tbuckley/cabot-search huggingface dataset:
Toxicity of Endogenous and Environmental Estrogens: What Is the Role of Elemental Interactions?
Authors: George M. Stancel, Holly L. Boettger-Tong, Constance Chiappetta, Salman M. Hyder, John L. Kirkland, Lata Murthy, David S. Loose-Mitchell
Journal: Environmental Health Perspectives (1995)

Many naturally occurring and man-made chemicals present in the environment possess estrogenic activity.Examples include plant and fungal products, pesticides, plasticizers, and other agricultural and industrial chemicals.These environmental estrogens as well as endogenous ovarian estrogens are thought to initiate their physiological actions in target tissues largely via interactions with a nuclear receptor system.The resultant estrogen-receptor complex in turn affects transcription via its interactions with nucleotide sequences known as estrogen response elements (EREs) present in the regulatory regions of hormone responsive genes.A "consensus" ERE sequence GGTCAnnnTGACC was originally identified in the vitellogenin genes of birds and amphibians, but it is now clear that most naturally occurring EREs differ from this sequence in one or more bases.We and others have obtained both in vivo and in vitro data suggesting a differential interaction of receptor complexes containing different ligands with the multiple EREs present in mammalian systems.This raises the possibility that the toxicity of environmental estrogens may arise in part from a differential pattern of ERE activation by environmental compounds relative to endogenous ovarian estrogens.The experimental basis for such a paradigm and its toxicological implications are discussed in this paper.
References and Reviews
Journal: JAMA (1969)

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Factual Error
Authors: Jayshil Patel, Paul Bergl
Journal: JAMA (2018)

To the Editor Dr Cifu 1 stated in his Viewpoint that diagnostic calibration is "…the relationship between diagnostic accuracy and physician confidence in that accuracy" and suggested static and dynamic influences determine diagnostic calibration.We agree with Cifu and Meyer et al 2 that the most worthwhile effort in improving diagnostic calibration is receiving regular feedback on diagnostic accuracy.However, we also advocate practicing metacognition and physicians educating themselves on the myriad cognitive biases that affect diagnostic decisions.These strategies promote the self-awareness that we believe is important for achieving appropriately calibrated confidence and diagnostic excellence.Static and dynamic influences determine diagnostic calibration and other factors such as fatigue, ambient conditions, and team dynamics contribute to diagnostic accuracy.Often, these static and dynamic factors lead physicians down an appropriate cognitive pathway or "cognitive disposition to respond" and to provide a correct diagnosis. 3However, during periods of uncertainty, the summation of numerous static and dynamic factors may promote diagnostic misadventures.Awareness of these factors may be promoted during realtime clinical decision making.For example, by conducting "cognitive and affective autopsies" or a "diagnostic timeout" on rounds, trainees can increase their awareness of static and dynamic factors and review their actual cognitive response.Physicians in practice may find a similar approach helpful by routinely asking themselves the simple question, "What else could this be?"These brief reflections allow learners and practicing clinicians alike to refine their diagnoses in the context of associated dispositions and response.More importantly, they give physicians pause and an opportunity to recognize their level of diagnostic confidence.Cognitive errors or errors in data synthesis or faulty knowledge are purportedly the most common cause of diagnostic error. 4Cognitive errors often occur as a result of overconfidence and overreliance on intuitive modes of thinking. 5Using metacognition forces use of more analytical modes of thinking.Coupled with regular feedback on diagnostic performance, awareness of factors that influence decisions may realign clinicians' diagnostic confidence and accuracy.In effect, diagnostic calibration itself may be recalibrated toward diagnostic harmonization.
The Role of Metals in Carcinogenesis: Biochemistry and Metabolism
Authors: K. Wetterhahn Jennette
Journal: Environmental Health Perspectives (1981)

The oxyanions of vanadium, chromium, molybdenum, arsenic, and selenium are stable forms of these elements in high oxidation states which cross cell membranes using the normal phosphate and/or sulfate transport systems of the cell. Once inside the cell, these oxyanions may sulfuryl transfer reactions. Often the oxyanions serve as alternate enzyme substrates but form ester products which are hydrolytically unstable compared with the sulfate and phosphate esters and, therefore, decompose readily in aqueous solution. Arsenite and selenite are capable of reacting with sulfhydryl groups in proteins. Some cells are able to metabolize redox active oxyanions to forms of the elements in other stable oxidation states. Specific enzymes may be involved in the metabolic processes. The metabolites of these elements may form complexes with small molecules, proteins and nucleic acids which inhibit their ability to function properly. The divalent ions of beryllium, manganese, cobalt, nickel, cadmium, mercury, and lead are stable forms of these elements which may mimic essential divalent ions such as magnesium, calcium, iron, copper, or zinc. These ions may complex small molecules, enzymes, and nucleic acids in such a way that the normal activity of these species is altered. Free radicals may be produced in the presence of these metal ions which damage critical cellular molecules.
THE ALLEGED EXCRETION OF MORPHIN INTO THE STOMACH
Journal: JAMA (1925)

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Medical Education and State Boards of Registration
Journal: JAMA (1913)

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The treatment of cancer in an aging population
Authors: J. E. Harris
Journal: JAMA (1992)

America is aging. The demographic data to support this statement are convincing and compelling.<sup>1</sup>At present, the population aged 55 years and older is over one fifth of the total population. By 2010, one fourth of the total US population (74.1 million persons) is projected to be at least 55 years old; one in seven Americans will be 65 years or older (39.3 million) and the number of persons aged 85 years and older will be 2.4% of the total population (6.8 million). Within the over-65 group, the most rapidly growing subgroup is the "oldest old" (those over 85 years old). Cancer is a disease that affects primarily older persons.<sup>2</sup>As our aging population increases in size, the incidence of cancer will rise. The growing elderly population will show a greater prevalence of cancer. Over half of all cancer is diagnosed in those over the age of 65
EXIT OF SCIENTISTS FROM MONTREAL.
Journal: JAMA (1884)

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Gants' Diseases of the Bladder and Hawe's Excessive Venery.—Excessive Venery, Masturbation, and Continence; the Ætiology, Pathology, and Treatment.
Authors: None E. W. A.
Journal: JAMA (1884)

This volume contains the substance of a course of lectures delivered in the University of New York, supplemented as the writer states, by an account of the peculiar methods of treatment of various American and European authorities, thus forming a manual of reference. The work has been done with no great thoroughness or completeness. In fact, as a work of reference it is not equal to several of the standard treatises from which it is largely compiled. Those parts of the work which are really most telling and attractive are the long quotations from Acton, Hammond (Male Impotence), and similar well-known works. We do not like the<i>tone</i>of the book. "Sons of Manhood" is a definition not too loose for the writer's taste, as he employs it more than once. The value of a work which expressly treats continence among the causes of disease and insanity (p. 62) is
Kinase-mediated regulation of common transcription factors accounts for the bone-protective effects of sex steroids
Authors: Stavroula Kousteni, Li Han, Jin-Ran Chen, Maria Almeida, Lilian I. Plotkin, Teresita Bellido, Stavros C. Manolagas
Journal: Journal of Clinical Investigation (2003)

It has been found that 4-estren-3α,17β-diol, a synthetic ligand for the estrogen receptor (ER) or androgen receptor (AR), which does not affect classical transcription, reverses bone loss in ovariectomized females or orchidectomized males without affecting the uterus or seminal vesicles, demonstrating that the classical genotropic actions of sex steroid receptors are dispensable for their bone-protective effects, but indispensable for their effects on reproductive organs. We have now investigated the mechanism of action of this compound. We report that, identically to 17β-estradiol or dihydrotestosterone, but differently from raloxifene, estren alters the activity of Elk-1, CCAAT enhancer binding protein–β (C/EBPβ), and cyclic adenosine monophosphate–response element binding protein (CREB), or c-Jun/c-Fos by an extranuclear action of the ER or AR, resulting in activation of the Src/Shc/ERK pathway or downregulation of JNK, respectively. All of these effects are non–sex specific, require only the ligand-binding domain of the receptor, and are indispensable for the antiapoptotic action of these ligands on osteoblastic and HeLa cells. Moreover, administration of 17β-estradiol or 4-estren-3α,17β-diol to ovariectomized mice induces phosphorylation of ERKs, Elk-1, and C/EBPβ, downregulates c-Jun, and upregulates the expression of egr-1, an ERK/SRE target gene. Kinase-initiated regulation of commonly used transcription factors offers a molecular explanation for the profound skeletal effects of sex steroid receptor ligands, including synthetic ones that are devoid of classical transcriptional activity.
Aerospace Medicine, St. Paul
Journal: JAMA (1964)

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Bone Scanning
Authors: Peter H. Cox
Journal: JAMA (1976)

<h3>To the Editor.—</h3> The comments of Freeman et al (235:1965, 1976) concerning Loeffler's interpretation of bone scintigrams (234:1228, 1975) are soundly based and can be supported from the many clinical reports that have appeared in the literature, with one exception. I would suggest that their comments with regard to the clinical significance of the degree of renal uptake of<sup>99m</sup>Tc phosphate complexes is open to criticism. It has been implied that poor kidney visualization on the skeletal scintigram indicates an enhanced uptake of polyphosphate complex in the skeleton due to the presence of a diffuse pathological process. If this were so, then in the case of a patient with highly active multiple skeletal metastases, such as may occur with prostatic or breast cancer, one would also expect to observe decreased renal activity, but in practice this is not so. Conversely, in cases of reduced skeletal uptake, for instance where
Fruits, vegetables, and stroke risk
Authors: J. D. Folts
Journal: JAMA (1995)

<h3>In Reply.</h3> —We appreciate Dr Folts' letter highlighting another possible mechanism by which the intake of fruits and vegetables may protect against the development of stroke. If the chief protective mechanism of flavonoids involves platelet inhibition, the benefit of these compounds might apply principally to ischemic stroke, since a platelet-inhibiting factor would not be expected to reduce the risk of hemorrhagic stroke. In our data, the intake of fruits and vegetables appeared to reduce the risk of both types of stroke, although the number of hemorrhagic strokes was small. It would be helpful if Hertog et al<sup>1,2</sup>or others with information on flavonoid intake could address directly the issue of stroke risk. As the comments of Folts also underscore, we examined the effect of a class of foods on stroke risk without knowing the identity of all beneficial (or harmful) substances these foods contain. However, much of dietary counseling
Lectures on the Pathology, Diagnosis, and Treatment of Bright's Disease
Authors: G. Johnson
Journal: BMJ (1873)

Synonyms.-General Symptoms.-Mieroscopie Appearances in the Uine.-M^orbidAnatomy of the Kidney.-Physiology of the AMorid Process.I IIAVE told you that the first great division of cases of Bright's disease is into acute and chronic, and I now proceed to give you the pathological history of acute Bright's disease.The synonyms for acute Bright's dis- ease, given in the Nomntclature of the Royal College of Physicians, are "acute albuminuria", "acute desquamative nephritis", and "acute renal dropsy".The renal disease associated with dropsy, which often occurs in connexion with scarlet fever, may be taken as a type of acute Bright's disease.I will first give you a sketch of the ordinary course of this form of disease, and I will then point out to you the chief varieties and modifications of the malady.The attack is usually ushered in by a sense of chilliness, which may amount to actual rigors; a quick and throbbing pulse, a hot and dry skin, a dry and coated tongue, thirst, loss of appetite, pain in the back and limbs, headache, and restlessness.In some cases, frequent vomiting occurs at the commencement of the attack.In most instances, dropsy is a very early symptom; the patient's attention, or that of his friends, being arrested by an appearance of unusual pallor and puffiness of the face, and especially of the eyelids; the swelling soon becomes general, affecting the subcutaneous areolar tissue throughout the body, and often one or more of the serous cavities.The urine is at this stage more or less scanty, occasionally almost or even altogether suppressed; usually it is dark-coloured from admixture with blood, the colour varying from a slight smokiness to a deep blood tinge, and it contains so large an amount of albumen as to become nearly solid with heat and nitric acid.
Selected Abstracts
Journal: JAMA (1979)

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American Medical History
Journal: JAMA (1999)

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Cancer Prayer
Authors: Marc J. Straus
Journal: JAMA (2006)

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