tbuckley/cabot-search huggingface dataset:
Angiotensin II increases plasminogen activator inhibitor type 1 and tissue-type plasminogen activator messenger RNA in cultured rat aortic smooth muscle cells.
Authors: R T van Leeuwen, A Kol, F Andreotti, C Kluft, A Maseri, G Sperti
Journal: Circulation (1994)

The role of angiotensin as a vasoconstrictor is well established. Lately, several other actions of this hormone on vascular smooth muscle (VSM) cells have been recognized including the induction of hypertrophy and/or DNA synthesis. Platelet-derived growth factor (PDGF), a mitogen recently shown to increase plasminogen activator inhibitor type 1 (PAI-1) synthesis in VSM cells, shares with angiotensin II (Ang II) several steps of its intracellular signaling pathway.The expression of PAI-1 and tissue-type plasminogen activator (TPA) mRNA in cultured rat VSM cells was studied. Northern blot analysis demonstrated a severalfold increase in the PAI-1 mRNA 3 to 8 hours after stimulation with 300 nmol/L Ang II. A similar response for TPA mRNA was observed. This induction did not require the synthesis of an intermediate protein or peptide because it was not affected by cycloheximide. In the cell-conditioned supernatant, the net result was an increase in PAI-1 activity from 4.18 +/- 1.8 to 13.2 +/- 6.8 IU/mL 6 hours after the addition of 300 nmol/L Ang II (mean +/- SD, P < or = .008, n = 6). The Ang II-induced increase in PAI activity was dose related, with a maximal effect at a concentration of 23 nmol/L (n = 3) and an ED50 of 3.3 +/- 1.5 nmol/L (n = 3). [Sar1-Ile8]angiotensin II, a specific competitive antagonist of Ang II, blocked 90 +/- 9% (n = 3) of the PAI activity induced by 10 nmol/L Ang II. In basal conditions, fibrin overlay zymography demonstrated the presence of free TPA. After stimulation with Ang II, lysis caused by the in situ dissociation of TPA was also present in the region of the TPA/PAI-1 complex. Angiotensin I (Ang I) elicited an increase in PAI activity similar to that obtained with equivalent doses of Ang II. Captopril (5 micrograms/mL), an inhibitor of the angiotensin-converting enzyme (ACE), completely prevented the Ang I effect, demonstrating that VSM cells display an ACE-like activity.Recent research has demonstrated the existence of a localized vascular renin-angiotensin system. The finding that Ang II can potentially modulate the plasminogen activation in the arterial wall has important biological and therapeutical implications for the evolution of arterial wall thrombi and the migration of cells through the vessel wall in the genesis of atherosclerotic lesions. We speculate that the reduction in thrombotic events observed in patients with a previous myocardial infarction and in high-renin, hypertensive patients treated with ACE inhibitors could be due at least in part to the decreased production of PAI-1 by VSM cells caused by these agents.
Myoglobinuria and Myocardial Infarction
Authors: Stanley H. Bernstein
Journal: JAMA (1975)

To the Editor.—  I should like to respond to the comments of Drs. Rock and Solomon regarding the diagnostic test for myocardial infarction utilizing myoglobinuria (229:1166, 1974).  I do agree that more data are needed regarding reproducibility of quantitation of myoglobin in the urine. The method of radial immunodiffusion assay may well be too insensitive to the small changes in the excretion of myoglobin. The data reported were gathered from patients with definite unequivocal infarcts— more subtle areas of myocardial necrosis may lead to levels of myoglobin in the urine in microgram amounts. We are presently investigating more sensitive immunologic techniques to demonstrate these changes and to be able to reproduce the results.  However, I do take issue with the conclusion that the myocardial isoenzyme of creatine phosphokinase may be the most productive measurement for infarction. Although skeletal muscle, as well as cardiac muscle, contains substantial amounts of myoglobin, a
Penicillin Blood Levels for Twenty-Four Hours Following a Single Intramuscular Injection of Calcium Penicillin in Beeswax and Peanut Oil
Authors: Monroe J. Romansky, George E. Rittman
Journal: New England Journal of Medicine (1945)

IN PREVIOUS reports, we1 2 3 have shown that after a single injection of a suspension of calcium penicillin in beeswax and peanut oil, effective levels of penicillin can be maintained in the blood for ten to twelve hours, with excretion continuing in the urine for twenty-four to thirty-two hours. Clinical results3 , 4 have proved as satisfactory by this method of administration as by the method utilizing penicillin in saline solution, which necessitates multiple injections. The preparation most satisfactory for obtaining the above results has proved to be a suspension of 100,000 units of calcium penicillin in 4 per cent beeswax by volume . . .
Sickle cell trait is not independently associated with susceptibility to end-stage renal disease in African Americans
Authors: Pamela J. Hicks, Carl D. Langefeld, Lingyi Lu, Anthony J. Bleyer, Jasmin Divers, Patrick H. Nachman, Vimal K. Derebail, Donald W. Bowden, Barry I. Freedman
Journal: Kidney International (2011)
Successful treatment of middle aged and elderly patients with end stage renal disease.
Authors: C G Winearls
Journal: BMJ (1983)

hormone: 2-3 U/I at 20 min and 2-5 U/I at 60 min.In addition, thyroxine concentration was low at 48 nmol/l (4 ug/100 ml) with inappropriately low thyroid stimulating hormone concentration (200 ,cg thyrotrophin releasing hormone test: thyroid stimulating hormone concentration at 0 min 2-4 mU/1, at 20 min 7-5 mU/i, and at 60 min 8-3 mU/l), the prolactin was slightly raised (200 ug thyrotrophin releasing hormone test: prolactin at 0 min 810 mU/l, at 20 min 1730 mU/1, and at 60 min 1240 mU/l).Cortisol showed no diurnal rhythm-midnight 63 nmol/l (2 ,ug/100 ml), 0800 68 nmol/l (2-5 ug/100 ml)-and a very poor response to hypoglycaemia (peak 280 nmol/l (10 ,ug/100 ml)).Growth hormone showed no response to hypoglycaemia.Urine osmolality increased during a short water deprivation test (plasma 291 mmol (mosmol)/kg; urine 762 mmol/kg).These tests confirmed that the patient had panhypopituitarism with preservation of posterior pituitary function only.Computed tomography of the pituitary fossa showed some enhancing tissue just above the sella posteriorly, and suprasellar cisternography showed a small rounded midline filling defect just anterior to the superior aspect of the dorsum sellae.These radiological studies showed a small midline mass just anterior to the tip of the dorsum sellae occupying the position of the pituitary stalk, suggesting the presence of a small hypothalamic tumour, probably a craniopharyngioma.There were no clinical features or investigation results to suggest a granulomatous or metastatic disease process.
TCT-627 Does direct DES stenting reduces restenosis; a randomized comparison of direct stent implantation to stenting with predilation or provisional stenting in elective PCI patients
Authors: Samer Somi, Wouter Remkes, Jan-Henk Dambrink, Marcel Gosselink, Jan Hoorntje, Harry Suryapranata, Jan Paul Ottervanger, Arnoud van 't Hof
Journal: Journal of the American College of Cardiology (2012)
Inhaled steroids in exacerbations of COPD
Authors: A. Singh
Journal: European Respiratory Journal (2007)

To the Editors: 

I read with interest the recent article by Gunen et al . 1, wherein the authors presented the hypothesis that nebulised budesonide might be an alternative to systemic corticosteroids in the treatment of patients with exacerbations of chronic obstructive pulmonary disease (COPD). There are certain points which need discussing regarding their hypothesis of nebulised inhaled corticosteroids in COPD exacerbations.

First, exacerbations of COPD were considered to be a purely local disease: there is now enough evidence to support …
Moses Maimonides' treatise on asthma.
Authors: F Rosner
Journal: Thorax (1981)

This paper contains an analysis and appreciation of one of Moses Maimonides9 authentic medical works, his Treatise on Asthma. After a brief biographical section, passages from the work are cited and analysed to illustrate the approach of this medieval physician who organised the knowledge of Greeks and others who preceded him. Maimonides presents a logical and systematic approach to the prevention, diagnosis, and treatment of disease, an approach which is clearly evident in his Treatise on Asthma.
Preventive Therapy for Tuberculosis in HIV Infection
Authors: Timothy F. Brewer
Journal: JAMA (1999)

Objective To determine whether preventive treatment for
				tuberculosis in adults infected with HIV reduces the frequency of
				tuberculosis and overall mortality.
			Design Systematic review and data synthesis of randomised placebo
				controlled trials.
			Main Outcome Measures Active tuberculosis, mortality, and adverse
				drug reaction requiring cessation of the study regimen. Outcomes
				stratified by status of purified protein derivative skin test.
			Results Four trials comprising 4055 adults from Haiti, Kenya, the
				United States, and Uganda were included. All compared isoniazid (6-12
				months) with placebo, and one trial also compared multidrug treatment
				for 3 months with placebo. Mean follow up was 15-33 months. Overall,
				frequency of tuberculosis (relative risk 0.57, 95% confidence interval
				0.41 to 0.79) was reduced in those receiving preventive treatment
				compared with placebo: mortality was not significantly reduced (0.93,
				0.83 to 1.05). In subjects positive for purified protein derivative
				receiving preventive treatment, the risk of tuberculosis was reduced
				substantially (0.32, 0.19 to 0.51) and the risk of death was reduced
				moderately (0.73, 0.57 to 0.95) compared with those taking placebo. In
				adults negative for purified protein derivative receiving preventive
				treatment, the risk of tuberculosis (0.82, 0.50 to 1.36) and the risk
				of death (1.02, 0.89 to 1.17) were not reduced significantly. Adverse
				drug reactions were more frequent, but not significantly so, in
				patients receiving drug compared with placebo (1.45, 0.98 to 2.14).
			ConclusionsPreventive treatment given for 3-12 months protects
				against tuberculosis in adults infected with HIV, at least in the short
				to medium term. Protection is greatest in subjects positive for
				purified protein derivative, in whom death is also less frequent. Long
				term benefits remain to be shown.
Complement component profiles in urticaria, dermatitis herpetiformis, and alopecia areata
Authors: L. BERRENS, E. JANKOWSKI, I. JANKOWSKI-BERNTSEN
Journal: British Journal of Dermatology (1976)

Insignificant variation was noted in the mean levels of the complement components C1q, C4, C2, C3, C5 and C3PA between various groups of sera from patients with urticaria, angio‐oedema, dermatitis herpetiformis, alopecia areata, or hay fever. No deficiencies were found. Elevated C9 levels in chronic urticaria and angio‐oedema refiected its nature as an acute phase protein. The assessment of C com‐ponents in single or sequential serum samples revealed only marginal variations. Similar results were recorded for plasminogen and the immunoglobulins G, A and M. Some evidence is provided for the primary involvement of the kallikrein‐kinin system in urticaria.
Abstract 559: Human ovarian cancer mesenchymal stem cells demonstrate abnormal BMP signaling and promote tumorigenesis
Authors: Ronald J. Buckanovich, Karen McLean, Ines Silva, Yusong Gong, Kathryn Pennington
Journal: Cancer Research (2010)

Abstract Numerous recent reports indicate a critical role for MSC in solid tumor growth. Unfortunately, very little is known about human solid tumor associated MSC. We analyzed over 15 samples of primary ovarian tumors for the presence MSC. MSC were isolated from over 90% of these samples. These cells had the morphologic appearance of CFU-F (colony forming unit-fibroblastic), a normal karyotype, and were non-tumorigenic. Phenotypic characterization of these cells indicates they express the surface markers normally associated with MSC; they express traditional MSC markers including SH2, SH3, and CD90, and do not express hematopoietic markers such CD34, CD14, or CD4. Functional characterization demonstrates that these cells are multipotent, capable of differentiating into adipose, cartilage, and bone. However, ovarian cancer-derived MSC appear to be somewhat less efficient at differentiation than the healthy donor control MSC. When combined with tumor cells in immune deficient mice, the promotion of tumor growth by ovarian cancer associated MSC was significantly greater than that seen with healthy donor control MSC. Gene expression analysis demonstrated that cancer associated MSC have significantly altered BMP family member expression. These studies suggest that cancer associated MSC are unique from their healthy tissue associated counterparts and play a critical role in cancer cell growth. 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 559.
Abstract 4941: A humanized bone model for preclinical monitoring of prostate cancer lesions by intravital multiphoton microscopy
Authors: Eleonora Dondossola, Stephanie Alexander, Steve Alexander, Boris M. Holzapfel, Christopher J. Logothetis, Dietmar W. Hutmacher, Peter Friedl
Journal: Cancer Research (2014)

Abstract Bone metastases are the initial site of progression and account for many of the complications experienced by men with metastatic prostate cancer (PCa), including resistance to therapy. The purpose of our study is to determine whether intravital multiphoton microscopy (iMPM) integrated with a novel mouse model can better inform clinical development of molecular therapeutics targeting bone metastases. iMPM can overcome limitations of existing models by monitoring the dynamic reciprocal cell-cell interplay at the center of PCa bone metastasis. To study PCa-stromal cell interactions and therapy response in bone, we established a humanized neo-bone in the mouse dermis, using grafted electrospun polycaprolactone scaffolds functionalized with human mesenchymal stem cells differentiated to osteoblasts. After in vivo maturation, bone scaffolds served for co-implantation of human fluorescent PCa cells (PC3) followed by multi-parameter iMPM through a body window, including: collagen and bone matrix (second harmonic generation), mineralized matrix (calcein blue), osteoblasts (H2B/mCherry in human mesenchymal stem cells), adipocytes and bone surface (third harmonic generation), blood vessels, stromal phagocytes and osteoclasts (fluorescence-labeled dextran), and PC3 cells (nuclear H2B eGFP with cytoplasmatic DsRed2). Using multi-parameter 3D reconstruction, tumor growth and invasion, reactive remodeling of the stroma and neovessel organization were monitored longitudinally, providing a baseline for evaluating preclinical disease and therapy response. The model provides new insight into PCa bone metastases and will be used to more efficiently develop and prioritize biologically founded therapy for clinical development. Citation Format: Eleonora Dondossola, Stephanie Alexander, Steve Alexander, Boris M. Holzapfel, Christopher J. Logothetis, Dietmar W. Hutmacher, Peter Friedl. A humanized bone model for preclinical monitoring of prostate cancer lesions by intravital multiphoton microscopy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4941. doi:10.1158/1538-7445.AM2014-4941
Interpretation of Electronically Determined Macrocytosis
Authors: PETER McPHEDRAN
Journal: Annals of Internal Medicine (1973)

Macrocytosis identified by electronic erythrocyte sizing equipment is clinically significant whether anemia is present or not. Half of all patients with marked macrocytosis (mean corpuscular volume of 115 µm3 or greater) identified in a hospital hematology laboratory had deficiency of folic acid or vitamin B12, or both, as defined by erythrocyte folate and plasma B12 measurements. The proportion of deficient patients increased with increasing degrees of macrocytosis. Of patients without deficiency, half had liver disease or alcoholism with probable liver disease. Screening patients with marked macrocytosis for deficiency of folic acid and vitamin B12 has a high diagnostic yield and has become a routine procedure in our laboratory.
The Medical Directive
Authors: Susan Nobel
Journal: JAMA (1990)

To the Editor.—  Drs Emanuel and Emanuel 1 have proposed a new medical directive that attempts to combine all aspects of terminal care in a single document. The Medical Directive has been proposed as an answer to limitations of the living will. The authors cite the rarity with which the living will is used in clinical practice, potential vagueness in terminology that could lead to problems of interpretation, and the fact that many patients sign living wills without involving their physicians. The proposed medical directive certainly goes some distance to ensure specificity in the signer's instructions, but it is difficult to see how such a document would solve the major problem—that the majority of people today simply do not make advance provision for health care decision making. If anything, the complexity of the proposed replacement could further discourage wide use.  Our experience as a patient advocacy organization confirms the fact
Hepatitis B virus X protein enhances the transcriptional activity of the androgen receptor through c-Src and glycogen synthase kinase-3β kinase pathways
Authors: Wan-Jen Yang, Ching-Ju Chang, Shiou-Hwei Yeh, Wei-Hsiang Lin, Sheng-Han Wang, Ting-Fen Tsai, Ding-Shinn Chen, Pei-Jer Chen
Journal: Hepatology (2009)

Abstract Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) occurs predominantly in men. By enhancing the transcriptional activity of the androgen receptor (AR) gene in a ligand-dependent manner, the HBV X protein (HBx) might contribute to this disparity between sexes. To dissect the mechanisms underlying HBx-enhanced AR transactivation, we investigated the effect of HBx on two critical steps in the regulation of ligand-stimulated AR activities. One step is the dimerization of AR (through the interaction of its N-termini and C-termini), and the other step is the activation of the AR N-terminal transactivation domain (NTD). HBx increased the NTD activation of the AR through c-Src kinase. HBx also enhanced AR dimerization by inhibiting glycogen synthase kinase-3β (GSK-3β) activity, which acts as a negative regulator of the interaction between AR and the N-termini and C-termini. The HBx-enhanced AR transactivation was abolished by blocking c-Src and activating GSK-3β kinases simultaneously, suggesting that these two kinases act as major switches in the activation process. The regulatory function of both kinases has been further verified in primary hepatocytes isolated from the livers of HBx transgenic male mice. Conclusion: Our study thus identified two key kinases through which HBx enhances the AR transcriptional activity. These kinases might be potential candidates for future prevention or therapy for HBV-related HCC in men. (Hepatology 2009.)
Edinburgh Emergency Asthma Admission Service: report on 10 years' experience.
Authors: G K Crompton, I W Grant, P Bloomfield
Journal: BMJ (1979)

In December 1968 an emergency service was begun in Edinburgh to expedite admission to hospital of patients with severe acute asthma. During the first 10 years requests were made to admit 112 patients to a respiratory unit with provision for intensive care on 360 occasions. Four of the patients died of their disease, one in hospital and three before admission. It was thought that the death rate would have been much higher had conventional admission procedures been observed. Owing to ethical objections to a controlled trial it was not possible to obtain substantive proof that the service reduced deaths from asthma. Nevertheless, there was strong circumstantial evidence that organised facilities for the immediate admission to hospital of patients with a history of life-threatening attacks would result in fewer deaths at home. Earlier admission also apparently reduced hospital mortality and the number of patients requiring tracheal intubation and mechanical ventilation. It is concluded that there is a prima facie case for an emergency asthma admission serivce similar to that operating in Edinburgh to be established in all cities and large towns.
Pharmacology for the Preoperative Visit
Authors: Leroy D. Vandam
Journal: JAMA (1969)

The seasoned editor or programmer realizes the importance of bestowing a provocative title on a book or lecture. With this approach the prospective reader or listener is thereby subconsciously impelled to look inside or at least to listen at first. J. S. Gravenstein intrigued me with the title given this volume. I trust that the phrasing was purposely enigmatic rather than accidentally abstruse. How far did he plan to go beyond obvious consideration of preanesthetic medication? The answer is that he has ranged far, bringing in specialists from other fields of medicine with a nonanesthetic outlook and encouraging them to write as if discussing their particular problems during a bedside consultation. It is not possible to present detailed criticism of each chapter in a review of this span. Moreover, as a reviewer I have tried to bear in mind the backgrounds and needs of the majority of physicians who might
ATRIAL HIGH RATE EPISODES AND ATRIAL FIBRILLATION BURDEN: ASSOCIATION WITH LEFT ATRIAL/VENTRICULAR FUNCTION AND REMODELING
Authors: Chee W. Khoo, Suresh Krishnamoorthy, Girish Dwivedi, Balu Balakrishnan, Gregory Y. Lip, Hoong S. Lim
Journal: Journal of the American College of Cardiology (2011)
RESECTION OF TWO INCHES OF THE HUMERUS AND WIRING, WITH A REPORT OF A CASE OF WIRING OF THE CLAVICLE FOR UNUNITED FRACTURE.
Authors: STEWART L. McCURDY
Journal: JAMA (1896)

It is a matter of selection, after excision of joints or resection of bones, whether nails are selected to secure the bones, or whether wire is used. Possibly I am stating the facts, when the statement is made that the majority of surgeons prefer spikes to wire. Especially is this true for excisions of the knee. It is not the adaptation of bones after excisions for chronic tubercular disease, I desire to consider, but rather the use of wire for the treatment of compound and irreducible fractures. That it is possible for me to secure a more perfect adaptation of bones by the use of wire goes without further discussion. That other operators can not get as perfect results with wire and use spikes instead, also goes with saying. Whether these men have tried wiring and discarded it for the nails, I am unable to say. To attempt to do
Mutations in RPE65 cause Leber's congenital amaurosis
Authors: Françoise Marlhens, Corinne Bareil, Jean-Michel Griffoin, Eberhart Zrenner, Pierre Amalric, Claudie Eliaou, Su-Yan Liu, Eddie Harris, T. Michael Redmond, Bernard Arnaud, Mireille Claustres, Christian P. Hamel
Journal: Nature Genetics (1997)
The Nomogram Epidemic: Resurgence of a Medical Relic
Authors: David A. Grimes
Journal: Annals of Internal Medicine (2008)

The obsolete calculators known as nomograms have become epidemic in recent medical literature. The frequency of articles in PubMed retrieved with this search term nearly doubled between 1990 to 1999 and 2000 to 2007. Popular in medicine from about 1925 to 1975, a nomogram is a crude graphical means for solving an equation by placing a straightedge across several scales. Today, most reported nomograms are inconsistent with both established definitions and half a century of clinical use. The need for nomograms disappeared with the advent of personal computing. Instead of constructing nomograms, authors should develop software, such as prediction models, that can either be downloaded to personal digital assistants or be used on the Internet. Modern computing features both accuracy and speed; nomograms offer only the latter.