tbuckley/cabot-search huggingface dataset:
Abstract B30: Src tyrosine kinase inhibitors activate protective, ULK1-dependent autophagy by downregulating oncomir-106-393-cluster expression in non-small cell lung cancer cells
Authors: Sacha I. Rothschild, Oliver Gautschi, Jasmin Batliner, Melanie Jost, Martin F. Fey, Mathias Gugger, Mario P. Tschan
Journal: Clinical Cancer Research (2012)

Abstract Autophagy has been proposed to play a role as cytoprotective mechanism for tumor cell survival under unfavorable conditions and upon anticancer treatment. In lung cancer autophagy is mostly studied as possible resistance mechanism to therapy. There is increasing evidence that protective autophagy occurs upon various types of anti-cancer treatments, including chemo- and radiation therapy. Src tyrosine kinase inhibitors (TKIs) have been shown to inhibit cell migration and invasion in non-small cell lung cancer (NSCLC) cell lines. In clinical trials, however, they show modest activity in combination with chemotherapeutic agents. In the current study we show a marked induction of autophagic activity upon incubation of NSCLC cell lines with Src TKIs as measured by an increased LC3-I to -II conversion, a significant increase in GFP-LC3 dot formation, and a decrease in p62/SQSTM1 protein expression. Increased autophagic activity was found in three NSCLC cell lines (A549, H460, H1299) with two different Src TKIs (saracatinib, dasatinib). Interestingly, the addition of pharmacological autophagy inhibitors such as chloroquine or bafilomycin resulted in cell death in combination with Src TKI treatment. Moreover, we found that Src TKI-induced autophagy is associated with ULK1 expression in all three cell lines investigated. This effect was Src-specific since knocking down endogenous Src using RNAi resulted in a similar induction of ULK1. Using shRNA targeting ULK1 we showed that Src inhibitor induced autophagy is ULK1-dependent. Furthermore, ULK1 is a novel target of microRNA (miR)-106a as shown by ULK1 3′-UTR luciferase experiments and ectopic expression of miR-106a and antimiR-106a in NSCLC cell lines resulting in decreased and increased ULK1 expression upon Src inhibition, respectively. Lastly, in human lung adenocarcinoma compared to matched normal lung tissue (n = 23) miR-106a levels were significantly increased (p&amp;lt;0.0001) whereas ULK1 mRNA expression levels were significantly lower (p&amp;lt;0.0002) in tumor tissue. In conclusion, Src inhibitor-induced protective autophagy might explain their low success in clinical trials. Autophagy induced by Src TKIs depends on ULK1 and combining Src with autophagy inhibitors results in massive cell death as compared to single treatments. Furthermore, downregulation of the ULK1 targeting miR-106a upon Src inhibition allows for the induction of protective autophagy. Combining Src and autophagy inhibitors or Src inhibitors and miR-106a expression may represent attractive treatment options for NSCLC.
MYCOSIS FUNGOIDES AND PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
Authors: I. CALDWELL, A.D. DAYAN
Journal: British Journal of Dermatology (1970)

SUMMARY.— A patient is described with generalized mycosis fungoides who became severely demented. Autopsy showed that the dementia was due to progressive multifocal leukoencephalopathy. The presumed pathogenesis of this rare disorder of the nervous system was demonstrated by electron microscopical examination of necropsy samples of brain, which showed intranuclear viral filaments and rounded particles. This bizarre viral invasion of the brain is thought to be an opportunistic infection due to impairment of immune defences by the generalized reticulosis and the chemotherapy received by the patient.
A double-blind trial of a zinc sulphate/citrate complex and tetracycline in the treatment of acne vulgaris
Authors: W.J. CUNLIFFE, B. BURKE, B. DODMAN, D.J. GOULD
Journal: British Journal of Dermatology (2006)

Forty-eight patients participated in a 3-month double-blind study to compare the effect of orally administered zinc sulphate/citrate complex and tetracycline hydrochloride in acne vulgaris. Tetracycline significantly reduced the overall grade, and the number of non-inflamed lesions, papules and pustules by the third month. It also reduced significantly the non-inflamed lesions and papules at the end of the second month. In contrast, zinc therapy only had a significant effect on the pustules at the third month. The results indicate that tetracycline is far superior to the zinc complex in patients with moderately severe acne.
TIMING OF LATE STENT THROMBOSIS OCCURRENCE: NECESSITY OF DUAL ANTIPLATELET THERAPY CONTINUATION FOR ACUTE MYOCARDIAL INFARCTION CASES AFTER ONE MONTH
Authors: Shunsuke Kubo, Kazushige Kadota, Seiji Habara, Takeshi Tada, Hiroyuki Tanaka, Naoki Oka, Harumi Katoh, Tuyoshi Goto, Kazuaki Mitsudo, Yasushi Fuku
Journal: Journal of the American College of Cardiology (2012)
Simplified Total Body Perfusion
Authors: Richard A. DeWall
Journal: JAMA (1962)

IN THE PAST 6½ years nearly 1,500 total body perfusions have been performed at this center and many thousands elsewhere. "Things are never so good that they might not be better" and this philosophy has stimulated us to reexamine our techniques for total body perfusion for open cardiotomy in light of our own experience and that of others. Promoters of the maximum flow techniques have not provided any convincing evidence that their more complicated methods have superiority, nor have the "deep coolers" in their efforts to achieve technical simplicity provided results, at least to date, that are likely to warm the hearts of their confreres. From the time open heart surgical procedures began there has been a trend towards increasingly complex pump-oxygenators, heating exchange units, numbers of personnel required, more complicated ancillary monitoring devices, and greater blood priming requirements, without any corresponding decrease in patient morbidity and mortality. It has
Corticosteroid Resistant (CR) Asthma Is Associated with Classical Activation Of Airway Macrophages and Exposure To Lipopolysaccharide (LPS)
Authors: P.J. Hauk, E. Goleva, A.H. Liu, C.F. Hall, D.W.H. Riches, R.J. Martin, D.Y.M. Leung
Journal: Journal of Allergy and Clinical Immunology (2006)
Beneficial effects of stress-dose corticosteroid therapy in canines depend on the severity of staphylococcal pneumonia
Authors: Caitlin W. Hicks, Daniel A. Sweeney, Robert L. Danner, Peter Q. Eichacker, Anthony F. Suffredini, Jing Feng, Junfeng Sun, Brad Moriyama, Robert Wesley, Ellen N. Behrend, Steven B. Solomon, Charles Natanson
Journal: Intensive Care Medicine (2012)
NOTES ON ONE THOUSAND CASES OF BILHARZIASIS TREATED BY ANTIMONY TARTRATE
Authors: F. O. Lasbrey, R. B. Coleman
Journal: BMJ (1921)

TM lj y 299and putting on a lint and ointment face-mask.This was done, and as her mother refused to take her home through the streets like tllat we had to adimit her.-On that Wed- nesday no raslh appeared, and she went, home next day, On the following Wednesday the rash reappeared,: but obviously -we could not find a bed for her every week.Wbhy slhe did it I do not know. I. TL-MR.CYRIL WALKFII..It is not easy to understand the motive wlicih induced the girl whose case is to be related to inflict so much pain upon lherself, but I have very little doubt that she was in some way tampering wvith her eyes long before the pieces of cotton-wool and tllread were discovered.L. G. came to me at the Bristol General Hospital as an out- patient in 1892 when she was 6 years old.She was then suffering from phlyctenular conjunctivitis and keratitis.She soon recovered under the usual treatment, but had very fre- quent recurrences, so that for some eight or ten years she was almost constantly under treatment.When she was 8 years old she had typical molluscum contagiosum of the eyelids-a disease, by the way, which is seldom seen amongst ophthalmic out-patients now.W'hen she was 12 she developed tuberculous glands in the neck, and in consequence underwent three extensive operations between the ages of 15 and 17.The corneae were at that time so much damaged by recurrent strumous keratitis that she could only read big print, and no examina- tion 'of the fundi was possible.When she wvas 18 she had an extremely severe and intractable attack of keratitis affecting both eyes, and accompanied by great photophobia and intense spasm of the orbicularis.She was an in-patient for some months, and towards the end of her stay in bospital it was noticed that on two or three occasions a tiny piece of cotton- wool or of thread from a bandage was found in the conjunctival sac.She was not definitely accused of having introduced these foreign bodies, but she was questioned about it and told to be very careful not to touch her eyes herself.Her general con- dition slowly improved, and her eyes gradually quieted down, The corneae had been rendered very opaque all over by the interstitial keratitis.No fundus reflex -could be obtained, and her vision was reduced to bare perception of light.The corneal condition was not enough to account for such great loss of sight, and it must be assumed that she had choroiditis at the same
Work and heart disease in Wisconsin. I. Medical basis for workmen's compensation awards over ten years
Authors: G. A. Hellmuth
Journal: JAMA (1966)

The problem of the medicolegal aspect of heart disease in Wisconsin industry has steadily increased. A study of cases heard between 1953 and 1962 by the Wisconsin Industrial Commission under the Workmen's Compensation Act was designed to determine causal relationship of a work-connected accident and an acute myocardial infarction. A detailed study was made of a significant number of cases to which American Heart Association criteria for determining causality were applied; the study shows that approximately half of the compensated and compromised claims were not medically justified. Results indicate that a system of fair adjudication of claims for cardiac disturbance should be evolved at the state level, with well-informed medical testimony and based on the medicolegal establishment of the fact that physical exertion at the time of the incident was clearly unusual for the person.
Non-European doctors and change in UK policy: What about highly skilled migrant doctors?
Authors: Krishnamoorthy Narayan
Journal: BMJ (2006)

EDITOR—The news article by O'Dowd tries to highlight a serious problem faced by overseas doctors who entered the United Kingdom in recent years, but it falls short of supporting their cause.1 The NHS trusts are showing their true colours. Why are they overenthusiastically rejecting applications from overseas doctors even if they do not need …
Screening cord blood for sickle haemoglobinopathies in Brent.
Authors: J Henthorn, E Anionwu, M Brozovic
Journal: BMJ (1984)

Between 1981 and 1983, 3165 consecutive specimens of cord blood were tested at the Central Middlesex Hospital for the presence of an abnormal haemoglobin: the incidence of sickle cell trait was 2.8%, of HbC trait 0.9%, and the overall incidence of an abnormal haemoglobin at birth was 6.9%. Five babies with homozygous sickle cell disease, three with HbSC, and three with either HbCC or HbC beta thalassaemia were detected. Twenty two per cent of the mothers were of Afro-Caribbean origin. The cost of the test was 30p. An H6000 blood count was carried out on 1000 consecutive cord blood samples. The mean red cell volume was 97.95 (SD 3.67) fl. Thirteen cord blood samples had a mean cell volume below 85 fl, and all contained Hb Barts. In addition, six samples with a mean cell volume between 86 and 92 fl also showed Hb Barts on electrophoresis. The overall incidence of Hb Barts was 2.1%. These results indicate that the incidence of HbSS and HbSC on neonatal screening in Brent is similar to that found in the urban areas of North America and that the number may be predicted from the number of births to mothers of Afro-Caribbean origin.
Cardiopulmonary hemodynamics for accurate diagnosis of portopulmonary hypertension: A redefinition to consider
Authors: Mateo Porres‐Aguilar, Debabrata Mukherjee
Journal: Hepatology (2014)

We have read with interest the review article by Machicao et al.1 We would like to share some thoughts regarding the importance of the appropriate interpretation of the main pulmonary hemodynamic parameters obtained during right heart catheterization (RHC) that can complicate portal hypertension/liver disease, since the therapeutic approach for each one is different and outcomes clearly differ: We think that the addition of the transpulmonary gradient (TPG) >12 mmHg represents an important hemodynamic parameter for the redefinition of portopulmonary hypertension (PoPH), given that the current 2004 European Respiratory Society (ERS) and the American Association for the Study of Liver Diseases (AASLD) guidelines take into account mean pulmonary arterial pressure (mPAP), pulmonary arterial occlusion pressure (PAOP), and pulmonary vascular resistance (PVR) as the most important hemodynamic parameters.2 Recently, TPG has been very well adopted by researchers in the field of PoPH, reflecting real vasoconstriction and vasobliterative changes within the pulmonary vasculature. We believe that the utility of TPG represents an important diagnostic key for PoPH, especially while facing challenging hemodynamic scenarios where both PVR and PAOP are elevated, and which may occur in up to 25%; of patients with PoPH,1 the existence of pulmonary vascular remodeling is clearly true when TPG >12 mmHg. In other forms of pulmonary hypertension (PH) (e.g., PH associated with left heart disease), the calculation of the diastolic pulmonary vascular pressure gradient [(DPG) = diastolic PAP - PAOP; normal value of DPG is <7 mmHg] may represent a better hemodynamic parameter when compared to TPG, not only to accurately identify patients with "reactive/out of proportion" PH beyond the passive transmission of hydrostatic pressure,4 but also the capability to identify the subgroup of patients that may portend worse prognosis, since TPG has the disadvantage to suffer variations because it is sensitive to changes in cardiac output and both distension and recruitment of pulmonary vessels.4 We know there is a lack of prospective studies in PoPH regarding the clinical significance of DPG. Having said that, we believe that DPG may play a potential role in detecting true PoPH, especially when facing cases with high PAOP (>15 mmHg), and also with regard to potential prognostic implications in PoPH, stimulating researchers to perform studies in its potential utility. Mateo Porres-Aguilar, M.D., FACP Debabrata Mukherjee, M.D., M.S., FACC 1Department of Internal Medicine/Division of Hospital Medicine 2Chairman, Department of Medicine; Chief, Division of Cardiovascular Diseases Texas Tech University Health Sciences Center Paul L. Foster School of Medicine El Paso, TX
Asymmetric Division of the Pulmonary Artery
Authors: FRANCIS L. GIKNIS, BRUCE F. BAISCH
Journal: Circulation (1964)

Asymmetric division of the pulmonary artery is reported in two cases. The right pulmonary artery arose immediately above the right cusp of the pulmonary valve, from a dilated trunk, which, although mistaken for main pulmonary artery, actually represented the proximal portion of the left pulmonary artery. A large interventricular septal defect, biventricular hypertrophy, and aortic hypoplasia complete the syndrome. In one case the malformation was not recognized at the time of a banding procedure. The infant died, and the unprotected lung showed marked congestion at autopsy. The nature of the pulmonary artery division may be such that an effective single band is technically impossible. Our case 1 suggests that unilateral banding in such an instance could be fatal if not immediately recognized and revised. Bilateral simultaneous banding would appear to be the palliative procedure of choice.
Cosmetic Formula Information
Authors: Cyril H. March
Journal: JAMA (1971)

Information concerning the ingredients of cosmetics is essential to the proper medical care of patients who are allergic to or irritated by one or more of the constituents of these products. The incidence of irritant or allergic reactions is small. Nevertheless, for those affected and for the physicians treating them, the problems of avoiding reexposure to the causative agent (s) are large. Identifying the offending product is helpful but does not suffice. What is accomplished if the patient switches to a new brand only to encounter unknowingly the same provoking ingredient? With a knowledge of the qualitative formula, a physician is in better position to carry out the specific diagnostic procedures that will identify the allergen. Since the patient's cosmetic needs and desires have not changed, the physician is then able to prescribe specially formulated cosmetic products or suggest products that are free of the specific allergen involved. Since few
Ocular Manifestations of Wegener's Granulomatosis
Authors: Allan J. Flach
Journal: JAMA (1995)

<h3>To the Editor.</h3> —I was surprised that the discussion of Wegener's granulomatosis in the Grand Rounds at the National Institutes of Health<sup>1</sup>made no mention of the ophthalmic clinical manifestations of this disease. Although the authors listed the eye and orbit as an organ system commonly affected (52% frequency) in Table 1, there was no specific mention of the many clinical ocular features of this disorder. This is surprising because unilateral or bilateral exophthalmos and optic neuritis with blindness are mentioned in the first description of Wegener's granulomatosis and continue to be a common presentation.<sup>2</sup>Exopthalmos can coexist with proptosis, eyelid edema, chemosis, limitation of extraocular movements, and exposure keratitis. It is of greatest significance that conjunctivitis can be the initial presentation for patients with this potentially fatal disease.<sup>3</sup>In addition, scleritis, episcleritis, and peripheral ring corneal ulcers have been described prior to the development of any
Caring for the Country: Family Doctors in Small Towns
Authors: John Gillies
Journal: BMJ (2005)

T his book is about the lives and work of family doctors in rural towns, mostly inPennsylvania. I live and work in a small rural town in Scotland and became aware of Howard Rabinowitz's contribution to rural health care in the mid-1990s, when I did a literature review of recruitment and retention of doctors to rural areas throughout the developed world.

The physician area shortage programme started by Jefferson Medical College, Philadelphia, in 1974 was one of the first, and its fruits are described in this engaging book. Rabinowitz has beenits committed director …
Urgent referrals for suspected cancer vary threefold among general practices
Authors: N. Hawkes
Journal: BMJ (2012)

The rate at which GPs refer patients for suspected cancer varies so widely that it indicates real differences in the standards of care being provided.

Some variation in referral rate would be expected because populations differ, but data published this week for individual practices by the National Cancer Intelligence Network shows that some GPs refer more than three times as many patients as others.1 Rates range from a low of under 830 in every 100 000 people a year to a high of over 2550. This is the first time such data have been made publicly available, enabling patients to compare the referral rate of every general practice in England.

Mick Peake, the network’s clinical lead, said, “The data are not easy to interpret, since we do …
Primary Care Physicians and AIDS
Authors: Barbara Gerbert
Journal: JAMA (1991)

To explore the extent to which primary care physicians are providing health care for people with human immunodeficiency virus (HIV) infection and to document barriers to HIV care giving.National random-sample mailed survey.Population-based random sample of 2004 US general internists, family physicians, and general practitioners in 1990. Response rate was 59%.HIV treatment experience, willingness to treat HIV-infected patients, negative attitudes toward homosexuals and intravenous drug users, fear of contagion of the acquired immunodeficiency syndrome (AIDS), perceived lack of information about AIDS, and time demands of HIV care.Most physicians (75%) had treated one or more patients with HIV infection. A majority (68%) believed that they had a responsibility to treat people with HIV infection, yet half (50%) indicated that they would not, if given a choice. Over 80% of respondents believed that they lacked information about AIDS and that caring for people with AIDS is time consuming. Further, 35% of respondents agreed that they "would feel nervous among a group of homosexuals" and 55% expressed discomfort about having intravenous drug users in their practice. Physicians who had treated 10 or more HIV-infected patients expressed less negativity toward members of these stigmatized groups who are likely to be HIV infected.These data suggest that many primary care physicians are responding professionally to the AIDS epidemic but that attitudinal barriers may be hindering some physicians from providing treatment to HIV-infected patients.
Staphylococcus epidermidis Causing Prosthetic Valve Endocarditis: Microbiologic and Clinical Observations as Guides to Therapy
Authors: ADOLF W. KARCHMER
Journal: Annals of Internal Medicine (1983)

Seventy-five episodes of prosthetic valve endocarditis from Staphylococcus epidermidis were studied retrospectively. Methicillin-resistant isolates caused 53 (87%) of 61 infections occurring within 1 year of surgery but only two of the nine after 1 year (p < 0.001). Resistance to methicillin was heterogeneic and extended to the cephalosporins. Of 55 isolates, 43 (78%) were susceptible to gentamicin and all to vancomycin and rifampin. In 55 patients, prosthetic valve endocarditis was complicated by tissue invasion or valve dysfunction. Among these 55 patients, 30 of the 32 who were cured needed surgery. Prosthetic valve endocarditis from methicillin-resistant S. epidermidis was cured in 21 of 26 patients treated with vancomycin and 10 of 20 treated with beta-lactam antibiotic therapy (p = 0.055). Cure rates of patients treated with vancomycin but not betalactam antibiotics were increased by the addition of rifampin or gentamicin to therapy. Prosthetic valve endocarditis from methicillin-resistant S. epidermidis should be treated with vancomycin plus rifampin, or an aminoglycoside. Surgical intervention is important in treating complications of prosthetic valve endocarditis.
Bird flu and pandemic flu
Authors: John T Macfarlane, Wei Shen Lim
Journal: BMJ (2005)

Bird flu and pandemic fluWhat's the message for GPs and hospital doctors?T he extensive media coverage of avian influenza (bird flu) over recent weeks has caused confusion and increasing concern that bird flu will imminently cause a human pandemic.This has been fuelled by the report of a parrot infected by the H5N1 strain of avian influenza in the United Kingdom this week.Is such a pandemic a flight of fantasy or a dead cert?The influenza pandemic contingency plan presented by the chief medical officer 1 is clear and comprehensive, but at nearly 450 pages, 11 downloadable documents, and many web links, it may not be ready reading for busy health professionals.Everyone is familiar with seasonal human flu, which typically affects 10-15% of the UK population each winter and leads to around 12 000 excess deaths.Although minor antigenic drift in the human influenza virus A occurs continuously, a major shift in its surface protein antigens H or N can trigger a worldwide influenza pandemic because of absence of population immunity.Fortunately, this happens only rarely-"Spanish" flu in 1918-9 (H1N1 virus) with an estimated 250 000 excess deaths in the UK, "Asian" flu in 1957-8 (H2N2) with 33 000 deaths, and "Hong Kong" flu in 1968-9 (H3N2) with 30 000 deaths.Many scientists believe that another pandemic is overdue.