tbuckley/cabot-search huggingface dataset:
Abstract 4897: Involvement of Akt isoforms in chemoresistance of carcinoma endometrial cells
Authors: Julie Girouard, Marie-Judith Lafleur, Valérie Leblanc, Eric Asselin
Journal: Cancer Research (2012)

Abstract Akt (also known as PKB) is a crucial survival kinase that is normally activated by growth factors, but in tumors, it is constitutively activated at a high frequency through oncogenic events affecting its upstream regulation. Since studies have demonstrated that the three Akt isoforms exhibit distinct physiological functions, we propose that Akt isoforms may contribute differently in chemoresistance of endometrial carcinoma cells. In order to determine the specific role of each Akt isoform, we have stably produced transfectants in which the expression of Akt is downregulated by specific shRNAs for Akt1, Akt2 and Akt3 using the KLE endometrial carcinoma cell line. This endometrial cell line is known to constitutively express the three Akt isoforms and to highly resist to chemotherapeutic treatment. In this study, we have demonstrated that the downregulation of Akt1 and Akt2 by RNA interference strongly sensitizes KLE cells to cisplatin, doxorubicin and taxol and affects cell proliferation. Moreover, cisplatin treatment of these cells induced the activation of pro-apoptotic factors such as the cleavage of caspase -3, -6, -9 and PARP and it also inhibited the expression of anti-apoptotic factors such as XIAP and Bcl-2. Alternatively, we used constitutively active Akt expression vectors for each isoform to produce stable transfectants using the chemosensitive Hec 1A endometrial cancer cell line, in which no Akt activity is detected. Constitutive Akt1 and Akt2 expression leads to an increase in cell proliferation, as well as resistance to apoptosis after chemotherapeutic treatment in these stable transfectants. Moreover, Akt isoforms contribute differently in other cancer cell processes, such as migration. We showed that Akt2 blocks cell motility, while the activation of Akt1 or Akt3 does not show any effect on our endometrial cancer cell model. Our findings highlight the contribution of Akt1 and Akt2 isoforms in the molecular mechanisms that govern chemoresistance of endometrial carcinoma. Furthermore, Akt isoform-specific transfectants will provide a solid model to determine the involvement of each Akt isoform in tumor progression and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4897. doi:1538-7445.AM2012-4897
TCTAP A-019 Clinical Features and Intermediate-Term Outcomes of Excimer Laser Coronary Angioplasty
Authors: Hirofumi Nagamatsu, Sho Torii, Tsutomu Murakami, Toshiharu Fujii, Masataka Nakano, Gaku Nakazawa, Naoki Masuda, Norihiko Shinozaki, Nobuhiko Ogata, Fuminobu Yoshimachi, Yuji Ikari
Journal: Journal of the American College of Cardiology (2015)
Humor Therapy: The Good News— No One Died; The Bad News— Jack Benny Did
Authors: Joseph K. Neumann
Journal: JAMA (1989)

To the Editor. —  Some anecdotal reports and laboratory studies with healthy populations suggest humor may be of therapeutic benefit to hospitalized patients. 1 These studies are generally not controlled and suffer from possible subject-selection bias as well as other methodological problems. The present report suggests the helpful effects of humor in hospitalized patients may be less than previously indicated.  Studies. —  After approval by the appropriate research committees, two groups of volunteers were recruited for these projects. All were competent, male veterans willing to sign the approved consent form. One group (8 patients) received transurethral prostate surgery under local anesthesia 2 and the second group (16 patients) received peripheral (leg) arteriography. 3   Subjects were randomly assigned to either a humor or ocean sound (control) audiotape condition. The humor tape consisted of a recording of an old Jack Benny radio show. About 85% of the humor-tape subjects described the tape
Doctor cleared of act “tantamount to euthanasia”
Authors: Owen Dyer
Journal: BMJ (2007)

A consultant neonatologist who gave lethal doses of the muscle relaxant pancuronium to hasten the deaths of two premature babies from whom treatment had been withdrawn was this week cleared of an act “tantamount to euthanasia” by the UK General Medical Council.

Michael Munro was found to have misled a hospital colleague investigating the deaths, and to have kept inadequate notes of the cases. But Dr Jacqueline Mitton, chairwoman of the GMC's fitness to practise panel, said these findings were not serious enough to suggest that Dr Munro's fitness to practise was impaired.

“I am satisfied that you have insight into the failings highlighted by this case,” she told Dr Munro. “It is neither necessary nor proportionate to issue a warning to you.” While hastening death had been an “anticipated consequence” of giving such a dose of pancuronium, the panel found, Dr Munro's primary purpose had …
Lysophosphatidylcholine Inhibits Endothelium-Dependent Hyperpolarization and <i>N</i> <sup>ω</sup> -Nitro- <scp>l</scp> -Arginine/IndomethacinResistant Endothelium-Dependent Relaxation in the Porcine Coronary Artery
Authors: Hiroshi Eizawa, Yoshiki Yui, Reiko Inoue, Kunihiko Kosuga, Ryuichi Hattori, Takeshi Aoyama, Shigetake Sasayama
Journal: Circulation (1995)

Background Oxidized LDL and lysophosphatidylcholine (LPC) have been reported to inhibit the endothelium-dependent relaxation (EDR) mediated by nitric oxide. Recently, a new vasorelaxing factor, endothelium-derived hyperpolarizing factor (EDHF), which hyperpolarizes and relaxes the porcine coronary artery in the presence of N ω -nitro- l -arginine (NNA) and indomethacin (IM), has been reported. We examined whether LPC also inhibits both the EDHF-mediated relaxation and membrane hyperpolarization of the porcine coronary artery. Methods and Results EDHF was evaluated as the bradykinin- or A23187-induced relaxation of the porcine coronary artery contracted by prostaglandin F 2α in the presence of NNA and IM. We also directly measured the membrane potential of the porcine coronary artery. The effects of LPC on both relaxation and membrane hyperpolarization were investigated. At concentrations of 0 to 20 μmol/L, LPC dose-dependently inhibited the NNA/IM-resistant EDR induced by bradykinin and A23187, and the relaxation was reversible after the absorption of LPC with albumin. LPC also inhibited the bradykinin- and A23187-induced hyperpolarization of the porcine coronary artery. Conclusions In the present study, LPC was found to inhibit not only nitric oxide–mediated but also EDHF-mediated relaxation of the porcine coronary artery. Our findings suggest a new regulatory mechanism in the atherosclerotic coronary artery.
Detection and Assessment of Mitral Regurgitation by Left Atrial Indicator-Dilution Curves
Authors: CHARLES P. NEWCOMBE, JOHN D. SINCLAIR, DAVID E. DONALD, EARL H. WOOD
Journal: Circulation Research (1961)

Indicator-dilution curves were recorded simultaneously from the left atrium and the femoral artery during injections of indocyanine green into the left ventricle in normal dogs and in dogs with chronic mitral regurgitation. A study was made-without the use of thoracotomy-of the effect of the following factors on the amount of early appearing indicator detected in the left atrium: (a) the timing of the injection of indicator in relation to the cardiac cycle, (b) the position of the injecting catheter in the left ventricle, and (c) the position of the sampling catheter in the left atrium. It was found that the time and site of the injection into the left ventricle had little effect on the amount of early appearing dye detected in the left atrium and that, although the position of the sampling catheter in the left atrium was important, reproducible results were attained when the sampling site was restricted to a region in close proximity to the mitral valve. A close correlation was demonstrated between the volume of regurgitation determined independently on a hydraulic basis and the volume estimated from the fraction of early appearing indicator detected in the left atrium. It is concluded that further work with this upstream-sampling technique is justified in order to study its possibilities as a practical method for detecting and quantitating mitral regurgitation in human beings.
Lung Volume Reduction Surgery Improves Maximal O<sub>2</sub> Consumption, Maximal Minute Ventilation, O<sub>2</sub> Pulse, and Dead Space-to-Tidal Volume Ratio during Leg Cycle Ergometry
Authors: JOSHUA O. BENDITT, SARAH LEWIS, DOUGLAS E. WOOD, LARRY KLIMA, RICHARD K. ALBERT
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Early experience suggests that lung volume reduction surgery improves exercise tolerance as measured by the 6-min walk distance in patients with emphysema. To identify the physiologic mechanism(s) by which lung volume reduction surgery improved exercise, we performed progressive cardiopulmonary exercise testing, including rest and peak exercise blood gas determinations, on 21 consecutive patients before and 3 mo after lung volume reduction surgery. Maximal work (median, range, % change) increased 17.5 watts ( − 13 to + 44 watts, 46%, p < 0.05), maximal oxygen consumption increased 0.16 L/min ( − 0.17 to + 0.48, 25%, p < 0.05), maximal ventilation increased 6.6 L/min ( − 7 to + 26 L/min, 27%, p < 0.05), and the dead space/tidal volume ratio at peak exercise decreased 0.07 ( − 0.22 to + 0.09, 12%, p < 0.05), exclusively as a result of an increase in the tidal volume. After lung volume reduction surgery heart rate decreased at the point of isowatt exercise, from 115 to 111 beats/min (p < 0.05). No difference was observed in the other physiologic variables measured at isowatt exercise. In 13 patients exercised while breathing room air, the alveolar-to-arterial O2 difference increased, and the arterial O2 tension decreased from rest to peak exercise both before and after the operation, but significant changes in this response were not observed after surgery. The primary problem limiting exercise performance in these patients was the limited ventilatory capacity as 16 and 13 of the 21 subjects developed acute respiratory acidemia at peak exercise before and after surgery, respectively. Lung volume reduction surgery in patients with severe emphysema improved maximal ventilation, thereby improving maximal exercise performance.
Upper age limit for bronchiolitis: 12 months or 6 months?
Authors: F. Midulla, R. Nenna
Journal: European Respiratory Journal (2012)

From the authors:

We thank M. Korppi and co-workers for their correspondence regarding our article [1]. In our prospective study, we identified rhinovirus (RV) infection and a positive family history for asthma as substantial risk factors for recurrent wheezing during 1-yr follow-up after the initial episode of bronchiolitis. The distinctive point of our study was that all the infants enrolled had clinically well-characterised bronchiolitis, defined as the first episode of acute lower airway infection that appears with a history of upper respiratory tract infection followed by acute onset respiratory distress with cough, tachypnoea, retraction and diffuse crackles on auscultation in infants <12 months of age [2]. Another strength of our study is that …
Age-related galactosylation of the N-linked oligosaccharides of human serum IgG.
Authors: R Parekh, I Roitt, D Isenberg, R Dwek, T Rademacher
Journal: The Journal of Experimental Medicine (1988)

In a study of 151 normal, healthy individuals of both sexes varying in age from 1-70 yr, it was found that the relative incidence of agalactosyl (with both outer arms terminating in N-acetylglucosamine) N-linked oligosaccharides on total serum IgG decreased from birth to a minimum (at 25 yr of age) and then increased with age. The relative incidence of digalactosyl structures varied inversely to this, and the relative incidence of monogalactosyl structures was constant. Galactosylation of the N-linked oligosaccharides of the human serum IgG of normal individuals is therefore an age-related molecular parameter. Several reports have suggested that rheumatoid arthritis is associated with a decreased galactosylation of serum IgG (3-5). The normal variation in galactosylation with age as described here allows a true assessment of disease-associated changes in this parameter, and raises the possibility that one of the lesions in rheumatoid arthritis is an accelerated aging of the immune system. In addition, heterogeneity within age groups may be due to intrinsic differences in genetic endowment, or may reflect the impact of extrinsic factors (8).
Management of severe acne
Authors: C.C. Zouboulis, V. Bettoli
Journal: British Journal of Dermatology (2015)

Acne is the most common skin disease, affecting up to 95% of adolescents. Severe episodes of acne can cause considerable physical and psychological scarring, and overexpression of transforming growth factor-β can lead to formation of hypertrophic scars and keloids. The severity of acne in adolescence is associated with a positive history of severe acne in first-degree relatives, especially the mother. In most cases acne is a chronic disease, and it is often a component of systemic diseases or syndromes. All forms of severe acne require systemic treatment. The available options include oral antibiotics, hormonal antiandrogens for female patients and oral isotretinoin, as well as other combination treatments. Oral isotretinoin is the only drug available that affects all four pathogenic factors of acne. However, due to possible serious side-effects, a European directive states that oral isotretinoin should be used only as a second-line therapy in cases of severe, nodular and conglobate acne. The pharmaceutical quality of generic isotretinoin products and the obtainability of isotretinoin through e-pharmacies without prescription raise new therapeutic problems. New anti-inflammatory compounds, such as the 5-lipoxygenase inhibitor zileuton, may replace systemic antibiotics in the future, especially under the scope of antibiotic resistance prevention. This review looks into the various options and latest approaches, and factors to consider, when combating severe acne.
Phosphorylation of TRAF2 within Its RING Domain Inhibits Stress-Induced Cell Death by Promoting IKK and Suppressing JNK Activation
Authors: Gregory S. Thomas, Laiqun Zhang, Ken Blackwell, Hasem Habelhah
Journal: Cancer Research (2009)

Tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) is an adaptor protein that modulates the activation of the c-Jun NH(2) terminal kinase (JNK)/c-Jun and IkappaB kinase (IKK)/nuclear factor-kappaB (NF-kappaB) signaling cascades in response to TNFalpha stimulation. Although many serine/threonine kinases have been implicated in TNFalpha-induced IKK activation and NF-kappaB-dependent gene expression, most of them do not directly activate IKK. Here, we report that protein kinase Czeta phosphorylates TRAF2 at Ser(55), within the RING domain of the protein, after TNFalpha stimulation. Although this phosphorylation event has a minimal effect on induction of the immediate/transient phase of IKK and JNK activation by TNFalpha, it promotes the secondary/prolonged phase of IKK activation and inhibits that of JNK. Importantly, constitutive TRAF2 phosphorylation increased both basal and inducible NF-kappaB activation and rendered Ha-Ras-V12-transformed cells resistant to stress-induced apoptosis. Moreover, TRAF2 was found to be constitutively phosphorylated in some malignant cancer cell lines and Hodgkin's lymphoma. These results reveal a new level of complexity in TNFalpha-induced IKK activation modulated by TRAF2 phosphorylation and suggest that TRAF2 phosphorylation is one of the events that are responsible for elevated basal NF-kappaB activity in certain human cancers.
SOME REMARKS CONCERNING THE OCULAR AND AURAL REQUIREMENTS OF RAILROAD EMPLOYES.
Authors: FRANK ALLPORT
Journal: JAMA (1904)

Some three years ago the Interstate Commerce Commission published an interesting report of railway accidents occurring in the United States in one brief year. There is no reason to suppose that this was an especially unfortunate year, and as the figures are instructive and full of significance, I will quote some of them. The total number of personal accidents was 51,743, and of these 7,123 were killed, 2,210 being railway employes; 334 employes were killed and 2,153 injured by collisions and derailment, and 82 passengers were killed and 1,557 passengers injured from the same cause. The causes of these accidents are doubtless numerous, but have not been, so far as I am aware, statistically enumerated, although such tabulation would be most interesting and instructive. A small minority of the accidents were perhaps in the ordinary course of events unavoidable, but a large majority were probably preventable, and due to carelessness
REHABILITATION OF PATIENTS WITH DEEP BURNS
Authors: James Barrett Brown
Journal: JAMA (1952)

Patients with large full thickness loss of skin from burns require skin grafting for healing, function, and rehabilitation. This group presents a major part of the burn problem, and a summary of their needs and their care is outlined here. In the extensive literature, much effort has been directed toward some method of local care, to taking care of acute and chronic shock, and to problems of deranged blood chemistry and metabolism. This work has been of great benefit and has stimulated a burn consciousness, so that excellent care may be afforded burned patients, and many more lives are saved, thus adding to the numbers who require later grafting and reconstruction. There still is, however, a lack of reports of completed care of patients who have been badly burned and not only have been saved from death but have had satisfactory surgical repair of open wounds and contractures and have
THE PARASITOLOGY AND CLINICAL ASPECTS OF MALARIA IN ANTIGUA
Authors: W. M. McDonald
Journal: BMJ (1922)

MTEC BRITNL 59 abnormnally sensitive to the vaccine, yet the clinical clhange for the better appears in a muclh shorter time, and we may therefore only conclude that tlle patient's general resistance does not coincide witlh hiis resistance at the focus of infection.This is demonstrated in a remarkable nmanner in cases of large carbuncles accompanied by grave toxic symptoms.The disappearance of the slate-blue colour round the lesion and its replacement by a brighlt red erytllema is a striking clhangce that occurs in a fcw hours.A possible explanation is tlat tlle first antibodies produced by the vaccine are all renmoved from thle circulation as quickly as they are formed by sonic process of concentration at tleu site of infection.Wlhetlher tlle inflamed tissues in tllat area play an active or a passive part in this fixation of tlhe.antibodies is a matter of speculation at present.Thle following cases are the first few treated with tlle vaccine, and nearly every one illustrates some point discussed above.rTlie cases lhave not been " selected," but are a true consecutive series..Case l.-Aged 26.Septic finger due to running dirty scissors into it.Next day, small pustule, lymphangitis, anid axillary adlenitis.The finger was fomented anld the lymphangitis disappeared, but swelling of the whole digit commenced.Serum only on iicisionI.General lassitide.Vaccinie given on seventhl day.Next day the swelling was rapidlv subsiding ; there was distiniet tenderness at the point of.original injiuy.Pus visible tiat eveniing; onl incisOll, a large qtlanjtity escaped aind there was comolete relief from pain.Next day, a clean granulatinl suLrface, which was completely healedl onl the fourth day after adminiistrationl of vaccine.Case 2.-Aged 11.Streptococcal peritonitis, apparently idiopathic.Abdomen opened, cIraii i iserted: proginosis hopeless.Vaccine givenl twetty-four holurs later, up to which time the patienit was mauiacal anid apparently dying.Heroin failed to calm the patienit.Six lhours after vaccine was given the patient wenit quietly to sleep, temperature and pulse fell, thje former several degrees, anld the case made an ulneventful recovery.Case 3.-Pyaemia; purulent arthritis of right elbow with abscesses in axilla anid groin.Temperature 1000 to 102.20, pulse 100 to 120.Vacciie given.The next day the temperature was still swinging, btut oni the down grade.A second dose was given fooLr days later, and temperature anld pulse settled finally oni the tenth day.Case 4.-Aged 11.Acute osteomyelitis of spine and infe^tion of canal.Prognosis hopeless.Vaccinie given on tthe sixth day at 11 a.m.That eveningr the tenmerature rose half a degree, hut the next morniing was down one degtree; the pulse fell from 140 to 110.The patient Nvas operated on that afternoon, anld died-early liext morning.Case 5.-Carbuncle of hand, involving half of palm, index finger,
THE PROPRIETARY SYSTEM AND ITS REMEDY.
Authors: F. E. STEWART
Journal: JAMA (1895)

<h3>THE PROPRIETARY SYSTEM.</h3> For the purpose of promoting progress in science and the useful arts the Constitution of the United States gives Congress the power to grant to authors and inventors for limited times the exclusive use of their respective writings and discoveries. Hence our copyright and patent laws. A patent is a contract between the government, representing the public at large, and the inventor. The consideration moving from the government is the granting of the exclusive use of the invention for a limited time. The consideration moving from the inventor is the invention of a new and useful article, and the giving to the public full knowledge of it by a proper application for a patent, so that, when the patent expires, the public may manufacture the invention. The wisdom of such a law seems apparent, for by it inventors are stimulated to produce new and useful articles, capital