tbuckley/cabot-search huggingface dataset:
Experimental Zinc Deficiency in Humans
Authors: ANANDA S. PRASAD
Journal: Annals of Internal Medicine (1978)

The effects of a mild zinc-deficient state in humans were studied. Four male volunteers received restricted zinc intake for several weeks under strict metabolic conditions. As a result of dietary zinc restriction, a decrease in zinc concentration of plasma, erythrocytes, leukocytes, and urine was observed. Changes in the activities of zinc-dependent enzymes in the plasma such as alkaline phosphatase and ribonuclease were also related to the dietary zinc status. An adverse effect of zinc restriction on total protein, total collagen, ribonucleic acid, and the activity of deoxythymidine kinase (a zinc-dependent enzyme) in the sponge connective tissue of the two volunteers in whom this test was done was noted. During the zinc restriction period, the ammonia level in the plasma was elevated. Weight loss occurred in all subjects as a result of dietary zinc restriction. Inasmuch as the zinc-deficient state was mild, this study provides a basis for developing diagnostic criteria for zinc deficiency in humans.
Health Care Ethics Consultation: An Update on Core Competencies and Emerging Standards from the American Society for Bioethics and Humanities’ Core Competencies Update Task Force
Authors: Anita J. Tarzian, None ASBH Core Competencies Update Task
Journal: The American Journal of Bioethics (2013)

Ethics consultation has become an integral part of the fabric of U.S. health care delivery. This article summarizes the second edition of the Core Competencies for Health Care Ethics Consultation report of the American Society for Bioethics and Humanities. The core knowledge and skills competencies identified in the first edition of Core Competencies have been adopted by various ethics consultation services and education programs, providing evidence of their endorsement as health care ethics consultation (HCEC) standards. This revised report was prompted by thinking in the field that has evolved since the original report. Patients, family members, and health care providers who encounter ethical questions or concerns that ethics consultants could help address deserve access to efficient, effective, and accountable HCEC services. All individuals providing such services should be held to the standards of competence and quality described in the revised report.
Abstract P5-11-01: Impact of CDK mediated Smad3 phosphorylation and Pin1 in triple negative breast cancer cell migration
Authors: R Hamdan, JS Jeruss
Journal: Cancer Research (2013)

Abstract Introduction: Estrogen receptor (ER), progesterone receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancers, also known as triple negative breast cancers can overexpress cyclins, such as cyclin D and E, which have been linked to cancer progression and metastasis. Cyclin/CDK complexes can phosphorylate and regulate Smads, downstream signaling proteins in the transforming growth factor-beta (TGF-b) superfamily. CDKs phosphorylate Smad3, predominantly in the linker region, resulting in the decreased tumor suppressive role of this protein. The peptidyl-prolyl cis/trans isomerase Pin1 is also overexpressed in breast cancer. Pin1 can bind phosphorylated Smads contributing to TGF-β induced cell migration and invasion. Inhibition of CDK-mediated Smad3 phosphorylation has been shown to restore Smad3 activity and decrease tumor cell migration in vitro. Based on these findings, we hypothesized that inhibition of Pin1 or CDK-mediated Smad3 phosphorylation would result in decreased triple negative breast cancer cell migration. Methods: Hs578T, MDA-MB-436, and MDA-MB-231 triple negative breast cancer cells (TN) were transfected with either an si control (siCN) or an siPin1 plasmid to knockdown Pin1 protein expression. Transwell migration assays were used to determine the effect of Pin1 knockdown on migration. TN cells were treated with CDK4 or CDK2 inhibitors alone or in combination. The study cells were also stably transduced with lentiviral empty vector, wild-type (WT) Smad3, or a Smad3 mutant (5M) resistant to CDK-mediated phosphorylation. The effect of pharmacologically or genetically inhibiting CDK-mediated Smad3 phosphorylation on Pin1 binding to phosphorylated Smad3 (p-Smad3) or total Smad3 was determined using a co-immunoprecipitation assay (Co-IP). Results: Transfecting the study cells with siPin1 resulted in decreased cell migration when compared to the siCN transfected cells. Treatment with the CDK4 or CDK2 inhibitors alone or in combination did not affect Pin1 protein levels, but resulted in decreased Pin1 binding to p-Smad3 with the greatest decrease found after treatment with combination therapy. Similarly, transduction of the study cells with the WT or the 5M Smad3 constructs had no effect on Pin1 levels but resulted in decreased Pin1 binding to Smad3. The greatest decrease was observed in the 5M transduced cells. Concusions: Inhibition of CDK-mediated Smad3 phosphorylation and knock down of Pin1 resulted in decreased migration of TN breast cancer cells. Inhibition of CDK-mediated Smad3 phosphorylation by mutation of the CDK phosphorylation sites or by treatment with CDK4 and CDK2 inhibitors negatively impacted Pin1 binding to Smad3. Together, these findings indicate that CDK-mediated Smad3 phosphorylation enhances Pin1 binding to Smad3 and promotes tumor cell migration in triple negative breast cancer cells. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-11-01.
Trends in Hospital Volume and Operative Mortality for High-Risk Surgery
Authors: Jonathan F. Finks, Nicholas H. Osborne, John D. Birkmeyer
Journal: New England Journal of Medicine (2011)

There were numerous efforts in the United States during the previous decade to concentrate selected surgical procedures in high-volume hospitals. It remains unknown whether referral patterns for high-risk surgery have changed as a result and how operative mortality has been affected.
Mental health legislation and decision making capacity: Capacity is more complex than it looks
Authors: Jacinta O A Tan, Tony Hope
Journal: BMJ (2006)

Editor—We agree with Doyal and Sheather that mental health legislation should respect decision making capacity because patients with a mental disorder should not be discriminated against. 1 The current legal test of capacity and the criteria of capacity in the forthcoming mental capacity act in England and Wales largely focus …
Differential Regulation of Circulating Mg <sup>2+</sup> in the Rat by β <sub>1</sub> - and β <sub>2</sub> -Adrenergic Receptor Stimulation
Authors: D. Keenan, A. Romani, A. Scarpa
Journal: Circulation Research (1995)

Abstract Extracellular Mg 2+ homeostasis was studied in vivo in the anesthetized rat. Animals were infused with isoproterenol (ISO) for 10 minutes, and serum Mg 2+ was measured after the infusion and then 10 and 20 minutes later. A dose-dependent increase in circulating Mg 2+ was observed in animals infused with ISO at a rate of 0.1 μg · kg −1 · min −1 or higher. The time course of the effect demonstrated that circulating Mg 2+ continued to increase 20 minutes after the end of the ISO infusion. A predicted maximal increase in serum Mg 2+ concentration of 19.3% was derived with a predicted EC 50 of 0.08 μg · kg −1 · min −1 . The maximal percent increase corresponded to a net increase of 6.7 μmol/300 g body wt. Because infusion of ISO resulted in changes in hemodynamic parameters, most notably a drop in blood pressure, a group of animals was infused with nitroprusside to mimic the hypotensive response via a nonadrenergic mechanism. Under these conditions, there was a transient increase in circulating Mg 2+ that was largely inhibited by propranolol, indicating that hypotension per se was not responsible for the mobilization of Mg 2+ . Infusion of salbutamol, but not prenalterol, also induced an increase in circulating Mg 2+ . Pretreatment with butoxamine, ICI-118551, or propranolol prevented the ISO-induced increase in serum Mg 2+ . Pretreatment with atenolol minimally affected the ISO-induced changes in circulating Mg 2+ . Pretreatment with CGP-20271A actually enhanced the ISO-induced increase in circulating Mg 2+ . This evidence demonstrates the existence of a pool of Mg 2+ that is mobilized into the circulation in response to selective β 2 -adrenergic stimulation.
Effect of brachial plexus co-activation on phrenic nerve conduction time
Authors: Y M Luo, M I Polkey, R A Lyall, J Moxham
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Diaphragm function can be assessed by electromyography of the diaphragm during electrical phrenic nerve stimulation (ES). Whether phrenic nerve conduction time (PNCT) and diaphragm electrical activity can be reliably measured from chest wall electrodes with ES is uncertain. <h3>METHODS</h3> The diaphragm compound muscle action potential (CMAP) was recorded using an oesophageal electrode and lower chest wall electrodes during ES in six normal subjects. Two patients with bilateral diaphragm paralysis were also studied. Stimulations were deliberately given in a manner designed to avoid or incur co-activation of the brachial plexus. <h3>RESULTS</h3> For the oesophageal electrode the PNCT was similar with both stimulation techniques with mean (SE) values of 7.1 (0.2) and 6.8 (0.2) ms, respectively (pooled left and right values). However, for surface electrodes the PNCT was substantially shorter when the brachial plexus was activated (4.4 (0.1) ms) than when it was not (7.4 (0.2) ms) (mean difference 3.0 ms, 95% CI 2.7 to 3.4, p&lt;0.0001). A small short latency CMAP was recorded from the lower chest wall electrodes during stimulation of the brachial plexus alone. <h3>CONCLUSIONS</h3> The results of this study show that lower chest wall electrodes only accurately measure PNCT when care is taken to avoid stimulating the brachial plexus. A false positive CMAP response to phrenic stimulation could be caused by inadvertent stimulation of the brachial plexus. This finding may further explain why the diaphragm CMAP recorded from chest wall electrodes can be unreliable with cervical magnetic stimulation during which brachial plexus activation occurs.
Laser Warning Sign
Authors: Jack De Ment, John P. Jarabak, Nilkanth M. PHATAK, Thorn Kinersly
Journal: JAMA (1964)

<h3>To the Editor:—</h3> Some 500 groups in the United States—involving as many as several thousand people—now work with lasers.<sup>1</sup>Many investigators are apparently unaware of, or scantily appreciate, the energy levels of such devices. However, there is increasing concern about the little-known dangers from acute, and especially<i>chronic</i>, exposure to laser light or coherent radiation,<sup>2,3</sup>including visual impairment and laser-induced blindness. The need for knowledge about these hazards applies, in particular, to those personnel outside the biosciences. We propose as an analog of the universally used, recognized, and accepted radioactivity warning sign<i>a standard laser-light warning sign</i>. This is an appropriate and distinctive laser symbol together with the word CAUTION or DANGER above that symbol and the expression LASER LIGHT below the device. The sign is simple and can be of any convenient size. The warning symbol has an arrow representing laser light emitted from a stylized trumpet-like
The Guardian's Little Helper: MicroRNAs in the p53 Tumor Suppressor Network
Authors: Xingyue He, Lin He, Gregory J. Hannon
Journal: Cancer Research (2007)

Abstract Several microRNAs (miRNAs) have been implicated in tumor development based on both changes in their expression patterns and gene structural alterations in human tumors. However, we are only now beginning to see how miRNAs interact with classic oncogene and tumor suppressor mechanisms. Several recent studies have implicated the miR-34 family of miRNAs in the p53 tumor suppressor network. The expression of miR-34a, miR-34b, and miR-34c is robustly induced by DNA damage and oncogenic stress in a p53-dependent manner. When overexpressed, miR-34 leads to apoptosis or cellular senescence, whereas reduction of miR-34 function attenuates p53-mediated cell death. These findings, together with the fact that miR-34 is down-regulated in several types of human cancer, show that miRNAs can affect tumorigenesis by working within the confines of well-known tumor suppressor pathways. [Cancer Res 2007;67(23):11099–101]
Alterations in vascular smooth muscle mass in the spontaneously hypertensive rat. Role of cellular hypertrophy, hyperploidy, and hyperplasia.
Authors: G K Owens, S M Schwartz
Journal: Circulation Research (1982)

In a previous brief report we demonstrated that differences in aortic smooth muscle mass between spontaneously hypertensive and Wistar-Kyoto rats were due to smooth muscle cell hypertrophy, without hyperplasia. Smooth muscle cell hypertrophy, however, was accompanied by an increase in the frequency of polyploid cells. This study reports (1) the relationship between changes in smooth muscle cell mass and DNA ploidy, (2) the proportion of the increase in mass of smooth muscle in spontaneously hypertensive rats that can be accounted for by polyploid cells, and (3) the time-course of changes in ploidy during the development of hypertension. Flow microfluorimetric and Feulgen-DNA microspectrophotometric measurements demonstrated that the frequency of polyploid smooth muscle cells was 2-3 times greater in spontaneously hypertensive rats than in Wistar-Kyoto rats at 3 months of age and older. The frequency of polyploid cells increased with age and level of blood pressure. No differences in the frequency of polyploid cells were apparent between prehypertensive 1-month spontaneously hypertensive and Wistar-Kyoto rats. By cytospectrophotometric analysis, spontaneously hypertensive rat diploid, tetraploid, and octaploid smooth muscle cells had 36%, 136%, and 377%, respectively, the protein content of Wistar-Kyoto rat diploid cells. The increase in mean cellular protein (53% by cystospectrophotometry) in spontaneously hypertensive rats could account for the total increase (56%) in aortic smooth muscle mass, measured by morphometry. Thus, smooth muscle cell hypertrophy alone can account for the increased mass of smooth muscle in spontaneously hypertensive rat aortas, while the majority of change in smooth muscle mass is due to the increased frequency and mass of polyploid cells.
Exhaled nitric oxide in contrasting population samples of Finnish and Russian Karelia
Authors: L. P. Malmberg, T. Laatikainen, L. von Hertzen, M. J. Mäkelä, E. Vartiainen, T. Haahtela
Journal: European Respiratory Journal (2010)

To the Editors: 

Considerable differences between countries in prevalence of asthma and atopy have been reported that show association between increased risk and western lifestyle and urbanisation 1. The allergy substudy of the National FINRISK Study and the Karelia Allergy Study, both carried out in North Karelia, Finland, and the Pitkaranta region, Russia, revealed a significantly higher occurrence of asthma and atopic diseases on the Finnish side, the disparity showing a growing generational trend 2, 3. Despite the geographical neighbourhood, the sensitisation rates for airborne allergens, determined with skin-prick tests or specific immunoglobulin (Ig)E levels, were four-fold in children and two- to three-fold in adults from Finnish Karelia, which may be attributed to the higher level of urbanisation, western type of living conditions and poor microbial environment 4.

Exhaled nitric oxide (eNO) is a noninvasive marker of airway inflammation, and is usually increased in patients with asthma. eNO is strongly associated with atopy in population-based studies 5–9. Also, many other factors, such as sex and anthropometric dimensions, tobacco smoking and acute respiratory infections, have been reported to influence eNO levels. To date, there are no reports of the differences in eNO levels between populations with different degrees of urbanisation and living conditions. We postulated that different atopic prevalences between Finnish and Russian Karelia might be reflected in the levels as well as the determinants of eNO. Therefore, in the Karelia Allergy follow-up study in 2007, we measured eNO levels in adult population samples from Finnish and Russian Karelia, and investigated the effect of several demographic, disease-related and environmental factors.

Random samples of adults aged 25–54 yrs were drawn from the population register and electoral rolls in Finnish and Russian Karelia, with …
Severe hypersensitivity reaction to fenbufen.
Authors: M. M. Muthiah
Journal: BMJ (1988)

Our patient had no features of phenytoin toxicity despite a concentration of 31-3 mg/I.After starting tolbutamide the phenytoin concentration decreased to 27-4 mg/I.The total concentration was measured, not the free level.Neither the Committee on Safety of Medicines nor the manufacturer knows of any other cases of phenytoin toxicity produced by tolbutamide.
Clinical experience with Ibuprofen in the treatment of rheumatoid arthritis.
Authors: T M Chalmers
Journal: Annals of the Rheumatic Diseases (1969)

The search continues for a compound with the anti-inflammatory and analgesic properties of aspirin, but without its occasionally troublesome side-effects.Ibuprofen (2-4'-isobutylphenylpropionic acid) is the latest member of a series of phenylalkanoic acids to be submitted for clinical trial.Boardman, Nuki, and Dudley Hart (1967) con- cluded that in twenty patients with rheumatoid arthritis Ibuprofen, when given in a daily dosage of 0-9 g., did not exhibit a significant therapeutic effect when compared with placebo.Similarly, in nine- teen patients with osteoarthritis, these authors found that clinically significant improvement was not obtained when Ibuprofen was given in a daily dosage of 0 6 g. daily for 14 days.Thompson, Fox, and Newell (1967), however, reported that Ibuprofen, in daily dosages of up to 0-6 g., was effective in relieving pain and morning stiffness in patients with rheumatoid arthritis, and useful for patients unable to take aspirin because of dyspepsia.The purpose of this paper is to report the results of the initial pilot trials of Ibuprofen in the treatment of patients with rheumatoid arthritis, together with a review of the effects of long-term administration of the drug. MethodsIbuprofen was given to six in-patients in each of two short clinical trials, and subsequently substituted for aspirin for maintenance therapy in a group of 27 outpatients.(1) In-Patient Trial Six patients, each with classical or definite rheumatoid arthritis as defined by the diagnostic criteria of the American Rheumatism Association (Ropes, Bennett,
THE INTERACTION OF TWO FRAGMENTS OF PULSATING HEART TISSUE
Authors: Albert Fischer
Journal: The Journal of Experimental Medicine (1924)

Fragments of heart from the same species, when cultivated in vitro, are capable of uniting and pulsating synchronously. This happens not only in fragments derived from the same heart but with those from different individuals of the same species. It was not possible, on the other hand, to obtain, under the conditions of experiment, any physiological union of a heart fragment from a duck embryo with one from a chicken embryo, though both pulsated in the same medium and though the tissue cells of the duck were capable of growth and multiplication. From the experiments it is evident that cell contact is essential for the development of physiological identity as just described. Since such a physiological identity cannot be obtained through the union of a fragment of a duck heart and a fragment of a chicken heart, one may suppose that anastomosis between the cells must play a very significant rôle in it.
Prospective analysis of creatine kinase muscle-brain fraction and comparison with troponin T to predict cardiac risk and benefit of an invasive strategy in patients with non–ST-elevation acute coronary syndromes
Authors: Neal S Kleiman, Nasser Lakkis, Christopher P Cannon, Sabina A Murphy, Peter M DiBattiste, Laura A Demopoulos, William S Weintraub, Eugene Braunwald
Journal: Journal of the American College of Cardiology (2002)
THE ROLE OF TEMPERATE BACTERIOPHAGE IN THE PRODUCTION OF ERYTHROGENIC TOXIN BY GROUP A STREPTOCOCCI
Authors: John B. Zabriskie
Journal: The Journal of Experimental Medicine (1964)

Non-lysogenic, non-toxinogenic Group A streptococci when infected by temperate bacteriophages isolated from known scarlatinal toxin-producing strains acquire the capacity to form erythrogenic toxin. This toxin causes a characteristic erythematous reaction in the skin of rabbits and is readily neutralizable by standard scarlatinal antitoxins. The production of toxin appears to be related to the synthesis of mature phage particles since ultraviolet enhancement of phage production results in a concomitant increase in toxin titer. In contrast, there is no increase in the production of another extracellular product, deoxyribonuclease, by these lysogenized streptococci. Furthermore, cellular disruption studies indicate that the toxin probably does not exist in a preformed state within the cell. Double diffusion reactions in agar indicate that a newly formed protein appears in the lysogenic culture filtrate and is absent in the non-lysogenic filtrates.
Gonorrhoea presenting as "sterile" pyuria.
Authors: M Clarke, R Maskell
Journal: BMJ (1981)

histolytica.3We feel it is important that there should be an awareness of the possibility that amoebiasis may exist in homosexual patients presenting with diarrhoea, since this may be misdiagnosed as inflammatory bowel disease and corticosteroids would be inappropriate in such cases and might result in fulminant amoebic infection.7