tbuckley/cabot-search huggingface dataset:
904. The Systemic Human Immune Response to Intraparenchymal Administration of AAV
Authors: Scott W.J. McPhee, Chris G. Janson, Chengwen Li, R. Jude Samulski, Angelique S. Camp, Jeremy S. Francis, David Shera, Andrew Freese, Anthony L. Aita, H. Warren Goldman, Paola Leone
Journal: Molecular Therapy (2006)

BACKGROUND Recombinant AAV-ASPA has been developed for gene delivery to the CNS for Canavan Disease, a rare leukodystrophy with no treatment. This NINDS funded project is the first clinical study of a viral vector used for gene delivery in a neurodegenerative disorder. METHODS Subjects were administered AAV serotype 2 at a maximum dose of 1 × 10E12 vector genomes per subject, via intraparenchymal infusions to the subcortex . The immune response and safety profiles were monitored in the follow- up of 13 subjects who ranged from 3–82 months of age at the time of vector administration. RESULTS Following rAAV2 administration, we found no evidence of AAV2 neutralizing antibody titers in serum for the majority of subjects tested. In a subset of subjects low to moderately high levels of AAV2 neutralizing antibody with respect to baseline were detected. In all subjects, there were minimal systemic signs of inflammation or immune stimulation. In subjects with catheter access to the brain lateral ventricle, cerebrospinal fluid was examined and there was a complete absence of neutralizing antibody titers with no overt signs of brain inflammation. CONCLUSIONS rAAV2 vector administration to the human CNS appears well tolerated. The low levels of immune response to AAV2 detected in this study suggest at this dose and with intraparenchymal administration this approach is relatively safe. Long-term monitoring of subjects and expansion to Phase II/III will be necessary in order to make definitive statements on safety and efficacy.
The Development of a Physician-Investigator Training Program
Authors: Gerald S. Levey, Denis C. Lehotay, Marcus Dugas
Journal: New England Journal of Medicine (1981)

Recent reports have vividly documented a decline in the number of physicians entering careers in investigation and the threat that this decline poses to the biomedical-research structure that has existed for the past 30 years.1 2 3 4 This curtailed interest and participation of physicians in biomedical research is mirrored by medical students' declining interest in research careers.5 , 6 The reasons for this change in attitude toward biomedical research include a shift in priorities secondary to the social upheaval produced by the Vietnam War, personal economic considerations, a decrease in the time devoted to research and laboratory work in medical school, an increase in . . .
Pre-Treatment of Mesenchymal Stem Cells With a Combination of Growth Factors Enhances Gap Junction Formation, Cytoprotective Effect on Cardiomyocytes, and Therapeutic Efficacy for Myocardial Infarction
Authors: Joo-Yong Hahn, Hyun-Ju Cho, Hyun-Jae Kang, Tack-Seung Kim, Mi-Hyung Kim, Jung-Hwa Chung, Jang-Whan Bae, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Journal of the American College of Cardiology (2008)
Abstract 2005: Analysis of gene expression and copy number variation in breast tumors using both sequencing and hybridization-based platforms.
Authors: Nadine Norton, Edith A. Perez, Yan W. Asmann, Jennifer M. Carr, Brian M. Necela, Jennifer M. Kachergus, Jin Jen, Bruce W. Eckloff, E Aubrey Thompson
Journal: Cancer Research (2013)

Abstract Next Generation Sequencing (NGS) technologies provide rapid genomic analyses of single nucleotide variants, RNA expression and DNA copy number. Application of these technologies to material isolated from formalin fixed paraffin embedded (FFPE) tissue and even degraded frozen material could provide powerful replication samples but remains challenging. We tested the nanoString platform to validate deep sequence analysis of gene expression and DNA copy number in degraded and FFPE material. Firstly, RNA from the Universal Human Reference RNA and a breast cancer cell line (MDA-MB-436) was artificially degraded to different degrees (RIN 1.2-6.8). We used the nanoString platform to simultaneously measure RNA expression across 226 genes in each degraded sample and the corresponding undegraded RNA. Secondly we isolated RNA and DNA from matched fresh frozen and FFPE tissues from nine breast cancer patients (3 HER2+/ER+/PR+, 2 HER2+/ER-/PR-, 2 HER2+/ER+/PR-, 2 HER2-/ER+/PR+) using the nanoString platform to compare expression and copy number across 226 and 86 genes respectively. Finally, we correlated expression and copy number data generated by nanoString with Illumina transcriptome and whole genome sequencing (WGS). NanoString log2 expression fold-change between all artificially degraded samples and their undegraded counterpart showed extremely high correlation (r2&amp;gt;0.91). NanoString DNA copy number between matched fresh-frozen and FFPE showed a high degree of correlation (r2=0.71). All gene amplifications with copy number ≥ 5 in DNA from fresh-frozen material (N=9) were successfully identified in DNA from FFPE material. We also observed good correlation of gene expression between whole transcriptome sequencing and the nanoString platform (r2 0.59 - 0.72) in FFPE and artificially degraded material and for DNA copy number between WGS and nanoString in DNA isolated from cancer cell lines (r2=0.96). The nanoString platform provides reliable data from highly degraded and FFPE material and correlates with sequence analysis of both expression and copy number from NGS platforms demonstrating potential for large-scale replication studies in FFPE material. Citation Format: Nadine Norton, Edith A. Perez, Yan W. Asmann, Jennifer M. Carr, Brian M. Necela, Jennifer M. Kachergus, Jin Jen, Bruce W. Eckloff, E Aubrey Thompson. Analysis of gene expression and copy number variation in breast tumors using both sequencing and hybridization-based platforms. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2005. doi:10.1158/1538-7445.AM2013-2005
Uncovering Common Principles in Protein Export of Malaria Parasites
Authors: Christof Grüring, Arlett Heiber, Florian Kruse, Sven Flemming, Gianluigi Franci, Sara F. Colombo, Elisa Fasana, Hanno Schoeler, Nica Borgese, Hendrik G. Stunnenberg, Jude M. Przyborski, Tim-Wolf Gilberger, Tobias Spielmann
Journal: Cell Host & Microbe (2012)
Prevention of graft coronary arteriosclerosis by antisense cdk2 kinase oligonucleotide
Authors: Jun-Ichi Suzuki, Mitsuaki Isobe, Ryuichi Morishita, Motokuni Aoki, Shiro Horie, Yoshio Okubo, Yasufumi Kaneda, Yoshiki Sawa, Hikaru Matsuda, Toshio Ogihara, Morie Sekiguchi
Journal: Nature Medicine (1997)
Predictive Accuracy of Nephrometric Scores Can Be Improved by Adding Clinical Patient Characteristics: A Novel Algorithm Combining Anatomic Tumour Complexity, Body Mass Index, and Charlson Comorbidity Index to Depict Perioperative Complications After Nephron-sparing Surgery
Authors: Marco Roscigno, Francesca Ceresoli, Richard Naspro, Francesco Montorsi, Roberto Bertini, Luigi Filippo Da Pozzo
Journal: European Urology (2013)
Uniqueness of human childhood and adolescence?
Authors: Glenn E. Weisfeld
Journal: Behavioral and Brain Sciences (2006)

Locke &amp; Bogin (L&amp;B) propose that humans are unique in possessing stages of childhood and adolescence. Arguments to the contrary include evidence for a similar and adaptive juvenile period in simians of slow growth, intense play and learning, and provisioning with solid food by adults. Likewise, simians as well as humans undergo a compensatory growth spurt during puberty.
Vagal Modulation of Epicardial Coronary Artery Size in Dogs
Authors: Julie A. Kovach, John S. Gottdiener, Richard L. Verrier
Journal: Circulation (1995)

Background Because the role of tonic vagus nerve activity in regulating conduit coronary artery size remains undefined, we investigated the response of epicardial coronary artery size to changes in resting vagal tone resulting from vagotomy and muscarinic receptor blockade. Methods and Results Using intravascular ultrasound to measure left circumflex coronary artery cross-sectional area continuously, we examined the effects of vagotomy on left circumflex cross-sectional area in nine dogs. Lumen area decreased 20% from 8.70±2.81 to 6.92±1.97 mm 2 after right vagotomy, 17% to 7.19±2.80 mm 2 after left vagotomy (both P &lt;.05 versus baseline), and 38% to 5.42±2.00 mm 2 after bilateral vagotomy ( P &lt;.05 versus unilateral vagotomy). Vasoconstriction occurred despite increases in heart rate and an unchanged rate-pressure product. In six additional dogs, after acetylcholine (100 μg/kg IV), lumen area increased by 18%, although heart rate, blood pressure, and rate-pressure product were unchanged. Vasodilation was prevented by prior muscarinic blockade with glycopyrrolate. With glycopyrrolate administration and heart rate control by pacing, lumen area decreased by 26% ( P =.011). When stellate stimulation was performed in a third group of eight dogs with heart rate, blood pressure, and rate-pressure product controlled by a combination of pacing and exsanguination, there was no change in coronary area, thus precluding reflex sympathetic activation as a contributor to the vasoconstriction produced by vagal withdrawal. Conclusions Vagus nerve activity maintains tonic dilation of the left circumflex coronary artery by muscarinic receptor activation. Each vagus nerve contributes approximately equally to the tonically dilated state. Vagotomy-induced vasoconstriction occurs independently of local metabolic factors and coronary distending pressure and is a result of cholinergic withdrawal rather than reflex sympathetic activation.
A universal classification of eukaryotic transposable elements implemented in Repbase
Authors: Thomas Wicker, François Sabot, Aurélie Hua-Van, Jeffrey L. Bennetzen, Pierre Capy, Boulos Chalhoub, Andrew Flavell, Philippe Leroy, Michele Morgante, Olivier Panaud, Etienne Paux, Phillip SanMiguel, Alan H. Schulman
Journal: Nature Reviews Genetics (2008)
Abstract 556: Extracellular matrix protein mixture isolated from cultures of human tumor and stromal cells supports growth of human tumor cells <i>in vitro</i> and <i>in vivo</i>
Authors: Pravin J. Mishra, Prasun J. Mishra, Hui Gao, John Glod, Debabrata Banerjee
Journal: Cancer Research (2010)

Abstract Carcinoma Associated Fibroblasts (CAFs) along with other cells present in the tumor milieu play a major role in tumor progression. We have previously demonstrated differentiation of human bone marrow derived mesenchymal stem cells to CAF like phenotype upon exposure to tumor conditioned medium. The present study evaluates the ability of these stromal components to support tumor progression. An in vitro system was used to study impact of the components of the tumor milieu on growth of luciferase expressing MDA MB 231 cells, representing basal subtype of human breast cancer. CAFs along with phorbol ester induced HL60 cells representing a macrophage like phenotype supported growth of MDAMB231 cells in vitro as measured by a luciferase assay. When injected subcutaneously in vivo in nu/nu mice, tumor cells comingled with CAFs or with differentiated HL60 cells showed almost similar tumor growth rate, whereas CAFs and differentiated HL60s when mixed together showed more than 4 fold increased tumor growth rate compared to the tumor cells alone and 2 fold compared to tumor cells plus MatrigelTM. Electrophoretic analysis of extracellular matrix protein mixture isolated from mixed cultures of CAFs plus MDAMB231 cells and differentiated HL60 cells (3 cells) using previously published methods showed presence of laminins and collagens, and demonstrated robust tumor cell growth compared to MatrigelTM. The ECM protein mixture derived from the three cell system offers a completely humanized substitute for MatrigelTM useful for study of tumor growth and response to therapy in vitro as well as in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 556.
Pesticide Testing on Human Subjects: Weighing Benefits and Risks
Authors: David B. Resnik, Christopher Portier
Journal: Environmental Health Perspectives (2005)

In the debate surrounding testing pesticides on human subjects, two distinct positions have emerged. The first position holds that pesticide experiments on human subjects should be allowed, but only under stringent scientific and ethical standards. The second position asserts that these experiments should never be allowed. In this article, we evaluate what we consider to be the strongest argument for the second position--namely, that the benefits of the experiments are not significant enough to justify the risks posed to healthy subjects. We challenge this argument by examining the benefits and risks of testing pesticides on human subjects. We argue that a study that intentionally exposes humans subjects to pesticides should be permitted if a) the knowledge gained from the study is expected to promote human health; b) the knowledge cannot be reasonably obtained by other means; c) the study is not expected to cause serious or irreversible harm to the subjects; and d) appropriate safeguards are in place to minimize harm to the subjects.
RELATIONSHIP BETWEEN QUANTITATIVE ADVERSE PLAQUE FEATURES FROM CORONARY CT ANGIOGRAPHY AND DOWNSTREAM IMPAIRED MYOCARDIAL FLOW RESERVE
Authors: Damini Dey, Mariana Diaz Zamudio, Annika Schuhbaeck, Luis E.J. Orozco, Yuka Otaki, Heidi Gransar, Debiao Li, Guido Germano, Stephan Achenbach, Daniel Berman, Aloha Meave, Erick Alexanderson Rosas, Piotr Slomka
Journal: Journal of the American College of Cardiology (2015)
A safe-by-design approach to the development of gold nanoboxes as carriers for internalization into cancer cells
Authors: Dania Movia, Valerie Gerard, Ciaran Manus Maguire, Namrata Jain, Alan P. Bell, Valeria Nicolosi, Tiina O'Neill, Dimitri Scholz, Yurii Gun'ko, Yuri Volkov, Adriele Prina-Mello
Journal: Biomaterials (2014)
Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia
Authors: Cornelius F. Boerkoel, Hiroshi Takashima, Joy John, Jiong Yan, Pawel Stankiewicz, Lisa Rosenbarker, Jean-Luc André, Radovan Bogdanovic, Antoine Burguet, Sandra Cockfield, Isabel Cordeiro, Stefan Fründ, Friederike Illies, Mark Joseph, Ilkka Kaitila, Giuliana Lama, Chantal Loirat, D. Ross McLeod, David V. Milford, Elizabeth M. Petty, Francisco Rodrigo, Jorge M. Saraiva, Beate Schmidt, Graham C. Smith, Jürgen Spranger, Anja Stein, Hannelore Thiele, Jane Tizard, Rosanna Weksberg, James R. Lupski, David W. Stockton
Journal: Nature Genetics (2002)
Leukaemia and reticuloses.
Authors: M. Tobias
Journal: BMJ (1968)

MEDIBALJOURNALgravidae.During all these years the Chelms- ford group had perinatal mortality rates a good deal lower than those for the country or tne region.It seems unlikely, therefore, that good unit rates were bought at the expense of unnecessary disasters in trans- ferred cases.-Iam, etc., DAVID CARGILL.
Sickle Cell Anemia — Basic Research Reaches the Clinic
Authors: Alan N. Schechter, Griffin P. Rodgers
Journal: New England Journal of Medicine (1995)

Fifty years ago this spring, a conversation between an eminent clinical investigator and an extraordinarily imaginative physical chemist led to the insight that introduced the era of molecular medicine. Although their recollections of the encounter differed slightly, this meeting of Drs. William B. Castle and Linus Pauling soon led to the identification, by Pauling's laboratory, of an abnormal hemoglobin molecule in the erythrocytes of patients with sickle cell anemia. In the subsequent decades, the techniques of genetics, biochemistry, and cell biology have all contributed to the detailed elucidation of the molecular and cellular pathophysiology of this inherited disease.Nevertheless, a . . .
Serum α-Hydroxybutyrate Dehydrogenase in Diagnosis
Authors: S. B. Rosalki, J. H. Wilkinson
Journal: JAMA (1964)

THE SERUM LACTATE DEHYDROGENASE (LDH) has been much used for the diagnosis of myocardial infarction, but because of its lack of specificity it is often combined with isoenzyme studies.<sup>1</sup>Of the five LDH isoenzymes, the electrophoretically fastest components, LDH<sub>1</sub>and LDH<sub>2</sub>, characteristic of heart muscle, are preferentially increased after myocardial infarction; we have shown<sup>2</sup>that these more readily reduce α-ketobutyrate than the slow-moving fractions, LDH<sub>4</sub>and LDH<sub>5</sub>found in the liver. This reduction of α-ketobutyrate has been termed "α-hydroxybutyrate dehydrogenase" (HBD) activity.<sup>3</sup>We have shown that determination of the serum HBD activity provides a useful diagnostic test for myocardial infarction and eliminates the need for isoenzyme separation.<sup>4,5</sup>As expected, raised serum HBD activities are not often encountered in liver diseases.<sup>6</sup> The value of the new test has been confirmed.<sup>7-11</sup>but as we have now had experience with it in 330
Assessment of Fecatest and Haemoccult for faecal occult blood testing.
Authors: F I Lee, F T Costello
Journal: BMJ (1982)

Details of the outcome of female patients admitted with fractured neck of femur during 1979 compared with those admitted to the Nottingham hospitals in 1977 are given in the table.Number of female patients admitted with fractured neck of femur to the ortho- geriatric ward in 1979 compared with that for all the Nottingham hospitals in 1977 1977
Use of therapeutic ultrasound in percutaneous coronary angioplasty. Experimental in vitro studies and initial clinical experience.
Authors: R J Siegel, J Gunn, A Ahsan, M C Fishbein, R J Bowes, D Oakley, C Wales, W Steffen, S Campbell, H Nita
Journal: Circulation (1994)

BACKGROUND Previous studies have shown the feasibility of peripheral arterial ultrasound angioplasty. METHODS AND RESULTS In this report, we describe the use of percutaneous therapeutic ultrasound for coronary angioplasty. In vitro, 11 postmortem, atherosclerotically occluded coronary arteries were obtained to assess catheter-delivered ultrasound for arterial recanalization as well as for assessment of the size of particulate debris. Clinically, coronary ultrasound angioplasty was performed in 19 patients (mean age, 56 years) to assess safety and feasibility for the treatment of obstructive coronary atherosclerosis. Three patients with unstable angina and 16 with exercise-induced myocardial ischemia were treated with a prototype 4.6F coronary catheter ultrasound ablation device with a 1.7-mm diameter ball tip. The ultrasound coronary catheter delivered ultrasound energy at 19.5 kHz, with a power output of 16 to 20 W at the transducer. Energy is delivered in a pulsed mode with a 50% duty cycle of 30 milliseconds. Patients were treated for a mean of 493 seconds (range, 130 to 890) with intracoronary ultrasound ablation. All lesions were treated with adjunctive balloon angioplasty. All 11 postmortem coronary occlusions were recanalized, and 99% of the particulates generated were &lt; 10 microns in diameter. We found that after ultrasound, mean (+/- SD) coronary arterial stenosis fell from 80 +/- 12% to 60 +/- 18% (P &lt; .001) and to 26 +/- 11% (P &lt; .001) after adjunctive balloon angioplasty. Mean pressures required to achieve full balloon inflation were 2.7 atm (range, 1 to 5.5) with a median of 3.0-mm balloon size (2.5 to 3.5). No ultrasound-related complications were identified. CONCLUSIONS Intracoronary ultrasound plaque ablation appears to be safe. Our findings suggest that catheter-delivered high-intensity, low-frequency ultrasound may be useful for lesion debulking and enhancing arterial distensibility, allowing balloon dilation at relatively low pressures.
A Holographic Model of a Psychosomatic Pattern: Freud&amp;rsquo;s Specimen Dream Re-Interpreted
Authors: Jill Bond Caire
Journal: Psychotherapy and Psychosomatics (1981)

The specimen dream which Freud used to elaborate his theories contains a representation of his cancer which manifested 28 years later. Re-interpretation of the dream in light of information available only after Freud's death suggests that the dream exhibited a nexus between Freud's psychological and somatic functioning. The dream suggests an image of how a disease may become symbolically linked to a psychological complex through the medium of subliminal physiological changes occurring as a result of behaviors attributed to the complex. The dream appears to operate like a holograph, exhibiting the seeds of a past trauma which profoundly influenced Freud's life just as it appeared to reflect around the corner to the future.
Effects of chronic fetal hyperglycemia upon oxygen consumption in the ovine uterus and conceptus.
Authors: A F Philipps, P J Porte, S Stabinsky, T S Rosenkrantz, J R Raye
Journal: Journal of Clinical Investigation (1984)

Hyperglycemia has been shown to induce arterial hypoxemia in the chronically catheterized fetal sheep. To investigate the mechanism behind this glucose-induced hypoxemia, eight pregnant ewes and their fetuses were studied. Fetal glucose infusion (11.9 +/- 0.6 mg glucose/kg per min) was associated with a doubling of the fetal plasma glucose concentration with concomitant elevation of the umbilical vein-distal arterial O2 content difference by 24 h of infusion (P less than 0.01). Calculated fetal O2 consumption increased from 8.1 +/- 0.4 ml/kg per min in the control period to a maximum value of 10.6 +/- 0.3 ml/kg per min by third infusion day (P less than 0.01), which is an increase of approximately 30%. The degree of stimulation of fetal O2 consumption was related to the degree of fetal hyperglycemia but not to the degree of fetal hyperinsulinemia. The increase in fetal O2 consumption was accompanied by a significant increase in fetal O2 extraction with no change in either fetal O2 delivery or fetal blood O2 affinity. In addition, fetal hypercapnea with a mild fetal respiratory acidosis was induced by fetal hyperglycemia. The increase in fetal arterial PCO2 was linearly related (P less than 0.001) to the magnitude of increase in fetal O2 consumption. These studies suggest that chronic fetal hyperglycemia induces a state of accelerated fetal oxidative metabolism and may be important in explaining the etiology behind certain unusual findings in human infants of diabetic mothers.
Value of 1-alpha-hydroxy vitamin D3 in treatment of primary hyperparathyroidism before parathyroidectomy.
Authors: D A Heath, W Van't Hoff, A D Barnes, J G Gray
Journal: BMJ (1979)

The postoperative course of six patients with primary hyperparathyroidism and obvious radiological evidence of bone disease pretreated with 1-alpha-hydroxy vitamin D3 (1 alpha HCC) was indistinguishable from that of six patients with a similar clinical and radiological picture who were not pretreated. 1alphaHCC may increase the hypercalcaemia in some cases and cannot be recommended for the routine preparation of such patients for surgery.