tbuckley/cabot-search huggingface dataset:
In vitro techniques for the assessment of neurotoxicity.
Authors: G J Harry, M Billingsley, A Bruinink, I L Campbell, W Classen, D C Dorman, C Galli, D Ray, R A Smith, H A Tilson
Journal: Environmental Health Perspectives (1998)

Risk assessment is a process often divided into the following steps: a) hazard identification, b) dose-response assessment, c) exposure assessment, and d) risk characterization. Regulatory toxicity studies usually are aimed at providing data for the first two steps. Human case reports, environmental research, and in vitro studies may also be used to identify or to further characterize a toxic hazard. In this report the strengths and limitations of in vitro techniques are discussed in light of their usefulness to identify neurotoxic hazards, as well as for the subsequent dose-response assessment. Because of the complexity of the nervous system, multiple functions of individual cells, and our limited knowledge of biochemical processes involved in neurotoxicity, it is not known how well any in vitro system would recapitulate the in vivo system. Thus, it would be difficult to design an in vitro test battery to replace in vivo test systems. In vitro systems are well suited to the study of biological processes in a more isolated context and have been most successfully used to elucidate mechanisms of toxicity, identify target cells of neurotoxicity, and delineate the development and intricate cellular changes induced by neurotoxicants. Both biochemical and morphological end points can be used, but many of the end points used can be altered by pharmacological actions as well as toxicity. Therefore, for many of these end points it is difficult or impossible to set a criterion that allows one to differentiate between a pharmacological and a neurotoxic effect. For the process of risk assessment such a discrimination is central. Therefore, end points used to determine potential neurotoxicity of a compound have to be carefully selected and evaluated with respect to their potential to discriminate between an adverse neurotoxic effect and a pharmacologic effect. It is obvious that for in vitro neurotoxicity studies the primary end points that can be used are those affected through specific mechanisms of neurotoxicity. For example, in vitro systems may be useful for certain structurally defined compounds and mechanisms of toxicity, such as organophosphorus compounds and delayed neuropathy, for which target cells and the biochemical processes involved in the neurotoxicity are well known. For other compounds and the different types of neurotoxicity, a mechanism of toxicity needs to be identified first. Once identified, by either in vivo or in vitro methods, a system can be developed to detect and to evaluate predictive ability for the type of in vivo neurotoxicity produced. Therefore, in vitro tests have their greatest potential in providing information on basic mechanistic processes in order to refine specific experimental questions to be addressed in the whole animal.
Activation of LKB1-Akt pathway independent of phosphoinositide 3-kinase plays a critical role in the proliferation of hepatocellular carcinoma from nonalcoholic steatohepatitis
Authors: Nuria Martínez-López, Marta Varela-Rey, David Fernández-Ramos, Ashwin Woodhoo, Mercedes Vázquez-Chantada, Nieves Embade, Luis Espinosa-Hevia, Francisco Javier Bustamante, Luis A. Parada, Manuel S. Rodriguez, Shelly C. Lu, José M. Mato, Maria L. Martínez-Chantar
Journal: Hepatology (2010)

LKB1, originally considered a tumor suppressor, plays an important role in hepatocyte proliferation and liver regeneration. Mice lacking the methionine adenosyltransferase (MAT) gene MAT1A exhibit a chronic reduction in hepatic S -adenosylmethionine (SAMe) levels, basal activation of LKB1, and spontaneous development of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). These results are relevant for human health because patients with liver cirrhosis, who are at risk to develop HCC, have a marked reduction in hepatic MAT1A expression and SAMe synthesis. In this study, we isolated a cell line (SAMe-deficient [SAMe-D]) from MAT1A knockout (MAT1A-KO) mouse HCC to examine the role of LKB1 in the development of liver tumors derived from metabolic disorders. We found that LKB1 is required for cell survival in SAMe-D cells. LKB1 regulates Akt-mediated survival independent of phosphoinositide 3-kinase, adenosine monophosphate protein–activated kinase (AMPK), and mammalian target of rapamycin complex (mTORC2). In addition, LKB1 controls the apoptotic response through phosphorylation and retention of p53 in the cytoplasm and the regulation of herpesvirus-associated ubiquitin-specific protease (HAUSP) and Hu antigen R (HuR) nucleocytoplasmic shuttling. We identified HAUSP as a target of HuR. Finally, we observed cytoplasmic staining of p53 and p-LKB1(Ser428) in a NASH-HCC animal model (from MAT1A-KO mice) and in liver biopsies obtained from human HCC derived from both alcoholic steatohepatitis and NASH. Conclusion: The SAMe-D cell line is a relevant model of HCC derived from NASH disease in which LKB1 is the principal conductor of a new regulatory mechanism and could be a practical tool for uncovering new therapeutic strategies. (Hepatology 2010)
Inflammatory responses in respiratory syncytial virus and other viral infections in infants: Cytokines, chemokines, and eosinopilic cationic protein
Authors: S. Kristjansson, S. Bjarnarson, I. Jonsdottir, T. Arnadottir, G. Wennergren, A. Haraldsson
Journal: Journal of Allergy and Clinical Immunology (2003)
Circulation Time Determinations from the Right Ventricle
Authors: ROBERT F. ZIEGLER
Journal: Circulation (1951)

The determination of the circulation time from the ventricle to the face using fluorescein and ultraviolet light eliminates all of the variable factors from the venous side of the circulation and gives evidence specifically of the presence or absence of an intraventricular right to left shunt. The most important clinical application is the differentiation of tetralogy of Fallot from pulmonary valvular stenosis with an intact ventricular septum, the first requiring a shunting type of operation and the second a pulmonary valvulotomy.
Inhaled Glucocorticoids in Chronic Obstructive Pulmonary Disease
Authors: Cristina Elisabetta Mapp
Journal: New England Journal of Medicine (2000)

Chronic obstructive pulmonary disease (COPD) is a group of disorders characterized by a poorly reversible limitation of airflow that is usually progressive and associated with a persistent inflammatory response of the lungs. It is caused by at least three distinct pathologic processes that may occur separately or concurrently (chronic bronchitis accompanied by the hypersecretion of mucus; the destruction of alveolar walls, which causes emphysema; and chronic asthma).Treating COPD is challenging. However, clinical studies of asthma have found that regular treatment with an inhaled glucocorticoid is effective in reducing symptoms and the frequency of exacerbations and in improving pulmonary function. . . .
Prediction of two-year survival and composite endpoints using the TIMI-7 risk score extended by N-terminal pro-brain natriuretic peptide levels
Authors: Rudolf Jarai, Robert Jarai, Ferenc Jarai, Nelly Iordanova, Walter S. Speidl, Wolfgang Woloszczuk, Georg Geyer, Johann Wojta, Kurt Huber
Journal: Journal of the American College of Cardiology (2003)
Early T wave inversion after thrombolytic therapy predicts better coronary perfusion: Clinical and angiographic study
Authors: Shlomi Matetzky, Gabriel I. Barabash, Amir Shahar, Babeth Rabinowitz, Shmuel Rath, Yedael Har Zahav, Oren Agranat, Elieser Kaplinsky, Hanoch Hod
Journal: Journal of the American College of Cardiology (1994)
Ezrin dephosphorylation/downregulation contributes to ursolic acid-mediated cell death in human leukemia cells
Authors: G Li, T Zhou, L Liu, J Chen, Z Zhao, Y Peng, P Li, N Gao
Journal: Blood Cancer Journal (2013)

Ezrin links the actin filaments with the cell membrane and has a functional role in the apoptotic process. It appears clear that ezrin is directly associated with Fas, leading to activation of caspase cascade and cell death. However, the exact role of ezrin in ursolic acid (UA)-induced apoptosis remains unclear. In this study, we show for the first time that UA induces apoptosis in both transformed and primary leukemia cells through dephosphorylation/downregulation of ezrin, association and polarized colocalization of Fas and ezrin, as well as formation of death-inducing signaling complex. These events are dependent on Rho-ROCK1 signaling pathway. Knockdown of ezrin enhanced cell death mediated by UA, whereas overexpression of ezrin attenuated UA-induced apoptosis. Our in vivo study also showed that UA-mediated inhibition of tumor growth of mouse leukemia xenograft model is in association with the dephosphorylation/downregulation of ezrin. Such findings suggest that the cytoskeletal protein ezrin may represent an attractive target for UA-mediated lethality in human leukemia cells.
Circadian Rhythm of Plasma Aldosterone Concentration in Patients with Primary Aldosteronism
Authors: David C. Kem, Myron H. Weinberger, Celso Gomez-Sanchez, Norman J. Kramer, Robert Lerman, Shunsuke Furuyama, Charles A. Nugent
Journal: Journal of Clinical Investigation (1973)

Plasma aldosterone, cortisol, and renin activity were measured in nine recumbent patients with hyperaldosteronism, including seven with adenomas, one with idiopathic hyperplasia, and one with glucocorticoid suppressible hyperplasia. All had peak values of plasma aldosterone concentration from 3 a.m. to noon and lowest values at 6 p.m. or midnight. This rhythm was similar to the circadian pattern of plasma cortisol in the same patients. When these data were normalized to eliminate the wide variation in ranges of plasma aldosterone and cortisol between individuals, there was an excellent correlation (r = + 0.87, P < 0.005) between the two hormones. In contrast, plasma aldosterone concentrations did not correlate with plasma renin activity before or after normalization of data.
Cysteinyl‐leukotriene release test (CAST) in the diagnosis of immediate drug reactions
Authors: B. Lebel, D. Messaad, V. Kvedariene, M. Rongier, J. Bousquet, P. Demoly
Journal: Allergy (2001)

Background: The diagnosis of allergic reactions to drugs is difficult. Most skin tests are not standardized, and in vitro tests are needed to avoid provocation tests. Cross‐linking of IgE on basophils is known to cause the release of both cysteinyl leukotriene (Cys‐LT) and histamine. We aimed to evaluate the diagnostic utility (sensitivity, specificity, and efficiency) of measurement of sulfidoleukotrienes in drug allergy. Methods: We performed a prospective study in 55 patients with proven immediate adverse reactions to drugs (30 to β‐lactams, six to acetaminophen, and 19 to aspirin) and 64 drug‐exposed nonallergic controls. Positive diagnosis was established by history, skin tests, and, if needed, oral provocation tests. Cys‐LT release was determined after drug‐allergen stimulation by the cellular antigen stimulation test (CAST®) technique. Histamine release was also assessed on the same samples by enzyme immunoassay. Spontaneous and anti‐FcεRIα‐induced mediator release was also studied in all subjects. Sensitivity, specificity, and efficiency were calculated. Results: Net Cys‐LT release was over the maximal threshold given by the manufacturer in 19/55 patients and in 9/64 controls. Net histamine release was over 5% of total histamine content in 28/55 patients and 34/64 controls. The efficiency of both tests was low. Conclusions: Thus, in most cases, the in vitro Cys‐LT test has little or no diagnostic utility and is not superior to histamine release.
An Atlas of Alzheimer's Disease
Authors: Murray Grossman
Journal: Annals of Internal Medicine (2000)

Medical Writings: Book Notes5 December 2000An Atlas of Alzheimer's DiseaseMurray Grossman, MDMurray Grossman, MDDepartment of Neurology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania. (Grossman)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-133-11-200012050-00032 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail de Leon MJ, ed. 149 pages. New York: Parthenon; 1999. $98.00. ISBN 18507091212. Order phone 800-735-4744.Field of medicine: Neurology and geriatric medicine.Format: Hardcover book.Audience: Physicians and trainees interested in the clinical and pathologic features of Alzheimer disease.Purpose: To provide an overview of Alzheimer disease.Content: The nine chapters of this book provide a concise but thorough and current survey of Alzheimer disease. The rich illustrations that accompany the text add an important dimension. The initial sections cover imaging studies and include positron emission tomographic images of regional cortical dysfunction and detailed in vivo neuroanatomic images obtained ... Author, Article, and Disclosure InformationAffiliations: Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania. (Grossman) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 5 December 2000Volume 133, Issue 11Page: 932KeywordsAlzheimer diseaseAmyloid proteinsChromosomal diseasesIn vivo imagingMagnetic resonance imagingNeurofibrillary tanglesNeurologyNeuronsProtein structureSoftware tools ePublished: 5 December 2000 Issue Published: 5 December 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Retention and Activation of Blood-Borne Proteases in the Arterial Wall
Authors: Xavier Houard, Anne Leclercq, Vincent Fontaine, Michèle Coutard, Jose-Luis Martin-Ventura, Benoît Ho-Tin-Noé, Ziad Touat, Olivier Meilhac, Jean-Baptiste Michel
Journal: Journal of the American College of Cardiology (2006)
Primary myelodysplastic syndrome and cancer.
Authors: R E Clark, H E Payne, A Jacobs, R R West
Journal: BMJ (1987)

CommentOur data contrast with those of Dow et aP in that they suggest that added testosterone is beneficial in alleviating psychosexual symptoms.One reason for the difference may be the selection process: Dow et al studied an unselected group of patients attending their menopause clinic while we chose patients in whom oral oestradiol had failed to relieve psychosexual symptoms.Perhaps only in this group is testosterone specifically effective.No significant side effects were experienced.We are grateful to Peter Dennis, Ken Outch, Nick Balazs, and Mohan Bangah for hormone and lipid assays, to Jill Volfsbergs for secretarial help, and to Robyn Redman for the artwork.Organon Australia
A genome-wide genotyping study in patients with ischaemic stroke: initial analysis and data release
Authors: Mar Matarín, W Mark Brown, Sonja Scholz, Javier Simón-Sánchez, Hon-Chung Fung, Dena Hernandez, J Raphael Gibbs, Fabienne Wavrant De Vrieze, Cynthia Crews, Angela Britton, Carl D Langefeld, Thomas G Brott, Robert D Brown, Bradford B Worrall, Michael Frankel, Scott Silliman, L Douglas Case, Andrew Singleton, John A Hardy, Stephen S Rich, James F Meschia
Journal: The Lancet Neurology (2007)
Trust mark launched as a guarantee of safety in the Netherlands
Authors: T. Sheldon
Journal: BMJ (2002)

One Dutch answer to ensuring reliable health information on the internet has been to develop a thorough system of self certification. TNO Health Trust, part of the large government funded technical research body based in Leiden, launches its internet “trust mark” this spring.

The trust mark is based on a quality management system called QMIC (Quality for Medical Information, Communication, and Transaction). Any organisation must first prove itself capable of meeting a …
Letter: Sick sinus syndrome.
Authors: D B Shaw, C A Kerwick, W C Brownless
Journal: BMJ (1975)

discontinuation of the therapy and the pat- ient with intractable diarrhoea relapsed while on therapy and died.No response was observed in the patient with acute myeloblastic leukaemia after two months of continuous therapy.No adverse or side effects were noted.On the basis of this limited experience we believe that loperamide is a valuable adjunct to the management of life-threatening diarr- hoea of varying aetiology and that further studies are warranted in larger series of pat- ients.-Weare, etc.,
Surgery for ruptured abdominal aortic aneurysm
Authors: M. Bjorck
Journal: BMJ (2014)

Trial reports comparable short term survival after open or endovascular repair

Two therapeutic alternatives exist in a patient with ruptured abdominal aortic aneurysm: immediate open repair or imaging with computed tomography followed by endovascular aneurysm repair if anatomically possible or open repair if not. The main advantage of the immediate open repair strategy is that further imaging is not required, and speed may save life. Endovascular repair, on the other hand, is less invasive and can in most cases be done under local anaesthesia, avoiding the life threatening severe hypotension associated with general anaesthesia in a bleeding patient. 

Here is a situation of true equipoise. Observational research from Switzerland suggests that both strategies give equally excellent results,1 2 and two small randomised controlled trials failed to show any difference in mortality.3 4 In a linked paper (doi:10.1136/bmj.f7661), Powell and colleagues report the results of the IMPROVE trial,5 a major scientific achievement. Conducting a large trial in this emergent situation is demanding, not least because informed consent can be difficult to obtain. The Mental Capacity Act makes randomising patients in the United Kingdom without informed consent possible, which is ethically sound when the patient has potentially life threatening hypotension, …
Bacillary Dysentery in Egypt, 1943–1944
Authors: John Black
Journal: Journal of the Royal Society of Medicine (2007)

I would like to add a personal anecdote to Scadding's article1 on bacillary dysentery in Egypt. In March 1944 I was admitted to hospital in Bangalore, India, with mild bacillary dysentery. My treatment consisted of repeated doses of a mixture of magnesium and sodium sulphate, the standard treatment at that time. It seemed to me that this purgation was perpetuating my original symptoms and that this might go on indefinitely. I therefore hatched a plot with the Italian orderly (Italian prisoners of war were employed as orderlies in hospitals in India) to chart my treatment but not to give it to me. The result was impressive; within 48 hours I was ‘formed’, and was discharged.

Scadding referred briefly to ‘Some probably harmful procedures were still sometimes advocated; for instance there was even the residue of the idea that saline purgation ought to be helpful in ridding the bowel of the infective agent.’ Exactly when sulphaguanide became available in India and South East Asia is not clear, but it was certainly in use in Singapore in September 1945. Stitt's Diagnosis, Prevention and Treatment of Tropical Diseases,2 published in 1943, clarifies the situation; after quoting a number of favourable trials of sulphaguanidine, it states, ‘A large supply of this drug has been very recently sent from the United States to Cairo for the use of the British armies in the Near East and Africa’—but not to India, apparently.

One wonders how many military man-hours were wasted by this useless purgative treatment.
Cyclopedia of American Medical Biographies.
Authors: Howard A. Kelly
Journal: JAMA (1907)

Baltimore, Jan. 8, 1907. <h3>To the Editor:</h3> —The letter published inThe Journal, Dec. 8, 1906, in regard to the Cyclopedia of Biographies brought responses from all parts of the country. I wish to report marked progress in the enterprise, and to put before the profession the organization of the plan up to the present. I have three sets of collaborators engaged in different fields of activity. First, there are men who take charge of large sections of the country or a state; second, those who have charge of the specialties, and third, a system of volunteer associates, or those who engage to write one or two biographies. Those who have charge of the states will be glad to have the specialists written up by men who are particularly familiar with their work. At the same time they will also be glad to have certain individual lives written by some
Lipoproteins and blood pressure as biological pathways for effect of moderate alcohol consumption on coronary heart disease.
Authors: R D Langer, M H Criqui, D M Reed
Journal: Circulation (1992)

BACKGROUND Several epidemiological studies have shown light-to-moderate alcohol consumption to have a net protective effect on the incidence of coronary heart disease (CHD). METHODS AND RESULTS Major components of this effect, both positive and negative, may be explored using models that include both alcohol and variables expected to mediate the observed alcohol effect. Such modeling in a cohort of men of Japanese descent followed in the Honolulu Heart Program indicates that about half of the observed protection against CHD afforded by moderate alcohol consumption is mediated by an increase in high density lipoprotein cholesterol. An additional 18% of this protection is attributable to a decrease in low density lipoprotein cholesterol, but it is counterbalanced by a 17% increase in risk due to increased systolic blood pressure. The explanation for the residual 50% benefit attributable to alcohol is unknown but may include interference with thrombosis. The results in this population replicate those in the Lipid Research Clinics cohort studied earlier with the same analytic technique. CONCLUSIONS The consistency of these findings across populations, along with the demonstration of reasonable biological pathways for this effect of alcohol, provides strong support for the hypothesis that light-to-moderate alcohol intake is protective against heart disease in men.
Mucoadhesive polymers in peroral peptide drug delivery. IV. Polycarbophil and chitosan are potent enhancers of peptide transport across intestinal mucosae in vitro
Authors: H.L Lueßen, C.-O Rentel, A.F Kotzé, C.-M Lehr, A.G de Boer, J.C Verhoef, H.E Junginger
Journal: Journal of Controlled Release (1997)