tbuckley/cabot-search huggingface dataset:
The Tumor Suppressor LKB1 Regulates Lung Cancer Cell Polarity by Mediating cdc42 Recruitment and Activity
Authors: Shumin Zhang, Katherine Schafer-Hales, Fadlo R. Khuri, Wei Zhou, Paula M. Vertino, Adam I. Marcus
Journal: Cancer Research (2008)

Abstract The tumor suppressor LKB1 is mutated in 30% of non–small cell lung cancer (NSCLC) tumors and cell lines and is proposed to be a key regulator of epithelial cell polarity; however, how LKB1 regulates cancer cell polarity is not known. The experiments described herein show for the first time that LKB1 is a dynamic, actin-associated protein that rapidly polarizes to the leading edge of motile cancer cells. LKB1 proves to be essential for NSCLC polarity, because LKB1 depletion results in classic cell polarity defects, such as aberrant Golgi positioning, reduced lamellipodia formation, and aberrant morphology. To probe how LKB1 regulates these events, we show that LKB1 colocalizes at the cellular leading edge with two key components of the polarity pathway — the small rho GTPase cdc42 and its downstream binding partner p21-activated kinase (PAK). Importantly, LKB1 functionality is required for cdc42 polarization to the leading edge, maintaining active cdc42 levels, and downstream PAK phosphorylation. To do this, LKB1 interacts only with active form of cdc42 and PAK, but not with inactive cdc42. Taken together, these results show that LKB1 is a critical mediator of the NSCLC polarity program in lung cancer cells through a novel LKB1-cdc42-PAK pathway. [Cancer Res 2008;68(3):740–8]
Treatment of the bronchial tree from beginning to end: targeting small airway inflammation in asthma
Authors: M. van den Berge, N. H. T. ten Hacken, E. van der Wiel, D. S. Postma
Journal: Allergy (2012)

Asthma is a chronic respiratory disease, characterized by airway obstruction and inflammation. Increasing evidence shows that the small airways contribute significantly to the clinical expression and severity of asthma. Traditionally, high levels of disease activity are thought to be necessary before symptoms occur in the small airways because of their large reserve capacity. However, this concept is being challenged and increasing evidence shows small airway disease to be associated with symptoms, disease severity, and bronchial hyper-responsiveness. Particle size and distribution are of key importance when developing inhaled treatments for small airway disease. The availability of small-particle aerosols such as HFA-ciclesonide and HFA-beclomethasone dipropionate (HFA-BDP) enables a higher drug deposition into the peripheral lung and potentially provides additional clinical benefits compared with large-particle treatment. However, improved methods are needed to monitor and assess small airway disease and its response to treatment because conventional spirometry mainly reflects large airway function. This remains a challenging area requiring further research. The aim of the current manuscript is to review the clinical relevance of small airway disease and the implications for the treatment of asthma.
Making Doctors: An Institutional Apprenticeship
Authors: S. Wessely
Journal: BMJ (1998)

Simon Sinclair Berg, £14.99, pp 347 ISBN 1 85973 955 5

Read this book. It is written by a qualified doctor who interrupted his career to study anthropology and undertook his field work by returning to medical school to observe the habits and dispositions of those who study and work there. It is in turn fascinating, nostalgic, and, ultimately, depressing.

Simon Sinclair has produced a masterful account of rites of passage, a study of initiation in which the raw recruits enter medical school and progress through its various nooks and crannies to exit as members of the tribe some five years later. During that time they acquire knowledge (a little), take part in rituals (several), and acquire attitudes (a lot). This is called medical education.

Sinclair observes the formal …
Everyday memory and activity
Authors: Richard Alterman
Journal: Behavioral and Brain Sciences (1996)

Abstract The target article interprets current psychological research on everyday memory in terms of a correspondence metaphor. This metaphor is based on a reduction of everyday memory to autobiographical and eyewitness memory. This commentary focuses on everyday memory as it functions in activity. Viewed from this perspective, the joining of everyday memory to a correspondence metaphor is problematic. A more natural way to frame the processes of everyday memory is in terms of context, practice, and pragmatics.
Retinal Nerve Fiber Layer Damage as Assessed by Optical Coherence Tomography in Eyes with a Visual Field Defect Detectedby Frequency Doubling Technology Perimetry but Not by Standard Automated Perimetry
Authors: Tae-Woo Kim, Linda M. Zangwill, Christopher Bowd, Pamela A. Sample, Neha Shah, Robert N. Weinreb
Journal: Ophthalmology (2007)
Thakorlal Vallabhdas Raivadera
Authors: Shreekant Raivadera
Journal: BMJ (2004)

Former general practitioner Birstall, Leicestershire (b Uganda 1934; q Mumbai, India, 1962), d 5 August 2004.​2004.




Figure 1




While he was studying medicine in Mumbai he met his future wife, Dr Suneeti Raivadera, who continues to work as a general practitioner in the village of Birstall. The family came to the United Kingdom as part of the 1972 exodus from Uganda, when the dictator Idi Amin expelled the Asians. The couple cared for patients in and around the village for over 28 years and were also casualty doctors at Loughborough Hospital.
Histochemical examination of energy metabolism in aortic vein grafts in rats
Authors: V. REMES, K. VON SMITTEN, T. WARIS, J. RAEKALLIO
Journal: Cardiovascular Research (1986)

The duration of the presumed metabolic depression of syngeneic vena cava to aorta transplants was determined in rats and the site and type of energy metabolism in the vein grafts assessed. The aerobic metabolic activity was measured from the histochemical reactivity of the enzymes, succinate dehydrogenase and cytochrome oxidase, and the anaerobic activity by staining with lactate dehydrogenase. The activity of the hexose-monophosphate shunt was assessed by the histochemical demonstration of glucose-6-phosphate dehydrogenase. Sixteen hours after grafting a pronounced metabolic depression was noted. Recovery occurred 24 hours after transplantation. The most intense staining was from lactate dehydrogenase in the vein grafts and in the non-transplanted veins. At the end of the observation period of four months the grafts were definitely more strongly stained than the non-transplanted veins, with most of the activity in the thickened intima. This layer had a metabolic profile resembling that of the media of the adjacent aorta.
Nervous system degeneration produced by acrylamide monomer.
Authors: P S Spencer, H H Schaumburg
Journal: Environmental Health Perspectives (1975)

Acrylamide, widely employed as a vinyl monomer in the polymer industry, is a potent neurotoxin to man and to animals. The cumulative effect of prolonged, low-level exposure to acrylamide monomer is the insidious development of a progressive peripheral neuropathy. Sensory symptoms begin in the hands and feet (numbness, pins and needles), certain reflexes are lost and, with severe exposure, muscle weakness and atrophy occur in the extremities. The peripheral neuropathy may be supplemented by symptoms indicative of central nervous system damage (ataxia, tremor, somnolence and mental changes). The neuropathologic basis for this clinical picture has been determined in cats. Here, chronic acrylamide intoxication produces selective peripheral and central nerve fiber degeneration. Degeneration first occurs in the extremities of long and large nerve fibers which later undergo a progressive, seriate proximal axonal degeneration known as dying-back. Especially vulnerable are sensory axons supplying Pacinian corpuscles and muscle spindles in the hindfoot toepads, while adjacent motor nerve axons die back later. Distal central nerve fiber degeneration is seen in the medulla and the cerebellum. The neurotoxic property of acrylamide is of practical concern in two areas. One major problem is the protection of factory workers engaged in the manufacture of acrylamide. A sensitive test of neurologic function in these individuals, i.e., touch sensation, based on the experimental observation of the exquisite vulnerability of Pacinian corpuscles in acrylamide intoxicated cats, is presently under consideration. The second area for concern is the exposure of the populace to minute amounts of neurotoxic acrylamide monomer which contaminate acrylamide polymers currently deployed in the environment. Federal restrictions on the maximum permitted exposure to acrylamide, based on a largely clinical study of acrylamide neurotoxicity conducted ten years ago, may require a re-evaluation in the light of recent advances which have pinpointed the initial sites of nerve fiber degeneration.
THE ACTION OF TETRAIODOPHENOLPHTHALEIN ON THE HEART
Authors: WILLIAM D. REID
Journal: JAMA (1927)

The reactions observed in many patients following the administration of tetraiodophenolphthalein in the roentgen-ray study of the gallbladder (i. e., in the performance of the Graham test) have often roused considerable concern as to the condition of the heart. The symptoms are various. Nausea, usually unattended by vomiting, and a feeling of lassitude are common; in more marked cases, the picture may be more that of a vasomotor collapse with palpitation, pallor, sweating and prostration. Graham and his co-workers1have urged caution when injecting patients with a cardiac lesion.  Accordingly, it was thought desirable to examine these cases electrocardiographically. Electrocardiograms were obtained before and at approximately one hour after the intravenous injection of tetraiodophenolphthalein and carefully examined for changes. Numerous detailed measurements were made. Such a study was made of thirteen cases. It resulted in the finding of no consistent changes from the controls. In seven cases, the rate
CULTURE OF THE GONOCOCCUS
Authors: P. S. Pelouze
Journal: JAMA (1927)

<h3>To the Editor:</h3> —From the many comments that have been received by me since the publication of "A New Medium for Gonococcus Culture" by Dr. L. E. Viteri and myself (The Journal, March 6, 1926, p. 684), it is obvious that the simplicity that this medium introduces in the culture of those bacteria, hitherto considered to require enrichment by albuminous substances for growth, has stimulated much interest. There is a phase of this matter that seems not to have received any great attention but which should be uppermost in the mind of every one who uses enriched mediums of any type if great and serious error is to be avoided. Particularly is this true in searches aimed at the discovery of the gonococcus in chronic discharges from the male or female genitalia. We constantly overlook the fact that all the cocci reproduce by fission and that at this stage of
Abstract 2411: Rapamycin sensitizes cancer cells to growth inhibition by the PARP inhibitor olaparib
Authors: Atsushi Osoegawa, Joell J. Gills, Shigeru Kawabata, Kenji Sugio, Phillip A. Dennis
Journal: Cancer Research (2014)

Abstract Poly (ADP-ribose) polymerase inhibitors (PARPi) have been developed and tested in a context of combining them with drugs that inhibit double-stranded (ds) DNA repair, because PARPi impair single-stranded (ss) DNA break repair, resulting in activation of dsDNA break repair machinery. Rapamycin, an mTOR inhibitor, has been widely prescribed for more than a decade, and recent studies revealed its ability to inhibit dsDNA break repair. The combination of the PARPi, olaparib, and rapamycin synergistically inhibited cell proliferation in non-small cell lung cancer (NSCLC) cells, as well as triple negative breast cancer (TNBC) cells that have BRCA1 mutations. Rad51, which forms a polymer on ssDNA upon dsDNA breaks, plays an essential role in homologous recombination. Olaparib induced Rad51 focus formation and rapamycin successfully inhibited it both in vivo and in vitro, suggesting this combination worked through blocking both ssDNA break repair and dsDNA break repair, resulting in cells that cannot go through G2/M checkpoint. The protein level of PARP was predictive for both PAR activity and Rad51 focus formation with this combination. Collectively, these data suggest that this combination could have a therapeutic potential to inhibit cancer with high PARP expression, or in combination with cytotoxic chemotherapy or radiation. Citation Format: Atsushi Osoegawa, Joell J. Gills, Shigeru Kawabata, Kenji Sugio, Phillip A. Dennis. Rapamycin sensitizes cancer cells to growth inhibition by the PARP inhibitor olaparib. [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 2411. doi:10.1158/1538-7445.AM2014-2411
Grip force adjustments during rapid hand movements suggest that detailed movement kinematics are predicted
Authors: J. Randall Flanagan, James R. Tresilian, Alan M. Wing
Journal: Behavioral and Brain Sciences (1995)

Abstract The λ model suggests that detailed kinematics arise from changes in control variables and need not be explicitly planned. However, we have shown that when moving a grasped object, grip force is precisely modulated in phase with acceleration-dependent inertial load. This suggests that the motor system can predict detailed kinematics. This prediction may be based on a forward model of the dynamics of the loaded limb.
IgE reactivity to α1 and α2 chains of bovine type 1 collagen in children with bovine gelatin allergy
Authors: Masahiro Sakaguchi, Hisae Hori, Shunji Hattori, Shinkichi Irie, Atsushi Imai, Makoto Yanagida, Hiroshi Miyazawa, Masako Toda, Sakae Inouye
Journal: Journal of Allergy and Clinical Immunology (1999)
Margaret McCartney: Female genital mutilation: a wise doctor and a foolish prosecution
Authors: M. McCartney
Journal: BMJ (2015)

Wisdom is recognisable for its facets of fair judgment, experience, carefulness, and compassion—but also a degree of risk taking. The wise people I know make choices that are based on likely consequences. They consider all options but are also decisive. They are fair minded, having little ego to get in the way of what might be best for others. Wise people make good role models, although they most likely hate this. Shakespeare had it right: “The fool doth think he is wise, but the wise man knows himself to be a fool.”

The risk taking is important; wise people are not interested in “covering their backs.” The jury judging Dhanuson Dharmasena rapidly acquitted him as innocent against charges that he had committed female genital …
Subcutaneous Emphysema Complicating Renal Infection by Gas-Forming Coliform Bacteria
Authors: Nathan J. Clifford, Isadore Katz
Journal: New England Journal of Medicine (1962)

DIABETES mellitus is a disease known for its many complications. One of the rarer complications is gas-producing coliform infection of the body tissues and fluids. Two patients seen recently at the Kings County Hospital Center were striking examples of this complication.Case ReportsCase 1. A 71-year-old Negro was admitted to the hospital on March 19, 1961, because of weakness and confusion. One month earlier he had experienced bilateral flank pain and had become bedridden but had not sought medical care. Two days before admission the pain had become intense on the right side of the abdomen. He became so . . .
An electronic nose in the discrimination of patients with asthma and controls
Authors: Silvano Dragonieri, Robert Schot, Bart J.A. Mertens, Saskia Le Cessie, Stefanie A. Gauw, Antonio Spanevello, Onofrio Resta, Nico P. Willard, Teunis J. Vink, Klaus F. Rabe, Elisabeth H. Bel, Peter J. Sterk
Journal: Journal of Allergy and Clinical Immunology (2007)
Current Status and Future Prospects for Acute Myocardial Infarction Therapy
Authors: Eric J. Topol
Journal: Circulation (2003)

Considerable new evidence has accumulated in randomized trials of myocardial reperfusion. The trials of catheter-based reperfusion compared with fibrinolytics have shown an advantage for angioplasty and stenting over pharmacologic therapy, even accounting for delays in transporting patients from facilities with intervention capabilities. On the basis of the recent trials, it is recommended that a regional center for infarct intervention be set up akin to regional trauma centers in the United States. Now that we have entered the third decade of myocardial reperfusion therapy, we can expect iterative improvement in all aspects, and ultimately a fused approach of pharmacology and mechanical therapies-to achieve the optimal outcomes and continue to lower the toll of fatality and morbidity of acute myocardial infarction (MI).
Single breath transfer factor for carbon monoxide in an asymptomatic population of never smokers.
Authors: A Gulsvik, P Bakke, S Humerfelt, E Omenaas, T Tosteson, S T Weiss, F E Speizer
Journal: Thorax (1992)

BACKGROUND: Data on reference values of transfer factor variables in general populations of asymptomatic never smokers are limited. The aim of this study was to examine the relation between test variables and age, height, haemoglobin concentration and carboxyhaemoglobin concentration. METHODS: Measurements of single breath transfer factor for carbon monoxide (TLCO) were obtained for a randomly selected sample of never smokers in north western Europe who were 18-73 years old and had no respiratory symptoms or disorders. Two recordings of TLCO with a ratio of inspiratory vital capacity to forced vital capacity of greater than 0.09 were obtained by standardised techniques for 304 subjects. RESULTS: The measurement errors expressed as a percentage of the common mean value of TLCO, volume adjusted TLCO (KCO), and alveolar volume (VA) were 4.5%, 4.2%, and 2.4% respectively. Multiple linear regressions showed sex specific effects of height and age on TLCO, and, in addition, of haemoglobin and carboxyhaemoglobin concentrations on KCO. VA was associated with height but not with age. The 5th and 95th centiles for TLCO and KCO in men and women were between 78% and 82% and between 120% and 127%, respectively, of predicted values when age and height were taken into account. CONCLUSION: Reference equations and normal values for transfer test variables in a large healthy population of never smokers are described in relation to age, height, and haemoglobin concentrations. To our knowledge, this is the first report of an association between carboxyhaemoglobin concentrations and KCO in a population of never smoking men and women.
Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation
Authors: Christoph Schmid, Myriam Labopin, Arnon Nagler, Dietger Niederwieser, Luca Castagna, Reza Tabrizi, Michael Stadler, Jürgen Kuball, Jan Cornelissen, Jiri Vorlicek, Gerard Socié, Michele Falda, Lars Vindeløv, Per Ljungman, Graham Jackson, Nicolaus Kröger, Andreas Rank, Emmanuelle Polge, Vanderson Rocha, Mohamad Mohty
Journal: Blood (2011)
THE SANITARIUM FOR CONSUMPTIVE SAILORS ESTABLISHED BY THE U. S. MARINE-HOSPITAL SERVICE AT FORT STANTON, N. M.
Authors: J. O. COBB
Journal: JAMA (1900)

There is a prevalent belief that the sailor does not have tuberculosis. Just because he is at sea breathing the purest air, we naturally think of him as having the greatest chance of escaping that dread infection. The public mind loses sight of the fact that the average sailor spends a great part of his life ashore, participating in drunken brawls, gambling in the vile holes underground in New York, San Francisco, Baltimore and all the large maritime commercial centers. The little time he spends in sleep when ashore is in sailors' boarding houses, usually filthy dives. In lieu of beds, there are rough bunks built in like a set of shelves clear up to the ceiling. Into these a little straw is thrown, and this is the bed of one man one night, and another the next, and so on. The straw is rarely, if ever, changed, and this
“Choose and book” does not solve any problems
Authors: Adrian K Midgley
Journal: BMJ (2005)

EDITOR—In his personal view Kare-Silver describes behind the scenes at the “Choose and book” initiative.1 Information technology does not work well when handled as a compulsory element in a political process, as the government and NHS should know.

In 1990 I could refer a patient to any specialist in the United Kingdom. What limited my use was that I did not know many specialists, most specialists …
Long Hours and Risks to and From Residents
Authors: Angelo P. Giardino
Journal: JAMA (1988)

To the Editor.  —The recent letter by Drs Wendt and Yen 1 concerning house staff moonlighting seems to have missed the point entirely in the growing debate over residency training and safety to the patient and house staff officer. Drs Wendt and Yen report seven surgical residents who they informally surveyed concerning exhaustion and falling asleep at the wheel after a presumed 36- to 40-hour night on call. The article reported that six of the residents fell asleep at the wheel and that three were actually involved in motor vehicle accidents. From this information, the authors conclude that house staff should not moonlight. Is this the appropriate conclusion?  A more reasoned approach to these disturbing statistics would be to evaluate why the residents were awake for such extended hours and what flaws in the training program are manifested in the expectation for residents to work long hours. Thus, if six
Lowered Cost Potential for Hepatitis B Vaccine
Authors: Robert M. Craig
Journal: JAMA (1985)

A disheartening aspect of the development of the hepatitis B vaccine is its limited use. A high degree of immunoreactivity and disease prophylaxis has been demonstrated in field trials; however, the vaccine has been underutilized even in high-risk, knowledgeable groups, including health care workers. Elsewhere in this issue ofThe Journal, Alter et al<sup>1</sup>have shown that only 6% of hemodialysis patients and 32% of hemodialysis staff have received all three hepatitis B vaccinations. Aside from financial considerations, the latter group has not availed itself of the vaccine mostly probably due to a fear of contracting the acquired immunodeficiency syndrome (AIDS), despite evidence to the contrary. Indeed, in male homosexuals, those who received the vaccine seem to have a lower incidence of AIDS than those who did not receive the vaccine.<sup>2,3</sup>In other populations, especially in underdeveloped countries, the cost of the vaccine has been a major impediment
Will More Donor Questions Make Blood Safer?
Authors: Charles Marwick
Journal: JAMA (1991)

SCREENING of blood donors based solely on geographic or national origins is being eliminated. In its place will be expanded oral interviews aimed at identifying donors who are at high risk of transmitting disease. These interviews will include direct questions regarding risk behaviors, especially sexual habits, for infection with the human immunodeficiency virus (HIV). The Food and Drug Administration (FDA) has sent an advisory notice to blood bankers outlining the changes in the donor deferral system. The new recommendations are being phased in now. Last April, an FDA advisory committee recommended that the agency drop its policy of excluding blood donors based on national origin as a way of reducing the risk of transmitting infection from HIV and other blood-borne pathogens. That originally proposed ban was strongly protested by Haitians, in particular, as discriminatory. The advisory notice also extends the existing donor-exclusion period from 6 to 12 months for those