tbuckley/cabot-search huggingface dataset:
Effect of locally applied tissue-type plasminogen activator on venous fibrinolytic activity: in vitro and in vivo investigations
Authors: M J Underwood, R S More, A H Gershlick, D P d. Bono
Journal: Cardiovascular Research (1993)

Objectives: The aim was to see if topically applied tissue-type plasminogen activator (tPA) would enhance the fibrinolytic activity of saphenous vein prepared before coronary artery surgery, persist in the vessel wall after perfusion, and reduce thrombus formation after vascular injury. Methods: Varying doses of tPA were applied to the intimal surface of the saphenous vein obtained from patients before coronary artery surgery. After flushing, biopsies were incubated on fibrin plates and areas of lysis quantified. Samples treated with tPA (1 mg·ml−1) were perfused in vitro for 30 minutes. Fibrinolytic activity was assessed on fibrin plates and tPA activity (in tissue extract) measured with chromogenic assays. The effect of locally applied tPA on thrombus formation was quantified with a rat vena cava model based on vascular injury and stasis. Results: Local application of 1 mg·ml−1 tPA enhanced fibrinolysis under static conditions [median (interquartile range) of diameter of lysis·mm−1 (n = 8 both groups), treated vein 16.5 (14.1-17.9), control 8.5 (5.75-10.37) (p < 0.05)]. This enhanced activity was retained after in vitro perfusion [median (interquartile range) of areas of lysis·mm−2 (n = 8 all groups), treated vein 170.8 (132.8-205.1), control (unperfused) 69.5 (45.2-87.6), perfused (untreated) 76.7 (58.3-98.9) (p < 0.01)]. Specific tPA activity in these samples was also increased (p < 0.05). Local application of tPA (1 mg·ml−l) to damaged rat vena cava reduced subsequent thrombus formation [median thrombus weight·mg−1 (interquartile range) (n = 8). tPA treated 2.5 (0.25-5.75), control 38.5 (32-43) (p < 0.001)1. Conclusions: Locally applied tPA enhances the fibrinolytic activity of damaged vessel wall, persists after perfusion, and reduces thrombus formation after vascular injury. This method of treating conduits before their use as vascular grafts merits further studv to see if it is effective in reducing early graft thrombosis while maintaining systemic haemostasis. Cardiovascular Research 1993;27:2270-2273
THE EFFECTS OF ANTIGENS AND OF PHYTOHEMAGGLUTININ ON RABBIT SPLEEN CELL SUSPENSIONS
Authors: G. Harris, R. J. Littleton
Journal: The Journal of Experimental Medicine (1966)

Phytohemagglutinin (PHA) stimulated the rate of DNA synthesis in rabbit spleen cell suspensions. Unlike antigens, previous immunization to PHA was not necessary and the specific response could not be transferred by macrophages, although lymphocytes primed by incubation in PHA were able to stimulate other spleen cells not directly exposed to PHA. When rabbits were stimulated by in vivo immunization with antigens, spleen cells proliferating in response to antigen were stimulated to divide by in vitro contact with PHA. Using the technique of specific hemolytic plaque formation by individual cells synthesizing γM-antibody to sheep red cells (plaque-forming cells), no evidence was obtained that stimulation of cell division by PHA resulted in specific antibody formation, although the presence of antigen resulted both in stimulation of cell proliferation and the production of plaque-forming cells. The presence of both sheep red cells and PHA in the medium of the same cell suspensions did not enhance the production of plaque-forming cells although there was a summative effect on DNA synthesis.
The Decreasing Risk of Transfusion-Associated AIDS
Authors: Jay E. Menitove
Journal: New England Journal of Medicine (1989)

The first report of the transmission of acquired immunodeficiency syndrome (AIDS) by transfused blood appeared in December 1982. In the absence of a known cause or a laboratory test to identify donors capable of transmitting AIDS to transfusion recipients, blood-collection agencies made changes in their procedures for donor qualification and recruitment to deter donation by those at risk for AIDS. This approach, which was supplemented by testing for human immunodeficiency virus (HIV) antibody in the spring of 1985, blunted but did not totally eliminate the threat of transfusion-associated AIDS. Three articles in this issue of the Journal illustrate the profound . . .
Oxidative cross-linking of immune complexes by human polymorphonuclear leukocytes.
Authors: H E Jasin
Journal: Journal of Clinical Investigation (1988)

Incubation of human serum albumin-anti-human serum albumin immune complexes bound to a plastic surface, with human polymorphonuclear leukocytes for 1 h at 37 degrees C resulted in covalent cross-linking of 8.5% +/- 0.5 of the complexes, corresponding to a minimum rate of 700 antibody molecules per cell per minute. Similar results were obtained with IgG-anti-IgG and type II collagen-anticollagen II human antibodies. Cross-linking was defined as the antibody remaining attached to plastic-bound antigen after extraction with 3 M MgCl2 and 0.1 N HCl solutions. The effects of addition of oxygen radical scavengers, heme-enzyme inhibitors, and omission of Cl- indicated that the cross-linking process was mediated by the myeloperoxidase-H2O2-Cl- system. Cross-linking was also obtained with cell lysates, polymorphonuclear granules, and purified human myeloperoxidase in the presence of a steady flux of H2O2 provided by glucose oxidase-glucose. Cross-linking by the cell-free systems was also abolished by sodium azide or omission of chloride ions. Cross-linked immune complexes were also generated by incubation with 20 to 50 microM solutions of freshly distilled hypochlorous acid. Addition of 10 mM hypochlorous acid to soluble IgG resulted in the formation of protein precipitates insoluble in 5 M guanidine, 0.1 N HCl, or boiling 2.3 M sodium dodecyl sulfate-1.4 M 2-mercaptoethanol. The remaining soluble IgG contained fluorescent high molecular aggregates (ex: 360 nm; em: 454 nm). Oxidative cross-linking of antigen-antibody molecules, and of immune complexes to connective tissue macromolecules may play a pathogenic role in acute and chronic inflammatory processes.
Uncertainties in Genetic Testing for Chronic Disease
Authors: H. Gilbert Welch, Wylie Burke
Journal: JAMA (1998)

Sequencing an individual’s DNA seems destined to become an increasingly prominent part of medical care. Once a genetic alteration has been identified and characterized by researchers, testing for it is relatively simple, requiring only white blood cells obtained via a routine blood draw. Because so many diseases are influenced by heredity, investigators are likely to identify numerous alterations associated with illness in the human genome. In the past, genetic testing concerned the next generation: decisions about whether to have a child (eg, TaySachs disease, cystic fibrosis, and Down syndrome) and screening of newborns (eg, phenylketonuria and sickle cell anemia). Increasingly, genetic testing now concerns the current generation: testing ourselves for susceptibility to chronic disease. This domain includes more common conditions (eg, heart disease, diabetes, and cancer) and a future has been promised in which medicine’s emphasis will be shifted from treatment of the sick to prevention in those at risk. 1 But the immediate future is more likely to be characterized by confusion. The confusion created by false-positive and false-negative tests will be familiar to clinicians. A less familiar source of confusion will also be present: because the absence of a genetic risk factor will rarely (if ever) reduce risk much below average, those with truly negative test results must be reminded that they remain at risk. However, the greatest challenge is what to tell those with truly positive test results. These persons may be best characterized as “pre-patients.” In this article, we examine 4 uncertainties that clinicians will have to communicate to prepatients: the nature of risk, the generalizability of risk estimates, the time at which risk information is useful, and the utility of intervention.
Reversible Lymphomas Associated with Epstein-Barr Virus Occurring during Methotrexate Therapy for Rheumatoid Arthritis and Dermatomyositis
Authors: Onsi W. Kamel, Matthijs van de Rijn, Lawrence M. Weiss, Gregory J. Del Zoppo, P. Kahler Hench, Bruce A. Robbins, Paul G. Montgomery, Roger A. Warnke, Ronald F. Dorfman
Journal: New England Journal of Medicine (1993)

An increased risk of lymphoproliferative disorders has been well documented in patients who are treated with immunosuppressive agents after organ transplantation1 and in patients with the acquired immunodeficiency syndrome2. The lymphomas that develop in immunosuppressed patients after transplantation are typically large-cell lymphomas that contain Epstein-Barr virus (EBV) and are closely linked to the level of competence of the immune system3. When treatment with immunosuppressive drugs is reduced or discontinued, these EBV-associated lymphomas may regress completely1; if the patient's immune status continues to be compromised, however, the tumor may continue to proliferate and result in death. Whether patients . . .
Adenosine and inosine increase cutaneous vasopermeability by activating A3 receptors on mast cells
Authors: Stephen L. Tilley, Victoria A. Wagoner, Christopher A. Salvatore, Marlene A. Jacobson, Beverly H. Koller
Journal: Journal of Clinical Investigation (2000)

Adenosine has potent effects on both the cardiovascular and immune systems. Exposure of tissues to adenosine results in increased vascular permeability and extravasation of serum proteins. The mechanism by which adenosine brings about these physiological changes is poorly defined. Using mice deficient in the A3 adenosine receptor (A3AR), we show that increases in cutaneous vascular permeability observed after treatment with adenosine or its principal metabolite inosine are mediated through the A3AR. Adenosine fails to increase vascular permeability in mast cell–deficient mice, suggesting that this tissue response to adenosine is mast cell–dependent. Furthermore, this response is independent of activation of the high-affinity IgE receptor (FcεR1) by antigen, as adenosine is equally effective in mediating these changes in FcεR1 β-chain–deficient mice. Together these results support a model in which adenosine and inosine induce changes in vascular permeability indirectly by activating mast cells, which in turn release vasoactive substances. The demonstration in vivo that adenosine, acting through a specific receptor, can provoke degranulation of this important tissue-based effector cell, independent of antigen activation of the high-affinity IgE receptor, supports an important role for this nucleoside in modifying the inflammatory response.
STUDY OF HOME CARE IN A MUNICIPAL HOSPITAL
Authors: DAVID UNTERMAN
Journal: JAMA (1949)

Home care represents an extension of medical and nursing service from the hospital to the home. It is one approach to the complex problem of providing continuous medical care to those segments of the population which do not enjoy this advantage at the present time. Home care is also an approach to the problem of hospital beds since it permits earlier discharge of the patient from the hospital and minimizes unnecessary readmissions through continuous medical follow-up. Experience has shown that it costs less to treat a patient at home than in the hospital, and, although such economy is by no means the prime objective of this program, it is nevertheless an important consideration in hospital administration.    A pilot study of home care was conducted on the Third and Fourth (New York University) Medical Divisions of Bellevue Hospital during the year beginning Jan. 1, 1948. This program was suggested by the
THE ERYTHROPOIETIC ACTION OF GERMANIUM DIOXID
Authors: Frederick S. Hammett
Journal: JAMA (1925)

To  Editor:  —InThe Journal, June 6, Bailey, Davidson and Bunting make certain criticisms of  conclusions drawn by me and my associates from observations on  erythropoietic action of germanium dioxid in  rat. These workers object to our use of  rat on  ground that the withdrawal of  amount of blood necessary for careful counts soon creates an anemic stimulus to  bone marrow which would tend to cloud  issue. In our paper ( J. Exper. Med . 35 :173 [Feb.] 1922), tables are given which definitely show that  control untreated rats did not exhibit any increase in  erythrocyte count of  blood as drawn by our technic which was in any way statistically valid or comparable to that found to occur in  rats receiving germanium dioxid. If we had not had these untreated controls for comparison,  criticism of Bailey, Davidson and
STUDIES WITH THE ELECTROCARDIOGRAPH ON THE ACTION OF THE VAGUS NERVE ON THE HUMAN HEART
Authors: Canby Robinson, George Draper
Journal: The Journal of Experimental Medicine (1912)

The electrocardiographic records taken during vagus stimulation by pressure from children suffering with chronic heart disease have shown that the stimulation of the vagi in these cases is strikingly effectual. In some of the cases, a definite difference was demonstrated between the action of the right and left vagi. The control of the rate of the heart-beat seemed to predominate usually in the right vagus nerve, while the control of stimulus conduction from auricles to ventricles apparently predominated usually in the left vagus. This difference in the two nerves probably exists on account of the difference in their anatomical distribution, the right vagus going especially to that part of the heart which controls the rate of contraction, the sinus node above the right auricle, and the left vagus going especially to that part in which the conducting mechanism is found. Each nerve, however, has to a lesser degree the function which predominates in the other. The whole heart seems to respond, as a rule, more promptly to right than to left vagus pressure, and fairly constant differences have been seen in the effects which stimulation of each nerve has on the various waves of the electrocardiograms. The stimulation of each vagus may influence directly the contractions of the ventricles, causing great diminution in their force. Right vagus stimulation was followed at times by a complete dissociation of auricles and ventricles. The auricular rhythm was slowed sufficiently at this time to allow the ventricles, whose inherent rhythmicity is apparently unaffected by right vagus stimulation, to take up their own independent rhythm. The heightened ventricular rhythmicity in these cases allowed this to take place after only moderate slowing of the auricles. The independent ventricular rhythm was sometimes established in the region of the node of Tawara, for no disturbance of the ventricular portion of the electrocardiogram occurred. At another time, some other point in the ventricles inaugurated the stimuli of the independent ventricular contractions and an abnormal electrocardiogram resulted. The resemblance of our curves, showing dissociation, to those obtained during right vagus and left accelerator stimulation in dogs is definite. That analogy, the clinical picture, and the form of the electrocardiograms of these cases have led us to the belief that an important feature in the pathological physiology of these cases is hypertonus of the cardiac accelerator nerves. This factor, as a cause of symptoms and as a hindrance to the establishment of cardiac rest, may prove of great importance, against which a new form of cardiac therapeutics must be directed.
A physiological approach to vectorcardiographic recognition of ventricular hypertrophy
Authors: A. C. Arntzenius
Journal: Cardiovascular Research (1970)

Journal Article A physiological approach to vectorcardiographic recognition of ventricular hypertrophy Get access A. C. Arntzenius A. C. Arntzenius 1 From the Department of Cardiology, University Hospital, Leiden, The Netherlands 1Present address: Department of Cardiology, Medical Faculty Rotterdam, Rotterdam, The Netherlands. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 4, Issue 1, January 1970, Pages 105–115, https://doi.org/10.1093/cvr/4.1.105 Published: 01 January 1970 Article history Accepted: 02 May 1969 Published: 01 January 1970
18-Hydroxy-Deoxycorticosterone in Human Hypertension
Authors: J. C. MELBY, S. L. DALE, T. E. WILSON
Journal: Circulation Research (1971)

18-Hydroxy-ll-deoxycorticosterone (18-OH-DOC) was isolated from human adrenal vein blood in concentrations of the same magnitude as is aldosterone, and its structure was proved by a variety of meth...
Points: Ethics and politics
Authors: S. Doxiadis
Journal: BMJ (1985)

SIR,-YOU may be one of those who plan your Christmas shopping well in advance, or one who leaves it until the very last minute.But however you set about this annual task I am asking you to spare a thought for those for whom Christmas brings little joy and probably some anxiety.I am referring to those beneficiaries of the Royal Medi- cal Benevolent Fund; some are doctors, some are widows with children, all are in need of our help and may be faced with prospect of having little with which to celebrate Christmas.The object of the Christmas appeal of the Royal Medical Benevolent Fund is to enable us to send financial gifts to our 780 beneficiaries this Christ- mas and also in Christmases to come.These are a special addition to the awards that we make throughout the year.The fund knows through the many letters received how much this little extra means, enabling those less fortunate than our- selves to have at least some joy and warmth at Christmas.
PTU-159 Self reporting of gluten sensitive GI symptoms in primary care: should we accept the diagnosis of coeliac disease without further investigations?
Authors: I Aziz, K E Evans, L Newrick, D S Sanders
Journal: Gut (2012)

<h3>Introduction</h3> Many unselected patients presenting to gastrointestinal (GI) clinics self-report that they have symptoms related to the ingestion of gluten. For this reason we undertook a prospective and systematic evaluation of this group of patients to ascertain the subsequent diagnostic yield. <h3>Methods</h3> All patients were referred to a dedicated coeliac or gluten sensitivity clinic by GPs through a choose and book system. The referral criteria were “GI symptoms attributed to gluten ingestion.” Investigations included baseline haematology, biochemistry, haematinics, C reactive protein and HLA status for the DQ2/DQ8 haplotypes. In addition, coeliac serology was performed: endomysial antibody (EMA), tissue transglutaminase antibody (tTG), immunoglobulins, as well as duodenal biopsies on a gluten containing diet. A diagnosis of coeliac disease was based on either the presence of villous atrophy or in cases with lesser degrees of the modified Marsh grading, an associated positive coeliac serology and/or HLA typing. <h3>Results</h3> 140 patients were investigated over a 5-year period. 80% were women and the median age of presentation was 37 yrs (range 16–88). In patients self-reporting symptoms related to the ingestion of gluten, the diagnosis of coeliac disease was reached in 10% (n 14). 85% (n 119) did not have coeliac disease but fulfilled the ROME criteria for irritable bowel syndrome (IBS). These patients were given a clinical diagnosis of gluten sensitive IBS (GS-IBS). Importantly, organic pathology was found in 5% (n 7) all of whom had additional alarm symptoms—mesenteric ischaemia, bacterial overgrowth, lactose intolerance, bile salt malabsorption, lymphocytic colitis, ulcerative colitis and pyloric stricture. A positive coeliac serology (p&lt;0.0001, exact fisher test) was significantly associated with coeliac disease. All patients with coeliac disease were HLA positive compared to 44% of GS-IBS cases. There was statistically no significant difference in gender, clinical symptoms or baseline bloods (haemoglobin, vitamin B<sub>12</sub>, folate, ferritin, calcium or albumin) between the groups, (p&gt;0.05). <h3>Conclusion</h3> Self-reporting of gluten related GI symptoms only results in a diagnosis of coeliac disease in 10% of cases. The majority of patients do not have overt coeliac disease but may belong to the spectrum of GS-IBS, a relatively new and under researched concept. Moreover, 5% had significant underlying disease. An empirical trial of gluten-free diet prior to referral may be unhelpful and delay the diagnosis in this group of patients. This data suggests that patients who self-report gluten induced GI symptoms should be considered for further investigations. <h3>Competing interests</h3> None declared.
MEPs approve stem cell research using human embryos
Authors: R. Watson
Journal: BMJ (2003)

Members of the European parliament have paved the way for the European Union to fund medical research involving embryonic stem cells derived from surplus human embryos.

The parliament's support for ending the existing moratorium has placed further pressure on EU governments to go down the same path. They must now give their formal approval–possibly within the next month–before any projects can be eligible for finance from the EU's €17bn (£12bn; $20bn) four year …
[387] INTRATUMORAL TREATMENT OF PRE-ESTABLISHED SUBCUTANEOUS HEPATOCELLULAR TUMORS WITH TUMOR LYSATE PUSED DENDRITIC CELLS ENGINEERED TO EXPRESS CD40L CONFERS HIGHER ANTITUMOR IMMUNITY THAN SUBCUTANEOUS OR INTRAVENOUS TREATMENT
Authors: M.A. Gonzalez-Carmona, A. Timmerman, E. Raskopf, M. Kornek, I.G. Schmidt-Wolf, W.H. Caselmann, T. Sauerbruch, V. Schmitz
Journal: Journal of Hepatology (2007)
Evaluation Criteria for Publishing in Top-Tier Journals in Environmental Health Sciences and Toxicology
Authors: Byung-Mu Lee
Journal: Environmental Health Perspectives (2011)

Background: Trying to publish a paper in a top-rated peer-reviewed journal can be a difficult and frustrating experience for authors. It is important that authors understand the general review process before submitting manuscripts for publication.Objectives: Editors-in-chief and associate editors from top-tier journals such as Environmental Health Perspectives (EHP), Toxicological Sciences, Journal of Pharmacology and Experimental Therapeutics, and Chemical Research in Toxicology were asked to provide guidance concerning the writing and submission of papers to their journals.Discussion: The editors reviewed the manuscript review process for their journals, elaborated on the evaluation criteria for reviewing papers, and provided advice for future authors in preparing their papers.Conclusions: The manuscript submission process was similar for all of the journals with the exception of EHP that includes an initial screening in which about two-thirds of submitted papers are returned to the authors without review. The evaluation criteria used by the journals were also similar. Papers that are relevant to the scope of the journal, are innovative, significantly advance the field, are well written, and adhere to the instructions to authors have a higher likelihood of being accepted. The editors advised potential authors to ensure that the topic of the paper is within the scope of the journal, represents an important problem, is carefully prepared according to the instructions to authors, and to seek editorial assistance if English is not the primary language of the authors.