tbuckley/cabot-search huggingface dataset:
Metastasis-associated PRL-3 induces EGFR activation and addiction in cancer cells
Authors: Abdul Qader Omer Al-aidaroos, Hiu Fung Yuen, Ke Guo, Shu Dong Zhang, Tae-Hoon Chung, Wee Joo Chng, Qi Zeng
Journal: Journal of Clinical Investigation (2013)

Metastasis-associated phosphatase of regenerating liver-3 (PRL-3) has pleiotropic effects in driving cancer progression, yet the signaling mechanisms of PRL-3 are still not fully understood. Here, we provide evidence for PRL-3–induced hyperactivation of EGFR and its downstream signaling cascades in multiple human cancer cell lines. Mechanistically, PRL-3–induced activation of EGFR was attributed primarily to transcriptional downregulation of protein tyrosine phosphatase 1B (PTP1B), an inhibitory phosphatase for EGFR. Functionally, PRL-3–induced hyperactivation of EGFR correlated with increased cell growth, promigratory characteristics, and tumorigenicity. Moreover, PRL-3 induced cellular addiction to EGFR signaling, as evidenced by the pronounced reversion of these oncogenic attributes upon EGFR-specific inhibition. Of clinical significance, we verified elevated PRL-3 expression as a predictive marker for favorable therapeutic response in a heterogeneous colorectal cancer (CRC) patient cohort treated with the clinically approved anti-EGFR antibody cetuximab. The identification of PRL-3–driven EGFR hyperactivation and consequential addiction to EGFR signaling opens new avenues for inhibiting PRL-3–driven cancer progression. We propose that elevated PRL-3 expression is an important clinical predictive biomarker for favorable anti-EGFR cancer therapy.
Antibody Response to Aerosolized Transgenic Human Alpha<sub>1</sub>-Antitrypsin
Authors: L. Terry Spencer, John E. Humphries, Mark L. Brantly
Journal: New England Journal of Medicine (2005)

To the Editor: The Department of Health and Human Services has recommended the development of recombinant counterparts to blood-derived therapeutic human proteins.1 In response to this recommendati...
Changes in Medical Education
Authors: Daniel K. Bloomfield
Journal: JAMA (1974)

To the Editor.—  When Dr. Visscher's data are broken down by number of respondents rather than by percentages, one might conclude with equal assurance that despite significant curriculum changes over the past ten years, there are as many medical school clinical department heads who believe that current basic science instruction is more effective than it was ten years ago as there are who think it is less. In fact, of 214 respondents, only 67 believed basic science instruction was less effective while 147 indicated it was at least as effective or more effective than ten years earlier.  The findings are a tribute to the newer curricula that have been subjected to a scrutiny never applied to more traditional programs. I do not understand why Dr. Visscher's letter emphasizes a negative view, except that the results may have conflicted with preconceived notions that generated it.
Dilated Fixed Pupils From Atropine
Authors: Frank J. Weinstock
Journal: JAMA (1974)

To the Editor.—  The appearance of a patient with unilateral or bilateral fixed, dilated pupils is usually a matter of grave concern, making one consider angle closure glaucoma, cerebral aneurysm, brain tumor, subdural or subarachnoid hemorrhage, or other conditions. It always requires a careful, thorough evaluation.  Several examples of less serious causes of such dilated pupils will be discussed.   A 12-year-old boy is seen in the emergency room in a dazed condition due to a sledding accident, with bilateral fixed, dilated pupils with some blurred vision but no papilledema. After repeated denials of medications or use of eye drops, urine positive for barbiturates induced him to admit to use of drugs from his friends and of atropine eye drops that his father had hidden after using them for an eye condition of the past.  A 24-year-old woman complained of blurred vision, headache, and a unilateral dilated pupil. When
Abstract 4575: Covalent incorporation of a new class of dye-based affinity baits in sieving hydrogel nanoparticles overcome roadblocks to cancer biomarker discovery
Authors: Alessandra Luchini, Davide Tamburro, Temple Douglas, Benjamin H. Espina, Benjamin S. Lepene, Weidong Zhou, Virginia Espina, Emanuel F. Petricoin, Lance A. Liotta
Journal: Cancer Research (2010)

Abstract Cancer biomarker discovery and clinical application has been seriously hampered by low abundance, instability and complex formation with high abundance proteins (e.g. albumin). N-isopropylacrylamide (NIPA) based hydrogel particles, consisting of a bait-containing core and a protective shell, overcome these major issues associated to biomarker discovery and measurement. Particles perform in one step, in solution, a) total sequestration and concentration, b) size sieving and c) complete protection form degradation of LMW protein biomarkers in blood and urine. In this study, novel dye molecules were selected as affinity ligands for broad classes of biomarkers; dyes were chosen for their ability to bind proteins, glycoproteins and nucleic acid for tissue histology, to bind textile proteins for fabric staining or for their known property to bind allergens. Dyes containing primary amine group (e.g. Acid Black 48, Basic Red 9) were coupled to NIPA/acrylic acid (AAc) particles by condensation of the amine group the carboxylic group. The ability of particles to capture and concentrate analytes was tested against a panel of low abundance, labile tumor relevant biomarker that include angiogenic growth factors (bFGF, VEGF, PDGF), IGF-1 and IGF binding proteins, interleukins (IL-6, IL-8), chemokines (CXCL12, CCL24), pro-apoptotic Bcl-2 proteins (Bak, Bax), and nucleic acids. Technologies used to screen dye functionalized particles include 1 D gel electrophoresis, western blotting, immunoassay, and mass spectrometry. Results showed that dye based baits have extremely high affinity for the target analytes so that particles capture all the analyte present in solution and that the affinity of biomarkers to the bait is unique and specific to the chemical structure of the bait molecule. 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 4575.
Characteristics of pregnant Japanese women who required hospitalization for treatment of pandemic (H1N1) 2009 - low mortality rate may be due to early antiviral use
Authors: Akihito Nakai, Hisanori Minakami, Nobuya Unno, Shigeru Saito, Mamoru Morikawa, Yasunori Yoshimura, Toshihiko Terao
Journal: Journal of Infection (2011)
Abstract 131: C-kit induces epithelial-mesenchymal transition and contributes to salivary adenoid cystic cancer progression
Authors: Xinhua Liang, Ya-ling Tang, Jian Jiang, Yun-long Fan
Journal: Cancer Research (2014)

Abstract Epithelial-mesenchymal transition (EMT) is associated with salivary adenoid cystic cancer (ACC) progression and metastasis. Here, we report that ectopic overexpression of c-kit in ACC cell lines is sufficient for acquisition of mesenchymal traits, enhanced cell invasion, along with stem cell properties defined by the presence of a CD133+/CD44+ cell subpopulation. c-kit positively regulated expression of known EMT inducers, also activating TGF-βto contribute to EMT. c-kit itself was induced by TGF-βin ACC cell lines and required for TGF-β-induced EMT. Xenograft experiments showed that c-kit cooperated with oncogenic Ras to promote tumorigenesis in vivo. Finally, in human specimens of ACC, we found that c-kit was abnormally overexpressed and correlated with the prognosis of ACC. Our findings define an important function for c-kit in ACC progression by orchestrating EMT, and they implicate this gene product as a marker of poor prognosis in this disease. Citation Format: Xinhua Liang, Ya-ling Tang, Jian Jiang, Yun-long Fan. C-kit induces epithelial-mesenchymal transition and contributes to salivary adenoid cystic cancer progression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 131. doi:10.1158/1538-7445.AM2014-131
Number of acquired melanocytic nevi in patients with melanoma and control subjects in Japan: nevus count is a significant risk factor for nonacral melanoma but not for acral melanoma
Authors: Shiho Rokuhara, Toshiaki Saida, Misae Oguchi, Kazuhiko Matsumoto, Sumio Murase, Shinji Oguchi
Journal: Journal of the American Academy of Dermatology (2004)
Browning reaction systems as sources of mutagens and antimutagens.
Authors: W D Powrie, C H Wu, V P Molund
Journal: Environmental Health Perspectives (1986)

Heated food systems contain hundreds of chemical compounds, some being mutagenic and others being antimutagenic. Studies have indicated that foods exposed to drying, frying, roasting, baking, and broiling conditions possess net mutagenic activity as assessed by the Ames/Salmonella/microsome mutagenicity test and the chromosome aberration assay with Chinese hamster ovary (CHO) cells. With the above-mentioned heat treatment of food, nonenzymic browning reactions are generally proceeding at rapid rates and are involved in the development of mutagens. Caramelization and Maillard reactions are two important pathways in the nonenzymic browning of food and are responsible for the formation of volatile aromatic compounds, intermediate nonvolatile compounds, and brown pigments called melanoidins. Heated sugar-amino acid mixtures possessed mutagenic activities which have been assessed by short-term bioassays. Purified Maillard and caramelization reaction products such as reductones, dicarbonyls, pyrazines, and furan derivatives have exhibited mutagenicity and clastogenicity. The water-insoluble fraction (WIF) of instant coffee and a model-system melanoidin (MSM) have been shown to inhibit the mutagenicity of known carcinogens--aflatoxin B1 (AFB1), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and benzo(a)pyrene (BP)--in aqueous dispersion. WIF and MSM were found to be effective binding agents for the carcinogens.
Series Introduction: Stem cells near the century mark
Authors: Pamela Gehron Robey
Journal: Journal of Clinical Investigation (2000)

The concept of a stem cell, now nearing its hundredth year as one of the organizing principles of developmental biology, shows no sign of losing its youthful luster. At a time when the transfer of biological concepts to clinical practice drives much of science, the properties of stem cells in various tissues are attracting increasing levels of interest. This attention is not restricted to the germ line and blood, the traditional domain of stem cells as defined by early 20th-century studies on animal development, but has been extended to tissues not typically thought to turn over. As novel sites, properties, and functions have been identified for these cells, the definition of a stem cell has shifted repeatedly. Like some stem cells, this concept has expanded greatly and has displayed a remarkable degree of plasticity.
Real space and represented space: Cross-cultural perspectives
Authors: J. B. Deregowski
Journal: Behavioral and Brain Sciences (1989)

Abstract This paper examines the contribution of cross-cultural studies to our understanding of the perception and representation of space. A cross-cultural survey of the basic difficulties in understanding pictures—ranging from the failure to recognise a picture as a representation to the inability to recognise the object represented in the picture— indicates that similar difficulties occur in pictorial and nonpictorial cultrues. The experimental work on pictorial space derives from two distinct traditions: the study of picture perception in “remote” populations and the study of the perceptual illusions. A comprison of the findings on pictorial space perception with those on real space perceptual illusions. A comparison of findings on pictorial space perception with those on real space perception and perceptual constancy suggersts that cross-cultural differences in the perception of both real and representational space involve two different types of skills: those related exclusively to either real space or representational space, and those related to both. Different cultural groups use different skills to perform the same perceptual tasks.
Managing hyperglycaemia in patients with type 2 diabetes and known cardiovascular disease
Authors: Tahseen A Chowdhury, Akhil Kapur
Journal: Journal of the Royal Society of Medicine (2012)

People with type 2 diabetes are more likely to develop cardiovascular disease (CVD), and are more likely to have adverse outcomes following acute myocardial infarction (AMI). There is considerable uncertainty about the management of hyperglycaemia following AMI, due to the inconsistent findings of the Diabetes Insulin Glucose Acute Myocardial Infarction (DIGAMI) studies.1,2 A number of recent randomized controlled trials (RCTs) also suggest that certain hyperglycaemic therapies may increase cardiovascular risk in diabetes subjects with known CVD.3 Moreover, some studies have raised concerns that tight glycaemic control may be deleterious in older patients with established or subclinical CVD.4
SECTION REPRESENTATION IN THE HOUSE OF DELEGATES
Authors: Edward Jackson
Journal: JAMA (1922)

<h3>To the Editor:</h3> —At the recent session of the Association at St. Louis, it was proposed to do away with the election of members of the House of Delegates from the sections of the Association. It was urged that each member of the Association had the right to be represented in the House of Delegates through his state medical society, and that for members of the sections also to choose delegates was "double representation," and therefore unfair. That this claim of unfairness is entirely without foundation becomes evident when the facts are examined. Every member of the American Medical Association has the right through his state medical society to take what part an individual member can in choosing members of the House of Delegates. Every member may, if he wishes, become a Fellow of the Association, and aid directly in supporting the organization. Every Fellow has an equal right to
No Itinerant Quacks in Kentucky.
Authors: J. N. McCormack
Journal: JAMA (1897)

Executive Office State Board of Health of Kentucky, Bowling Green, Aug. 7, 1897. <h3>To the Editor:</h3> —After careful examination of the authorities Judge Thompson of Louisville has just handed down his opinion in our test case with the osteopaths. They had plenty of money and were ably defended, but after the proof was heard we never had any doubt as to the result. They are not only the most ignorant, but also the most unscrupulous lot of empirics with which we have yet had to contend in this State. Our law has now been in operation nearly four years. It has been tested upon every point and so far we have not failed to secure a conviction in each case tried. We convicted the Copeland people, the "K. &amp; K.'s," and all other concerns of that kind doing business here, and are able to report that there is not
Drugs In Man
Authors: James A. Hagans
Journal: JAMA (1967)

<h3>To the Editor:—</h3> The responsibility for drugs in man must rest somewhere, and it would seem ideal that it should be somewhere within the medical profession. It would also seem clear from recent past and current experiences that the profession, be it academic, private, government, or industrial, is not adequately or appropriately organized accept it. The time is past due that we, as members of the profession, must actively and quickly seek to throw off the shackles of self-interest, and plan for the needs of today and the pressing needs of tomorrow. Human pharmacology is clearly divisible into two major areas, namely,<i>clinical pharmacology</i>and<i>experimental therapeutics</i>. Recognition of this seems to be apparent in the increasingly frequent appointment of persons to the departments of both pharmacology and medicine. In practice, some members of the department of pharmacology are appointed in medicine, and some members of the department of medicine
Cardiac Toxicity 4 to 20 Years After Completing Anthracycline Therapy
Authors: Laurel J. Steinherz
Journal: JAMA (1991)

--To assess the cardiac status of long-term survivors of pediatric malignancies who received chemotherapy, including anthracyclines.-Patients were evaluated by echocardiogram from 4 to 20 years (median, 7 years) after completion of anthracyclines, with prospective and retrospective analysis.--The consecutive sample of 201 patients had received a total anthracycline dose of 200 to 1275 mg/m2 (median, 450 mg/m2), and 51 patients had mediastinal radiotherapy.--The overall incidence and severity of abnormal systolic cardiac function were determined for the entire cohort. Risk factors of total anthracycline dose, mediastinal radiotherapy, age during treatment, and length of follow-up were examined.--Twenty-three percent (47/201) of the cohort had abnormal cardiac function on noninvasive testing at long-term follow-up. Correlation between total cumulative dose, length of follow-up, and mediastinal irradiation with incidence of abnormalities was significant. Fifty-six patients were followed up for 10 years or more (median, 12 years), with a median anthracycline dose of 495 mg/m2. Thirty-eight percent (21/56) of these patients, compared with 18% (26/145) of patients evaluated after less than 10 years, had abnormal findings. Sixty-three percent of patients followed up for 10 years or more after receiving 500 mg/m2 or more of anthracyclines had abnormal findings. Nine of 201 patients had late symptoms, including cardiac failure and dysrhythmia, and three patients died suddenly. Microscopic examination of the myocardium on biopsy and autopsy revealed fibrosis.--The 23% incidence of late cardiac abnormalities warrants continued evaluation of patients after anthracyclines to guide patient care and the design of future chemotherapeutic protocols.
Ulcerative tracheo-oesophageal fistula during treatment by tracheostomy and intermittent positive pressure ventilation
Authors: H. R. S. Harley
Journal: Thorax (1972)

Forty-four collected cases of ulcerative tracheo-oesophageal fistula following tracheostomy and assisted ventilation are reviewed. The condition followed this form of treatment in 0·5% of cases and must be distinguished from fistulae caused by accident or surgery, and also from laryngotracheal paralysis or dysfunction. The symptomatology, diagnosis, and treatment are discussed in detail. Spontaneous cure of fistulae is rare, and operative closure should be the aim. In one patient in six, surgical closure is excluded by rapid death. When surgery is possible its timing requires critical judgement. Factors requiring assessment are the condition of the patient and of the tissues around the fistula, the necessity to continue assisted ventilation, and the ability to control nutrition, tracheal aspiration from the mouth or stomach, and pulmonary infection. The mortality of those who did not die too rapidly to receive treatment was 61% without surgery and 45·5% with surgery.
Therapy in Acute Coronary Care
Authors: Raymond Harris
Journal: JAMA (1972)

This manual, in paperback format, is a well-intentioned and serious attempt to improve therapy in acute coronary care. However, it begins with two strikes against it. The first is the belief that a writer can compile a basic outline of such therapy from numerous reference sources in the medical literature, without integrating them skillfully and judiciously into the text. Were this true, computers could grind out books, and experienced authors would become obsolete! The second strike is the attempt to present in outline form large amounts of data requiring judgment and selection by the user. The background information so essential for understanding the origin and prevention of the complications must be obtained from the 273 references to the medical literature or from better written books. As a result, this book fails to present sufficient clinical judgment on which a reader may base therapy, and becomes a superficial compilation of therapeutics,
Serum Cholesterol and Atherosclerosis in Man
Authors: K. S. MATHUR, N. L. PATNEY, V. KUMAR, R. D. SHARMA
Journal: Circulation (1961)

Two hundred cases were selected from medicolegal autopsies for a study of the relationship of serum cholesterol to the amount and severity of atherosclerosis in the aorta and the coronary and cerebral arteries. A preliminary study of cholesterol before and after death in 20 cases showed a close parallel between the two when the sample of blood was taken within 16 hours of death. The mean serum total cholesterol showed a tendency to rise from 122 mg. per cent ±16 in the first decade to 176 mg. per cent ±28 in the fifth decade. A statistically significant correlation was found between serum total cholesterol levels and age up to the fifth decade. No correlation could be observed between the serum cholesterol level and the amount and severity of atherosclerosis in the arteries. When all the cases were divided into arbitrary groups according to the amount of atherosclerosis, a rise in the levels of mean serum total cholesterol was seen in the first six successive groups of aortic atherosclerosis. But when age was excluded from the correlation between atherosclerosis and serum cholesterol, the interrelationship between the two was found to be statistically insignificant.
Fitness and freezing: vector biology and human health
Authors: J. Stephen Dumler
Journal: Journal of Clinical Investigation (2010)

Microbes transmitted to mammals by arthropods contend with many factors that could impede survival. To survive, host fitness with infection must outweigh costs. In this issue of the JCI, Neelakanta et al. demonstrate that ticks infected with Anaplasma phagocytophilum show enhanced fitness against freezing injury owing to induced expression of tick "antifreeze glycoprotein." This allows A. phagocytophilum to successfully propagate and survive to cause disease in nonnatural hosts, such as humans. How an intracellular microbe with a small genome subverts host cell function for survival provides insight into the control of some cellular function programs and underscores how vector biology can have an impact on human health.
Resuscitation and patients' views
Authors: J A Wall, R N Palmer
Journal: BMJ (1994)

babies should thereafter be given either 25 p.g daily or 1 mg weekly orally from 1 week until 3 months of age.All suspected cases of haemorrhagic disease of the newbom were collected by a surveillance system similar to that in Germany and Britain and based on active monthly reporting by all paediatric departments.From 1 October 1992 until 31 August 1994 no cases of serious bleeding or intracranial haemorrhage were reported.Only one case could be validated as idiopathic late haemor- rhagic disease of the newbom.3This was in a healthy 8 week old Turkish boy who was admitted with persistent nasal bleeding.He had been exclusively breast fed and had never received extra vitamin K.Thus over 23 months only one case of idiopathic late haemorrhagic disease of the newbom was reported, in a boy who had not received prophy- laxis.In the Netherlands an incidence of 7/100 000 was found before prophylaxis was introduced4; this is comparable to the incidence in Britain5 and Germany.6As about 200 000 babies are bom in the Netherlands each year and about 70% are breast fed it is strildng that we did not encounter a single case in which prophylaxis failed; the surveillance system obtained a mean response rate of 90% (range 87-93%).In contrast, many cases of failure of oral prophylaxis were found in Germany, where a response rate of 77-88% was achieved.2We assume that this is because only two or three doses are given in Germany.In accordance with our data, the British Paediatric Surveillance Unit stated in 1993 that a considerable proportion of babies in Britain probably received repeated oral doses and that it had not been notified of any failure (unpublished report).