tbuckley/cabot-search huggingface dataset:
The <i>PAX3-FKHR</i> Fusion Gene of Rhabdomyosarcoma Cooperates with Loss of p16INK4A to Promote Bypass of Cellular Senescence
Authors: Corinne M. Linardic, Sarasija Naini, James E. Herndon, Chimen Kesserwan, Stephen J. Qualman, Christopher M. Counter
Journal: Cancer Research (2007)

Abstract Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood and adolescence. Despite advances in therapy, patients with a histologic variant of rhabdomyosarcoma known as alveolar rhabdomyosarcoma (ARMS) have a 5-year survival of &amp;lt;30%. ARMS is characterized by a chromosomal translocation generating the PAX3-FKHR fusion gene. However, ectopic expression of PAX3-FKHR often induces inhibition of cell proliferation, or cell death, when expressed in nonmuscle cells. This prompted us to explore the effect of expressing PAX3-FKHR in more relevant cells, specifically primary human skeletal muscle cells because these cells can be converted to a tumorigenic state that mimics rhabdomyosarcoma. PAX3-FKHR expression promoted both fetal and postnatal primary human skeletal muscle cell precursors to bypass the senescence growth arrest checkpoint. This bypass was accompanied by epigenetic DNA methylation of the p16INK4A promoter and correspondingly a loss of expression of this tumor suppressor. Knockdown of p16INK4A cooperated with PAX3-FKHR to drive proliferation past senescence, whereas reintroduction of wild-type p16INK4A in post-senescent cells caused growth arrest. Thus, PAX3-FKHR acts in concert with loss of p16INK4A to promote inappropriate proliferation of skeletal muscle cells. This association between PAX3-FKHR expression and p16INK4A loss was seen in human ARMS tumor tissue, as both human rhabdomyosarcoma cell lines and tissue microarrays showed a trend toward down-regulation of p16INK4A protein in alveolar subsets. We surmise that the generation of the PAX3-FKHR fusion protein may require loss of p16INK4A to promote malignant proliferation of skeletal muscle cells as an early step in ARMS tumorigenesis. [Cancer Res 2007;67(14):6691–9]
Symposium on Byzantine Medicine
Authors: John Muendel
Journal: JAMA (1986)

The<i>Symposium on Byzantine Medicine</i>is made up of 21 papers that were originally delivered in 1983 at the Dumbarton Oaks Research Library and Collection in Washington, DC. Unlike many scholarly compilations, which incorporate a variety of studies to elaborate on a general theme, this assemblage of articles can be read with a decided sense of continuity and understanding because of the organizational skill of its editor, John Scarborough. The first six presentations relate the Byzantine physician to the society and institutions within which he worked from the time of Galen (129-c 210 AD) to the fall of Constantinople in 1453. Vivian Nutton, Barry Baldwin, and John Duffy show that, despite the influence of the faith healers of the early church, Byzantine medical practitioners maintained a position of respectability in all levels of society. While a skilled medical encyclopedist such as Oribasius (c 320-c 400 AD) could be highly regarded
352. Gene Transfer of Angiogenic Inhibitors Suppresses Lung Tumor Growth in Spontaneous Pulmonary Metastasis Mouse Model
Authors: Kexia Cai, Mai Har Sham, Weidong Xiao, Paul Tam, Ruian Xu
Journal: Molecular Therapy (2005)

Top of pageAbstract
Lung cancer is the most important lethal neoplasm in the United States and worldwide. There will be an estimated 172,000 new cases of lung cancer in the USA in 2004, 85% of which will lead to death within five years, despite new therapeutic strategies and progresses in surgical oncology. There is no gold-standard therapy and currently used cytotoxics offer unsatisfactory response.

Gene therapy of cancer has shown to be applicable in several clinical situations and these strategies are already proving their full potential in cancer treatment. Anti-angiogenic therapy is currently considered to represent a new promising approach to suppress tumor growth without detectable toxicity. In this study, we introduced primary tumor in immunocompromised mice by subcutaneous injection of high metastatic Lewis lung carcinoma (hm-LLC) cells. Angiogenic inhibitor, vasostatin 1, the N-terminal domain of human calreticulin inclusive of amino acids 1-180, was tested in this mouse model alone or combined with angiostatin. Our studies revealed that overexpression of vasostatin successfully inhibited the growth and pulmonary metastasis of subcutaneous tumor. The primary tumor growth was significantly inhibited in the group received hm-LLC cells infected by AAV harboring human vasostatin gene, compared to the control group received AAV/eGFP-transfected hm-LLC cells (18days, p=0.0014). Pulmonary metastatic burden assessed by counting surface pulmonary tumors also showed significant reduction in the treatment group when compared to the control group (18 days, p=0.0023). Combination of AAV/angiostatin therapy with intratumoral administration of AAV/vasostatin further suppressed primary tumor growth and metastasis than each agent along, though complete tumor regression was not observed.

All these encouraging data suggest a feasible and effective form of AAV/angiostatin and AAV/vasostatin in the treatment of lung caner. The mechanism responsible for the observed effects remains to be further elucidated.
Increased Transcapillary Escape Rate of Albumin in Microalbuminuric Type II Diabetic Patients
Authors: Monica Nannipieri, Loredana Rlzzo, Antonella Rapuano, Alessandro Pilo, Giuseppe Penno, Renzo Navalesi
Journal: Diabetes Care (1995)

To evaluate microvascular permeability by the transcapillary escape rate of albumin (TERalb) in type II diabetic patients with normo- and microalbuminuria.The TERalb has been measured following intravenous injection of 125I-labeled human serum albumin in 32 normotensive type II diabetic patients and 9 healthy control subjects matched for sex and age. Type II diabetic subjects were grouped in normoalbuminuric, albumin excretion rate (AER) < 20 micrograms/min (n = 18), and microalbuminuric, AER 20-200 micrograms/min (n = 14) categories.In type II diabetic patients, no differences were noted between normo- and microalbuminuric groups for known diabetes duration (8.3 +/- 5.9 vs. 11.7 +/- 8.0 years), blood pressure (BP) (129/76 +/- 16/8 vs. 131/76 +/- 14/5 mmHg), current metabolic control (HbA1c: 8.0 +/- 1.4 vs. 8.5 +/- 1.6%), and serum lipids. However, previous 2-year mean HbA1c levels were significantly higher in microalbuminuric patients (8.7 +/- 1.45 vs. 7.6 +/- 1.29%; P < 0.05). The TERalb was similar in control subjects and normoalbuminuric patients (5.16 +/- 1.09 vs. 5.71 +/- 1.66 %/h) and significantly higher in the microalbuminuric group (8.98 +/- 1.35 %/h; P < 0.0001). The increased leak of albumin was not explained by differences in diabetes duration, BP, or metabolic control at the time of investigation and was independently related to the presence of microalbuminuria (r = 0.63, percent explained variance approximately 40) and mean "historical" HbA1c (multiple r = 0.705; total explained variance approximately 50%).Type II diabetic patients with microalbuminuria show an increased TERalb, i.e., a widespread microvascular damage that may be important in the pathogenesis of long-term complications. Our findings may contribute to the explanation of why albuminuria seems to be an independent cardiovascular risk factor in type II diabetes.
Simple dosage guide for suncreams will help users
Authors: S. Taylor
Journal: BMJ (2002)

EDITOR—The sun protection factor (SPF) of a sunscreen is determined after phototesting in vivo at an internationally agreed application thickness of 2 mg/cm2. Yet studies have shown that consumers apply much less than this—typically between 0.5 and 1.5 mg/cm2.1 This has an appreciable effect on protection, with typical application rates achieving a sun protection factor of perhaps one third of that stated on the product.2 This mismatch may be one contributing factor why sunscreens have been reported to be a risk factor in melanoma.3

No …
Pigmented Villonodular Synovitis with Bony Invasion
Authors: George A. Snook
Journal: JAMA (1963)

IT IS THE PURPOSE of this paper to document two cases of pigmented villonodular synovitis of joints with bony invasion. McMaster<sup>1</sup>has recently presented a paper on this subject and added 6 new cases, bringing the total reported to 16. The new cases reported here are significant because of the joints involved and the ages of the patients. <h3>Report of Cases</h3><h3>Case 1.</h3> An 82-yr-old woman was first seen on March 21, 1959, because of intermittent pain of many months' duration in her right shoulder. During the 2 weeks prior to her first visit, swelling had appeared and gradually increased. Pain had become quite severe and was vaguely localized at the lateral aspect of the shoulder. The patient noticed limitation of motion in abduction and external rotation. There was no history of injury or of bleeding diathesis. Physical examination revealed marked fluctuant enlargement of the entire shoulder with no
Labour Party calls for action as a fifth of hospitals fail inspections
Authors: J. Wise
Journal: BMJ (2014)

A fifth of hospitals in England are failing inspections of the standard of care, and a sixth of hospitals operate below safe staffing levels, show figures released by the Labour Party.

Data from the Care Quality Commission showed that there had been a sharp decline in standards in England’s hospitals over the past 12 months, it said.

Labour said that in the year to March 2014 the CQC had listed 45 …
Burden of disease during quiescent periods in patients with pemphigus
Authors: S. Tabolli, C. Pagliarello, A. Paradisi, G. Cianchini, P. Giannantoni, D. Abeni
Journal: British Journal of Dermatology (2014)

Studies conducted using different tools have invariably observed that physical and mental components of health status are seriously compromised in patients with pemphigus. An improvement in quality of life (QoL) has been commonly observed over the treatment period.The aim of the study is to verify whether the patients' wellbeing is affected by pemphigus also in absence of cutaneous and mucosal lesions.The clinical records of 203 patients were analysed. A total of 47 patients were without bullae/erosions and reported a score = 0 for both the Patient Global Assessment and the Ikeda index. In order to assess the QoL we used the Skindex-17 and the 12-item General Health Questionnaire (GHQ-12).Patients without bullae/erosions had a better QoL when compared with patients with active lesions. This difference, with a reduction of approximately 30% of the Skindex-17 scores in the patients without lesions, was statistically significant, for both the symptoms and the psychosocial scales. The proportion of patients at risk of anxiety/depression (GHQ-positive cases) was 44% lower in patients without lesions compared with patients with lesions. In a multiple linear regression model the presence of bullae/erosions negatively influences QoL with an average increase of Skindex-17 symptoms and psychosocial scale scores of 11·7 and 10·6 points, respectively. Female patients had a statistically significantly worse QoL than males on the symptoms but not on the psychosocial Skindex-17 scales.While patients without lesions reported a better QoL than patients with bullae/erosions, their Skindex-17 scores remained elevated. Dermatologists should be aware that a clearing of the skin manifestations does not mean 'perfect health' for the patient.
Low-field paramagnetic resonance imaging of tumor oxygenation and glycolytic activity in mice
Authors: Shingo Matsumoto, Fuminori Hyodo, Sankaran Subramanian, Nallathamby Devasahayam, Jeeva Munasinghe, Emi Hyodo, Chandramouli Gadisetti, John A. Cook, James B. Mitchell, Murali C. Krishna
Journal: Journal of Clinical Investigation (2008)

A priori knowledge of spatial and temporal changes in partial pressure of oxygen (oxygenation; pO(2)) in solid tumors, a key prognostic factor in cancer treatment outcome, could greatly improve treatment planning in radiotherapy and chemotherapy. Pulsed electron paramagnetic resonance imaging (EPRI) provides quantitative 3D maps of tissue pO(2) in living objects. In this study, we implemented an EPRI set-up that could acquire pO(2) maps in almost real time for 2D and in minutes for 3D. We also designed a combined EPRI and MRI system that enabled generation of pO(2) maps with anatomic guidance. Using EPRI and an air/carbogen (95% O(2) plus 5% CO(2)) breathing cycle, we visualized perfusion-limited hypoxia in murine tumors. The relationship between tumor blood perfusion and pO(2) status was examined, and it was found that significant hypoxia existed even in regions that exhibited blood flow. In addition, high levels of lactate were identified even in normoxic tumor regions, suggesting the predominance of aerobic glycolysis in murine tumors. This report presents a rapid, noninvasive method to obtain quantitative maps of pO(2) in tumors, reported with anatomy, with precision. In addition, this method may also be useful for studying the relationship between pO(2) status and tumor-specific phenotypes such as aerobic glycolysis.
Neutropenia, Elevated Rheumatoid Factor, Splenomegaly, and Absence of Rheumatoid Arthritis
Authors: G. G. CORNWELL
Journal: Annals of Internal Medicine (1974)

Letters1 April 1974Neutropenia, Elevated Rheumatoid Factor, Splenomegaly, and Absence of Rheumatoid ArthritisG. G. CORNWELL III, M.D., L. R. ZACHARSKI, M.D.G. G. CORNWELL III, M.D.Search for more papers by this author, L. R. ZACHARSKI, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-80-4-555 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: A 56-year-old man first sought medical attention in September 1970 for recurrent perineal ulcerations; he had no history of joint disease.The spleen tip was palpable beneath the left costal margin. The hemoglobin was 8.3 g/100 ml, and the leukocyte count was 700/mm3, with 30% mature neutrophils, 14% stabs, 36% lymphocytes, 18% monocytes, and 2% eosinophils. The platelet estimate, Coombs' test, and serum protein electrophoresis were normal. The bone marrow was hypercellular, with increased eosinophils and marked reduction in segmented neutrophils; iron stores were absent. The rheumatoid factor was positive in a dilution of 1 to 5120....Reference1. ROGERSLANGLEY HF: Neutropenia associated with splenomegaly and atrophic arthritis (Felty's syndrome): report of a case in which splenectomy was performed. Ann Intern Med 32:745-754, 1950 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Dartmouth Medical School Hanover, New Hampshire 03755 and the Veterans Administration Hospital White River Junction, Vermont PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByThree-years follow-up of a case of non-articular Felty Syndrome treated solely with corticosteroidsWhat does the diagnosis of Felty's syndrome mean and how to formulate it?Felty’s SyndromeEXTRA-ARTICULAR MANIFESTATIONS OF RHEUMATOID ARTHRITISNeutropaenia and splenomegaly without arthritis: think rheumatoid arthritisFelty's syndrome without rheumatoid arthritis?Felty's Syndrome as an initial presentation of Rheumatoid Arthritis: a case reportSplenic involvement in rheumatic diseasesChronische Polyarthritis und Felty-SyndromFelty syndrome 1 April 1974Volume 80, Issue 4Page: 555-556KeywordsEosinophilsMonocytesNeutropeniaNeutrophilsPlateletsRheumatoid arthritisSerum proteinsSpleenSplenomegalyUlcers Issue Published: 1 April 1974 PDF DownloadLoading ...
Long-Term Ascorbic Acid Administration Reverses Endothelial Vasomotor Dysfunction in Patients With Coronary Artery Disease
Authors: Noyan Gokce, John F. Keaney, Balz Frei, Monika Holbrook, Mariusz Olesiak, Benoy J. Zachariah, Christiaan Leeuwenburgh, Jay W. Heinecke, Joseph A. Vita
Journal: Circulation (1999)

Background —Loss of endothelium-derived nitric oxide (EDNO) contributes to the clinical expression of coronary artery disease (CAD). Increased oxidative stress has been linked to impaired endothelial vasomotor function in atherosclerosis, and recent studies demonstrated that short-term ascorbic acid treatment improves endothelial function. Methods and Results —In a randomized, double-blind, placebo-controlled study, we examined the effects of single-dose (2 g PO) and long-term (500 mg/d) ascorbic acid treatment on EDNO-dependent flow-mediated dilation of the brachial artery in patients with angiographically established CAD. Flow-mediated dilation was examined by high-resolution vascular ultrasound at baseline, 2 hours after the single dose, and 30 days after long-term treatment in 46 patients with CAD. Flow-mediated dilation improved from 6.6±3.5% to 10.1±5.2% after single-dose treatment, and the effect was sustained after long-term treatment (9.0±3.7%), whereas flow-mediated dilation was 8.6±4.7% at baseline and remained unchanged after single-dose (7.8±4.4%) and long-term (7.9±4.5%) treatment with placebo ( P =0.005 by repeated-measures ANOVA). Plasma ascorbic acid concentrations increased from 41.4±12.9 to 115.9±34.2 μmol/L after single-dose treatment and to 95.0±36.1 μmol/L after long-term treatment ( P &lt;0.001). Conclusions —In patients with CAD, long-term ascorbic acid treatment has a sustained beneficial effect on EDNO action. Because endothelial dysfunction may contribute to the pathogenesis of cardiovascular events, this study indicates that ascorbic acid treatment may benefit patients with CAD.
Suppression of allergic inflammation by the prostaglandin E receptor subtype EP3
Authors: Tomonori Kunikata, Hana Yamane, Eri Segi, Toshiyuki Matsuoka, Yukihiko Sugimoto, Satoshi Tanaka, Hiroyuki Tanaka, Hiroichi Nagai, Atsushi Ichikawa, Shuh Narumiya
Journal: Nature Immunology (2005)
Enhanced expression of the heat shock protein gene in peripheral blood mononuclear cells of patients with active systemic lupus erythematosus.
Authors: Y Deguchi, S Kishimoto
Journal: Annals of the Rheumatic Diseases (1990)

The spontaneous increase in the transcription of the heat shock protein (hsp 70) gene in peripheral blood mononuclear cells of patients with active systemic lupus erythematosus (SLE) is shown by nuclear run on transcription assay. The transcription of hsp 70 gene in the peripheral blood mononuclear cells of five patients with active SLE was more than 10 times greater than that in five normal healthy subjects or three patients with bronchial asthma as controls. This suggests that heat shock proteins may be produced during an active immune response in patients with active SLE and play a part in a change related to lupus of the essential intracellular functions of peripheral blood mononuclear cells.
1012-133 Statin therapy can improve cardiac function and survival after heart failure in rats
Authors: Sahoko Ichihara, Akiko Noda, Akira Yamada, Tomoko Kato, Kohzo Nagata, Mitsunori Iwase, Toyoaki Murohara, Mitsuhiro Yokota
Journal: Journal of the American College of Cardiology (2004)
Impaired neutrophil chemotaxis in sepsis associates with GRK expression and inhibition of actin assembly and tyrosine phosphorylation
Authors: Sandra Mara A. Arraes, Marta S. Freitas, Simone V. da Silva, Heitor A. de Paula Neto, Jose Carlos Alves-Filho, Maria Auxiliadora Martins, Anibal Basile-Filho, Beatriz M. Tavares-Murta, Christina Barja-Fidalgo, Fernando Q. Cunha
Journal: Blood (2006)
Indications for Surgery in Severe Bell's Palsy
Authors: A. Tumarkin
Journal: BMJ (1936)

M1JDJCAL Jo.rnNAt * Glycerin of pepsin, 1914 B.P., contains 10 per cent. of pepsin and 1.15 per cent. of HCl.Summary 1. Excessive primary haemorrhage is the chief source of difficulty in endoscopic resection of the prostate, and leads to inadequate removal of tissue.It can be nminimized by the local infiltration of the prostate with a solution containing adrenaline.2. Secondary haemorrhage from infection is likely to follow incomplete emptying of the bladder due to in- adequate removal of tissue; it may lead to clot retention, 3.In the event of clot retention an attempt should be made to break up the clot by the injection of pepsin.Only if this fails is it necessary to open the bladder.
Abstract B43: Intratumoral heterogeneity of ovarian cancer stem cells and their interactions with the tumor microenvironment
Authors: Maty Tzukerman, Sagi Abelson, Yeela Shamai, Liron Berger, Karl Skorecki
Journal: Cancer Research (2015)

Abstract Intratumoral heterogeneity challenges existing paradigms for anti-cancer therapy. We have previously demonstrated that the human embryonic stem cells (hESC)-derived cellular microenvironment in immunocompromised mice, enables functional distinction of heterogeneous tumor cells, including cells which do not grow into a tumor in conventional direct tumor xenograft platform. We have identified and characterized six cancer cell subpopulations each clonally expanded from a single cell, derived from human ovarian clear cell carcinoma of a single tumor, to demonstrate striking intratumoral phenotypic heterogeneity that is dynamically dependent on the tumor growth microenvironment. These cancer cell subpopulations, characterized as cancer stem cell subpopulations, faithfully recapitulate the full spectrum of histological phenotypic heterogeneity known for human ovarian clear cell carcinoma. Each of the six subpopulations displays a different level of morphologic and tumorigenic differentiation wherein growth in the hESC-derived microenvironment favors growth of CD44+/aldehyde dehydrogenase positive pockets of self-renewing cells that sustain tumor growth through a process of tumorigenic differentiation into CD44-/aldehyde dehydrogenase negative derivatives. Strikingly, these derivative cells display microenvironment-dependent plasticity with the capacity to restore self-renewal markers and CD44 expression. We delineated the distinct gene expression and epigenetic profiles of two such subpopulations, representing extremes of phenotypic heterogeneity in terms of niche-dependent self-renewal and tumorigenic differentiation. By combining Gene Set Enrichment, Gene Ontology and Pathway-focused array analyses with methylation status and secretome analyses, we propose a suite of robust differences in tumor self-renewal and differentiation pathways, and interaction with stromal cells in the tumor microenvironment that underlay the striking intratumoral phenotypic heterogeneity which characterized this and other solid tumor malignancies. Citation Format: Maty Tzukerman, Sagi Abelson, Yeela Shamai, Liron Berger, Karl Skorecki. Intratumoral heterogeneity of ovarian cancer stem cells and their interactions with the tumor microenvironment. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B43. doi:10.1158/1538-7445.CHTME14-B43