tbuckley/cabot-search huggingface dataset:
Abstract 13433: Angiotensin II Type 2 Receptor Regulates Skeletal Myoblast Differentiation: Implications for treatment of Cachexia and Skeletal Muscle Wasting
Authors: Tadashi Yoshida, Patrice Delafontaine
Journal: Circulation (2014)

Patients with advanced congestive heart failure (CHF) or chronic kidney disease (CKD) often have increased angiotensin II (Ang II) levels and cachexia. We previously demonstrated that Ang II infusion in rodents causes skeletal muscle wasting and decreases muscle regenerative potential via Ang II type 1 receptor (AT1R) signaling, likely contributing to cachexia in CHF and CKD. However, the potential role of Ang II type 2 receptor (AT2R) signaling in skeletal muscle physiology remains unknown. We found that AT2R expression was robustly increased in mouse skeletal myoblasts during differentiation, suggesting that the AT2R plays an important role in skeletal muscle regeneration. To test this hypothesis, we infused mice with AT2R antagonist PD123319 (PD, 30 mg/kg/d) or agonist CGP123319 (CGP, 1 μg/kg/min) during cardiotoxin (CTX)-induced muscle injury and regeneration. PD reduced the size of regenerating myofibers (727.5±54.6 and 516.0±37.0 μm2 in sham and PD, respectively, p<0.05) and expression of the myoblast differentiation markers myogenin and eMyHC (56.9% and 40.2% decrease in PD, respectively. p<0.01), whereas CGP had the opposite effects. siRNA mediated AT2R knockdown in mouse primary myoblasts suppressed the increase of myogenin and desmin, resulting in lowered differentiation. We analyzed changes in phosphoprotein levels in myoblasts after AT2R knockdown by phosphoprotein array and identified multiple changes, including increased phospho-ERK1/2 levels. Importantly, inhibition of ERK1/2 restored normal myoblast differentiation in the setting of AT2R knockdown, suggesting the AT2R positively regulates myoblast differentiation by reducing ERK1/2 activity. Furthermore, we found that skeletal muscle regeneration was reduced (decreased regenerating myofiber size and myogenin/desmin expression) in a mouse myocardial infarction model of CHF, concomitantly with markedly blunted increase of AT2R expression, strongly suggesting that the AT2R plays an important role in the reduction of skeletal muscle function in CHF. These data indicate that AT2R signaling positively regulates myoblast differentiation and potentiates skeletal muscle regeneration, providing a new therapeutic target in wasting disorders such as CHF and CKD.
An association between viral genes and human oncogenic alterations: The adenovirus E1A induces the Ewing tumor fusion transcript EWS–FLI1
Authors: Ricardo Sanchez-Prieto, Enrique de Alava, Teresa Palomino, Juan Guinea, Victor Fernandez, Silvia Cebrian, Matilde LLeonart, Pablo Cabello, Pilar Martin, Carlos San Roman, Rafael Bornstein, Javier Pardo, Ana Martinez, Fernando Diaz-Espada, Yve Barrios, Santiago Ramon y Cajal
Journal: Nature Medicine (1999)
Lehrbuch der Mund- und Kieferchirurgie.
Authors: Erich Sonntag, Wolfgang. Rosenthal
Journal: JAMA (1931)

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 2682: ELTD1 as a target for anti-cancer therapy in rodent gliomas
Authors: Rheal A. Towner, Richard Pody, Nataliya Smith, Debra Saunders, Charity Njoku, Jonathan D. Wren
Journal: Cancer Research (2014)

Abstract Despite current therapies, glioblastoma multiforme (GBM) is a devastating cancer with a very poor prognosis. Specific protein biomarkers for GBM enable not only new prognostic avenues to tailor treatment, but valuable therapeutic targets to interfere with GBM growth. We recently discovered a new biomarker for high-grade gliomas, ELTD1 (epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1), via a novel bioinformatics approach, GAMMA (Global microarray meta-analysis). ELTD1 was found to be significantly higher (p&amp;lt;0.05) in high-grade gliomas (50 patients) compared with low-grade gliomas (21 patients). ELTD1 gene expression was found to be associated with tumor grade, survival across grade, and an increase in the mesenchymal subtype. From our previous results we hypothesized that ELTD1 may be a potential therapeutic target in high-grade gliomas. We tested the hypothesis in an orthotopic GL261 mouse glioma model in animals treated with an anrti-ELTD1 antibody, compared to those that were treated with an anti-VEGF antibody or an anti-c-Met antibody, and untreated tumors. Tumor volumes were measured by morphological magnetic resonance imaging (MRI). Our data in orthotopic GL261 glioma-bearing mice shows that injection of anti-ELTD1 antibodies lead to a significant decrease in tumor volumes (p&amp;lt;0.0001) and a significant increase in animal survival (p&amp;lt;0.05), superior to that achieved by a mouse anti-VEGF antibody or an antibody against c-Met, when compared to untreated mice. Tumor volumes were obtained at various time-points, and compared at 21 days following intracerebral implantation of GL261 cells in male C57BL6 mice. These tumor volumes at 21 days were 86.03+/-41.54 mm3 for untreated mice (n=5); 13.04+/-5.35 mm3 for anti-ELTD1 treated mice (n=5); 33.16+/-12.48 mm3 for anti-VEGF treated mice (n=4); and 28.49+/-11.11 mm3 for anti-c-Met treated mice (n=5). The mean days of survival for untreated, ELTD1, VEGF or c-Met treatment groups were 23.8+/-1.79, 28.2+/-2.39, 27+/-1.15 or 27+/-1.87 days, respectively. These pre-clinical results indicate that an additional therapy in the form of an anti-ELTD1 antibody either as a sole agent or in combination with current or new therapies could potentially provide high-grade glioma patients with a better prognostic outcome. Citation Format: Rheal A. Towner, Richard Pody, Nataliya Smith, Debra Saunders, Charity Njoku, Jonathan D. Wren. ELTD1 as a target for anti-cancer therapy in rodent gliomas. [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 2682. doi:10.1158/1538-7445.AM2014-2682
Abstract 17009: Clinical Characteristics and In-hospital Outcomes of Cardiac Transplant Recipients With Allograft Vasculopathy Undergoing Percutaneous Coronary Intervention: Insights from the National Cardiovascular Data Registry
Authors: Selim R Krim, Mohamad Alkhouli, Tarun W Dasari, Gregg C Fonarow, Jorge F Saucedo, Rene Alvarez, Homam Ibrahim, David Dai, Marco Costa, Tracy Y Wang, JoAnn Lindenfeld, John Messenger
Journal: Circulation (2014)

Introduction: Cardiac Allograft Vasculopathy (CAV) is a major limiting factor for long-term survival among cardiac transplant recipients. Large-scale data pertaining to the clinical characteristics and in-hospital outcomes in such patients undergoing Percutaneous Coronary Intervention (PCI) is lacking. Methods: We analyzed 1,897,328 patients from the NCDR CathPCI registry™ who underwent PCI of at least 1 native vessel between July 2009-December 2013 from 1477 centers, of which 542 patients (0.03%) had previous cardiac transplantation. After 4:1 propensity matching, clinical characteristics and in-hospital outcomes were compared between 538 cardiac transplant recipients and 2128 non-transplant patients. Results: Cardiac transplant recipients were more likely to have prior PCI, dyslipidemia, Canadian class 3/4 angina and were less likely to be smokers or present with ST segment-elevation myocardial infarction (0.9% vs. 7.1%, p&lt;0.01) compared to the general population. Transplant recipients had fewer type C lesions (36% vs. 41% p=0.02) and were more likely to receive drug-eluting stents (DES: 81% vs. 76% p&lt;0.01). In-hospital mortality, composite of death/MI/stroke, and bleeding complications were not significantly different between propensity-matched groups. (Table) Conclusions: Our large database analysis demonstrate that despite some differences in clinical characteristics, in-hospital outcomes among cardiac transplant recipients undergoing PCI for focal lesions associated with CAV were similar to the general population. Use of DES was higher in this group.
Predictors of Pregnancy Outcomes in Patients With Lupus
Authors: Jill P. Buyon, Mimi Y. Kim, Marta M. Guerra, Carl A. Laskin, Michelle Petri, Michael D. Lockshin, Lisa Sammaritano, D. Ware Branch, T. Flint Porter, Allen Sawitzke, Joan T. Merrill, Mary D. Stephenson, Elisabeth Cohn, Lamya Garabet, Jane E. Salmon
Journal: Annals of Internal Medicine (2015)

Background: Because systemic lupus erythematosus (SLE) affects women of reproductive age, pregnancy is a major concern. Objective: To identify predictors of adverse pregnancy outcomes (APOs) in patients with inactive or stable active SLE. Design: Prospective cohort. Setting: Multicenter. Patients: 385 patients (49% non-Hispanic white; 31% with prior nephritis) with SLE in the PROMISSE (Predictors of Pregnancy Outcome: Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus) study. Exclusion criteria were urinary protein–creatinine ratio greater than 1000 mg/g, creatinine level greater than 1.2 mg/dL, prednisone use greater than 20 mg/d, and multifetal pregnancy. Measurements: APOs included fetal or neonatal death; birth before 36 weeks due to placental insufficiency, hypertension, or preeclampsia; and small-for-gestational-age (SGA) neonate (birthweight below the fifth percentile). Disease activity was assessed with the Systemic Lupus Erythematosus Pregnancy Disease Activity Index and the Physician's Global Assessment (PGA). Results: APOs occurred in 19.0% (95% CI, 15.2% to 23.2%) of pregnancies; fetal death occurred in 4%, neonatal death occurred in 1%, preterm delivery occurred in 9%, and SGA neonate occurred in 10%. Severe flares in the second and third trimesters occurred in 2.5% and 3.0%, respectively. Baseline predictors of APOs included presence of lupus anticoagulant (LAC) (odds ratio [OR], 8.32 [CI, 3.59 to 19.26]), antihypertensive use (OR, 7.05 [CI, 3.05 to 16.31]), PGA score greater than 1 (OR, 4.02 [CI, 1.84 to 8.82]), and low platelet count (OR, 1.33 [CI, 1.09 to 1.63] per decrease of 50 × 109 cells/L). Non-Hispanic white race was protective (OR, 0.45 [CI, 0.24 to 0.84]). Maternal flares, higher disease activity, and smaller increases in C3 level later in pregnancy also predicted APOs. Among women without baseline risk factors, the APO rate was 7.8%. For those who either were LAC-positive or were LAC-negative but nonwhite or Hispanic and using antihypertensives, the APO rate was 58.0% and fetal or neonatal mortality was 22.0%. Limitation: Patients with high disease activity were excluded. Conclusion: In pregnant patients with inactive or stable mild/moderate SLE, severe flares are infrequent and, absent specific risk factors, outcomes are favorable. Primary Funding Source: National Institutes of Health.
German research society apologises to victims of Nazis
Authors: A. Tuffs
Journal: BMJ (2001)

After more than 50 years Germany's main research organisation, the Max Planck Society, has accepted historical responsibility for crimes committed by Nazi doctors.

At a symposium on biomedical sciences and human experimentation at the Kaiser Wilhelm Institute in Berlin last week, the president of the society, biologist Hubert Markl, apologised to all victims of Nazi doctors, some of whom were present at the symposium.

“Like other German institutions, the Max Planck Society has ignored its historical responsibility too long,” said Professor Markl.

The society was founded …
Neonatal Signs After In Utero Exposure to Selective Serotonin Reuptake Inhibitors
Authors: Bennett Lavenstein
Journal: JAMA (2005)

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
THE EARLY DEVELOPMENT OF SYPHILITIC AORTITIS
Authors: F S HOUSER, E M KLINE
Journal: Annals of Internal Medicine (1947)

ExcerptThe clinical diagnosis of aortitis is usually made late in the course of syphilitic infection. Although the literature contains references to its early development, it is not generally appreciated that the condition may sometimes be found within a short time after the primary infection. In the case to be reported symptoms appeared 10 months after infection and death from heart failure occurred 22 months later.CASE REPORTA colored male, aged 41 years, was seen in the Out-Patient Department October 25, 1944, complaining of dyspnea and orthopnea since August, 1943.The past history is irrelevant except for the following important...
Canadian doctors welcome public health initiatives in wake of SARS
Authors: Kermode-Scott Barbara
Journal: BMJ (2004)

The Canadian government has committed $C665m (£280m; $US500m; €415m) over three years to various new public health initiatives, including a national public health agency, a national immunisation strategy, and a pan-Canadian public health network.

The new Canadian public health agency will play a similar role in Canada to that played by the Centers for Disease Control and Prevention (CDC) in the United States. Like the CDC, the Canadian agency will focus equally on the prevention of infectious and chronic diseases and of disabilities.

It will build on existing public …
Increased Mucosal B-Lymphocyte Apoptosis During Polymicrobial Sepsis Is a Fas Ligand But Not an Endotoxin-Mediated Process
Authors: Alfred Ayala, Ying Xin Xu, Carol A. Ayala, Diane E. Sonefeld, Shannon M. Karr, Tracy A. Evans, Irshad H. Chaudry
Journal: Blood (1998)
Abstract P151: Neighborhood-Level Socioeconomic Deprivation Is Associated with Diabetes Mellitus in a Multi-Ethnic Population: The Dallas Heart Study
Authors: Michael McClurkin, Colby Ayers, Tammy Leonard, Rebecca Cooper-McCann, Christine Hoehner, Tiffany M Powell-Wiley
Journal: Circulation (2014)

Background: Although neighborhood-level socioeconomic deprivation has been associated with obesity, its relationship with diabetes, a cardio-metabolic risk factor and determinant of cardiovascular health, is poorly understood. Methods and Results: We examined the relationship between neighborhood-level socioeconomic deprivation and prevalent diabetes in the Dallas Heart Study (DHS), a multi-ethnic, population-based sample of Dallas County residents aged 18-65 (N=1621). Participants underwent detailed examination between 2000-2002. Geo-coded home addresses defined neighborhood block groups; a neighborhood-level deprivation index (NDI) for Dallas County was created using factor analysis based on 21 Census block-group characteristics (higher scores=greater neighborhood-level deprivation). Diabetes was defined by self-report, use of anti-hyperglycemic medication, or fasting glucose≥126 mg/dl. Logistic regression modeling was used to determine odds of prevalent diabetes for those in highest vs. lowest NDI tertile. In DHS, diabetes prevalence was 5%, 13%, and 16% across NDI tertiles (p&lt;0.001). In modeling diabetes, we found a significant interaction between race and NDI (p=0.03); therefore, models were race-stratified. White, Hispanic, and black DHS participants in neighborhoods in the highest NDI tertile were up to seven times more likely to have diabetes than those living in the lowest tertile (Table). In whites and Hispanics, higher deprivation remained associated with a greater likelihood of diabetes after adjustment for age, sex, smoking, and education and was only attenuated after adjusting for income. In contrast, adjustment for confounders attenuated the relationship between NDI and diabetes among blacks. Conclusions: Residing in socioeconomically deprived neighborhoods is associated with prevalent diabetes among whites and Hispanics in DHS. These data suggest racial/ethnic disparities in cardio-metabolic risk within areas of higher socioeconomic deprivation in Dallas County.
Abstract 19769: Cardiac Injury and Stunning after Ischemia is Related to Loss of PBEF/Nampt Function and is Rescued by PTEN Inhibition
Authors: Jing Li, Zuo-Hui Shao, Chang-Qing Li, Sy-Jou Chen, Xiangdong Zhu, Shaun Harty, Terry L Vanden Hoek
Journal: Circulation (2014)

Introduction: Therapeutic hypothermia protection during cardiovascular resuscitation has been associated by us with preservation of heart tissue Pre-B-cell colony-enhancing factor (PBEF)/nicotinamide phosphoribosyltransferase (Nampt) level. This finding was associated with increased heart Akt activity that is negatively regulated by the phosphatase PTEN. We hypothesized that the PTEN inhibitor, VO-OHpic (VO), can improve heart cell survival and contractility via its role in energetic recovery following ischemia. Methods: Primary neonatal heart cells were exposed to 90 min ischemia and 180 min reperfusion to evaluate viability by propidium iodide uptake. Contractility was assessed in a stunning model of 30 min ischemia and 90 min reperfusion. VO (1μM) was given at reperfusion and PBEF/Nampt inhibitor FK866 (100 nM) was administered 1 h prior to ischemia. Akt phosphorylation and PBEF expression was detected by Western blot and ELISA assay, respectively. ATP content was measured by a fluorescent assay kit. Results: Compared to control cells, VO improved cell survival (56.3 ± 7.3 vs. 32.5 ± 7.6%, p &lt; 0.05), a protective effect blocked by FK866. VO also rapidly improved contractile recovery following 30 min ischemia and decreased PBEF/Nampt release from heart cells, protective effects blocked by FK866. Improved contraction was related to increased Akt Thr308 and Ser473 phosphorylation and total ATP content. Conclusions: PTEN inhibition improves heart cell survival, ATP content and contractile recovery after ischemia. Protection is associated with attenuation of PBEF/Nampt cell release and is blocked by PBEF/Nampt inhibitors.
AMN107: Inhibitory profile against non-mutated and mutated forms of the Bcr-Abl tyrosine kinase
Authors: Paul W. Manley, Jürgen Mestan, Sandra Cowan-Jacob, Markus Wartmann, Ellen Weisberg, Doriano Fabbro, D. Gary Gilliland, James D. Griffin
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5985 

Imatinib (Gleevec®, Novartis Pharma AG) is an effective first line therapy for CML, although in advanced stage CML and Ph+ ALL, but relapse can occur due to the development of resistance. Relapse often results from the clonal expansion of cells expressing Bcr-Abl kinase domain mutants, which are resistant to inhibition by imatinib. Utilising the crystal structure of the Abl-imatinib complex, AMN107 (4-methyl- N -[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl) phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide) was designed as more potent and highly selective inhibitor of Bcr-Abl tyrosine kinase. AMN107 reduces the cellular Bcr-Abl autophosphorylation and the proliferation of Ba/F3 Bcr-Abl cells with a mean IC50 values of 21 and 25 nM, respectively (Imatinib: 220 and 649 nM). In addition to inhibiting the non-mutated enzyme, AMN107 potently inhibits the Bcr-Abl activity of many imatinib-resistant mutants in transfected Ba/F3 cells (mean autophosphorylation / mean proliferation IC50; nM): G250E (n.d. / 54), E255K (150 / 566), E255V (246 / 681), E292K (31 / 94), F317L (41 / 80), M351T (31 / 33) and F486S (43 / 87), but does not inhibit the T315I mutant. Like imatinib, AMN107 also inhibits the c-Kit and PDGFR receptor kinases, with mean anti-proliferative IC50 values of 160 nM (exon13 mutant Kit expressing GIST cells), 26 nM (del 560-561 expressing Ba/F3 cells), 3.5 nM (FIPL1-PDGFRα expressing Ba/F3 cells) and 57 nM (Tel-PDGFRβ expressing Ba/F3 cells). As in the case of T315I Bcr-Abl mutant, the corresponding FIPL1-T674I-PDGFRα gatekeeper mutant is less sensitive to AMN107 (IC50 1340 nM). AMN107 shows an attractive kinase selectivity profile, having no effect on the viability of Ba/F3 cell lines engineered to express a panel of other receptor and non-receptor tyrosinse kinases, or on parental Ba/F3 cells grown in the presence of IL-3. AMN107 shows a good pharmacokinetic profile is well tolerated in rodents and dogs, and represents a promising new Bcr-Abl tyrosine kinase inhibitor which is currently undergoing evaluation in Phase I clinical trials.