tbuckley/cabot-search huggingface dataset:
E-Cadherin/β-Catenin/T-Cell Factor Pathway Is Involved in Smooth Muscle Cell Proliferation Elicited by Oxidized Low-Density Lipoprotein
Authors: Aurélie Bedel, Anne Nègre-Salvayre, Sylvia Heeneman, Marie-Hélène Grazide, Jean-Claude Thiers, Robert Salvayre, Françoise Maupas-Schwalm
Journal: Circulation Research (2008)

The E-cadherin/beta-catenin/T-cell factor (Tcf) signaling pathway plays a crucial role in embryogenesis and carcinogenesis and has recently emerged in atherosclerosis. The aim of this work was to investigate whether this signaling pathway is involved in smooth muscle cell proliferation induced by oxidized low-density lipoprotein (LDL). In human aortic smooth muscle cells, mitogenic concentration of mildly oxidized LDL induced the activation of beta-catenin, as assessed by the dissociation of the beta-catenin/cadherin complex, and the concomitant rise of active beta-catenin in the cytosol. The oxidized LDL-induced rise of active beta-catenin required metalloproteinase activation, as well as epidermal growth factor receptor and Src signaling, as assessed by the use of pharmacological inhibitors and cells overexpressing a SrcK-inactive form. The concomitant phosphatidylinositol 3-kinase/Akt activation and glycogen synthase kinase 3-beta phosphorylation induced the inhibition of the proteasomal degradation of beta-catenin. Then active beta-catenin associated with Tcf4 and translocated into the nucleus. This enhanced the expression of the cell cycle activator cyclin D1. This crucial role of beta-catenin in the mitogenic effect of oxidized LDL was confirmed by silencing beta-catenin by specific small interfering RNA that blocked DNA synthesis. Immunohistochemistry staining of stable and disrupted plaques from carotid endarterectomy sections showed a correlation between active beta-catenin and Ki67, a proliferation marker, and a more intense staining in the smooth muscle cell layer surrounding the lipid core of disrupted plaques. In conclusion, the beta-catenin pathway is required for the mitogenic effect of oxidized LDL on human aortic smooth muscle cells. This study highlights the putative important role of the E-cadherin/beta-catenin/Tcf signaling pathway in atherosclerosis.
Bilateral Versus Unilateral Internal Mammary Revascularization in Patients With Diabetes
Authors: Masahiro Endo, Yasuko Tomizawa, Hiroshi Nishida
Journal: Circulation (2003)

This historical cohort study evaluated the benefit of bilateral internal mammary artery (BIMA) grafts in coronary bypass grafting (CABG) for patients with diabetes.We performed elective, isolated, primary, multiple CABG using skeletonized internal mammary artery (IMA) grafts for multivessel disease in 1131 patients, 467 (41.3%) of whom had type 2 diabetes mellitus. The early and long-term results were compared between 277 patients with diabetes using single IMA (SIMA) grafts and 190 using BIMA grafts (median follow-up, 8.1 years). Hospital mortality was similar in both groups. Early patency rate of all grafts was significantly higher using BIMA than using SIMA (97.7% versus 93.8%, P=0.0012). Survival rates were not significantly different between SIMA and BIMA groups. Late cardiac mortality was significantly higher in patients with low ejection fraction (0.4 or lower) compared with preserved ejection fraction (higher than 0.4) (P=0.0001). In patients with preserved ejection fraction, 10-year survival rate was significantly higher using BIMA than using SIMA (87.8+/-3.5% versus 75.2+/-3.4%, P=0.04), and 10-year all death-free or repeat CABG or recurrent myocardial infarction-free rate was significantly higher using BIMA than using SIMA (86.6+/-3.6% versus 69.0+/-3.7%, P=0.0086). The hazard ratio for all death or repeated CABG or recurrent myocardial infarction in patients with preserved ejection fraction was markedly lower in the BIMA group (0.53; 95% CI, 0.31 to 0.9; P=0.019).Skeletonized BIMA grafts are beneficial in coronary revascularization for diabetic patients with preserved ejection fraction but have limited survival benefit for those with reduced ejection fraction attributable to high cardiac mortality.
Neutron Capture Therapy
Authors: George R. Meneely
Journal: JAMA (1965)

<h3>To the Editor:—</h3> In the Sept 6 issue (<b>193</b>: adv p 33, 1965) a Medical News item "Neutron Capture Therapy" states, "At least two other groups are at work on neutron capture therapy... " This is indeed the case although the statement earlier in the article, "the method, under development since 1958...," is misleading. It may well be that the Argonne National Laboratory program dates from that point in time; however, the implication that neutron capture therapy dates from 1958 is incorrect (Farr, L.E., et al: Neutron Capture Therapy with Boron...,<i>Amer J Roentgen</i><b>71</b>:279, 1954). A complete list of the writings of Farr and his associates would number 38. This is not to deprecate the accomplishments of the scientists at the Argonne nor the fine work of Drs. Bond and Sweet, both specifically mentioned in the news item, but to point out that Dr. Farr's activities in this area,
Book Review The Codification of Medical Morality: Historical and Philosophical Studies of the Formalization of Western Medical Morality in the Eighteenth and Nineteenth Centuries Vol. 1. Medical ethics and etiquette in the eighteenth century. (Philosophy and Medicine. Vol. 45.) Edited by Robert Baker, Dorothy Porter, and Roy Porter. 230 pp. Boston, Kluwer Academic, 1993. $87. 0-7923-1921-4
Authors: Samuel B. Thielman
Journal: New England Journal of Medicine (1994)
Prolactin and Growth Hormone Aggregates in Secretory Granules: The Need to Understand the Structure of the Aggregate
Authors: Priscilla S. Dannies
Journal: Endocrine Reviews (2012)

Prolactin and GH form reversible aggregates in the trans-Golgi lumen that become the dense cores of secretory granules. Aggregation is an economical means of sorting, because self-association removes the hormones from other possible pathways. Secretory granules containing different aggregates show different behavior, such as the reduction in stimulated release of granules containing R183H-GH compared with release of those containing wild-type hormone. Aggregates may facilitate localization of membrane proteins necessary for transport and exocytosis of secretory granules, and therefore understanding their properties is important. Three types of self-association have been characterized: dimers of human GH that form with Zn2+, low-affinity self-association of human prolactin caused by acidic pH and Zn2+ with macromolecular crowding, and amyloid fibers of prolactin. The best candidate for the form in most granules may be low-affinity self-association because it occurs rapidly at Zn2+ concentrations that are likely to be in granules and reverses rapidly in neutral pH. Amyloid may form in older granules. Determining differences between aggregates of wild type and those of R183H-GH should help to understand why granules containing the mutant behave differently from those containing wild-type hormone. If reversible aggregation of other hormones, including those that are proteolytically processed, is the crucial act in forming granules, rather than use of a sorting signal, then prohormones should form reversible aggregates in solution in conditions that resemble those of the trans-Golgi lumen, including macromolecular crowding.
On the cross-linguistic validity of a dual-mechanism model
Authors: Margherita Orsolini
Journal: Behavioral and Brain Sciences (1999)

Recent studies of Italian past definite and past participle forms show that human performance with regular and irregular inflections is not dissociated as Clahsen's model would predict. Some performance profiles, accounted for by dual-mechanism models in terms of an underlying symbol-manipulating combinatorial procedure, are generated in Italian by the higher learnability and generalizability of phonologically regular morphological processes.
Flawed immunisation policies in India led to polio paralysis
Authors: G. Mudur
Journal: BMJ (1998)

In accordance with World Health Organization (WHO) recommendations, India introduced 3 doses per child of oral poliomyelitis vaccine (OPV) into its immunization program during the late 1970s. It was hoped that infants would be protected from polio after having received the 3-dose vaccine course. However, the provision of only 3 doses of OPV contradicted research which suggested that additional doses would be necessary to protect children from wild polioviruses in India's tropical environment. During the 1980s, hundreds of thousands of children in India developed polio because of the inadequate vaccine protection they received under WHO recommendations. Moreover, the introduction of diphtheria/tetanus/pertussis (DTP) vaccine without adequately protecting infants from circulating wild polioviruses increased the risk of provocation poliomyelitis, a phenomenon in which an injection given to a child with silent poliovirus infection can trigger paralysis in the injected limb. Massive outbreaks of provocation poliomyelitis occurred. Given the appropriate policies, India could have eradicated polio a decade ago. However, it now seems unlikely that India will eradicate polio by the target year of 2000.
Cidofovir for Cytomegalovirus Retinitis
Authors: Stephen Kravcik
Journal: Annals of Internal Medicine (1997)

Letters15 September 1997Cidofovir for Cytomegalovirus RetinitisStephen Kravcik, MD, FRCPCStephen Kravcik, MD, FRCPCOttawa General Hospital; Ottawa, Ontario K1H 8L6, CanadaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-6-199709150-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The demonstration of the effectiveness of cidofovir to treat cytomegalovirus (CMV) retinitis adds a welcome third drug to the list of anti-CMV therapies. However, it is most disturbing to find that the two clinical studies of this compound [1, 2] compared it with no treatment (“deferred therapy”).There is no doubt that the natural history of untreated CMV retinitis is one of relentless progression and that ganciclovir [3] and foscarnet [4] are both effective. Therefore, the withholding of proven therapy (even with close follow-up) in the context of a clinical trial to demonstrate the effectiveness of cidofovir ...References1. Lalezari JP, Stagg RJ, Kuppermann BD, Holland GN, Kramer F, Ives DV, et al. Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS. A randomized, controlled trial. Ann Intern Med. 1997; 126:257-63. Google Scholar2. Studies of Ocular Complications of AIDS Research Group in Collaboration with the AIDS Clinical Trial Group. Parenteral cidofovir for cytomegalovirus retinitis in patients with AIDS: the HPMPC Peripheral Cytomegalovirus Retinitis Trial. A randomized, controlled trial. Ann Intern Med. 1997; 126:264-74. Google Scholar3. Collaborative DHPG Study Group. Treatment of serious cytomegalovirus infections with 9-(1,3-dihydroxy-2-propoxymethyl) guanine in patients with AIDS and other immunodeficiencies. N Engl J Med. 1986; 314:801-5. Google Scholar4. Studies of Ocular Complications of AIDS Research Group, in collaboration with the AIDS Clinical Trial Group. Mortality in patients with the acquired immunodeficiency syndrome treated with either ganciclovir or foscarnet for cytomegalovirus retinitis. N Engl J Med. 1992; 326:213-20. Google Scholar Author, Article, and Disclosure InformationAffiliations: Ottawa General Hospital; Ottawa, Ontario K1H 8L6, Canada PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByBeyond Urban Penalty and Urban Sprawl: Back to Living Conditions as the Focus of Urban Health 15 September 1997Volume 127, Issue 6Page: 490KeywordsClinical trialsCryptococcal meningitisCytomegalovirus infectionDrug therapyOpportunistic infectionsPneumocystis carinii pneumoniaRetinitis Issue Published: 15 September 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Chronic Hepatitis B
Authors: Jay H. Hoofnagle
Journal: New England Journal of Medicine (1990)

Chronic hepatitis B is said to affect at least 5 percent of the world's population and to be the chief cause of cirrhosis and hepatocellular carcinoma.1 The World Health Organization lists hepatitis B as the ninth major cause of death worldwide, close behind chronic pulmonary disease and well ahead of the acquired immunodeficiency syndrome. These estimates suggest that chronic hepatitis B virus (HBV) infection is the most important chronic viral infection affecting humans.The portrayal of chronic hepatitis B as a major health risk must strike most U.S. physicians as somewhat forced or exaggerated. In this country and other developed . . .
Elevated Plasma Homocysteine Level Is an Independent Predictor of Coronary Heart Disease Events in Patients with Type 2 Diabetes Mellitus
Authors: Minna Soinio, Jukka Marniemi, Markku Laakso, Seppo Lehto, Tapani Rönnemaa
Journal: Annals of Internal Medicine (2004)

Background: High plasma homocysteine level has been associated with increased risk for coronary heart disease (CHD) events in nondiabetic individuals, especially in those with previously diagnosed CHD. In persons with type 2 diabetes mellitus, the association between homocysteine level and cardiovascular disease may be stronger than that in nondiabetic individuals, but no large prospective studies have examined the relationship between homocysteine level and CHD mortality in persons with type 2 diabetes. Objective: To investigate whether moderately elevated plasma homocysteine levels are independently related to increased incidence of fatal and nonfatal CHD events in persons with type 2 diabetes. Design: Prospective study. Setting: Finnish sample of patients with type 2 diabetes. Patients: 462 men and 368 women who were 45 to 64 years of age at baseline. Measurements: Coronary heart disease mortality and incidence of nonfatal myocardial infarction during the 7-year follow-up. Results: Participants with plasma homocysteine levels of 15 µmol/L or more at baseline had a higher risk for CHD death than those with plasma homocysteine levels less than 15 µmol/L (26.1% and 13.5%, respectively; P = 0.005). The risks for all CHD events were 36.2% and 22.6%, respectively (P = 0.011). In Cox regression analyses, elevated plasma homocysteine level was significantly associated with CHD mortality (P < 0.001) and all CHD events (P = 0.002) even after adjustment for confounding variables, including creatinine clearance. In participants without myocardial infarction at baseline, moderate hyperhomocysteinemia was also associated with CHD mortality and all CHD events in univariate (P < 0.001 and P = 0.006, respectively) and multivariate Cox regression analyses (P < 0.001 and P = 0.004, respectively). Conclusions: In this large cohort of patients with type 2 diabetes, plasma homocysteine level was a strong and independent risk factor for CHD events.
Age-related changes in beta-adrenergic neuroeffector systems in the human heart.
Authors: M White, R Roden, W Minobe, M F Khan, P Larrabee, M Wollmering, J D Port, F Anderson, D Campbell, A M Feldman
Journal: Circulation (1994)

BACKGROUND Aging decreases cardiac beta-adrenergic responsiveness in model systems and in humans in vivo. The purpose of this study was to comprehensively evaluate the age-related changes in the beta-receptor-G protein-adenylyl cyclase complex in nonfailing human hearts. METHODS AND RESULTS Twenty-six nonfailing explanted human hearts aged 1 to 71 years were obtained from organ donors and subjected to pharmacological investigation of beta-adrenergic neuroeffector systems. When the population was subdivided into the 13 youngest and 13 oldest subjects, total beta-receptor density assessed by maximum [125I]ICYP binding (beta max) was reduced in older hearts by 37% in left ventricles and 31% in right ventricles (both P &lt; .05), and the downregulation was confined to the beta 1 subtype (r = .78 left ventricle beta 1 density versus donor age). Older donor hearts exhibited a 3- to 4-fold rightward shift of ICYP-isoproterenol (ISO) competition curves and demonstrated 43% fewer receptors in a high-affinity agonist binding state (P &lt; .05). Older hearts exhibited decreased adenylyl cyclase stimulation by ISO, by zinterol (beta 2-agonist), and by the G protein-sensitive probes forskolin, Gpp(NH)p, and NaF. In contrast, there was no change in response to manganese, a specific activator of the adenylyl cyclase catalytic subunit. Toxin-catalyzed ADP ribosylation in membranes prepared from older versus younger hearts revealed a 29% to 30% reduction (P &lt; .05) with cholera toxin (Gs) but no difference with pertussis toxin (Gi). The systolic contractile response of isolated right ventricular trabeculae to ISO was decreased by 46%, with a 10-fold increase in ISO EC50 in older relative to younger donor hearts. CONCLUSIONS There is a profound decrease in cardiac beta-adrenergic responsiveness with aging. This occurs by multiple mechanisms including downregulation and decreased agonist binding of beta 1-receptors, uncoupling of beta 2-receptors, and abnormal G protein-mediated signal transduction.
When going into urinary retention, call a… vet?
Authors: Bridget Pearson, Rowland Illing
Journal: BMJ (2006)

Environmental tobacco smoke was related to a moderately increased risk of all cause mortality and mortality due to lung cancer and cardiovascular disease.Given the high prevalence of exposure to environmental tobacco smoke (83.1%) in this population, a moderate association with a hazard ratio of 1.15 would yield an attributable risk in the population of 11.1%.The impact of environmental tobacco smoke on all cause mortality could be substantial.
Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study
Authors: B. Levy, P.-E. Bollaert, C. Charpentier, L. Nace, G. Audibert, P. Bauer, P. Nabet, A. Larcan
Journal: Intensive Care Medicine (1997)
The rationality debate from the perspective of cognitive-experiential self-theory
Authors: Seymour Epstein
Journal: Behavioral and Brain Sciences (2000)

A problem with Stanovich &amp; West's inference that there a nonintellectual processing system independent from an intellectual one from data in which they partialled out global intelligence is that they may have controlled for the wrong kind of intellectual intelligence. Research on cognitive-experiential self-theory over the past two decades provides much stronger support for two independent processing systems.
Shawn Cato Bateman
Authors: Jim Mathewson
Journal: BMJ (2004)

Former British Airways medical officer Manchester Airport (b Coleraine, Northern Ireland, 1924; q Queen's University, Belfast, 1952), died from cardiac failure on 13 April 2004.​2004.




Figure 1




During the second world war he trained as a navigator/wireless operator and did an operational tour in photographic reconnaissance Mosquitoes in the 2nd Tactical Air Force. For his bravery he was awarded the Distinguished Flying Medal. He studied medicine after the war and, following spells as an assistant in general practice, he joined British Airways as a medical officer, looking after staff and passengers at Manchester Airport. He took part in various research projects, including a study of the effect on time zone changes on sleep patterns. He leaves a wife, Beryl; and a daughter.
Coexistence of diffuse plane normolipaemic xanthoma and amyloidosis in a patient with monoclonal gammopathy
Authors: G.F. BUEZO, J.I. PORRAS, J. FRAGA, E. SANCHEZ, M. ARAGüES, E. DAUDÉEN
Journal: British Journal of Dermatology (1996)

Diffuse plane normolipaemic xanthomatosis (DPNX) is a well-defined clinicopathological entity that characteristically presents with yellow-orange plaques in the periorbital areas, the neck, the upper trunk and the flexural folds. DPNX has been reported in association with lymphoproliferative disorders and, occasionally, with miscellaneous, probably coincidental disorders. A case of DPNX in a patient with an IgG lambda monoclonal gammopathy and systemic amyloidosis is reported. Clinical and histopathological findings revealed typical features of DPNX and amyloidosis coexisting in the cutaneous lesions. To our knowledge this is the first reported case showing coexistence of xanthoma and amyloidosis in cutaneous lesions in a patient with a monoclonal gammopathy.
Rethinking sexual health clinics
Authors: Y. Stedman, M. Elstein
Journal: BMJ (1995)

which a patient can reasonably be thought to have a continued interest."5The level of treament will depend on the result of clinical assessment by the physician and discussion with the patient's family or other decision makers.The place of high technology treatments (mechanical ventilation, dialysis, cardiopulmonary resuscitation) and routine drugs (such as antibiotics) or other treatments such as supplementary oxygen can be determined only in the context of the individual case.2 3The BMA has recommended that "if it is apparent at the end of a twelve month period of insentience due to persistent vegetative state that the patient's condition is irreversible doctors will consider whether it is in the patient's best interest to continue with treatment to prolong life."7The findings of the American Multi-Society Task Force challenge these recommendations by suggesting that a persistent vegetative state is almost always permanent at three months if the cause was a non-traumatic cerebral insult.Although the evidence is strong, experience (particularly in the subgroups) is not yet still adequate to recommend a change in the British recommendations-but these are currently under review by a working party established by the royal colleges.Both the medical and the legal authorities have advised that in some circumstances when the patient's condition is irreversible withdrawal of life sustaining treatment, including tube feeding, may be legitimate and ethically acceptable.12Such a decision requires independent evaluation of the diagnosis and prognosis, the likely benefits or burdens of treatment, the patient's views if known, and the views of the people close to the patient.In Britain the decision to withdraw artificial nutrition from a patient in a persistent vegetative state requires consultation with the courts.
OBSERVATIONS ON THE COMPARATIVE EFFECTS OF TRANQUILIZERS ON PATIENTS PREVIOUSLY TREATED WITH PROCHLORPERAZINE
Authors: WERNER M. MENDEL
Journal: American Journal of Psychiatry (1958)

We have attempted to demonstrate a possible approach to the evaluation of drugs by using patients as their own control. This avoids the obvious error inherent in considering a diagnostic category as representing a uniform population group. We have attempted to be more precise in our observations of the patients by avoiding socially determined criteria, such as discharge from hospital, movement to open ward, etc. The study has further raised a number of interesting questions. We wonder whether in tranquilizers, as in some other medications, rapid-release of the drug from the tablet is perhaps more effective than a sustained, even release from the spansule. In this study the tablets were more effective milligram for milligram than the spansule. We raise the possibility of. using a number of phenothiazine derivatives in sequence in the treatment of disturbed psychotic patients. In our study-patients improved on a new phenothiazine derivative even though they had improved previously on prochlorperazine and had reached a very satisfactory plateau.