tbuckley/cabot-search huggingface dataset:
Sarcomatous Change and Maintenance of Differentiation in Long-Term Cultures of Mouse Mammary Carcinoma
Authors: Katherine K. Sanford, Thelma B. Dunn, Benton B. Westfall, Anne B. Covalesky, Lartius T. Dupree, Wilton R. Earle
Journal: JNCI Journal of the National Cancer Institute (1961)

This study had 2 objectives: 1) to follow the behavior in vitro of cells cultured from C3H mouse mammary carcinomas with respect to maintenance of differentiation as assayed in vivo and 2) to supply additional evidence regarding the “sarcomatous” transformation which epithelial tumors frequently undergo and which appeared in cell strains of this study. Cell strains were established in culture from 18 different tumors of mammary-gland origin. Cells cultured in a serumembyro extract medium and transferred from culture to mice during the first 5 months in vitro grew as differentiated mammary carcinomas, but cells transferred after this period produced sarcoma-like tumors. Experimental evidence indicated that the “sarcomatous” changes in the various cell strains resulted from two entirely different phenomena: 1) neoplastic transformation of stromal cells in culture, and 2) morphologic alteration of carcinoma cells to resemble sarcoma cells of connective-tissue origin. One strain cultured from the long-transplanted C3HBA mammary carcinoma and grown in serum-supplemented chemically defined medium continued to reproduce in mice the epithelial glandular architecture of the original tumor after 1½ years and 35 transplant generations of growth in vitro. The high arginase activity characteristic of C3H mammary carcinomas was also maintained. Apparently two factors accounted for the maintenance of recognizable differentiation in cells of this strain: 1) the type of culture medium used, and 2) the stabilization of tumor morphology and differentiation during numerous passages in vivo before explantation of tumor tissue to culture.
Abstract 89: Development of preclinical lung adenocarcinoma model
Authors: Young-Ah Suh, Minsuh Kim, Sun-Hye Lee, Chae Lim Jung, Hye-Min Mun, Ju-Hee Oh, Eun Kyung Choi, Se Jin Jang
Journal: Cancer Research (2014)

Abstract Lung cancer is a leading cause of cancer death in worldwide. 85% of lung cancers are classified as non-small cell lung cancers (NSCLC), and adenocarcinoma (ADC) type is the most prevalent cancer in NSCLC. Approximately 50% of non-small cell lung cancer (NSCLC) patients have mutations in some oncogenes. The K-ras activation due to the mutant is notorious in many kinds of cancer types, including pancreatic cancer and lung adenocarcinoma, as is generally accepted as driving mutation for lung malignancy of lung adenocarcinoma. Another predominantly alternated gene in lung cancer is the EGFR that would hit the similar signaling with K-ras activation, to which small molecules and antibodies target to halt the tumor progression. The tumor suppressor p53 is also often altered in almost all kinds of cancers and lung cancer. In this reason, K-ras activated mouse is utilized as lung cancer mouse model. K-ras activated mouse eventually develops lung adenocarcinoma, which can be accelerated with mutated p53. Due to the gain-of-function, mutant p53 protein contributes to tumor metastasis and shortening the latency of tumor progression. Thereby activated K-ras/mutant p53 mouse is preferentially used as lung adenocarcinoma preclinical model. Here, we have used mouse tumor cells derived from activated K-ras/mutant p53 mouse to establish syngeneic lung cancer mouse model, allowing in vivo imaging. We asked whether the gain-of-function metastatic phenotype observed in the mouse is responsible for the formation of lung tumors when inoculated intravenously. Tumor cells from the mice could efficiently develop tumors in four weeks at the same genetic background. Tumors from the mice were histologically identical with original lung adenocarcinoma, suggesting that these cells are the efficient tools to generate preclinical lung tumor mouse model. We have examined this model for evaluating the efficiency of chemotherapeutics and signaling pathways involved in tumor growth regulation. Citation Format: Young-Ah Suh, Minsuh Kim, Sun-Hye Lee, Chae Lim Jung, Hye-Min Mun, Ju-Hee Oh, Eun Kyung Choi, Se Jin Jang. Development of preclinical lung adenocarcinoma model. [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 89. doi:10.1158/1538-7445.AM2014-89
Lesson of the week: Abdominal pain in acute infectious mononucleosis
Authors: A. L N Chapman
Journal: BMJ (2002)

Abdominal pain in patients with infectious mononucleosis may signal splenic rupture 

Abdominal pain and tachycardia are unusual in patients with acute infectious mononucleosis. We present a case in which abdominal pain and tenderness signalled the presence of a potentially fatal complication of infectious mononucleosis.

A previously fit 20 year old man was admitted with a three day history of fever, sore throat, dyspnoea, and malaise. Ten days before admission he had fallen on to his left side and had attended the casualty department with pain over the left chest wall. A chest radiograph did not show a fracture, but the pain had been sufficiently severe to warrant overnight observation in the casualty department.

On admission he was feverish, with a temperature of 39.7°C, and had generalised lymphadenopathy, non-exudative pharyngitis, mild hepatomegaly, and splenomegaly of 2 cm. He looked pale but well, and his blood pressure was 115/95 mm Hg, with a pulse rate of 96 beats/min. He had mild left and right hypochondrial tenderness without guarding.

Initial investigations showed a haemoglobin concentration of 10.9 g/dl, and a total leukocyte …
UK physicians work 21 hours a week more than contracted
Authors: Susan Mayor
Journal: BMJ (2001)

Consultant physicians in the NHS are working an average of 21 hours each week more than they are contracted to, a survey published last week has shown.

Consultants taking part in the survey reported that they worked an average of an additional six sessions (notional half days of 3.5 hours) each week more than contracted.

On average, consultants spent just over 11 hours in general medicine each week and 24 hours in their main specialty. In addition, 11% of consultants worked more than 8.6 hours in a further specialty. Physicians in acute specialties spent about 23 hours each week in generic general duties. This totalled 58 hours each week for consultants not taking an additional specialty and nearly 67 hours for those who did.

Alan Maynard, professor of health economics at the University of York, pointed out the potential pitfalls of this type of research: “One-off, self reported studies are interesting, but there is the potential problem of self reporting bias.” He said that there was likely to be enormous variation in consultants' workloads. “Some may be doing a lot more, while others may be doing a lot less.”

The survey is available from the Medical Workforce Unit of the Royal College of Physicians of London (tel 020 7953 1174, ext 242 or 475).
Abstract 18665: Galectin-3 Predicts Left Ventricular Ejection Fraction After Myocardial Infarction
Authors: A. Rogier van der Velde, Chris P.H. Lexis, Wouter C. Meijers, Iwan C.C. van der Horst, Erik Lipsic, Martin M. Dokter, Dirk J. van Veldhuisen, Pim van der Harst, Rudolf A. de Boer
Journal: Circulation (2014)

Introduction:  Galectin-3 has been shown to be a strong prognostic marker for heart failure (HF) and predicts HF development. Although galectin-3 correlates with markers of cardiac remodeling, no definite data are available on its role in post-myocardial infarction (MI) setting. Therefore, the aim of this study was to investigate the predictive value of galectin-3 on cardiac remodeling in post-MI patients.   Methods:  The GIPS-III study was a double-blind, placebo-controlled study in 380 patients who underwent primary PCI for STEMI and studied the effect of metformin on left ventricular ejection fraction (LVEF). In 263 patients (age 57.8±11.6 years; 78.0% men), both baseline galectin-3 levels and MRI data after 4 months were available. Multivariable analysis was performed to determine the association of galectin-3 levels and LVEF at 4 months after STEMI.   Results:  Median baseline galectin-3 level was 13.4 ng/mL (IQR: 11.5-16.4). Galectin-3 levels were divided in quartiles: patients with the highest galectin-3 levels had the lowest LVEF, 4 months after STEMI (median LVEF in quartiles of galectin-3: 56.6, 57.3, 54.8, 53.6; P = 0.003). Multivariable regression analysis showed that galectin-3 was an independent and strong predictor for LVEF, after adjustment for age, sex, NT-proBNP, myocardial blush, treatment effect, creatine kinase, creatinine and BMI (P = 0.001). Finally, using the FDA-approved cutpoint of 17.8 ng/mL, patients with elevated galectin-3 levels had significant lower LVEF after 4 months (P    Conclusion:  Galectin-3 is a strong and independent predictor for LVEF after 4 months in patients with a first MI. Possibly, the described pro-fibrotic effects of galectin-3 have deleterious effects on cardiac remodeling.
Troponin and C-reactive protein have different relations to subsequent mortality and myocardial infarction after acute coronary syndrome
Authors: Stefan K James, Paul Armstrong, Elliott Barnathan, Robert Califf, Bertil Lindahl, Agneta Siegbahn, Maarten L Simoons, Eric J Topol, Per Venge, Lars Wallentin
Journal: Journal of the American College of Cardiology (2003)
Transcatheter and surgical aortic valve replacement did not differ for mortality in severe aortic stenosis
Authors: James Brophy
Journal: Annals of Internal Medicine (2015)

Source Citation Mack MJ, Leon MB, Smith CR, et al; PARTNER 1 trial investigators. 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet. 2015 Mar 15. Epub ahead of print. 25788234
Phase <scp>II</scp> study results of a replacement therapy for hereditary angioedema with subcutaneous C1‐inhibitor concentrate
Authors: B. L. Zuraw, M. Cicardi, H. J. Longhurst, J. A. Bernstein, H. H. Li, M. Magerl, I. Martinez‐Saguer, S. M. M. Rehman, P. Staubach, H. Feuersenger, R. Parasrampuria, J. Sidhu, J. Edelman, T. Craig
Journal: Allergy (2015)

Hereditary angioedema (HAE) due to C1 inhibitor deficiency manifests as recurrent swelling attacks that can be disabling and sometimes fatal. Long-term prophylaxis with twice-weekly intravenous injections of plasma-derived C1-inhibitor (pdC1-INH) has been established as an effective treatment. Subcutaneous (SC) administration of pdC1-INH has not been studied in patients with HAE.This open-label, dose-ranging, crossover study (COMPACT Phase II) was conducted in 18 patients with type I or II HAE who received two of twice-weekly 1500, 3000, or 6000 IU SC doses of highly concentrated volume-reduced CSL830 for 4 weeks each. The mean trough plasma levels of C1-INH functional activity, C1-INH and C4 antigen levels during Week 4, and overall safety and tolerability were evaluated. The primary outcome was model-derived steady-state trough C1-INH functional activity.After SC CSL830 administration, a dose-dependent increase in trough functional C1-INH activity was observed. C1-INH and C4 levels both increased. The two highest dose groups (3000 and 6000 IU) achieved constant C1-INH activity levels above 40% values, a threshold that was assumed to provide clinical protection against angioedema attacks. Compared with intravenous injection, pdC1-INH SC injection with CSL830 showed a lower peak-to-trough ratio and more consistent exposures. All doses were well tolerated. Mild-to-moderate local site reactions were noted with pain and swelling being the most common adverse event.Subcutaneous volume-reduced CSL830 was well tolerated and led to a dose-dependent increase in physiologically relevant functional C1-INH plasma levels. A clinical outcome study of SC CSL830 in patients with HAE warrants further investigation.
Abstract 3507: STAT3beta suppresses tumorigenesis via modulating the phosphorylation dynamics and transcription activity of STAT3alpha in esophageal squamous cell carcinoma
Authors: Haifeng Zhang, Raymond Lai, Enmin Li, Liyan Xu
Journal: Cancer Research (2014)

Abstract While the oncogenic role of STAT3 is well-documented, a number of studies have described that STAT3 carries tumor suppressor functions. We hypothesized that the relative abundance of STAT3α and STAT3β, the two STAT3 isoforms, dictate its exact functional roles in cancer cells. Using Western blots and a cohort of esophageal squamous cell carcinoma (ESCC)(n=91), we found that STAT3β significantly correlated with a shorter survival (P=0.030), whereas phospho-STAT3α-Tyr705 and total STAT3 did not carry significant prognostic value. Correlating with these observations, STAT3β significantly suppressed the oncogenic effects of STAT3α in ESCC cell lines in a soft-agar clonogenic assay. Interestingly, while STAT3β suppressed the transcriptional activity of STAT3α, it enhanced the phosphorylation of STAT3α-Tyr705 and its nuclear translocation. STAT3β also prolonged the phosphorylation of STAT3α-Tyr705 and increased its cytoplasmic localization following cytokine stimulation. Furthermore, the substantial increase in phospho-STAT3α-Tyr705 in this setting was related to STAT3β-mediated inhibition of dephosphorylation. Taken together, our findings have highlighted the tumor suppressor roles of STAT3β via its interactions with STAT3α at different levels. Our data also strongly suggests that, an accurate interpretation of the oncogenic activity of STAT3α in tumors based on the detection of nuclear STAT3 or phospho-STAT3-Tyr705 requires the knowledge of the STAT3β expression status. Citation Format: Haifeng Zhang, Raymond Lai, Enmin Li, Liyan Xu. STAT3beta suppresses tumorigenesis via modulating the phosphorylation dynamics and transcription activity of STAT3alpha in esophageal squamous cell carcinoma. [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 3507. doi:10.1158/1538-7445.AM2014-3507
Conditional expression of a suicide gene by the telomere reverse transcriptase promoter for post-therapeutic deletion of insertional mutagenesis
Authors: Richard G. Painter, Nicholas A. Lanson, Zhengmin Jin, Frank Park, Guoshun Wang
Journal: Molecular Therapy (2004)

The success of gene therapy for human X-linked severe combined immunodeficiency (X-SCID) has been recently clouded by the occurrence of post-therapeutic cancers caused by vector-associated insertional mutagenesis. Improving the safety feature of integrating vectors becomes imperative and challenging. We demonstrated a gene expression cassette that can be possibly exploited in integrating vector systems to eliminate the rare but existing adverse events. The Herpes simplex virus thymidine kinase (HSV-TK) gene under the transcriptional control of the human telomerase reverse transcriptase (hTERT) promoter was incorporated into a self-inactivating HIV-based lentiviral vector. Theoretically, the hTERT promoter is silent in normal somatic cells and re-activated in tumor cells. Therefore, normal gene-corrected cells should not express HSV-TK. However, if some gene-corrected cells subsequently become tumorigenic and the hTERT promoter is re-activated, application of ganciclovir (GCV), a clinically used anti-virus drug, will achieve selective deletion of the cancerous cells. To prove the principle, we transduced tumor cells, including HT-1080 cells (fibrosarcoma), 293T (transformed human embryonic kidney cells), SCCLSU-1 (primary head and neck squamous cell carcinoma cells), and Jurkat cells (acute T cell leukemia cells), and normal cells, including primary human airway fibroblast cells and human marrow mesenchymal stem cells, with 10 MOIs of the HIV-CMV-EGFP-hTERT-TK vector and the HIV-CMV-EGFP control vector, respectively. GCV application only eradicated the tumor cells transduced with vector containing the hTERT-TK element, but had no effects on the normal cells received an identical treatment, suggesting the hTERT-TK cassette in the lentiviral vector was adequate to differentiate tumor cells from normal, thus destroying tumor cells selectively. HT1080 cells with single HIV-CMV-EGFP-hTERT-TK integration was implanted into left flanks of nu/nu mice and the cells with HIV-CMV-EGFP integration to the right flanks of the same animals. After establishment of tumors, GCV administration ablated the left-side tumors but not the right-side tumors. These results suggest the potential of hTERT-TK cassette in integrating vectors as a safety valve for human gene therapy to control post-therapeutic insertional mutagenesis.
The Use of Histamin Hydrochloric Acid As a Test Meal
Authors: Henry H. Haft
Journal: Annals of Internal Medicine (1932)

Article1 March 1932The Use of Histamin Hydrochloric Acid As a Test MealHENRY H. HAFT, M.D., F.A.C.P.HENRY H. HAFT, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-5-9-1175 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn recent years there has been a revival of interest and a tendency to evaluate in their proper worth, the various test meals that have been used to determine gastric secretion. Briefly, the Ewald test meal with coffee, tea and toast; seven per cent alcohol; the Schmidt test meal containing meat, bread and vegetables; the raisin and rice evening meal;—all have been given careful scrutiny. The consensus of opinion seems to be that any one test if standardized by one man or in one clinic will give the desired information sought by the investigator.In functional anacidity, in chronic gastritis... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Syracuse, N.Y.*Read before the Alumni of Syracuse Medical College at the University Hospital, May 29, 1931.†Received for publication, July 13, 1931. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1932Volume 5, Issue 9Page: 1175-1177KeywordsAlcoholsAlumniBreadCoffeeGastritisHydrochloric acidMeatTea ePublished: 1 December 2008 Issue Published: 1 March 1932 PDF downloadLoading ...
Intraperitoneal Chemotherapy: A Possible Role in the Treatment of Hepatic Metastases
Authors: James L. Speyer
Journal: Liver Cancer (1985)

In recent years there have been a number of clinical investigations utilizing intraperitoneal (IP) chemotherapy for the treatment of intracavitary and intrahepatic disease. The aim of this locoregional therapy is to provide high intratumor concentrations of antineoplastic agents while reducing the systemic exposure to these toxic drugs.
Abstract 2485: Magnetocardiography (MCG) Can Predict Clinical Response to Cardiac Resynchronization Therapy (CRT)
Authors: Shogo Oishi, Hiroshi Takaki, Emi Yamashita, Shuji Hashimoto, Ikutaro Nakajima, Toshiyuki Tanaka, Wataru Shimizu, Masaru Sugimachi, Siro Kamakura
Journal: Circulation (2009)
First Results of the DEB-AMI (Drug Eluting Balloon in Acute ST-Segment Elevation Myocardial Infarction) Trial
Authors: Anouar Belkacemi, Pierfrancesco Agostoni, Hendrik M. Nathoe, Michiel Voskuil, ChunLai Shao, Eric Van Belle, Thierry Wildbergh, Luigi Politi, Pieter A. Doevendans, Giuseppe M. Sangiorgi, Pieter R. Stella
Journal: Journal of the American College of Cardiology (2012)
A memorable patient: An ad hoc blood bank
Authors: K. M. Leighton
Journal: BMJ (1998)

On a wet afternoon in 1953 a truck drew up at the foot of the steps of the hospital. Four Indian men carried a young boy inside. They operated a saw mill in the bush, they said. That morning the boy had fallen across the blade, which cut his leg off above the knee and then turned him around and went up his thigh and into the hip joint. He seemed to be dead so they covered him with a sack and carried on sawing.

Later, someone thought that they could see that he …
Comparative effect of pre‐coseasonal and continuous grass sublingual immunotherapy in children
Authors: I. Stelmach, I. Kaluzińska‐Parzyszek, J. Jerzynska, P. Stelmach, W. Stelmach, P. Majak
Journal: Allergy (2011)

To cite this article: Stelmach I, Kaluzińska‐Parzyszek I, Jerzynska J, Stelmach P, Stelmach W, Majak P. Comparative effect of pre‐coseasonal and continuous grass sublingual immunotherapy in children. Allergy 2012; 67 : 312–320. Abstract Background: One of the most important aspects of sublingual immunotherapy (SLIT) is the regimen of administration. The aim of the study was to compare the efficacy and the safety of SLIT given pre‐coseasonally (starting before the pollen season and continuing until the end of it) and continuously (all year round, independent of the pollen season) in children allergic to grass pollen. Methods: Sixty children aged 6–18, sensitive only to grass pollen, with rhinitis (20 patients had concomitant asthma) participated in the 2‐year prospective, randomized, double‐blind, placebo‐controlled trial. Results: Both pre‐coseasonal and continuous SLIT were associated with a substantial reduction in the combined symptoms/medication score when compared with placebo; there were no significant differences between the regimens (mean difference: 18.1 ± 12.4, P &gt; 0.05). Similar changes were observed in the total symptoms score. Pre‐coseasonal therapy, compared with continuous, was more effective in the reduction of nasal symptoms (mean difference: −18.0 ± 2.5, P = 0.006). We did not observe significant differences in medication, ocular, and asthma scores between the regimens. We did not observe changes in morning PEF, FEV1, and PD20 in any of the three groups nor between the groups throughout the study. We showed a significant decrease in FeNO level comparable in both active groups. There were no differences between groups in the induction of CD4CD25Foxp3‐positive cells in peripheral blood during the study. Conclusion: Both protocols were effective compared with placebo and showed similar decreases for combined symptoms/medication score and all secondary endpoints, with the exception of nasal symptoms that were lower in the pre‐coseasonal group.