tbuckley/cabot-search huggingface dataset:
The Making of a Myth
Authors: L. Eugene Arnold
Journal: JAMA (1973)

In 1967, Millichap and Fowler<sup>1</sup>published a valuable review of the available literature studying drug treatment of hyperkinetic children. They broke down the adequately controlled studies into several tables. They further digested the information by combining and averaging the results from many studies to get the average percentages improved with each drug. Using these percentages, they listed the drugs in the order of apparent efficacy as "the closest approximation possible with the evidence available." At the head of the list, with 83% improvement, was methylphenidate hydrochloride (Ritalin). Next came dextroamphetamine sulfate (Dexedrine) with 69% improvement. The casual reader might jump to the conclusion that methylphenidate's superiority to dextroamphetamine had been established. However, the rest of the article had already made it clear that these two percentages were based on separate studies of different drugs by different investigators on different population samples with different dosages and different criteria of improvement.
Cellular and Molecular Electrophysiology of Atrial Fibrillation Initiation, Maintenance, and Progression
Authors: Jordi Heijman, Niels Voigt, Stanley Nattel, Dobromir Dobrev
Journal: Circulation Research (2014)

Atrial fibrillation (AF) is the most common clinically relevant arrhythmia and is associated with increased morbidity and mortality. The incidence of AF is expected to continue to rise with the aging of the population. AF is generally considered to be a progressive condition, occurring first in a paroxysmal form, then in persistent, and then long-standing persistent (chronic or permanent) forms. However, not all patients go through every phase, and the time spent in each can vary widely. Research over the past decades has identified a multitude of pathophysiological processes contributing to the initiation, maintenance, and progression of AF. However, many aspects of AF pathophysiology remain incompletely understood. In this review, we discuss the cellular and molecular electrophysiology of AF initiation, maintenance, and progression, predominantly based on recent data obtained in human tissue and animal models. The central role of Ca(2+)-handling abnormalities in both focal ectopic activity and AF substrate progression is discussed, along with the underlying molecular basis. We also deal with the ionic determinants that govern AF initiation and maintenance, as well as the structural remodeling that stabilizes AF-maintaining re-entrant mechanisms and finally makes the arrhythmia refractory to therapy. In addition, we highlight important gaps in our current understanding, particularly with respect to the translation of these concepts to the clinical setting. Ultimately, a comprehensive understanding of AF pathophysiology is expected to foster the development of improved pharmacological and nonpharmacological therapeutic approaches and to greatly improve clinical management.
Detection of Early Antiangiogenic Effects in Human Colon Adenocarcinoma Xenografts:<i>In vivo</i>Changes of Tumor Blood Volume in Response to Experimental VEGFR Tyrosine Kinase Inhibitor
Authors: Young Ro Kim, Anna Yudina, JoseLuis Figueiredo, Wilfried Reichardt, Dana Hu-Lowe, Alexander Petrovsky, Hye Won Kang, Denise Torres, Umar Mahmood, Ralph Weissleder, Alexei A. Bogdanov
Journal: Cancer Research (2005)

Abstract Antiangiogenesis is emerging as efficient strategy for targeting and potentially eliminating neoplastic tumor vessels. The main goal of this study was to establish whether absolute tumor blood volume (Vb) change could be used as an early predictor of antiangiogenesis in ectopic and orthotopic colon carcinomas. To assess therapy-induced changes of Vb, we did comparative analysis of signal intensities in tumors and muscle using steady-state magnetic resonance imaging (MRI) assisted with an intravascular paramagnetic contrast agent [gadolinium-labeled protected graft copolymer (PGC-Gd)]. Athymic mice with implanted human MV522 tumors were treated with vascular endothelial growth factor type 2 receptor tyrosine kinase inhibitor (VEGFR2-TKI) that has been shown to inhibit VEGFR2 phosphorylation and tumor growth in vivo. Animals were imaged either after a single day or after a 1-week course of treatments. The measured Vb in ectopic tumors was 2.5 ± 1.5% of total tissue volume 1 week after the implantation (n = 8). Two doses of VEGFR2-TKI (25 mg/kg, p.o., b.i.d.) resulted in a decrease of Vb to 1.3 ± 0.3%. In orthotopic tumors, the measured Vb was initially higher (11.9 ± 2.0%); however, VEGFR2-TKI treatment also resulted in a statistically significant decrease of Vb. The absolute Vb was not affected in the muscle as a result of treatments. MRI measurements were corroborated by using isotope and correlative histology experiments. Our results show that steady-state MRI is highly sensitive to early antiangiogenic effects caused by small molecule drugs.
Allogeneic Hematopoietic Stem-Cell Transplantation in Patients With Hematologic Malignancies After Dose-Escalated Treosulfan/Fludarabine Conditioning
Authors: Jochen Casper, Daniel Wolff, Wolfgang Knauf, Igor W. Blau, Tapani Ruutu, Liisa Volin, Hannes Wandt, Kerstin Schäfer-Eckart, Jerzy Holowiecki, Sebastian Giebel, Johan Aschan, Axel R. Zander, Nicolaus Kröger, Inken Hilgendorf, Joachim Baumgart, Heidrun A. Mylius, Uwe Pichlmeier, Mathias Freund
Journal: Journal of Clinical Oncology (2010)

Purpose Treosulfan was introduced recently as a conditioning agent for allogeneic blood stem-cell transplantation. The favorable nonhematologic toxicity profile at 3 × 10 g/m 2 was the basis for dose escalation in this prospective, multicenter trial. Patients and Methods Fifty-six patients with various hematologic malignancies who were not eligible for standard conditioning were treated with one of three doses: 10 g/m 2 , 12 g/m 2 , or 14 g/m 2 of intravenous treosulfan, which was administered on days −6 to −4 combined with fludarabine 30 mg/m 2 on days −6 to −2. Patients in complete remission (CR; 42%) or non-CR (58%) received grafts from matched related (47%) or matched unrelated (51%) donors; one patient had a mismatched related donor (2%). Results No engraftment failure occurred. Overall, extramedullary toxicity and the nonrelapse mortality rate at 2 years (20%) were low and did not increase with dose. Cumulative incidence of relapse/progression reached 31%. The overall survival and progression-free survival rates were 64% and 49%, respectively, in the total study population. An inverse dose dependency of relapse incidence was indicated in the subgroup receiving transplantations from matched related donors (P = .0568). Conclusion Treosulfan-based conditioning was feasible at all three doses. The 3 × 14 g/m 2 dose was selected for additional studies, because it combines desired characteristics of low toxicity and a low relapse rate.
Chymase is not unique to mast cells: Presence in epithelial, endothelial and fibroblast cells
Authors: Sharon L Wanstall, Parimal D Sheth, Audrey Richter, Saiki Hase, J Manuel Tumon de Lara, John Pedersen, Andrew F Walls, alan R McEuen
Journal: Journal of Allergy and Clinical Immunology (2002)
Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study
Authors: Alan F. List, Kenneth J. Kopecky, Cheryl L. Willman, David R. Head, Diane L. Persons, Marilyn L. Slovak, Robert Dorr, Chatchada Karanes, Harry E. Hynes, James H. Doroshow, Muhammad Shurafa, Frederick R. Appelbaum
Journal: Blood (2001)
Phase I Trial of a Personalized Peptide Vaccine for Patients Positive for Human Leukocyte Antigen–A24 With Recurrent or Progressive Glioblastoma Multiforme
Authors: Mizuhiko Terasaki, Soichiro Shibui, Yoshitaka Narita, Takamitsu Fujimaki, Tomokazu Aoki, Koji Kajiwara, Yutaka Sawamura, Kaoru Kurisu, Toshihiro Mineta, Akira Yamada, Kyogo Itoh
Journal: Journal of Clinical Oncology (2010)

Purpose Personalized selection of suitable peptides for patients could offer a novel approach to developing cancer vaccines that boost anticancer immunity. We present the results of a phase I trial of 14 kinds of vaccine candidates (ITK-1) in patients with recurrent or progressive glioblastoma multiforme (GBM). Patients and Methods From January 2006 to January 2008, 12 patients from eight Japanese hospitals who were positive for human leukocyte antigen–A24, including 10 patients refractory to temozolomide (TMZ), were enrolled. The dose escalation trial included three dose groups (1, 3, and 5 mg) to determine the safety and tolerability of ITK-1 peptides. Immunologic response was monitored by measuring levels of cytotoxic T-lymphocyte precursors and peptide-specific immunoglobulin G. In another ITK-1 phase I trial for advanced prostate cancer, the vaccination schedule was skipped or discontinued in all three patients receiving the highest dose (5 mg/peptide) because of injection site reactions. This trial was therefore ended without enrollment for the highest dose, and data were analyzed by intention to treat. Results No serious adverse drug reactions were encountered, and treatment was well tolerated. The vaccine induced dose-dependent immune boosting. The recommended dose of ITK-1 peptides is 3 mg/peptide. Conclusion Personalized vaccination with ITK-1 peptides could be recommended in further stages of clinical trials. The safety and increased frequency of immune boosting offers potential clinical benefits in cases of recurrent or progressive GBM, even in TMZ-refractory settings.
Integrating diffusion kurtosis imaging, dynamic susceptibility-weighted contrast-enhanced MRI, and short echo time chemical shift imaging for grading gliomas
Authors: Sofie Van Cauter, Frederik De Keyzer, Diana M. Sima, Anca Croitor Sava, Felice D'Arco, Jelle Veraart, Ronald R. Peeters, Alexander Leemans, Stefaan Van Gool, Guido Wilms, Philippe Demaerel, Sabine Van Huffel, Stefan Sunaert, Uwe Himmelreich
Journal: Neuro-Oncology (2014)

We assessed the diagnostic accuracy of diffusion kurtosis imaging (DKI), dynamic susceptibility-weighted contrast-enhanced (DSC) MRI, and short echo time chemical shift imaging (CSI) for grading gliomas. In this prospective study, 35 patients with cerebral gliomas underwent DKI, DSC, and CSI on a 3 T MR scanner. Diffusion parameters were mean diffusivity (MD), fractional anisotropy, and mean kurtosis (MK). Perfusion parameters were mean relative regional cerebral blood volume (rrCBV), mean relative regional cerebral blood flow (rrCBF), mean transit time, and relative decrease ratio (rDR). The diffusion and perfusion parameters along with 12 CSI metabolite ratios were compared among 22 high-grade gliomas and 14 low-grade gliomas (Mann–Whitney U-test, P < .05). Classification accuracy was determined with a linear discriminant analysis for each MR modality independently. Furthermore, the performance of a multimodal analysis is reported, using a decision-tree rule combining the statistically significant DKI, DSC-MRI, and CSI parameters with the lowest P-value. The proposed classifiers were validated on a set of subsequently acquired data from 19 clinical patients. Statistically significant differences among tumor grades were shown for MK, MD, mean rrCBV, mean rrCBF, rDR, lipids over total choline, lipids over creatine, sum of myo-inositol, and sum of creatine. DSC-MRI proved to be the modality with the best performance when comparing modalities individually, while the multimodal decision tree proved to be most accurate in predicting tumor grade, with a performance of 86%. Combining information from DKI, DSC-MRI, and CSI increases diagnostic accuracy to differentiate low- from high-grade gliomas, possibly providing diagnosis for the individual patient.
Nitroglycerin Fails to Lower Blood Pressure in Redox-Dead Cys42Ser PKG1α Knock-In Mouse
Authors: Olena Rudyk, Oleksandra Prysyazhna, Joseph R. Burgoyne, Philip Eaton
Journal: Circulation (2012)

Although nitroglycerin has remained in clinical use since 1879, the mechanism by which it relaxes blood vessels to lower blood pressure remains incompletely understood. Nitroglycerin undergoes metabolism that generates several reaction products, including oxidants, and this bioactivation process is essential for vasodilation. Protein kinase G (PKG) mediates classic nitric oxide-dependent vasorelaxation, but the 1α isoform is also independently activated by oxidation that involves interprotein disulfide formation within this homodimeric protein complex. We hypothesized that nitroglycerin-induced vasodilation is mediated by disulfide activation of PKG1α.
Allogeneic hematopoietic stem cell transplantation in China: where we are and where to go
Authors: Meng Lv, Xiao-Jun Huang
Journal: Journal of Hematology & Oncology (2012)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and sometimes the only curative therapy for patients with certain hematological diseases. Allo-HSCT has been practiced in China for approximately 30 years, and great improvements have been made within the past decade, particularly in fields such as the haploidentical HSCT system, strategies to overcome relapse and GVHD, and modified HSCT for elderly patients. This review will describe the current situation and provide a prospective of these unique aspects of Allo-HSCT in China.
Occupational risk factors for Wegener's granulomatosis: a case-control study
Authors: A. Knight, S. Sandin, J. Askling
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Background</h3> Wegener9s granulomatosis is a systemic vasculitis of unknown aetiology. Previous studies have presented environmental exposures such as silica and farming as potential risk factors. <h3>Objective</h3> To investigate the potential risk for Wegener9s granulomatosis associated with occupations involving contact with animals and various airway exposures, using a population-based approach. <h3>Methods</h3> In the Swedish Register of inpatient care 2288 cases with Wegener9s granulomatosis were identified. Ten matched controls for every case were selected from the Swedish Population Register. By linking the cases and controls to the Swedish population censuses, information on employments before the diagnosis of Wegener9s granulomatosis was collected. Relative risks were assessed as odds ratios using conditional logistic regression. <h3>Results</h3> Odds ratios for specific occupations ranged from 0.6 to 1.9, and centred symmetrically around 1. No statistically significant increased risk was noted for the investigated occupations.
Variations in the transcriptome of Alzheimer's disease reveal molecular networks involved in cardiovascular diseases
Authors: Monika Ray, Jianhua Ruan, Weixiong Zhang
Journal: Genome biology (2008)

Because of its polygenic nature, Alzheimer's disease is believed to be caused not by defects in single genes, but rather by variations in a large number of genes and their complex interactions. A systems biology approach, such as the generation of a network of co-expressed genes and the identification of functional modules and cis-regulatory elements, to extract insights and knowledge from microarray data will lead to a better understanding of complex diseases such as Alzheimer's disease. In this study, we perform a series of analyses using co-expression networks, cis-regulatory elements, and functions of co-expressed gene modules to analyze single-cell gene expression data from normal and Alzheimer's disease-affected subjects. We identified six co-expressed gene modules, each of which represented a biological process perturbed in Alzheimer's disease. Alzheimer's disease-related genes, such as APOE, A2M, PON2 and MAP4, and cardiovascular disease-associated genes, including COMT, CBS and WNK1, all congregated in a single module. Some of the disease-related genes were hub genes while many of them were directly connected to one or more hub genes. Further investigation of this disease-associated module revealed cis-regulatory elements that match to the binding sites of transcription factors involved in Alzheimer's disease and cardiovascular disease. Our results show the extensive links between Alzheimer's disease and cardiovascular disease at the co-expression and co-regulation levels, providing further evidence for the hypothesis that cardiovascular disease and Alzheimer's disease are linked. Our results support the notion that diseases in which the same set of biochemical pathways are affected may tend to co-occur with each other.
Penicillamine-Induced Insulin Antibodies
Authors: RICHARD C. BECKER
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 January 1986Penicillamine-Induced Insulin AntibodiesRICHARD C. BECKER, M.D., RAQUEL G. MARTIN, D.O.RICHARD C. BECKER, M.D.Search for more papers by this author, RAQUEL G. MARTIN, D.O.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-104-1-127_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: A recent letter (1) discusses the effect of D-penicillamine on carbohydrate metabolism. This phenomenon has, in fact, been described previously (2) and has been ascribed to the presence of insulin antibodies. D-Penicillamine is known to cause a number of autoimmune diseases including Goodpasture's syndrome, myasthenia gravis, polymyositis, and systemic lupus erythematosus (3). It has been postulated that penicillamine-containing sulfhydryl groups may interact with disulfide bonds of endogenous proteins (insulin included), altering their structure and making them immunogenic (2). Hypoglycemia may result from the dissociation of insulin from its binding antibody during the fasting state. Spontaneously occurring antibodies...References1. ELLINGELLING PH. Penicillamine, captopril, and hypoglycemia [Letter]. Ann Intern Med. 1985;103:644. LinkGoogle Scholar2. BENSONHEALEYBARRON ELE. Insulin antibodies in patients receiving penicillamine. Am J Med. 1985;78:857-60. CrossrefMedlineGoogle Scholar3. DAWKINSZILKOCARRANOGARLEPPMCDONALD RPJMB. Immunology of D-penicillamine. J Rheumatol. 1981;8:56-61. Google Scholar4. FOLLINGNORMAN IN. Hyperglycemia, hypoglycemic attacks and production of anti-insulin antibodies without previous known immunization. Diabetes. 1972;21:814-26. CrossrefMedlineGoogle Scholar5. GOLDMANBALDWINRUBENSTEIN JDA. Characterization of circulating insulin and proinsulin-binding antibodies in autoimmune hypoglycemia. J Clin Invest. 1979;63:1050-9. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Cleveland Clinic Foundation Cleveland, OH 44106 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByPenicillamineGLUCOCORTICOIDS AND DISEASE – MODIFYING ANTIRHEUMATIC DRUGSENDOCRINE AND METABOLIC ADVERSE EFFECTS OF NON-HORMONAL AND NON-METABOLIC DRUGSPenicillamineMetal antagonists 1 January 1986Volume 104, Issue 1Page: 127-128KeywordsAntibodiesAutoimmune diseasesCarbohydrate metabolismHypoglycemiaInsulinLupus erythematosusMyasthenia gravisPolymyositisProtein structure Issue Published: 1 January 1986 PDF DownloadLoading ...
DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines
Authors: Jordana T Bell, Athma A Pai, Joseph K Pickrell, Daniel J Gaffney, Roger Pique-Regi, Jacob F Degner, Yoav Gilad, Jonathan K Pritchard
Journal: Genome biology (2011)

DNA methylation is an essential epigenetic mechanism involved in gene regulation and disease, but little is known about the mechanisms underlying inter-individual variation in methylation profiles. Here we measured methylation levels at 22,290 CpG dinucleotides in lymphoblastoid cell lines from 77 HapMap Yoruba individuals, for which genome-wide gene expression and genotype data were also available.Association analyses of methylation levels with more than three million common single nucleotide polymorphisms (SNPs) identified 180 CpG-sites in 173 genes that were associated with nearby SNPs (putatively in cis, usually within 5 kb) at a false discovery rate of 10%. The most intriguing trans signal was obtained for SNP rs10876043 in the disco-interacting protein 2 homolog B gene (DIP2B, previously postulated to play a role in DNA methylation), that had a genome-wide significant association with the first principal component of patterns of methylation; however, we found only modest signal of trans-acting associations overall. As expected, we found significant negative correlations between promoter methylation and gene expression levels measured by RNA-sequencing across genes. Finally, there was a significant overlap of SNPs that were associated with both methylation and gene expression levels.Our results demonstrate a strong genetic component to inter-individual variation in DNA methylation profiles. Furthermore, there was an enrichment of SNPs that affect both methylation and gene expression, providing evidence for shared mechanisms in a fraction of genes.
Abstinence only programmes do not change sexual behaviour, Texas study shows
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

Sex education programmes that teach only abstinence have little impact on adolescents' behaviour, a study in Texas, George Bush's home state, has concluded.

The number of adolescents who had had sexual intercourse did not change or increased after they had received abstinence only sex education, according to the report ‘Abstinence Education Evaluation Phase 5 Technical Report’ from the Texas health department.

The evaluation was prompted after Henry Waxman, a Democratic senator, and 18 other congressional representatives complained that 11 of the 13 commonly used …
Effect of running and swimming activities on selected cardiac risk factors among middle aged men
Authors: Ajay Kumar Koorma, S Chidambara Raja
Journal: British Journal of Sports Medicine (2010)

The purpose of the study was to find out the effect of running and swimming activities on coronary heart disease risk factors. Thirty male teachers aged between 35 and 40 years who knew swimming were selected for the study. They were divided into three equal groups, each group consisted of 10 subjects in which group I underwent running activity and group II underwent swimming activity, 3 days per week for 12 weeks, and group III acted as control, who did not participate in any training. The subjects were tested on selected criterion variables such as total cholesterol, high-density lipoprotein, systolic and diastolic blood pressure prior to and immediately after the training period. The analysis of covariance was used to find out the significant difference if any, between the experimental groups and control group on selected criterion variables separately. The selected criterion variables such as high-density lipoprotein were improved significantly for both the training groups when compared with the control group and the systolic blood pressure was reduced significantly only for running activity group and swimming activity group. The diastolic blood pressure and total cholesterol were not changed significantly for both the training groups.