tbuckley/cabot-search huggingface dataset:
Phytoestrogens and Breast Cancer Prevention: Possible Mechanisms of Action
Authors: Sarah M. Mense, Tom K. Hei, Ramesh K. Ganju, Hari K. Bhat
Journal: Environmental Health Perspectives (2008)

Phytoestrogens display an array of pharmacologic properties, and in recent years investigation of their potential as anticancer agents has increased dramatically. In this article we review the published literature related to phytoestrogens and breast cancer as well as suggest the possible mechanisms that may underlie the relationship between phytoestrogens and breast cancer.Electronic searches on phytoestrogens and breast cancer were performed on MEDLINE and EMBASE in June 2007. No date restriction was placed on the electronic search.We focused on experimental data from published studies that examined the characteristics of phytoestrogens using in vivo or in vitro models. We also include human intervention studies in this review.We evaluated evidence regarding the possible mechanisms of phytoestrogen action. Discussions of these mechanisms were organized into those activities related to the estrogen receptor, cell growth and proliferation, tumor development, signaling pathways, and estrogen-metabolizing enzymes.We suggest that despite numerous investigations, the mechanisms of phytoestrogen action in breast cancer have yet to be elucidated. It remains uncertain whether these plant compounds are chemoprotective or whether they may produce adverse outcomes related to breast carcinogenesis.
Infant Death Rates
Authors: Otto C. Phillips
Journal: JAMA (1971)

<h3>To the Editor.—</h3> The editorial by Balfe, "Infant Death Rates" is an interesting example of nationalistic, defensive, propaganda writing. The author refutes statements of unidentified, and therefore defenseless writers, and he refers to emotional discussion based on inadequate data and erroneous conclusions. In addition, he repeatedly criticizes "implications" that he himself reads into statements, a precarious basis at best for any charge. Balfe does make several points in rebuttal to the uncited targets of his editorial. Infant mortality is not a good indicator of the health status of the nation. Infant mortality is not a good criterion for international ranking of health status. Mr. Balfe points out that statistical comparability is questionable and that the implications [italics mine] are invalid. Dr. I. M. Moriyama, Chief, Office of Health Statistics Analysis of the Department of Health, Education, and Welfare, after reviewing international data, has stated that The difference between
Noninvasive Assessment of LV Contraction Patterns Using CMR to Identify Responders to CRT
Authors: Manav Sohal, Anoop Shetty, Simon Duckett, Zhong Chen, Eva Sammut, Sana Amraoui, Gerry Carr-White, Reza Razavi, Christopher Aldo Rinaldi
Journal: JACC. Cardiovascular imaging (2013)
Effect of Plasma Protein Adsorption on Protein Excretion in Kidney-Transplant Recipients with Recurrent Nephrotic Syndrome
Authors: Jacques Dantal, Edith Bigot, Willy Bogers, Angelo Testa, Faical Kriaa, Yannick Jacques, Bruno Hurault de Ligny, Patrick Niaudet, Bernard Charpentier, Jean P. Soulillou
Journal: New England Journal of Medicine (1994)

Among patients with the idiopathic nephrotic syndrome who have focal and segmental glomerulosclerosis and undergo renal transplantation, 15 to 55 percent have recurrent nephrotic syndrome. The recurrence may be caused by a plasma factor or factors that increase glomerular permeability, because plasma exchange transiently decreases or abolishes proteinuria in some patients. We studied the effect on proteinuria of the removal of protein (mostly immunoglobulins) by adsorption onto protein A from the plasma of patients with recurrent nephrotic syndrome.
Expiratory flow pattern following single-lung transplantation in emphysema.
Authors: J P Herlihy, J G Venegas, D M Systrom, R E Greene, K A McKusick, J C Wain, L C Ginns
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

In single lung transplantation (SLT) recipients, a "plateau" of the maximal expiratory flow volume curve (MEFV) and a "biphasic" MEFV have been reported to reflect anastomosis pathology. A plateau is defined as constant airflow over a large expired volume early in the MEFV. A biphasic MEFV has an initial period of high flow followed by a terminal low flow phase. Models of expiratory flow limitation by wave speed, however, predict that the MEFV of SLT recipients with emphysema should both be biphasic and demonstrate a plateau even without anastomosis pathology. Review of the spirometries and clinical courses of our first ten patients receiving SLT for emphysema demonstrated a biphasic MEFV, and a plateau of the MEFV in all patients. No patient showed evidence of anastomosis pathology. Independent lung spirometries, generated by a novel technique, revealed that the initial high flow phase of the MEFV came from the transplanted lung and the terminal low flow from the native emphysematous lung. The location of the flow limitation was demonstrated to be immediately downstream from the anastomosis. Therefore, the MEFV of SLT recipients with emphysema routinely demonstrates both a biphasic pattern and a plateau, neither of which necessarily reflect anastomosis pathology.
Anticardiolipin antibodies in Adamantiades-Behcet's disease
Authors: Ch.C. ZOUBOULIS, P. BUTTNER, B. TEBBE, C.E. ORFANOS
Journal: British Journal of Dermatology (1993)

Moderately raised levels of circulating anticardiolipin antibodies were found in 14 of 30 patients with active Adamantiades-Behçet's disease (46.7%) who were not receiving treatment. Three patients showed the IgG isotype, nine the IgM isotype, and two had both IgG and IgM isotypes. Statistical analysis, to determine possible correlations between anticardiolipin antibodies and clinical features, and meta-analysis of the data available, were performed. A positive correlation between erythema nodosum and histologically confirmed cutaneous vasculitis and the presence of circulating anticardiolipin antibodies of the IgM isotype was found (P = 0.017 and 0.018, respectively), whereas the IgG isotype did not correlate with any clinical feature. Evaluation of data on other clinical manifestations showed no correlation, either with the IgG or IgM isotypes. In particular, there was no association of circulating anticardiolipin antibodies with the incidence of thrombosis, systemic vasculitis, retinal involvement or neurological features. These results suggest that anticardiolipin antibodies do not play a major pathogenetic role in Adamantiades-Behçet's disease, but they may serve as an additional marker for a risk of the development of cutaneous vasculitis such as erythema nodosum.
Fibrosis of atria and great vessels in response to angiotensin II or aldosterone infusion
Authors: Y Sun
Journal: Cardiovascular Research (1997)

Objective: Myocardial fibrosis, associated with increased expression of angiotensin converting enzyme (ACE) and bradykinin (BK) receptor binding at sites of tissue repair, accompanies chronic elevations in circulating angiotensin II (AngII) and/or aldosterone (ALDO) that simulate chronic cardiac failure. A role for increased ventricular wall stress, associated with arterial hypertension, that can accompany such neurohormonal activation when ventricular function is not compromised, has been held responsible for this structural remodeling. To address this proposition, we monitored morphology of right and left atria and pulmonary artery, where stress is not increased, and compared these structures with hypertensive aorta. Methods: Experimental groups included: (1) unoperated and untreated controls; (2) intact rats receiving AngII (9 μg/h) for 2 weeks and which causes arterial hypertension; (3) uninephrectomized control rats on a high sodium diet for 6 weeks; and (4) uninephrectomized rats receiving ALDO (0.75 μg/h) and a high sodium diet for 6 weeks and which results in gradual onset arterial hypertension. Fibrosis was identified by light microscopy in sections stained with collagen specific picrosirius red, while ACE, AngII and BK receptor binding were localized and quantitated by in vitro autoradiography using 125I-351A, 125I[Sar1,Ile8]AngII, and 125I[Tyr8]BK, respectively. AngII receptor subtype was defined by the presence of excess AT1 (losartan) or AT2 (PD123177) receptor antagonists, respectively. Results: With either AngII or ALDO administration, and compared to controls, we found: (1) microscopic scarring that replaced lost myocytes in both left and right atria; (2) an increase in adventitial collagen of both pulmonary artery and aorta (perivascular fibrosis); (3) markedly increased ACE binding at fibrous tissue sites in both atria and great vessels; (4) unchanged atrial and great vessel AT1 receptor binding; and (5) significantly increased BK receptor binding at sites of atrial and perivascular fibrosis. Conclusions: Thus, the appearance of atrial fibrosis and perivascular fibrosis of aorta and pulmonary artery, together with associated increase in ACE and BK receptor binding, in rats receiving AngII or ALDO suggests these responses are not related to altered ventricular wall stress or arterial hypertension, but rather to these effector hormones of the circulating renin–angiotensin–aldosterone system. Local BK, regulated by ACE found in fibrous tissue and BK receptor binding may play a role in structural remodeling of atria and great vessels in these rat models that simulate chronic cardiac failure.
Altered Distribution of Tritiated Digoxin in the Infarcted Canine Left Ventricle
Authors: GEORGE A. BELLER, THOMAS W. SMITH, WILLIAM B. HOOD
Journal: Circulation (1972)

In order to determine the distribution pattern of digoxin in infarcted and ischemic tissue, the early uptake of tritiated digoxin ( 3 H-digoxin) in the acutely and chronically infarcted canine left ventricle (LV) was studied. Seven open-chest anesthetized dogs were given 3 H-digoxin intravenously 1 hour following acute anterior-wall infarction produced by serial coronary arterial branch ligations. Central and peripheral zones of infarction, ischemic border zones, and nonischemic myocardium were demarcated by epicardial electrode mapping. Two hours after 3 H-digoxin administration, animals were sacrificed and epicardial and endocardial samples from each zone were analyzed for 3 H-digoxin uptake. Significantly lower digoxin concentrations (ng/g wet weight ± ( sem ) were found in both endocardial (endo) and epicardial (epi) regions of the center (endo 27 ± 11; epi 58 ± 10) and periphery (endo 51 ± 13; epi 112 ± 13) of the infarct as compared to the border (endo 217 ± 21; epi 242 ± 15) and nonischemic (endo 256 ± 22; epi 220 ± 20) zones. Significant transmural gradients of the glycoside observed in infarct zones (endo/epi ratio 0.46) were the reverse of those found in nonischemic portions of the myocardium (endo/epi ratio 1.16). Four dogs with chronic infarcts showed 3 H-digoxin uptake patterns similar to acutely infarcted animals. In four sham-operated dogs, 3 H-digoxin uptake was homogeneous in all areas of the LV. This marked alteration of early 3 H-digoxin uptake by the infarcted LV may predispose to electrical instability and the genesis of ectopic rhythm disturbances. The pattern of LV digoxin uptake appears to reflect, at least in part, regional blood flow to infarcted, ischemic, and nonischemic tissue.
Progressive multifocal leukoencephalopathy after fludarabine therapy for low‐grade lymphoproliferative disease
Authors: Brynjar Vidarsson, Deane F. Mosher, M. Shahriar Salamat, Helgi J. Isaksson, Pall T. Onundarson
Journal: American Journal of Hematology (2002)

Fludarabine is becoming the initial therapy for low-grade lymphoproliferative malignancies, such as CLL and follicular lymphoma. Fludarabine is highly immunosuppressive in addition to being myelosuppressive and has been associated with neurotoxicity. Progressive multifocal leukoencephalopathy (PML) is an infection with JC virus of the white matter of the central nervous system seen mostly in immunosuppressed patients. We describe two patients treated with fludarabine who developed PML. Immunolabeling was positive for JCV in both patients, but PCR was repeatedly negative in one of them. We suggest that fludarabine may increase the risk of PML in patients with lymphoproliferative diseases.
AN EXPERIMENTAL AND CLINICAL STUDY OF THE VALUE OF CLAY-MIXTURE POULTICES.
Authors: AUGUSTUS H. ROTH
Journal: JAMA (1905)

One of the most interesting phenomena ih the trend of our modern therapeutics is the present extensive use by physicians of the variously medicated clay mixtures as external applications in the treatment of pneumonia, bronchitis, pleurisy, rheumatism, synovitis, boils, etc., in place of the cotton jacket, mustard and flaxseed poultices, blisters, cupping, camphorated oils and hot stupes. By a clay mixture I mean any one of the various proprietary preparations which are said to have an antiphlogistic action in inflammations of superficial and deep structures. The essential composition of all such clay mixtures is a base consisting of silicate of alumina and magnesia combined with salicylic acid, peppermint, wintergreen, eucalyptus, iodin or ammonium iodid and iron carbonate. The glycerin is added to give the kaolin or white clay its thick, jelly-like consistency so as to allow of easy spreading, while the other substances are added for whatever
The Role of Effort in Coronary Occlusion-Reply
Authors: Arthur M. Master
Journal: JAMA (1961)

<h3>To the Editor:—</h3> May I note that my paper concentrated on the exertion and type of employment of the patient. Everyone realizes that mental or emotional strain may impose a burden on the circulatory apparatus. Are we to conclude from Dr. Hyman's statement that this strain causes acute coronary occlusion? Not in my opinion, but it may precipitate angina pectoris or acute coronary insufficiency without occlusion. It has been an uphill struggle to demonstrate that acute coronary occlusion, unlike other types of acute coronary episodes, is not precipitated by effort. At one time, I was a voice in the wilderness; now, this is an opinion of a multitude. In my first "compensation" case appearances, 1928 to 1930, I testified that coronary occlusion was precipitated by effort; this was then the commonly accepted belief. It was only when I began studying the patients in the wards of the old New York
More models of the cerebellum
Authors: James C. Houk, Andrew G. Barto
Journal: Behavioral and Brain Sciences (1996)

Neural models are needed at many levels, ranging from the biophysically based to connectionist abstractions. The adjustable pattern generator (APG) model of the cerebellum discussed in the target article by Houk, Buckingham, and Barto operates at an intermediate level and is constrained by a large body of anatomical and physiological data. The associative memory model originally proposed by Marr (1969) and Albus (1971) on the basis of the microcircuitry of the cerebellar cortex is still relevant today, although it needs to be coupled to the problem of motor pattern generation. In considering the problem of cerebellar learning, one needs some source of training information to adjust network performance so that it performs fruitful interactions with the environment; however, it is not true that this “teacher” needs to be particularly smart. We address these and other important issues raised by the commentators.
Urographic Changes in Acute Papillary Necrosis in the Rat
Authors: R. A. Risdon, C. L. Berry, A. R. Chrispin
Journal: BMJ (1970)

Intravenous high-dosage urography was performed in rats which had renal papillary necrosis induced with ethyleneimine or renal tubular necrosis produced with mercuric chloride. In both groups, nephrograms were abnormally persistent. In animals treated with ethyleneimine dense selective opacification of the necrotic renal pyramid occurred. It is suggested that this selective opacification may be a valuable radiological sign of recent renal papillary necrosis.
P-selectin mediates adhesion of platelets to neuroblastoma and small cell lung cancer.
Authors: J P Stone, D D Wagner
Journal: Journal of Clinical Investigation (1993)

Activated platelets and stimulated endothelial cells express P-selectin, an integral membrane protein receptor that binds monocytes and neutrophils. P-selectin mediates adhesion to glycoproteins with carbohydrate structures containing sialyl-Lewis X. Since many carcinoma cells also express these carbohydrate structures and are known to interact with platelets, we asked whether P-selectin may mediate this interaction. Both small cell lung cancer and neuroblastoma cell lines bound to activated platelets, and this interaction was blocked with inhibitory anti-P-selectin antibodies and by pretreatment of these cancer cells with neuraminidase or trypsin. Platelet binding to the small cell lung cancer cells was not inhibited with anti-GP IIb-IIIa antibody or Arg-Gly-Asp-Ser peptide. Pretreatment of the neuroblastoma cells with inhibitors of N-linked carbohydrate biosynthesis had little effect on binding to P-selectin, indicating that relevant carbohydrate ligand(s) may be O-linked. In addition, lipospheres containing P-selectin specifically bound to cryostat sections derived from a small cell lung tumor and two neuroblastoma tumors, but not to sections of normal lung. These observations demonstrate that P-selectin mediates binding of platelets to small cell lung cancer and to neuroblastoma and suggest a possible role for this lectin in metastasis.
More on treating homosexuality as a sickness: Homosexuality is punishable in India
Authors: Vikas Dhikav
Journal: BMJ (2004)

Sulfadoxine-pyrimethamine for uncomplicated falciparum malaria Sulfadoxine-pyrimethamine is not working in MalawiEditor-The paper by Plowe et al entitled "Sustained clinical efficacy of sulfadoxinepyrimethamine for uncomplicated falciparum malaria" might be better titled "Sustained lack of efficacy of sulfadoxinepyrimethamine. ..." 1 By the start of the study period five years ago, molecular genotyping showed that Plasmodium falciparum in Malawi had already acquired significant resistance to the combination. 1 2This explains the sustained lack of efficacy; 28 day cure rates in children with acute falciparum malaria remained steadily less than 40% over the five year study period.This is confirmed by the Malawi component of recent WHO-Special Programme for Research and Training in Tropical Diseases (TDR) multicentre trials; the 28 day cure rate with sulfadoxine-pyrimethamine in children with acute falciparum malaria was only 23%, 3 and this for a major killing disease of childhood.A 77% failure rate is among the worst responses ever documented.Only 7% (5/71) of reported trials on sulfadoxinepyrimethamine have had worse failure rates. 4efore sulfadoxine-pyrimethamine was introduced widely it was very effective in Malawi, but, since then, efficacy has fallen dramatically (table).The front page of the BMJ was wrong: sulfadoxine-pyrimethamine is not "still working."A drug giving a cure rate of consistently less than 40% for a potentially life threatening infection cannot be described as having "good efficacy," particularly when highly effective alternatives exist.Can you imagine endorsing an antibiotic with a more than 60% failure rate for use in European or American children with those words?Demographic surveillance system data from eastern and southern Africa show that mortality attributable to malaria in children almost doubled between 1990 and 1998, whereas by contrast non-malaria related mortality fell.The use of ineffective drugs, such as sulfadoxine-pyrimethamine in Malawi, may well be to blame.
Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis
Authors: Hyung J. Chun, Ziad A. Ali, Yoko Kojima, Ramendra K. Kundu, Ahmad Y. Sheikh, Rani Agrawal, Lixin Zheng, Nicholas J. Leeper, Nathan E. Pearl, Andrew J. Patterson, Joshua P. Anderson, Philip S. Tsao, Michael J. Lenardo, Euan A. Ashley, Thomas Quertermous
Journal: Journal of Clinical Investigation (2008)

Apelin and its cognate G protein–coupled receptor APJ constitute a signaling pathway with a positive inotropic effect on cardiac function and a vasodepressor function in the systemic circulation. The apelin-APJ pathway appears to have opposing physiological roles to the renin-angiotensin system. Here we investigated whether the apelin-APJ pathway can directly antagonize vascular disease-related Ang II actions. In ApoE-KO mice, exogenous Ang II induced atherosclerosis and abdominal aortic aneurysm formation; we found that coinfusion of apelin abrogated these effects. Similarly, apelin treatment rescued Ang II–mediated increases in neointimal formation and vascular remodeling in a vein graft model. NO has previously been implicated in the vasodepressor function of apelin; we found that apelin treatment increased NO bioavailability in ApoE-KO mice. Furthermore, infusion of an NO synthase inhibitor blocked the apelin-mediated decrease in atherosclerosis and aneurysm formation. In rat primary aortic smooth muscle cells, apelin inhibited Ang II–mediated transcriptional regulation of multiple targets as measured by reporter assays. In addition, we demonstrated by coimmunoprecipitation and fluorescence resonance energy transfer analysis that the Ang II and apelin receptors interacted physically. Taken together, these findings indicate that apelin signaling can block Ang II actions in vascular disease by increasing NO production and inhibiting Ang II cellular signaling.
Genomewide Analysis of Aryl Hydrocarbon Receptor Binding Targets Reveals an Extensive Array of Gene Clusters that Control Morphogenetic and Developmental Programs
Authors: Maureen A. Sartor, Michael Schnekenburger, Jennifer L. Marlowe, John F. Reichard, Ying Wang, Yunxia Fan, Ci Ma, Saikumar Karyala, Danielle Halbleib, Xiangdong Liu, Mario Medvedovic, Alvaro Puga
Journal: Environmental Health Perspectives (2009)

The vertebrate aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates cellular responses to environmental polycyclic and halogenated compounds. The naive receptor is believed to reside in an inactive cytosolic complex that translocates to the nucleus and induces transcription of xenobiotic detoxification genes after activation by ligand.We conducted an integrative genomewide analysis of AHR gene targets in mouse hepatoma cells and determined whether AHR regulatory functions may take place in the absence of an exogenous ligand.The network of AHR-binding targets in the mouse genome was mapped through a multipronged approach involving chromatin immunoprecipitation/chip and global gene expression signatures. The findings were integrated into a prior functional knowledge base from Gene Ontology, interaction networks, Kyoto Encyclopedia of Genes and Genomes pathways, sequence motif analysis, and literature molecular concepts.We found the naive receptor in unstimulated cells bound to an extensive array of gene clusters with functions in regulation of gene expression, differentiation, and pattern specification, connecting multiple morphogenetic and developmental programs. Activation by the ligand displaced the receptor from some of these targets toward sites in the promoters of xenobiotic metabolism genes.The vertebrate AHR appears to possess unsuspected regulatory functions that may be potential targets of environmental injury.