tbuckley/cabot-search huggingface dataset:
Endothelial Dysfunction, Impaired Endogenous Fibrinolysis, and Cigarette Smoking
Authors: David E. Newby, Robert A. Wright, Catherine Labinjoh, Christopher A. Ludlam, Keith A. A. Fox, Nicholas A. Boon, David J. Webb
Journal: Circulation (1999)

Background —Effective endogenous fibrinolysis requires rapid release of tissue plasminogen activator (tPA) from the vascular endothelium. Smoking is a known risk factor for arterial thrombosis and myocardial infarction, and it causes endothelial dysfunction. We therefore examined the effects of cigarette smoking on substance P–induced tPA release in vivo in humans. Methods and Results —Blood flow and plasma fibrinolytic factors were measured in both forearms of 12 smokers and 12 age- and sex-matched nonsmokers who received unilateral brachial artery infusions of substance P (2 to 8 pmol/min). In both smokers and nonsmokers, substance P caused dose-dependent increases in blood flow and local release of plasma tPA antigen and activity ( P &lt;0.001 for all) but had no effect on the local release of plasminogen activator inhibitor type 1. Compared with nonsmokers, increases in forearm blood flow ( P =0.03) and release of tPA antigen ( P =0.04) and activity ( P &lt;0.001) caused by substance P were reduced in smokers. The area under the curve for release of tPA antigen and activity decreased by 51% and 53%, respectively. Conclusions —Cigarette smoking causes marked inhibition of substance P–induced tPA release in vivo in humans. This provides an important mechanism whereby endothelial dysfunction may increase the risk of atherothrombosis through a reduction in the acute fibrinolytic capacity.
Early closure of the tricuspid valve in a case of Ebstein's anomaly with type B Wolff-Parkinson-White Syndrome.
Authors: Y Koiwaya, H Narabayashi, S Koyanagi, H Matsuguchi, S Tanaka, T Imaizumi, A Kuroiwa, M Nakamura, T Hirata
Journal: Circulation (1979)

Echocardiographic studies of a 19-year-old female with Ebstein's anomaly and type B Wolff-Parkinson-White syndrome showed an earlier closure of the anterior tricuspid leaflet (ATL) than of the anterior mitral leaflet (AML), contrary to the previous reports. The interval between the closure of the ATL and the AML was 20 msec and 30 msec, respectively, before and after administration of edrophonium chloride. However, closure of the AML preceded that of the ATL after administration of atropine sulfate and during supraventricular tachycardia by 10 msec and 60 msec, respectively, concomitant with the shortening of the duration of the QRS complex. We conclude that early closure of the ATL may depend on preexcitation of the right ventricle.
Value of urinary copper excretion after penicillamine challenge in the diagnosis of Wilson's disease
Authors: Claudia Martins Da Costa, Dianne Baldwin, Bernard Portmann, Yvette Lolin, Alex P. Mowat, Giorgina Mieli-Vergani
Journal: Hepatology (1992)

To investigate the diagnostic value of 24-hr urinary copper excretion testing after penicillamine challenge in the diagnosis of Wilson's disease, 75 consecutive children referred for a variety of liver problems and in whom parameters of copper metabolism had been investigated were analyzed retrospectively. Seventeen had Wilson's disease, 22 had autoimmune chronic active hepatitis, 6 had primary sclerosing cholangitis, 12 had chronic liver disease of various etiologies, 4 had cryptogenic acute liver failure, 6 had acute hepatitic illnesses and 8 had a variety of disorders featuring normal liver histological appearance. Serum ceruloplasmin and total copper levels were significantly lower in Wilson's disease patients compared with all other groups, but three children with Wilson's disease had normal ceruloplasmin levels and seven had normal total copper levels. No significant difference was found for free serum copper levels and liver copper content between Wilson's disease patients and the other groups. Baseline 24-hr urinary copper excretion was significantly higher in Wilson's disease patients compared with that of the other patients, but six children with Wilson's disease had levels just above the upper limit of normal, overlapping with values obtained in three children with liver failure, two with acute hepatitis, two with autoimmune chronic active hepatitis and three with primary sclerosing cholangitis. The 24-hr urinary copper excretion after penicillamine challenge proved the most accurate single diagnostic test; levels more than 25 mumol/24 hr were present in 15 of 17 patients with Wilson's disease, but in only 1 child with liver failure of the 58 with other disorders.(ABSTRACT TRUNCATED AT 250 WORDS)
SUDDEN DEATH IN HEART DISEASE
Authors: George V. LeRoy
Journal: JAMA (1942)

To the Editor:—  Dr. Baer's communication toThe Journal, January 17, commenting on our article  Sudden Death of Patients with Few Symptoms of Heart Disease interests us very much because it represents the fairly typical reaction of some physicians when confronted by a proposed therapeutic regimen whose basis is physiologic experimentation. The objections offered to the use of theophylline with ethylene diamine intravenously are: However,  feel it is not entirely just to develop the (proposed) therapeutic regimen in man; There are a number of additional reasons why  think the routine administration of theophylline with ethylene diamine (aminophylline) and atropine is inadvisable; I believe a patient with an acute myocardial infarct should have as little intravenous medication as possible.  These are not very logical objections.  It is recognized by most physicians that a powerful vasodilating drug should be given intravenously with caution to any patient, and particularly when
Efficacy and tolerability of racecadotril in the treatment of cholera in adults: a double blind, randomised, controlled clinical trial
Authors: N H Alam
Journal: Gut (2003)

Background: The enkephalins, endogenous opiate substances, act as neurotransmitters along the entire digestive tract where they elicit intestinal antisecretory activity without affecting intestinal transit time or motility. Racecadotril, through inhibition of enkephalinase, reinforces the physiological activity of endogenous enkephalins and, therefore, shows intestinal antisecretory activity. Aim: We conducted the study to determine the role of racecadotril as an adjunct to the standard treatment of cholera in adults. Methods: The study was a double blind, randomised, placebo controlled clinical trial involving 110 adult male cholera patients who received either racecadotril or placebo in addition to standard cholera treatment. The major outcome measures (stool output, oral rehydration solution (ORS) intake, requirements for unscheduled intravenous fluid infusion, and duration of diarrhoea) were compared between the groups. Results: Of 110 patients enrolled, 54 received racecadotril and 56 received placebo. Admission clinical characteristics were comparable between the groups. There was no significant difference in (mean (SD)) total stool output (racecadotril v placebo 315 (228) v 280 (156) g/kg), total ORS intake (390 (264) v 369 (240) ml/kg), or duration of diarrhoea (35 (15) v 32 (13) hours) between the groups. Clinical success, defined as resolution of diarrhoea within 72 hours of initiation of study intervention, was similar in both groups (racecadotril v placebo 96% v 89%). The number of patients receiving unscheduled intravenous infusions was not significantly different between the groups (racecadotril v placebo 22% v 14%). No drug related adverse effect was noted. Conclusion: The study demonstrated that racecadotril therapy, although found to be safe, does not provide additional benefit in the treatment of severe cholera in adults.
Abstract 540: Lactate as a mediator of mesenchymal stem cell interactions within the tumor microenvironment
Authors: Yanique I. Rattigan, Alister F. Martin, John Glod, Debabrata Banerjee
Journal: Cancer Research (2010)

Abstract Mesenchymal stem cells (MSCs) are multipotent stromal precursor cells that have the capacity to migrate, proliferate, differentiate and contribute in vivo to the hypoxic tumor stroma. Cancer cells primarily depend on the anaerobic breakdown of glucose to generate ATP, even in the presence of oxygen. A consequence of this altered metabolic phenotype of cancer cells is the accumulation and secretion of lactate. Recent reports suggest that lactate produced by cancer cells may be taken up by stromal cells and recycled to regenerate pyruvate. Interestingly, stromal cells can efflux pyruvate to serve as a power supply to sustain the metabolic needs of cancer cells. Here we provide evidence that MDA-MB-231 and MCF-7 breast cancer cell lines secrete enhanced levels of lactate (2-fold) under hypoxia (1.5% O2) as compared to normoxia (21% O2). Analysis of MSC migration, showed that 15mM lactate enhanced MSC migration over 3-fold compared to control medium. Lactate stimulation of MSCs induced expression of a functional monocarboxylate transporter MCT-1, one of the proteins involved in lactate transport, at both mRNA and protein levels. Furthermore, activation of Stat3 signaling leading to enhanced MSC migration and NF-[[Unable to Display Character: &amp;#312;]]B regulated survival pathways following lactate stimulation was observed suggesting that lactate plays a role in the metabolic fate of cancer cells through the recruitment of MSCs. Delineating the interaction between MSCs, lactate and the tumor microenvironment will be fundamental in understanding tumor cell metabolism and provide knowledge for the development of novel anticancer therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 540.
Spores, Plagues and History: The Story of Anthrax
Authors: Itzhak Brook
Journal: BMJ (2004)

T his book begins dramatically with compelling information about the bioterrorism attack involving anthrax sent through the postal system in the United States in 2001. Holmes describes the patients' cases in great detail, combining medical descriptions (radiological and clinical pictures) with the drama of the events as they emerged. He then summarises the use of anthrax, as well as other microbes, as agents of bioterrorism and warfare agents. More generally, …
Proteomic Profiling of the Amniotic Fluid to Detect Inflammation, Infection, and Neonatal Sepsis
Authors: Catalin S Buhimschi, Vineet Bhandari, Benjamin D Hamar, Mert-Ozan Bahtiyar, Guomao Zhao, Anna K Sfakianaki, Christian M Pettker, Lissa Magloire, Edmund Funai, Errol R Norwitz, Michael Paidas, Joshua A Copel, Carl P Weiner, Charles J Lockwood, Irina A Buhimschi
Journal: PLoS Medicine (2007)

Background Proteomic analysis of amniotic fluid shows the presence of biomarkers characteristic of intrauterine inflammation. We sought to validate prospectively the clinical utility of one such proteomic profile, the Mass Restricted (MR) score. Methods and Findings We enrolled 169 consecutive women with singleton pregnancies admitted with preterm labor or preterm premature rupture of membranes. All women had a clinically indicated amniocentesis to rule out intra-amniotic infection. A proteomic fingerprint (MR score) was generated from fresh samples of amniotic fluid using surface-enhanced laser desorption ionization (SELDI) mass spectrometry. Presence or absence of the biomarkers of the MR score was interpreted in relationship to the amniocentesis-to-delivery interval, placental inflammation, and early-onset neonatal sepsis for all neonates admitted to the Newborn Special Care Unit (n = 104). Women with “severe” amniotic fluid inflammation (MR score of 3 or 4) had shorter amniocentesis-to-delivery intervals than women with “no” (MR score of 0) inflammation or even “minimal” (MR score of 1 or 2) inflammation (median [range] MR 3–4: 0.4 d [0.0–49.6 d] versus MR 1–2: 3.8 d [0.0–151.2 d] versus MR 0: 17.0 d [0.1–94.3 d], p < 0.001). Nonetheless, a “minimal” degree of inflammation was also associated with preterm birth regardless of membrane status. There was a significant association between the MR score and severity of histological chorioamnionitis (r = 0.599, p < 0.001). Furthermore, neonatal hematological indices and early-onset sepsis significantly correlated with the MR score even after adjusting for gestational age at birth (OR for MR 3–4: 3.3 [95% CI, 1.1 to 9.2], p = 0.03). When compared with other laboratory tests routinely used to diagnose amniotic fluid inflammation and infection, the MR score had the highest accuracy to detect inflammation (white blood cell count > 100 cells/mm3), whereas the combination of Gram stain and MR score was best for rapid prediction of intra-amniotic infection (positive amniotic fluid culture). Conclusions High MR scores are associated with preterm delivery, histological chorioamnionitis, and early-onset neonatal sepsis. In this study, proteomic analysis of amniotic fluid was shown to be the most accurate test for diagnosis of intra-amniotic inflammation, whereas addition of the MR score to the Gram stain provides the best combination of tests to rapidly predict infection.
Bone matrix constituents stimulate interleukin-1 release from human blood mononuclear cells.
Authors: R Pacifici, A Carano, S A Santoro, L Rifas, J J Jeffrey, J D Malone, R McCracken, L V Avioli
Journal: Journal of Clinical Investigation (1991)

To test the hypothesis that mononuclear cells are stimulated to release interleukin 1 (IL-1) by bone fragments released in the bone microenvironment during the remodeling cycle, we have investigated the effects of bone matrix and some of its constituents on IL-1 secretin from peripheral blood mononuclear cells (PBMC). Increases in IL-1 activity were observed when either PBMC or adherent monocytes, but not lymphocytes depleted of monocytes, were co-cultured with either human or rat bone particles but not with latex particles of similar size. Co-culture of PBMC with bone particles in a transwell system where the cells were physically separated from the bone particles, or with osteoblast- or osteoclast-covered bone particles, did not stimulate IL-1 release, indicating that a physical contact between PBMC and the bone surface is required for eliciting IL-1 release. This was confirmed by the finding of a lower stimulatory effect of bone particles pretreated with etidronate, a bisphosphonate which decreases the bone binding capacity of PBMC. Constituents of bone matrix, such as collagen fragments, hydroxyproline, and, to a lesser extent, transforming growth factor-beta, but not osteocalcin, alpha 2HS glycoprotein, fragments of either bone sialoprotein or osteopontin, and fibronectin, stimulated PBMC IL-1 release in a dose-dependent fashion. Collagen-stimulated IL-1 release was partially and specifically inhibited by a monoclonal antibody directed against the alpha 2 beta 1-integrin cell surface collagen receptor. These data demonstrate that products of bone resorption, known to be chemotactic for mononuclear cells, stimulate PBMC IL-1 activity. These findings may help explain previous documentation of increased IL-1 secretion by circulating monocytes obtained from patients with high turnover osteoporosis.
The expression of cell cycle related proteins in rat hepatocytes is distinct from human hepatocytes when cultured in serum-free media supplemented with HGF (hepatocyte growth factor) and EGF (epidermal growth factor)
Authors: Jens Walldorf, Christoph Koehler, Hongbo Cai, Sina Kleist, Dieter Runge, Stephen Strom, Wolfgang E. Fleig, H. Aurich
Journal: Journal of Hepatology (2002)
Let's Face Facts
Authors: Naomi Vaisrub
Journal: JAMA (1986)

My late father was a wise man, in possession of a wry sense of humor. Throughout most of his life, he had strictly adhered to the health habits advocated by the medical profession, including proper diet, exercise, and regular physical examinations. When he learned he had lung cancer, caused by cigarettes he had given up 30 years previously, the irony of the development did not escape him. He doggedly underwent the tortuous treatments proffered, including unsuccessful surgery, radiation, and chemotherapy; but, realizing that clogged arteries would not likely be his downfall, he began to indulge in hitherto forbidden foods—his favorite being fried salami with eggs. There was no denial on his part of his imminent death, only a hearty attempt to remain productive until the end and to prepare his family. In striking contrast to my father, the physician responsible for his care indulged in a hopeless and harmful deception,
British Columbian judge says Canada's ban on physician assisted dying is unconstitutional
Authors: C. Dyer
Journal: BMJ (2012)

The ban on physician assisted dying in Canada’s criminal code has been ruled unconstitutional by British Columbia’s Supreme Court, opening the way for a woman with a terminal illness to ask the court to allow her doctor to end her life.

The judge, Lynn Smith, declared that the absolute ban unjustifiably infringes Gloria Taylor’s rights to life, liberty, and security of the person and her right to equality under Canada’s Charter of Rights and Freedoms.

The judge suspended the effect of her ruling for a year, to allow time for the legislature to draft and consider legislation remedying the law. But in the meantime, she ruled that Taylor will …
Phobia of Hydrophobia Justified
Authors: Stanley A. Plotkin, Hilary Koprowski
Journal: New England Journal of Medicine (1979)

A morbid, almost mystical fear of rabies is not uncommon, particularly among city dwellers who are rarely in contact with wild animals. On the other hand, hunters, foresters, dogcatchers, veterinarians and others who are in frequent contact with animals often display such a cavalier attitude that they forget having been licked or bitten by animals, including bats — second only to skunks as vectors of rabies.1 Such a course may have occurred in Case 1, described by Houff and his colleagues in this issue of the Journal. He was a forest ranger who must have had a great deal . . .
New insights into the regulation of inflammation by adenosine
Authors: J. Linden
Journal: Journal of Clinical Investigation (2006)

Adenosine, long known as a regulator of cardiovascular function, has recently been identified as a significant paracrine inhibitor of inflammation that acts primarily by activation of A2A adenosine receptors (A2AARs) on lymphoid or myeloid cells. In this issue of the JCI, Yang et al. describe a proinflammatory phenotype resulting from deletion of the gene encoding the A2B adenosine receptor (A2BAR) in the mouse, suggesting that activation of the A2BAR can also have antiinflammatory effects (see the related article beginning on page 1913). Nevertheless, the role of the A2BAR remains enigmatic since its activation can either stimulate or inhibit the release of proinflammatory cytokines in different cells and tissues.
Upregulation of Cardiac Uptake <sub>1</sub> Carrier in Ischemic and Nonischemic Rat Heart
Authors: Martin Ungerer, Andreas Chlistalla, Gert Richardt
Journal: Circulation Research (1996)

Neuronal uptake1 constitutes the main elimination process of cardiac norepinephrine under normoxic conditions. Uptake1 may be subject to changes during myocardial ischemia. We therefore studied the regulation of the uptake1 carrier in isolated perfused rat hearts, comparing ischemic and nonischemic conditions. Radioligand binding with [3H]mazindol was used to determine carrier densities and affinities, whereas cardiac clearance of[3H]norepinephrine served as a measure of the transport capacity of the uptake1 carrier. When exocytotic norepinephrine release was induced in nonischemic rat hearts by electrical field stimulations, we observed an increase in the cardiac density of uptake1 carriers (Bmax) to 210 +/- 5 fmol/mg protein (versus 134 +/- 3 fmol/mg in control hearts). Simultaneously, the cardiac clearance of [3H]norepinephrine increased to 41 +/- 4% versus 30 +/- 4% in control hearts. Both carrier density and norepinephrine clearance returned to baseline values within a period of 40 minutes after stimulation. Carrier affinities (Kd values) did not differ between the groups. Stop-flow ischemia induced a substantial overflow of norepinephrine by itself. Additionally, carrier density was increased to 144% after 40 minutes of stop-flow ischemia (P < .005 versus control hearts). When ischemia was followed by 20 minutes of reperfusion, the Bmax of the uptake1 carrier remained significantly elevated. With a further extension of the reperfusion period to 40 minutes, however, carrier density declined to baseline values. Kd values were not influenced by any of these interventions. Clearance of [3H]norepinephrine was suppressed (to 5 +/- 2%) in the first minutes of reperfusion, which may reflect the inverse transport direction of the norepinephrine carrier known to occur in ischemia. After 20 minutes of reperfusion, clearance increased to 39 +/- 5% (P < .005 versus control hearts) and then fell to 29 +/- 5% after 40 minutes of reperfusion (NS). These results demonstrate that after both electrical field stimulation and myocardial ischemia, the density of uptake1 carrier proteins temporarily increases, which may result in an increased transport capacity for norepinephrine.
Analysis of a T cell receptor gene as a target of the somatic hypermutation mechanism.
Authors: J Hackett, C Stebbins, B Rogerson, M M Davis, U Storb
Journal: The Journal of Experimental Medicine (1992)

In an effort to identify cis-acting elements required for targeting of the somatic hypermutation process in mice, we examined whether a T cell receptor (TCR) transgene under the control of the immunoglobulin (Ig) heavy (H) chain intron enhancer would be mutated in antigen-stimulated B cells. Hybridomas were established from splenic B cells of mice carrying two copies of the TCR transgene after hyperimmunization with phosphorylcholine keyhole limpet hemocyanin. Northern analysis revealed that all of the transgene-containing hybridomas expressed the TCR mRNA. Multiple somatic point mutations were found in seven of eight endogenous Ig VH genes examined. In contrast, 29 of 32 TCR genes examined contained no mutations. One potential mutation was seen in each of the three other TCR genes. Our data indicate that although the TCR transgene is expressed in B cells, it is not efficiently targeted by the mutator mechanism. Furthermore, the presence of an Ig H chain enhancer is itself not sufficient for targeting of the somatic hypermutation mechanism.
Examination of complement C3 metabolism in rheumatoid arthritis using 2-dimensional immunoelectrophoresis.
Authors: M F Shadforth, D C McNaughton
Journal: Annals of the Rheumatic Diseases (1978)

A previous report that C3 activation products are demonstrable in the plasma of subjects with rheumatoid arthritis was reinvestigated using 2-dimensional immunoelectrophoresis. Initially it seemed that results were in agreement, but the occurrence of similar patterns in normal sera and poor reproducibility of results suggested the findings were artefacts. When calcium and magnesium ions were removed with EDTA, C3 activation products were no longer demonstrable in plasma from normal subjects or from patients with rheumatoid arthritis. The results obtained without EDTA in the buffer showed a greater degree of complement activation in patients with rheumatoid arthritis, suggesting that in this condition the serum may have a greater potential ability to bring about complement activation.