tbuckley/cabot-search huggingface dataset:
Abstract 335: Resveratrol Confers Cardioprotection Against Ischemia/Reperfusion Injury by Inhibition of JNK via AMPK
Authors: Hsien-Hao Huang, Chang-Qing Li, Zuo-Hui Shao, Jun-Jie Yin, Jing Li, Terry L Vanden Hoek
Journal: Circulation (2014)

Introduction: Resveratrol (trans-3, 4’, 5-trihydroxystilbene) is a naturally occurring polyphenolic compound found in grapes, fruits and root of plant Polygonum cuspidatum. It modulates ROS generation, energy metabolism and cell death. We hypothesized that resveratrol cardioprotection against ischemia/reperfusion is regulated by free radicals scavenging activities, inhibition of JNK and activation of AMPK. Methods: Primary chick embryonic ventricular cardiomyocytes (4-5 days old) were exposed to1 h simulated ischemia and 3 h reperfusion. Free radical scavenging capacity of resveratrol was analyzed using electron spin resonance spectrometry for 1-diphenyl-2picrylhydrazyl (DPPH), superoxide and hydroxyl radical. Viability was assessed by propidium iodide uptake (PI) and LDH release. Intracellular ROS was measured by 2’, 7’-dichlorofluorescin diacetate (DCF). Phosphorylation of JNK and AMPK were analyzed by western blot. Resveratrol (50 μM) was given at reperfusion and JNK inhibitor (SP600125, 10 μM), AMPK i...
Early Detection of Viral Resistance by Determination of Hepatitis B Virus Polymerase Mutations in Patients Treated by Lamivudine for Chronic Hepatitis B
Authors: Si Nafa Si Ahmed, David Tavan, Christian Pichoud, Françoise Berby, Lieven Stuyver, Mark Johnson, Philippe Merle, Hassane Abidi, Christian Trépo, Fabien Zoulim
Journal: Hepatology (2000)

We have analyzed the molecular dynamics of emergence of drug-resistant strains in patients receiving lamivudine therapy for chronic hepatitis B. Twenty consecutive patients with lamivudine resistance were studied (13 hepatitis B e antigen [HBeAg]-positive patients and 7 HBe antibody [anti-HBe]-positive patients). Determination of viral genotype, precore mutants, and polymerase gene mutants (L528M, M552V, M552I) was performed using the research version of Lipa-HBV. Quantitative analysis of HBV DNA was performed using both branched DNA (bDNA) and polymerase chain reaction (PCR) assays. Polymerase mutants (genotypic resistance) were found in 16 of 20 patients. Genotypic resistance was detected earlier than the phenotypic resistance (P =.004). Quantitative PCR allowed detection of viral DNA throughout the entire study period in 16 of 20 patients. Analysis of pretreatment variables showed that high alanine transaminase (ALT) levels (>3 x the upper limit of normal [ULN]) was associated with a more rapid selection of drug-resistant mutants (P =.027) and a high hepatitis B virus (HBV) DNA level (>1,497 Meq/mL, bDNA) with a more rapid occurrence of phenotypic resistance (P =.04). At the time of viral breakthrough, the mean serum HBV-DNA values were not different from the pretreatment values (P =.37). ALT levels were higher in anti-HBe-positive patients compared with pretreatment values and to HBeAg-positive patients (P =.01). In 8 patients, antiviral therapy was modified after viral breakthrough, with the introduction of famciclovir and/or interferon alfa. Viral DNA became undetectable by bDNA in 3 patients who received interferon. Our results suggest that genotypic assays for polymerase mutant detection and quantitative determination of viremia with highly sensitive assay are warranted for an optimal monitoring of antiviral therapy of chronic hepatitis B.
Abstract 1618: Clinical Spectrum of Tako-Tsubo-Cardiomyopathy in a Western Population: Results of the Tako-Tsubo-Registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenkenhausaerzte (ALKK)
Authors: Birke Schneider, Anastasios Athanasiadis, Wolfgang Pistner, Rainer Schamberger, Wolfgang Toepel, Ralph Schoeller, Angelika Bublak, Birgit Gerecke, Christoph Stellbrink, Uta Gottwald, Johannes Schwab, Kay Peters, Jürgen Stein, Udo Sechtem
Journal: Circulation (2007)

Purpose: Tako-tsubo-cardiomyopathy (TTC), initially described in Japan, has increasingly been recognized in western countries over the past years. Most studies, however, comprise relatively few patients. A German tako-tsubo-registry has been initiated to further characterize the clinical profile of this syndrome in a western population. Methods: So far 119 patients (P) were included according to following criteria: acute chest symptoms, ischemic ECG changes with ST-segment elevation ± T-wave inversion, reversible left ventricular akinesia not corresponding to a single coronary artery territory, absence of significant coronary artery stenoses. Results: Among 119 P (age 68±13 years) 104 were female (87%) and 15 male (13%). Triggering events present in 112 P (94%) consisted of emotional (n=82) or physical stress (n=59); 29 P (24%) experienced combined stress. The admission ECG showed ST-segment elevation (78%), reciprocal ST-segment depression (17%), negative T-waves (47%) and QTc prolongation (498±78 msec). Q-waves present in 27% on admission resolved during follow-up. Cardiac markers were slightly elevated (CK 264±573 U/l, troponin I 15±52 ng/ml). Ejection fraction was reduced (EF 54±15%). Left ventriculography showed apical ballooning in 83 (70%) and mid-ventricular ballooning in 36 P (30%). Except for a lower EF (50±15 vs 56±14%, p&lt;0.05) in mid-ventricular ballooning, both variants had an identical clinical profile. Right ventricular involvement was seen in 30 P (25%). Complications included pulmonary edema (19%), intraventricular pressure gradient (7%), VT (2%), cardiogenic shock (4%), 1 P died. Cardiac MRI performed in 66 P (55%) displayed no late enhancement within the regional wall motion abnormality. Echocardiography showed normalization of LV function within 3 months. ECG changes completely resolved within 6 months. Recurrence of TTC occurred in 4 P (4%) after 2–35 months. Regarding all parameters, no gender difference was observed. Conclusion: TTC predominantly occurs in elderly patients after a stressful event. Atypical mid-ventricular ballooning and right ventricular involvement are common. Cardiac MRI typically shows no late enhancement within the wall motion abnormality. The recurrence rate appears to be low.
Formoterol fumarate, a new β<sub>2</sub>‐adrenoceptor agonist
Authors: C.‐G. Löfdahl, N. Svedmyr
Journal: Allergy (1989)

Four double‐blind, double‐dummy, randomized, crossover studies were performed in nine asthmatic patients to evaluate β 2 ‐adrenoceptor selectivity and the duration of effect of formoterol. One study with cumulatively increasing doses of formoterol and salbutamol showed that with the inhaled route, formoterol was 5–15 times more potent than salbutamol with respect to bronchodilation. In a second study, 6 μg formoterol and 0.1 mg salbutamol were given for comparison of effect duration. Five hours after salbutamol inhalation the FEV 1 values were back to basal. Eight hours after formoterol inhalation about 75% of the maximum bronchodilation remained and the FEV 1 was significantly higher than after salbutamol inhalation. By oral route, a study with cumulatively increasing doses showed that as a bronchodilator formoterol was about 50 times more potent than salbutamol. The same potency difference was seen for increase of heart rate and decrease of diastolic blood pressure, indicating that the clinical selectivity for β 2 ‐adrenoceptors is equal for the two drugs. In a fourth study comparable doses by oral route did not show any difference in the duration of bronchodilation. We conclude that inhaled formoterol is 5–15 times more potent than salbutamol. Inhaled formoterol produces longer duration of bronchodilation, with clinically relevant bronchodilation for at least 8 h. The prolonged duration of formoterol was not seen with oral treatment.
Circumvention of drug resistance in human tumors harboring wild-type p53.
Authors: Zahid H. Siddik, Guangan He, Masayuki Watanabe, Kalpana Mujoo, Abdul R. Khokhar, Jian Kuang
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5420 

A seminal player in apoptosis is the tumor suppressor p53, which is often mutated in cancers and this causes drug resistance. What is not readily appreciated is the clinical significance of drug resistance in tumors harboring wild-type p53. In fact, such tumors are highly prevalent, accounting for 35-100% of resistant breast, non-small cell lung, testicular and ovarian cancers. Moreover, resistance of wild-type p53 tumors can be significantly greater than mutant p53 tumors. In our panel of clinically resistant human ovarian cancer, the IC50 of cisplatin in mutant p53 tumors was 1.2-3.3 μM (mean, 2.0), whereas in wild-type p53 tumors this range was 2.8-9.9 μM (mean, 5.7). This represents 9- and 26-fold resistance, respectively, compared to sensitive wild-type p53 ovarian A2780 cells. A common factor to emerge was the inability of cisplatin-treated wild-type p53 resistant tumors to activate the p53/p21 pathway, which then attenuates p21-dependent inhibition of G1-phase cyclin-dependent kinase (Cdk) complexes. Activation of the p53/p21 pathway, inhibition of Cdk, and cell death were observed with DAP, a DACH-Pt(IV) analog with axial acetates. These effects of DAP were also seen in intrinsic cisplatin-resistant breast and prostate cancers harboring wild-type p53. More importantly, p21-deleted HCT-116 cell lines were 2- to 3-fold resistant to the two platinum drugs. The differential effects of cisplatin and DAP in resistant tumor cells may be due in part to the mechanism of post-translational modification to induce/activate p53. In this respect, cisplatin induces p53 phosphorylation at Ser-392 in sensitive MCF-7 cells, but DAP does not. Similarly, dephosphorylation at Ser-376 was maximal at 4 h after DAP treatment (20 μM), whereas equimolar cisplatin did not induce dephosphorylation at this time, but dephosphroylated p53 appeared by 8-16 h at about 50% of maximal levels seen with DAP. The temporal profile of Ser-15 phosphorylation and induction of total p53 mirrored dephosphorylation of Ser-376, and provides a correlative relationship between these three cellular events. Since Ser-376 dephosphorylation and a lack of Ser-392 phosphorylation are properties associated with ionizing radiation, which induces p53 in an ATM-dependent manner, we explored whether p53 induction by DAP involved ATM. Systematic knockdowns with siRNA indicated that p53 induction by cisplatin was ATR/Chk1-dependent, but not ATM/Chk2-dependent, whereas p53 induction by DAP was independent of either of these two pathways. These results demonstrate that cisplatin and DAP activate p53 through different pathways, and this provides a basis for reactivation of the p53/p21 pathway by DAP to circumvent cisplatin resistance. (Supported by NCI RO1 CA 77332, 82361 and 93941).
An Englishman in Moscow
Authors: M Therese Southgate
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
Discontinuing Prophylactic Transfusions Used to Prevent Stroke in Sickle Cell Disease
Authors: Robert J Adams, Donald Brambilla
Journal: New England Journal of Medicine (2005)

Prophylactic transfusion prevents strokes in children with sickle cell anemia who have abnormalities on transcranial Doppler ultrasonographic examination. However, it is not known how long transfusion should be continued in these children.We studied children with sickle cell disease who had a high risk of stroke on the basis of a transcranial Doppler screening examination and who had received transfusions for 30 months or longer, during which time the Doppler readings became normal. The children were randomly assigned to continued transfusion or no continued transfusion. Children with severe stenotic lesions on cerebral magnetic resonance angiography were excluded. The composite primary end point was stroke or reversion to a result on Doppler examination indicative of a high risk of stroke.The study was stopped after 79 children of a planned enrollment of 100 underwent randomization. Among the 41 children in the transfusion-halted group, high-risk Doppler results developed in 14 and stroke in 2 others within a mean (+/-SD) of 4.5+/-2.6 months (range, 2.1 to 10.1) of the last transfusion. Neither of these events of the composite end point occurred in the 38 children who continued to receive transfusions. The average of the last two transcranial Doppler results before transfusion was started was the only predictor of the composite end point (P=0.05).Discontinuation of transfusion for the prevention of stroke in children with sickle cell disease results in a high rate of reversion to abnormal blood-flow velocities on Doppler studies and stroke. (ClinicalTrials.gov number, NCT00006182.)
Submicroscopic Morphology of Protoplasm and Its Derivatives
Authors: A. Frey-wyssling
Journal: JAMA (1949)

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 13258: Statin Reduces Cardiac Events after Acute Myocardial Infarction in Patients with High Lipoprotein (a)
Authors: Hiroki Ikenaga, Masaharu Ishihara, Ichiro Inoue, Takuji Kawagoe, Yuji Shimatani, Fumiharu Miura, Yasuharu Nakama, Kazuoki Dai, Takayuki Ohtani, Yoshimasa Morimoto, Kentaro Ejiri, Nozomu Oda, Masayuki Nakamura, Takashi Miki
Journal: Circulation (2010)

Purpose: Lipoprotein(a) [Lp(a)] is associated with development of new coronary lesions after acute myocardial infarction (AMI), and Lp(a) value remains consistent within individuals across their li...
Abstract 1456: Microrna-499 Regulates (cardio)myocyte Differentiation in Human-Derived Cardiomyocyte Progenitor Cells
Authors: Joost P Sluijter, Alain van Mil, Piet van Vliet, Corina H Metz, Pieter A Doevendans, Marie-José Goumans
Journal: Circulation (2008)

To improve regeneration of the injured myocardium, it is necessary to enhance the intrinsic capacity of the heart to regenerate itself and/or replace the damaged tissue by cell transplantation. One of the potential sources for cell replacement therapy are heart-derived progenitor cells. Cardiomyocyte progenitor cells (CMPCs) are obtained from human fetal hearts and adult human biopsies, easily expanded in culture, and efficiently differentiated into beating cardiomyocytes. Recently, several studies have demonstrated that microRNAs (miRNAs) are important for transcriptional regulation during angiogenesis, heart development, and maintenance of stem cell populations by translational repression. We hypothesize that, since miRNAs regulate stem cell maintenance and differentiation, miRNAs are involved in differentiation of human cardiomyocyte progenitor cells in vitro . Methods and results: Human fetal CMPCs were isolated, cultured, and efficiently differentiated into beating cardiomyocytes. miRNA expression was profiled in proliferating and differentiated CMPCs. We observed that miRNA-499 was highly upregulated upon differentiation (&gt;100 fold, microarray and qRT-PCR). Since tissue distribution of miRNA-499 was unknown, several mouse tissues were analyzed. qRT-PCR demonstrated that miRNA-499 is highly enriched in cardiac tissue. This was confirmed via in situ-hybridization, miRNA-499 was localized in cardiomyocytes in human fetal and adult hearts. Transient transfection of miRNA- 499 in undifferentiated CMPCs reduced their proliferation rate by 15% (MTT assay and FACS analysis). Moreover, upon miR-499 transfection spontaneous beating was observed earlier and expression levels of cardiac troponin T, alpha-cardiac actinin, and Mlc-2v was increased. This enhanced cardiomyocyte differentiation occurred via repression of Sox6. Conclusion: Our results demonstrate a strong regulatory role of miRNAs in human CMPC proliferation and differentiation into cardiomyocytes. By modulating miRNA-499 expression levels, the differentiation of CMPCs is affected, resulting in enhanced cardiomyogenesis.
Abstract 580: Epigenetic silencing of ARRDC3 expression in basal-like breast cancer cells
Authors: Young Hwa Song, Jun Chung
Journal: Cancer Research (2014)

Abstract Arrestin domain-containing 3 (ARRDC3) is a tumor suppressor whose expression is either lost or suppressed in basal-like breast cancer (BLBC). However, the mechanism by which BLBC suppresses ARRDC3 expression is not established. Here, we show that expression of ARRDC3 in BLBC cells is suppressed at the transcriptional level. Suppression of ARRDC3 expression in BLBC cells involves epigenetic silencing as inhibitors of class III histone deacetylases (HDACs) significantly restores ARRDC3 levels in BLBC cells. SIRT2, among class III HDACs, plays a major role in epigenetic silencing of ARRDC3 in MDA-MB-231 cells. Acetylation levels of the ARRDC3 promoter in BLBC cells is significantly lower than that of other sub-types of BC cells. Chromatin immunopreciptitation analysis established SIRT2 binding at ARRDC3 promoter in BLBC cells. Our studies indicate that SIRT2 dependent epigenetic silencing of ARRDC3 is one of the important events that may contribute to the aggressive nature of BLBC cells. Citation Format: Young Hwa Song, Jun Chung. Epigenetic silencing of ARRDC3 expression in basal-like breast cancer cells. [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 580. doi:10.1158/1538-7445.AM2014-580
Abstract 4266: Moving beyond in vitro models and addressing the challenges of pooled RNAi screens in mouse xenografts
Authors: Donato Tedesco, Kyle Bonneau, Mikhail Makhanov, Debbie Deng, Paul Diehl, Peiqing Sun, Alex Chenchik
Journal: Cancer Research (2014)

Abstract RNAi loss-of-function screening with pooled shRNA expression libraries has proven to be a useful tool to identify essential cancer genes and drug resistance mechanisms in numerous cell lines in vitro. The effects of knocking down large numbers of genes on cancer cell growth and viability can be measured simultaneously using this approach. Now there is considerable interest to adapt RNAi viability screens to ex vivo xenograft mouse models. However, small take rates, growth rate variance of cells, and differing cell microenvironments in these more complex tumor models impose significant challenges to this sort of assay. We have developed a novel approach based on the use of pooled shRNA libraries with clonal barcodes that enables proliferation measurements of clonal populations produced by the individual shRNA-expressing founder cells that produce the tumor. This RNAi clonal analysis provides a basis to separate, across large cell populations, the external parameters that strongly influence cell growth rates from shRNA-induced growth inhibition in these systems. We will present in vivo RNAi screening validation data for several cancer models. Citation Format: Donato Tedesco, Kyle Bonneau, Mikhail Makhanov, Debbie Deng, Paul Diehl, Peiqing Sun, Alex Chenchik. Moving beyond in vitro models and addressing the challenges of pooled RNAi screens in mouse xenografts. [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 4266. doi:10.1158/1538-7445.AM2014-4266
Risk factors for decreased work ability among middle-aged men having asthma from youth
Authors: Irmeli Lindström, Antti Karjalainen, Ritva Luukkonen, Paula Pallasaho, Hille Suojalehto, Antti Lauerma
Journal: European Respiratory Journal (2011)

Background: Occupational exposure to irritants and dusts has shown to contribute to respiratory work disability (Toren et al Thorax 2009;64(4):339-44).

Aims: We studied the effect of asthma which begins in youth on work ability in men around the age of 40, and analysed the risk factors for asthma-related work disability.

Methods: Finnish Defence Force registers in 1986-1990 were used to select: 1. conscripts with asthma representing a mild asthma group (n=485), 2. asthmatics who were exempted from military service representing a moderate/severe asthma group (n=393) and 3. a control group (n=1500) without asthma. 54% of the men in the first asthma group, 44% of the men in the second asthma group and 44% of the controls answered the questionnaire in spring 2009. The coded occupational history was matched with the asthma-specific Job Exposure Matrix in order to evaluate occupational exposure to asthmogens and respiratory irritants. Logistic regression analyses were used when examining the associations between risk factors and decreased work ability.

Results: Self-assessed current work ability compared with lifetime best in scale 0-10 was decreased (<8) in 28.9% of the first asthma group, in 31.1% of the second asthma group, and in 19.7% of the controls (p=0.0007). Current smoking (OR 2.5), being a manual worker (OR 2.7), exposure to irritants (OR 1.7) and abnormal temperatures (OR 1.7) and current severe asthma (OR 3.8) associated with decreased work ability among the asthmatics.

Conclusions: The reduction of work ability in men having asthma from youth may be partly preventable, if young asthmatics are advised to avoid work involving exposure to the irritants or abnormal temperatures and smoking.