pressure Target in Septic Shock
Authors: Ronan M G Berg, Ronni R Plovsing, Kirsten Møller
Journal: New England Journal of Medicine (2014)

To the Editor: As noted by Asfar et al. (April 24 issue),1 a major concern related to targeting a relatively low mean arterial blood pressure in patients with septic shock is that the brain is at risk for ischemia in this condition. The risk of potential brain ischemia is particularly pertinent among patients with a history of arterial hypertension, because their cerebral autoregulatory curve may be shifted to the right.2 Indeed, cerebral ischemia may contribute to sepsis-associated encephalopathy and persistent neurocognitive dysfunction.3 However, neither the primary nor the secondary outcomes in the study by Asfar et al. involved any measures of neurocognitive function. A mean arterial blood pressure of approximately 65 to 90 mm Hg describes the lower limit of autoregulation in healthy persons,4 and the same level appears to be present in critically ill patients with sepsis who do not have a history of hypertension.5 Before the findings by Asfar et al. are implemented in major guidelines, we think that further studies should address the way in which cerebral hemodynamics are specifically affected in patients with sepsis and a history of hypertension, as well as whether targeting a relatively high mean arterial blood pressure improves long-term neurocognitive function.
Abstract 16318: Clinical and Economic Value of Maximizing Response to Cardiac Resynchronization Therapy (CRT): Evidence From 5 Randomized Controlled Trials
Authors: Eugene S Chung, Jagmeet P Singh, David O Martin, William T Abraham, Stelios I Tsintzos, Tyson B Rogers, Simon Eggington, Sarah L Bril, Tom F Goss, Devon Ptak, Bernd Brüggenjürgen, Martin R Cowie
Journal: Circulation (2014)

BACKGROUND: Cardiac Resynchronization Therapy (CRT) is clinically effective and cost-effective, although some patients realize 6-Month (6M) improvements while others do not. Long-term differences in outcomes among short term “responders” and “non-responders” are not reported. We compared survival, burden of Heart Failure (HF) hospitalization, and Average Length of Stay (ALOS), by Clinical Composite Score (CCS) at 6M post-implant, which was used to assess short-term CRT response. METHODS: MIRACLE, MIRACLE-ICD, InSync III Marquis, PROSPECT and Adaptive CRT were pooled. Classification of responder status was made at 6M; patients who died post-implant and before CCS assessment at 6M were excluded. We adjusted for differences in baseline characteristics between CCS. HF hospitalizations before 6M were excluded from HF rate calculations. Hospitalizations resulting in death were excluded from the ALOS analysis. Mortality was assessed via Kaplan-Meier curves and Cox regression; HF hospitalization rates using Poisson regression with robust variance estimates; long-term extrapolations used Markov modelling. RESULTS: We identified 1,089 Improved (“I”, 67.94%), 235 Unchanged (“U”, 14.66%) and 279 Worsened (“W”, 17.4%) patients. 18M post-implant, 91.5% I patients were alive vs. 89.9% U and 69.9% W (Unadjusted HR I vs. U 0.68 (0.37-1.27), I vs. W 0.24 (0.15-0.37), and U vs. W 0.34 (0.18-0.65), Log-Rank p&lt;0.001). I patients were projected to survive 8.007 years vs. 7.967 U and 1.815 W. Post-CCS assessment HF hospitalization rates in the first year were 0.13 for I, 0.27 for U and 0.90 for W (p&lt;0.0001) leading to a lifetime projection of 1.04, 2.14 and 2.54 total hospitalizations per patient respectively. Adjusted ALOS was directionally favoring I (4.87, 8.06 and 8.38 respectively) but non-significant (p=0.14). CONCLUSIONS: Patients who improve or remain unchanged 6M after CRT implant are projected to live longer and consume fewer resources than patients who worsen.