tbuckley/cabot-search huggingface dataset:
A Therapeutic Strategy for Choroidal Neovascularization Based on Recruitment of Mesenchymal Stem Cells to the Sites of Lesions
Authors: Hui-Yuan Hou, Hong-Liang Liang, Yu-Sheng Wang, Zhao-Xia Zhang, Bai-Ren Wang, Yuan-Yuan Shi, Xiao Dong, Yan Cai
Journal: Molecular Therapy (2010)

Choroidal neovascularization (CNV) is a common cause of severe and irreversible visual loss; however, the treatment of CNV has been hindered by its complex and poorly understood pathogenesis. It has been postulated that bone marrow (BM)–derived cells (BMCs) contribute to CNV, but little is known about the role of mesenchymal stem cells (MSCs) in CNV and their therapeutic potential for CNV treatment. We found that BM-derived MSCs transplanted by intravenous injection into laser-induced CNV mouse models were specifically recruited into CNV lesions, where they differentiated into multiple cell types and participated in the development of neovascularization, without stagnation in other organs. By taking advantage of this recruitment potential, engineered MSCs were used to produce the antiangiogenic pigment epithelial-derived factor (PEDF) at the CNV sites, thereby inhibiting the growth of CNVs and stimulating regressive features. Further studies indicated that the effect may be mediated, at least partly, by retinal pigment epithelial (RPE) cells, which function as important regulators for CNV development. These results suggest that MSCs contribute to CNV and could serve as delivery vehicles of antiangiogenic agents for the treatment of a range of CNV-associated diseases. Choroidal neovascularization (CNV) is a common cause of severe and irreversible visual loss; however, the treatment of CNV has been hindered by its complex and poorly understood pathogenesis. It has been postulated that bone marrow (BM)–derived cells (BMCs) contribute to CNV, but little is known about the role of mesenchymal stem cells (MSCs) in CNV and their therapeutic potential for CNV treatment. We found that BM-derived MSCs transplanted by intravenous injection into laser-induced CNV mouse models were specifically recruited into CNV lesions, where they differentiated into multiple cell types and participated in the development of neovascularization, without stagnation in other organs. By taking advantage of this recruitment potential, engineered MSCs were used to produce the antiangiogenic pigment epithelial-derived factor (PEDF) at the CNV sites, thereby inhibiting the growth of CNVs and stimulating regressive features. Further studies indicated that the effect may be mediated, at least partly, by retinal pigment epithelial (RPE) cells, which function as important regulators for CNV development. These results suggest that MSCs contribute to CNV and could serve as delivery vehicles of antiangiogenic agents for the treatment of a range of CNV-associated diseases.
Endoscopic Coagulation for Gastrointestinal Bleeding
Authors: David Fromm
Journal: New England Journal of Medicine (1987)

There is little argument that emergency operation for upper gastrointestinal nonvariceal hemorrhage is associated with a higher mortality than the same operation performed electively. Two controlled trials of elective treatment of duodenal ulcer show no operative mortality,1 , 2 whereas the mortality figures from some centers still approach 20 percent for emergency surgery for bleeding ulcer.3 It is therefore important that endoscopically applied techniques have the potential to stop bleeding from the lower esophagus, stomach, or duodenum. At best, the patient may not require subsequent invasive treatment; at worst, an indicated operation can be performed electively if the initial endoscopic approach is . . .
Local Staging of Esophageal Cancer Using Endoscopic Magnetic Resonance Imaging: Prospective Comparison with Endoscopic Ultrasound
Authors: D. Kulling, D. R. Feldman, C. L. Kay, B. J. Hoffman, C. E. Reed, J. W. R. Young, R. H. Hawes
Journal: Endoscopy (1998)

Background and Study Aims: The magnetic resonance endoscope consists of a non-ferrous endoscope with a radiofrequency receiver coil incorporated into its tip. The aim of this study was to assess the accuracy of endoscopic magnetic resonance imaging for the local staging of esophageal cancer.
Hyposensitivity to vasopressin in patients with hepatitis B–related cirrhosis during acute variceal hemorrhage
Authors: Yang-Te Tsai, Fa-Yauh Lee, Han-Chieh Lin, Shou-Dong Lee, Hsiao-Chung Hsia, Wen-Jeh Lin, Sun-Sang Wang, Chii-Shyan Lay, Kwok-Hung Lai, Kwang-Juei Lo
Journal: Hepatology (1991)

It has been suggested that vasopressin given during hemorrhage may be less effective than when given during a stable state in a portal-hypertensive rat model. This study was designed to evaluate the hemodynamic response to vasopressin infusion in 25 HBsAgpositive cirrhotic patients. Nine patients had active variceal hemorrhage before vasopressin infusion, and the other 16 patients were in a stable condition at the time of infusion. The two groups of patients were similar in baseline values except that a higher heart rate was found in patients with hemorrhage (96 ± 20 vs. 73 ± 10 beats/min, mean ± S.D., p &lt; 0.01). Thirty minutes after vasopressin infusion (0.66 units/min), hepatic venous pressure gradient significantly decreased in both bleeding and stable patients (from 21 ± 9 to 18 ± 9 mm Hg, p &lt; 0.05; and from 18 ± 4 to 8 ± 3 mm Hg, p &lt; 0.000 1, respectively). However, the decrease of hepatic venous pressure gradient was less obvious in bleeding patients as compared with stable patients (4 ± 3 vs. 9 ± 2 mm Hg, p &lt; 0.0001). A significant reduction of hepatic venous pressure gradient after vasopressin infusion was found in five bleeding patients without shock (from a median of 16 mm Hg [range = 12 to 26] to 11 mm Hg [range = 6 to 18], p &lt; 0.05), but not in four bleeding patients with shock (from 28 [range = 15 to 36] to 25 [range = 18 to 33] mm Hg, p &gt; 0.05). Vasopressin infusion resulted in a significantly lower heart rate and cardiac output with a concomitantly higher systemic vascular resistance in both groups of patients (p &lt; 0.05). Mean arterial pressure increased after vasopressin infusion in stable patients (p &lt; 0.000 1), but it remained unchanged in bleeding patients (p &gt; 0.05). These findings confirm that vasopressin given during acute variceal hemorrhage, especially in cirrhotic patients with shock, may be less effective than when given during a stable state. (Hepatology 1991;13:407-412.)
Increased [18F]Fluorodeoxyglucose Accumulation in Right Ventricular Free Wall in Patients With Pulmonary Hypertension and the Effect of Epoprostenol
Authors: Minako Oikawa, Yutaka Kagaya, Hiroki Otani, Masahito Sakuma, Jun Demachi, Jun Suzuki, Tohru Takahashi, Jun Nawata, Tatsuo Ido, Jun Watanabe, Kunio Shirato
Journal: Journal of the American College of Cardiology (2005)
THE RELATIVE VALUE OF HOMATROPIN AS A CYCLOPLEGIC: A CLINICAL STUDY.
Authors: E. C. ELLETT
Journal: JAMA (1900)

The question of the value of homatropin as a cycloplegic was brought before the Section last year by Dr. Culver; nevertheless I believe we can profitably discuss it again. On account of the short time required for the effect of homatropin to pass off, it is a cycloplegic much to be desired provided it is effective, and this is a matter in regard to which opinions vary. I am a firm believer in the necessity of using a cycloplegic for measuring the refraction if we desire to do work which will be lasting in its effects and which will reflect credit upon us in its results, though I am aware that there are many men whose opinions carry much weight who seem content with the results obtained by estimating and correcting the dynamic refraction. I take it, however, that we can dispense with any arguments as to why we are
Constitutively active phosphatase inhibitor-1 improves cardiac contractility in young mice but is deleterious after catecholaminergic stress and with aging
Authors: Katrin Wittköpper, Larissa Fabritz, Stefan Neef, Katharina R. Ort, Clemens Grefe, Bernhard Unsöld, Paulus Kirchhof, Lars S. Maier, Gerd Hasenfuss, Dobromir Dobrev, Thomas Eschenhagen, Ali El-Armouche
Journal: Journal of Clinical Investigation (2010)

Phosphatase inhibitor-1 (I-1) is a distal amplifier element of β-adrenergic signaling that functions by preventing dephosphorylation of downstream targets. I-1 is downregulated in human failing hearts, while overexpression of a constitutively active mutant form (I-1c) reverses contractile dysfunction in mouse failing hearts, suggesting that I-1c may be a candidate for gene therapy. We generated mice with conditional cardiomyocyte-restricted expression of I-1c (referred to herein as dTGI-1c mice) on an I-1–deficient background. Young adult dTGI-1c mice exhibited enhanced cardiac contractility but exaggerated contractile dysfunction and ventricular dilation upon catecholamine infusion. Telemetric ECG recordings revealed typical catecholamine-induced ventricular tachycardia and sudden death. Doxycycline feeding switched off expression of cardiomyocyte-restricted I-1c and reversed all abnormalities. Hearts from dTGI-1c mice showed hyperphosphorylation of phospholamban and the ryanodine receptor, and this was associated with an increased number of catecholamine-induced Ca2+ sparks in isolated myocytes. Aged dTGI-1c mice spontaneously developed a cardiomyopathic phenotype. These data were confirmed in a second independent transgenic mouse line, expressing a full-length I-1 mutant that could not be phosphorylated and thereby inactivated by PKC-α (I-1S67A). In conclusion, conditional expression of I-1c or I-1S67A enhanced steady-state phosphorylation of 2 key Ca2+-regulating sarcoplasmic reticulum enzymes. This was associated with increased contractile function in young animals but also with arrhythmias and cardiomyopathy after adrenergic stress and with aging. These data should be considered in the development of novel therapies for heart failure.
Uric acid excretion and surgery.
Authors: M L Snaith, J T Scott
Journal: Annals of the Rheumatic Diseases (1972)

Surgical operation has long been considered capable of precipitating acute gouty arthritis (Hench, 1935; Linton and Talbott, 1943) but details of uric acid metabolism in this situation are unknown.This paper describes a study of postoperative uric acid levels in plasma and urine in a number of patients undergoing surgical operation.* Urine collections for patient No. 11 were incomplete and only plasma levels were available.
A Computer Data Base for Information on Cancer Treatment
Authors: Susan Molloy Hubbard, Jane E. Henney, Vincent T. DeVita
Journal: New England Journal of Medicine (1987)

The Physician Data Query (PDQ) system is a clinically oriented computer data base developed to make recent information on cancer treatment widely available to the medical community. It represents an effort by the National Cancer Institute to promote diffusion of information about the treatment of cancer throughout the country, facilitate access to clinical trials, and accelerate the practical application of advances in research. The computer system provides information about state-of-the-art cancer treatment, which is updated monthly by an editorial board. It also includes a file of active cancer-research protocols and a directory of physicians and organizations providing cancer care to which physicians can gain access by geographic location as well as other features. PDQ was designed for physicians who may not be familiar with computers, to permit them to search for and display information without learning a specialized search language. PDQ uses a computer mainframe, which allows a large amount of data to be stored and made available to physicians rapidly and accurately. Transmission of information about cancer over commercial telecommunication networks gives health professionals access to PDQ by means of a computer terminal and local telephone lines.
Abstract 2460: APC regulates COX-2 independent of Wnt signaling in breast cancer
Authors: Monica K. VanKlompenberg, Claire Bedalov, Jenifer R. Prosperi
Journal: Cancer Research (2014)

Abstract Breast cancer is the leading cause of cancer-related death in non-smoking women, and the most commonly diagnosed cancer in women. The Adenomatous Polyposis Coli (APC) tumor suppressor gene is mutated or silenced by hypermethylation in 18-70% of sporadic breast cancers depending on subtype; however, the molecular mechanisms downstream of APC loss in the breast remain largely unexplored. While inactivation of APC most commonly leads to increased signaling through the Wnt/β-catenin pathway, there are multiple, less-investigated functions of APC, including regulation of GSK3β-mediated signaling, proliferation, epithelial polarity, cytoskeletal organization, and DNA repair. Given that restoration of tumor suppressors is a hurdle in treating tumors arising from loss of gene function, it is critical to investigate and understand the downstream signaling pathways involved in tumorigenesis. Our laboratory is particularly interested in investigating the effect of APC loss or mutation in breast cancer, and the complex Wnt-independent signaling downstream of APC loss in the breast. We previously demonstrated that Apc mutation accelerates the mouse mammary tumor virus-Polyoma middle T antigen (MMTV-PyMT) transgenic model of breast tumorigenesis independently of Wnt/β-catenin signaling. Interestingly, focal adhesion kinase (FAK)/Src/JNK signaling was up-regulated and required for the enhanced proliferation and squamous phenotype mediated by Apc mutation. Despite the lack of Wnt/β-catenin pathway activation, Apc-mutant mammary tumor cell lines demonstrated enhanced expression of Cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2), known to be important in triple-negative and inflammatory breast cancers, two aggressive breast cancer subtypes. While treatment with the Src inhibitor (PP2) decreases COX-2 protein expression, there is no effect on the level of phosphorylated JNK, indicating a non-linear signaling pathway. Consistent with this, treatment with an inhibitor of JNK (SP600125) has no effect on COX-2 expression. These data suggest that while Src activation downstream of Apc mutation enhances COX-2 in a Wnt-independent manner, the pathway does not travel through activation of JNK. Therefore, the mechanisms by which Apc mutation initiates this stream of events to enhance mammary tumorigenesis, and the contribution of COX-2 to the phenotypes acquired in Apc-mutant breast cancer remain unclear. Citation Format: Monica K. VanKlompenberg, Claire Bedalov, Jenifer R. Prosperi. APC regulates COX-2 independent of Wnt signaling in breast cancer. [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 2460. doi:10.1158/1538-7445.AM2014-2460
ASSOCIATION OF ALBUMIN AND HIGH SENSITIVE CARDIAC TROPONIN T AND I LEVELS AMONG CHEST PAIN PATIENTS PRESENTING TO EMERGENCY DEPARTMENT
Authors: Affan Irfan, Raphael Twerenbold, Karin Wildi, Rubini-Gimenez Maria, Cedric Jaeger, Michael Freese, Tobias Reichlin, Christian Mueller
Journal: Journal of the American College of Cardiology (2015)
Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin
Authors: Hans Christian Hennies, Uwe Kornak, Haikuo Zhang, Johannes Egerer, Xin Zhang, Wenke Seifert, Jirko Kühnisch, Birgit Budde, Marc Nätebus, Francesco Brancati, William R Wilcox, Dietmar Müller, Paige B Kaplan, Anna Rajab, Giuseppe Zampino, Valentina Fodale, Bruno Dallapiccola, William Newman, Kay Metcalfe, Jill Clayton-Smith, May Tassabehji, Beat Steinmann, Francis A Barr, Peter Nürnberg, Peter Wieacker, Stefan Mundlos
Journal: Nature Genetics (2008)
Do It Yourself Hallucinogens
Authors: David R. Rubin
Journal: JAMA (1967)

To the Editor:—  I think that there is a sufficient amount of question in the letter of John C. Kramer, MD ( 201 :892, 1967) to merit clarification. At the time of my previous communication, Do It Yourself Hallucinogens, I was aware of the amendment to the California Health and Safety Code which Dr. Kramer refers to. Any California restriction of diethyltryptamine (DET) depends upon the fine point of judgment as to whether DET is a salt of dimethyltryptamine (DMT). As Dr. Kramer says, this provision  be interpreted as restricting DET as well. It also might be interpreted as not restricting DET.  As to the mode of administration, if one were to add DMT or DET to a marijuana cigarette, it would be extremely difficult to allocate the psychic effects to the individual drugs. As far as adding DMT or DET to tobacco, the effect would likely parallel that of
Type II pneumocytes in mixed cell culture of human lung: a light and electron microscopic study.
Authors: L Bingle, T B Bull, B Fox, A Guz, R J Richards, T D Tetley
Journal: Environmental Health Perspectives (1990)

Alveolar Type II epithelial cells dedifferentiate rapidly in vitro. Studies with animal tissue suggest that cell-cell and extracellular matrix-cell interactions are important in the retention of Type II cell morphology in vitro. Thus, in this study with human tissue, alveolar Type II cells, alveolar macrophages, and spindle cells were prepared from the same sample of lung (obtained following lobectomy for cancer, n = 3), cocultured on glass cover slips or tissue culture plastic, and studied by light microscopy with scanning (SEM) and transmission (TEM) electron microscopy for 8 days. The primary cell isolates contained approximately 45% Type II cells; the remainder were macrophages or unidentifiable cells. Clusters, made up of a single layer of cuboidal Type II cells around a central core of connective tissue (largely collagen and some elastic tissue), formed above a monolayer of spindle cells. The Type II cells were morphologically similar to those seen in vivo. The cells were still cuboidal at 8 days but had lost their lamellar bodies, which were released into the medium via the apical surface. The clusters increased in size with time (area, microns 2: day 1, 29(5-143) x 10(2); day 8, 63(10-311) x 10(2); mean(range); p less than 0.02) without changing in number per culture, suggesting Type II cell proliferation. This may have been due to factors produced by the other cells and adherence to the extracellular matrix (ECM); (free collagen fibers, present in the original preparation, spindle cells, and/or Type II cells could be responsible for presence of ECM). We propose this as a useful model for the study of human Type II epithelial cells in vitro.
Recent molecular discoveries in angiogenesis and antiangiogenic therapies in cancer
Authors: Jonathan Welti, Sonja Loges, Stefanie Dimmeler, Peter Carmeliet
Journal: Journal of Clinical Investigation (2013)

Four decades ago, angiogenesis was recognized as a therapeutic target for blocking cancer growth. Because of its importance, VEGF has been at the center stage of antiangiogenic therapy. Now, several years after FDA approval of an anti-VEGF antibody as the first antiangiogenic agent, many patients with cancer and ocular neovascularization have benefited from VEGF-targeted therapy; however, this anticancer strategy is challenged by insufficient efficacy, intrinsic refractoriness, and resistance. Here, we examine recent discoveries of new mechanisms underlying angiogenesis, discuss successes and challenges of current antiangiogenic therapy, and highlight emerging antiangiogenic paradigms.
945 EPIDEMIOLOGY, NATURAL HISTORY AND OUTCOMES OF PRIMARY BILIARY CIRRHOSIS IN SOUTHERN ISRAEL: A FOLLOW-UP STUDY UP TO 20 YEARS
Authors: J.-S. Delgado, A. Vodonos, B. Delgado, A. Jotkowitz, A. Rosenthal, A. Fich, V. Novack
Journal: Journal of Hepatology (2012)
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Robert G. Petersdorf, Willis R. Keene, Ivan L. Bennett
Journal: The Journal of Experimental Medicine (1957)

The "endogenous serum pyrogen" that appears in the circulating blood after a single intravenous injection of endotoxin does not produce leukopenia in normal animals, fails to provoke the local Shwartzman reaction, and elicits no "tolerance" when injected daily. Suppression of the febrile response to endotoxin by prednisone does not prevent the appearance of pyrogen in the blood. Animals given large amounts of endotoxin daily continue to respond with high fevers despite failure of endogenous serum pyrogen to appear in detectable amounts after the first two or three injections. Analysis of the response to daily injections shows clearly that the fever during the first 2 hours after administration of endotoxin is unrelated to levels of endogenous serum pyrogen; in contrast, the magnitude of the fever after the 2nd hour correlates well with endogenous pyrogen in some instances. The leukopenic response to endotoxin could not be correlated with the appearance of endogenous serum pyrogen. The differences between endotoxin and endogenous pyrogen and the similarities between leukocyte extracts (sterile exudates) and endogenous pyrogen are summarized and discussed. Dissociation of the febrile response to bacterial endotoxin and levels of endogenous serum pyrogen are discussed and it is concluded that a mechanism involving both direct and indirect action of endotoxins offers the best explanation for the pyrogenic action of these bacterial products.
Regional Effects of an Antivascular Endothelial Growth Factor Receptor Monoclonal Antibody on Receptor Phosphorylation and Apoptosis in Human 253J B-V Bladder Cancer Xenografts
Authors: Darren W. Davis, Keiji Inoue, Colin P. N. Dinney, Daniel J. Hicklin, James L. Abbruzzese, David J. McConkey
Journal: Cancer Research (2004)

Abstract Vascular endothelial growth factor (VEGF) is a key angiogenic factor in a variety of solid tumors, making it one of the most attractive therapeutic targets. VEGF promotes the proliferation, survival, and differentiation of vascular endothelial cells by stimulating autophosphorylation and activation of VEGF receptor-2 (VEGFR-2, fetal liver kinase-1, and kinase insert domain-containing receptor). We developed fluorescence-based, quantitative methods to measure total VEGFR-2, VEGFR-2 phosphorylation, apoptosis, and microvessel density and size within whole tumor cross-sections using a laser scanning cytometer. Using these methods, we characterized the effects of DC101, a blocking antibody specific for murine VEGFR-2, on orthotopic human 253J-BV bladder tumors growing in nude mice. Basal levels of receptor phosphorylation were heterogeneous, with approximately 50% of endothelial cells positive for phosphorylated VEGFR-2 at baseline. DC101 therapy resulted in a 50% decrease in overall VEGFR-2 phosphorylation and a 15-fold and 8-fold increase in endothelial cell (CD31-positive) and tumor cell apoptosis, respectively. DC101 also decreased overall tumor microvessel density, but it mostly affected smaller CD105-negative microvessels located in the periphery of the tumor. Intriguingly, anti-VEGFR-2 therapy resulted in increased mean vessel size and an increase in overall VEGFR-2 levels. Increases in total VEGFR-2 levels were localized to the tumor core and were associated with increased expression of the oxygen-sensitive transcription factor, hypoxia inducible factor-1α. These data suggest that VEGFR inhibitors preferentially target discrete populations of tumor endothelial cells associated with the smaller peripheral blood vessels. Thus, agents that target a single receptor (e.g., VEGFR-2) may not be sufficient to completely inhibit tumor angiogenesis.
934 NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) AS A RISK FACTOR OF CORONARY HEART DISEASE; RELATION OF NAFLD TO CORONARY ARTERY CALCIFICATION SCORE BY MULTI-DETECTOR COMPUTED TOMOGRAPHY
Authors: D.H. Kim, S.Y. Choi, E.H. Park, J.I. Yang, W. Kim, Y.J. Kim, J.H. Yoon, H.S. Lee, C.S. Shin, S.H. Cho, B.H. Oh
Journal: Journal of Hepatology (2008)