tbuckley/cabot-search huggingface dataset:
Abstract 633: Inhibition of TGFβ as a strategy to convert the irradiated tumor into in situ individualized vaccine
Authors: Claire I. Vanpouille-Box, Julie M. Diamond, Jiri Zavadil, James Babb, Dörthe Schaue, Mary Helen Barcellos-Hoff, William H. McBride, Silvia C. Formenti, Sandra Demaria
Journal: Cancer Research (2014)

Abstract Accumulating data support the concept that ionizing radiation therapy (RT) has the potential to convert the tumor into an in situ, individualized vaccine; however this potential is rarely realized by RT alone. Transforming growth factor β (TGFβ) is an immunosuppressive cytokine that is activated by RT and inhibits the antigen-presenting function of dendritic cells and the differentiation of effector CD8+ T cells. Here we tested the hypothesis that TGFβ hinders the ability of RT to promote anti-tumor immunity. Development of tumor-specific immunity was examined in two pre-clinical models of metastatic breast cancer and analyzed in patients with metastatic breast cancer treated with local radiotherapy and the TGFβ-neutralizing antibody Fresolimumab. Mice bearing established 4T1 and TSA mouse mammary carcinomas treated with pan-isoform specific TGFβ neutralizing antibody, 1D11, showed significantly improved control of the irradiated tumor and non-irradiated metastases, but no effect in the absence of RT. Notably, whole tumor transcriptional analysis demonstrated the selective upregulation of genes associated with immune-mediated rejection only in tumors of mice treated with RT+TGFβ blockade. Mice treated with RT+TGFβ blockade exhibited cross-priming of CD8+ T cells producing IFNγ in response to three tumor-specific antigens in tumor-draining lymph nodes, which was not evident for single modality treatment. Likewise, HLA-A2.1+ metastatic breast cancer patients (n=8) enrolled in NCT01401062 trial of local RT and fresolimumab were examined for CD8+ T cells specific for the tumor antigen survivin by tetramer staining. Three patients developed increased frequencies of survivin-specific CD8+ T cells in the blood during treatment, while two patients negative at baseline became positive. Analysis of the immune infiltrate in mouse tumors showed a significant increase in CD4+ and CD8+ T cells only in mice treated with the combination of RT+TGFβ blockade. Depletion of CD4+ or CD8+ T cells abrogated the therapeutic benefit of RT+TGFβ blockade. These data identify TGFβ as a master inhibitor of the ability of RT to generate an in situ tumor vaccine, which supports testing inhibition of TGFβ during radiotherapy to promote therapeutically effective anti-tumor immunity. Supported by DOD BCRP Multi-Team Award BC100481. Citation Format: Claire I. Vanpouille-Box, Julie M. Diamond, Jiri Zavadil, James Babb, Dörthe Schaue, Mary Helen Barcellos-Hoff, William H. McBride, Silvia C. Formenti, Sandra Demaria. Inhibition of TGFβ as a strategy to convert the irradiated tumor into in situ individualized vaccine. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 633. doi:10.1158/1538-7445.AM2014-633
Sweet Reprieve: One Couple's Journey to the Frontiers of Medicine
Authors: Byers W. Shaw
Journal: JAMA (1991)

Maybe I shouldn't be the one to review this book. After all, at least on the surface, the subject would appear to be my very livelihood. Frank Maier was a patient with liver disease who received a liver transplant. I am a transplant surgeon who eats, drinks, and sleeps liver transplantation and has done so for the past ten years. So how could I possibly provide an objective assessment of a journalist's chronicle of his experience as a patient, first with liver disease and later with a transplant? But this book, and in fact its most important message, has very little to do with liver transplantation as a specific entity. It is instead the story of a man and his wife who prepared to face death from a chronic, incurable disease and then found rescue in a formerly exotic but recently routine surgical therapy. The lessons from their struggle that
Hepatic Amyloidosis in an IV Drug Abuser Detected by Bone Scintigraphy
Authors: EUGENE M. FERRARO, FILIPINAS R. ALFELOR, MARGARET LEE, TUNG T. POON
Journal: Clinical Nuclear Medicine (1987)

A case of diffuse hepatic uptake of Tc-99m MDP in an intravenous drug abuser with biopsy-proven hepatic amyloidosis is presented. The association of parenteral drug addiction and amyloidosis, as well as current concepts regarding hepatic uptake of bone seeking radiopharmaceuticals in amyloidosis and its potential clinical implications are discussed.
Mutations in the Hepatitis C Virus <i>core</i> Gene Are Associated with Advanced Liver Disease and Hepatocellular Carcinoma
Authors: Sarah L. Fishman, Stephanie H. Factor, Cinzia Balestrieri, Xiaofeng Fan, Adrian M. DiBisceglie, Suresh M. Desai, Gary Benson, Andrea D. Branch
Journal: Clinical Cancer Research (2009)

Hepatitis C virus (HCV) infection can promote the development of hepatocellular carcinoma (HCC). Published data implicate the HCV core gene in oncogenesis. We tested the hypothesis that core gene sequences from HCC patients differ from those of patients without cirrhosis/HCC.Full-length HCV sequences from HCC patients and controls were obtained from the investigators and GenBank and compared with each other. A logistic regression model was developed to predict the HCC risk of individual point mutations and other sequence features. Mutations in partial sequences (bases 36-288) from HCC patients and controls were also analyzed. The first base of the AUG start codon was designated position 1.A logistic regression model developed through analysis of full-length core gene sequences identified seven polymorphisms significantly associated with increased HCC risk (36G/C, 209A, 271U/C, 309A/C, 435A/C, 481A, and 546A/C) and an interaction term (for 209A-271U/C) that had an odds ratio <1.0. Three of these polymorphisms could be analyzed in the partial sequences. Two of them, 36G/C and 209A, were again associated with increased HCC risk, but 271U/C was not. The odds ratio of 209A-271U/C was not significant.HCV core genes from patients with and without HCC differ at several positions. Of interest, 209A has been associated with IFN resistance and HCC in previous studies. Our findings suggest that HCV core gene sequence data might provide useful information about HCC risk. Prospective investigation is needed to establish the temporal relationship between appearance of the viral mutations and development of HCC.
Modeling the human 8p11-myeloproliferative syndrome in immunodeficient mice
Authors: Helena Ågerstam, Marcus Järås, Anna Andersson, Petra Johnels, Nils Hansen, Carin Lassen, Marianne Rissler, David Gisselsson, Tor Olofsson, Johan Richter, Xiaolong Fan, Mats Ehinger, Thoas Fioretos
Journal: Blood (2010)
Video laryngoscopy versus direct laryngoscopy for orotracheal intubation in the intensive care unit: a systematic review and meta-analysis
Authors: Audrey De Jong, Nicolas Molinari, Matthieu Conseil, Yannael Coisel, Yvan Pouzeratte, Fouad Belafia, Boris Jung, Gérald Chanques, Samir Jaber
Journal: Intensive Care Medicine (2014)
Experiences with Drumine as a Local Anaesthetic
Authors: A. Ogston
Journal: BMJ (1887)

emphasis on that ring of ligatures which he so carefully applied around the anus.This was really the real protection against hemorrhage.After some remarks from Mr. HEMMING, Professor PANCOAST stated that he was much interested in Mr. Whitehead's paper.He liked the surgical character of the treatment, and was impressed by the statement that the patients were ab!e
266 FXR DIRECTLY CONTROLS THE TUMOR SUPPRESSOR NDRG2 AND FXR AGONISTS REDUCE TUMOR GROWTH AND METASTASIS IN AN ORTHOTOPIC XENOGRAFT MOUSE MODEL
Authors: U. Deuschle, O. Kinzel, A. Schulz, J. Schüler, C. Kremoser
Journal: Journal of Hepatology (2012)
Activation in vitro of rheumatoid synovial collagenase from cell cultures.
Authors: C A Vater, C L Mainardi, E D Harris
Journal: Journal of Clinical Investigation (1978)

Rheumatoid synovial cells dissociated from matrix and adherent to culture dishes released a latent form of collagenase into culture medium. Previous studies have shown that the latent enzyme does not complex with alpha2-macroglobulin and binds to fibrillar substrate. We now show that serum-free culture medium of the synovial cells contains an inhibitor of collagenase as well as latent enzyme; the two were separated on a column of acrylamide/agarose. Latent collagenase (estimated mol wt 45,000-49,000) was transformed by trypsin to active collagenase of approximately equal to mol wt 33,000. When mixed with inhibitor the active enzyme formed an inactive complex again with approximately equal to mol wt 45,000-49,000. The inhibitor(s) itself was found in one major peak of mol wt 33,000-35,000 and several minor peaks eluting with lower apparent molecular weight. Mersalyl, an organic mercurial compound, effectively activated latent collagenase producing an active enzyme with approximately equal to mol wt 33,000. Bacterial collagenase did not activate latent enzyme. We suggest that latent rheumatoid synovial collagenase, as it is harvested from synovial cells in culture, is an enzyme-inhibitor complex.
Sleep fragmentation: comparison of two definitions of short arousals during sleep in OSAS patients
Authors: M.V. Smurra, M. Dury, G. Aubert, D.O. Rodenstein, G. Liistro
Journal: European Respiratory Journal (2001)

The measurement of arousals during sleep is useful to quantify sleep fragmentation. The criteria for electroencephalography (EEG) arousals defined by the American Sleep Disorders Association (ASDA) have recently been criticized because of lack of interobserver agreement. The authors have adopted a scoring method that associates the increase in chin electromyography (EMG) with the occurrence of an α-rhythm in all sleep stages (Université Catholique de Louvain (UCL) definition of arousals). The aim of the present study was to compare the two scoring definitions in terms of agreement and repeatability and the time taken for scoring in patients with obstructive sleep apnoea syndrome (OSAS) of varying severity. Two readers using both ASDA and UCL definitions scored twenty polysomnographies (PSGs) each on two occasions. The PSGs were chosen retrospectively to represent a wide range of arousal index (from 6–82) in OSAS patients. There was no difference in the arousal indices between readers and between scoring methods. The mean±sd difference between the two definitions (the bias) was 1.1±3.76 (95% confidence interval: −0.66–2.86). There was a strong linear relationship between the arousal index scored with the two definitions (r=0.981, p&lt;0.001). Mean±sd scoring duration was significantly shorter for UCL than for ASDA definitions (18.5±5.4 versus 25.3±6.6 min, p&lt;0.001). In conclusion, it has been found that in obstructive sleep apnoea syndrome patients, the American Sleep Disorders Association and Université Catholique de Louvain definitions were comparable in terms of agreement and repeatability.
Standard of Care and Anesthesia Liability
Authors: Frederick W. Cheney
Journal: JAMA (1989)

For the past 3 years, the Committee on Professional Liability of the American Society of Anesthesiologists has been studying records of closed malpractice claims files for anesthesia-related patient injuries. The database of 1004 lawsuits was examined to define the impact of the "standard of care," as judged by a practicing group of anesthesiologists, on the likelihood and amount of financial recovery. We found that payment was made in more than 80% of claims made by patients who were judged to have received substandard anesthetic care. Payment also was made in more than 40% of claims when the anesthesia care was judged to be appropriate. We conclude that in the tort-based system of compensation for anesthesia-related injury, the patient has a high probability of financial recovery for injury caused by substandard care. However, if the anesthesiologist provides appropriate care there is still a greater than 40% chance that payment will be made for the claim of malpractice.
A patient with a large recurrent pheochromocytoma demonstrating the pitfalls of diagnosis
Authors: Jörg Singer, Christian A. Koch, Woubet Kassahun, Peter Lamesch, Graeme Eisenhofer, Regine Kluge, Thomas Lincke, Matthias Seiwerts, Gudrun Borte, Katrin Schierle, Ralf Paschke
Journal: Nature Reviews Endocrinology (2011)
Apolipoprotein E4 genotype and gallbladder motility influence speed of gallstone clearance and risk of recurrence after extracorporeal shock-wave lithotripsy
Authors: P Portincasa, K J van Erpecum, P C van de Meeberg, G M Dallinga-Thie, T W A de Bruin, G P van Berge-Henegouwen
Journal: Hepatology (1996)

Extracorporeal shock–wave lithotripsy (ESWL) is an effective treatment in selected gallstone patients, but stone recurrence is a major drawback. Factors potentially influencing gallstone clearance and recurrence were studied in 84 patients in whom stone dissolution was diagnosed after ESWL plus bile salt therapy for initial solitary (n = 55) or multiple (n = 29) radiolucent stones. Apolipoprotein E (apoE) genotyping and gallbladder motility (sonography) were studied in a representative subgroup of patients (n = 50). The median follow–up after ESWL was 36 months (range, 4.5–67 months). Gallstone clearance was achieved after 8.7 months (range, 0.2–30 months). Independent factors significantly enhancing gallstone clearance were the presence of E4 allele; small initial gallstone size and number; effectiveness of fragmentation; and good gallbladder emptying ( P = .002). Gallstone recurrence was seen in 30 patients after 18.6 months (range, 1.0–50 months). Cumulative gallstone recurrence rate (life–table analysis) was 15% within 1 year, increasing to 60% within 5.5 years. Although the probability of gallstone recurrence tended to be smaller in patients with initial solitary stones than in those with multiple stones during early follow–up, differences disappeared after long–term follow–up. Effective gallbladder emptying (residual volume &lt; or = 6 mL) and apolipoprotein E4 (apoE4) independently influenced gallstone recurrence. Recurrence rate was higher (log rank test, P = .037) in those patients who were homozygous and heterozygous for the E4 allele compared with the individuals who were not expressing the apoE4 allele. Accordingly, there was an overrepresentation of the allele frequency for E4 in the group with gallstone recurrence ( P = .03). Patients with small postprandial residual gallbladder volumes (≤ 6 mL) had a lower probability of stone recurrence than those with large residual gallbladder volumes (log rank test, P = .0215). Biliary pain was more frequent with recurrence (55% vs. 13%, P = .001). The present study indicates that apoE4 genotype is associated with increased speed of gallstone clearance as well as a high risk of recurrence after ESWL. This finding points to a possible role for genetic factors in the pathogenesis of cholesterol gallstones. Effective gallbladder emptying is important for speed of clearance and prevention of recurrence. Patients with initial solitary stones have a decreased early– but not long–term gallstone recurrence rate.
Urinary incontinence: prevalence, need for treatment, and effectiveness of intervention by nurse.
Authors: J O'Brien, M Austin, P Sethi, P O'Boyle
Journal: BMJ (1991)

OBJECTIVE--To measure the unmet need of patients with regular urinary incontinence (incontinence twice or more a month) treatable by a nurse. DESIGN--Self completed postal questionnaire and randomised controlled trial of assessment and intervention by a nurse. SETTING--One urban and one rural general practice in Somerset. SUBJECTS--7300 adults randomly selected from 10,300 aged 35 and over on the combined practice lists. 515 women and 185 men with regular incontinence were offered assessment and treatment, of whom 134 women and 49 men had no intervention for three months (historical controls). They then joined the assessment and treatment programme. INTERVENTION--Four sessions of pelvic floor exercises and bladder retraining supervised by non-specialist nurse who had taken a three week course on assessing and treating uncomplicated incontinence. MAIN OUTCOME MEASURES--Number of patients desiring treatment; self reported cure, improvement, or deterioration in continence after three months. RESULTS--The questionnaire achieved a 79% response. Validated responses showed a prevalence of 4.4% in men and 16.4% in women aged 35-64. 315 (45%) of the 700 patients offered assessment refused it and seven had moved away or died, 64 men and 41 women were referred to their general practitioner. 197 of 292 treated women (68%) reported cure or improvement compared with seven (5%) of controls. 22 of the 86 men desiring treatment were suitable for intervention by the nurse. Seventeen were cured or improved compared with none of the men in the control group. CONCLUSIONS--About half the people with regular urinary incontinence took up the offer of treatment (9.2% of women and 3.4% of men in the study population). This condition can be effectively managed by a nurse with limited training.
Intact signaling by transforming growth factor β is not required for termination of liver regeneration in mice
Authors: Shoshiro Oe, Eric R. Lemmer, Elizabeth A. Conner, Valentina M. Factor, Per Levéen, Jonas Larsson, Stefan Karlsson, Snorri S. Thorgeirsson
Journal: Hepatology (2004)

Transforming growth factor beta (TGF-beta) is a potent inhibitor of hepatocyte proliferation in vitro and is suggested to be a key negative regulator of liver growth. To directly address the role of TGF-beta signaling in liver regeneration in vivo, the TGF-beta type II receptor gene (Tgfbr2) was selectively deleted in hepatocytes by crossing "floxed" Tgfbr2 conditional knockout mice with transgenic mice expressing Cre under control of the albumin promoter. Hepatocytes isolated from liver-specific Tgfbr2 knockout (R2LivKO) mice were refractory to the growth inhibitory effects of TGF-beta1. The peak of DNA synthesis after 70% partial hepatectomy occurred earlier (36 vs. 48 hours) and was 1.7-fold higher in R2LivKO mice compared with controls. Accelerated S-phase entry by proliferating R2LivKO hepatocytes coincided with the hyperphosphorylation of Rb protein and the early upregulation of cyclin D1 and cyclin E. However, by 120 hours after partial hepatectomy, hepatocyte proliferation was back to baseline in both control and R2LivKO liver. Regenerating R2LivKO liver showed evidence of increased signaling by activin A and persistent activity of the Smad pathway. Blockage of activin A signaling by the specific inhibitor follistatin resulted in increased hepatocyte proliferation at 120 hours, particularly in R2LivKO livers. In conclusion, TGF-beta regulates G(1) to S phase transition of hepatocytes, but intact signaling by TGF-beta is not required for termination of liver regeneration. Increased signaling by activin A may compensate to regulate liver regeneration when signaling through the TGF-beta pathway is abolished, and may be a principal factor in the termination of liver regeneration.
Foley-catheter induction of labor.
Authors: W G Dawson
Journal: BMJ (1972)

and diphenhydramine2 have shown no ad- vantage over placebo from the point of view of patient or doctor.In a brief experience so far our patients appear to have tolerated examinations satisfactorily without any pharyngeal anaesthesia.It may thus be un- necessary as well as potentially dangerous.-Iam, etc.,
Herpes Zoster Vaccine Effectiveness against Incident Herpes Zoster and Post-herpetic Neuralgia in an Older US Population: A Cohort Study
Authors: Sinéad M. Langan, Liam Smeeth, David J. Margolis, Sara L. Thomas
Journal: PLoS Medicine (2013)

Sinead Marie Langan and colleagues studied a cohort of more than 750,000 individuals over the age of 65 years to assess whether herpes zoster vaccine is effective against incident zoster and post-herpetic neuralgia in an older population.
Influenza Virus-Host Interactome Screen as a Platform for Antiviral Drug Development
Authors: Tokiko Watanabe, Eiryo Kawakami, Jason E. Shoemaker, Tiago J.S. Lopes, Yukiko Matsuoka, Yuriko Tomita, Hiroko Kozuka-Hata, Takeo Gorai, Tomoko Kuwahara, Eiji Takeda, Atsushi Nagata, Ryo Takano, Maki Kiso, Makoto Yamashita, Yuko Sakai-Tagawa, Hiroaki Katsura, Naoki Nonaka, Hiroko Fujii, Ken Fujii, Yukihiko Sugita, Takeshi Noda, Hideo Goto, Satoshi Fukuyama, Shinji Watanabe, Gabriele Neumann, Masaaki Oyama, Hiroaki Kitano, Yoshihiro Kawaoka
Journal: Cell Host & Microbe (2014)
The Interaction of Sympathetic Stimulation and Blockade on the Calcium Uptake of the Sarcoplasmic Reticulum
Authors: R. White, E. Shinebourne
Journal: Cardiovascular Research (1969)

A study has been made of the effects of propranolol and of combinations of propranolol with noradrenaline or isoprenaline on the calcium uptake of the cardiac sarcoplasmic reticulum. The depressant action of propranolol is confirmed and this depression is partially reversed by both noradrenaline and isoprenaline.
Gonococcal Conjunctivitis-Reply
Authors: King K. Holmes
Journal: JAMA (1982)

<h3>In Reply.—</h3> We did not cite Dr Tight's case report because his patient did develop symptoms after 13 days, although the incubation period was long. The number of citations allowed inJOURNALCLINICAL NOTES is restricted, and we chose to cite the Valenton-Abendanio report because it had the longest well-documented incubation period. The usual incubation period for gonococcal conjunctivitis in the new-born and for gonococcal urethritis in the adult is less than a week. It is clear from the literature that the incubation period for gonococcal urethral infection can occasionally be longer and that some infected men never have urethritis develop. Although gonococcal conjunctivitis has been less extensively studied, these anecdotal reports suggest that conjunctival gonococcal infection also may have a prolonged incubation period or may remain asymptomatic.
The Interval between Pregnancies and the Outcome of Subsequent Births
Authors: Mark A. Klebanoff
Journal: New England Journal of Medicine (1999)

Is there a “natural” interval between pregnancies in humans? Our nearest animal relatives, the chimpanzees and gorillas, breast-feed their offspring for long periods, and the median time from the birth of one offspring to the conception of the next is approximately 3.5 to 5 years.1 The median birth-to-conception interval among women in less developed countries who breast-feed their infants is approximately three years,1 but the interval might be shorter in women from better-nourished populations, even if their practices of breast-feeding and sexual intercourse are similar to those of women in the less developed areas. Some groups of people have cultural . . .
Technicalities of Endoscopic Biopsy
Authors: G. N. J. Tytgat, J.-G. Ignacio
Journal: Endoscopy (1995)

Despite the wealth of biopsy forceps currently available, it is obvious that there are sufficient drawbacks and shortcomings to reconsider the overall design of the endoscopic biopsy depth, the short lifespan of reusable forceps, damage to the working channel, excessive time consumption, cleaning and disinfection difficulties, etc. Improvements should be possible that approach the same degree of sophistication as is currently available in endoscopic equipment. Fully-automated, repetitive, quickly targeted biopsy sampling should be possible, but it will require the utmost technical ingenuity and expertise to achieve.