tbuckley/cabot-search huggingface dataset:
Targeted Delivery of Plasmid DNA to Myogenic Cells via Transferrin-Conjugated Peptide Nucleic Acid
Authors: Kenneth W. Liang, Eric P. Hoffman, Leaf Huang
Journal: Molecular Therapy (2000)

We describe a novel approach to conjugate a targeting ligand to plasmid DNA without affecting either its supercoiled conformation or its ability to be efficiently transcribed. A 14-mer peptide nucleic acid (PNA) containing lysine and cysteine on each end was designed to target to a unique sequence located at the antibiotic resistance gene of the plasmid. The binding of PNA to the plasmid was found to be dose-dependent and sequence-specific and not to change the conformation of the plasmid. Transferrin (Tf) was conjugated with PNA via a reversible disulfide bond using N-succinimidyl-3-(2-pyridyldithio)propionate. Tf–PNA retained the ability to the plasmid in a sequence-specific manner. The efficiency of this bioconjugate for delivering plasmid was examined in cultured myoblasts and myotubes. Naked DNA and Tf–PNA/DNA showed no transfection activity in either myoblasts or myotubes. Polyethyleneimine (PEI) is required for significant increase of the transfection efficiency. At N:P ratio of 5, Tf–PNA enhanced gene transfection about fourfold over that of the DNA/PEI complex in both myoblasts and myotubes. This enhancement could be inhibited by excess free Tf, indicating that the enhancement of transfection was through Tf-mediated endocytosis. These findings suggest that this targeting system may have the potential for gene transfer to myogenic cells in vivo.
Lithium-carbamazepine neurotoxicity and risk factors
Authors: S Shukla, C D Godwin, L E Long, M G Miller
Journal: American Journal of Psychiatry (1984)

Five rapid-cycling manic patients developed neurotoxic syndromes when treated with a combination of lithium and carbamazepine, although all five had therapeutic plasma levels of both drugs. The risk factors for development of neurotoxicity with this drug combination are discussed.
Is There a Role for SV40 in Human Cancer?
Authors: Danielle L. Poulin, James A. DeCaprio
Journal: Journal of Clinical Oncology (2006)

The question of whether Simian Virus 40 (SV40) can cause human tumors has been one of the most highly controversial topics in cancer research during the last 50 years. The longstanding debate began with the discovery of SV40 as a contaminant in poliovirus vaccine stocks that were used to inoculate approximately 100 million children and adults in the United States between 1955 and 1963, and countless more throughout the world. Concerns regarding the potential health risk of SV40 exposure were reinforced by studies demonstrating SV40's potential to transform human cells and promote tumor growth in animal models. Many studies have attempted to assess the relationship between the potential exposure of humans to SV40 and cancer incidence. Reports of the detection of SV40 DNA in a variety of cancers have raised serious concerns as to whether the inadvertent inoculation with SV40 has led to the development of cancer in humans. However, inconsistent reports linking SV40 with various tumor types has led to conflicting views regarding the potential of SV40 as a human cancer virus. Several recent studies suggest that older detection methodologies were flawed, and the limitations of these methods could account for most, if not all, of the positive correlations of SV40 in human tumors to date. Although many people may have been exposed to SV40 by polio vaccination, there is inadequate evidence to support widespread SV40 infection in the population, increased tumor incidence in those individuals who received contaminated vaccine, or a direct role for SV40 in human cancer.
Abstract 3545: Autophagy inhibition as a therapeutic strategy in cancer
Authors: Ning Chen, Sandy Price, Vassiliki Karantza
Journal: Cancer Research (2011)

Abstract Autophagy is an evolutionarily conserved process involving degradation of cellular components in lysosomes to maintain protein and organelle quality control, and temporarily sustain cell viability in response to stressful stimuli. Several studies have demonstrated the dual role of autophagy in tumorigenesis as both a tumor suppressor and a protector of cancer cell survival under stress. It is well recognized that anticancer therapies, such as chemotherapy and irradiation (RT), induce autophagy as a pro-survival response, likely resulting in therapeutic resistance. Therefore, concurrent autophagy inhibition as a chemo- and RT-sensitizer has generated great interest in cancer therapy. We generated Beclin1+/+ and Beclin1+/- immortalized mouse mammary epithelial cells (iMMECs) stably expressing the apoptosis inhibitor BCL-2 and the autophagy marker EGFP-LC3 to investigate how acute autophagy inhibition and chronic autophagy deregulation impact tumor sensitivity to anticancer drugs commonly used against breast cancer. We also used human cancer cell lines, including MCF-7, PANC-1, MIA PaCa-2 and HCT-116 cells, to explore whether pharmacologic autophagy inhibition or genetic knockdown of autophagy regulators exhibits a synergistic anticancer effect with newer antineoplastic drugs, such as mTOR inhibitors (CCI-779 and RAD001) and novel antimicrotubule agents (ixabepilone). Treatment efficacy was evaluated by clonogenic survival and cytotoxicity assays in 2D- and 3D-epithelial cell culture in vitro and by tumor responsiveness assays in mice in vivo. Autophagy inhibition sensitized Beclin1+/+ apoptosis-defective iMMECs to doxorubicin, but not to paclitaxel, and had an even greater impact on autophagy-deficient cells. Moreover, autophagy inhibition via choloroquine or Beclin1 knockdown enhanced the treatment efficacy of mTOR inhibitors on MCF-7, PANC-1, MIA PaCa-2 and HCT116 cells in vitro and in xenograft tumors in nude mice in vivo. These studies provide insight into how autophagy functional status in tumors impacts treatment responsiveness and into how to best incorporate pharmacologic autophagy modulation in the decision tree for cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3545. doi:10.1158/1538-7445.AM2011-3545
Effect of salmeterol on airway eosinophils
Authors: M M M PIZZICHINI
Journal: Thorax (2000)

Dente et al 1used the examination of induced sputum cell counts (as well as sputum eosinophil cationic protein (ECP), blood eosinophils and serum ECP) to examine the inhibitory effects of a single dose of placebo and salmeterol on allergen induced inflammatory (as well as asthmatic) responses. They performed a crossover randomised study in 11 subjects who had two allergen challenges four weeks apart and found that salmeterol inhibited the allergen induced increases in sputum eosinophils but had no effect on the other inflammatory parameters.

The results differ from the negative results reported by us2 and Dante et al 1 attribute this to differences in study design. We agree with this explanation but not for the reasons given. Their study design has a major flaw in the use of only one baseline measurement to investigate two distinct interventions four weeks apart. The time of baseline measurements in relation to the randomised crossover design study was not given; we presume that it was at some appropriate point before the first allergen challenge. It will therefore be relevant only for half of the subjects. This design therefore ignores a basic rule of the randomised …
Transplantation of the Larynx — A Case Report That Speaks for Itself
Authors: Anthony P. Monaco
Journal: New England Journal of Medicine (2001)

In this issue of the Journal, Strome and colleagues1 describe the extraordinary case of the first successful transplantation of the larynx in a human. The recipient was a 40-year-old man who was aphonic as a result of a severe laryngeal injury. This thoughtfully executed application of laryngeal transplantation, initiated after a series of careful experimental studies, is a wonderful example of bench-to-bedside research for which the authors are to be commended.Several details of this unique case deserve emphasis. The patient's larynx had been destroyed by trauma, not cancer. There was complete HLA matching between the donor and the recipient. . . .
EXTRA-UTERINE PREGNANCY.Read in the Section of Obstetrics and Diseases of Women, at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: A. H. CORDIER
Journal: JAMA (1893)

A few years ago the report of a case of extra-uterine pregnancy was a rare event. They are frequent at this time; in fact, one can scarcely glance over a medical journal without seeing one or more cases reported. These cases are being recognized and reported with such frequency that one feels like apologizing to the members of a national organization for offering an addition to the list. However, it has been through the rehashing (so to speak) of this topic that this familiarity of the subject has been attained and the tabulation of these good results made possible. 1 shall dwell upon the pathology of ectopie gestation only so far as is necessary to sustain the position I hold, relative to the mooted location of the foetus in some instances, i. e. intra-ligamentous. While my experience in extra-uterine pregnancy has not been an extensive one, it has been characterized
THE GROWTH OF THE TUBERCLE BACILLUS AND ORGANISMS RESEMBLING IT ON FRUITS AND VEGETABLES.
Authors: M. J. ROSENAU
Journal: JAMA (1903)

At one time the tubercle bacillus was looked on as standing in a class by itself, sharply differentiated from all other micro-organisms, but not long after its recognition two important points came to light; first, that there are other organisms, especially the streptothricæ, that have the power of producing lesions resembling the tuberculous granulomata; and secondly, that there are other organisms resembling the tubercle bacillus in some of its biologic and staining characteristics. The fact that the tubercle bacillus stains with difficulty and decolorizes with corresponding difficulty was for a long time regarded as peculiar to this organism. This staining peculiarity was looked on as a definite and final test, quite as specific as a chemical reaction. But now we know a whole group of acid-proof bacteria widely distributed in Nature, that resemble the tubercle bacillus closely enough in certain features to cause confusion and errors in diagnosis. These
A highly specific isolation of rat sinusoidal endothelial cells by the immunomagnetic bead method using SE-1 monoclonal antibody
Authors: Takuo Tokairin, Yuji Nishikawa, Yuko Doi, Hitoshi Watanabe, Toshiaki Yoshioka, Mu Su, Yasufumi Omori, Katsuhiko Enomoto
Journal: Journal of Hepatology (2002)
Ribavirin and acute bronchiolitis in infancy.
Authors: P. A. White, N. Dunne
Journal: BMJ (1989)

The National Audit Office came to this unit for the data and despite being given graphs and bar charts requested the raw data as well.The published graph of male trends in mortality was prepared here.The bar chart of comparative mortality, however, which was reproduced in the BMJ and by the national media, originated within the National Audit Office.It makes out Sweden to have the highest coronary heart disease mortality of the developed economies.Unfortunately, my exhortation not to use crude all ages rates cannot have been passed on to whoever prepared the graph, which was not checked with me.
Enhanced coronary vasoconstriction to oxidative stress product, 8-epi-prostaglandinF2α, in experimental hypercholesterolemia
Authors: Stephanie H. Wilson, Patricia J.M. Best, Lilach O. Lerman, David R. Holmes, Darcy M. Richardson, Amir Lerman
Journal: Cardiovascular Research (1999)

The F2-isoprostanes are a family of novel prostaglandin isomers and a stable product of in vivo oxidative stress. 8-epi-prostaglandinF2 alpha, a member of this isoprostane family, is a vasoconstrictor and its local release may contribute to the abnormal vasomotor tone associated with hypercholesterolemia. We therefore aimed to outline the role of 8-epi-prostaglandinF2 alpha as a coronary vasoconstrictor in experimental hypercholesterolemia.Pigs were randomized to two experimental groups (each n = 9): normal (N) and high cholesterol (HC) diet. To determine the vasoconstrictive effects of 8-epi-prostaglandinF2 alpha in vitro, doses from 10(-9) to 10(-5) M were used to constrict coronary epicardial rings. Plasma total and LDL cholesterol levels were significantly higher in the HC group compared with the N group (P < 0.005) as were plasma 8-epi-prostaglandinF2 alpha levels (P < 0.001). 8-epi-prostaglandinF2 alpha immunoreactivity was present in the vessel wall in both groups. Normal vessels with intact endothelium (n = 8 rings) contracted to 8-epi-prostaglandinF2 alpha (maximal contraction 15.5 +/- 8.74%). In the HC group, rings with intact endothelium had a greater contractile response to 8-epi-prostaglandinF2 alpha compared to normals (72.3 +/- 7.9%; n = 8; P < 0.0001). This was reversed by preincubation with NOR-3, a NO donor (maximal contraction 6.7 +/- 1.56%; n = 5; P < 0.0001). Enhanced contraction in normal vessels occurred with endothelial denudation (98.4 +/- 3.56%; n = 6; P < 0.0001) and with preincubation of the endothelium-intact rings with L-NMMA (N-monomethyl-L-arginine), an NO synthase inhibitor (85.5 +/- 10.3%, n = 6, P < 0.001). The enhanced contraction seen with hypercholesterolemia did not occur with other prostanoid vasoconstrictors.Experimental hypercholesterolemia leads to a significant increase in 8-epi-prostaglandinF2 alpha levels in addition to enhanced 8-epi-prostaglandinF2 alpha-induced coronary vasoconstriction, in vitro. These findings support a role for the F2-isoprostanes in the regulation of coronary vasomotor tone in pathophysiologic states.
Mallory body induction in drug-primed mouse liver
Authors: Q X Yuan, N Marceau, B A French, P Fu, S W French
Journal: Hepatology (1996)

The aim of this study was to determine the various factors that are involved in the induction of Mallory body (MB) formation. A model was developed where MB formation was induced by refeeding either of the drugs griseofulvin or diethyl 1,4–dihydro–1,4,6–trimethyl–3,5– pyridinedicarboxylate (DDC). Mice were fed the drugs for 5 months, followed by withdrawal of the drugs for 1 month (drug–primed livers). The drugs were refed for 1,3,5,7, or 11 days. Early MBs first appeared as small, enlarged aggregates of filaments in the perinuclear or pericanalicular location on the third day of refeeding. Mature MBs appeared on the fifth day of refeeding. MBs reached maximum concentration on day 5 of refeeding. Western blots showed a progressive increase in the cytokeratin proteins (CK49 and CK55) and actin while refeeding the drugs. Liver cell regeneration, as indicated by the percent of proliferating cell nuclear antigen (PCNA)–positive nuclei, increased on the third day of refeeding. However, there was no correlation between the frequency of MBs and the percent of PCNA– positive nuclei. It is concluded that MB formation is not related to the liver cell regeneration response to injury but rather involves a separate regulation pathway. The MBs were heavily ubiquitinated and were associated with increased ubiquitin–protein conjugates as indicated by Western blotting, suggesting that ubiquitinization of cytokeratin protein are involved in the formation of MB aggregation.
Investigation of blunt abdominal trauma
Authors: Jan O Jansen, Steven R Yule, Malcolm A Loudon
Journal: BMJ (2008)

#### Summary points

Concealed haemorrhage is the second most common cause of death after trauma,1 and missed abdominal injuries are a frequent cause of morbidity and late mortality in patients who survive the early period after injury. Appropriate and expeditious investigation facilitates definitive management and minimises the risk of complications, so it is crucially important.

#### Sources and selection criteria 

We searched the Medline database for reviews and clinical trials using the terms “blunt abdominal trauma”, “blunt abdominal injury”, “investigation”, “computed tomography”, “ultrasound”, “FAST”, and “diagnostic peritoneal lavage”. Search results were individually reviewed and manually cross referenced. We also searched the Cochrane Library and Clinical Evidence databases, reviewed guidelines from the American College of Radiology and the Royal College of Radiologists, and used references from our personal collections. The literature is dominated by non-randomised studies, and few systematic reviews and meta-analyses are available. Most of the evidence is level II-IV.

Several high quality prospective and retrospective studies have shown non-operative management of solid organ injury to be safe and effective, and this strategy is now accepted into mainstream practice.2 3 4 In parallel, a paradigm shift has occurred in imaging algorithms, with greater emphasis being put on the detection of specific findings, rather than the mere detection of intraperitoneal fluid, which does not predict the need for intervention.5 The greater availability of computed tomography and ultrasound in emergency departments has contributed to changes in practice, but it has also created new controversies—diagnostic peritoneal lavage is now rarely performed, but the diagnosis of hollow …
Practical Pediatric Imaging: Diagnostic Radiology of Infants and Children
Authors: Jeremiah Kelleher
Journal: JAMA (1984)

Donald Kirks justifies the appearance of another textbook of pediatric radiology on the grounds that a practical overview of pediatric imaging using all modalities is not currently available. I think he is correct and that this book will fill a void.  The first chapter deals with the practical techniques of imaging in the pediatric patient. The concept of problem-oriented pediatric radiology is to the forefront. There are useful hints on equipment, protection, and special examinations. The subsequent seven chapters are divided by traditional organ systems and emphasize techniques of examination followed by excellent descriptions of common general abnormalities, including normal variants and rarer specific abnormalities. All chapters include excellent clear lists and diagrams, are profusely illustrated, and have excellent references. Finally, there are four appendices dealing with patient preparation, suggested projections, radiation dosage, and recommended techniques.  Dr Kirks has directed this book at, among others, trainee radiologists, radiologists in general
Urticarial vasculitis: a presentation of C3 nephritic factor
Authors: A.J. Carmichael, J.R. Marsden
Journal: British Journal of Dermatology (1993)

Journal Article Urticarial vasculitis: a presentation of C3 nephritic factor Get access A.J. Carmichael, A.J. Carmichael The Skin Hospital, Edgbaston, Birmingham B15 1PR, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.R. Marsden J.R. Marsden The Skin Hospital, Edgbaston, Birmingham B15 1PR, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 128, Issue 5, 1 May 1993, Page 589, https://doi.org/10.1111/j.1365-2133.1993.tb00245.x Published: 01 May 1993
Tissue transglutaminase generates deamidated epitopes on gluten, increasing reactivity with hydrolyzed wheat protein–sensitized IgE
Authors: Ryosuke Nakamura, Rika Nakamura, Shinobu Sakai, Reiko Adachi, Akiko Hachisuka, Atsuo Urisu, Yuma Fukutomi, Reiko Teshima
Journal: Journal of Allergy and Clinical Immunology (2013)
VOLUNTARY CONTROL OF THE HEART RATE THROUGH RESPIRATION
Authors: C. W. Lueders
Journal: JAMA (1922)

<h3>To the Editor:</h3> —The editorial comment on voluntary acceleration of the heart (The Journal, Oct. 21, 1922, p. 1432) brought to my mind the fact that, invariably in my experience, one can voluntarily control the rate of the heart by so simple a means as the respiration. I have proved this relation on myself as well as on patients, including the tuberculous, the thyrotoxic and the diabetic. It is reasonable to state that the heart, during the demonstration, must be uninfluenced by drugs such as morphin, digitalis, atropin, strychnin, caffein, epinephrin and quinidin. Deep, slow respirations cause a slowing of the pulse; rapid, shallow breathing, an increase in the rate. Holding the breath after maximum inspiration produces a slowing of the pulse rate of ten or more beats each minute. A corresponding increase in rate follows holding the breath after maximum expiration. If, however, the breath is held for long,
Molecular Biology of Thyrotropin
Authors: MARGARET A. SHUPNIK, E. CHESTER RIDGWAY, WILLIAM W. CHIN
Journal: Endocrine Reviews (1989)

THE pituitary glycoprotein hormone TSH is synthesized and secreted by the thyrotropes in the anterior pituitary. TSH acts on the thyroid gland to increase the production of the thyroid hormones T3 and T4, which then act on organs throughout the body to modulate growth and various metabolic processes. High levels of the thyroid hormones in turn feed back at the level of the pituitary to suppress synthesis and secretion of TSH, and the thyroid hormone concentration is the most important physiological regulator of TSH levels (1–5). Additional regulation can occur via hypothalamic hormones such as TRH and dopamine, which stimulate and suppress TSH levels, respectively (1, 2) (Fig. 1). Thyroid and hypothalamic hormones interact to modulate both circulating levels of TSH and the transcription of the genes encoding the hormone. TSH is one of three pituitary glycoprotein hormones that consists of two dissimilar noncovalent subunits, α and β. The α-subunit is common to all three, including TSH and the two gonadotropin hormones LH and FSH, while the β-subunits are unique for each hormone and confer biological specificity (3). The subunits are synthesized as separate peptides from distinct messenger RNAs (mRNAs) (6–9). The α-subunits have molecular weights of approximately 20,000–22,000 and contain two relinked carbohydrate groups. The TSH subunits molecular weights are approximately 18,000 and contain one Nlinked complex carbohydrate (1).
New Medical Schools
Authors: Kenneth E. Penrod
Journal: JAMA (1971)

Although I agreed to address myself to this title, I shall take the liberty of complying with the spirit but not the letter. Rather than speak of establishing new medical schools, I prefer to discuss ways of achieving the same ends through different means. The fact that there must be a major expansion of medical education needs no elaboration. Somewhere between 4,000 and 9,000 additional entering places must be made available before the end of the decade to meet the various goals that have been announced. Such demands clearly call for new thinking. Several factors of significance to medical education have appeared recently. The medical curriculum has undergone critical examination and change in most schools. Meanwhile, long overdue educational reforms have been taking place over the entire span from the lower grades through college. While the newer concepts of learning have by no means been universally adopted, many of those
STUDIES ON EPIDEMIC INFLUENZA VIRUS
Authors: Edwin H. Lennette, Frank L. Horsfall
Journal: The Journal of Experimental Medicine (1940)

Evidence is presented which indicates that influenza virus elaborates a soluble antigen. The antigen is considerably smaller than the virus and can be separated from it, but the virus has not been washed free of antigen. The properties of the antigen suggest that it is an unstable protein of relatively large size.
PLATELET ACTIVATION INDUCES TRASCRIPTOME AND PROTEOME REORGANIZATON VIA MODULATION OF MIRNA EXPRESSION PROFILE
Authors: Giovanni Cimmino, Roberta Tarallo, Giovanni Nassa, Maria Rosaria De Filippo, Maria Ravo, Stefano Conte, Grazia Pellegrino, Plinio Cirillo, Paolo Calabro, Tuula A Nyman, Alessandro Weisz, Paolo Golino
Journal: Journal of the American College of Cardiology (2014)