tbuckley/cabot-search huggingface dataset:
Abstract 19821: 3D Tri-culture Model Promotes Enhanced Mechanical Forces and Sustained Long-Term Contractility of Human Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Karina Nakayama, Paul Burridge, Scott Metzler, Oscar Abilez, Chelsey Simmons, Marc Bruce, Yuka Matsuura, Paul Kim, Joseph Wu, Manish Butte, Phillip Yang, Ngan Huang
Journal: Circulation (2014)

BACKGROUND:  Engineered myocardial tissue represents a promising methodology for cardiac repair and regeneration, but the survival and contractility of the cardiomyocytes (CMs) in the engineered tissue remains a limiting factor. Since native CMs interact with endothelial and stromal cells, we generated a three-dimensional (3D) engineered myocardial tissue to study the role of cell-cell interactions on CM survival and function.   HYPOTHESIS:  Using human pluripotent stem cells (hPSCs) as a therapeutic cell source, we hypothesize that 3D tri-culture of hPSC-derived CMs (hCMs), hPSC-derived endothelial cells (hECs), and human amniotic mesenchymal stem cells (hAMSCs) will enable sustained, long-term contractility of the hCM population.   METHODS AND RESULTS:  We engineered myocardial tissues by culturing combinations of the three cell populations, within a 3D hydrogel for up to 6 weeks as follows: 1) hCMs only (mono-culture), 2) hCMs + hECs (co-culture), 3) hCMs + hAMSCs (co-culture), and 4) hCMs + hECs + hAMSCs (tri-culture). Timelapse imaging was used to compare contractility frequency and beating area, troponin T protein expression using immunofluorescence staining, and cardiac gene expression by qPCR. Quantification of contractility demonstrated enhanced function of hCMs in tri-culture. Expression of cTNT was up-regulated in the tri-culture vs. other culture conditions, which was supported by qPCR measurement of cardiac genes related to maintenance of CM structure (TNNT2 or β-myosin heavy chain, P    CONCLUSION:  These findings demonstrate that the 3D tri-culture system enabled significantly greater long-term contractility, sustained survival, and enhanced cardiac lineage-related gene expression of hCMs when compared to mono- and co-culture conditions. This study highlights the role of 3D hydrogels and cell-cell interactions to maintain cardiac phenotype and survival.
Low Plasma Ascorbic Acid Independently Predicts the Presence of an Unstable Coronary Syndrome
Authors: Joseph A Vita, John F Keaney, Khether E Raby, Jason D Morrow, Jane E Freedman, Sean Lynch, Spyridon N Koulouris, Beth R Hankin, Balz Frei
Journal: Journal of the American College of Cardiology (1998)

Objectives. This study sought to investigate the relations between plasma antioxidant status, extent of atherosclerosis and activity of coronary artery disease. Background. Previous studies indicate that increased antioxidant intake is associated with decreased coronary disease risk, but the underlying mechanisms remain controversial. Methods. Plasma samples were obtained from 149 patients undergoing cardiac catheterization (65 with stable angina, 84 with unstable angina or a myocardial infarction within 2 weeks). Twelve plasma antioxidant/oxidant markers were measured and correlated with the extent of atherosclerosis and the presence of an unstable coronary syndrome. Results. By multiple linear regression analysis, age (p < 0.001), diabetes mellitus (p < 0.001), male gender (p < 0.001) and hypercholesterolemia (p = 0.02) were independent predictors of the extent of atherosclerosis. No antioxidant/oxidant marker correlated with the extent of atherosclerosis. However, lower plasma ascorbic acid concentration predicted the presence of an unstable coronary syndrome by multiple logistic regression (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.40 to 0.89, p = 0.01). The severity of atherosclerosis also predicted the presence of an unstable coronary syndrome (OR 1.7, 95% CI 1.14 to 2.47, p = 0.008) when all patients were considered. When only patients with significant coronary disease were considered (at least one stenosis >50%), ascorbic acid concentration (OR 0.56, 95% CI 0.37 to 0.85, p = 0.008) and total plasma thiols (OR 0.52, 95% CI 0.34 to 0.80, p = 0.004) predicted the presence of an unstable coronary syndrome, whereas the extent of atherosclerosis did not. Conclusions. These data are consistent with the hypothesis that the beneficial effects of antioxidants in coronary artery disease may result, in part, by an influence on lesion activity rather than a reduction in the overall extent of fixed disease.
Posters_Tuesday 13 October 2009
Authors: G. Ehnsio, J. Norderfeldt, Joakim Alfredsson, Sören Berg
Journal: Intensive Care Medicine (2009)

The question of optimum serum glucose levels in the critically ill, and the effect on outcome continues to be keenly debated.A recent large trial has shown that intensive glucose control increased ICU mortality among adults in ICU [1]. OBJECTIVES.To compare two protocols with different triggers for starting insulin sliding scales for glucose control, in a district general hospital ICU in the UK and to observe the effects on our patient outcomes. METHODS.In May 2007 our ICU protocol trigger for starting insulin sliding scales for glucose control changed from glucose level greater than 8 mmol/l (group 1) to 10 mmol/l (group 2).No other policies were changed during this period.We compared 208 patients in group 1 to 659 patients in group 2. Only patients on an insulin sliding scale were included.A severe hypoglycaemic patient day was defined as a day in which a patient had at least one blood glucose reading \2.1 mmol/l. RESULTS.In Group 1, 39.9% of patients were female versus 42.9% in group 2 (p = 0.47).In group 1 and group 2, 15.4 versus 20.8% were admitted from A&E, 52.9 versus 50.1% admitted from theatre and 31.7 versus 29.1% admitted from other locations, respectively (p = 0.23).The mean age was 67 versus 64 years (p = 0.02) in group 1 and group 2, respectively.There was no significant difference between the two groups regarding all cause mortality within 28 days (p = 0.44), 90 day mortality (p = 0.20), ICU mortality (p = 0.16) or length of stay in ICU (0.21).There was no significant difference in the number of severe hypoglycaemic patient days (p = 0.86) or in the number of patients having severe hypoglycaemic days (p = 1.00).The ICU and hospital mortality (p = 0.00) was significantly greater in the group of patients who had severe hypoglycaemic patient days.The odds ratio for a patient who had a severe hypoglycaemic patient day dying in hospital was 8.978 (95% CI 3.640-22.145)and for dying in ICU was 14.728 (95%CI 6.622-32.760)greater than those for those who did not.The relative risk of those who did not have a severe hypoglycaemic patient day dying in ICU and hospital was 80 and 61% less, respectively, than in those with severe hypoglycaemic patient days.CONCLUSIONS.Changing our policy on glucose control from a treatment trigger of [8 to [10 mmol/l had no significant difference on the incidence of severe hypoglycaemic patient days or ICU mortality but the group of patients with severe hypoglycaemic patient days had higher mortality.
Abstract 273: Knowledge of First Aid and Cardiopulmonary Resuscitation by Faculty and Staff of Public Schools in São Paulo
Authors: Nilton F Assis, Isadora Liberato, Ana Laura Mathey, Renan Gianotto-Oliveira, Gustavo G Oliveira, Maria M Gonzalez, Sergio Timerman, Roberto Kalil Filho
Journal: Circulation (2014)

Background: Knowledge of first aid and cardiopulmonary resuscitation (CPR) is very important in schools, where children, teens and even employees are subject. Our objective was to evaluate the knowledge of teachers and employees of public schools in São Paulo on first aid and CPR with automated external defibrillator (AED). Methods: A questionnaire on the content that is covered in the course of First Aid from the American Heart Association was applied to faculty and staff of public schools in São Paulo. After answering the questionnaire, all volunteers took the course First Aid with CPR and AED. Results: The study included 563 volunteers: 227 (40%) teachers and 336 (60%) school staff. The mean age was 42 ± 12 years, 101 (18%) were male and 80 participants (14%) had already done a course in First Aid and / or CPR. The mean number of correct answers was 6.5 (46%) in a total of 14 questions. The questions with the greatest number of errors were: frequency of chest compressions (82%), depth of chest compressions (78%), handling of automated external defibrillator (77%), what to do with an unconscious victim (64%), compression ratio and ventilation (61%), conduct on a victim with nosebleed (53%) and conduct on a victim with convulsion (52%). When asked if they were interested in doing a course in first aid, 95% answered yes, 89% believe that the contents of first aid should be placed in the grade of students albeit in a simplified manner. Conclusion: We conclude that the degree of knowledge of teachers and employees of public schools in São Paulo is quite insufficient, although the vast majority has an interest in pursuing a course that addresses the topic of first aid and CPR with AED. It would therefore be very interesting that the government underscored the importance of the subject and stimulate training for teachers, school staff and students.
Immunoregulatory and anti-metastatic activities of several herbal medicinal acupuncture
Authors: Soojin Lee, Myoungdong Kim
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

C74 

In the traditional medicine of many Asian countries, acupuncture is considered as one of the most effective treatments. In a treatment with a herbal medicinal acupuncture, a fixed amount of the herbal extracts, repeatedly distillated with water for extreme purity, is injected into a specific point (acupoint) of the body, which has been empirically proven effective in the treatment of specific disorders. Also, it has been reported that several acupuncture stimulation suppresses relapse of cancer patients and reduces adverse effects of radiotherapy through enhancing cellular immunity. In the present study, we have investigated whether several herbal medicinal acupuncture treatment would cause anti-cancer and immunoregulatory activities. Anti-metastatic activities were investigated by in vivo metastatic model. Immunoregulatory activities were investigated by measurement of cell proliferation (XTT assay) and cell differentiation (FACS analysis), and stimulation of cytokine (IFN-γ and IL-4) in vitro , in murine lymphoid cells.
Health Woes Grow in Shrinking World
Authors: M F Goldsmith
Journal: JAMA (1998)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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 16870: Dissociation of Mitochondrial HK-II Triggers Mitochondria Specific Autophagy
Authors: Shigeki Miyamoto, David J Roberts, Valerie P Tan-Sah
Journal: Circulation (2014)

Introduction: There is emerging evidence that the metabolic pathway interplays with the survival pathway to preserve cellular homeostasis. Hexokinases (HKs) catalyze the first step of glucose metabolism and hexokinase-II (HK-II) is the predominant isoform in the heart. Our recent study revealed that HK-II positively regulates general autophagy in the absence of glucose. Mitochondrial HK-II (mitoHK-II) is regulated by Akt and provides cardioprotection while it is decreased in the ischemic heart. Hypothesis: We tested the hypothesis that mitoHK-II dissociation triggers mitochondria specific autophagy (mitophagy). Results: As previously reported, mitoHK-II levels were decreased by ~40% in the perfused mouse heart subjected to global ischemia and in neonatal rat ventricular myocytes (NRVMs) subjected to simulated ischemia. To assess the role of mitoHK-II dissociation, mitoHK-II dissociating peptide (15NG) was expressed in NRVMs. MitoHK-II was decreased by 40% in NRVMs expressing 15NG which was accompanied with Parkin translocation to mitochondria and ubiquitination of mitochondrial proteins. This response was attenuated by Parkin knockdown and reversed by the recovery of mitoHK-II by co-expression of HK-II but not by that of mitochondria binding deficient mutant. 15NG expression did not induce mitochondrial membrane depolarization nor PINK1 stabilization at mitochondria, suggesting that the effects of mitoHK-II dissociation is not dependent on the previously established mitochondria depolarization/PINK1 pathway. This was confirmed by the experiments using PINK1 siRNA. Modest dissociation of mitoHK-II (by 20%) did not induce mitophagic responses but remarkably enhanced FCCP induced mitophagy, indicating that these two pathways are synergetic. We will be analyzing 15NG transgenic mice generated in our lab to determine the mitophagic role of mitoHK-II dissociation in vivo. Conclusions: These results suggest that mitoHK-II dissociation can regulate Parkin dependent mitophagy, in conjunction with depolarization dependent mechanisms and that HK-II could confer cardioprotection by switching the cell from an energy production to an energy conservation mode under ischemia.
Abstract 13242: Insulin Treated Patients With Diabetes Derive Reduction in Mortality From Cardiac Resynchronization Therapy - Results From the Madit-Crt in Trial Experience
Authors: Barbara Szepietowska, Valentina Kutyifa, Martin H Ruwald, Scott D Solomon, Anne-Christine H Ruwald, Scott McNitt, Slava Polonsky, Arthur Moss, Wojciech Zareba
Journal: Circulation (2014)

Methods: We aimed to analyze the risk for death and HF and the effect of CRT on HF/death in diabetic patients with or without insulin treatment compared to none diabetic population. The study comprised 1278 patients with left bundle branch block in the MADIT-CRT trial with an average follow-up of 3.3y. We used time dependent survival analysis and Cox proportional hazards regression method. Results: In ICD arm patients with diabetes receiving insulin treatment had 2.4-fold higher risk of all-cause mortality (p=0.008), and 2.2-fold higher risk of HF (p&lt;0.001) when compared to non diabetic patients, and 2.8-fold higher risk of death (p=0.01), and 1.6-fold higher risk of HF (p=0.06) when compared to patients with diabetes not treated with insulin. Treatment with CRT-D was associated with a significant 75% risk reduction in all-cause mortality (hazard ratio [HR ] 0.25; 95% confidence interval [CI]: 0.08-0.77; p=0.016) in patients with diabetes receiving insulin. Noteworthy, during the 3-year follow-up, reduction in all-cause mortality was not observed in patients not treated with insulin or in patients with no diabetes (interaction p-value=0.038). Significant risk reduction in HF and in HF/death after CRT treatment was observed across all three investigated groups. There were not significant differences in left ventricular reverse remodeling after CRT-D among diabetic patients with or without insulin treatment compared to the nondiabetic population. Conclusions: Patients with insulin treated diabetes derive significant reduction in mortality and heart failure after implantation of cardiac resynchronization therapy. Patients with diabetes and no insulin and patient without diabetes benefit from CRT by reduction of HF events.
Lymphocyte Activation Antigen CD70 Expressed by Renal Cell Carcinoma Is a Potential Therapeutic Target for Anti-CD70 Antibody-Drug Conjugates
Authors: Che-Leung Law, Kristine A. Gordon, Brian E. Toki, Andrew K. Yamane, Michelle A. Hering, Charles G. Cerveny, Joseph M. Petroziello, Maureen C. Ryan, Leia Smith, Ronald Simon, Guido Sauter, Ezogelin Oflazoglu, Svetlana O. Doronina, Damon L. Meyer, Joseph A. Francisco, Paul Carter, Peter D. Senter, John A. Copland, Christopher G. Wood, Alan F. Wahl
Journal: Cancer Research (2006)

Metastatic renal cell carcinoma (RCC) is an aggressive disease refractory to most existing therapeutic modalities. Identifying new markers for disease progression and drug targets for RCC will benefit this unmet medical need. We report a subset of clear cell and papillary cell RCC aberrantly expressing the lymphocyte activation marker CD70, a member of the tumor necrosis factor superfamily. Importantly, CD70 expression was found to be maintained at the metastatic sites of RCC. Anti-CD70 antibody-drug conjugates (ADC) consisting of auristatin phenylalanine phenylenediamine (AFP) or monomethyl auristatin phenylalanine (MMAF), two novel derivatives of the anti-tubulin agent auristatin, mediated potent antigen-dependent cytotoxicity in CD70-expressing RCC cells. Cytotoxic activity of these anti-CD70 ADCs was associated with their internalization and subcellular trafficking through the endosomal-lysosomal pathway, disruption of cellular microtubule network, and G2-M phase cell cycle arrest. The efficiency of drug delivery using anti-CD70 as vehicle was illustrated by the much enhanced cytotoxicity of antibody-conjugated MMAF compared with free MMAF. Hence, ADCs targeted to CD70 can selectively recognize RCC, internalize, and reach the appropriate subcellular compartment(s) for drug release and tumor cell killing. In vitro cytotoxicity of these ADCs was confirmed in xenograft models using RCC cell lines. Our findings provide evidence that CD70 is an attractive target for antibody-based therapeutics against metastatic RCC and suggest that anti-CD70 ADCs can provide a new treatment approach for advanced RCC patients who currently have no chemotherapeutic options.
Claspin but not Brca1 is required to mediate the gemcitabine-induced S phase checkpoint
Authors: Jingxuan Pan, William Plunkett
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2269 

The nucleoside analog, gemcitabine, arrests cell lines derived from solid tumors in S phase. Investigations in several cell models demonstrated that checkpoint activation requires the Chk1 DNA damage kinase, that is phosphorylated in an ATR-dependent manner. Also, S-phase arrest is associated with an increase in Y15 phosphorylation of the cyclin-dependent kinase, Cdk2. Finally, although the S-phase checkpoint mediators, Claspin and Brca1, are phosphorylated during the gemcitabine-induced arrest, their precise contribution to the checkpoint elicited by gemcitabine remains unclear. The present study was aimed at comparing the relative contribution of Claspin and Brca1 in a single model. We used a small interfering (siRNA) knockdown approach to test the effect of Claspin and Brca1 on gemcitabine-induced S phase arrest in U2OS cells. Transfection with siRNA to Claspin decreased its protein level by 90%, whereas there was no significant effect of control siRNA. After a subsequent 24-h exposure to 10 nM gemcitabine, the proportion of cells in S-phase transfected by control siRNA increased from 26% to 77%. In contrast, following transfection with siRNA against Claspin, the S phase population increased to only 43%. Brca1 siRNA significantly reduced Brca1 protein levels, but this had little effect on gemcitabine-induced S phase accumulation (25% to 65% in S phase). Upon transfection with a siRNA mixture against Brca1 and Claspin, cells in S phase increased from 26% to 47% upon gemcitabine exposure, suggesting that Claspin, but not Brca1, is required for S phase checkpoint activation. Consistent with these results, Claspin silencing attenuated the increase of the inhibitory phosphorylation of Cdk2 on Y15 in gemcitabine-treated cells as detected by immunoblotting, whereas knockdown of Brca1 had no effect. Again, the combination siRNA transfection did not further decrease the gemcitabine-induced Cdk2 phosphorylation. These results suggested that Claspin contributed to the regulation of the activity of Cdk2, which governs S phase progression. Finally, we examined the impact of silencing Brca1, Claspin, or both on Chk1 activation. In cells transfected with control siRNA, phosphorylation of Chk1 at Ser-317 and Ser-345 underwent an approximate 20-fold increase upon gemcitabine treatment. Knocking down Brca1 did not significantly diminish Chk1 phosphorylation. However, Chk1 phosphorylation induced by gemcitabine was diminished to 10% of control siRNA cells in Claspin knockdown cells, and also in combination knockdown cells. These results argue that Claspin is more important for Chk1 activation by gemcitabine than Brca1. In conclusion, Claspin appears to be an important mediator for S phase checkpoint activation during gemcitabine treatment.
Ustekinumab: effective in a patient with severe recalcitrant generalized pustular psoriasis
Authors: E. Daudén, D. Santiago-et-Sánchez-Mateos, E. Sotomayor-López, A. García-Díez
Journal: British Journal of Dermatology (2010)

Conflicts of interest: E.D. has been an advisory board member and consultant, received grants, research support and honoraria for speaking, or participated in clinical trials, with Abbott, Astellas, Biogen, Centocor Ortho Biotech Inc., Galderma, Glaxo, Janssen‐Cilag, Leo Pharma, Merck‐Serono, Novartis, Pfizer, Schering‐Plough, Stiefel, Wyeth Pharmaceuticals and 3M. A.G.‐D. has been an advisory board member and consultant, and received research support from Abbott and Serono. The other authors declare no conflicts of interest. Madam, Generalized pustular psoriasis is a rare and disabling variant of psoriasis. Its treatment is often challenging, as an unsatisfactory response is frequent. Ustekinumab, a fully human monoclonal antibody that binds to the shared p40 subunit of interleukin 12/23, has proven to be effective and safe for the treatment of moderate‐to‐severe plaque‐type psoriasis.1–4 A 47‐year‐old man presented with recurrent episodes of widespread and often generalized flares of classic plaque‐type psoriasis, which he had experienced since the age of 14. His medical history included hypertension, dyslipidaemia, hyperuricaemia and depression. His psoriasis was first treated with multiple topical agents, etretinate, acitretin, retinoids with psoralen plus ultraviolet A and methotrexate, with only partial response. In February 2007, he started treatment with infliximab, achieving an almost complete clearance of the plaques. However, withdrawal of the drug after seven infusions was necessary because of an elevation of transaminases up to six times the baseline values. Efalizumab was then initiated, but owing to only a slight improvement with this drug and the suspension of commercialization, therapy was withdrawn. A gradual deterioration of his skin involvement led, one and a half months later, to a significant flare of pustular psoriasis. Physical examination was remarkable for diffusely scattered pruriginous pustules on an erythematous base involving his head, trunk and upper/lower limbs (Fig. 1). A biopsy showed the characteristic findings of pustular psoriasis. Complementary tests were normal or negative except for a slight increase in cholesterol and triglycerides. His weight was 92 kg. The baseline situation was as follows: Psoriasis Area and Severity Index (PASI) score modified for pustular psoriasis manifestations (scaling substituted by pustules) 23·3; body surface area (BSA) 25%; Physician's Global Assessment (PGA) very severe; visual analogue scale (VAS, 0–10) for pruritus 7.