tbuckley/cabot-search huggingface dataset:
Effect of flavin compounds on glutathione reductase activity: in vivo and in vitro studies
Authors: Ernest Beutler
Journal: Journal of Clinical Investigation (1969)

Increases or decreases of red cell glutathione reductase (GR) have been described in connection with many clinical abnormalities. We find that GR activity as measured in hemolysates represents only a portion of the available GR activity. The addition of small amounts of flavin adenine dinucleotide (FAD), but not of flavin mononucleotide or riboflavin, activates the GR of hemolysates. 1 muM FAD results in a maximal activation within 10 min; gradually increasing activation occurs at much lower, for example, 20 mmuM FAD concentrations. Once FAD has activated GR, dilution or dialysis does not reverse activation of the enzyme. Activation of GR by FAD can be inhibited by adenosine triphosphate (ATP), and to a lesser extent by adenosine diphosphate (ADP) and adenosine monophosphate (AMP), if these adenine nucleotides are added before the addition of FAD, but only to a slight extent if FAD is added before the adenine nucleotides. The addition of FAD to GR does not alter its electrophoretic mobility but produces intensification of the bands. The administration of 5 mg of riboflavin daily produces marked stimulation of red cell GR activity within only 2 days. After cessation of riboflavin administration, the GR activity again begins to fall. The degree of stimulation of GR activity by riboflavin is inversely correlated with the level of dietary riboflavin intake. The base line GR activity of normal individuals is directly correlated with the level of dietary riboflavin intake. The previously unexplained variations of glutathione reductase in health and disease must be reevaluated in light of the state of riboflavin nutrition and metabolism of the subject.
Diffuse Histiocytic Lymphoma
Authors: Brian H. Weinerman
Journal: JAMA (1977)

Fifteen patients with stage III and IV diffuse histiocytic lymphoma were treated with combination chemotherapy: cyclophosphamide, vincristine sulfate, prednisone, and procarbazine hydrochloride (COPP). Eight achieved a complete clinical remission. Of these, five relapsed, but remission was reinduced in three of these. Median survival of partial responders was 52 weeks compared to more than 129 weeks for complete responders. Complete clinical remission in diffuse histiocytic lymphomas did not presage a long disease-free interval as has been reported in biopsy proved remission series. Biopsy and staging by pathologic examination appear necessary to document remission in this disease.
CYLOSERINE AS AN ANTIDEPRESSANT AGENT
Authors: GEORGE E. CRANE
Journal: American Journal of Psychiatry (1959)

Cycloserine appears to be a psychopharmacological agent in that 1. It reverses depressions to normal or hyperactive mood and at the same time causes subtle changes in behavior; 2. It may aggravate mental disorders; and 3. It seems to potentiate Marsilid. Cycloserine may become a valuable tool in psychopharmacological research and may also find therapeutic use in depressions, provided the initial dose does not exceed 500 mg. a day and potentially psychotic patients receive more than average supervision.
Overcoming social segregation in health care in Latin America
Authors: Daniel Cotlear, Octavio Gómez-Dantés, Felicia Knaul, Rifat Atun, Ivana C H C Barreto, Oscar Cetrángolo, Marcos Cueto, Pedro Francke, Patricia Frenz, Ramiro Guerrero, Rafael Lozano, Robert Marten, Rocío Sáenz
Journal: The Lancet (2014)
Studies of venereal disease. II. Observations on the incidence, etiology, and treatment of the postgonococcal urethritis syndrome
Authors: King K. Holmes, David W. Johnson, Thomas M. Floyd, Paul A. Kvale
Journal: JAMA (1967)

Postgonococcal urethritis (PGU) occurred in nearly two thirds of men with gonorrhea acquired in the Far East who were "successfully" treated with 2,400,000 units of procaine penicillin G plus probenecid. PGU occurred less often after treatment of gonorrhea with tetracycline hydrochloride, and PGU itself responded to tetracycline, suggesting a microbial etiology for the condition. The syndrome was associated to a highly significant degree with<i>Mycoplasma</i>infection of the urethra, and occurred more often after infection with Neisseria<i>gonorrhoeae</i>of lessened penicillin sensitivity. The high incidence of the syndrome, one of the most common infectious diseases among military personnel in the Far East, requires a reexamination of the traditional use of penicillin in the treatment of gonorrhea in men.
Acute poststreptococcal polymyalgia.
Authors: N Harats, H Gur, A Rubinow
Journal: Annals of the Rheumatic Diseases (1986)

Three patients developed severe incapacitating diffuse pain and tenderness of the skeletal muscles after acute streptococcal infection. There was no evidence of concomitant arthritis, glomerulonephritis, or inflammatory muscle disease in any of the cases. All patients responded promptly to anti-inflammatory therapy. Severe myalgia should be considered an additional complication of immunologically mediated poststreptococcal response.
Isolation of high density lipoproteins from rat intestinal epithelial cells.
Authors: A M Magun, T A Brasitus, R M Glickman
Journal: Journal of Clinical Investigation (1985)

Previous studies have defined forms of high density lipoproteins (HDL) in rat mesenteric lymph, suggesting that they have a secretory origin. This study describes the isolation and characterization of intestinal intracellular HDL. Two preparations were made as follows: (a) Rat enterocytes were isolated and a Golgi organelle fraction was prepared. (b) Cell homogenates were subjected to nitrogen cavitation and a cytoplasmic fraction was prepared. Lipoproteins were isolated from both preparations by sequential ultracentrifugation. When the HDL fraction (1.07-1.21 g/ml) was subjected to isopyknic density gradient ultracentrifugation, a peak of apoproteins A-I and B (apoA-I and apoB, respectively) was found at a density of 1.11-1.14 g/ml. Electron microscopy of the fraction showed spherical particles ranging in size from 6 to 13 nm. Immunoelectrophoresis revealed a precipitin arc in the alpha region against apoA-I which extended into the pre-beta region where a precipitin arc against apoB was also seen. ApoB antisera depleted the pre-beta particles whereas the alpha migrating particles remained. Lipid analysis of the whole HDL fraction revealed phospholipid, cholesteryl ester, and triglyceride as the major lipids. [3H]leucine was then administered into the duodenum and a radiolabeled intracellular HDL fraction was isolated. The newly synthesized apoproteins of the HDL fraction, as determined by gel electrophoresis, were apoB, apoA-I, and apolipoprotein A-IV (ApoA-IV). Immunoprecipitation of the apoB particles revealed apoA-I and apoA-IV in the supernatant. These data demonstrate that there are at least two intracellular intestinal forms of HDL particles, one of which contains apoB. The other particle contains apoA-I and apoA-IV, has alpha mobility, is spherical, and resembles a particle found in the lymph.
Abstract 5116: Identification and rapid <i>in vivo</i> validation of a novel drug combination for treating melanoma
Authors: Jason D. Berndt, Jason Frazier, Marc Grenley, Bahram Bahrami, Randall T. Moon, Jim Olson, Richard Klinghoffer
Journal: Cancer Research (2012)

Abstract The well-established capability of tumors to resist single agent chemotherapies underscores the need to identify novel synergistic drug combinations to treat patients with cancer. Here we use an innovative arrayed needle technology to provide rapid in vivo validation of findings from a genome scale RNAi screen and reveal the potential of an unexpected drug combination to treat patients with melanoma. Our efforts focused on the β-catenin pathway. The β-catenin pathway impacts cancer progression in a context dependent manner. In some malignancies such as colon cancer, increased β-catenin activity drives oncogenesis. In contrast activation of β-catenin has been associated with decreased tumor proliferation and improved prognosis in patients with melanoma. A screen with an arrayed library of 14,000 lentiviral shRNA vectors revealed that silencing of dihydrofolate reductase, the target of the classic chemotherapeutic methotrexate, led to synergistic activation of the β-catenin pathway when combined with an inhibitor of GSK3. We therefore explored whether combination therapy, consisting of a GSK3 inhibitor and methotrexate could represent a potential treatment for melanoma patients. Two distinct small molecule inhibitors of GSK3, 6-bromoindirubin-3αoxime (BIO) and Chiron 99021, demonstrated synergy with methotrexate to activate β-catenin signaling in the melanoma cell line A375. To rapidly assess whether the observed synergy translates to the context of a living tumor, precision multiplexed microinjection using Presage technology was performed on mice harboring flank melanoma tumors. Discreet positions on each tumor were injected with either vehicle control, methotexate as a single agent, Chiron 99021 as a single agent, or the combination of the two agents. Analysis of the activation of beta-catenin and histology for markers of cellular proliferation, death, and differentiation allowed us to rapidly evaluate the efficacy of this drug combination. This rapid in vivo validation approach sets the stage for full preclinical evaluation of combined methotrexate and GSK3 inhibitor therapy using advanced co-clinical models of melanoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5116. doi:1538-7445.AM2012-5116
Bone Marrow Embolism Following Closed Chest Cardiac Massage
Authors: Erwin C. Winkel
Journal: JAMA (1961)

PULMONARY artery bone marrow embolism is a rarely reported entity. In most cases it has been associated with fractures of bones containing red marrow, and may or may not have been a contributing cause of death. In the following case, bone marrow emboli were found in the pulmonary vascular bed as an unsuspected finding in a patient who died of coronary artery thrombosis with associated myocardial infarct, and who had received terminal closed chest massage at the time. <h3>Report of a Case</h3><h3>Clinical Aspects.—</h3> A 61-year-old female was awakened from her sleep with severe pain across the posterior aspect of her shoulders. She was seen almost immediately by her physician who found her in obvious pain and in shock. There was no history of trauma. She improved on nitroglycerin and morphine sulfate, and within the hour was admitted to the hospital. Review of systems was noncontributory, except that she did
Intravenous and oral MDL 17043 (A new inotrope-vasodilator agent) in congestive heart failure: Hemodynamic and clinical evaluation in 38 patients
Authors: Dean Kereiakes, Kanu Chatterjee, William W. Parmley, Beverley Atherton, Deirdre Curran, Anne Kereiakes, Robert Spangenberg
Journal: Journal of the American College of Cardiology (1984)
[143] VALIDATION OF THE SPANISH VERSION OF THE LIVER DISEASE QUALITY OF LIFE (LDQOL) IN CANDIDATES FOR LIVER TRANSPLANT
Authors: T. Casanovasb Taltavull, L. Jane Cabre, M.J. Herdman, A. Casado Collado, B. Prat Pubill, J. Fabregat Prous
Journal: Journal of Hepatology (2007)
Spontaneous disappearance of an IgA anti‐factor IX inhibitor in a child with christmas disease
Authors: Robert R. Carroll, Richard S. Panush, Craig S. Kitchens
Journal: American Journal of Hematology (1984)

Abstract The few inhibitors to blood coagulation factor IX in patients with Christmas disease (hemophilia B) that have been studied have been shown to belong to the IgG class of immunoglobulins. We report the first case in which a factor IX inhibitor was of the IgA class. Additionally, he appears to be the youngest patient with hemophilia B to have developed an inhibitor. His inhibitor complicated treatment of the patient for several years because of its anamnestic rise following factor IX concentrate administration. It then spontaneously vanished and has not returned in spite of repeated factor IX complex administration.
Decreased Activity of the <scp>l</scp> -Arginine–Nitric Oxide Metabolic Pathway in Patients With Congestive Heart Failure
Authors: Stuart D. Katz, Tehreen Khan, Guillermo A. Zeballos, Leena Mathew, Prathibha Potharlanka, Mathias Knecht, James Whelan
Journal: Circulation (1999)

Background —Impaired endothelium-dependent, nitric oxide (NO)–mediated vasodilation may contribute to increased vasomotor tone in patients with heart failure. Whether decreased endothelium-dependent, NO-mediated vasodilation in patients with heart failure is due to decreased synthesis or increased degradation of NO is unknown. Methods and Results —To specifically assess the synthetic activity of the l -arginine–NO metabolic pathway, urinary excretion of [ 15 N]nitrates and [ 15 N]urea was determined after a primed continuous intravenous infusion of l -[ 15 N]arginine (40 μmol/kg) in 16 patients with congestive heart failure and 9 age-matched normal control subjects at rest and during submaximal treadmill exercise. After infusion of l -[ 15 N]arginine, 24-hour urinary excretion of [ 15 N]nitrates was decreased in patients with congestive heart failure at rest (2.2±0.5 versus 8.0±2.3 μmol/24 h) and during submaximal exercise (2.4±1.2 versus 11.4±4.0 μmol/24 h) compared with control subjects (both P &lt;0.01). After infusion of l -[ 15 N]arginine, 24-hour urinary excretions of [ 15 N]urea at rest in patients with congestive heart failure and control subjects were not different (1.1±0.3 versus 1.2±0.2 mmol/24 h, P &gt;0.20). Conclusions —A specific decrease in synthetic activity of the l -arginine–NO metabolic pathway contributes to decreased endothelium-dependent vasodilation in patients with congestive heart failure.
A Novel Sialyltransferase Inhibitor Suppresses FAK/Paxillin Signaling and Cancer Angiogenesis and Metastasis Pathways
Authors: Jia-Yang Chen, Yen-An Tang, Sin-Ming Huang, Hsueh-Fen Juan, Li-Wha Wu, Ying-Chieh Sun, Szu-Chi Wang, Kuan-Wei Wu, Gopula Balraj, Tzu-Ting Chang, Wen-Shan Li, Hung-Chi Cheng, Yi-Ching Wang
Journal: Cancer Research (2011)

Abstract Increased sialyltransferase (ST) activity promotes cancer cell metastasis, and overexpression of cell surface sialic acid correlates with poor prognosis in cancer patients. To seek therapies targeting metastasis for cancer treatment, we developed a novel ST inhibitor, Lith-O-Asp, and investigated its antimetastatic and antiangiogenic effects and mechanisms. We found that cells treated with Lith-O-Asp showed a reduction of activity on various ST enzymes by in vitro and cell-based activity analyses. Lith-O-Asp inhibited migration and invasion abilities in various cancer cell lines and showed inhibitory effect on the angiogenic activity of human umbilical vein endothelial cells. Indeed, Lith-O-Asp treatment consequently delayed cancer cell metastasis in experimental and spontaneous metastasis assays in animal models. Importantly, Lith-O-Asp decreased the sialic acid modification of integrin-β1 and inhibited the expression of phospho-FAK, phospho-paxillin, and the matrix metalloprotease (MMP) 2 and MMP9. Lith-O-Asp attenuated the Rho GTPase activity leading to actin dynamic impairment. In addition, 2DE-MS/MS and immunoblotting analyses showed that Lith-O-Asp altered the protein expression level and phosphorylation status of various proteins involved in crucial metastasis and angiogenesis pathways such as vimentin and ribonuclease/angiogenin inhibitor RNH1. Furthermore, Lith-O-Asp treatment significantly inhibited the invasive ability exerted by ectopic overexpression of various ST enzymes catalyzing α-2,6- or α-2,3-sialylation. Our results provide compelling evidence that the potential pan-ST inhibitor, Lith-O-Asp, suppressed cancer cell metastasis likely by inhibiting FAK/paxillin signaling and expressing antiangiogenesis factors. Lith-O-Asp is worthy for further testing as a novel antimetastasis drug for cancer treatment. Cancer Res; 71(2); 473–83. ©2011 AACR.
Autologous Hematopoietic Stem Cell Therapy in Severe Systemic Sclerosis
Authors: Dinesh Khanna, George E. Georges, Daniel R. Couriel
Journal: JAMA (2014)

Systemic sclerosis is a life-threatening disease that includes a subset of patients with diffuse cutaneous systemic sclerosis (defined as widespread skin involvement) and internal organ involvement and has a mortality of 30% to 50% at 5 years.1 Conventional-dose immunosuppressive therapy has limited efficacy in preventing disease progression, and there are few data to support survival benefit.2 High-dose immunosuppression is an alternative to conventional-dose immunosuppression. Despite the increased risk of toxicity, the rationale for high-dose immunosuppression is that systemic sclerosis is an autoimmune disorder that progressively damages internal organs and is associated with chronic inflammation and systemic immunological abnormalities.3 Studies of high-dose immunosuppression (with autologous hematopoietic stem cell transplantation [HSCT]) in patients with systemic sclerosis have demonstrated efficacy in preventing disease progression,1,4 and a single-center trial (Autologous Non-myeloablative HSCT Compared With Pulse Cyclophosphamide Once per Month for Systemic Sclerosis [ASSIST]) demonstrated superiority of autologous HSCT over conventional therapy.4
Low-molecular-weight heparin reduces neointimal proliferation after coronary stent implantation in hypercholesterolemic minipigs.
Authors: A B Buchwald, C Unterberg, K Nebendahl, H J Gröne, V Wiegand
Journal: Circulation (1992)

BACKGROUND Intracoronary stents have been suggested as a method of reducing the restenosis rate after balloon angioplasty. Proliferation of vascular smooth muscle cells is a major contributing factor to the restenosis process. Heparin and some of its derivatives have been shown to inhibit smooth muscle cell proliferation. We investigated the effect of low-molecular-weight heparin on the proliferative response after implantation of a balloon-expandable tantalum stent in previously deendothelialized coronary artery segments of hypercholesterolemic minipigs. METHODS AND RESULTS Minipigs were fed a diet containing 2% cholesterol, starting 1 month before balloon denudation of the endothelium in a coronary artery. One month later, a stent was implanted at this site. Animals were killed after 4 weeks (group 1, n = 6) or 3 months (group 2, n = 6). Animals in group 3 (n = 6), also followed for 4 weeks after stenting, received subcutaneous low-molecular-weight heparin at a dose of 200-300 units/kg anti-factor Xa activity per day in addition to the chronic acetylsalicylic acid (100 mg/day) also administered to groups 1 and 2. Eighteen of 22 animals survived to the end of the study. Angiography revealed patent stents in all surviving animals. In group 1, histological analysis showed extensive neointimal proliferation around stent struts. Maximal neointimal thickness seen in group 1 averaged 0.93 +/- 0.11 mm, was lower after 3 months (0.8 +/- 0.14 mm) in group 2, but was significantly reduced (0.44 +/- 0.18 mm, p less than 0.01) in group 3. CONCLUSIONS These data show a significant reduction of the neointimal proliferative response to coronary stent implantation by low-molecular-weight heparin.
Endothelial Nuclear Factor-κB–Dependent Regulation of Arteriogenesis and Branching
Authors: Daniela Tirziu, Irina M. Jaba, Pengchun Yu, Bruno Larrivée, Brian G. Coon, Brunella Cristofaro, Zhen W. Zhuang, Anthony A. Lanahan, Martin A. Schwartz, Anne Eichmann, Michael Simons
Journal: Circulation (2012)

Arteriogenesis and collateral formation are complex processes requiring integration of multiple inputs to coordinate vessel branching, growth, maturation, and network size. Factors regulating these processes have not been determined.We used an inhibitor of NFκB activation (IκBαSR) under control of an endothelial-specific inducible promoter to selectively suppress endothelial nuclear factor-κB activation during development, in the adult vasculature, or in vitro. Inhibition of nuclear factor-κB activation resulted in formation of an excessively branched arterial network that was composed of immature vessels and provided poor distal tissue perfusion. Molecular analysis demonstrated reduced adhesion molecule expression leading to decreased monocyte influx, reduced hypoxia-inducible factor-1α levels, and a marked decrease in δ-like ligand 4 expression with a consequent decrease in Notch signaling. The latter was the principal cause of increased vascular branching as treatment with Jagged-1 peptide reduced the size of the arterial network to baseline levels.These findings identify nuclear factor-κB as a key regulator of adult and developmental arteriogenesis and collateral formation. Nuclear factor-κB achieves this by regulating hypoxia-inducible factor-1α-dependent expression of vascular endothelial growth factor-A and platelet-derived growth factor-BB, which are necessary for the development and maturation of the arterial collateral network, and by regulating δ-like ligand 4 expression, which in turn determines the size and complexity of the network.
Quantitation of the pathways of hepatic glycogen formation on ingesting a glucose load.
Authors: I Magnusson, V Chandramouli, W C Schumann, K Kumaran, J Wahren, B R Landau
Journal: Journal of Clinical Investigation (1987)

Diflunisal, 5-(2',4'-difluorophenyl)salicylic acid, excreted in urine as its glucuronide, was given to normal humans (n = 6) along with a glucose load specifically labeled with 14C. Glucuronide excreted by each subject was reduced to its glucoside and glucose from it degraded to yield the distribution of 14 C in its six carbons. Randomization of the 14C from the specifically labeled glucose was taken as a measure of the extent to which glucose was deposited indirectly (i.e., glucose----lactate----glucose----6-P----glycogen), rather than directly (i.e., glucose----glucose-6-P----glycogen). The maximum contribution to glycogen formation by the direct pathway was estimated to be 65 +/- 1%, on the assumption that glucuronide and glycogen are derived from the same hepatic pool of glucose-6-P in liver. Evidence that supports that assumption was obtained by comparing the randomization of 14C in the urinary glucuronide with that in glucose in blood from the hepatic vein of four of the subjects before and after they were given glucagon. Other evidence supporting the assumption was obtained by comparing in two subjects 3H/14C ratios in glucose from hepatic vein blood before and after glucagon administration with that in urinary glucuronide, having labeled the uridine diphosphate (UDP)-glucose in their livers with 14C by giving them 1-[14C]galactose and their circulating glucose with 3H by giving a 5-[3H]glucose-labeled load. It is concluded that glucuronide formation in humans can be used to trace glucose metabolism in the liver, and that in humans the indirect pathway of glucose metabolism is active.
The Volatile Nitrites
Authors: Sidney Cohen
Journal: JAMA (1979)

AMYL nitrite was introduced into medical practice as a coronary vasodilator more than a century ago; for much of that time, it was a mainstay, along with nitroglycerin, for angina pectoris. At present it is not used much, having been displaced by the organic nitrates. However, amyl nitrite along with its six-carbon analog, isobutyl nitrite, has come on a renewed popularity—as a drug of abuse. These are the volatile nitrites. The news media have amply reported on their abuse, but articles have appeared in the scientific literature only infrequently.<sup>1</sup> <h3>Pharmacology</h3> Amyl nitrite is a yellowish, volatile, flammable liquid with a fruity odor. It is unstable and decomposes in the presence of air and light. The severe chest pain of coronary insufficiency can be relieved within 30 seconds by amyl nitrite, and its effects will last for five minutes or more. Amyl nitrite relieves coronary spasm by relaxing smooth muscle fibers