tbuckley/cabot-search huggingface dataset:
Modified Foxp3 mRNA protects against asthma through an IL-10–dependent mechanism
Authors: Lauren E. Mays, Susanne Ammon-Treiber, Benedikt Mothes, Mohammed Alkhaled, Jennifer Rottenberger, Eva Sophie Müller-Hermelink, Melanie Grimm, Markus Mezger, Sandra Beer-Hammer, Esther von Stebut, Nikolaus Rieber, Bernd Nürnberg, Matthias Schwab, Rupert Handgretinger, Marco Idzko, Dominik Hartl, Michael S.D. Kormann
Journal: Journal of Clinical Investigation (2013)

Chemically modified mRNA is capable of inducing therapeutic levels of protein expression while circumventing the threat of genomic integration often associated with viral vectors. We utilized this novel therapeutic tool to express the regulatory T cell transcription factor, FOXP3, in a time- and site-specific fashion in murine lung, in order to prevent allergic asthma in vivo. We show that modified Foxp3 mRNA rebalanced pulmonary T helper cell responses and protected from allergen-induced tissue inflammation, airway hyperresponsiveness, and goblet cell metaplasia in 2 asthma models. This protection was conferred following delivery of modified mRNA either before or after the onset of allergen challenge, demonstrating its potential as both a preventive and a therapeutic agent. Mechanistically, FOXP3 induction controlled Th2 and Th17 inflammation by regulating innate immune cell recruitment through an IL-10–dependent pathway. The protective effects of FOXP3 could be reversed by depletion of IL-10 or administration of recombinant IL-17A or IL-23. Delivery of Foxp3 mRNA to sites of inflammation may offer a novel, safe therapeutic tool for the treatment of allergic asthma and other diseases driven by an imbalance in helper T cell responses.
The Prevalence of Bulimia nervosa in a Hungarian College and Secondary School Population
Authors: P Szabó, F Túry
Journal: Psychotherapy and Psychosomatics (1991)

A two-stage survey was conducted to determine the prevalence of bulimia and bulimic behavior in 2 Hungarian nonclinical samples. In the college sample 1.3% of females and 0.8% of males met DSM-III-R diagnostic criteria for bulimia nervosa. In the adolescent sample no bulimic subjects were found, weight control behaviors are infrequent, but the attitudinal antecedents of bulimia are present in females.
<i>In Vivo</i> Localization of 90Y and 177Lu Radioimmunoconjugates Using Cerenkov Luminescence Imaging in a Disseminated Murine Leukemia Model
Authors: Ethan R. Balkin, Aimee Kenoyer, Johnnie J. Orozco, Alexandra Hernandez, Mazyar Shadman, Darrell R. Fisher, Damian J. Green, Mark D. Hylarides, Oliver W. Press, D. Scott Wilbur, John M. Pagel
Journal: Cancer Research (2014)

Cerenkov radiation generated by positron-emitting radionuclides can be exploited for a molecular imaging technique known as Cerenkov luminescence imaging (CLI). Data have been limited, however, on the use of medium- to high-energy β-emitting radionuclides of interest for cancer imaging and treatment. We assessed the use of CLI as an adjunct to determine localization of radioimmunoconjugates to hematolymphoid tissues. Radiolabeled (177)Lu- or (90)Y-anti-CD45 antibody (Ab; DOTA-30F11) was administered by tail vein injection to athymic mice bearing disseminated murine myeloid leukemia, with CLI images acquired at times afterward. Gamma counting of individual organs showed preferential uptake in CD45(+) tissues with significant retention of radiolabeled Ab in sites of leukemia (spleen and bone marrow). This result was confirmed in CLI images with 1.35 × 10(5) ± 2.2 × 10(4) p/s/cm(2)/sr and 3.45 × 10(3) ± 7.0 × 10(2) p/s/cm(2)/sr for (90)Y-DOTA-30F11 and (177)Lu-DOTA-30F11, respectively, compared with undetectable signal for both radionuclides using the nonbinding control Ab. Results showed that CLI allows for in vivo visualization of localized β-emissions. Pixel intensity variability resulted from differences in absorbed doses of the associated energies of the β-emitting radionuclide. Overall, our findings offer a preclinical proof of concept for the use of CLI techniques in tandem with currently available clinical diagnostic tools.
Coronary anatomy and left ventricular function in the first 12 hours of acute myocardial infarction: the Western Washington Randomized Intracoronary Streptokinase Trial.
Authors: M L Stadius, C Maynard, J K Fritz, K Davis, J L Ritchie, F Sheehan, J W Kennedy
Journal: Circulation (1985)

The relationships among clinical variables, coronary anatomy, and left ventricular function during the early hours of acute myocardial infarction (AMI) were evaluated from data acquired in the Western Washington Intracoronary Streptokinase Trial. All patients had symptoms and electrocardiographic changes typical of AMI. All data were obtained before treatment with streptokinase. Mean time to catheterization was 4.1 hr after onset of symptoms. Coronary angiograms (n = 245) were analyzed for location of infarct-related occlusion and collateral flow to the infarct bed. Left ventricular ejection fraction and regional left ventricular function were quantitated in 227. Sixty-two percent of occlusions were in the most proximal segment of the involved coronary artery. Collateral circulation was seen in 42% overall, in 31% with left anterior descending artery (LAD) occlusion, and in 52% with right coronary artery (RCA) occlusion (p less than .005). Left ventricular ejection fraction was lowest and regional function was most abnormal in the group with proximal LAD occlusion. Hyperkinesis was present in 32%; in those with hyperkinesis, hyperkinetic segment length was longest in those with RCA or circumflex occlusion. Multivariate analysis identified proximal LAD occlusion as the factor most closely associated with left ventricular ejection fraction and with measures of left ventricular regional hypofunction. We conclude that (1) AMI is usually caused by occlusion or subtotal occlusion in the most proximal portion of the involved coronary artery, (2) collateral circulation is more frequent with RCA than with LAD occlusion, and (3) location of the infarct-related occlusion is the most important determinant of global and regional left ventricular function in the early hours of AMI.
Phospho-Dependent Functional Modulation of GABAB Receptors by the Metabolic Sensor AMP-Dependent Protein Kinase
Authors: Nobuyuki Kuramoto, Megan E. Wilkins, Benjamin P. Fairfax, Raquel Revilla-Sanchez, Miho Terunuma, Keisuke Tamaki, Mika Iemata, Noel Warren, Andrés Couve, Andrew Calver, Zsolt Horvath, Katie Freeman, David Carling, Lan Huang, Cathleen Gonzales, Edward Cooper, Trevor G. Smart, Menelas N. Pangalos, Stephen J. Moss
Journal: Neuron (2007)
Literature and Medicine: Contributions to Clinical Practice
Authors: Richard C. Horton
Journal: Annals of Internal Medicine (1995)

Letters15 December 1995Literature and Medicine: Contributions to Clinical PracticeRichard C. Horton, MBRichard C. Horton, MBThe Lancet, London, United KingdomAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-12-199512150-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Charon and colleagues [1] correctly draw attention to the rich value of a literary approach to the patient's history. A narrative-based perspective emphasizes the uniqueness of the clinical story and provides a humanistic bridge between the scientific practice and physicians' attempts to address the personal needs and anxieties of their patients. However, Charon and associates omit a further, and potentially equally important, contribution from literary studies; that is, critical theory as applied to the interpretation of clinical research, a discipline that I have called clinical hermeneutics [2].The "correct" interpretation of clinical research rests largely on understanding ...References1. Charon R, Banks JT, Connelly JE, Hawkins AH, Hunter KM, Jones AH, et al . Literature and medicine: contributions to clinical practice. Ann Intern Med. 1995;122:599-606. LinkGoogle Scholar2. Horton RC. Antihypertensive drugs: assessing the published results. In: Kendall MJ, Kaplan NM, Horton RC, eds. Difficult Hypertension: Practical Management and Decision-Making. London: Martin Dunitz; 1995:265-88. Google Scholar3. Rennie D. Reporting randomized, controlled trials. JAMA. 1995;273:1054-5. CrossrefMedlineGoogle Scholar4. Horton R. The rhetoric of research. BMJ. 1995;310:985-88. CrossrefMedlineGoogle Scholar5. Horton RC. Journals versus journalists. European Science Editing. 1995;54:3-7. Google Scholar Author, Article, and Disclosure InformationAffiliations: The Lancet, London, United Kingdom PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 December 1995Volume 123, Issue 12Page: 965KeywordsAnxietyEpidemiologyFallsHistory of medicineResearch and reporting methods Issue Published: 15 December 1995 CopyrightCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Effect of corticosteroids on post-intubation tracheal stenosis.
Authors: J Braidy, G Breton, L Clement
Journal: Thorax (1989)

A 57 year old patient presented with progressive tracheal stenosis two months after intubation. An intraluminal polypoid lesion was found at the site of the cuff of the endotracheal tube. It disappeared within five days of treatment with inhaled beclomethasone. Further improvement of forced expiratory and inspiratory flow occurred after systemic corticosteroid treatment, with resolution of peritracheal oedema. Topical and systemic corticosteroids may be useful in the management of early post-intubation tracheal stenosis.
Fat Absorption During Inhibition of Protein Synthesis: Studies of Lymph Chylomicrons
Authors: R. M. Glickman, K. Kirsch, K. J. Isselbacher
Journal: Journal of Clinical Investigation (1972)

The effect of protein synthesis inhibition on the absorption of oleic acid from micellar solution was studied in mesenteric lymph fistula rats. A micellar solution of oleic acid labeled with tracer doses of oleic acid-(14)C was administered by intraduodenal infusion to rats with indwelling mesenteric lymph cannulas. Protein synthesis was inhibited by intraperitoneal acetoxycycloheximide (ACH), 0.25 mg/kg, 1 hr before lipid infusion. Lymph chylomicrons labeled with oleic acid-(14)C were collected from control and protein inhibited animals at various times after lipid infusion and subjected to sucrose density gradient centrifugation to determine changes in size. In control animals there was a transient increase in chylomicron size during maximal triglyceride absorption; however, in protein-inhibited animals there was a marked and sustained increase in chylomicron size as late as 4 hr after lipid infusion. Triglyceride and phospholipid determinations on washed chylomicrons from both groups indicated a greater triglyceride/phospholipid ratio after protein synthesis inhibition supporting a greater chylomicron size. Electron microscopy of lymph from both groups further confirmed a markedly increased chylomicron size after protein synthesis inhibition. It is proposed that an increase in size conserves chylomicron surface components, i.e. apoprotein, during conditions of inhibition of protein synthesis. These studies clearly demonstrate that the intestinal inhibition of protein synthesis is associated with an increase in the size of intestinal lymph chylomicrons and support the concept that protein synthesis is important in the formation and transport of chylomicrons from the mucosal cell into the lymph.
Complications of ileal conduit diversion in adults with cancer followed up for at least five years.
Authors: D E Neal
Journal: BMJ (1985)

A total of 111 adults with malignant disease of the bladder were studied to determine the long term complications of ileal conduit diversion. Each patient had survived at least five years (mean 10 years) after cystectomy. At final follow up the radiological appearance of one or both kidneys had deteriorated in 50 (47%) of 107 patients: deterioration worsened significantly (p less than 0.01) with increasing duration of follow up. Eighteen patients (16%) developed biochemical evidence of impaired renal function, of whom four died of complications of renal failure. Bilateral upper tract dilatation was noted in 30 patients (28%), and in 21 its cause was obscure. Ten patients formed renal stones, and an additional 12 required further operations on the conduit or stoma. Despite the age of patients with bladder cancer and the poor prognosis of those with invasive tumours clinically important side effects were observed in a significant proportion of the long term survivors. Further efforts to determine the aetiology of upper tract dilatation in patients with an ileal conduit diversion are justified.
Validity of the 13C-caffeine breath test as a noninvasive, quantitative test of liver function
Authors: Gordon Jung-Hyuk Park, Peter Harry Katelaris, Brian D. Jones, Francis Seow, David George Le Couteur, Meng Chong Ngu
Journal: Hepatology (2003)

The properties of caffeine render it an ideal substrate for a quantitative test of liver function. The aim of this study was to determine whether the caffeine breath test (CBT) using orally administered 13 C–caffeine correlates reliably with plasma caffeine clearance and reflects varying degrees of liver dysfunction. The CBT was performed in 25 healthy controls; 20 subjects with noncirrhotic, chronic hepatitis B or C; and 20 subjects with cirrhosis. Plasma caffeine clearance was assayed simultaneously with the CBT in a cohort of these subjects. Over a broad range of caffeine clearances, the CBT exhibited a highly significant correlation with plasma clearance ( r = 0.85, P &lt; .001). Cirrhotic patients were characterized by significantly reduced CBT values (1.15 ± 0.75 Δ‰ mg -1 ) compared with controls (2.23 ± 0.76; P = .001) and hepatitic patients (1.83 ± 1.05; P = .04). There was a significant inverse relationship between the CBT and Child–Pugh score ( r = -.74, P = .002). The intraclass correlation coefficient between repeated CBTs in 20 subjects with normal and cirrhotic livers was 0.89. Although smoking was associated with an 86% to 141% increase in CBT in all groups, the CBT was able to distinguish control, hepatitic, and cirrhotic smokers (5.36 ± 0.82, 3.63 ± 1.21, and 2.14 ± 1.14, respectively, P = .001). Multivariate analysis revealed that only smoking ( P &lt; .001) and disease state ( P = .001) were significant predictors of the CBT. In conclusion, the 13 C–CBT represents a valid indicator of plasma caffeine clearance and correlates reproducibly with hepatic dysfunction.
Human platelet-mediated cytotoxicity against Toxoplasma gondii: role of thromboxane.
Authors: E C Yong, E Y Chi, T R Fritsche, W R Henderson
Journal: The Journal of Experimental Medicine (1991)

Human platelets, in the absence of antibody, are cytotoxic to tachyzoites of Toxoplasma gondii as determined by vital staining, transmission electron microscopy, and the failure of Toxoplasma to survive and replicate in mice after in vitro interaction of the organisms with platelets. Platelet to T. gondii ratios as low as 1:3 were toxic to the organisms with direct cell-cell contact essential for platelet-mediated cytotoxicity. Adherence of platelets to T. gondii and disruption of surface membranes and cytoplasmic contents of the organisms were observed ultrastructurally. Reactive oxygen species were not implicated in the platelet-mediated toxicity. The interaction of T. gondii with platelets resulted in a marked increase in thromboxane B2 (TXB2) production compared with that by unstimulated platelets. The cyclooxygenase inhibitors acetylsalicylic acid and indomethacin inhibited platelet-mediated cytolytic activity as did the selective TXA2 synthetase inhibitor dazmegrel, indicating a role for thromboxane in the platelet-induced cytotoxicity. Further, toxoplasmacidal activity was retained in the TXA2 synthetase-containing microsomal fractions of platelets disrupted by freezing and thawing; cytolytic activity was absent in microsome-depleted platelet supernatant fractions. Both the TXA2-generating platelet microsome system and a stable TXA2 analogue induced damage to the cellular membranes of the Toxoplasma as noted by transmission electron microscopy. These findings suggest that platelets may play a role in the host defense against Toxoplasma and that release of thromboxane may be important in this cytolytic process.
Recurrence and re-recurrence of gall stones after medical dissolution: a longterm follow up.
Authors: L D O'Donnell, K W Heaton
Journal: Gut (1988)

One hundred patients with radiolucent gall stones less than or equal to 1.5 cm in functioning gall bladders have received oral bile acid dissolution therapy since 1975. Complete data are available on 93 who have received at least six months' treatment. The complete dissolution rate in appropriately selected patients who complied with and tolerated an adequate course of treatment was 55%. By life table analysis the recurrence rates were 13% at one year, 21% at two years, 31% at three years, and 43% at four years. Thereafter the recurrence rate levelled out, being 49% at 11 years. Redissolution was achieved in all seven patients who had a second course of therapy, but was usually followed by re-recurrence. Patients whose gall stones recurred did not differ significantly from those who remained stone free with respect to age, sex, body weight, or time required for dissolution.
Efficacy of Peripheral Vascular Surgery-Reply
Authors: D. Craig Miller
Journal: JAMA (1979)

The plangent commentary by Dr Fisch that pertains to our essay concerning the lack of prospective, randomized, and controlled clinical studies on the efficacy of peripheral vascular reconstructive surgery is timely and commendable. Dr Fisch excludes surgery for abdominal aortic aneurysm from his comments, based on the belief that the "dismal course of the untreated disease appears to be well documented." The efficacy of surgical treatment of abdominal aortic aneurysms, however, is assumed only by inference from natural history studies. To my knowledge, no controlled, prospective clinical studies on this subject have been performed. This is also true for most other peripheral vascular surgical procedures, with the exception of carotid endarterectomy stenosis. It is unlikely that such will be carried out in the future, principally because of the heterogeneity of the disease process (atherosclerosis), which precludes strict stratification of patients and accurate indexing of most patient-related variables, excluding
Influence of viability on canine allograft heart valve structure and function
Authors: D. J. WHEATLEY, C. G. A. McGREGOR
Journal: Cardiovascular Research (1977)

A study was undertaken to determine whether, in antibiotic sterilised and stored valves, the state of preimplantation leaflet viability could be shown to influence valve structure and function following isotopic allotransplantation in dogs. Fourteen viable and 12 nonviable valves were assessed after periods of up to 8 weeks' implantation. Assessment of valve structure was made macroscopically with measurement of leaflet surface areas, and microscopically. Pressure measurements were made across the allografted valve both at insertion and at removal. The results of this study indicate that preimplantation viability results in gross valve leaflet distortion and shrinkage with consequent loss of function. Nonviable valves, in contrast, showed minimal alteration in valve dimensions with retention of normal function. These findings have considerable implications in the preparation and clinical use of allograft heart valves.
Airway Inflammation after Cessation of Exposure to Agents Causing Occupational Asthma
Authors: Karim Maghni, Catherine Lemière, Heberto Ghezzo, Wu Yuquan, Jean-Luc Malo
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Subjects with occupational asthma (OA) generally present asthma symptoms and airway hyperresponsiveness after cessation of exposure. We hypothesized that they are also left with airway inflammation. We assessed 133 subjects with OA at a mean interval of 8.7 years (0.5-20.8 years) after cessation of exposure by questionnaire, airway caliber, and responsiveness to methacholine. Satisfactory samples of induced sputum were obtained from 98 subjects. We defined three groups of subjects: (1) cured: normalization of the concentration of methacholine provoking a 20% decrease in FEV1 (PC20), (2) improved: increase in PC20 by 3.2-fold or more but PC20 still abnormal, and (3) not improved: no significant change in PC20. In all, 9/28 subjects (32.1%) with no improvement versus 6/56 (10.7%) subjects with partial and complete improvements had sputum eosinophils equal to or greater than 2% and 11/28 (39.3%) subjects versus 11/56 (19.6%) subjects showed sputum neutrophils equal to or greater than 61%. Levels of interleukin-8 and of the neutrophil-derived myeloperoxidase were significantly more elevated in sputum of subjects with no improvement. Those in the cured or improved groups had a significantly longer time lapse since diagnosis and a higher PC20 at the time of diagnosis. We conclude that failure to improve after cessation of exposure to an agent causing OA is associated with airway inflammation at follow-up.
Community exposures to airborne agricultural pesticides in California: ranking of inhalation risks.
Authors: Sharon Lee, Robert McLaughlin, Martha Harnly, Robert Gunier, Richard Kreutzer
Journal: Environmental Health Perspectives (2002)

We assessed inhalation risks to California communities from airborne agricultural pesticides by probability distribution analysis using ambient air data provided by the California Air Resources Board and the California Department of Pesticide Regulation. The pesticides evaluated include chloropicrin, chlorothalonil, chlorpyrifos, S,S,S-tributyl phosphorotrithioate, diazinon, 1,3-dichloropropene, dichlorvos (naled breakdown product), endosulfan, eptam, methidathion, methyl bromide, methyl isothiocyanate (MITC; metam sodium breakdown product), molinate, propargite, and simazine. Risks were estimated for the median and 75th and 95th percentiles of probability (50, 25, and 5% of the exposed populations). Exposure estimates greater than or equal to noncancer reference values occurred for 50% of the exposed populations (adults and children) for MITC subchronic and chronic exposures, methyl bromide subchronic exposures (year 2000 monitoring), and 1,3-dichloropropene subchronic exposures (1990 monitoring). Short-term chlorpyrifos exposure estimates exceeded the acute reference value for 50% of children (not adults) in the exposed population. Noncancer risks were uniformly higher for children due to a proportionately greater inhalation rate-to-body weight ratio compared to adults and other factors. Target health effects of potential concern for these exposures include neurologic effects (methyl bromide and chlorpyrifos) and respiratory effects (1,3-dichloropropene and MITC). The lowest noncancer risks occurred for simazine and chlorothalonil. Lifetime cancer risks of one-in-a-million or greater were estimated for 50% of the exposed population for 1,3-dichloropropene (1990 monitoring) and 25% of the exposed populations for methidathion and molinate. Pesticide vapor pressure was found to be a better predictor of inhalation risk compared to other methods of ranking pesticides as potential toxic air contaminants.
Preclinical assessment of a novel small molecule inhibitor of tryptophan 2,3-dioxygenase 2 (TDO2)
Authors: Stefano Crosignani, Gregory Driessens, Michel Detheux, Benoît Van den Eynde, Sandra Cauwenberghs
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts iTeos leverages the science of LICR to target metabolism of the tumor microenvironment and develops small molecule immunomodulators. TDO2 is a heme-containing enzyme highly expressed in the liver, in specific brain regions and liver/brain tumors. It catalyses the first and rate-