tbuckley/cabot-search huggingface dataset:
Suppression of Deacetylase SIRT1 Mediates Tumor-Suppressive NOTCH Response and Offers a Novel Treatment Option in Metastatic Ewing Sarcoma
Authors: Jozef Ban, Dave N.T. Aryee, Argyro Fourtouna, Wietske van der Ent, Max Kauer, Stephan Niedan, Isidro Machado, Carlos Rodriguez-Galindo, Oscar M. Tirado, Raphaela Schwentner, Piero Picci, Adrienne M. Flanagan, Verena Berg, Sandra J. Strauss, Katia Scotlandi, Elizabeth R. Lawlor, Ewa Snaar-Jagalska, Antonio Llombart-Bosch, Heinrich Kovar
Journal: Cancer Research (2014)

The developmental receptor NOTCH plays an important role in various human cancers as a consequence of oncogenic mutations. Here we describe a novel mechanism of NOTCH-induced tumor suppression involving modulation of the deacetylase SIRT1, providing a rationale for the use of SIRT1 inhibitors to treat cancers where this mechanism is inactivated because of SIRT1 overexpression. In Ewing sarcoma cells, NOTCH signaling is abrogated by the driver oncogene EWS-FLI1. Restoration of NOTCH signaling caused growth arrest due to activation of the NOTCH effector HEY1, directly suppressing SIRT1 and thereby activating p53. This mechanism of tumor suppression was validated in Ewing sarcoma cells, B-cell tumors, and human keratinocytes where NOTCH dysregulation has been implicated pathogenically. Notably, the SIRT1/2 inhibitor Tenovin-6 killed Ewing sarcoma cells in vitro and prohibited tumor growth and spread in an established xenograft model in zebrafish. Using immunohistochemistry to analyze primary tissue specimens, we found that high SIRT1 expression was associated with Ewing sarcoma metastasis and poor prognosis. Our findings suggest a mechanistic rationale for the use of SIRT1 inhibitors being developed to treat metastatic disease in patients with Ewing sarcoma.
Polymorphonuclear neutrophil contribution to induced tolerance to bacterial lipopolysaccharide.
Authors: J Barroso-Aranda, G W Schmid-Schönbein, B W Zweifach, J C Mathison
Journal: Circulation Research (1991)

The objective of this study was to investigate mechanisms by which polymorphonuclear neutrophils (PMNs) contribute to the tolerance induced by repeated lipopolysaccharide (LPS) injections. Tolerance was developed by daily intraperitoneal injections of sublethal doses of LPS for 4 days (LPS-tolerant group); controls were not pretreated (LPS-control group). Both groups were challenged with 9 mg/kg i.v. Escherichia coli LPS, a dose that resulted in 25% survival in LPS-control rats compared with 100% survival in LPS-tolerant rats. LPS injection caused an initial neutropenia in both groups. The neutropenia persisted throughout the experiment in LPS-control rats, whereas in LPS-tolerant rats the circulating PMN count increased dramatically; after 6 hours, the PMN count was 16-fold higher than that in LPS-control rats. Activation of circulating PMNs, PMN adhesion to nylon fibers, and tumor necrosis factor/cachectin activity were all increased in control rats given LPS. In contrast, LPS-tolerant rats had low activation of circulating PMNs, no trend for PMN adhesion to nylon fibers, and markedly reduced tumor necrosis factor activity. To determine whether neutropenia was associated with a trapping of PMNs in the microcirculation, we used a carbon perfusion technique 6 hours after LPS injection and examined histological sections of the myocardium. All of the arterioles and venules in both groups contained carbon; only capillaries showed evidence of obstruction. A significantly higher percentage of obstructed capillaries was observed in LPS-control rats than in LPS-tolerant rats. Obstruction of capillaries was consistently associated with trapped leukocytes. We conclude that PMN cytotoxicity induced by LPS involves microcirculatory entrapment and activation of PMNs. Repeated LPS pretreatment reduces dramatically circulating PMN activation and adhesion and is associated with an elevated circulating PMN count, a low degree of microvascular plugging, and survival after a normally lethal dose of LPS.
Respiratory gas exchange in patients with spontaneous pneumothorax
Authors: R. M. Norris, J. G. Jones, J. M. Bishop
Journal: Thorax (1968)

Pulmonary gas exchange was studied in 12 patients with spontaneous pneumothorax by measuring the partial pressure of oxygen and carbon dioxide in arterial blood and expired gas when breathing air and 100% oxygen. The arterial oxygen tension was below 80 mm. Hg in nine patients, and the alveolar-arterial difference in oxygen tension was abnormally large in 10, but the physiological dead space was generally normal. There was a positive correlation between the size of the anatomical shunt and the extent of the pneumothorax as measured from the chest radiograph. Calculations indicated that the fall in arterial oxygen tension when breathing air could be fully accounted for by the increased anatomical shunt. After the air had been removed ventilation—perfusion relationships appeared to become more uneven, and the anatomical shunt was greater than would have been expected from the size of the lung. Observations during infusions of acetylcholine suggested that active vasoconstriction in poorly ventilated regions may have occurred to a slight or moderate degree in four out of eight patients.
ASSOCIATION BETWEEN ADMISSION HEMOGLOBIN LEVEL AND GUIDELINE-BASED THERAPY IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: AN ANALYSIS FROM THE NCDR&amp;reg;
Authors: Robert F. Riley, L. Kristin Newby, Creighton Don, Sanjay Gandhi, Karen Alexander, S. Andrew Peng, Michael Kutcher, Ezra Amsterdam, David Herrington
Journal: Journal of the American College of Cardiology (2012)
Tumor Vascularity in the Prognostic Assessment of Primary Cutaneous Melanoma
Authors: Mohammed Kashani-Sabet, Richard W. Sagebiel, Carlos M.M. Ferreira, Mehdi Nosrati, James R. Miller
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The vascular supply of the primary tumor is recognized to play an important role in the progression of a number of solid tumors. However, the role of tumor vascularity in the prognostic assessment of melanoma remains unclear. The purpose of this study was to determine the prognostic impact of patterns of vascularity on the outcome associated with cutaneous melanoma. PATIENTS AND METHODS: Tumor vascularity was documented prospectively using routine histopathologic analysis of 417 primary cutaneous melanomas from the University of California at San Francisco Melanoma Center database. Four patterns of tumor vascularity were recorded: absent, sparse, moderate, and prominent. RESULTS: Increasing tumor vascularity significantly increased the risk of relapse and death associated with melanoma, corresponding to reduced relapse-free and overall survival. By multivariate analysis, tumor vascularity was the most important determinant of overall survival, surpassing tumor thickness. Increasing tumor vascularity was associated with increased incidence of ulceration in the primary tumor. CONCLUSION: Tumor vascularity is an important prognostic factor in melanoma, rivaling tumor thickness. Increasing tumor vascularity is highly correlated with ulceration, possibly helping to explain the biologic basis of this known prognostic factor.
Increased expression of endothelin receptors in the vasculature of portal hypertensive rats: Role in splanchnic hemodynamics
Authors: Paul A. Cahill, Ming-chih Hou, Richard Hendrickson, Yi-ning Wang, Shuangmin Zhang, Eileen M. Redmond, James V. Sitzmann
Journal: Hepatology (1998)

Portal hypertension (PHT) is characterized by increased portal pressure caused in part by a reduction in mesenteric vascular resistance. The aim of this study was to evaluate the role of endothelin (ET) and specific ET receptors in maintaining the vasculopathy of PHT. PHT was created in Sprague-Dawley rats by a partial portal vein ligation. Control animals were sham-operated. ET receptor expression was determined in the superior mesenteric artery of sham and PHT rats by in situ autoradiography, radioligand binding analysis, and reverse-transcription polymerase chain reactions (RT-PCR). The pressor response to ET-1 was determined in vitro using isolated vascular rings and in vivo by measuring mean arterial pressure, splanchnic blood flow, and portal venous pressure following treatment with ET and selective ET receptor antagonists. The pressor response to ET in vitro was significantly enhanced in PHT concomitant with increased ET-A and ET-B receptor expression. There was a significant increase in the peak pressor response to ET (10 microg/kg intravenously) in portal hypertensive rats without any significant change in plasma ET-1 levels. There was no significant difference in the peak splanchnic blood flow or portal venous pressure response following ET-A receptor blockade with JKC-301 infusion (200 microg/kg intravenously). In contrast, ET-B receptor blockade with IRL-1038 (200 microg/kg intravenously) preferentially decreased splanchnic blood flow and portal venous pressure in portal hypertensive rats. These data suggest that enhanced ET-B receptor expression in portal hypertensive vessels contributes to the maintenance of elevated portal pressure in these animals.
THE CHEMOTHERAPY OF LOCAL SUPPURATION: ACRIFLAVINE AND BORIC ACID COMPARED
Authors: J. G. Graham
Journal: BMJ (1925)

I MxDICALJOUIRevent familiar to every house-surgeoni; henice thel surgeon's lament:My fingers ache with tying manv knots, On catgut, tendon, silk, and linen tlhreads, And examlining patients in their cotsOr stitching wounds in faces, limbs, and lheads.A slipping ligature might disgrace me, Filling a recent wound witlh ugly clot, And filling my mind with anythllng but glee, By bringing the patient to a state of shock.Perchance I might commit felo-de-se, Even be drawn into a court of law, And rather than count failure don't you see,It would be wise to close the surgery door: For many patients in these busy davs, Though glad to be heal'd are too slhy to praise.
Diarrhea in neutropenic patients: a prospective cohort study with emphasis on neutropenic enterocolitis
Authors: D.Y. Aksoy, M.D. Tanriover, O. Uzun, P. Zarakolu, S. Ercis, S. Ergüven, A. Oto, U. Kerimoglu, M. Hayran, O. Abbasoglu
Journal: Annals of Oncology (2006)
A Quantitative Method for Measuring Gene Expression Magnitude and Volume Delivered by Gene Therapy Vectors
Authors: Kenneth N Barton, Xueqing Xia, Hui Yan, Hans Stricker, Gregory Heisey, Fang-Fang Yin, Tavarekere N Nagaraja, Guopei Zhu, Andrew Kolozsvary, Joseph D Fenstermacher, Mei Lu, Jae Ho Kim, Svend O Freytag, Stephen L Brown
Journal: Molecular Therapy (2004)

This study describes a quantitative method to measure the magnitude and distribution of gene expression following local delivery of an adenoviral vector containing the human sodium iodide symporter (hNIS) reporter gene into the canine prostate. Following systemic administration of Na99mTcO4, autoradiographs of prostate sections depicting hNIS-dependent 99mTcO4− uptake were digitized and stacked to produce a three-dimensional reconstruction of gene expression. Frequency histograms reflecting hNIS gene expression magnitude and volume were used to quantify hNIS function. The method demonstrated submillimeter resolution allowing for precise measurements of gene expression magnitude and volume in vivo. The method developed here could be applied to other reporter gene systems in which the readout can be digitized from thin tissue sections.
Improvement of doxorubicin induced cardiomyopathy in rats treated with insulin-like growth factor I
Authors: G R Ambler, B M Johnston, L Maxwell, J B Gavin, P D Gluckman
Journal: Cardiovascular Research (1993)

Objectives: This study was designed to assess the effects of treatment with insulin-like growth factor-I (IGF-I) on cardiac function and structure in rats with an established cardiomyopathy. Methods: Adult male Wistar rats were injected with doxorubicin (2 mg·kg−1 subcutaneously) weekly for 12 weeks and either rhIGF-I (0.8 mg·kg−1·day−1; n=16, D-I group) or saline (n=25, D-S group) subcutaneously via an osmotic pump from weeks 9 to 12. A non-doxorubicin injected control group was also studied. After 12 weeks survivors were anaesthetised and cardiac output determined with radiolabeled microspheres. At postmortem pleural effusion and ascitic volumes were measured and the heart was removed for histological examination by light and transmission electron microscopy. Results: Doxorubicin treated animals showed less mean weight gain from week 2 than the untreated control group. Animals treated with IGF-I from week 9 showed a significant (p<0.05) but non-sustained increase in weight. Survival to 12 weeks was 56% in the D-I group and 44% in the D-S group (p=0.2). Evidence of cardiac failure was seen in the D-I and the D-S groups, but there was a tendency (p=0.06) for less ascites in the D-I group (21(SEM 8) ml) than in the D-S group (46(10) ml). Cardiac output was significantly higher in the D-I than in the D-S group (132(7.2) v 91.4(6.4) ml·min−1, p<0.01), as was stroke volume (0.323(0.03) v 0.226(0.02) ml, p<0.01). There was focal cardiac damage in both D-I and D-S animals. Scattered groups of myocytes showed prominent vacuolation of the nuclear envelope, sarcoplasmic reticulum, and t tubular system, mild to severe mitochondrial swelling, and loss of orientation and definition of myofibrils. No clear morphological differences were evident between the two groups. Conclusions: Administration of IGF-I may improve the function of damaged myocardium, although the mechanisms are unclear. Further studies with earlier coadministration of IGF-I, quantitative histological analysis, and with other models of cardiac injury are indicated. Cardiovascular Research 1993;27:1368-1373
Status of blood group carbohydrate chains in ontogenesis and in oncogenesis.
Authors: K Watanabe, S I Hakomori
Journal: The Journal of Experimental Medicine (1976)

Blood group ABH determinants in human erythrocytes are carried by four kinds of glycolipid carbohydrate chains, differing in their structural complexity. They are Aa, Ab, Ac, and Ad for A variants, and H1, H2, H3, and H4 for H variants (Table I and Fig 1). Based on the surface labeling of A variants and on the reactivity of erythrocytes to antibodies directed against H3 and against its degradation products, it is concluded that complex variants of A or H determinants (Ac and Ad/or H3 and H4) are absent or significantly low in fetal erythrocytes (80-150 days after gestation) and in new born erythrocytes, whereas these complex structures are fully developed in adult erythrocytes. In contrast, A determinants linked to simpler carbohydrate chains (Aa, Ab variants) are fully developed before birth and do not show significant change after birth. The precursor of blood group carbohydrate chains seems to be abundant in fetal or newborn erythrocytes. This assumption is based on the higher reactivity of fetal or newborn erythrocytes to an antibody, which is directed against the precursor N-acetylglucosaminly beta1 leads to 3 galactosyl beta1 leads to 4 glucosylceramide than in adult erythorocytes. Reactions of glycolipids of gastrointestinal mucosa, with antibodies directed against H3 glycolipid and its degradation products, were compared to that of gastrointestinal tumors. The reaction to bela Glc NAc1 leads to 3 beta Gall leads to 4 Glc leads to ceramide (structure 4), which is the precursor of all blood group glycolipids, was consistently high in many cases of tumor glycolipid than that of normal glycolipid. This as well as other evidence supports a general concept that the process of ontogenesis of a blood group carbohydrate chain occurs as step-by-step elongation and arborization, and that blocking of such a development of a carbohydrate chain occurs in the process of oncogenesis.
PEMPHIGUS: A REVIEW OF SEVEN CASES
Authors: JOHN KINNEAR
Journal: British Journal of Dermatology (1938)

Journal Article PEMPHIGUS: A REVIEW OF SEVEN CASES Get access JOHN KINNEAR, M.D., M.E.C.P.ED. JOHN KINNEAR, M.D., M.E.C.P.ED. Physician for Diseases of the Skin, Dundee Royal Infirmary; Lecturer in Diseases of the Skin, University of St. Andrews Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 50, Issue 5, 1 May 1938, Pages 236–243, https://doi.org/10.1111/j.1365-2133.1938.tb10554.x Published: 01 May 1938
Breast cancer management and outcome according to surgeon's affiliation: a population-based comparison adjusted for patient's selection bias
Authors: F. Taban, E. Rapiti, G. Fioretta, Y. Wespi, D. Weintraub, A. Hugli, H. Schubert, G. Vlastos, M. Castiglione, C. Bouchardy
Journal: Annals of Oncology (2012)
The selection of resistance to and the mutagenicity of different fluoroquinolones in Staphylococcus aureus and Streptococcus pneumoniae
Authors: J.M. Sierra, J.G. Cabeza, M. Ruiz Chaler, T. Montero, J. Hernandez, J. Mensa, M. Llagostera, J. Vila
Journal: Clinical Microbiology and Infection (2005)
The association of early IQ and education with mortality: 65 year longitudinal study in Malmo, Sweden
Authors: A Lager, S Bremberg, D Vagero
Journal: BMJ (2009)

<b>Objectives </b>To establish whether differences in early IQ explain why people with longer education live longer, or whether differences in father's or own educational attainment explain why people with higher early IQ live longer. <b>Design </b>Population based longitudinal study. Mortality risks were estimated with Cox proportional hazards regressions. <b>Setting</b> Malmö, Sweden. <b>Participants </b>1530 children who took IQ tests at age 10 and were followed up until age 75. <b>Results</b> Own educational attainment was negatively associated with all cause mortality in both sexes, even when early IQ and father's education were adjusted for (hazard ratio (HR) for each additional year in school 0.91 (95% CI 0.85 to 0.97) for men and HR 0.88 (95 % CI 0.78 to 0.98) for women). Higher early IQ was linked with a reduced mortality risk in men, even when own educational attainment and father's education were adjusted for (HR for one standard deviation increase in IQ 0.85 (95 % CI 0.75 to 0.96)). In contrast, there was no crude effect of early IQ for women, and women with above average IQ had an increased mortality risk when own educational attainment was adjusted for, but only after the age of 60 (HR 1.60 (95 % CI 1.06 to 2.42)). Adding measures of social career over and above educational attainment to the model (for example, occupational status at age 36 and number of children) only marginally affected the hazard ratio for women with above average IQ (&lt;5%). <b>Conclusions</b> Mortality differences by own educational attainment were not explained by early IQ. Childhood IQ was independently linked, albeit differently, to male adult mortality and to female adult mortality even when father's education and own educational attainment was adjusted for, thus social background and own social career seem unlikely to be responsible for mortality differences by childhood IQ. The clear difference in the effect of IQ between men and women suggests that the link between IQ and mortality involves the social and physical environment rather than simply being a marker of a healthy body to begin with. Cognitive skills should, therefore, be addressed in our efforts to create childhood environments that promote health.
Studies on the Mechanism of Immunological Enhancement of Tumor Homografts. 1. Specificity of Immunological Enhancement&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Göran Möller
Journal: JNCI Journal of the National Cancer Institute (1963)

This study of the specificity of immunological enhancement attempts to differentiate between the various hypotheses explaining the phenomenon of antibody-induced enhancement of tumor growth. Different mouse sarcomas were tested in systems designed to direct the antibodies against a number of antigenic components differentiating tumor and host, all belonging to the H-2 system. This was accomplished by variation of the specificity of the antiserum or the genotype of the recipients. All systems gave analogous results: a strong enhancing effect when the antibodies were directed against all tumor antigens foreign to the host, but no or diminished enhancement when only some of these antigens were covered by antibodies. Inhibition was directly related to the number or “strength” of the antigens remaining uncovered by antibodies. Passively transferred antibodies inhibited the humoral antibody response to tumor inoculation. Antibody action was specific in this system too: Passively transferred antibodies inhibited the immune response only against corresponding antigens, while other isoantigens on the same tumor cells still immunized efficiently. The pronounced specificity of the enhancing effect was incompatible with the hypotheses postulating antibody-induced alterations of tumor-cell characteristics, such as increased growth rate or increased resistance to the homograft reaction, but agreed with the assumption that antibodies interfere with the immunological relationship between tumor and host.
Expression of the pancreatic secretory trypsin inhibitor gene in the liver infected with hepatitis B virus
Authors: Yoshitaka Ohmachi, Atsuo Murata, Takushi Yasuda, Kazunori Kitagawa, Syuuji Yamamoto, Morito Monden, Takesada Mori, Nariaki Matsuura, Kenichi Matsubara
Journal: Journal of Hepatology (1994)
Treatment of active Crohn's disease in children using partial enteral nutrition with liquid formula: a randomised controlled trial
Authors: T Johnson
Journal: Gut (2005)

Total enteral nutrition (TEN) with a liquid formula can suppress gut inflammation and induce remission in active Crohn's disease. The mechanism is obscure. Studies have suggested that long term nutritional supplementation with a liquid formula (partial enteral nutrition (PEN)) may also suppress inflammation and prevent relapse. The aim of this study was to compare PEN with conventional TEN in active Crohn's disease.
Altered Fiber Distribution and Fiber-Specific Glycolytic and Oxidative Enzyme Activity in Skeletal Muscle of Patients With Type 2 Diabetes
Authors: Andreas Oberbach, Yvonne Bossenz, Stefanie Lehmann, Josef Niebauer, Volker Adams, Ralf Paschke, Michael R. Schön, Matthias Blüher, Karla Punkt
Journal: Diabetes Care (2006)

OBJECTIVE—We investigated whether alterations of glycolytic and oxidative enzyme capacity in skeletal muscle of patients with type 2 diabetes pertain to specific muscle fibers and are associated with changes in muscle fiber composition. RESEARCH DESIGN AND METHODS—Vastus lateralis muscle was obtained by percutaneous biopsy from 10 patients with type 2 diabetes and 15 age- and BMI-matched healthy volunteers. Using cytophotometry, muscle fiber composition and fiber type–specific glycolytic and oxidative enzyme activities were measured in slow oxidative, fast oxidative glycolytic, and fast glycolytic fibers. RESULTS—In the whole muscle, oxidative activity was decreased in patients with type 2 diabetes. The slow oxidative fiber fraction was reduced by 16%, whereas the fast glycolytic fiber fraction was increased by 49% in skeletal muscle from the diabetic patients. Both oxidative and glycolytic enzyme activities were significantly increased in fast glycolytic and fast oxidative glycolytic fibers of type 2 diabetic patients. However, the fiber-specific ratio of glycolytic enzyme activity relative to oxidative activity was not different between type 2 diabetic patients and the control subjects. The myofibrillic ATP activity was significantly lower in all fiber types of patients with type 2 diabetes and correlates with glucose infusion rate during the steady state of a euglycemic-hyperinsulinemic clamp and maximal aerobic capacity and negatively with HbA1c values. CONCLUSIONS—Reduced oxidative enzyme activity in muscle of type 2 diabetic patients is most likely due to a reduction in slow oxidative fibers. Increased glycolytic and oxidative enzyme activities in individual muscle fibers are closely related to measures of long-term glycemic control and whole-body insulin sensitivity and could therefore represent a compensatory mechanism of the muscle in function of the altered glucose metabolism.