tbuckley/cabot-search huggingface dataset:
Antitumor Activity of the Selective Pan-RAF Inhibitor TAK-632 in BRAF Inhibitor-Resistant Melanoma
Authors: Akito Nakamura, Takeo Arita, Shuntarou Tsuchiya, Jill Donelan, Jouhara Chouitar, Elizabeth Carideo, Katherine Galvin, Masanori Okaniwa, Tomoyasu Ishikawa, Sei Yoshida
Journal: Cancer Research (2013)

The mitogen-activated protein kinase (MAPK) pathway is particularly important for the survival and proliferation of melanoma cells. Somatic mutations in BRAF and NRAS are frequently observed in melanoma. Recently, the BRAF inhibitors vemurafenib and dabrafenib have emerged as promising agents for the treatment of melanoma patients with BRAF-activating mutations. However, as BRAF inhibitors induce RAF paradoxical activation via RAF dimerization in BRAF wild-type cells, rapid emergence of acquired resistance and secondary skin tumors as well as presence of few effective treatment options for melanoma bearing wild-type BRAF (including NRAS-mutant melanoma) are clinical concerns. Here, we demonstrate that the selective pan-RAF inhibitor TAK-632 suppresses RAF activity in BRAF wild-type cells with minimal RAF paradoxical activation. Our analysis using RNAi and TAK-632 in preclinical models reveals that the MAPK pathway of NRAS-mutated melanoma cells is highly dependent on RAF. We also show that TAK-632 induces RAF dimerization but inhibits the kinase activity of the RAF dimer, probably because of its slow dissociation from RAF. As a result, TAK-632 demonstrates potent antiproliferative effects both on NRAS-mutated melanoma cells and BRAF-mutated melanoma cells with acquired resistance to BRAF inhibitors through NRAS mutation or BRAF truncation. Furthermore, we demonstrate that the combination of TAK-632 and the MAPK kinase (MEK) inhibitor TAK-733 exhibits synergistic antiproliferative effects on these cells. Our findings characterize the unique features of TAK-632 as a pan-RAF inhibitor and provide rationale for its further investigation in NRAS-mutated melanoma and a subset of BRAF-mutated melanomas refractory to BRAF inhibitors.
A Prospective Study of Diagnostic Methods in Adenoma Follow-up
Authors: C.B. Williams, F.A. Macrae, C.I. Bartram
Journal: Endoscopy (1982)

Three hundred and thirty patients having had previous colonoscopic polypectomy of adenomas were recalled for follow-up and submitted to all available diagnostic methods: occult blood testing, digital examination, rigid proctosigmoidoscopy, fibre-optic sigmoidoscopy, total colonoscopy and double contrast barium enema. Polyps up to 7 mm diameter were electro-coagulated during diagnostic endoscopy but larger polyps were left in situ for barium enema before polypectomy at a later date. Disparities between endoscopy and X-ray were rechecked by one or both procedures. Occult blood testing, digital examination and rigid proctosigmoidoscopy were found to be inaccurate or ineffective in diagnosis of the 37% of patients with further adenomas or carcinomas. Double contrast barium enema demonstrated 71% of larger lesions compared to the 92% shown by colonoscopy. The commonest sites of X-ray inaccuracy were in the sigmoid colon and caecum. Colonoscopy permits immediate electrocoagulation or snare polypectomy of any lesions seen, as well as being the more accurate investigation and is, therefore, the procedure of choice in post polypectomy follow-up. The mean time taken for diagnostic total colonoscopy in this series was 15.3 minutes, comparable to the time taken for barium enema. Postal questionnaire showed both procedures to be equally well tolerated by the patients. Thirty per cent of colonoscopies were, however, considered technically difficult by the endoscopist, and for these patients it is suggested that follow-up should be by the combination of fibre-sigmoidoscopy using carbon dioxide insufflation and immediate double contrast barium enema. Should this combination indicate a need for total colonoscopy, then almost all adenomas and cancers would be detected. Total examination of the colon by one or other means is essential, over half the patients with adenomas and three of the five patients with carcinoma showing no pathology in the territory of fibresigmoidoscopy or limited colonoscopy.
POSTERIOR PITUITARY IN PYELITIS
Authors: J. I. Hofbauer
Journal: JAMA (1934)

To the Editor:—  The interesting article of Ward Darley and W. B. Draper inThe Journal(March 3, p. 677), emphasizing atony of the musculature of the renal pelvis and ureter with the resultant sluggish drainage as an important factor in the development and course of pyelitis, refers to the experimental work of Gruber. He showed that the ureteral muscle responds with increased peristalsis to solution of pituitary ( J. Urol.  20 :27 [July] 1928), as they confirmed ( J. Urol.  26 :1 [July] 1931).  At the meeting of the American Gynecological Society in 1927 I presented a preliminary report of work done at Johns Hopkins on the etiology of pyelitis gravidarum, in which the occurrence of dilatation and atony of the upper urinary tract as physiologic phenomena in pregnant woman was stressed. The use of solution of pituitary was suggested for stimulating ureteral peristalsis in cases of pyelitis gravidarum that do
Motorcycle Helmet Use and Injuries
Authors: David L. Nunley
Journal: JAMA (1995)

<h3>To the Editor.</h3> —The article by Dr Kraus and colleagues<sup>1</sup>concerning effects of a mandatory motorcycle helmet law in California is an excellent example of how medical bias can produce studies designed chiefly to support a preconceived conclusion. In analyzing the precipitous drop in motorcycle crash fatalities following implementation of a helmet law, the authors completely fail to take into consideration the major determinant of that decline—the unprecedented reduction in the number of accidents involving motorcyclists. Both common sense and statistics inform us that if fewer crashes are occurring, then fewer motorcyclists will be killed or injured. During the 4 years preceding the helmet law, motorcycle crashes declined at an average rate of 9% annually, and motorcycle-related deaths showed nearly an identical decrease of 8.6% per year. However, motorcycle crashes in California decreased from 18203 in 1991 to 13568 in 1992.<sup>2</sup>This 26% decrease is nearly three times
Detection of latent coronary stenosis in conscious dogs: regional functional and electrocardiographic responses to isoprenaline
Authors: A. BATTLER, K. P GALLAGHER, V. F FROELICHER, T. KUMADA, W S. KEMPER, J. ROSS
Journal: Cardiovascular Research (1980)

A conscious animal model was developed in which coronary stenosis could be produced while regional myocardial function and local surface electrocardiograms were measured. Responses to isoprenaline stress in the presence of mild (latent) coronary stenosis were then examined. In the absence of coronary stenosis, isoprenaline produced increases in regional function and no change in the surface VCG; at higher doses, increases in the endocardial ST segments occurred. After partial coronary stenosis, which produced no apparent regional dysfunction or electrocardiographic changes, isoprenaline infusion for 3 min (0.02 microgram . kg-1 . min-1) rapidly produced decreases in percentage wall thickening (average 17 +/- 4%, mean +/- SE, P < 0.01) and increases in the mean sum of VCG ST segments by 0.23 +/- 0.06 mV (P < 0.05). 1 min after stopping isoprenaline, most dogs showed further significant deterioration of both measures of ischaemia, but by 5 min there was no significant mean change from control. We conclude that in the presence of latent partial coronary stenosis, stress due to mild sympathomimetic stimulation alone can rapidly induce regional myocardial ischaemia. Deterioration of regional myocardial contractile function during such stress can provide as sensitive means of detecting latent coronary obstruction.
Antigen-reactive T cell clones restricted by mixed isotype A beta d/E alpha d class II molecules.
Authors: M Matsunaga, K Seki, T Mineta, M Kimoto
Journal: The Journal of Experimental Medicine (1990)

Mixed isotype A beta dE alpha d class II molecule-restricted antigen-reactive T cell clones were obtained from (BALB/c x B6E alpha d)F1 mice. These T cell clones responded to keyhole limpet hemocyanin in the presence of (BALB/c x B6E alpha d)F1 but not CBF1 APCs. Both anti-A beta d and anti-E alpha mAbs blocked the proliferative responses of these clones. The frequency of such mixed isotype A beta E alpha-restricted T cell clones in (BALB/c x B6E alpha d)F1 mice was estimated to be approximately 10% from our limiting dilution cloning. The existence of such mixed isotype class II molecule-restricted T cells would have important implications for the expansion of the T cell repertoire as well as the induction of autoimmunity.
Preemptive Liver Transplantation from a Living Related Donor for Primary Hyperoxaluria Type I
Authors: Rainer W. Gruessner
Journal: New England Journal of Medicine (1998)

To the Editor: Primary hyperoxaluria type I is an autosomal recessive disorder characterized by a deficiency of liver-specific peroxisomal alanine–glyoxylate aminotransferase (EC 2.6.1.44). The dis...
THE CORRECTION OF EXOPHORIA BY DEVELOPMENT OF THE INTERNI.
Authors: W. H. ROBERTS
Journal: JAMA (1905)

There are sins of omission as well as sins of commission in every profession. Oculists are guilty of the former when they treat asthenopic symptoms as though all were accommodative and none muscular. This paper does not aim at bringing out anything new in the way of diagnosis, or treatment, but simply recommends the necessity of determining the muscle balance in all refraction cases, and emphasizes a known and tried method of relieving the vast majority of cases in which exophoria exists. This subject has been impressed on me by seeing numerous cases that have passed through the hands of competent oculists, wearing glasses practically correct, with asthenopic symptoms unabated because of an unsought for and unrelieved exophoria. I wish also to sound a note of warning against the indiscriminate performance of the various tenotomies, with or without advancements, wherever imbalance is found. While not opposed to operative measures when
Ultrasound-Guided Thrombin Injection for the Treatment of Postcatheterization Pseudoaneurysms
Authors: Lucy La Perna, Jeffrey W. Olin, Debbie Goines, Mary Beth Childs, Kenneth Ouriel
Journal: Circulation (2000)

This prospective study was designed to assess the safety and efficacy of using bovine thrombin injection to treat pseudoaneurysms.From April 1998 through December 1999, 70 pseudoaneurysm were injected with bovine thrombin under the guidance of color duplex ultrasound. The most superficial pseudoaneurysm chamber was entered with a 1.5-inch, 19- to 22-gauge or spinal needle. Bovine thrombin, in a 1000 U/cc solution, was injected into the chamber. A total of 36 women and 34 men underwent ultrasound-guided thrombin injection (UGTI). Their mean age was 69.5 years. Most pseudoaneurysms were associated with diagnostic cardiac catheterization or percutaneous coronary intervention (80%). Two pseudoaneurysms arose from the brachial artery; the remainder were in the groin. Twenty-one patients were being treated with either heparin or warfarin, and the majority of the others were on antiplatelet therapy with aspirin or clopidogrel. UGTI was successful in 66 of the 70 patients (94%). The first patient in the series had 2 attempts at thrombin injection and refused further attempts. Two patients had undergone stent graft placement and had short, wide tracts. Both of these patients required surgical repair of their pseudoaneurysms. The fourth patient had a nearly complete pseudoaneurysm thrombosis and was lost to follow-up on discharge. No arterial thrombotic events occurred. One patient had a soleal vein thrombosis in the ipsilateral leg.UGTI was safe and effective in 94% of patients with postcatheterization pseudoaneurysms. Anticoagulant use did not hinder successful thrombosis. UGTI should be the initial treatment of choice for patients with postcatheterization pseudoaneurysms.
Increased Brain Retention of Tc-99m HMPAO Following Acetazolamide Administration
Authors: ROBERT W. BURT, ROBERT M. WITT, DELORES CIKRIT, JAMES CARTER
Journal: Clinical Nuclear Medicine (1991)

Sixty-five patients rferred for Tc-99m HMPAO SPECT brain perfusion studies had measurements of global Tc-99m HMPAO retention after injection at rest and after acetazolamide pretreatment. Acetazolamide produced relative changes in Tc-99m HMPAO retention similar to those previously reported with Xe-133 regional cerebvral blood flow (rCBF) measurements. This adition to imaging protocols allows another objective evaluation of the cerebral vascular reserve.
Human leukocyte antigen class I and II alleles in non-Hodgkin lymphoma etiology
Authors: Sophia S. Wang, Amr M. Abdou, Lindsay M. Morton, Rasmi Thomas, James R. Cerhan, Xiaojiang Gao, Wendy Cozen, Nathaniel Rothman, Scott Davis, Richard K. Severson, Leslie Bernstein, Patricia Hartge, Mary Carrington
Journal: Blood (2010)
(35) Severe dominant dystrophic epidermolysis bullosa
Authors: M.J. Tidman, R.A. Marsden
Journal: British Journal of Dermatology (1985)

Journal Article (35) Severe dominant dystrophic epidermolysis bullosa Get access M.J. Tidman, M.J. Tidman Guy's Hospital, London SE1 Search for other works by this author on: Oxford Academic Google Scholar R.A. Marsden R.A. Marsden St George's Hospital, London SW17 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue s29, 1 July 1985, Pages 80–81, https://doi.org/10.1111/j.1365-2133.1985.tb13050.x Published: 01 July 1985
ANTIPNEUMOCOCCIC IMMUNITY REACTIONS IN INDIVIDUALS OF DIFFERENT AGES
Authors: W. D. Sutliff, Maxwell Finland
Journal: The Journal of Experimental Medicine (1932)

1. The incidence of pneumococcidal power of the whole defibrinated blood in human beings has been shown to vary with age. The age distribution of other type-specific antibodies varies similarly, insofar as they are frequent enough to be compared or technically demonstrable. 2. The incidence of pneumococcidal power of the whole defibrinated blood for Type I, Type II, and Type III differs. Type I is the rarest, Type II is the most frequent, and Type III is of intermediate frequency. The type-specific antibodies responsible for the other tests employed show a similar relative frequency in regard to Types I and II, but some variation in regard to Type III. 3. The skin reactions to the acetic acid-predpitable proteins and autolysates of the pneumococci are negative or rarely positive in infants, infrequently positive in childhood, and positive in a high percentage of adults.
Comparison of Echocardiographic Dyssynchrony Assessment by Tissue Velocity and Strain Imaging in Subjects With or Without Systolic Dysfunction and With or Without Left Bundle-Branch Block
Authors: Chinami Miyazaki, Brian D. Powell, Charles J. Bruce, Raul E. Espinosa, Margaret M. Redfield, Fletcher A. Miller, David L. Hayes, Yong-Mei Cha, Jae K. Oh
Journal: Circulation (2008)

Background— Several echocardiographic dyssynchrony indexes have been proposed to identify responders to cardiac resynchronization therapy using tissue velocity and strain. The present study aimed to compare tissue velocity–derived and strain-derived dyssynchrony indexes in patients with or without systolic dysfunction and left bundle-branch block. Methods and Results— Tissue Doppler imaging was performed in 120 subjects divided into 4 groups: group 1 (n=40), normal subjects; group 2 (n=20), normal left ventricular ejection fraction and left bundle-branch block; group 3 (n=20), left ventricular ejection fraction &lt;35% and normal conduction; and group 4 (n=40), left ventricular ejection fraction &lt;35% and left bundle-branch block. Dyssynchrony indexes based on time to peak tissue velocity (septal-lateral delay, anteroseptal-posterior delay, and SD in time to peak systolic velocity in the 12 left ventricular segments) and strain (SD of time to peak strain in 12 segments) were measured. The SD in time to peak systolic velocity in the 12 left ventricular segments was greater in group 4 (54 ms; 25th and 75th percentiles, 46 to 64 ms) than group 1 (44 ms; 25th and 75th percentiles, 28 to 53 ms; P =0.006), but there was a considerable overlap of all tissue velocity–derived indexes among 4 groups, with 40% to 68% of group 1 having values proposed for predicting the responders of cardiac resynchronization therapy. The SD of time to peak strain in 12 segments distinguished these groups with much less overlap ( P &lt;0.01 for all pairwise comparisons). Conclusions— A substantial proportion of normal subjects have tissue velocity–derived dyssynchrony indexes higher than the cutoff value proposed for predicting beneficial effect of cardiac resynchronization therapy. Strain-derived timing index appears to be more specific for dyssynchrony in patients with systolic dysfunction and left bundle-branch block. Identifying an optimal tissue velocity– or strain-derived dyssynchrony index requires a large prospective clinical trial.
56 DYNAMICS OF HCV QUASISPECIES DURING TELAPREVIR TREATMENT DISSECTED USING ULTRA-DEEP PYROSEQUENCING: TREATMENT FAILURE IN 100% OF GENOTYPE 1A PATIENTS
Authors: P. Pinson, P. Trimoulet, J. Papuchon, J. Foucher, J. Vergniol, F. Chermak, L. Wittkop, W. Merrouche, S. Reigadas, M. Kann, H. Fleury, V. de Lédinghen
Journal: Journal of Hepatology (2012)
Health improvement programmes: really too complex to evaluate?
Authors: L. Bond, P. Craig, M. Egan, K. Skivington, H. Thomson
Journal: BMJ (2010)

Imagine an intervention whose effects vary within and between individuals and depend on subtle interactions between deliverers and recipients, and in which exposure is uncertain. Given this complexity, who would contemplate conducting a randomised controlled trial? In fact, all these issues must be dealt with in drug or therapeutic trials, as well as in …
Rosiglitazone reduces serum homocysteine levels, smooth muscle proliferation, and intimal hyperplasia in Sprague-Dawley rats fed a high methionine diet
Authors: Subramanyam N. Murthy, Demian F. Obregon, Natasha N. Chattergoon, Neil A. Fonseca, Debasis Mondal, Jeffrey B. Dunne, Jose G. Diez, James R. Jeter, Philip J. Kadowitz, Krishna C. Agrawal, Dennis B. McNamara, Vivian A. Fonseca
Journal: Metabolism (2005)
Potential impact of physical activity and sport on the immune system--a brief review.
Authors: R J Shephard, P N Shek
Journal: British Journal of Sports Medicine (1994)

Description is given of methods that can evaluate the main functional elements of the immune system. Acute responses to exercise depend on the intensity and duration of the required activity relative to the individual's fitness level. Moderate endurance exercise causes either no change or an enhancement of such indices as total leucocyte count, granulocyte, monocyte, lymphocyte and natural killer cell count, total T cell count, helper:suppressor cell ratio, cell proliferation in response to mitogens, serum immunoglobulin levels, and in vitro immunoglobulin production. However, exhausting exercise tends to produce adverse changes in these same indices, particularly if the physical activity is accompanied by environmental or competitive stress. Moderate, appropriately graded training reduces reactions to any given absolute intensity of exercise. When pursuing a more demanding training regimen, it is important that the exerciser optimize immune responses. If athletic preparation is pursued to the level of staleness and/or muscle damage, it can have substantial negative implications for many aspects of immune function, including resistance to acute infections, HIV infections, ageing, cancer and other conditions influenced by the immune system.
Serum-Plasma Differences in Total Cholesterol: What Correction Factor Should Be Used?
Authors: Gary G. Wickus
Journal: JAMA (1992)

To the Editor.  —Cloey et al 1 reported that the mean cholesterol concentration in plasma samples prepared with disodium EDTA (ethylenediaminetetraacetic acid) was 4.7% lower than the mean cholesterol concentration in serum samples. The difference they observed is larger than the previously established value. 2,3 However, Lipid Research Clinics Laboratory Methods Committee 2 reported mean plasma cholesterol concentrations that ranged from 1% to 4% lower than the mean serum cholesterol concentration. The reevaluation report 1 suggested that the increased difference was due to a higher concentration of disodium EDTA, now routinely used in blood collection tubes.  We drew blood samples from 110 patients (aged 53 ± 14 years) who presented for lipoprotein analysis. Samples were collected with Vacutainer Systems collection tubes, (Becton-Dickinson, Rutherford, NJ) and the collection order of the paired serum and plasma specimens was alternated. Disodium EDTA tubes (final concentration, 4.46 mmol/L) were completely filled and mixed.
Excitability and Electrical Activity of Human Myocardial Strips from the Left Atrial Appendage in Cases of Rheumatic Mitral Stenosis
Authors: R. T. VAN DAM, D. DURRER
Journal: Circulation Research (1961)

In isolated strips of human left atrium, ob tamed during commissurotomy for rheumatic mitral stenosis, recordings of the electrical action phenomena were made and determina tiorms of the resting excital)ility amid of the ex citability cycle were carried out. Two of the four strips did not show any appreciable spontaneous electrical activity and were found to be inexcitable by applied current pulses. These strips were obtained from pa tients in whom permanent or temporary atrial fibrillation existec1 prior to operation, and in whom the left atrial appendage was grossly dilated. In the two other strips, obtained from patients with a sinus rhythm prior to opera tion and with left atrial. appendages of ap proximately normal size, determinations of strength/duration and strength/interval re quirements, together with the recorded com plexes, demonstrated the occurrence of a functional dissociation between various elements in these muscle strips, which increased during the refractory period. This functional dissociation is thought to be related to the development of connective tissue between the muscle fibers, observed by microscopic exam ination, and due to the rheumatic process. Its significance in the genesis of atrial arrhyth mias in cases of mitral stenosis is discussed. Strophanthin in a concentration of 10-8 was found to shorten the refractory period and to cause a lowering of the resting threshold for stimuli with a duration of less than 5 msec., and a rise in the threshold for larger stimuli.
Statins for Atherosclerosis — As Good as It Gets?
Authors: Michael R. Ehrenstein, Elizabeth C. Jury, Claudia Mauri
Journal: New England Journal of Medicine (2005)

If ever there were a perfect marriage of drug with disease it might be between statins and atherosclerosis. At first the relationship was simple: statins inhibited synthesis of the cholesterol that contributed to atheroma, and less cholesterol meant less atheroma. Just as married couples often adapt to each other, so it is with statins and atheroma, or to be more precise, an increased understanding of their relationship has revealed an apparent adaptation. Atherosclerosis is now recognized to have a notable inflammatory component, and in parallel, statins appear to inhibit inflammatory processes directly. Rheumatologists pondering this phenomenon from the outside (and . . .