tbuckley/cabot-search huggingface dataset:
Airway stents provide symptomatic relief
Authors: P Macedo
Journal: Thorax (2003)

▴ Wood DE, Liu Y, Vallières E, et al. Airway stenting for malignant and benign tracheobronchial stenosis. Ann Thorac Surg2003;76:167–74[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] This paper reports the indications, techniques, and results of tracheobronchial stenting in the authors’ unit. One hundred and forty three patients underwent 309 stent procedures between May … [1]: {openurl}?query=rft.jtitle%253DThe%2BAnnals%2Bof%2BThoracic%2BSurgery%26rft.stitle%253DAnn.%2BThorac.%2BSurg.%26rft.aulast%253DWood%26rft.auinit1%253DD.%2BE.%26rft.volume%253D76%26rft.issue%253D1%26rft.spage%253D167%26rft.epage%253D174%26rft.atitle%253DAirway%2Bstenting%2Bfor%2Bmalignant%2Band%2Bbenign%2Btracheobronchial%2Bstenosis%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0003-4975%252803%252900033-X%26rft_id%253Dinfo%253Apmid%252F12842534%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/S0003-4975(03)00033-X&link_type=DOI [3]: /lookup/external-ref?access_num=12842534&link_type=MED&atom=%2Fthoraxjnl%2F58%2F10%2F900.atom [4]: /lookup/external-ref?access_num=000183968400035&link_type=ISI
Flavonoids as RTK inhibitors and potential anticancer agents
Authors: Florence Teillet, Ahcene Boumendjel, Jean Boutonnat, Xavier Ronot
Journal: Medicinal Research Reviews (2007)

Abstract Tyrosine kinase receptors (RTKs) play a crucial role in the regulation of the cell division cycle. Currently more than 50 RTKs divided into several subfamilies have been described. The inhibition of these enzymes has emerged as an important research‐area. Compounds able to inhibit the activity of these enzymes are expected to display antiproliferative properties. Flavonoids are representative of various small molecules acting as RTK inhibitors. These naturally occurring compounds are able to bind to the ATP‐binding site of several kinases. The most plausible current hypothesis explaining the action of these substances on kinases is that the chromenone moiety of the flavonoid acts as a mimetic of the adenine moiety of ATP, the receptor co‐factor. In this review, we report recent results on the activity of natural and synthetic derivatives of flavonoids as inhibitors of RTKs. Mechanistic aspects, the therapeutic usefulness, and the potential clinical use are discussed. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 5, 715–745, 2008
Fixed drug eruption masquerading as herpes simplex labialis.
Authors: J Boyle, B Moul
Journal: BMJ (1984)

The correlation between Pao2 and serum concentrations of testosterone, FSH, thyroid hormones, and hormone binding globulins suggests a causal association.Normal basal LH and FSH concentrations and normal pituitary responses to injected GnRH in this case and patients with respiratory disease3 suggest hypothalamic suppression, though additional hypoxic testicular suppression seems possible.While thyroid hormone values tended to increase with improved Pao2 the rise was less than with testosterone, and in respiratory disease also the hypothalamopituitary-testicular axis seems to be particularly sensitive to hypoxia.Absent TSH responses to injected TRH before weight reduction and their return to normal after diet along with a rise in serum thyroxine concentration suggested reversible pituitary suppression of TSH even though serum thyroxine values were normal throughout.These normal values were also found in occasional in- stances in our patients with respiratory disease3 in the presence of pituitary suppression of TSH.
Biosynthesis of bile acids in man. Hydroxylation of the C27-steroid side chain.
Authors: I Björkhem, J Gustafsson, G Johansson, B Persson
Journal: Journal of Clinical Investigation (1975)

The first step in the degradation of the steroid side chain during biosynthesis of bile acids from cholesterol in man was studied in microsomal and mitochondrial fraction of homogenate of livers from 14 patients. The microsomal fraction was found to catalyze an efficient 25-hydroxylation of 5,8-cholestane-3a,7a,12atriol. A small extent of 23-, 24-, and 26-hydroxylation of the same substrate was observed. 53-Cholestane-3a,7adiol was hydroxylated in the 25-position only to a very small extent. The mitochondrial fraction was found to catalyze 26-hydroxylation of cholesterol, 5-cholestene-3P,7a-diol, 5P-cholestane-3a,7a-diol, 7a-hydroxy-4-cholesten-3-one, and 5,0-cholestane-3a,7a,12a-triol. Addition of Mg++ stimulated the 26-hydroxylation of cholesterol but had no effect or an inhibitory effect on 26-hydroxylation of the other substrates, indicating a heterogeneity of the mitochondrial 26-hydroxylating system. The level of 26-hydroxylase activity towards different substrates varied considerably with different mitochondrial preparations. The roles of the microsomal and mitochondrial 26- hydroxylations as well as the microsomal 25-hydroxylation in biosynthesis of bile acids in man are discussed. The results indicate that microsomal 26-hydroxylation is less important than mitochondrial 26-hydroxylation under normal conditions. The possibility that microsomal 25-hydroxylation is important cannot be ruled out.
Minister steps in to meet new deal targets
Authors: L Beecham
Journal: BMJ (1994)

The minister for health, Mr Gerald Malone, is urging NHS trusts and health authorities to “step up the momentum” to meet the targets on junior doctors' hours. The next target date is 31 December, when no doctor should be contracted to work more than 72 hours on an on call rota in hard pressed posts. Such posts, Mr Malone says, are “no longer tolerable.”

From 1 January 1995 many of the targets, especially those related to contracted hours, become part of junior doctors' terms and conditions of service, and trusts and authorities will have to ensure that the contractual obligations are met. The minister emphasises that this must not be a paper exercise. “Changes in contracts must genuinely reflect reductions in rostered hours and in hours of work or work intensity.” It was not acceptable “to achieve reductions at the expense of services to patients or to rely on unauthorised extra junior doctor posts of questionable educational value.”

The minister wants junior doctors to be involved in collecting and validating data and for regional task forces to report to him if they meet any problems. He also wants to see evidence in the coming year that trusts and their purchasers are cooperating in delivering care through consultant based services. In the next 12 months the Audit Commission will be visiting trusts to examine reductions in hours and improvements in living conditions.

Senior hospital doctors are worried about the lack of opportunities for giving medical advice in the streamlined NHS. Last week the Central Consultants and Specialists Committee approved comments on …
A Case of Haemophilia
Authors: C. R. Francis
Journal: BMJ (1882)

It has recently been proposed that post-translational modification of not only the M3–M4 linker but also the M1–M2 linker of pentameric ligand-gated ion channels modulates function <i>in vivo</i>. To estimate the involvement of the M1–M2 linker in gating and desensitization, we engineered a series of mutations to this linker of the human adult-muscle acetylcholine receptor (AChR), the α3β4 AChR and the homomeric α1 glycine receptor (GlyR). All tested M1–M2 linker mutations had little effect on the kinetics of deactivation or desensitization compared with the effects of mutations to the M2 α-helix or the extracellular M2–M3 linker. However, when the effects of mutations were assessed with 50 Hz trains of ∼1 ms pulses of saturating neurotransmitter, some mutations led to much more, and others to much less, peak-current depression than observed for the wild-type channels, suggesting that these mutations could affect the fidelity of fast synaptic transmission. Nevertheless, no mutation to this linker could mimic the irreversible loss of responsiveness reported to result from the oxidation of the M1–M2 linker cysteines of the α3 AChR subunit. We also replaced the M3–M4 linker of the α1 GlyR with much shorter peptides and found that none of these extensive changes affects channel deactivation strongly or reduces the marked variability in desensitization kinetics that characterizes the wild-type channel. However, we found that these large mutations to the M3–M4 linker can have pronounced effects on desensitization kinetics, supporting the notion that its post-translational modification could indeed modulate α1 GlyR behavior.
Twenty-First Annual Pezcoller Symposium: Unconventional Therapeutic Targets in Cancer
Authors: Enrico Mihich, Pier Paolo Pandolfi, David Livingston
Journal: Cancer Research (2009)

The 21st Pezcoller Symposium, entitled “Unconventional Therapeutic Targets in Cancer,” was held in Trento, Italy, on June 11–13, 2009. The focus of the Symposium was on identifying nontraditional targets for anticancer drug action and using new concepts for drug development.

Sean Morrison (
False-Positive I-131 Uptake at a Tracheostomy Site Discernment With TI-201 Imaging
Authors: KENNETH B. AIN, WEI-JEN SHIH
Journal: Clinical Nuclear Medicine (1994)

I-131 whole-body imaging is used in the follow-up evaluation of differentiated thyroid carcinoma. The authors report a case of spurious I-131 localization at a patient's tracheostomy stoma. Demonstration of this I-131 uptake as false positive was achieved by showing no TI-201 localization at this site and a low thyroglobulin while the patient was hypothyroid. This strategy may discern spurious I-131 uptake and help avoid unnecessary I-131 therapy.
Sympathetic-Block Persistence After Spinal or Epidural Analgesia
Authors: Felisaring G. Daos
Journal: JAMA (1963)

A PATIENT who had received an epidural block for a surgical procedure was observed to have gained return of both motor and sensory functions, so was permitted to become ambulatory. However, the patient fainted when he stood up. A possible explanation of this phenomenon is that sympathetic function, which might have produced vasoconstriction and prevented pooling of blood in the lower extremities, was still blocked. To learn whether or not this might have been true, a series of measurements of duration of loss of motor, sensory, and sympathetic functions following blocks of the lower part of the body were made. <h3>Method</h3> Ninety-six patients who were to have regional analgesia for surgical procedures were studied. Forty-two of these had epidural anesthesia, and 54 had spinal blocks. The psychogalvanic reflex (PGR), which "is a definite indication of whether or not a sympathetic nerve block, either chemical or surgical has been obtained,"<sup>1,2</sup>
The impact of ageing on natural killer cell function and potential consequences for health in older adults
Authors: Jon Hazeldine, Janet M. Lord
Journal: Ageing Research Reviews (2013)

Forming the first line of defence against virally infected and malignant cells, natural killer (NK) cells are critical effector cells of the innate immune system. With age, significant impairments have been reported in the two main mechanisms by which NK cells confer host protection: direct cytotoxicity and the secretion of immunoregulatory cytokines and chemokines. In elderly subjects, decreased NK cell activity has been shown to be associated with an increased incidence and severity of viral infection, highlighting the clinical implications that age-associated changes in NK cell biology have on the health of older adults. However, is an increased susceptibility to viral infection the only consequence of these age-related changes in NK cell function? Recently, evidence has emerged that has shown that in addition to eliminating transformed cells, NK cells are involved in many other biological processes such as immune regulation, anti-microbial immune responses and the recognition and elimination of senescent cells, novel functions that involve NK-mediated cytotoxicity and/or cytokine production. Thus, the decrease in NK cell function that accompanies physiological ageing is likely to have wider implications for the health of older adults than originally thought. Here, we give a detailed description of the changes in NK cell biology that accompany human ageing and propose that certain features of the ageing process such as: (i) the increased reactivation rates of latent Mycobacterium tuberculosis, (ii) the slower resolution of inflammatory responses and (iii) the increased incidence of bacterial and fungal infection are attributable in part to an age-associated decline in NK cell function.
The effect of size and age of subject on airway responsiveness in children.
Authors: P N Le Souëf, M R Sears, D Sherrill
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Methodologies used to assess airway responsiveness (AR) in children administer the same dosage schedule to all children despite the great range in the size of subjects. The aim of this study was to examine the hypothesis that the level of AR is size dependent within same-age cohorts and between different ages. Among a birth cohort of 1,037 New Zealand children participating in a longitudinal study, 818 had at least two measurements of airway responsiveness between ages 9 and 15 yr. Each child performed spirometry and a four-dose methacholine inhalation test. A continuous slope index of methacholine responsiveness was computed. AR slope indexes were analyzed using longitudinal methods, which included an indicator variable for subjects who reported having any wheeze. AR was lowest in both males and females in the upper quartile for height than those in the lower quartile, independently of age. AR tended to be higher (responded to lower concentrations of methacholine) in boys than girls and to decline with age among wheezers. The greater level of responsiveness in smaller or younger children could be explained by these individuals having received a dose of methacholine that was relatively large for their size.
Australia exports an academic-powered news website to the UK
Authors: M. Sweet
Journal: BMJ (2013)

The Conversation, an academic-powered news and commentary website that began in Australia two years ago, is due to be launched in the United Kingdom in May, with the support of the research and university sector.

Billed as combining “academic rigour and journalistic flair,” the Australian website (http://theconversation.com/au) has had wide ranging, in-depth coverage of health, medicine and science, including series on death and dying, climate change, overdiagnosis, and transparency in medicine.

Thirteen UK universities are supporting the launch of The Conversation UK, a not for profit company based in London, which will operate in partnership with the Melbourne based charity.

Also supporting the UK venture are the Wellcome Trust, the Nuffield Foundation, the Higher Education Funding Council for England, the Higher Education Funding Council for Wales, and the Scottish Funding Council.

In Australia, …
EFFECT OF N-3 POLYUNSATURATED FATTY ACIDS AND ROSUVASTATIN ON LEFT VENTRICULAR FUNCTION IN PATIENTS WITH CHRONIC HEART FAILURE. A SUBSTUDY OF THE GISSI-HF TRIAL
Authors: Stefano Ghio, Laura Scelsi, Ermanno Eleuteri, Michela Palvarini, Olga Vriz, Serge Masson, Renato Urso, Roberto Latini, Michele Pasotti, Gianni Tognoni, Luigi Tavazzi, Stefano Ghio
Journal: Journal of the American College of Cardiology (2010)
Developing without concepts
Authors: Yevdokiya Yermolayeva, David H. Rakison
Journal: Behavioral and Brain Sciences (2010)

Abstract We evaluate the heterogeneity hypothesis by considering the developmental time course and the mechanism of acquisition of exemplars, prototypes, and theories. We argue that behavioral and modeling data point to a sequential emergence of these three types of concepts within a single system. This suggests that similar or identical underlying cognitive processes – rather than separate ones – underpin representation acquisition.
Breast Cancer Detection by B7-H3–Targeted Ultrasound Molecular Imaging
Authors: Sunitha V. Bachawal, Kristin C. Jensen, Katheryne E. Wilson, Lu Tian, Amelie M. Lutz, Jürgen K. Willmann
Journal: Cancer Research (2015)

Abstract Ultrasound complements mammography as an imaging modality for breast cancer detection, especially in patients with dense breast tissue, but its utility is limited by low diagnostic accuracy. One emerging molecular tool to address this limitation involves contrast-enhanced ultrasound using microbubbles targeted to molecular signatures on tumor neovasculature. In this study, we illustrate how tumor vascular expression of B7-H3 (CD276), a member of the B7 family of ligands for T-cell coregulatory receptors, can be incorporated into an ultrasound method that can distinguish normal, benign, precursor, and malignant breast pathologies for diagnostic purposes. Through an IHC analysis of 248 human breast specimens, we found that vascular expression of B7-H3 was selectively and significantly higher in breast cancer tissues. B7-H3 immunostaining on blood vessels distinguished benign/precursors from malignant lesions with high diagnostic accuracy in human specimens. In a transgenic mouse model of cancer, the B7-H3–targeted ultrasound imaging signal was increased significantly in breast cancer tissues and highly correlated with ex vivo expression levels of B7-H3 on quantitative immunofluorescence. Our findings offer a preclinical proof of concept for the use of B7-H3–targeted ultrasound molecular imaging as a tool to improve the diagnostic accuracy of breast cancer detection in patients. Cancer Res; 75(12); 2501–9. ©2015 AACR.
Regulation by fasting of rat insulin-like growth factor I and its receptor. Effects on gene expression and binding.
Authors: W L Lowe, M Adamo, H Werner, C T Roberts, D LeRoith
Journal: Journal of Clinical Investigation (1989)

We have examined, in liver and extrahepatic tissues, the effects of fasting on total insulin-like growth factor I (IGF-I) mRNA levels, on levels of different IGF-I mRNAs generated by alternative splicing of the primary IGF-I transcript, and on IGF-I receptor binding and mRNA levels. A 48-h fast decreased total IGF-I mRNA levels by approximately 80% in lung and liver, approximately 60% in kidney and muscle, and only approximately 30-40% in stomach, brain, and testes. In heart, IGF-I mRNA levels did not change. The levels of the different splicing variants, however, were essentially coordinately regulated within a given tissue. Specific 125I-IGF-I binding in lung, testes, stomach, kidney, and heart was increased by fasting by approximately 30-100%, whereas in brain 125I-IGF-I binding did not change in response to fasting. In tissues in which fasting increased IGF-I receptor number, receptor mRNA levels increased approximately 1.6- to 2.5-fold, whereas when IGF-I receptor number was unchanged in response to fasting, receptor mRNA levels did not change. These data demonstrate that the change in IGF-I and IGF-I receptor mRNA levels during fasting is quantitatively different in different tissues and suggest that regulation of IGF-I and IGF-I receptor gene expression by fasting is discoordinate.
Eradication of wild poliovirus type 3 may be within reach, say CDC and WHO
Authors: M. McCarthy
Journal: BMJ (2014)

No cases of wild poliovirus type 3 (WPV3) have been detected for two years, indicating that transmission has been interrupted and that the virus may have been eradicated, says a new report from the US Centers for Disease Control and Prevention (CDC) and the World Health Organization.

The report1 said that the last known case of WPV3 was isolated from an 11 month old infant in Yobe, Nigeria, who had onset of paralysis on 10 November 2012, and the latest environmental isolate came from a sample collected the next day in Lagos, Nigeria.

“This virus has disappeared, and we think it may …
Construction and Preclinical Characterization of Fc-mGITRL for the Immunotherapy of Cancer
Authors: Peisheng Hu, Robyn S. Arias, Rebecca E. Sadun, Yu-Chih Nien, Nan Zhang, Helen Sabzevari, M.E. Christine Lutsiak, Leslie A. Khawli, Alan L. Epstein
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To provide proper costimulation required for effective cancer T-cell immunity, Fc-GITRL fusion proteins were generated for use in immunotherapy protocols. Experimental Design: Soluble fusion proteins consisting of the Fc fragment of immunoglobulin and the murine glucocorticoid-induced tumor necrosis factor–related receptor ligand (mGITRL) connected with different linkers were genetically engineered and tested for their potency in two BALB/c solid tumor models. Results: In vivo, construct #178-14 (−5aa, −linker) showed the best activity (&amp;gt;90% tumor reduction) at doses ranging from 5 to 25 μg and was found to be intact by gel electrophoresis. Similar doses used with construct #175-2 (-linker) produced good but not as high tumor regression. Construct #5-1 (+linker), which was found to be relatively unstable by SDS gel electrophoresis, produced &amp;lt;60% tumor regression and required a higher dose (100 μg) to produce optimal results. Survival curves showed that Fc-mGITRL treatment extended the life of 80% of tumor-bearing mice to &amp;gt;3 months compared with controls that died by day 40. T-cell depletion studies showed that CD8+ T cells play a major role in Fc-mGITRL immunotherapy, and tumors removed from Fc-mGITRL– and DTA-1–treated mice showed a significant influx of granzyme B+ lymphocytes compared with controls. Finally, T regulatory (Treg) cell assays showed that, unlike other Fc fusion proteins, all three Fc-mGITRL constructs profoundly suppressed Treg activity. Conclusions: These studies suggest that a stable, intact Fc-mGITRL fusion protein can provide missing costimulation for the immunotherapy of solid tumors. In addition, Fc-mGITRL may alter Treg activity to enhance its effectiveness for tumor immunotherapy.
Relief of Chest Pain by Tetraethylammonium Chloride
Authors: Harold L. Israel, Earle L. Keeter, Frederic E. Urbach, William D. Willis
Journal: New England Journal of Medicine (1949)

THE intravenous administration of tetraethylammonium chloride to a patient acutely ill with thrombophlebitis and pulmonary infarction unexpectedly relieved the patient's severe pleuritic pain. As a result of this observation, the effect of tetraethylammonium administration has been studied in other patients with chest pain.The present report concerns observations made on 35 male and 5 female patients with chest pain due to infarction, trauma, pneumonia, pleuritis, tuberculosis, neoplasm, mediastinal emphysema or myocardial infarction.Tetraethylammonium chloride was given intravenously, each cubic centimeter of solution containing 100 mg. of the drug. Syringe injection was made slowly, while the blood pressure was being measured . . .