tbuckley/cabot-search huggingface dataset:
Organ Registries Still Limited
Authors: Brian Vastag
Journal: JAMA (2002)

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 18692: Reciprocal Regulation of Metabolic and Signaling Pathways Correlates with Disease Severity in Heart Failure
Authors: Andreas S Barth, Ami Kumordzie, Kenneth B Margulies, Thomas P Cappola, Gordon F Tomaselli
Journal: Circulation (2010)

Background: Systolic heart failure (HF) is a complex systemic syndrome that can result from a wide variety of clinical conditions and genetic mutations. Despite phenotypic similarities, characteriz...
Abstract 13560: Adverse Influence of Adiposity on Wave Reflection in Healthy Children
Authors: Satoru Sakuragi, Richard D Telford, Walter P Abhayaratna
Journal: Circulation (2010)

Background:  The relationship between childhood obesity and adverse cardiovascular outcomes during adulthood may be mediated through the promotion of impaired vascular function. Wave reflection is an index of arterial function that is determined by arterial stiffness and is predictive of adverse cardiovascular events in adults. We evaluated the influence of adiposity on wave reflection in healthy children.   Methods:  We examined 570 healthy children during 2007 (mean age 10.1±0.4, 50% boys). Adiposity was assessed by percentage body fat (%BF) quantitated by dual-energy x-ray absorptiometry. Insulin resistance was evaluated using a homeostasis model assessment (HOMA-IR). Cardiorespiratory fitness (CRF) was assessed using a 20-meter shuttle run. Radial artery wave reflection was assessed in using applanation tonometry (SphygmoCor, Atcor Medical, Sydney, Australia). The second peak of radial systolic blood pressure (SBP2) was obtained from the radial arterial waveform.   Results:  In univariable analysis, body mass index (r=0.176), waist circumference (r=0.194) and %BF (r=0.232) were associated with radial SBP2 (all p   Conclusion:  Increased adiposity is related to greater wave reflection in healthy children, independently of blood pressure and heart rate. Further studies are required to evaluate whether public health efforts to promote healthy lifestyles and weight loss in children will attenuate the progression of subclinical cardiovascular disease, and prevent the development of subsequent cardiovascular events in the community.
Two novel recessive mutations in KRT14 identified in a cohort of 21 Spanish families with epidermolysis bullosa simplex
Authors: M. García, J.L. Santiago, A. Terrón, A. Hernández-Martín, A. Vicente, C. Fortuny, R. De Lucas, J.C. López, N. Cuadrado-Corrales, A. Holguín, N. Illera, B. Duarte, C. Sánchez-Jimeno, S. Llames, E. García, C. Ayuso, L. Martínez-Santamaría, D. Castiglia, N. De Luca, A. Torrelo, D. Mechan, D. Baty, G. Zambruno, M.J. Escámez, M. Del Río
Journal: British Journal of Dermatology (2011)

Background Basal epidermolysis bullosa simplex (EBS) is a group of blistering genodermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14. Recessive mutations represent about 5% of all EBS mutations, being common and specific in populations with high consanguinity, where affected patients show severe phenotypes. Objectives To accomplish the first mutational analysis in patients of Spanish origin with EBS and to delineate a comprehensive genotype–phenotype correlation. Methods Twenty-one EBS families were analysed. Immunofluorescence mapping at the dermoepidermal junction level was performed on skin biopsies from patients. Mutation screening of the entire coding sequences of KRT5 and KRT14 in genomic DNA was assessed by polymerase chain reaction and direct sequencing. Results KRT5 or KRT14 causative mutations were identified in 18 of the 21 EBS families. A total of 14 different mutations were disclosed, of which 12 were dominant missense mutations and two truncating recessive mutations. Five of the 14 mutations were novel including three dominant in KRT5 (p.V186E, p.T321P and p.A428T) and two recessive in KRT14 (p.K116X and p.K250RfsX8). The two patients with EBS carrying homozygous recessive mutations were affected by severe phenotypes and belonged to consanguineous families. All five families with the EBS Dowling–Meara subtype carried recurrent mutations affecting the highly conserved ends of the α-helical rod domain of K5 and K14. The seven mutations associated with the localized EBS subtype were widely distributed along the KRT5 and KRT14 genes. Two families with mottled pigmentation carried the P25L mutation in KRT5, commonly associated with this subtype. Conclusions This study further confirms the genotype–phenotype correlation established for EBS in other ethnic groups, and is the first in a Mediterranean country (excluding Israel). This study adds two novel recessive mutations to the worldwide record to date, which includes a total of 14 mutations. As in previous reports, the recessive mutations resulted in a lack of keratin K14, giving rise to a generalized and severe presentation.
Premature discontinuation of clinical trial for reasons not related to efficacy, safety, or feasibility Commentary: Early discontinuation violates Helsinki principles
Authors: M. Lievre
Journal: BMJ (2001)

# Premature discontinuation of clinical trial for reasons not related to efficacy, safety, or feasibility {#article-title-2}

Editorial by Evans and Pocock 

When investigators embark on a clinical trial, they naturally expect that the journey will end with the completion of the scheduled patient follow up and publication of the results. Some trials may sink en route because of organisational or ethical reasons, and such misfortunes must be accepted. Sometimes, however, trials are scuttled by their sponsors. Such premature discontinuation not only is frustrating for investigators but may have important medical implications. In this article we analyse the case of a clinical trial that was recently stopped for financial reasons, discuss the consequences of such discontinuations, and make some proposals to avoid recurrence.

#### Summary points

Some trials are discontinued prematurely by their sponsor for strategic reasons

Clinical trials should be discontinued only for reasons pertaining to efficacy, safety, or feasibility

Premature discontinuation of trials for strategic reasons deceives the patients, jeopardises the patient-doctor relationship, and harms the medical community

Giving more power to steering committees that are mostly independent of the sponsor and include patient representatives, may limit the risk of premature discontinuation of trials for strategic reasons

Public financial and scientific participation in some trials and increasing the length of patents may be useful

Although two trials have shown the efficacy of statins for primary prevention of cardiovascular disease in middle aged people with hypercholesterolaemia, 1 2 the benefits and costs of such treatments in older men and women are unclear, especially in low cardiovascular risk populations.3-5 In April 1997, a group of French academics submitted to several pharmaceutical companies the protocol of the first placebo controlled trial of a statin for primary prevention in hypercholesterolaemic men and women aged 70 to 85 in low cardiovascular risk countries. Novartis agreed to fund the study in June 1998, when the company executives were convinced that this study was …
1059. The Lymphocytic Choriomeningitis Virus Envelope Glycoprotein Targets Lentivirus to Neural Progenitors in the Murine Brain
Authors: Colleen S. Stein, Ines Martins, Beverly L. Davidson
Journal: Molecular Therapy (2004)

Feline immunodeficiency virus (FIV) based lentiviral vectors can be targeted to restricted cell types by pseudotyping with envelopes from other viruses. An FIV vector expressing bacterial beta-galactosidase (beta-gal) and pseudotyped with lymphocytic choriomeningitis virus (LCMV) strain WE54 envelope glycoprotein was injected unilaterally into the mouse brain striatum to determine neural cell-type transduction. At 3 weeks and 7 weeks, beta-gal-expressing cells were found in the striatum, in the subventricular zone of the lateral ventricle, along the rostral migratory stream, and in the olfactory bulb on the injected side. Immunofluorescent staining and confocal microscopy showed that transgene expression in the striatum and the subventricular zone co-localized predominantly with glial fibrillary acidic protein (GFAP), an astrocyte cell marker. Beta-gal positive cells in the olfactory bulb were dispersed throughout the parenchyma, and cell morphology and staining with a neuronal cell marker demonstrated that these cells were neurons. Within the rostral migratory stream, co-localization of  with class III beta-tubulin identified these cells as migratory neuroblasts. This pattern of transgene expression was suggestive of neural progenitor cell transduction and we hypothesized that GFAP-expressing neural progenitors within the subventricular zone (type B astrocytes) were transduced. To test this, an LCMV-pseudotyped FIV vector with the GFAP promoter driving expression of cre recombinase was injected into  stop loxP beta-gal transgenic reporter mice. Beta-gal expression in these mice is dependent on cre recombinase-mediated DNA recombination. Seven weeks after unilateral injection into the striatum,  positive neurons were detected in the ipsilateral olfactory bulb, and  positive neuroblasts were detected in the rostral migratory stream on the ipsilateral side. Beta-gal expression indicated that these cells derived from a transduced GFAP-expressing precursor, most likely the type B astrocyte. Thus, LCMV(WE54)-pseudotyped FIV provides a novel vector for transducing neural progenitors in vivo.
783. Compared Stability and Antitumour Activity of Recombinant Endostatin Protein Expressed in Yeast with Recombinant Adenovirus Carrying Endostatin Gene
Authors: Zhihui Liang, Jialin Huang, wenlin Huang
Journal: Molecular Therapy (2004)

Inhibition of endostatin has been shown to be an effective way in cancer therapy in murine. However, its widespread application has been hampered by difficulties in the larger-scale production and unstability of endostatin protein. This limitation may be resolved by delivery and expression of the endostatin gene. In this study, we have compared stability and antitumour activity of recombinant endostatin protein expressed in yeast with recombinant adenovirus carrying endostatin gene. In vivo, recombinant adenovirus and recombinant endostatin protein were injected into nude mice inoculum BEL-7402 respectively; antiumour activity of the former was more effective than the latter. In vitro, recombinant endostatin protein expressed in yeast is more easily degradation than protein expressed by recombinant advenovirus in the same temperature and time. This found suggest structure of protein expressed by recombinant advenovirus may be different with recombinant endostatin protein by pichia, this difference result in their different antitumour activity. The bio-availability of recombinant endostatin protein compared with protein expressed by recombinant advenovirus is under experiment in our lab, through this work, we will investigate their antitumour mechanism.
Knockdown of SUMO-activating enzyme subunit 2 (SAE2) suppresses cancer malignancy and enhances chemotherapy sensitivity in small cell lung cancer
Authors: Xiaoke Liu, Yong Xu, Zongguo Pang, Fuchun Guo, Qing Qin, Tao Yin, Yaxiong Sang, Chengjun Feng, Xiaoyu Li, Li Jiang, Pei Shu, Yongsheng Wang
Journal: Journal of Hematology & Oncology (2015)

SUMO-activating enzyme subunit 2 (SAE2) is the sole E1-activating enzyme required for numerous important protein SUMOylation, abnormal of which is associated with carcinogenesis. SAE2 inactivation was recently reported to be a therapeutic strategy in cancers with Myc overexpression. However, the roles of SAE2 in small cell lung cancer (SCLC) are largely unknown. Stably SAE2 knockdown in H446 cells were established with a lentiviral system. Cell viability, cell cycle, and apoptosis were analyzed using MTT assay and flow cytometric assay. Expression of SAE2 mRNA and protein were detected by qPCR, western blotting, and immunohistochemical staining. Cell invasion and migration assay were determined by transwell chamber assay. H446 cells with or without SAE2 knockdown, nude mice models were established to observe tumorigenesis. SAE2 was highly expressed in SCLC and significantly correlated with tumorigenesis in vivo. Cancer cells with RNAi-mediated reduction of SAE2 expression exhibited growth retardation and apoptosis increasing. Furthermore, down-regulation of SAE2 expression inhibited migration and invasion, simultaneously increased the sensitivity of H446 to etoposide and cisplatin. SAE2 plays an important role in tumor growth, metastasis, and chemotherapy sensitivity of H446 and is a potential clinical biomarker and therapeutic target in SCLC with high c-Myc expression.
Cordyceps sinensis enhances the anti-tumor effects of taxol by promoting the recovery of taxol-caused leukopenia and immunosuppression.
Authors: Chi-Shiun Chiang, Wei-Lin Chuang, Hsiang-Ling Huang, Wei-Chung Liu, Ji-Hong Hong
Journal: Cancer Research (2006)

5440   This study aimed to evaluate the immune-modulating function of  Cordyceps sinensis  (CS) as healthy supplement following taxol chemotherapy. CS is a fungal parasite of larvae of moths ( Lepidoptera ) in the genera  Hepitalus  and  Thitarodes  that has been widely used in traditional Chinese medicine as a tonic agent in the absence of severe side effects. In this study, we used taxol as a chemotherapeutic drug to treat mice bearing TRAMP-C1 tumor, which is a murine prostate cancer cell. Two days after taxol treatment, the mice were orally administered with hot-water extract from CS daily for 3 weeks. Mice were then sacrificed at indicated times to examine the recovery of taxol-caused leukopenia and immunosupresion. Following taxol treatment, the decreased WBC counts in the peripheral blood of CS-treated mice had returned to control levels after 28 days whereas in the control this took 42 days. To further analyze the effects of CS on the recovery of blood cells, an  in vitro  colony forming-differentiation assay was performed. The data show that CS enhances the colony forming ability of both CFU-GM and osteogenic colonies. We also found that the administration of CS enhances taxol-caused tumor growth delay although CS alone has no effects on the growth of TRAMP-C1 tumor. To further analyze the effect of CS on the anti-tumor activity of taxol, phagocytosis and immune functional assays were performed to examine the functions of peritoneal macrophages and splenocytes, respectively, following treatment. The MLR and CTL assays demonstrated that CS administration facilitates the recovery of taxol-caused suppression of T cell reactivity, but it has no effects on the phagocytotoxic activity of peritoneal macrophages. In summary, these results indicate that the supplement of CS following taxol treatment enhances the chemotherapeutic effects of taxol by enhancing the differentiation of bone marrow stem cells and promoting the functional recovery of leukocytes and T cells. (This work is supported by NSC94-2320-B-007-002 grant.)
Abstract 16476: Safety Profile of Bivalirudin in the Treatment of ST-Segment Elevation Myocardial Infarction Patients in Clinical Practice - Results From the Bremen STEMI Registry
Authors: Robert Zabrocki, Eduard Fiehn, Harm Wienbergen, Susanne Seide, Johannes Schmucker, Daniela Garstka, Rainer Hambrecht
Journal: Circulation (2014)

Introduction: Previous studies demonstrated that treatment of patients (pts) being affected by ST-segment elevation myocardial infarction (STEMI) with bivalirudin (biv) instead of heparin (hep) reduced rates of major bleedings. Results regarding a reduction in all-cause mortality are inconclusive, stent thromboses however were slightly increased. Real world data in pts with STEMI treated with biv in the era of new anti-thrombotic treatment are still spare. The aim of this study was to evaluate safety of biv for all-comers. Methods: All pts with STEMI from the metropolitan area of Bremen (Germany) are admitted to the Bremen heart center and documented in the Bremen STEMI-registry (BSR) since 2006. In May 2013 we adapted our anticoagulation strategy to the current guidelines from hep with glycoprotein IIb/IIIa inhibitors (GPI) to biv with provisional use of GPI. Pts receiving biv were compared to all pts until April 2013 in the BSR without chronic renal failure. Results: Baseline and interventional characteristics of 530 consecutive pts treated with biv and 5197 pts treated with hep are shown in table 1. Despite a higher portion of pts after resuscitation (10.3% vs 8.6%; p&lt;0.01) and a higher incidence of Killip class 3 or 4 (15% vs 8%; p&lt;0.001) in the biv group inhospital all-cause mortality showed no difference (biv: 6.8% vs hep: 7.3%, p=0.66). However pts treated with biv demonstrated highly significant lower bleeding rates (TIMI major/minor bleedings: 0.8% vs 3.7%, p&lt;.01). Stent-thromboses showed a trend towards an increased event rate with biv (1.3%, 7pts vs 1.0%, 52pts, p=0.07). Conclusions: In one of the largest all-comers registries treatment with biv was associated with significantly lower minor and major bleedings. There is only a trend for a higher rate of stent thromboses in the biv group. Therefore, data from our all-comers registry support the beneficial safety profile of biv observed in clinical studies.
Abstract 104: ATF7IP does not alter the substrate specificity of the lysine methyltransferase SETDB1
Authors: Aravind Basavapathruni, Jodi Gureasko, Margaret Porter Scott, P. Ann Boriack-Sjodin, Timothy J. Wigle, Thomas V. Riera, Robert A. Copeland
Journal: Cancer Research (2015)

Abstract The histone methyltransferase (HMT) SETDB1 is a strong candidate oncogene in melanoma and lung carcinomas. SETDB1 methylates lysine 9 of histone 3 (H3K9), utilizing S-adenosylmethionine (SAM) as the methyl donor. Its activity has been shown to be regulated by its partner protein ATF7IP, and here we examine the contribution of ATF7IP to the in vitro activity and substrate specificity of SETDB1. SETDB1 and ATF7IP were co-expressed in Sf21 insect cells and 1:1 stoichiometric complexes were purified for comparison against apo-SETDB1 enzyme. We employed both radiometric flashplate-based and MALDI mass spectrometry assays to follow methylation on histone 3 15-mer peptides where lysine 9 was either unmodified, mono-, or di-methylated. These two methods provide orthogonal readouts on H3K9 methylation: the radiometric flashplate-based assay employs 3H-labeled SAM and provides quantitation of labeled, methylated peptide. The MALDI mass spectrometry assay offers quantitation of consumption and accumulation of each individual H3K9 methylation state (H3K9me0, me1, me2, and me3). Results show that both apo-SETDB1 and SETDB1:ATF7IP complex catalyzed both monomethylation and dimethylation of H3K9 peptide substrates, but were unable to perform H3K9 trimethylation. While ATF7IP did not impact the substrate methylation profile, the activity of the complex was lower than apo-SETDB1 by a factor of 4. This difference was due to a decrease in the value of kcat as the substrate KM values were comparable between apo-SETDB1 and the SETDB1:ATF7IP complex. ATF7IP therefore does not alter SETDB1's substrate specificity. H3K9 monomethylation and dimethylation by SETDB1 occurred in a distributive manner and was unaffected by the presence of ATF7IP. This finding is important as H3K9 can be methylated by HMTs other than SETDB1 and a distributive mechanism would allow for interplay between multiple HMTs on H3K9me1 and H3K9me2. The results presented here indicate that ATF7IP does not alter substrate specificity of SETDB1 in vitro, and though it decreases SETDB1's catalytic activity, our data points to a nonenzymatic function of ATF7IP in regulating SETDB1 function. Citation Format: Aravind Basavapathruni, Jodi Gureasko, Margaret Porter Scott, P. Ann Boriack-Sjodin, Timothy J. Wigle, Thomas V. Riera, Robert A. Copeland. ATF7IP does not alter the substrate specificity of the lysine methyltransferase SETDB1. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 104. doi:10.1158/1538-7445.AM2015-104
MSH2 genomic deletions are a frequent cause of HNPCC
Authors: Juul Wijnen, Heleen van der Klift, Hans Vasen, P. Meera Khan, Fred Menko, Carli Tops, Hanne Meijers Heijboer, Dick Lindhout, Pål Møller, Ricardo Fodde.
Journal: Nature Genetics (1998)
Funding in Peril for Evidence-Based Health Care Research
Authors: Laura Buchholz
Journal: JAMA (2015)

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
Effects of mental stress on coronary epicardial vasomotion and flow velocity in coronary artery disease: relationship with hemodynamic stress responses11The opinions and assertions expressed herein are those of the authors and should not be construed as reflecting those of the USUHS or the US Department of Defense.
Authors: Willem J Kop, David S Krantz, Robert H Howell, Michael A Ferguson, Vasilios Papademetriou, David Lu, Jeffrey J Popma, John F Quigley, Marina Vernalis, John S Gottdiener
Journal: Journal of the American College of Cardiology (2001)
Abstract 4595: Unprotected Left Main Stenting With a Second Generation Drug-Eluting Stent. Preliminary Results of the LEMAX Pilot Study
Authors: Neus Salvatella, Marie-Claude Morice, Didier Carrie, Olivier Darremont, Philippe Garot, Yves Louvard, Thierry Lefevre, Jean Louis Leymarie, N Hammami, Nicolas Boudou, Bernard Chevalier
Journal: Circulation (2009)