tbuckley/cabot-search huggingface dataset:
Prostaglandin E2 Inhibits p53 in Human Breast Adipose Stromal Cells: A Novel Mechanism for the Regulation of Aromatase in Obesity and Breast Cancer
Authors: Xuyi Wang, Maria M. Docanto, Hironobu Sasano, Camden Lo, Evan R. Simpson, Kristy A. Brown
Journal: Cancer Research (2015)

Abstract Obesity is a risk factor for postmenopausal breast cancer and the majority of these cancers are estrogen dependent. Aromatase converts androgens into estrogens and its increased expression in breast adipose stromal cells (ASC) is a major driver of estrogen receptor–positive breast cancer. In particular, obesity-associated and tumor-derived factors, such as prostaglandin E2 (PGE2), have been shown to drive the expression of aromatase by stimulating the activity of the proximal promoter II (PII). The tumor-suppressor p53 is a key regulator of cell-cycle arrest and apoptosis and is frequently mutated in breast cancer. Mutations in p53 are rare in tumor-associated ASCs. Therefore, it was hypothesized that p53 is regulated by PGE2 and involved in the PGE2-mediated regulation of aromatase. Results demonstrate that PGE2 causes a significant decrease in p53 transcript and nuclear protein expression, as well as phosphorylation at Ser15 in primary human breast ASCs. Stabilization of p53 with RITA leads to a significant decrease in the PGE2-stimulated aromatase mRNA expression and activity, and PII activity. Interaction of p53 with PII was demonstrated and this interaction is decreased in the presence of PGE2. Moreover, mutation of the identified p53 response element leads to an increase in the basal activity of the promoter. Immunofluorescence on clinical samples demonstrates that p53 is decreased in tumor-associated ASCs compared with ASCs from normal breast tissue, and that there is a positive association between perinuclear (inactive) p53 and aromatase expression in these cells. Furthermore, aromatase expression is increased in breast ASCs from Li–Fraumeni patients (germline TP53 mutations) compared with non-Li–Fraumeni breast tissue. Overall, our results demonstrate that p53 is a negative regulator of aromatase in the breast and its inhibition by PGE2 provides a novel mechanism for aromatase regulation in obesity and breast cancer. Cancer Res; 75(4); 645–55. ©2015 AACR.
THE SUBSTITUTE FEEDING IN INFANTS
Authors: T. H. Sanderson-Wells
Journal: BMJ (1905)

CASE: II[.(For notes of this case I am indebted to Mr. Lloyd-Owen.)E. S. was thrown off his bicycle and received a slight wound in the region of the left external angular process.He was unconscious for about an hour.Three months later his left vision was little more than perception of light, and that only on the nasal side.The temporal field was lost up to the point of fixation.The optic disc was atrophic, and the retinal arteries smaller than those on the right side.The right eye was normal and field of vision full. CASE IV.H. A. fell off his bicycle and struck his right temple.Six months later his condition was as follows:Right eye: Atrophy of the optic nerve, with some narrowing of the retinal arteries.Visual field contracted to within IOO of the fixation point on the temporal side.R V. = i8 + .50D.Left eye: Normal; field of vision full.L V. = + .soD. CASE V.E C., a miner, was struck by a " coal tub" on the left side of fore- head and face one month before his admission to the Birmingham Eye Hospital.There was no loss of consciousness; there was some bleeding from each nostril, and the left eye was hidden by swollen and ecohy- mosed eyelids.Four days later, when the swelling had subsided and he was able to open the lids, he found that the sight of the left eye was defective.On admission there was a large scar involving the outer third of the left eyebrow, and with two other smaller scars, one at the junction of the outer and mtddle third of the inferior orbital margin and the other on the left side of the bridge of the nose, showed the extent of the injury.The left pupil was very slightly larger than the right, and its reaction to light was very sluggish, but its associated and con- sensual reflexes were good.There was no interference with the motility of the eye.The optic disc was pale, the pallor being more decided on the temporal side.The temporal field was lost up to within Io deg. of the point of fixation (vide chart).L V. = Fingers at 2 metres.The right pupil was somewhat dilated (about so mm. in dull daylight).The direct and associated reflexes were brisk, but the consensual reflex was deficient.The visual field was normal.R.V. = f.This case being a recent one, is still under observation.
Increased expression of IL-16 immunoreactivity in bronchial mucosa after segmental allergen challenge in patients with asthma
Authors: Sophie Laberge, Stephane Pinsonneault, Eva-Maria Varga, Stephen J. Till, Kayhan Nouri-Aria, Mikila Jacobson, William W. Cruikshank, David M. Center, Qutayba Hamid, Stephen R. Durham
Journal: Journal of Allergy and Clinical Immunology (2000)
In vivo synergy of radiation and hu14.18-IL2 immunocytokine results in a memory T cell response in a syngeneic murine melanoma model
Authors: Zachary S Morris, Emily Guy, David Francis, Monica Gressett, Richard Yang, Alexander Rakhmilevich, Jaquelyn Hank, Stephen Gillies, Paul Harari, Paul Sondel
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Tumor-specific monoclonal antibodies (mAb) are a common type of immunotherapy capable of engaging innate immune cells to elicit antibody-dependent cell-mediated cytotoxicity (ADCC). We recently demonstrated in vivo synergy between radiation (RT) and ADCC using the anti-GD2 hu14.18
Hereditary Nonprogressive Chorea of Early Onset
Authors: A. F. Haerer, R. D. Currier, J. F. Jackson
Journal: New England Journal of Medicine (1967)

THIS report describes the clinical, laboratory and genetic investigations of a large Negro family, many of whose members exhibit choreiform movements of early onset and nonprogressive nature. As far as is known, this hereditary syndrome in the absence of other neurologic or psychiatric manifestations represents a unique and previously unreported entity.Clinical ObservationsIn late 1964, 2 teen-age brothers from southern Mississippi were referred for evaluation and treatment of "nervousness." Both exhibited involuntary jerking movements, best described as choreiform. It was learned that several other members of the family had identical involuntary motor activity. For this reason, as many of . . .
Courts too deferential to doctors, says judge
Authors: C. Dyer
Journal: BMJ (2001)

The English courts were “excessively deferential” to doctors in the past in their reluctance to find them guilty of negligence, England's top judge said this week. Lord Woolf, the Lord Chief Justice, said that judges were now less willing to allow the medical profession to determine what amounted to negligent practice.

The change happened after it became clear to the courts that the hospitals and the medical professions could not be relied on to resolve justified complaints justly, he added.

Medical negligence litigation was “a disaster area,” in which the courts grew increasingly conscious of the …
TWO AND ONE-HALF YEARS' EXPERIENCE WITH SALVARSAN AND NEOSALVARSAN
Authors: WILLIAM THOMAS CORLETT
Journal: JAMA (1913)

From laboratory experiments on animals infected with the syphilitic organism it was at first thought that a sufficient amount of the synthetic arsenic compound known as salvarsan might be administered at one time to cause a complete sterilization or destruction of the spirochetes in man; hence the name under which it was possibly not most ethically heralded to the world—<i>therapia sterilisans magna</i>. Contrary to what was first supposed, however, we now know that one dose is not expected to cure a case of lues even in its primary stage. But the value of these compounds, which have been used so extensively during the past two or three years, has been sufficiently proved to warrant the assertion that Ehrlich has made the greatest advance in the therapy of syphilis since it was first noted, several hundreds of years ago, that luetics improved under treatment with mercury. From clinical experience it
Book ReviewThe Practitioner's Illustrated Dermatology. By Howard T. Behrman, M.D. With the collaboration of Theodore A. Labow, M.D. 4°, cloth, 10 + 189 pp., with 56 illustrations in color. New York: Grune and Stratton, Incorporated, 1965. $9.75.
Authors: Richard Masters
Journal: New England Journal of Medicine (1965)
Progress in Understanding the Hemoglobin Switch
Authors: Bernard G. Forget
Journal: New England Journal of Medicine (2011)

During fetal development and the first 6 months of neonatal life, a complex pattern of globin gene expression occurs called the hemoglobin switch (Figure 1). After a brief period of embryonic globin gene expression, the γ-globin chain of fetal hemoglobin (HbF, or α2γ2) is predominantly expressed, then is progressively replaced by the β-globin chain of adult hemoglobin (HbA, or α2β2).2 This process is clinically important because the persistence or reactivation of HbF production can be highly beneficial in attenuating the severity of the symptoms of inherited β-globin gene disorders, such as β-thalassemia . . .
Is closure of patent foramen ovale to prevent ischaemic stroke ever justified?
Authors: R. A. Henderson, P. M. W. Bath
Journal: BMJ (2013)

The foramen ovale is a tunnel in the interatrial septum of the fetal heart that allows oxygenated placental blood to bypass the lungs and flow into the systemic circulation. At birth, inflation of the lungs causes physiological closure of the foramen, and in most people the interatrial communication seals completely over time. In around a quarter of the population, however, incomplete closure of the foramen results in a persistent (or patent) foramen ovale that provides a potential route for bloodborne material from the venous circulation to enter the systemic circulation.

Case reports of thrombus straddling a patent foramen ovale confirm that material from the venous circulation can pass through the interatrial communication and cause systemic embolism to the brain and other organs,1 but the frequency and clinical relevance of this phenomenon are controversial. Case-control studies to assess whether patent foramen ovale is more common in people with stroke are confounded by selection and case ascertainment biases and have produced conflicting results. Nevertheless, meta-analyses of these studies support an association between a patent foramen ovale and stroke without an identifiable cause (“cryptogenic stroke”), especially in young patients (age <55 years).2 3 Differences in the prevalence of conventional risk factors for stroke, and in patterns of ischaemic brain injury, also suggest discrepant mechanisms of stroke in those with and without a patent foramen ovale.4 5

Prospective data to determine the risk of stroke in otherwise healthy people with patent foramen ovale are limited. In one population based study the incidence rate of ischaemic stroke was 1.22 and 0.89 per 100 person years in subjects with and without patent foramen ovale respectively, but this difference was not statistically significant (adjusted hazard ratio 1.64 (95% confidence interval 0.87 to 3.09)).6 The mean age of subjects in this study was 69 …
The Artist as Scientist
Authors: Nancy J. C. Andreasen
Journal: JAMA (1976)

SHAKESPEARE was fascinated with the idea of madness. In fact, most Elizabethans were. Elizabethan drama began with a play about insanity—<i>The Spanish Tragedy, or Hieronimo Is Mad Again</i>. For the Elizabethan, a trip to the theatre was a movie, a television documentary, a Broadway musical, and a visit to a zoo or amusement park, all in one. Shakespeare was showman enough to capitalize on his audience's taste for the varied and bizarre. Each of his four major tragedies is a sensitive exploration of psychopathology.<i>Hamlet</i>portrays manic-depressive illness in Hamlet and schizoaffective disorder in Ophelia.<i>Macbeth</i>shows both major characters suffering from ambition that leads to crime and the punishment of depression. Lear has a mild organic brain syndrome that develops under stress into a reactive psychosis, while Gloucester becomes depressed and Edgar feigns classic schizophrenia as Poor Tom. Othello develops a suspiciousness bordering on paranoia, while Iago's delight
Three political avenues to health
Authors: W. Russell
Journal: BMJ (1983)

Perivascular epithelioid cell tumour (PEComa) of the liver is very uncommon and may be overlooked in the clinical and histological differential diagnosis of a liver tumour. We report the case of an incidentally discovered liver mass suspicious for hepatocellular carcinoma, which on biopsy was suggestive of a pseudocyst but after resection was found to be hepatic PEComa with some of the usual characteristics of this neoplasm as well as several less familiar features. We have also reviewed cases of hepatic PEComa from the literature in order to provide insight into recognising possible PEComa preoperatively and assessing its risk of malignancy after diagnosis.
Abstract 3378: E-cadherin suppresses breast cancer cell growth and interleukin-6 production
Authors: Nicholas J. Sullivan, Jonathan S. Schick, Judith A. Riggenbach, Kathleen L. Tober, Brett M. Hall, Tatiana M. Oberyszyn
Journal: Cancer Research (2010)

Abstract Carcinomas arise from epithelial tissues and represent the most common type of human cancer. E-cadherin is an epithelial-specific intercellular adhesion molecule, which localizes to epithelial cell adherens junctions and is a critical mediator of carcinoma cell invasion and metastasis. Although impaired E-cadherin expression can be clinically utilized to predict breast cancer cell invasiveness, metastasis, and patient survival, E-cadherin has received less attention for its role as a putative regulator of epithelial cell growth. We have previously shown that interleukin-6 (IL-6), a pleiotropic inflammatory cytokine associated with poor clinical outcome in breast cancer patients, is a potent growth factor and repressor of E-cadherin in human breast cancer cells. Consistent with clinical reports and our previous findings, we hypothesized that E-cadherin repression may be responsible for IL-6-induced breast cancer cell growth. The current study demonstrated that IL-6 enhanced the growth rates of estrogen receptor-alpha (ERα)-positive breast cancer cells in a three-dimensional (3D) tumor growth assay (TGA) in a dose-dependent manner. We showed that IL-6 also repressed E-cadherin protein levels in ERα-positive breast cancer cells in a 3D TGA in a dose-dependent manner. We have previously shown that IL-6 treatment does not affect E-cadherin-negative MDA-MB-231 cell growth, and the current study showed similar results in MCF-7 cells which express Twist and therefore lack E-cadherin. MDA-MB-231 cells lack E-cadherin and express IL-6, thus allowing us to express stable ectopic E-cadherin to evaluate its impact on cell growth and IL-6 production. Ectopic E-cadherin expression significantly suppressed MDA-MB-231 cell growth (P-value &amp;lt; 0.005) and IL-6 production (P-value &amp;lt; 0.00005) as measured by 3D TGA and ELISA, respectively. Our current findings reveal an association between enhanced breast cancer cell growth and E-cadherin repression following exposure to IL-6. Furthermore, we demonstrated that E-cadherin suppresses breast cancer cell growth and IL-6 production, which suggests a positive feedback loop in which IL-6 promotes E-cadherin repression, thereby inducing autocrine IL-6 production in breast cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3378.
THE SURFACE SKIN FAT IN SEBORRHOEIC DERMATITIS.
Authors: I. S. HODGSON-JONES, R. M. B. MACKENNA, V. R. WHEATLEY
Journal: British Journal of Dermatology (1953)

Journal Article THE SURFACE SKIN FAT IN SEBORRHOEIC DERMATITIS. Get access I. S. HODGSON‐JONES, M.D., M.R.C.P., I. S. HODGSON‐JONES, M.D., M.R.C.P. Departments of Dermatology and Biochemistry, St. Bartholomew's Hospital, London Search for other works by this author on: Oxford Academic Google Scholar R. M. B. MACKENNA, M.D., E.R.C.P., R. M. B. MACKENNA, M.D., E.R.C.P. Departments of Dermatology and Biochemistry, St. Bartholomew's Hospital, London Search for other works by this author on: Oxford Academic Google Scholar V. R. WHEATLEY, Ph.D. V. R. WHEATLEY, Ph.D. Departments of Dermatology and Biochemistry, St. Bartholomew's Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 65, Issue 7-8, 1 July 1953, Pages 246–251, https://doi.org/10.1111/j.1365-2133.1953.tb13746.x Published: 01 July 1953
A Course of Lectures on Urine, Urinary Deposits, and Calculi
Authors: L. Beale
Journal: BMJ (1860)

tant practical points in phthisis by those who see much of the disease n'ould suirely tend to clear up some doubts, and give us truer notions of tlhe malady; and I can only express my regret that the time allotted does not permit miie to refer to other points wlhichi have occupied my own attention.
711-2 Recombinant-hirudin (CGP 39 393) Reduces the Incidence of Major Adverse Cardiac Events, Reported within the First 96 Hours Post-Angioplasty in Unstable Patients (Braunwald Classification) Pre-treated by Heparin
Authors: Patrick W. Serruys, Keith A.A. Fox, Jean-Paul R. Herrman, Doris Bach, Philip Close, Jaap W. Deckers
Journal: Journal of the American College of Cardiology (1995)
Incidence and host determinants of work‐related rhinoconjunctivitis in apprentice pastry‐makers
Authors: D. Gautrin, H. Ghezzo, C. Infante‐Rivard, J.‐L. Malo
Journal: Allergy (2002)

Background: The authors recently assessed the incidence and determinants of immunologic sensitization to flour in apprentice pastry‐makers. The aim of this work was to determine the incidence of work‐related rhinoconjunctivitis (RC) symptoms and their determinants. Methods: For this 188/230 entrants (81.7%) were evaluated before starting exposure to flour, and again 10.8 and 16.8 months after. Questionnaires and skin prick testing to common and work‐related allergens were administered at each visit. Bronchial responsiveness to methacholine was assessed at baseline in all subjects and in a subgroup at follow‐up. Results: Thirty subjects (16.1%) reported new work‐related RC symptoms (13.1 per 100 person–years); in three subjects (1.6%), these were accompanied by incident skin prick test reactivity to flour‐derived allergens. Skin prick test reactivity to grass pollens (OR = 3.0, 95% CI, 1.3–6.7) and to pets (OR = 2.5, 95% CI, 1.1–5.9), persistent rhinitis (OR = 3.1, 95% CI, 1.1–8.4), seasonal RC (OR = 2.5, 95% CI, 1.1–5.5), RC on contact with pets (OR = 2.3, 95% CI, 1.03–5.0) and skin prick test reactivity to wheat flour (OR = 10.5, 95% CI, 2.3–46.8), assessed at baseline, were significantly associated with the incidence of work‐related RC symptoms. Multivariate logistic regression analysis yielded significant OR of skin prick test reactivity to wheat flour at baseline (OR = 7.1, 95% CI, 1.7–35.1) and persistent rhinitis (OR = 3.9, 95% CI, 1.01–9.6) for the incidence of work‐related RC symptoms. Increased bronchial hyperresponsiveness at follow‐up was more frequent, although not significantly, in subjects positive to skin prick test to flour on entry and reporting new work‐related symptoms (3/5), than in other subjects (4/17). Conclusions: The incidence of work‐related RC symptoms among apprentice pastry‐makers was high (16.1% 30/186), while a minority (3/30) also developed skin prick test reactivity to flour. Skin prick test reactivity to wheat flour and persistent allergic rhinitis on starting exposure to flour are significant determinants for the development of work‐related RC symptoms.
Outptient Management of Diabetic Children
Authors: Z. Laron, M. Karp
Journal: BMJ (1969)

CRIBJo 357 between the smegma and the cervix may be exerting a beneficial effect in this respect.It would seem important, therefore, that the authors should again attempt to identify those women whose husbands are circumcised, and if this proves impossible in the present series it could perhaps be evaluated in the future.If indeed the incidence of uncircum- cised husbands remains the same in all ethnic groups examined and the statistical difference between diaphragm and steroid methods remains the same, it would seem that the diaphragm acting as a barrier against smegma might possibly be one of the explanations for this difference.-Iam, etc.,
The Economics of American Medicine
Authors: Amasa B. Ford
Journal: JAMA (1964)

In this major work Seymour E. Harris, Littauer Professor of Economics at Harvard, throws new light on controversial issues and new fuel on the fires of controversy. He develops his argument in a dispassionate and scholarly style, with voluminous but clear documentation. He starts with the frank avowal that his major interest is "to exploit financial institutions in such a manner as to increase resources going into medicine, making the most effective use of the resultant inputs, and in particular to bring about an improvement in the distribution of medicine." Some of his conclusions are familiar, several are arguable, but each is supported by a chapter of closely analyzed data. He finds drug costs excessive and points to indications of monopoly. There are, in his view, both an overall shortage and an uneven distribution of doctors in this country. With rising population, the physician is "forced to raise his price."
Infectious Mononucleosis
Authors: James C. Niederman, George Miller, Howard A. Pearson, Joseph S. Pagano, James M. Dowaliby
Journal: New England Journal of Medicine (1976)

In an examination of excretion patterns of Epstein-Barr virus in 104 throat washings from 20 patients with infectious mononucleosis we found that three persons regularly shed virus from the second week through the third month after onset; 15 demonstrated intermittent excretion over three months, and in two cases, no virus was detected. In oral secretions, the virus appeared to be located extracellularly. Transforming activity was demonstrated in aliquots after centrifugation and filtration, in a sample in which cells were disrupted before filtration, and in specimens after two years' storage. Multiple oropharyngeal sites were examined for presence of the virus. In one patient, virus was regularly demonstrated in throat washings and saliva; swabs from Stensen's duct orifices yielded virus in three of four cases. Demonstration of virus in these oropharyngeal specimens explains increased transmissibility in age groups in which salivary exchange is high.
RASSF1A Suppresses the c-Jun-NH2-Kinase Pathway and Inhibits Cell Cycle Progression
Authors: Young Mi Whang, Yeul Hong Kim, Jun Suk Kim, Young Do Yoo
Journal: Cancer Research (2005)

Abstract Some oncogenes, such as activated Ras, cause the malignant transformation of lung cells. c-Jun-NH2-kinase (JNK) activation is essential for the oncogenic function of these cells. In this study, we show that RASSF1A inhibits the growth of lung cancer cells by blocking the JNK pathway. The exogenous expression of RASSF1A suppressed JNK phosphorylation, and cells stably transfected with RASSF1A showed reduced JNK and c-Jun phosphorylation and Cyclin D1 down-regulation. An in vitro kinase assay showed that the exogenous expression of RASSF1A inhibited JNK activity and that JNK activity suppression due to ectopically expressed RASSF1A was revived by RASSF1A siRNA treatment. Based on our data, we suggest that RASSF1A exerts a tumor-suppressing effect by blocking oncogene-mediated JNK activation in lung cells.