tbuckley/cabot-search huggingface dataset:
Interaction of environmental chemicals with the estrogen and progesterone receptors from the oviduct of the American alligator.
Authors: P M Vonier, D A Crain, J A McLachlan, L J Guillette, S F Arnold
Journal: Environmental Health Perspectives (1996)

Reports of reproductive abnormalities in the American alligator from Lake Apopka, Florida, have been linked to a spill of DDT and other pesticides suspected of having hormonelike activity. To determine whether environmental chemicals had the potential to function as exogenous hormones in the American alligator, we examined the ability of chemicals to bind the estrogen receptor (aER) and progesterone receptor (aPR) in a protein extract prepared from the oviduct of the alligator. In competition binding assays with [3H]17 beta-estradiol, some DDT metabolites showed inhibition of [3H]17 beta-estradiol binding to aER. A combination of DDTs demonstrated an additive decrease in [3H]17 beta-estradiol binding to aER. Modern-use chemicals such as alachlor, trans-nonachlor, endosulfan, and atrazine also competed with [3H]17 beta-estradiol for binding to the aER. To test the effect of chemicals identified in alligator eggs from Lake Apopka on [3H]17 beta-estradiol binding, we mixed these chemicals at concentrations measured in eggs in the competition binding assay. 2,2-bis(4-chlorophenyl)-N-(methoxymethyl)acetamide (p,p'-DDD) and trans-nonachlor, both found in Lake Apopka, interacted with aER, whereas others such as chlordane and toxaphene did not. Surprisingly, combinations of these chemicals decreased [3H]17 beta-estradiol binding in a greater than additive manner. To assess the ability of chemicals to interact with aPR, we performed commpetition binding assays with the synthetic progestin [3H]R5020. Most of the chemicals tested did not reduce [3H]R5020 binding to aPR, whereas endosulfan, alachlor, and kepone inhibited binding. These results provide the first evidence that environmental chemicals bind the aER and aPR from the American alligator, supporting the hypothesis that the reported reproductive abnormalities may be related to the modulation of endocrine-related responses. The findings that combinations of chemicals demonstrated a greater than additive interaction with the aER and some chemicals bind to the aPR in the competition binding assay are novel. This suggests that interactions of these chemicals with the endocrine system are complex.
Use of the Term "Monster"
Authors: H. E. Thelander
Journal: JAMA (1964)

<h3>To the Editor:—</h3> In the Nov 16, 1963, issue ofThe Journal(<b>186</b>:728) there are pictures with the following legends quoted in part, "sireniform monsters." The pictures looked so incongruous with the legends that I turned to<i>Dorland's Illustrated Medical Dictionary</i>for a definition of monster. This is what I found, "An infant born with an anomaly so pronounced that it interferes with the general or local development of the body." The authors therefore were technically correct. I then turned to Webster and found this definition, "[... orig., a divine omen, indicating misfortune.] 1. An animal or plant departing greatly in form or structure from the usual type of species, a monstrosity.... Anything monstrous, esp. a person of unnatural ugliness, cruelty, etc." The Webster definition I think indicates the basis and the usual connotation of the word. Parents of a deformed child have enough difficulties with which to deal without
Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion. Evidence that myocardial "stunning" is a manifestation of reperfusion injury.
Authors: R Bolli, M O Jeroudi, B S Patel, O I Aruoma, B Halliwell, E K Lai, P B McCay
Journal: Circulation Research (1989)

Recent evidence suggests that postischemic myocardial dysfunction ("stunning") may be mediated by oxygen free radicals, but the exact time window during which the critical radical-mediated damage develops remains unknown. Furthermore, the evidence for the oxyradical hypothesis is indirect and, therefore, inconclusive. Thus, the potent and cell-permeable antioxidant N-(2-mercaptopropionyl)-glycine (MPG) was administered as an intra-coronary infusion (8 mg/kg/hr) to three groups of open-chest dogs undergoing a 15-minute coronary occlusion followed by 4 hours of reperfusion. In group I (n = 8), the infusion of MPG was started 15 minutes before occlusion and ended 2 hours after reperfusion; in group II (n = 9), MPG was started 1 minute before reperfusion and ended 2 hours thereafter; in group III (n = 10), MPG was started 1 minute after reperfusion and ended 2 hours and 15 minutes thereafter. Control dogs (group IV) (n = 10) received vehicle. Recovery of contractile function (assessed as systolic wall thickening) was equivalent in groups I and II, and in both groups it was substantially greater than in controls (p less than 0.005 at 4 hours). In contrast, in group III recovery of function was indistinguishable from controls. To determine whether the protection afforded by MPG was due to inhibition of free radical reactions, myocardial production of free radicals was directly assessed by intracoronary infusion of the spin trap alpha-phenyl N-tert-butyl nitrone (PBN). In control dogs (group VII, n = 6), radical adducts of PBN were released in the coronary venous blood after reperfusion, with a burst occurring in the first 5 minutes. MPG given as in group II (group V, n = 5) markedly suppressed myocardial production of PBN adducts (delta = -98% over 3 hours, p less than 0.01 vs. controls); this effect was evident immediately after reperfusion. MPG given as in group III (group VI, n = 5) also suppressed PBN adduct production (delta = -83% over 3 hours, p less than 0.025 vs. controls), but this effect was delayed. Hence, the radicals important in myocardial stunning appear to be those generated immediately after reperfusion. In vitro studies demonstrated that MPG is an exceptionally powerful scavenger of .OH (rate constant = 8.1 x 10(9) M-1 sec-1 by pulse radiolysis) but has no significant effect on .O2- (rate constant less than 10(3) M-1 sec-1), H2O2 (rate constant = 1.6 M-1 sec-1), or non-.OH-initiated lipid peroxidation, suggesting that removal of .OH is the major mechanism of the beneficial effects of MPG.(ABSTRACT TRUNCATED AT 400 WORDS)
The Effect of the 65-mph Speed Limit on Fatalities in New Mexico
Authors: Donald J. Mirate
Journal: JAMA (1990)

<h3>To the Editor.—</h3> In their analysis of the effects of the 65-mph speed limit on interstate highway fatalities, Gallaher et al<sup>1</sup>have overlooked the most important difference in data that occurred after the change in speed limit. Although there was slight reduction in the percent of victims using a seat belt, from 11.9% to 10.5%, there was a great increase in the percent of victims ejected from the vehicle, from 53% to 70%. These data support the need for mandatory seat belt use rather than any decrease in speed limit.
Further Observations on the Effects of Autonomic Blocking Agents in Patients with Hypertension
Authors: DAVID GROB, HERBERT G. LANGFORD, BARBARA ZIEGLER
Journal: Circulation (1953)

Hexamethonium and pentamethonium produced a greater reduction in blood pressure in patients with malignant hypertension who had low serum concentration of sodium or severe encephalopathy than in those with benign hypertension. Concurrent administration of hydrazinophthalazine resulted in an additive effect on the blood pressure of most patients, with slower development of tolerance and less marked postural hypotension. In many patients there was improvement in signs and symptoms attributable to hypertension. Harmful effects of reduction in blood pressure occurred mainly in patients with malignant hypertension and consisted of renal insufficiency and evidence of myocardial and retinal ischemia.
Need for Additional Nomenclature.
Authors: A. Rose
Journal: JAMA (1906)

New York, April 21, 1906. <h3>To the Editor:</h3> —Permit me to say to Dr. Thomas G. Atkinson's proposition under the above heading inThe Journal, April 21, that wherever additional nomenclature is needed we should not accept terms like Dr. Atkinson's hemafecia and pyofecia; our onomatology is disfigured already by such monstrosities and needs reform instead of new horrors.
AN OBJECTIVE EVALUATION OF THE TREATMENT OF SYSTEMIC SCLERODERMA WITH DISODIUM EDTA, PYRIDOXINE AND RESERPINE*
Authors: Farid J. D. Fuleihan, Amal K. Kurban, Raja T. Abboud, Naila Beidas Jubran, Fuad S. Farah
Journal: British Journal of Dermatology (1968)

Journal Article AN OBJECTIVE EVALUATION OF THE TREATMENT OF SYSTEMIC SCLERODERMA WITH DISODIUM EDTA, PYRIDOXINE AND RESERPINE Get access FARID J. D. FULEIHAN, FARID J. D. FULEIHAN Divisions of Respiratory Diseases and Dermatology, Department of Interval Medicine, American University Hospital, Beirut, Lebanon Search for other works by this author on: Oxford Academic Google Scholar AMAL K. KURBAN, AMAL K. KURBAN Divisions of Respiratory Diseases and Dermatology, Department of Interval Medicine, American University Hospital, Beirut, Lebanon Search for other works by this author on: Oxford Academic Google Scholar RAJA T. ABBOUD, RAJA T. ABBOUD Divisions of Respiratory Diseases and Dermatology, Department of Interval Medicine, American University Hospital, Beirut, Lebanon Search for other works by this author on: Oxford Academic Google Scholar NAILA BEIDAS JUBRAN, NAILA BEIDAS JUBRAN Divisions of Respiratory Diseases and Dermatology, Department of Interval Medicine, American University Hospital, Beirut, Lebanon Search for other works by this author on: Oxford Academic Google Scholar FUAD S. FARAH FUAD S. FARAH Divisions of Respiratory Diseases and Dermatology, Department of Interval Medicine, American University Hospital, Beirut, Lebanon Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 80, Issue 3, 1 March 1968, Pages 184–189, https://doi.org/10.1111/j.1365-2133.1968.tb12290.x Published: 01 March 1968 Article history Accepted: 11 September 1967 Published: 01 March 1968
Differentiation of Geriatric Major Depression From Alzheimer’s Disease With CSF Tau Protein Phosphorylated at Threonine 231
Authors: Katharina Buerger, Raymond Zinkowski, Stefan J. Teipel, Hiroyuki Arai, John DeBernardis, Daniel Kerkman, Cheryl McCulloch, Frank Padberg, Frank Faltraco, Alexander Goernitz, Tero Tapiola, Stanley I. Rapoport, Tuula Pirttilä, Hans-Jürgen Möller, Harald Hampel
Journal: American Journal of Psychiatry (2003)

Differentiation of geriatric major depression from Alzheimer's disease is hampered by overlapping symptoms. Increased CSF concentrations of tau protein phosphorylated at threonine 231 (p-tau(231)) have been suggested as a biomarker for Alzheimer's disease. The authors asked whether p-tau(231) levels improve the differential diagnosis between geriatric major depression and Alzheimer's disease.Included were 34 depression subjects, 64 with probable Alzheimer's disease, 17 with possible Alzheimer's disease, and 21 healthy comparison subjects. P-tau(231) concentrations were measured with an enzyme-linked immunosorbent assay.P-tau(231) levels were significantly higher in Alzheimer's disease than in geriatric major depression patients and healthy comparison subjects. For differentiation of probable Alzheimer's disease from major depression, p-tau(231) correctly allocated 87% of subjects. When possible mild Alzheimer's disease was compared to major depression, p-tau(231) correctly allocated 78% of subjects.CSF p-tau(231) should be evaluated as a potential biological marker for differentiation of geriatric depression from Alzheimer's disease.
Thresholds for normal blood pressure and serum cholesterol: Fig 1
Authors: Steinar Westin, Iona Heath
Journal: BMJ (2005)

Lower thresholds mean that 90% of people over 50 years are identified as patients 

F or several years, disagreement has been growing in health services about ever lower thresholds for “normal” blood pressure and serum cholesterol, the most common biological risk factors for cardiovascular disease. This was most publicly expressed in 1999, when more than 800 doctors, pharmacists, and scientists from 42 countries signed an open letter to the then director general Gro Harlem Brundtland, outlining fears that the World Health Organization's new hypertension guidelines would result in increased use of antihypertensive drugs, at great expense and for little benefit.1 2 The simplistic linear structuring of many research questions and the extrapolation of research results over prolonged and unstudied time periods produce guidelines that make many doctors, and particularly general practitioners, feel uneasy about the high proportion of their patients who are being labelled as sick.

General practitioners are aware of the side effects of undue medicalisation and tend to question the external validity of randomised controlled trials under experimental conditions.3 They …
Benefit of exercise in lowering breast cancer risk is lost in postmenopausal women who had gained weight, US study finds
Authors: S. Mayor
Journal: BMJ (2012)

Physical activity reduces women’s risk of breast cancer except among postmenopausal women who gained substantial weight during adulthood, shows a US study.1

The study compared 1504 women with breast cancer with 1555 matched controls (aged 20-98 years) who were part of the Long Island breast cancer study project, which is investigating possible environmental causes of breast cancer.

Although physical activity is known to reduce the risk of breast cancer, the researchers wanted to clarify the duration and intensity of activity needed to reduce risk. They also wanted to identify whether there were any particular periods during a woman’s life when activity was associated with …
High reprint orders in medical journals and pharmaceutical industry funding: case-control study
Authors: A. E. Handel, S. V. Patel, J. Pakpoor, G. C. Ebers, B. Goldacre, S. V. Ramagopalan
Journal: BMJ (2012)

To assess the extent to which funding and study design are associated with high reprint orders.Case-control study.Top articles by size of reprint orders in seven journals, 2002-09.Lancet, Lancet Neurology, Lancet Oncology (Lancet Group), BMJ, Gut, Heart, and Journal of Neurology, Neurosurgery & Psychiatry (BMJ Group) matched to contemporaneous articles not in the list of high reprint orders.Funding and design of randomised controlled trials or other study designs.Median reprint orders for the seven journals ranged from 3000 to 126,350. Papers with high reprint orders were more likely to be funded by the pharmaceutical industry than were control papers (industry funding versus other or none: odds ratio 8.64, 95% confidence interval 5.09 to 14.68, and mixed funding versus other or none: 3.72, 2.43 to 5.70).Funding by the pharmaceutical industry is associated with high numbers of reprint orders.
Transfer of high cost drugs to NICE risks fragmentation of care of rare diseases
Authors: C. J. Hendriksz
Journal: BMJ (2012)

It seems like deja vu for those affected by rare diseases, and once again political change is to blame. Only two years ago the chief medical officer stated: “Services for those with rare diseases are fragmented and often poorly coordinated.”1

Commissioning of services for conditions individually affecting only 10% of the population presents challenges to value, fairness, and equity. Since 2005 the establishment of a UK National Commissioning Group for Rare Disorders (latterly National Specialist Commissioning Team) and Advisory Group for National Specialised Services …
Abstract A2: Cells of origin of the different subtypes of lung cancer
Authors: Caitlin Filby, Kati Viitaniemi, Jonathan McQualter, Philip Antippa, Lou Irving, Ivan Bertoncello, Marie-Liesse Asselin-Labat
Journal: Clinical Cancer Research (2012)

Abstract Lung cancer is the leading cause of cancer death worldwide. Five-year lung cancer survival is only 15% and lung cancer is responsible for more deaths than prostate, colon, pancreas, and breast cancers combined. Understanding the cellular and molecular mechanism at the origin of lung cancer will generate great insights for better management of the disease. However, the lack of cell surface markers to identify and isolate early progenitor or stem cells in the normal lung represents a gap of knowledge that needs to be filled to identify cells of origin of lung cancers. By macroscopic isolation of different morphological region of the human lung and staining with cell surface markers, we have isolated distinct cell subpopulations by flow cytometry. Interestingly, these markers are expressed in some types of lung cancers but not others. We are characterizing the different subpopulations by immunostaining of cytospun cells and evaluating their in vitro colony formation capacity. In order to address potential cells of origin for the different lung tumor subtypes, gene signatures of the different normal epithelial subpopulations will be compared to the gene expression profiles of lung carcinomas available from public database. These cell surface markers may be critical tools to identify stem/progenitor cells in the normal lung that could be the cell of origin of one type of lung cancer and not others.
Modulation of human endothelial thrombomodulin by neutrophils and their release products.
Authors: I R MacGregor, A M Perrie, S C Donnelly, C Haslett
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Pulmonary microvascular injury, one of the earliest events in adult respiratory distress syndrome (ARDS), is caused by the release of injurious products from stimulated neutrophils and other inflammatory cells in the lung microvessels. An increased level of the endothelial cell-surface anticoagulant protein thrombomodulin (TM) in plasma from patients with ARDS as shown in this study may be one consequence of this, and our objective in this investigation was to define the mechanisms by which TM is modulated by neutrophils, using an endothelial tissue culture system. Human neutrophils in contact with endothelium caused a fourfold reduction in cell-surface TM activity, but only after prior neutrophil priming and activation. Neutrophil release products elastase and cathepsin G caused rapid dose-related reductions in endothelial cell-surface TM activity, with complete abolition at 5 microg/ml in the absence of endothelial detachment. H2O2 also reduced TM activity. TM antigen accumulated in culture supernatant after treatment of endothelium with cathepsin G, indicating proteolytic release of cell-surface TM. We conclude that primed activated neutrophils are potent modulators of endothelial TM in vitro.
Post‐infarction treatment with simvastatin reduces myocardial no‐reflow by opening of the K<sub>ATP</sub> channel
Authors: Yue‐Jin Yang, Jing‐Lin Zhao, Shi‐Jie You, Yong‐Jian Wu, Zhi‐Cheng Jing, Run‐Lin Gao, Zai‐Jia Chen
Journal: European Journal of Heart Failure (2006)
Imogen 38: a novel 38-kD islet mitochondrial autoantigen recognized by T cells from a newly diagnosed type 1 diabetic patient.
Authors: S D Arden, B O Roep, P I Neophytou, E F Usac, G Duinkerken, R R de Vries, J C Hutton
Journal: Journal of Clinical Investigation (1996)

Cell-mediated autoimmune attack directed against islet proteins of approximately 38 kD in size has been associated with type 1 diabetes. A novel murine cDNA encoding an antigen of this size was cloned using a screening procedure based on the proliferative response of a human diabetic T cell clone (1C6) to a recombinant antigen epitope library. Membrane preparations from COS 7 cells transfected with the full-length 1,267-bp cDNA elicited a proliferative response from the reporter T cells comparable to that of the defined peptide epitope and native insulinoma antigen. In vitro translation and transfection experiments suggested that the protein is initially synthesized as a 44-kD protein and then processed to the native 38-kD form through the proteolytic removal of a 54-aa NH2-terminal mitochondrial targeting sequence. Differential centrifugation, Percoll density gradient centrifugation, and immunofluorescence studies confirmed localization of the antigen to mitochondria. Northern blot, Western blot, and 1C6 T cell proliferation assays showed that, although imogen 38 was more highly expressed in beta cell than alpha cell lines, it was also present in other tissues. It is concluded that imogen 38 may be a target for bystander autoimmune attack in diabetes rather than a primary autoantigen.
A comparison of psoralen plus ultraviolet A (PUVA) monotherapy, tacalcitol plus PUVA and tazarotene plus PUVA in patients with chronic plaque-type psoriasis
Authors: S. Tzaneva, A. Seeber, H. Honigsmann, A. Tanew
Journal: British Journal of Dermatology (2002)

Numerous studies have shown that the additional administration of topical or systemic antipsoriatic agents might serve as an effective means to increase the efficacy of photochemotherapy [psoralen plus ultraviolet (UV) A (PUVA)] for psoriasis.To compare the therapeutic response to tacalcitol plus PUVA, tazarotene plus PUVA and PUVA monotherapy in patients with chronic plaque-type psoriasis. In addition, we also assessed the duration of remission induced by each regimen and the tolerability of the two combination treatments.Thirty-one patients with chronic plaque-type psoriasis were included in this observer-blinded, intrapatient comparison trial. PUVA treatment was given four times weekly. Additionally, tacalcitol ointment and 0.1% tazarotene gel were applied separately on two target areas once daily in the evening. At the onset of therapy and every 2 weeks thereafter the response to treatment was determined by the Psoriasis Severity Index score, which assesses the degree of erythema, infiltration and scaling of the psoriatic lesions. After complete or near complete clearing patients were followed-up until relapse.Twenty-four patients completed the study. The treatment requirements to induce complete or near complete clearing were significantly lower for both combination treatments than for PUVA monotherapy (P < 0.01). The median cumulative UVA dose and number of exposures were 30.6 J cm-2 (95% confidence interval, CI 22.5-71.2) and 14 (95% CI 11-16) for tacalcitol plus PUVA, 32.3 J cm-2 (95% CI 22.5-73.8) and 14 (95% CI 11-19) for tazarotene plus PUVA, and 37.0 J cm-2 (95% CI 29.5-83.9) and 16 (95% CI 14-22) for PUVA monotherapy. No difference between the three regimens was observed with regard to duration of remission. Adverse reactions occurred more often with 0.1% tazarotene than with tacalcitol but were in general mild and completely reversible upon using a lower concentration of 0.05% tazarotene.Tacalcitol ointment and tazarotene gel are both comparably effective in improving the therapeutic result of PUVA therapy in patients with chronic plaque-type psoriasis. Besides accelerating the treatment response, both agents, by virtue of their UVA dose-sparing effect, might also help to reduce possible long-term hazards of PUVA treatment.