tbuckley/cabot-search huggingface dataset:
Phospholipase D-modified low density lipoprotein is taken up by macrophages at increased rate. A possible role for phosphatidic acid.
Authors: M Aviram, I Maor
Journal: Journal of Clinical Investigation (1993)

Macrophage uptake of modified forms of LDL leads to cellular cholesterol accumulation. Upon incubation of LDL with phospholipase D (PLase D), a time- and enzyme dose-dependent production of phosphatidic acid (PA), paralleled by a rapid reduction in LDL phosphatidyl choline content (up to 65% within 15 min of incubation) was noted. No lipid peroxidation could be found in PLase D-modified LDL. Upon in vitro incubation of PLase D-LDL with copper ions, however, this modified LDL was substantially oxidized. The addition of 100 micrograms PA/ml to native LDL for the period of its in vitro oxidation resulted in a 63% elevation in the lipoprotein peroxides content. Incubation of PLase D-LDL with J-774A.1 macrophage-like cell line resulted in an increase in its cellular binding and degradation (up to 91 and 110%, respectively) in comparison with native LDL (via the LDL receptor). When PA was added to LDL before its incubation with the macrophages, a PA dose-dependent elevation in the cellular uptake of LDL (by up to twofold) was noted in comparison with LDL that was incubated without PA, suggesting that PA production in PLase D-LDL may be involved in the increased cellular uptake of PLase D-LDL. PLase D activity towards LDL was demonstrated in J-774A.1 macrophages. Human plasma was also shown to possess PLase D activity. Thus, PLase D modification of LDL may take place under certain pathological conditions and PLase D-LDL interaction with arterial wall macrophages can potentially lead to foam cell formation.
Doctors' Dilemmas: Medical Ethics and Contemporary Science
Authors: James M. Humber
Journal: JAMA (1985)

While reading this text I experienced severe ambivalence. On the one hand, the authors achieve their stated purpose; on the other hand, their purpose is such that it virtually requires superficiality. Hence my ambivalence. In the preface, the authors state their purpose: We think that these issues [in medical ethics] should be argued in a reasoned, reasonable manner that ordinary people can understand so that they too can participate in the determination of a framework which can guide the application of medical science. Our book is aimed at the interested public.... (page ix) The authors accomplish this purpose. Their text is well written, easily understandable, and a palatable introduction to many of the issues troubling medical ethicists today, eg, genetic engineering, euthanasia, abortion, brain death, tissue transplants, artificial insemination, and genetic screening. In addition, the authors have appended ethical codes such as the Hippocratic Oath, the International Code of Medical
Distinct Contributions of Rod, Cone, and Melanopsin Photoreceptors to Encoding Irradiance
Authors: Gurprit S. Lall, Victoria L. Revell, Hiroshi Momiji, Jazi Al Enezi, Cara M. Altimus, Ali D. Güler, Carlos Aguilar, Morven A. Cameron, Susan Allender, Mark W. Hankins, Robert J. Lucas
Journal: Neuron (2010)

SummaryPhotoreceptive, melanopsin-expressing retinal ganglion cells (mRGCs) encode ambient light (irradiance) for the circadian clock, the pupillomotor system, and other influential behavioral/physiological responses. mRGCs are activated both by their intrinsic phototransduction cascade and by the rods and cones. However, the individual contribution of each photoreceptor class to irradiance responses remains unclear. We address this deficit using mice expressing human red cone opsin, in which rod-, cone-, and melanopsin-dependent responses can be identified by their distinct spectral sensitivity. Our data reveal an unexpectedly important role for rods. These photoreceptors define circadian responses at very dim "scotopic" light levels but also at irradiances at which pattern vision relies heavily on cones. By contrast, cone input to irradiance responses dissipates following light adaptation to the extent that these receptors make a very limited contribution to circadian and pupillary light responses under these conditions. Our data provide new insight into retinal circuitry upstream of mRGCs and optimal stimuli for eliciting irradiance responses.Highlights•Red cone knockin (Opn1mwR) mice reveal rod, cone, and melanopsin phases to NIF vision•Rods drive circadian responses to very low irradiances (scotopic threshold)•Circadian responses to light in the photopic range can be rod driven•Light adaptation limits the influence of cones on NIF vision
THE INFLUENCE OF BARBITURATES ON COUMARIN PLASMA LEVELS AND PROTHROMBIN RESPONSE*
Authors: Peter G. Dayton, Yavuz Tarcan, Theodore Chenkin, Murray Weiner
Journal: Journal of Clinical Investigation (1961)

Wide individual variations in response to drugs is a common clinical problem, and is especially evi- dent with coumarin anticoagulant therapy (1-3).A possible contributing factor to such variations could be the influence of another presumably un- related drug upon the response to the coumarin anticoagulant.Reports from several laboratories (4-7) indicate that barbiturates can reduce the prothrombin response to coumarin anticoagulants.This report presents initial results of studies de- signed to determine the manner by which barbitu- rates alter the response to coumarins in man, guinea pig and dog. MATERIAL AND METHODSGuinea pigs.Diet, method of handling guinea pigs, and blood sample collection have been reported (8).Drugs were administered to guinea pigs intraperitoneally, barbi- tal and acenocoumarin as aqueous solutions of their so- dium salts in 0.5 to 1 ml, and chlorobutanol in 1.0 ml of peanut oil.Dogs.Dogs were maintained on Kibbled dog food
Prognosis of Cortical Blindness Following Cardiac Arrest in Children
Authors: Howard A. Weinberger
Journal: JAMA (1962)

Three patients between the ages of 2 and 3 years are described, in whom severe neuropsychiatric deficits, cortical blindness in particular, which followed cardiac arrest were largely dissipated over long follow-up periods. The degree of recovery from postarrest cortical blindness cannot be immediately gauged, but absolute pessimism is unwarranted. Total body cooling following cardiac arrest is stressed, as are other routine measures in the management of these patients.
Normal Arterial Pressure in Patients With Renal Arterial Stenosis
Authors: Harriet P. Dustan, Alfred W. Humphries, Victor G. de Wolfe, Irvine H. Page
Journal: JAMA (1964)

EARLY CLINICAL EXPERIENCE with renal arterial stenosis<sup>1,2</sup>suggested that the accompanying hypertension was severe and often of the malignant variety. Later, it became apparent that such lesions could be associated with extremely fluctuant arterial pressure levels<sup>3,4</sup>and that occasionally hypertension disappeared.<sup>5</sup>Sutton and associates,<sup>6</sup>and, more recently, Eyler and co-workers<sup>7</sup>have reported finding severe renal arterial stenosis in normotensive patients who were investigated because of peripheral vascular disease. This report describes a study of hypertension and renal arterial stenosis in a group of patients in whom renal arteriograms were obtained incidentally in the course of translumbar aortography for peripheral vascular disease. About 40% were found to have stenosis of one or both main renal arteries, but one half of these were normotensive. <h3>Plan of Study</h3> A review of translumbar aortograms, performed for diagnosis of aorto-iliac occlusive arterial disease since 1953, yielded 149 renal arteriograms of
ENDONASAL LOCALIZATION OF BLOOD BORNE VIABLE AND NON VIABLE PARTICULATE MATTER
Authors: M.W. Kanan, T.J. Ryan
Journal: British Journal of Dermatology (1975)

Journal Article ENDONASAL LOCALIZATION OF BLOOD BORNE VIABLE AND NON VIABLE PARTICULATE MATTER Get access M.W. Kanan, M.W. Kanan Department of Dermatology, Slade Hospital, Oxford Search for other works by this author on: Oxford Academic Google Scholar T.J. Ryan T.J. Ryan Department of Dermatology, Slade Hospital, Oxford Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 92, Issue 4, 1 April 1975, Pages 475–478, https://doi.org/10.1111/j.1365-2133.1975.tb03111.x Published: 01 April 1975
Effects of Aging on the Responsiveness of the Human Cardiac Sympathetic Nerves to Stressors
Authors: Murray D. Esler, Jane M. Thompson, David M. Kaye, Andrea G. Turner, Garry L. Jennings, Helen S. Cox, Gavin W. Lambert, Douglas R. Seals
Journal: Circulation (1995)

Background Aging increases human sympathetic nervous activity at rest. Because of the probable importance of neural stress responses in the heart as triggers for clinical end points of coronary artery disease, it is pertinent to investigate whether sympathetic nervous responses to stresses are increased by aging. Methods and Results We applied kinetic methods for measuring the fluxes to plasma of neurochemicals relevant to sympathetic neurotransmission in younger (aged 20 to 30 years) and older (aged 60 to 75 years) healthy men during mental stress (difficult mental arithmetic), isometric exercise (sustained handgrip), and dynamic exercise (supine cycling). The increase in total norepinephrine spillover to plasma with mental stress was unaffected by age. In contrast, the increase in cardiac norepinephrine spillover was two to three times higher in the older subjects ( P &lt;.05). The probable mechanism of this higher cardiac norepinephrine spillover was reduced neuronal reuptake of the transmitter, because age had no influence on the overflow of the norepinephrine precursor, dihydroxyphenylalanine, or intraneuronal metabolite, dihydroxyphenylglycol (levels of these two substances reflect rates of cardiac norepinephrine synthesis and intraneuronal metabolism), and the transcardiac extraction of plasma radiolabeled norepinephrine was lower in the older subjects ( P &lt;.05). An almost identical pattern of neurochemical response was seen with isometric exercise. During cycling, total norepinephrine spillover was 16% lower in the older men, but cardiac norepinephrine spillover was 53% higher. Conclusions Reduced norepinephrine reuptake increases the overflow of the neurotransmitter to plasma from the aging heart during stimulation of the cardiac sympathetic outflow. Failure of transmitter inactivation at postjunctional receptors with aging would amplify the neural signal, and in the presence of myocardial disease could trigger adverse stress-induced cardiovascular events, particularly when accompanied by an age-dependent reduction in vagal tone. Reduction of postsynaptic adrenergic responsiveness with aging, however, might protect against this, as indicated by our finding that in no case was the heart rate increase during stress greater in older men, despite their having larger increases in cardiac norepinephrine spillover.
Acute Perforated Peptic Ulcer
Authors: F. A. Jones, P. J. Parsons, B. White
Journal: BMJ (1950)

This paper records a study of 490 consecutive cases of acute perforation of peptic ulcer treated in this hospital from 1938 to 1948 inclusive, and discusses the factors which may have contributed to the considerable fall in mortality during that time.Recent papers provide evidence that the mortality from acute perforation has declined from the high levels which prevailed before the war.DeBakey (1940) reviewed the literature published between 1930 and 1940, and his collected series of cases showed a total mortality of 25.2% in 16,752 cases and an operative mortality of 23.4% in 15,340 cases.Published series that allow a comparative analysis of the mortality in recent years show a uniform decrease in Great Britain, America, and Scandinavia (Table I).TABLE I.-Comparative Degrees of Mortality from Perforated
Tether, Contracture and Deformity
Authors: W J W Sharrard
Journal: BMJ (1977)

For example, in the chapters entitled "Principles of diagnosis and treatment" and "Therapeutic schedules in asthma" cromolyn sodium (sodium cromoglycate) is mentioned only briefly and in terms which suggest that the authors have little experience of this drug, but in a later chapter, by a British author, its undoubted therapeutic efficacy is documented at great length.It is difficult for respiratory physicians in Great Britain to conceive that their colleagues in the United States are still using and recommending outdated bronchodilators, such as adrenaline and isoprenaline, when they could be exploiting the advantages of selective P,-adrenoreceptor stimulants such as salbuta- mol, and still have no real understanding of the role of sodium cromoglycate and aerosol corticosteroids in the treatment of asthma.After interminable delays all these modern forms of treatment are now available in the United States, but it is clear from this book that they are not yet being widely used in spite of well-documented evidence of their efficacy and safety.It is unfortunate that the sections of this
Pigment anomalies of the skin in the human chimaera: their relation to systematized naevi
Authors: G.H. FINDLAY, P.P. MOORES
Journal: British Journal of Dermatology (1980)

Double fertilization of the egg may lead to a chimaeric state, in which the cell composition of the individual derives from two zygotes. Some special types of naevoid hyperpigmentation may result Two new cases are added to the three published cases of chimaerism with skin manifestations.
Synergistic Anticancer Effects of Pam3CSK4 and Ara-C on B-Cell Lymphoma Cells
Authors: Sae-Kyung Lee, Jyh Y. Chwee, Cheryl A.P. Ma, Nina Le Bert, Caleb W. Huang, Stephan Gasser
Journal: Clinical Cancer Research (2014)

The low immunogenicity of many cancer cells and the immunosuppression by various cancers and anticancer therapies have been an obstacle in the development of efficacious immunotherapies. Our goal was to test whether Toll-like receptor (TLR) agonists and anticancer chemotherapeutic agents synergize in rendering tumor cells more immunogenic.We treated B-cell lymphoma cells with the TLR1/2 agonist Pam3CSK4 and the genotoxic anticancer agent 1-β-D-arabinofuranosylcytosine (Ara-C). The effects on the immunogenicity of tumor cells were measured in transfer experiments and in vitro studies.The treatment of B-cell lymphoma cells with the TLR1/2 agonist Pam3CSK4 enhanced the anticancer effects of the genotoxic agent Ara-C. Mice injected with cotreated tumor cells survived longer than mice challenged with Pam3CSK4 or Ara-C-treated cells. Administration of Pam3CSK4 or Ara-C reduced the tumor load of mice injected with tumor cells. Cotreatment had no effect on the rate of apoptosis or proliferation of Ara-C-treated cells, but upregulated the expression of several immunomodulatory molecules. Consistent with an increased immunogenicity of Pam3CSK4 and Ara-C-treated B-cell lymphoma cells, rejection of cotreated tumor cells required natural killer cells and T cells. We demonstrate that the upregulation of immunomodulatory molecules in response to Pam3CSK4 and Ara-C depended in part on NF-κB.TLR agonists can increase the efficacy of conventional cancer therapies by altering the immunogenicity of B-cell lymphoma cells.
Rwandan genocide survivors denied AIDS treatment
Authors: Lindsey Hilsum
Journal: BMJ (2004)

On 20 April the London based Survivors' Fund (SURF) is to launch a campaign for free antiretroviral treatment for survivors of the Rwandan genocide.

Ten years after the genocide, in which 800 000 people were murdered, thousands of survivors are dying of AIDS. The Rwandan Widows' Association says that an estimated 70% of its 25 000 members are HIV positive, mainly because they were gang-raped during the massacres.

“We have women who were raped the whole three months of the genocide,” said Esther Mujawayo, a survivor and founder member of the Widows' Association.

In April 1994, extremists from Rwanda's Hutu majority …
Chronic myocardial infarction in the mouse: cardiac structural and functional change
Authors: E Lutgens
Journal: Cardiovascular Research (1999)

Objectives: We studied the effects of chronic left coronary artery ligation on cardiac structure and function in the mouse. Methods: Morphometric studies of the left ventricle were performed in coronary artery-ligated and sham-operated animals at one, two, three and five weeks after surgery. The fraction of DNA-synthesizing cells was determined as the fraction of cells incorporating 5′-bromo-2′-deoxyuridine, which was infused by osmotic minipumps one week before sacrifice. Collagen content of the septum was determined morphometrically. Left ventricular pressure and its derivatives were measured in separate groups of animals at one and three weeks after surgery. Results: Ligation of the main left coronary artery resulted in antero-apical infarction of the left ventricular wall, involving ∼40% of left ventricular circumference. Infarction resulted in thinning of the infarcted area and left ventricular dilatation. DNA synthesis increased, peaking between one and two weeks in the border-zone of the infarct (22-fold), septum (ten-fold) and right ventricle (five-fold). At five weeks, DNA synthesis was still increased in the border zone of the infarct. Septal collagen content increased ~eight-fold in infarcted mice at two weeks, and decreased thereafter; it was still significantly elevated at five weeks. Left ventricular systolic pressure, and maximal positive and negative dP/dt decreased following infarction; left ventricular end-diastolic pressure was elevated at three weeks, but this effect was not statistically significant. Conclusion: These data provide basic information on changes in cardiac structure and function in mice following chronic coronary artery ligation. They indicate the feasibility of induction of chronic myocardial infarction in this species. Furthermore, they show the similarity of cardiac structural and functional consequences of chronic myocardial infarction in mice to those previously described in rats.
Ion channels, oxygen sensation and signal transduction in pulmonary arterial smooth muscle
Authors: R. Z. Kozlowski
Journal: Cardiovascular Research (1995)

In contrast to systemic arteries those of the pulmonary circulation constrict in response to hypoxia: a mechanism known as "hypoxic pulmonary vasoconstriction" (HPV). It is has been established that changes in alveolar oxygen tension are the primary stimulus for triggering HPV. The mechanisms underlying this unique response are unknown. Neither the role of the endothelium nor that of the smooth muscle of the pulmonary arteries in oxygen sensing has been elucidated, although both tissues may be involved. Evidence is accumulating to suggest that K+ channels located in the plasma membranes of pulmonary arterial smooth muscle cells may play an important role in oxygen sensing. This process may involve novel mechanisms of signal transduction and K+ channel regulation by charged intermediates, redox reactions or membrane-delimited factors.
Recurrent Hyperthyroidism After Normal Response To Liothyronine
Authors: Paul Cushman
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Long-term remissions occur in approximately 50% of patients with Graves' disease after discontinuation of protracted antithyroid drug treatment.<sup>1</sup>Criteria that can be used to distinguish patients whose remissions will be maintained from those who will have relapses are of clinical importance and theoretical interest. Recently, it has been observed that after treatment with antithyroid drugs some patients with Graves disease exhibit reduction in their thyroid radioactive iodine uptakes following administration of exogenous thyroid<sup>2</sup>or liothyronine triiodothyronine, T-3.<sup>3</sup>These patients tend to remain euthyroid during the period of follow-up. In contrast, patients who fail to show suppression of iodine uptakes have a high incidence of recurrence of hyperthyroidism. Therefore, testing with exogenous thyroid or liothyronine may be of considerable prognostic value. The present study reports the first case of recrudesence of hyperthyroidism in a euthyroid patient with Graves' disease shortly after a normal response to
Great Aunt Rose
Authors: E. Clarke
Journal: BMJ (2000)

“You know Betty, they should have just taken my leg off. I was a young woman then, I would have coped with it but not now.”Great Aunt Rose, my grandfather's oldest sister, was talking to my mother while I was eating my sticky iced gingerbread. I was 4 years old and just about the right size to be sitting at eye level with my great aunt's offending leg. I was incredulous. Perhaps it was because grown ups chopping off their legs seemed so bizarre to me that I remembered it for so long.

Her leg seemed enormous, tightly bound in a thick orange stocking, as it sat propped up on a leather poof. I have no clear …
Gold binding to blood cells and serum proteins during chrysotherapy.
Authors: R J van de Stadt, B Abbo-Tilstra
Journal: Annals of the Rheumatic Diseases (1980)

The binding of gold to peripheral erythrocytes and serum protein fractions was studied during chrysotherapy of 1 to 2 years' duration in 43 patients with rheumatoid arthritis. In 45% of the patients more than 10% of the gold was found to be strongly bound to blood cells. 5--15% of the metal is bound to non-albumin protein fractions at serum gold concentrations larger than 2 microgram/ml. In contrast to the cellular binding of gold the relative binding of gold to non-albumin proteins was inversely proportional to the serum concentrations. Binding to neither blood cells nor to non-albumin protein fractions was found to be correlated with clinical parameters.
Physicians With Heart
Authors: George J. Cohen
Journal: JAMA (1991)

<h3>To the Editor.</h3> —Medical News &amp; Perspectives<sup>1</sup>recently ran several articles on physicians whose efforts for the medically underserved have made a positive impact. Another such hero is H. Arnold Meyersburg, a psychiatrist in private practice in Kensington, Md. Almost two dozen years ago, as president of a voluntary tutoring group for children from low-income families, he became aware of their difficulty in obtaining health care in affluent Montgomery County, Maryland. Under Dr Meyersburg's leadership, perseverance, and activism, and with help from a few dedicated community leaders, Mobile Medical Care was born after a difficult labor and delivery. In April 1970, its first clinic opened in a church in Ken-Car, a low-income black community, literally "on the other side of the railroad tracks." The Ken-Car citizens' association helped coordinate activities, a small foundation donated seed money, the local Red Cross chapter offered supplies and recruited nurse volunteers, and a
Inhibition of transforming growth factor β receptor I kinase blocks hepatocellular carcinoma growth through neo-angiogenesis regulation
Authors: Antonio Mazzocca, Emilia Fransvea, Gabriela Lavezzari, Salvatore Antonaci, Gianluigi Giannelli
Journal: Hepatology (2009)

Curative therapies for patients with hepatocellular carcinoma (HCC) are mainly invasive, and with the exception of sorafenib, no medical treatments are available for advanced or metastatic stages of HCC. We investigated the antitumoral effect of blocking the transforming growth factor beta (TGF-beta) signaling pathway in HCC with LY2109761, a kinase inhibitor of TGF-beta receptor I kinase. The antitumor activity of LY2109761 was associated with inhibition of molecular pathways involved in neo-angiogenesis and tumor growth of HCC. This anti-angiogenic effect is more effective than that of bevacizumab, which specifically targets vascular endothelial growth factor (VEGF). We found that the paracrine cross-talk between HCC and endothelial cells is blocked by LY210976, inhibiting blood vessel formation. This effect was mediated by SMAD2/3 and affected the secretion of VEGF. Finally, LY2109761 does not show significant effects on physiological angiogenetic development.These data support the rationale for targeting TGF-beta signaling in patients with HCC.