tbuckley/cabot-search huggingface dataset:
CASE OF FATAL INTESTINAL HAeMORRHAGE COMING ON THIRTY-FIVE HOURS AFTER BIRTH
Authors: R. Neale
Journal: BMJ (1854)

I AM induced, by reading the valuable and imtructive papers which have been lately published in the AssocIATION JOURNAL, on the subject of puerper cn sions, to send the particulars, as far as I recollect them, of a fatal case which occurred in my practice two years ago.'CAM.I was called on the night of the 23rd August 1852 to M. B., a young unmarried girl of seventeen; her father, who fetched me, stated that his daughter was very ill, and "that they could make nothing of her".I went immedi-
Observations ON GUNSHOT WOUNDS OF THE HEAD
Authors: H. M. W. Gray
Journal: BMJ (1916)

We (Bradfield et al., 2013) have demonstrated previously that parafascicular thalamic nucleus (PF)-controlled neurons in the posterior dorsomedial striatum (pDMS) are critical for interlacing new and existing action–outcome contingencies to control goal-directed action. Based on these findings, it was suggested that animals with a dysfunctional PF–pDMS pathway might suffer a deficit in creating or retrieving internal contexts or "states" on which such information could become conditional. To assess this hypothesis more directly, rats were given a disconnection treatment using contralateral cytotoxic lesions of the PF and pDMS (Group CONTRA) or ipsilateral control lesions (Group IPSI) and trained to press a right and left lever for sucrose and pellet outcomes, after which these contingencies were reversed. The rats were then given an outcome devaluation test (all experiments) and a test of outcome-specific reinstatement (Experiments 1 and 3). We found that devaluation performance was intact for both groups after training of initial contingencies, but impaired for Group CONTRA after reversal. However, performance was restored by additional reversal training. Furthermore, when tested a second time after reversal training, rats in both groups demonstrated responding in accordance with the original contingencies, providing direct evidence of modulation of action selection by state. Finally, we found that external context could substitute for internal state and so could rescue responding in Group CONTRA, but only in the reinstatement test. Together, these findings suggest that animals use internal state information to guide action selection and that this information is modulated by the PF–pDMS pathway. <b>SIGNIFICANCE STATEMENT</b> Individuals with Parkinson9s disease dementia often suffer a characteristic deficit in "cognitive flexibility." It has been suggested that neurodegeneration in the pathway between the centromedian/parafascicular thalalmic nucleus (PF) and striatum might underlie such deficits (Smith et al., 2014). In rats, we have similarly observed that a functional disconnection of the PF–posterior dorsomedial striatal pathway produces a specific impairment in the ability to alter goal-directed actions (Bradfield et al., 2013). It was suggested that this impairment could be a result of a deficit in state modulation. Here, we present four experiments that provide evidence for this hypothesis and suggest several ways (e.g., extended practice, providing external cues) in which this state modulation can be rescued.
PRIMA-1 Reactivates Mutant p53 by Covalent Binding to the Core Domain
Authors: Jeremy M.R. Lambert, Petr Gorzov, Dimitry B. Veprintsev, Maja Söderqvist, Dan Segerbäck, Jan Bergman, Alan R. Fersht, Pierre Hainaut, Klas G. Wiman, Vladimir J.N. Bykov
Journal: Cancer Cell (2009)
Chemotherapy for Advanced Gastric Carcinoma-Reply
Authors: Charles G. Moertel
Journal: JAMA (1986)

<h3>In Reply—</h3> We are very pleased that Drs Haller and Schein agree that the literature should not encourage the physician to accept FAM as established therapy for pancreatic cancer. Our data unequivocally support that conclusion, as does the randomized study led by Dr Schein that showed only a trivial 13% response rate and no survival advantage whatsoever when FAM was compared with a number of completely inactive drugs.<sup>1</sup>Since Dr Schein and his Georgetown group had stimulated the widespread use of FAM for pancreatic cancer, based on a claim of high response rates and responders living longer than nonresponders, we consider this to be a particularly courageous disclaimer and congratulate Dr Schein. We hope that now the book is closed on this issue and that FAM will no longer be promoted or used for advanced carcinoma of the pancreas. We are perplexed that Drs Haller and Schein, and Dr
ANTIGEN RECOGNITION: IN VITRO STUDIES ON THE SPECIFICITY OF THE CELLULAR IMMUNE RESPONSE
Authors: Stuart F. Schlossman, Judith Herman, Arieh Yaron
Journal: The Journal of Experimental Medicine (1969)

Studies of the immunochemical specificity of antigen-induced thymidine-2-(14)C incorporation in lymph node cells obtained from animals immunized to a series of closely related alpha-DNP-oligolysines, epsilon-DNP-oligolysines, and oligolysines have shown that the sensitized cell exhibits an extraordinary degree of specificity for antigen. The sensitized cell is maximally stimulated by the homologous immunizing antigen and can discriminate among compounds which differ from one another only in the position of a dinitrophenyl group or D-lysine residue on an identical oligolysine backbone. These studies support the view that the immunogen is not degraded prior to the induction of the immune response, and that the majority of cells produced as a consequence of immunization have stereospecific antigen receptors for the DNP-oligolysine used to induce the response; a smaller and more variably sized population of cells is produced with receptors specific for the oligolysine portion of the immunizing antigen. When specifically sensitized lymph node cell cultures are stimulated in vitro by heterologous DNP-oligolysines, the oligolysine- and not the DNP-oligolysine-sensitive population of cells appears to play a crucial role in the specificity of such cross-reactions. It is concluded from these studies that the antigen receptor on the sensitized lymph node cell differs in both kind and degree from conventional antibody. The chemical nature of the receptor and the means by which this receptor reacts with antigen to initiate the biosynthetic or proliferative cellular immune response still remain undefined.
Hepatic Imaging: A Comparison of Tc-99m-Sulfur Colloid and PIPIDA in the Detection of Defects
Authors: JOHN L. FLOYD, FREDERICK L. WEILAND, ALBERT S. HALE, MARTIN L. NUSYNOWITZ
Journal: Clinical Nuclear Medicine (1981)

A prospective investigation comparing Tc-99m-PIPIDA with Tc-99m-sulfur colloid in the detection of defects of the liver was carried out in 30 volunteers. By acquiring images of 1 million counts from 5-10 minutes postinjection, high quality hepatic images could be obtained with PIPIDA. Separate interpretations by three nuclear physicians yielded similar results between paired PIPIDA and sulfur colloid studies (KAV = 0.95 ± .09, P <0.001). Early multiview imaging of the liver in the course of hepatobiliary evaluation with PIPIDA may yield valuable information relative to the presence of lesions.
MiR-377 targets E2F3 and alters the NF-kB signaling pathway through MAP3K7 in malignant melanoma
Authors: Liron Zehavi, Hagit Schayek, Jasmine Jacob-Hirsch, Yechezkel Sidi, Raya Leibowitz-Amit, Dror Avni
Journal: Molecular Cancer (2015)

The incidence of cutaneous malignant melanoma continues to rise, and once the disease metastasizes it is almost inevitably fatal. We recently reported that a large miRNAs cluster on human chromosome 14q32, implicated in many types of cancers, is significantly down-regulated in melanoma. miR-377, one of the miRNAs located within this cluster, was studied here.qRT-pCR was used to quantify miR-377 levels in melanoma cell lines and samples. Melanoma cell lines ectopically expressing miR-377 were generated by stable transfection, mRNA expression was assessed using mRNA arrays and protein expression was assessed by Western blot analysis. Potential targets of miR-377 were identified through luciferase reporter assays. Cellular proliferation, migration and soft-agar colony formation were monitored in control and miR-377-expressing cells using cell biology techniques.miR-377 is expressed in normal melanocytes but not in melanoma cell lines or samples. Its ectopic stable expression in melanoma cell lines decreased their proliferative and migratory capacity and their colony-forming capability. mRNA arrays of melanoma cells over-expressing miR-377 pointed to several down-regulated mRNAs that have putative binding sites for miR-377 in their 3'UTR, of which both E2F3 and MAP3K7 were found to be direct targets of miR-377. E2F3, a potent transcriptional inducer of cell-cycle progression, was found to be elevated in melanoma cell lines, but decreased following ectopic expression of miR-377. Ectopic miR-377 also led to a decrease in the activity of a reporter plasmid containing three E2F DNA-binding sites linked to a luciferase cDNA sequence, demonstrating that miR-377 down-regulates E2F3-induced transcription. MAP3K7 (known as TAK1), a serine/threonine kinase along the MAPK signaling pathway, was over-expressed in melanoma but decreased following ectopic expression of miR-377. MAP3K7 is involved in the activation of NF-κB. MiR-377 over-expression led to decreased activity of a reporter plasmid containing two NF-κB DNA-binding sites and to decreased output along the NF-kB signaling pathway.Our results suggest that miR-377 is an important negative regulator of E2F and MAP3K7/NF-kB signaling pathway in melanoma cells; it is tempting to speculate that its silencing in melanoma promotes the tumorigenic and metastatic potential of the cells through activation of these pathways.
Assessing Medical Technology
Authors: Stanley Joel Reiser
Journal: JAMA (1981)

To the Editor.—  In 1891 the noted Philadelphia physician S. Weir Mitchell complained to his colleagues, You know, alas! that we now use as many instruments as a mechanic. 1 Mitchell would be dismayed by practice today. Technology is pervasive in its scope and effects on the physician's actions, the patient's body, and the public's purse. It is fitting to debate how to appropriately harness technology to medical need and understandable that divergent views emerge on how best to do it, as illustrated by the article of Drs Perry and Eliastam (1981;245:2510) in support of the National Center for Health Care Technology (NCHCT), and the editorial (1981;245:2519) reporting the American Medical Association's opposition to the Center.  Both the AMA and the NCHCT agree that technology assessment is difficult and crucial and that the activity must be sustained and nurtured. I know of no responsible person in medicine who argues to
Congestive Heart Failure: Mechanisms, Evaluation and Treatment
Authors: Irwin R. Callen
Journal: JAMA (1977)

This multi-authored book, edited and written in part by Dr Dean T. Mason, is up to date, well written, and profusely referenced and illustrated. The authors are among the foremost investigators and therapeutic experts in the area of congestive heart failure. Dr Mason divides the subjects into three main themes: mechanisms, evaluation, and treatment. Part 1, "The Mechanisms," presents a review of biochemistry, phase and electron microscopy, and physiological studies performed in experimental animal and human laboratories before 1976. While the authorities who present the material are outstanding experimenters, there is too much repetition. The editor could have deleted more than one third of the 179 pages. Part 2, "Evaluation," is superb. Included are lucid descriptions of the physical examination, echocardiography, and cardiac catheterization in congestive heart failure. The final chapter in this section discusses cardiac catheterization in coronary heart disease. Its inclusion in this book was unnecessary, but it
Exceptions in Search of a Rule
Authors: Samuel Vaisrub
Journal: JAMA (1974)

An "exception proves a rule" only in the realm of the humanities. A scientific rule brooks no exceptions. If these occur, they must be subsumed under a new rule or a modification of the old one. Exceptions now crowd the rule that angina and myocardial infarction are caused by coronary artery disease. Angina, even myocardial infarction (in a communication in this issue p 804), have been reported in young people whose coronary arteries show no abnormalities on the angiogram or at postmortem examination. Can we find a new rule for these exceptions? On reviewing a six-year experience with 200 patients who had angina despite normal coronary arteriograms, Kemp et al<sup>1</sup>analyzed some current hypotheses. Apparently none passed muster. The psychosomatic hypothesis fails to explain away the myocardial damage. The coronary artery spasm theory has not been confirmed by evidence that spasms occur spontaneously. Occlusions of small vessels undetectable by
Studies with Rhinoviruses in Volunteers: Production of Illness, Effect of Naturally Acquired Antibody, and Demonstration of a Protective Effect Not Associated with Serum Antibody*
Authors: Thomas R. Cate, Robert B. Couch, Karl M. Johnson
Journal: Journal of Clinical Investigation (1964)

The term "rhinovirus" (1-3) is now used to designate a group of immunologically distinct re- spiratory viruses, possessing many properties of enteroviruses but differing by lability in acid media (4-6) and almost exclusive multiplication in the nasopharynx.The first agents isolated that fit this description were the JH and 2060 strains of ECHO 28 isolated by Price (7) and Pelon, Mo- gabgab, Phillips, and Pierce (8) in 1956 and classified by Pelon (9).Modifications in tissue cul- ture technique for isolating these and similar agents, i.e., incubation on a rotating drum and re- duction in pH to 7.0 to 7.3, were introduced by Pelon and Mogabgab (10) and extended by Tyr- rell and associates (4) and Tyrrell and Parsons (5) to include an incubation temperature of 330 C and use of human tissues.Subsequently, many rhinoviruses, reported under a variety of names, have been isolated in association with mild respira- tory illnesses (11)(12)(13)(14)(15)(16).Some of the strains grow only in tissues of human origin (H strains) and some as well in monkey kidney tissue culture (M strains) (3, 5).It has been estimated that rhino- viruses account for 35 to 40%o of the common colds in adults (17).Tyrrell, Bynoe, and co-workers (4, 18-20) and Jackson, Dowling, and Mogabgab (21), who have administered rhinoviruses to volunteers, have dem- onstrated that the viruses can infect and produce common colds and that protection is associated with the presence of specific neutralizing antibody in the serum.After the isolation of other strains of rhinovirus, NIH 353, 1734, and 11757, by
Historical review: some reflections on Bowditch's original work, a philosophy of science point of view, and implications for present research on force-interval relations
Authors: J. SCHAEFER, R. K LIE, W. DEPPERT, D. BURKHOFF
Journal: Cardiovascular Research (1988)

Journal Article Historical review: some reflections on Bowditch's original work, a philosophy of science point of view, and implications for present research on force-interval relations Get access JOCHEN SCHAEFER, JOCHEN SCHAEFER * Search for other works by this author on: Oxford Academic PubMed Google Scholar REIDAR K LIE, REIDAR K LIE †From the Department of Medical Humanities, School of Medicine, East Carolina University. Greenville, NC 27858-4354, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar WOLFGANG DEPPERT, WOLFGANG DEPPERT ‡From the Philosophisches Seminar, Christian-Albrechts-Universität zu Kiel, 2300 Kiel, FRG Search for other works by this author on: Oxford Academic PubMed Google Scholar DAN BURKHOFF DAN BURKHOFF §From the Department of Biomedical Engineering, Johns Hopkins University, Baltimore 21205, Md, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 22, Issue 8, August 1988, Page 585, https://doi.org/10.1093/cvr/22.8.585 Published: 01 August 1988
Generalized Concentration Addition Predicts Joint Effects of Aryl Hydrocarbon Receptor Agonists with Partial Agonists and Competitive Antagonists
Authors: Gregory J. Howard, Jennifer J. Schlezinger, Mark E. Hahn, Thomas F. Webster
Journal: Environmental Health Perspectives (2009)

Predicting the expected outcome of a combination exposure is critical to risk -assessment. The toxic equivalency factor (TEF) approach used for analyzing joint effects of dioxin-like chemicals is a special case of the method of concentration addition. However, the TEF method assumes that individual agents are full aryl hydrocarbon receptor (AhR) agonists with parallel dose-response curves, whereas many mixtures include partial agonists.We assessed the ability of generalized concentration addition (GCA) to predict effects of combinations of full AhR agonists with partial agonists or competitive antagonists.We measured activation of AhR-dependent gene expression in H1G1.1c3 cells after application of binary combinations of AhR ligands. A full agonist (2,3,7,8-tetrachlorodibenzo-p--dioxin or 2,3,7,8-tetrachlorodibenzofuran) was combined with either a full agonist (3,3 ,4,4 ,5-penta-chloro-biphenyl), a partial agonist (2,3,3 ,4,4 -pentachlorobiphenyl or galangin), or an antagonist (3,3 -diindolylmethane). Combination effects were modeled by the TEF and GCA approaches, and goodness of fit of the modeled response surface to the experimental data was assessed using a nonparametric statistical test.The GCA and TEF models fit the experimental data equally well for a mixture of two full agonists. In all other cases, GCA fit the experimental data significantly better than the TEF model.The TEF model overpredicts effects of AhR ligands at the highest concentration combinations. At lower concentrations, the difference between GCA and TEF approaches depends on the efficacy of the partial agonist. GCA represents a more accurate definition of additivity for mixtures that include partial agonist or competitive antagonist ligands.
THE UTILITY OF ENDOTHELIAL FUNCTION AS ASSESSED BY REACTS HYPEREMIA–PERIPHERAL ARTERIAL TNONOMETRY IN PREDICTING DEEP VENOUS THROMBOSIS AFTER ORTHOPEDIC SURGERY
Authors: Hiroyuki Suzuki, Yasushi Matsuzawa, Masaaki Konishi, Eiichi Akiyama, Kiyoshi Hibi, Toshiaki Ebina, Masami Kosuge, Kazuo Kimura
Journal: Journal of the American College of Cardiology (2013)
Water Quality Influences Reproduction in Female Mosquitofish ( <i>Gambusia holbrooki</i> ) from Eight Florida Springs
Authors: Thea M. Edwards, Hilary D. Miller, Louis J. Guillette
Journal: Environmental Health Perspectives (2005)

Contamination of freshwater ecosystems with nitrate is a growing global concern. Although nitrate pollution is recognized as a cause of aquatic eutrophication, few studies have examined the possible physiological impacts of nitrate exposure. In this study, we surveyed several reproductive variables of viviparous female Gambusia holbrooki (Poeciliidae) captured from eight springs in Florida. The eight springs represent a gradient of nitrate contamination (1-5 mg/L nitrate-nitrogen). We had two objectives in this study: to describe reproductive biology of female mosquitofish in the springs and to understand reproductive variation in the context of water quality, particularly the nitrate concentration. Our data show a significant negative association between nitrate and both dry weight of developing embryos and rate of reproductive activity among mature females. In addition, variation in Gambusia condition index and embryo number and dry weight was related to temperature variation, and hepatic weight was negatively related to dissolved oxygen concentration. Finally, we observed that many of the measured reproductive variables were interrelated and changeable, depending on gestational stage. Specifically, we provide evidence that maternal support of the embryo occurs at least during the first two thirds of gestation and that female fecundity is affected by an apparent tradeoff between embryo size and embryo number.
PURIFICATION AND PHYSICAL PROPERTIES OF GROUP C STREPTOCOCCAL PHAGE-ASSOCIATED LYSIN
Authors: Vincent A. Fischetti, Emil C. Gotschlich, Alan W. Bernheimer
Journal: The Journal of Experimental Medicine (1971)

A purification procedure for the Group C phage-associated lysin is described utilizing tetrathionate to protect the enzyme's -SH group(s) from thiol-inactivating agents. A 652-fold purification has been accomplished yielding a solution in which the enzyme activity corresponds to essentially a single band on polyacrylamide gel which accounts for 70% of the total protein in the preparation. A molecular weight of 101,000 and frictional ratio of 1.526 was determined for the lysin utilizing experimentally determined values for its Stokes radius and sedimentation coefficient.
Lymphocyte subsets in pagetoid reticulosis
Authors: D. Slater, J. Goepel, Anne Walker, P. Corbett
Journal: British Journal of Dermatology (1984)

Journal Article Lymphocyte subsets in pagetoid reticulosis Get access D. Slater, D. Slater Royal Hallamshire Hospital, Sheffield Weston Park Hospital, Sheffield Chesterfield Royal Hospital Weston Park Hospital, Sheffield Search for other works by this author on: Oxford Academic Google Scholar J. Goepel, J. Goepel Royal Hallamshire Hospital, Sheffield Weston Park Hospital, Sheffield Chesterfield Royal Hospital Weston Park Hospital, Sheffield Search for other works by this author on: Oxford Academic Google Scholar Anne Walker, Anne Walker Royal Hallamshire Hospital, Sheffield Weston Park Hospital, Sheffield Chesterfield Royal Hospital Weston Park Hospital, Sheffield Search for other works by this author on: Oxford Academic Google Scholar P. Corbett P. Corbett Royal Hallamshire Hospital, Sheffield Weston Park Hospital, Sheffield Chesterfield Royal Hospital Weston Park Hospital, Sheffield Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue 2, 1 August 1984, Pages 244–246, https://doi.org/10.1111/j.1365-2133.1984.tb04053.x Published: 01 August 1984
U46619-induced bronchoconstriction in asthmatic subjects is mediated by acetylcholine release.
Authors: H G Saroea, M D Inman, P M O'Byrne
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Thromboxane A2 (TxA2) has been implicated in the pathogenesis of airway hyperresponsiveness. U46619 is a chemical that mimics the effects of TxA2. Both TxA2 and U46619 have been demonstrated to act presynaptically to enhance the release of acetylcholine from cholinergic nerves in canine airway smooth muscle. The purpose of this study was to determine whether the bronchoconstriction caused by inhaled U46619 in asthmatic subjects is caused by acetylcholine release. Airway responsiveness to inhaled methacholine and U46619 was measured in eight subjects with mild stable asthma and expressed as the provocation concentration causing a 20% fall in FEV1 (PC20). Subjects were studied on 4 d, each separated by 3 days. On each study day, subjects inhaled a cholinergic antagonist ipratropium bromide (80 micrograms), or placebo, and 1 h later, increasing doubling doses of methacholine or U46619 were inhaled, and a PC20 value was obtained. The mean methacholine PC20 on the placebo day was 1.42 mg/ml (%SEM, 1.47) and after treatment with ipratropium bromide this increased to 127.33 mg/ml (%SEM, 1.29) (p = 0.0001), a mean 89.4-fold (%SEM, 1.19) increase. The mean U46619 PC20 on the placebo day was 2.09 micrograms/ml (%SEM, 1.56) and after treatment with ipratropium bromide this increased to 47.54 micrograms/ml (%SEM, 1.43) (p = 0.0001), a mean 22.8-fold (%SEM, 1.36) increase. The ability of ipratropium bromide to attenuate responsiveness to the noncholinergic mediator histamine was also investigated in six subjects. The mean increase in histamine PC20 was a 3.09-fold (%SEM, 1.17) increase, significantly less than the increase seen for both methacholine and U46619 (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)