tbuckley/cabot-search huggingface dataset:
Suppression of Antiviral Innate Immunity by Sunitinib Enhances Oncolytic Virotherapy
Authors: Babal K Jha, Beihua Dong, Carvell T Nguyen, Irina Polyakova, Robert H Silverman
Journal: Molecular Therapy (2013)

The use of lytic viruses to preferentially infect and eliminate cancer cells while sparing normal cells is a promising experimental therapeutic approach for treating cancer. However, the efficacy of oncolytic virotherapy is often limited by two innate immunity pathways, the protein kinase PKR and the 2′-5′-oligoadenylate (OAS)/RNase L systems, which are widely present in many but not all tumor cell types. Previously, we reported that the anticancer drug, sunitinib, an inhibitor of VEGF-R and PDGF-R, has off-target effects against both PKR and RNase L. Here we show that combining sunitinib treatments with infection by an oncolytic virus, vesicular stomatitis virus (VSV), led to the elimination of prostate, breast, and kidney malignant tumors in mice. In contrast, either virus or sunitinib alone slowed tumor progression but did not eliminate tumors. In prostate tumors excised from treated mice, sunitinib decreased levels of the phosphorylated form of translation initiation factor, eIF2-α, a substrate of PKR, by 10-fold while increasing median viral titers by 23-fold. The sunitinib/VSV regimen caused complete and sustained tumor regression in both immunodeficient and immunocompetent animals. Results indicate that transient inhibition of innate immunity with sunitinib enhances oncolytic virotherapy allowing the recovery of tumor-bearing animals. The use of lytic viruses to preferentially infect and eliminate cancer cells while sparing normal cells is a promising experimental therapeutic approach for treating cancer. However, the efficacy of oncolytic virotherapy is often limited by two innate immunity pathways, the protein kinase PKR and the 2′-5′-oligoadenylate (OAS)/RNase L systems, which are widely present in many but not all tumor cell types. Previously, we reported that the anticancer drug, sunitinib, an inhibitor of VEGF-R and PDGF-R, has off-target effects against both PKR and RNase L. Here we show that combining sunitinib treatments with infection by an oncolytic virus, vesicular stomatitis virus (VSV), led to the elimination of prostate, breast, and kidney malignant tumors in mice. In contrast, either virus or sunitinib alone slowed tumor progression but did not eliminate tumors. In prostate tumors excised from treated mice, sunitinib decreased levels of the phosphorylated form of translation initiation factor, eIF2-α, a substrate of PKR, by 10-fold while increasing median viral titers by 23-fold. The sunitinib/VSV regimen caused complete and sustained tumor regression in both immunodeficient and immunocompetent animals. Results indicate that transient inhibition of innate immunity with sunitinib enhances oncolytic virotherapy allowing the recovery of tumor-bearing animals.
289 THE ACTIN CYTOSKELETON AS A NOVEL TARGET OF AMP-ACTIVATED PROTEIN KINASE (AMPK) IN HEPATIC STELLATE CELLS
Authors: K. Rombouts, C. Tosti Guerra, A. Caligiuri, C. Bertolani, E. Rovida, F. Vizzutti, G. Laffi, M. Pinzani, F. Marra
Journal: Journal of Hepatology (2009)
WARFARIN DOSING ALGORITHM REFINEMENTS AFTER 7-9 DAYS OF THERAPY BASED ON PHARMACOGENETIC, PHARMACOKINETIC, CLINICAL, AND LABORATORY DATA
Authors: Benjamin D. Horne, Petra A. Lenzini, Mia Wadelius, Andrea L. Jorgensen, Stephen E. Kimmel, Niclas Eriksson, Jeffrey L. Anderson, Munir Pirmohamed, Nita A. Limdi, James K. Burmester, Daniel Kurnik, Charles M. Stein, Michael D. Caldwell, Charles S. Eby, Anders Rane, John D. Lindh, Jae-Gook Shin, Ho-Sook Kim, Pantep Angchaisuksiri, Jinbo Chen, John F. Carlquist, Gloria R. Grice, Kathryn E. Kronquist, Brian F. Gage
Journal: Journal of the American College of Cardiology (2010)
The relationship between upper respiratory infections and hospital admissions for asthma: a time-trend analysis.
Authors: S L Johnston, P K Pattemore, G Sanderson, S Smith, M J Campbell, L K Josephs, A Cunningham, B S Robinson, S H Myint, M E Ward, D A Tyrrell, S T Holgate
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We have shown that viruses are associated with 80 to 85% of asthma exacerbations in school-age children in the community. We hypothesize that viral infections are also associated with severe attacks of asthma precipitating hospital admissions. To investigate this, we conducted a time-trend analysis, comparing the seasonal patterns of respiratory infections and hospital admissions for asthma in adults and children. During a 1-yr study in the Southampton area of the United Kingdom, 108 school-age children monitored upper and lower respiratory symptoms and took peak expiratory flow rate (PEFR) recordings. From children reporting a symptomatic episode or a decrease in PEFR, samples were taken for detection of viruses and atypical bacteria. A total of 232 respiratory viruses and four atypical bacteria were detected. The half-monthly rates of upper respiratory infection were compared with the half-monthly rates for hospital admissions for asthma (International Classification of Diseases [ICD] code 493) for the same time period for the hospitals serving the areas from which the cohort of schoolchildren was drawn. The relationships of upper respiratory infections and hospital admissions for asthma with school attendance were studied. Strong correlations were found between the seasonal patterns of upper respiratory infections and hospital admissions for asthma (r = 0.72; p < 0.0001). This relationship was stronger for pediatric (r = 0.68; p < 0.0001) than for adult admissions (r = 0.53; p < 0.01). Upper respiratory infections and admissions for asthma were more frequent during periods of school attendance (87% of pediatric and 84% of total admissions), than during school holiday periods (p < 0.001). These relationships remained significant when allowance was made for linear trend and seasonal variation using multiple regression analysis (p < 0.01). Not surprisingly, school attendance, because it is a major factor in respiratory virus transmission, was found to be a major confounding variable in children. This study demonstrates that upper respiratory viral infections are strongly associated in time with hospital admissions for asthma in children and adults. Rhinoviruses were the major pathogen implicated, and the majority of viral infections and asthma admissions occurred during school attendance.
Chemotherapy better tolerated when matched to body's rhythm
Authors: Z. Kmietowicz
Journal: BMJ (1997)

Giving chemotherapy as a variable infusion that mimics circadian rhythms rather than as a constant infusion reduces fivefold the adverse events in patients with colorectal cancer, according to the results of a randomised trial. The technique of variable drug infusion, known as chronotherapy, may benefit all patients with cancer requiring drug therapy by improving response and tolerance, believe French researchers.

In their trial the investigators assigned 186 patients with previously untreated metastases from colorectal …
THE NUMBER OF VERY EARLY ENDOTHELIAL PROGENITOR CELL COLONIES CORRELATES WITH ATHEROSCLEROSIS BURDEN IN ACUTE CORONARY SYNDROMES
Authors: Remi Kouz, Colin Berry, Eric Rheaume, Geneviève Brand, Anne-Elen Kernaleguen, Jean Grégoire, Reda Ibrahim, Jacques Lespérance, Philippe L'Allier, Stéphane Noble, Philippe Meyer, Marie-Claude Guertin, Jean-Claude Tardif
Journal: Journal of the American College of Cardiology (2011)
Protein kinase SGK1 enhances MEK/ERK complex formation through the phosphorylation of ERK2: Implication for the positive regulatory role of SGK1 on the ERK function during liver regeneration
Authors: Minho Won, Kyeong Ah Park, Hee Sun Byun, Young-Rae Kim, Byung Lyul Choi, Jang Hee Hong, Jongsun Park, Jeong Ho Seok, Young-Ho Lee, Chung-Hyun Cho, In Sang Song, Yong Kyung Kim, Han-Ming Shen, Gang Min Hur
Journal: Journal of Hepatology (2009)
Salaries of Research Workers
Authors: R. Schofield, T. M. Dexter, A. J. Bateman, R. Saffhill, S. Muldal, C. H. Ockey, P. T. Iype, T. Allen, N. Testa, M. Fox, D. Scott, J. H. Hendry, L. G. Skinner, R. F. Itzhaki, B. Fox, N. J. F. Dodd, B. I. Lord, M. Moore, J. L. M. Boyle, C. S. Potten, B. Cercek, P. J. O'Connor, M. Potter, J. V. Davies, M. Ebert, P. M. Naha, D. J. Pilinger
Journal: BMJ (1975)
RADIOACTIVE IRON AND ITS EXCRETION IN URINE, BILE, AND FECES
Authors: P. F. Hahn, W. F. Bale, R. A. Hettig, M. D. Kamen, G. H. Whipple
Journal: The Journal of Experimental Medicine (1939)

Radioactive iron as ferrous gluconate given by vein enables us to study iron excretion in urine, bile, and feces. There is an initial extra output in urine and feces during a few days (3 to 15 days) following the iron injection and this may total 2 to 8 per cent of the injected iron. Following this initial reaction the urinary excretion of radio-iron drops to traces or even to zero. The feces always contain measurable amounts of radio-iron-in five dogs receiving 100 to 250 mg. of radio-iron the fecal excretion per day settled down to 0.05 to 0.4 mg. per day. Blood destruction (acetyl-phenylhydrazine) causes a definite increase in radio-iron eliminated in the feces (0.1 to 1.0 mg. per day). Probably most of this excess iron comes through the biliary tract (bile fistula). The bile under usual conditions contributes very little iron to the intestine (0.01 mg. radio-iron per day or less). The body controls its iron stores by absorption or lack of it rather than by its capacity to eliminate it. The evidence is overwhelming that the dog excretes iron with difficulty and in small amounts (even in the plethoric state) by means of the biliary and gastro-intestinal tracts.
A Defense of the Bicycle.
Authors: George S. Brown
Journal: JAMA (1896)

Birmingham, Ala., Aug. 21, 1896. <h3>To the Editor:</h3> —Will you kindly allow me space to comment briefly on an editorial in the Journal of the 15th inst. entitled "Bicycling Pro and Con." I would like to ask how many cases of deformity of the female pelvis from this cause have been noted? Also, how many patients have applied for treatment for vesical and prostatic irritation caused by the bicycle saddle? To place the bicycle in its proper place as a machine for good or evil, it would seem to be necessary to compare all such damage done with the good it has accomplished. The great advantage which the wheel has over all other modes of exercise is the pleasure it affords. The therapeutic value of fun is, I think, undisputed. It combines fun with plenty of fresh air and exercise, and if there is any better combination from a health
STUDIES ON THE GENERALIZED SHWARTZMAN REACTION
Authors: Lewis Thomas, Joel Brunson, Richard T. Smith
Journal: The Journal of Experimental Medicine (1955)

Lesions indistinguishable from those of the generalized Shwartzman reaction occured in rabbits when a single intravenous injection of Gram-negative bacterial endotoxin was accompanied, or followed, by an injection of one of the following synthetic, heparin-like, acidic polymers-sodium polyanethol sulfonate, dextran sulfate, or sodium polyvinyl alcohol sulfonate. These reactions were produced by doses of polymer or of endotoxin which were without demonstrable effect when given singly. Heparin, in those similar to those previously shown to protect rabbits against the lesions of the generalized Shwartzman reaction, prevented the reaction to the combined injection of endotoxin and acidic polymers. Nitrogen mustard, which was previously shown to prevent the lesions of the generalized Shwartzman reaction from occurring after two intravenous injections of endotoxin, had no protective action against the lesions produced by the combined injection of endotoxin and polymer. Cortisone did not affect the reaction to endotoxin and polymer. The role of fibrinogen in the reaction under study is discussed in the paper which follows.
Thirty‐Minute Total Synthesis of Microfluidic Systems and Functionalized Porous Elements via “Living” Radical Photo‐Polymerization
Authors: Vinay V. Abhyankar, Anson V. Hatch
Journal: Advanced Healthcare Materials (2012)

A “living” radical photo-polymerization (LRPP) technique is used to rapidly fabricate microfluidic channels and micro-patterned porous polymer monoliths. Surface-initiated LRPP is then used to functionalize porous elements in a robust one-step surface modification process. Assay-ready platforms can be fully realized in less than 30 minutes. An application relevant to clinical diagnostics is presented. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Rules and similarity processes in artificial grammar and natural second language learning: What is the “default”?
Authors: Peter Robinson
Journal: Behavioral and Brain Sciences (2005)

Are rules processes or similarity processes the default for acquisition of grammatical knowledge during natural second language acquisition? Whereas Pothos argues similarity processes are the default in the many areas he reviews, including artificial grammar learning and first language development, I suggest, citing evidence, that in second language acquisition of grammatical morphology “rules processes” may be the default.
Intubation in Epiglottitis
Authors: Edmund N. Pressman
Journal: JAMA (1974)

<h3>To the Editor.—</h3> I found the article quite well done. However, I did find one point troublesome. The authors give the impression that endotracheal intubation and tracheotomy are mutually exclusive, with tracheotomy the safer procedure. In our experience, this condition is best treated by the combined anesthesia and ear, nose, and throat services. First, a decision is made in the question of nasotracheal intubation vs tracheotomy. In cases where tracheotomy is the chosen treatment, the patients are first orally intubated as an emergency measure. Thus, the chance of acute respiratory decompensation is eliminated. Then tracheotomy may be done, with the endotracheal tube in place, under optimal surgical and respiratory conditions. In skilled hands, tracheal intubation is a small risk as compared to tracheotomy in a severely hypoxic child with impending respiratory collapse.
Surveys of workers occupationally exposed to PCBs and of yusho patients.
Authors: M Takamatsu, M Oki, K Maeda, Y Inoue, H Hirayama, K Yoshizuka
Journal: Environmental Health Perspectives (1985)

Surveys of workers occupationally exposed to polychlorinated biphenyls (PCBs) in the production of thread or of paint, and of yusho patients were carried out from 1973 to 1982. PCB concentrations in the plasma of the workers ranged from 2 to 521 ppb, and some showed higher PCB levels in the plasma than typical Japanese yusho patients. Gas chromatographic patterns of plasma PCBs of the workers with high PCB levels were shown to match the patterns of the PCBs to which they had been exposed in the workplace. Japanese yusho children showed remarkable decrease with time, but no such decrease was observed in the yusho adults and the workers. Polychlorinated quaterphenyls (PCQs) were detected in the blood of typical Japanese and Taiwanese yusho patients, but PCQ levels in the plasma of the workers were below the detection limit of 0.02 ppb. Clinical findings and subjective complaints of the workers were usually slight compared with typical yusho patients, though some of them had mild dermal manifestations and their PCB levels were suspected to be related to serum triglyceride values. On the basis of these results, we discussed the relationship between the health status of the subjects and their contamination with PCBs or related compounds.
CASE OF INTERNAL UTERINE HAeMORRHAGE
Authors: G. King
Journal: BMJ (1853)

JAN. 14, will require modifcations of treatment, which must be left to the tact of the medical attendant to regulate; but, in rew feece to the disase itself, I would remark, that the smallest possible quantity of food, and of the least irritating nature, is absolutely to be insisted on: wine, spirits, ale, hlould be avoided, and even the mildest kind of food, such as milk, arrow-root, etc., must not be given in sufficient quantity to distend the organ.As the emaciation, during the progress of the disease, often becomes very great, some food must be given to support life.The difficulty in the
Vascular endothelium, cytokines, and the pathogenesis of inflammatory synovitis.
Authors: A Kaul, D R Blake, J D Pearson
Journal: Annals of the Rheumatic Diseases (1991)

A limited number of whole-cell assays allow monitoring of receptor tyrosine kinase (RTK) activity in a signaling pathway-specific manner. We present the general use of the bioluminescence resonance energy transfer (BRET) technology to quantitatively study the pharmacology and signaling properties of the receptor tyrosine kinase (RTK) superfamily. RTK BRET-2 assays monitor, in living cells, the specific interaction between RTKs and their effector proteins, which control the activation of specific downstream signaling pathways. A total of 22 BRET assays have been established for nine RTKs derived from four subfamilies [erythroblastic leukemia viral (v-erb-b) oncogene homolog (ErbB), platelet-derived growth factor (PDGF), neurotrophic tyrosine kinase receptor (TRK), vascular endothelial growth factor (VEGF)] monitoring the interactions with five effectors (Grb2, p85, Stat5a, Shc46, PLCγ1). These interactions are dependent on the RTK kinase activity and autophosphorylation of specific tyrosine residues in the carboxyl terminus. RTK BRET assays are highly sensitive for quantifying ligand-independent (constitutive), agonist-induced, or antagonist-inhibited RTK activity levels. We studied the signaling properties of the PDGF receptor, α polypeptide (PDGFRA) isoforms (V561D; D842V and Δ842–845) carrying activating mutations identified in gastrointestinal stromal tumors (GIST). All three PDGFRA isoforms are fully constitutively activated, insensitive to the growth factor PDGF-BB, but show differential sensitivity of their constitutive activity to be inhibited by the inhibitor imatinib (Gleevec). Epidermal growth factor receptor (EGFR) BRET structure-function studies identify the tyrosine residues 1068, 1114, and 1148 as the main residues mediating the interaction of EGFR with the adapter protein Grb2. The BRET technology provides an assay platform to study signaling pathway-specific RTK structure-function and will facilitate drug discovery efforts for the identification of novel RTK modulators.
Diagnostic algorithms for liver fibrosis in hepatitis C: Are they ready to avoid liver biopsy?
Authors: Giada Sebastiani, Alfredo Alberti
Journal: Hepatology (2011)

We appreciated the article by Boursier et al.1 about the comparison of diagnostic algorithms for liver fibrosis in hepatitis C. The purpose of combining unrelated noninvasive methods is to increase the performance of each individual method and to minimize the number of liver biopsies needed. The authors found an impressive 0% rate in liver biopsies needed with a synchronous combination of FibroScan and FibroMeter. We believe that this article deserves several comments. Boursier et al. refer to SAFE biopsy as intended for binary diagnosis. The authors state that their synchronous algorithm guarantees a more precise classification of liver fibrosis because it provides six diagnostic classes. We wish to underline that SAFE biopsy algorithms have been modeled to address the main clinical endpoints for decision-making: significant fibrosis (≥F2 by METAVIR) and cirrhosis, as defined by international guidelines.2, 3 Importantly, some of the classes (F2 ± 1 and F3 ± 1) included in the classification of Boursier et al. imply a delta of up to two stages of fibrosis in the same class. This may make it difficult to distinguish between stages that have a different management in clinical practice, such as F1 versus F2 or F3 versus F4. An advantage of SAFE biopsy in clinical practice is that it uses APRI as an initial screening test, which has virtually no cost and global availability. A recent meta-analysis concluded that APRI should still be regarded as a first-line screening test for liver fibrosis in hepatitis C in countries with limited health care resources.4 Another important issue is that SAFE biopsy algorithms adopt widely available and validated tests. When compared with APRI and FibroTest, FibroMeter has been less evaluated independently. Moreover, FibroMeter is not licensed in as many countries as FibroTest.5 Finally, even though liver biopsy is an imperfect standard, it is still regarded as the standard of reference by international guidelines.2 We conclude that combination algorithms are excellent tools to screen liver fibrosis in hepatitis C in clinical practice. The choice of the algorithm could be based on local resources, the clinical setting, and clinician preference. Whether combination algorithms could completely avoid liver biopsy deserve further independent investigation. Giada Sebastiani*, Alfredo Alberti , * Division of Gastroenterology, Department of Medicine, Royal Victoria Hospital, McGill University Health Center, Montreal, QC, Canada, Department of Histology, Microbiology, and Medical Biotechnologies, University of Padova, Padova, Italy.
CHAMPAGNE AND STRYCHNIN IN CHEST TROUBLES OF THE AGED.Read in the Section on Practice of Medicine, at the Forty-fifth Annual Meeting of the American Medical Association, held In San Francisco, June 5-8, 1894.
Authors: G. EDWARD BUXTON
Journal: JAMA (1894)

the application of a solution of mercuric bichlorid.This method of treatment I regard as being most promising as well as rational.It was certainly, in three instances in which it was resorted to in my own practice, followed by rather brilliant results, moder¬ ating more particularly the severity of the local in¬ flammation.Dr. Morris Booth Miller observed in the wards of the Pennsylvania Hospital quite uniformly good results from the local use of ichthyol ointment with lanolin, in the service of Dr. Da Costa and others.Before making trial of the corrosive sublimate solu¬ tion I had used ichthyol locally, but the results were not brilliant.Dr. Charles J. Whalen has reported, in a recent issue of the Journal of the American Medical Association (April 28, 1894), most strik¬ ingly favorable results in four cases of facial erysipe¬ las, from the use of external applications of guaiacol -a mode of treatment which richly deserves a more extended trial.Lastly, from the results of these statistical inves¬ tigations into the subject of the treatment of erysipe¬ las by personal observation and experience, I have arrived at the few brief conclusions following :1. Proper attention to the diet is of paramount importance.2. Stimulants are rarely necessary if the dietetic requirements are fully satisfied, but may be freely exhibited when indicated.3. Of drugs, iron has been widely tested and found to be of great value, though it matters little which salt or preparation is employed.4. Quinin when administered with iron, reduces the temperature, supporting at the same time the vital functions.5. The use of antiseptics per oram is to be recom¬ mended.6. Pilocarpus is in a small proportion of cases, powerful to abort the affection.To reduce temper¬ ature merely, pilocarpus should be employed in in¬ tense pyrexia, particularly where the favorable morning remissions do not occur.7. The question of the local treatment of erysipe¬ las has not as yet been set at rest, but agents in¬ tended to exclude the air and such as possess a germicidal power, especially corrosive sublimate, are highly useful.8. That the erysipelococcus of Fehleisen which is found chiefly in the more superficial channels of the corium, may be attacked directly by the corrosive sublimate solution when the latter is used after scar¬ ification, is quite probable.9.In erysipelas migrans the germicide should be injected beneath the skin, just beyond the edge of the part inflamed.