tbuckley/cabot-search huggingface dataset:
Abstract 520: Inhibition of uPAR and uPA reduces invasion and degradative potential in papillary thyroid carcinoma cells
Authors: Theodore S. Nowicki, Nicolas T. Kummer, Codrin Iacob, Nina Suslina, Augustine Moscatello, Stimson Schantz, Steven Schaefer, Edward Shin, Raj K. Tiwari, Jan Geliebter
Journal: Cancer Research (2010)

Abstract Papillary thyroid cancer (PTC) is the most prevalent endocrine and thyroid malignancy. The ability of PTC to invade and migrate great distances contributes to distant metastases, which represent the most common cause of PTC-related death. The urokinase plasminogen activator (uPA) and the urokinase plasminogen receptor (uPAR) are key mediators of tumor invasion. Upon binding to uPAR, pro-uPA is converted to its active form, which is then capable of cleaving plasminogen to plasmin. Plasmin can then degrade components of the basement membrane and extracellular matrix, a prerequisite for tumor cell invasion and metastasis. The binding of uPA by uPAR also seems to mediate several signaling events that contribute to a migratory phenotype, as well as various growth signals. In this study, we analyzed uPA and uPAR expression in PTC and normal thyroid tissue, and examined in vitro how uPA and uPAR contribute to an invasive/metastatic phenotype, as well as the functional consequences of inhibiting this system. uPA and uPAR RNA were also significantly higher in patients with metastatic disease. Casein-plasminogen zymography and western blotting demonstrated increased active uPA secreted by BCPAP cells compared to NTHY-Ori-3-1. Fluorimetric assays revealed that BCPAP CM was able to activate plasminogen, resulting in measureable casein hydrolysis. This casein hydrolysis was prevented by the addition of several specific uPA inhibitors. The in vitro invasion phenotype of BCPAP cells was augmented by the addition of plasminogen, and this augmentation was reversed by inhibitory anti-uPA and anti-uPAR antibodies. Cells transfected with siRNA against uPAR demonstrated decreased migratory and invasive potentials as measured by Matrigel invasion assays. Finally, uPAR-knockdown cells exhibited decreased proliferation when compared to non-targeting siRNA transfectant cells. These data provide new functional evidence of the uPA/uPAR system's role in PTC invasion/metastasis and demonstrate the attractiveness of uPA and uPAR as molecular biomarkers and therapeutic targets. 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 520.
A subepidermal blistering disease with histopathological features of dermatitis herpetiformis and immunofluorescence characteristcs of bullous pemphigoid: a novel subepidermal blistering disease or a variant of bullous pemphigoid?
Authors: W. SALMHOFER, Y. KAWAHARA, H.P. SOYER, H. KERL, T. NISHIKAWA, T. HASHIMOTO
Journal: British Journal of Dermatology (1997)

A 64-year-old man presented with a bullous eruption which clinically and histopathologically resembled dermatitis herpetiformis. However, direct immunofluorescence analysis showed IgG deposits at the basement membrane zone, indicating a relationship with bullous pemphigoid or epidermolysis bullosa acquisita. Indirect immunofluorescence studies on salt-split skin showed binding of IgG mainly on the dermal side of the blister. Immunoblot analysis revealed a novel 200 kDa dermal antigen that could be associated with a major pathogen in this blistering a disease. The histopathological similarity to dermatitis herpetiformis and the immunofluorescence findings indicating bullous pemphigoid or epidermolysis bullosa acquisita seem typical of a distinct subepidermal blistering disease characterized by this 200 kDa antigen. However, the pathogenetic role of autoantibodies against this antigen should be further elucidated before confirming whether this case represents a novel subepidermal blistering disease or a special variant of bullous pemphigoid.
Prolonged Half-life Following Diuretic Radionuclide Urography as Evidence of Ureteral Obstruction
Authors: Andrew Taylor, Richard Bedont, Rodney Raabe
Journal: Clinical Nuclear Medicine (1985)

Diuretic radionuclide urography is an accurate technique for detecting obstruction as a possible cause of nephroureteral dilatation. This technique was used to evaluate radioisotope retention in the renal pelvis noted on the bone scan of a patient with prostate carcinoma. There was some washout of the pelvic radioactivity following intravenous furosemide, but the half-life was markedly prolonged, allowing the correct diagnosis of partial obstruction to be made.
Predisposing Factors and Prognostic Value of Sustained Monomorphic Ventricular Tachycardia in the Early Phase of Acute Myocardial Infarction
Authors: Lluís Mont, Juan Cinca, Pedro Blanch, José Blanco, Jaume Figueras, Carlos Brotons, Jordi Soler-Soler
Journal: Journal of the American College of Cardiology (1996)
1015. Inhibition of Tumor Growth in Xenografted Nude Mice with Adenovirus-Mediated Endostatin Gene Comparison with Recombinant Endostatin Protein
Authors: Zhihui Liang, Wenlin Huang
Journal: Molecular Therapy (2005)

Top of pageAbstract
Background: Inhibition of endostatin has been shown to be an effective strategy in cancer therapy in mice. However, its widespread application has been hampered by difficulties in the large-scale production of the recombinant endostatin protein, long-term storage of bioactive protein, and the cumbersome daily administration. These limitations may be resolved by in vivo delivery and expression of the endostatin gene. In this study, we observe the effect and advantage of endostatin gene therapy mediated by a recombinant type5 adenoviral vector (Ad/hEndo) on the growth of hepatocellular carcinoma BEL-7402 xenografted tumors, comparison with recombinant endostatin protein.

Methods: Hepatocellular carcinoma BEL-7402 cells were inoculated subcutaneously in the flank of Balb/c nude mice. Nine days after tumor cell inoculation, animals were given a cycle of four courses of intra-tumoral injections of Ad/hEndo of 5 |[times]| 108 pfu (low-dose group) and 1 |[times]| 109 pfu (high-dose group) at intervals of six days, respectively. Recombinant human endostatin protein (rhEndo) was administrated daily subcutaneously at a dose of 10 mg.kg|[minus]|1.day|[minus]|1 at a site nearby the tumor for ten days. The expression of endostatin mRNA in tumor tissue was analyzed by RT-PCR after Ad/hEndo injection in testing animals. Dynamic changes of concentration of endostatin protein in tumor tissue were quantitated by enzyme-linked immunosorbent assay (ELISA).

Results: After 4 courses of treatment, the growth of treated tumors of high-dose treated group which received 1 |[times]| 109 pfu of Ad/hEndo were inhibited by 42.26% compared with the Ad/LacZ control group (P=0.001) and by 46.26% compared with the NIH buffered control group (P=0.003), respectively. However, in this study, Ad/hEndo at low dose of 5 |[times]| 108 pfu failed to demonstrate significant inhibition of tumor growth, compared with control groups. After daily administration of recombinant human endostatin protein (rhEndo) for 9 days, the ratio of T/C (rhEndo group versus PBS group) was less than 47%. However, two days after rhEndo treatment ceased, the ratio of T/C was more than 50%.

The peak of expression of endostatin mRNA in tumor tissue was at 2 or 3 days after administration intratumorally with Ad/hEndo and gradually dropped undetectable by day 7. Dynamic analysis of endostatin concentration in tumor tissue showed that the highest level of mRNA is up at third day after injection, and dropped to basal level three weeks later.

Conclusion: Endostatin gene therapy mediated by a recombinant adenoviral vector had significantly inhibited the growth of hepatocellular carcinoma BEL-7402 xenografted tumors at a high dose of 1 |[times]| 109 pfu compared with other groups. The analysis of dynamic expression of endostatin in vivo indicated that Ad/hEndo had acquired a high-level, relatively long-term expression in vivo and bioactivity capability.
TUBERCULAR MENINGITIS.REPORT OF THREE CASES.
Authors: WILLIAM FITCH CHENEY
Journal: JAMA (1905)

To the physician who sees much of disease in children, tubercular meningitis is a specter that forever haunts the scene. Sometimes we fail to observe it as it lurks in the shadow, not yet ready to declare itself openly; more often, perhaps, we imagine we see it hovering over our patient, when subsequent developments prove we were deluded. How to recognize this evil spirit, so that we may know from the beginning with what we are contending, is a problem worthy of our utmost effort; and it is to this that I wish to direct your attention. During 1904 I saw three cases of tubercular meningitis, an account of which will serve to emphasize the difficulties in the way of making a diagnosis and the steps to be taken to overcome them. <h3>Case 1.</h3> —A boy, aged 3, always previously well, was taken by his parents to Los Angeles early in January, 1904.
Condoms and the Prevention of AIDS
Authors: G. Y. Minuk
Journal: JAMA (1986)

<h3>To the Editor.—</h3> In the April 4 issue of<i>JAMA</i>, Conant et al<sup>1</sup>indicate that commercial condoms, including those derived from sheep intestinal membranes (natural condoms), are effective in preventing the in vitro transmission of retrovirus infection.<sup>1</sup>Their conclusion is based on experiments in which condoms containing a solution of either mouse retrovirus or acquired immunodeficiency syndrome-associated retrovirus were fit over the plunger of a 12-mL plastic syringe, reinserted inside syringe barrels, and submerged in a beaker containing sterile culture media. After repeated aspirations and expulsions the authors found the beaker culture media to be free of retrovirus. In a somewhat similar series of experiments addressing the issue of hepatitis B virus infection, we reported that, while synthetic condoms do indeed prevent leakage of iodine 125-labeled hepatitis B surface antigen (HBsAg), natural condoms do not.<sup>2</sup> There are a number of possible explanations for the apparent discrepancy between
Humanitarianism Under the Gun
Authors: Victoria L. Sharp
Journal: JAMA (1997)

The call came at 5:30 AM on Sunday, January 19. The unthinkable had happened: our humanitarian mission in Rwanda had been attacked. Three volunteers were shot and killed, and our project director was severely injured.<sup>1</sup> The mission, in place just 3 weeks, was providing medical services to health clinics in the town of Ruhengeri, home to thousands of newly returning refugees. It was a US project, sponsored by Doctors of the World and affiliated with the French organization Médecins du Monde. Four armed men forced their way into the Doctors of the World compound, demanded passports and papers, and without warning, opened fire with a machine gun. A doctor, a nurse, and a logistician, volunteers from Spain, were shot in the head and died immediately. The US volunteer, Nitin Madhav, dived under a table but was nonetheless wounded in the leg. He reacted with remarkable presence of mind: unable
Scintigraphic Evaluation of Pamidronate and Corticosteroid Therapy in a Patient with Progressive Diaphyseal Dysplasia (Camurati-Engelmann Disease)
Authors: TSUTOMU INAOKA, NORIYUKI SHUKE, JUNICHI SATO, YUKIO ISHIKAWA, KOJI TAKAHASHI, TAMIO ABURANO, YOSHIO MAKITA
Journal: Clinical Nuclear Medicine (2001)

A 27-year-old woman with progressive diaphyseal dysplasia (Camurati-Engelmann disease) received pamidronate and corticosteroid therapy for bone pain. During therapy, disease activity was assessed serially using bone scintigraphy with Tc-99m HMDP. With pamidronate administration, the bone pain became worse and diaphyseal uptake of Tc-99m HMDP increased, whereas corticosteroid administration improved the bone pain and reduced the diaphyseal uptake. In this case, pamidronate and corticosteroid produced different effects. Bone scintigraphy allowed an objective assessment of the response to these treatments, accurately reflecting clinical symptoms.
Simultaneous presentation of upper lobe fibrobullous disease and spinal pseudarthrosis in a patient with ankylosing spondylitis.
Authors: M Hakala, E Kontkanen, O Koivisto
Journal: Annals of the Rheumatic Diseases (1990)

A 51 year old man with a 20 year history of ankylosing spondylitis and pronounced thoracic gibbus presented with two simultaneous complications of longstanding ankylosing spondylitis, upper lobe fibrobullous disease, and spinal pseudarthrosis. No neurological sequelae developed and treatment was conservative. Both these lesions mimic tuberculosis, and so it is important to determine them accurately to avoid unnecessary antituberculosis treatment. Both of these complications are reported to occur in longstanding ankylosing spondylitis and their simultaneous presentation may be more common than is realised. This case is believed to be the first such report of their association.
Ban the bottle
Authors: J. Nelson
Journal: BMJ (1997)

<h3>Abstract</h3> The study aims to determine the shared genetic architecture between COVID-19 severity with existing medical conditions using electronic health record (EHR) data. We conducted a Phenome-Wide Association Study (PheWAS) of genetic variants associated with critical illness (n=35) or hospitalization (n=42) due to severe COVID-19 using genome-wide association summary from the Host Genetics Initiative. PheWAS analysis was performed using genotype-phenotype data from the Veterans Affairs Million Veteran Program (MVP). Phenotypes were defined by International Classification of Diseases (ICD) codes mapped to clinically relevant groups using published PheWAS methods. Among 658,582 Veterans, variants associated with severe COVID-19 were tested for association across 1,559 phenotypes. Variants at the <i>ABO</i> locus (rs495828, rs505922) associated with the largest number of phenotypes (n<sub>rs495828</sub>= 53 and n<sub>rs505922</sub>=59); strongest association with venous embolism, odds ratio (OR<sub>rs495828</sub> 1.33 (p=1.32 × 10<sup>−199</sup>), and thrombosis OR<sub>rs505922</sub> 1.33, p=2.2 x10<sup>−265</sup>. Among 67 respiratory conditions tested, 11 had significant associations including <i>MUC5B</i> locus (rs35705950) with increased risk of idiopathic fibrosing alveolitis OR 2.83, p=4.12 × 10<sup>−191</sup>; <i>CRHR1 (</i>rs61667602) associated with reduced risk of pulmonary fibrosis, OR 0.84, p=2.26× 10<sup>−12</sup>. The <i>TYK2</i> locus (rs11085727) associated with reduced risk for autoimmune conditions, e.g., psoriasis OR 0.88, p=6.48 x10<sup>−23</sup>, lupus OR 0.84, p=3.97 × 10<sup>−06</sup>. PheWAS stratified by genetic ancestry demonstrated differences in genotype-phenotype associations across ancestry. <i>LMNA</i> (rs581342) associated with neutropenia OR 1.29 p=4.1 × 10<sup>−13</sup> among Veterans of African ancestry but not European. Overall, we observed <b>a</b> shared genetic architecture between COVID-19 severity and conditions related to underlying risk factors for severe and poor COVID-19 outcomes. Differing associations between genotype-phenotype across ancestries may inform heterogenous outcomes observed with COVID-19. Divergent associations between risk for severe COVID-19 with autoimmune inflammatory conditions both respiratory and non-respiratory highlights the shared pathways and fine balance of immune host response and autoimmunity and caution required when considering treatment targets.
Regulation of Animal Experimentation-Reply
Authors: Bruce D. Sales
Journal: JAMA (1986)

<h3>In Reply.—</h3> Dresser makes a number of assertions that are generally already covered in our examination of the regulation of animal experimentation. However, we think it is necessary to respond to several of her comments because they illustrate a more general failure on the part of Dresser and others to understand and appreciate the real issues and interests that are at the heart of this controversy. We take strong exception to Dresser's statement that we see no legitimate reason for the current debate over animal experimentation. In fact, we quite clearly recognize that "few would argue that animal rights advocates have certain concerns that must be seriously addressed by the scientific community." The point that we make repeatedly is that recent proposals for additional regulation are<i>not</i>satisfactory means to address these concerns. Thus, our attitude is hardly a serious threat to biomedical research. On the contrary, we believe that
Clinical pharmacology and antiarrhythmic efficacy of encainide in patients with chronic ventricular arrhythmias.
Authors: R A Winkle, F Peters, R E Kates, C Tucker, D C Harrison
Journal: Circulation (1981)

We determined the pharmacokinetics, efficacy and therapeutic plasma concentration of encainide, a new antiarrhythmic drug that affects His-Purkinje conduction but not ventricular refractoriness. Nine patients with frequent and complex premature ventricular complexes were studied in a 3-day double-blind protocol. Each day, each patient received 75 mg of i.v. or oral encainide or placebo. Frequent blood samples for encainide plasma concentration determination and continuous ambulatory ECGs were obtained. There was a marked intersubject variation in bioavailability (mean 42 +/- 24%, range 7.4-82%), clearance (13.2 +/- 5.6 ml/min/kg, range 3.75-22.1 ml/min/kg) and half-life (3.4 +/- 1.7 hours i.v., 2.5 +/- 0.8 hours oral). Eight of nine patients had more than 90% suppression of premature ventricular complexes for 3-36 hours. Minimal antiarrhythmic plasma concentration was higher (39 +/- 54 ng/ml, range 3.5-170 ng/ml) after i.v. dosing than after oral dosing (14 +/- 16 ng/ml, range 1.5-48 ng/ml), suggesting an active metabolite after oral dosing in many patients. Minimal side effects were seen despite high peak plasma concentrations (range 794-1556 ng/ml i.v., 36-495 ng/ml oral). The minimal ratio of toxic to therapeutic plasma concentration ranged from 4.3-326 (median 23) after oral dosing. Antiarrhythmic action was associated with an 11-44% widening of the QRS complex that was not associated with other adverse effects. We conclude that encainide effectively suppresses ventricular arrhythmias. Despite a variable bioavailability, high clearance and short half-life, its wide ratio of toxic to therapeutic concentration and probable active metabolite permit a long duration of action, which should allow a reasonable dose schedule in most patients during chronic oral dosing.
Experimental PVC Material Challenge in Subjects with Occupational PVC Exposure
Authors: Anneli Tuomainen, Harri Stark, Markku Seuri, Maija-Riitta Hirvonen, Markku Linnainmaa, Anne Sieppi, Hannu Tukiainen
Journal: Environmental Health Perspectives (2006)

Polyvinyl chloride (PVC) materials have been linked to asthma in several epidemiologic studies, but the possible causal factors remain unknown.We challenged 10 subjects experimentally to degraded PVC products under controlled conditions. All of the subjects had previously experienced respiratory symptoms suspected to be caused by this kind of exposure in their work place. Five subjects had doctor-diagnosed asthma.The subjects were exposed to degraded PVC material in an exposure chamber ; a challenge with ceramic tile was used as the control test. We followed exhaled nitric oxide, nasal NO, lung functions, cytokines [tumor necrosis factor-alpha (TNF-alpha) , interleukin-4 (IL-4) , IL-6, and IL-12] and NO in nasal lavage fluid (NAL) during and after the exposures. We also measured 2-ethylhexanol in exhaled breath samples and NAL.On the morning after the PVC exposure, subjects reported respiratory tract symptoms significantly more often than they did after the control test (50% vs. 0%, respectively ; p = 0.029 ; n = 10) . We did not detect any changes in lung functions or levels of exhaled NO, nasal NO, or NO in NAL after PVC challenge compared with the control test. Cytokine levels increased after both exposures, with no statistically significant difference between situations. All of the exhaled breath samples collected during the PVC exposure contained 2-ethylhexanol.PVC flooring challenge can evoke respiratory tract symptoms in exposed subjects. Our results do not support the hypothesis that PVC materials themselves evoke immediate asthmatic reactions. The chamber test used is well suited to this type of exposure study.
Radiology: A New Strategy For Searching The Shadows
Authors: W.J. Tuddenham
Journal: JAMA (1966)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Bailey and Love's Short Practice of Surgery
Authors: K. Robertson
Journal: BMJ (2008)

I love this book. I have a big, fat clothbound 1984 edition—there have been more since, but it is mine I love. I love everything about it, from its sheer weight to its extravagance. It was at the time the single most expensive thing I had ever bought. (I didn’t have a car.) I love the complete confidence it represented (it covered everything, without shame) and the beauty of studying a specialty in which a “short” practice manual had 1301 pages.

It didn’t actually take me very long—I read it, cover to cover—to realise that it was old fashioned and in the main …
Effects of hyperthermal stress on the ultrastructure of platelets with reference to the localization of platelet peroxidase and fibrinogen in vivo
Authors: Hitoshi Kurabayashi, Kazuo Kubota, Hitoshi Take, Kousei Tamura, Takuo Shirakura
Journal: American Journal of Hematology (1997)

Ultrastructure of platelets with the localization of platelet peroxidase and fibrinogen through 3-min 47°C hot-spring bathing was investigated in eight healthy volunteers. The mean sublingual temperature rose about 1.8°C 5 min after the start of bathing. The frequencies of fold, pseudopods, vacuoles, and centralization were increased after bathing. Platelet peroxidase activity was decreased after bathing. Furthermore, fibrinogen was decreased in α-granules after bathing. Thus, hyperthermal stress in vivo may activate platelets, resulting in consumption of platelet peroxidase and fibrinogen. Am. J. Hematol. 56:244–247, 1997. © 1997 Wiley-Liss, Inc.