tbuckley/cabot-search huggingface dataset:
EZH2 Modulates Angiogenesis In Vitro and in a Mouse Model of Limb Ischemia
Authors: Tijana Mitić, Andrea Caporali, Ilaria Floris, Marco Meloni, Micol Marchetti, Raul Urrutia, Gianni D Angelini, Costanza Emanueli
Journal: Molecular Therapy (2014)

Epigenetic mechanisms may regulate the expression of pro-angiogenic genes, thus affecting reparative angiogenesis in ischemic limbs. The enhancer of zest homolog-2 (EZH2) induces thtrimethylation of lysine 27 on histone H3 (H3K27me3), which represses gene transcription. We explored (i) if EZH2 expression is regulated by hypoxia and ischemia; (ii) the impact of EZH2 on the expression of two pro-angiogenic genes: eNOS and BDNF; (iii) the functional effect of EZH2 inhibition on cultured endothelial cells (ECs); (iv) the therapeutic potential of EZH2 inhibition in a mouse model of limb ischemia (LI). EZH2 expression was increased in cultured ECs exposed to hypoxia (control: normoxia) and in ECs extracted from mouse ischemic limb muscles (control: absence of ischemia). EZH2 increased the H3K27me3 abundance onto regulatory regions of eNOS and BDNF promoters. In vitro RNA silencing or pharmacological inhibition by 3-deazaneplanocin (DZNep) of EZH2 increased eNOS and BDNF mRNA and protein levels and enhanced functional capacities (migration, angiogenesis) of ECs under either normoxia or hypoxia. In mice with experimentally induced LI, DZNep increased angiogenesis in ischaemic muscles, the circulating levels of pro-angiogenic hematopoietic cells and blood flow recovery. Targeting EZH2 for inhibition may open new therapeutic avenues for patients with limb ischemia. Epigenetic mechanisms may regulate the expression of pro-angiogenic genes, thus affecting reparative angiogenesis in ischemic limbs. The enhancer of zest homolog-2 (EZH2) induces thtrimethylation of lysine 27 on histone H3 (H3K27me3), which represses gene transcription. We explored (i) if EZH2 expression is regulated by hypoxia and ischemia; (ii) the impact of EZH2 on the expression of two pro-angiogenic genes: eNOS and BDNF; (iii) the functional effect of EZH2 inhibition on cultured endothelial cells (ECs); (iv) the therapeutic potential of EZH2 inhibition in a mouse model of limb ischemia (LI). EZH2 expression was increased in cultured ECs exposed to hypoxia (control: normoxia) and in ECs extracted from mouse ischemic limb muscles (control: absence of ischemia). EZH2 increased the H3K27me3 abundance onto regulatory regions of eNOS and BDNF promoters. In vitro RNA silencing or pharmacological inhibition by 3-deazaneplanocin (DZNep) of EZH2 increased eNOS and BDNF mRNA and protein levels and enhanced functional capacities (migration, angiogenesis) of ECs under either normoxia or hypoxia. In mice with experimentally induced LI, DZNep increased angiogenesis in ischaemic muscles, the circulating levels of pro-angiogenic hematopoietic cells and blood flow recovery. Targeting EZH2 for inhibition may open new therapeutic avenues for patients with limb ischemia.
VITAMIN K AND BLOOD TRANSFUSIONS
Authors: Joseph K. Narat
Journal: JAMA (1941)

To the Editor:—  In view of the widespread use of vitamin K products, this preliminary report seems to be justified, especially because a cursory perusal of the literature failed to disclose a similar observation.  It was thought that the patient on whom I operated for acute hemorrhagic pancreatitis might need a blood transfusion. Dr. J. J. Kearns, the head of the laboratories at the St. Elizabeth Hospital, found that the serum of the patient, who belonged to group B, agglutinated red blood corpuscles not only of an A donor but also of those belonging to groups B and O. A search for the cause of this strange condition disclosed that this patient, as well as others whose blood showed a similar behavior, had been given intramuscularly 3 mg. of a synthetic vitamin K product. A checkup two weeks after the first blood test showed that the recipient's serum no longer
Critical illness-related corticosteroid insufficiency and community-acquired pneumonia: back to the future!
Authors: D. Annane, G. Umberto Meduri, P. Marik
Journal: European Respiratory Journal (2008)

In the past decade, emphasis in the study of the pathogenesis of infectious diseases has shifted from determining the function of the cellular players in the inflammatory response to the mediators that orchestrate activation and regulation of this response 1. According to current thinking, pulmonary sepsis begins when pathogens invade the sterile lower respiratory tract, leading to activation of the innate immune response to produce local and systemic inflammation 2. Whereas restricted inflammation is beneficial, excessive or persistent inflammation incites tissue destruction and disease 3; it is the lack of regulation (dysregulated systemic inflammation) of this vital response that is central to the pathogenesis of sepsis-associated morbidity and mortality 2, 4. Among patients with community-acquired pneumonia (CAP), nonsurvivors, unlike survivors, exhibit persistent elevation in plasma inflammatory cytokine levels over time 5–7.

An intact hypothalamic-pituitary-adrenal (HPA) axis with effective intracellular glucocorticoid anti-inflammatory activity is indispensable for host survival after exposure to an infectious agent 8. That the integrity of the axis is fundamental to surviving critical illness has been well demonstrated by the increased risk of death following: removal of the adrenal cortex in lipopolysaccharide-challenged animals 9; bilateral adrenal haemorrhage in patients with severe sepsis 10; and inadvertent suppression of …
Increased Densities of Peripheral–Type Benzodiazepine Receptors in Brain Autopsy Samples From Cirrhotic Patients With Hepatic Encephalopathy
Authors: Joel Lavoie, Gilles Pomier Layrargues, Roger F. Butterworth
Journal: Hepatology (1990)

Peripheral–type benzodiazepine receptors were evaluated using the specific ligand [ 3 H]–PK 11195 in brain homogenates from nine cirrhotic patients who died in hepatic coma and from an equal number of age–matched control subjects. Histopathological studies showed evidence of severe Alzheimer type II astrocytosis in the brains of all cirrhotic patients. Saturation–binding assays revealed a single saturable binding site for [ 3 H]–PK 11195 in brain, with affinities in the 2– to 3–nmol/L range. Diazepam was found to be a relatively potent inhibitor of 3 H–PK 11195 binding (IC 50 = 253 nmol/L), whereas the central benzodiazepine antagonist Ro 15–1788 displaced 3 H–PK 11195 binding with low affinity (IC 50 &gt;40 μmol/L). Densities of [ 3 H]–PK 11195 binding sites were found to be increased by 48% (p &lt; 0.01) and 25% (p &lt; 0.05) in frontal cortex and caudate nuclei, respectively, from cirrhotic patients. Densities of [ 3 H]–PK 11195 binding sites in frontal cortex from two nonencephalopathic cirrhotic patients were not significantly different from control values. No concomitant changes of affinities of these binding sites were observed. Because it has been suggested that peripheral–type benzodiazepine receptors may be localized on mitochondrial membranes and may therefore be involved in cerebral oxidative metabolism, the alterations observed in this study could be of pathophysiological significance in hepatic encephalopathy.(HEPATOLOGY 1990; 11:874–878.)
Cost-effectiveness of Hepatitis B Virus Immunization-Reply
Authors: Harold S. Margolis
Journal: JAMA (1996)

<h3>In Reply.</h3> —We agree with Dr Edmunds and colleagues that ongoing immunization will ultimately lower the risk of HBV infection in a population. Modeling the dynamics of infection risk into evaluations of immunization strategies would provide better assessment of long-term prevention effectiveness. However, few such analyses exist, making cost comparisons with other infectious diseases difficult. We have dynamically modeled the expected reduction in HBV infection associated with various immunization strategies in populations with varying endemicity of infection (P. J. C., unpublished data, 1995). In populations in which infections occur predominantly during early childhood (eg, Gambians and Alaskan Natives), infant immunization combined with catch-up immunization of young children would dramatically reduce infection risk in a decade. In such a setting, the force of infection resides in a limited young age group and is rapidly eliminated by immunization. However, in low-endemicity populations, most infections are transmitted among young adults over a wide
Hormone Assays and Their Clinical Application
Authors: William P. Deiss
Journal: JAMA (1967)

This second edition bears little resemblance to the first (1957), for the field of endocrine assays has experienced a phenomenal growth in the past ten years. The authors aim to assess the reliability of currently used assays and to discuss their use and interpretation in clinical practice. These goals have been satisfactorily achieved. The authors are to be praised for having used almost entirely data from the human. Roughly the first third relates to pituitary hormones. The information is up-to-date and the gonadotropin evaluation is excellent. Now that sensitive radioimmunoassays for human growth hormone are available in more and more centers, information on this is of great interest. The importance of provocative tests with induced hypoglycemia and arginine infusion in promoting growth hormone secretion is not stressed. This is unfortunate, since the major usefulness of these assays will be in screening children with growth failure. It is unfair to criticize
Bcl-2 and Glutathione Depletion Sensitizes B16 Melanoma to Combination Therapy and Eliminates Metastatic Disease
Authors: Salvador Mena, María Benlloch, Angel Ortega, Julian Carretero, Elena Obrador, Miguel Asensi, Ignacio Petschen, Bob D. Brown, José M. Estrela
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Advanced melanoma resists all current therapies, and metastases in the liver are particularly problematic. Prevalent resistance factors include elevated glutathione (GSH) and increased expression of bcl-2 in melanoma cells. GSH has pleiotropic effects promoting cell growth and broad resistance to therapy, whereas Bcl-2 inhibits the activation of apoptosis and contributes to elevation of GSH. This study determined the in vivo efficacy of combination therapies administered while GSH and Bcl-2 were individually and simultaneously decreased in metastatic melanoma lesions. Experimental Design: Highly metastatic murine B16 melanoma (B16M-F10) cells have elevated levels of both GSH and Bcl-2. B16M-F10 cells were injected i.v. to establish metastatic lesions in vivo. GSH was decreased using an l-glutamine–enriched diet and administration of verapamil and acivicin, whereas Bcl-2 was reduced using oligodeoxynucleotide G3139. Paclitaxel, X-rays, tumor necrosis factor-α, and IFN-γ were administered as a combination therapy. Results: Metastatic cells were isolated from liver to confirm the depletion of GSH and Bcl-2 in vivo. Reduction of Bcl-2 and GSH, combined with partial therapies, decreased the number and volume of invasive B16M-F10 foci in liver by up to 99% (P &amp;lt; 0.01). The full combination of paclitaxel, X-rays, and cytokines eliminated B16M-F10 cells from liver and all other systemic disease, leading to long-term survival (&amp;gt;120 days) without recurrence in 90% of mice receiving the full therapy. Toxicity was manageable; the mice recovered quickly, and hematology and clinical chemistry data were representative of accepted clinical toxicities. Conclusions: Our results suggest a new strategy to induce regression of late-stage metastatic melanoma.
Serological Tests for Syphilis in Diseases of the Thyroid
Authors: Fuad S. Ashkar
Journal: JAMA (1970)

<h3>To the Editor.—</h3> False positive results in serological tests for syphilis occur in numerous pathological states, which include rheumatoid arthritis, lupus erythematosus, and many others. Thyroid diseases such as hyperthyroidism, hypothyroidism, diffuse nontoxic goiter, acute subacute thyroiditis, and chronic thyroiditis have not been studied thoroughly for the incidence of false reactive syphilis serological tests. Although numerous workers have suggested that various thyroid disorders could be based on an autoimmune reaction, the only thyroid disease that has been reported to give a false reactive test is Hashimoto's disease, described by Selenkow et al in 1961.<sup>1</sup> A total of 1,102 cases of various thyroid diseases which include hyperthyroidism, hypothyroidism, diffuse nontoxic goiter, and thyroiditis were reviewed between 1961 and 1969 at Jackson Memorial Hospital. The incidence of reactive VeneralDisease Research Laboratory tests (VDRL) was recorded; out of the total 1,102 patients, only 7 patients were shown to have reactive VDRL
Clinical Surgery in General: RCS Course Manual
Authors: R W Hoile
Journal: BMJ (1994)

Ed R M Kirk, Averil O Mansfiled, John Cochrane Churchill Livingstone, £40, pp 448 ISBN 0-443-04574-7

Surgical training and examinations have changed and will continue to change. The current examination in Clinical Surgery in General (as conducted by the Royal College of Surgeons of England) represents a transition in knowledge between the basis sciences and clinical practice. Based on the course run by the college, Clinical Surgery in General provides a …
SECOND-GENERATION DRUG-ELUTING STENTS VERSUS BARE-METAL STENTS IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Sungmin Lim, Ik Jun Choi, Mineok Chang, Jin Jin Kim, Minkyu Kang, Byung-Hee Hwang, Tae-Hun Kim, Suk Min Seo, Yoon Seok Koh, Pum Joon Kim, Kiyuk Chang, Wook Sung Chung, Eun ho Choo, Donggyu Moon, Jae Gyung Kim, Ki-Bae Seung
Journal: Journal of the American College of Cardiology (2013)
Where are the unemployed doctors?
Authors: C Ruddlesdin
Journal: BMJ (1985)

admission was severity of symptoms or admission for social reasons.I found it surprising that there was no mention of pleural pain, since this is a relatively common reason for admission to hospital and in my experience prevents effective coughing in some patients.I am yet to be convinced of the value of physiotherapy in the treatment of primary pneumonia, but this paper has not caused me to question my present therapeutic practice of asking the physiotherapist to help expectoration in patients with pneumonia, especially those with pleural pain.
Differences between - and -Chain Mutants of Human Haemoglobin and between - and -Thalassaemia. Possible Duplication of the -Chain Gene
Authors: H. Lehmann, R. W. Carrell
Journal: BMJ (1968)

Human adult haemoglobin consists of two unlike pairs of polypeptide chains, and can be described as alpha(2)beta(2). Amino-acid substitutions in either of the two types of chain result in alpha- and beta-chain variants. In thalassaemia, which causes a lowered production of haemoglobin, the alpha or the beta chain can be affected, the result being alpha- or beta-thalassaemia. There is a quantitative difference in the proportion of alpha- and beta-chain variants to normal haemoglobin in the respective heterozygotes, and there is also a difference in the pattern of inheritance of alpha- and beta-thalassaemia: these could possibly be explained by assuming that man has one gene for the beta- and two for the alpha-chain.
TCT-229 The Safety and Feasibility of Nicorandil Compared to Adenosine Triphosphate as Hyperemic Agents for Fractional Flow Reserve Measurements
Authors: Daiki Kato, Hiroaki Takashima, Akiyoshi Kurita, Shinichiro Sakurai, Tomofumi Mizuno, Kenji Asai, Yasuo Kuroda, Takashi Kosaka, Yasushi Kuhara, Hirohiko Ando, Kazuyuki Maeda, Yusuke Nakano, Toru Niwa, Kentaro Mukai, Shigeko Sato, Masahiro Takeshita, Masanobu Fujimoto, Katsuhisa Waseda, Tetsuya Amano
Journal: Journal of the American College of Cardiology (2012)
CUTANEOUS REACTIONS WITH CULTURE FILTRATES OF THE COLON TYPHOID TYPE
Authors: E. E. Ecker, H. Welch
Journal: The Journal of Experimental Medicine (1930)

The observations of Ecker and Rimington on the production of skin reactions with synthetic medium culture filtrates (concentrated and dialyzed) of organisms belonging to the colon-typhoid group have been confirmed and extended. The filtrates show a marked degree of thermostability and marked resistance to ultraviolet radiation. Intravenous injections of the filtrates stimulate the production of precipitins. No precipitins are produced in the sera of rabbits that receive intracutaneous injections only. At no time during the course of immunization was the skin reaction obliterated. An indurative process was noted at the site of injection (skin) during the course of immunization. Mixtures of the filtrates with their homologous antisera, obtained from animals immunized by the intravenous route, and injected into skin, also failed to obliterate the erythema and edema. The observations of Shwartzman have been confirmed; the Shwartzman phenomenon appears to be group or species specific. Filtrates from enterococci failed to produce the phenomenon. Filtrates of other unrelated organisms have not been studied. The products of Shwartzman and of Ecker and Rimington appear to be the same.
Information Needs and Decisional Preferences in Women With Breast Cancer
Authors: Lesley F. Degner
Journal: JAMA (1997)

<h3>Objective.</h3> —To determine the degree of involvement women with breast cancer wanted in medical decision making, extent to which they believed they had achieved their preferred level of involvement, and types of information they judged to be most important. <h3>Design and Setting.</h3> —Cross-sectional survey at 2 tertiary oncology referral clinics and 2 community hospital oncology clinics in Winnipeg, Manitoba. <h3>Patients.</h3> —Consecutive sample of 1012 women with a confirmed diagnosis of breast cancer who were scheduled for a visit at 1 of 4 hospital oncology clinics. <h3>Main Outcome Measures.</h3> —The following measures were used: (1) Preferences about various levels of participation in treatment decision making; (2) the extent to which subjects believed they had achieved their preferred levels of involvement in decision making; and (3) priority needs for information and how these needs differed by selected sociodemographic, disease, and treatment variables. <h3>Results.</h3> —A total of 22% of women wanted to select their own cancer treatment, 44% wanted to select their treatment collaboratively with their physicians, and 34% wanted to delegate this responsibility to their physicians. Only 42% of women believed they had achieved their preferred level of control in decision making. The 2 most highly ranked types of information were related to knowing about chances of cure and spread of disease. Women younger than 50 years rated information about physical and sexual attractiveness as more important than did older women (<i>P</i>&lt;.001); women older than 70 years rated information about self-care as more important than did younger women (<i>P</i>=.002); and women who had a positive family history of breast cancer rated information about family risk as more important than did other women (<i>P</i>=.03). <h3>Conclusions.</h3> —The substantial discrepancy between women's preferred and attained levels of involvement in treatment decision making suggests that systematic approaches to assess and respond to women's desired level of participation in treatment decision making need to be evaluated. Priorities for information identified in this study provide an empirical basis to guide communication with women seeking care for breast cancer.
THE CURE OF BASAL CELL EPITHELIOMA
Authors: BERNARD F. SCHREINER
Journal: JAMA (1930)

This paper sets forth the end-results of our efforts to treat basal cell epithelioma, in a series of 355 cases, five or more years ago. The literature of today on the treatment of skin cancer, particularly that referring to basal cell epitheliomas, is extensive and somewhat misleading as to the eventual outcome of these cases. Our institution was established in 1898 for the express purpose of research in the cancer problem. In 1913 this research was extended to cancer in the human being, at which time we were provided with a small hospital for the care of a limited number of patients. It has been our endeavor and hope to help in the establishment of the value of various forms of treatment in the different types of malignant disease, whether radiation, endothermy, surgery or the use of the various medicaments which have been proposed. The present paper deals with a
A New System for Rapid Large-Caliber Percutaneous Transhepatic Drainage in Patients with Obstructive Jaundice: A Prospective Randomized Trial
Authors: E. Frimberger, T. Vente, S. Wagenpfeil, P. Gerein, P. Born, N. Fritz, H.-D. Allescher, R. Ott, N. Weigert, M. Classen, T. Rösch
Journal: Endoscopy (2001)

Background and Study Aims: Percutaneous access to the biliary tract is an important diagnostic and therapeutic tool in the management of biliary diseases. It is usually chosen when the endoscopic approach via endoscopic retrograde cholangiopancreatography (ERCP) fails, or is not possible. Once established, the percutaneous tract is then used for the treatment of biliary stones and strictures. To establish a percutaneous tract with a caliber large enough for cholangioscopy to be performed, or for a large-bore permanent drainage tube to be inserted, stepwise dilation up to 14 Fr or 16 Fr is usually required. We present here a new method of rapid dilation using specially designed materials, including a stiffenable guide wire and specially adapted bougies.
THE LS-ANTIGEN OF VACCINIA
Authors: Theodore Shedlovsky, Joseph E. Smadel
Journal: The Journal of Experimental Medicine (1942)

Virus-free filtrate, obtained from suspensions of vaccine virus-infected dermal pulp of rabbits and rich in the soluble substances of vaccinia, was shown to contain four distinct components in electrophoresis experiments. Electrophoretic and serological observations served as a guide in developing a method for separating these components from one another. This method depended upon changes in the solubilities of the components with alterations of pH. Three of the four components appeared to be serologically inert when tested with anti-vaccinia sera. All of the L- and S-activity was found to be associated with a single component which was electrically homogeneous at several values of pH and which was homogeneous in the ultracentrifuge. This single substance, designated as LS-antigen, precipitates in equal titers with optimal amounts of L- and of S-antibody and is completely removed from solution by absorption with either antibody. The LS-antigen of vaccinia appears to be a protein molecule with two antigenically distinct parts, L and S. Heating modifies the L-portion in such a manner that the substance no longer precipitates with L-antibody; this degraded antigen still combines with L-antibody, as is shown by inhibition tests, and still precipitates with S-antibody. Similarly, treatment with heat and dilute alkali modifies the S-portion of LS-antigen so that it combines but does not precipitate with S-antibody; and at the same time all recognizable immunological properties of the L-portion are destroyed.