tbuckley/cabot-search huggingface dataset:
Abstract 2197: Epithelial <i>Mig-6</i> is critical for a tumor suppressor function in endometrial cancer
Authors: Tae Hoon Kim, Sung Nam Cho, Michael J. Large, Russell R. Broaddus, Grant D. Orvis, Richard R. Behringer, Jae-Wook Jeong
Journal: Cancer Research (2011)

Abstract Normal endometrial function requires a balance of progesterone (P4) and estrogen (E2) action. A bias toward E2 action and away from P4 action underlies the tumorigenesis of endometrial adenocarcinoma which is the fourth most common cancer in women. In previous studies, we have identified mitogen-inducible gene 6 (Mig-6) as a downstream target of PR (progesterone receptor) action in the uterus. Mig-6 is expressed in both the epithelium and stroma of the uterus. Conditional ablation of Mig-6 in all compartments of the uterus (PRcre/+ Mig-6f/f) results in infertility and leads to the development of endometrial hyperplasia and estrogen-induced endometrial cancer. Our central hypothesis is that Mig-6 is a critical mediator of stromal-epithelial communication in pregnancy, steroid hormone regulation and tumor suppressor function. In order to understand the role of epithelial Mig-6 in the uterus, we generated a mouse model in which we specifically ablate epithelial endometrial Mig-6 using Wnt7a-cre mice (Wnt7acre+ Mig-6f/f). Wnt7acre+ Mig-6f/f mice are subfertile due to embryo abortion and display normal P4 attenuation of E2-mediated uterine hypertrophy. However, Wnt7acre+ Mig-6f/f mice develop endometrial hyperplasia at 5 months of age as well as estrogen-induced endometrial cancer. The expression of PR is reduced in Wnt7acre+ Mig-6f/f mice compared to control Mig-6f/f mice. Interestingly, the hyperplasia exhibited by the Wnt7acre+ Mig-6f/f mice is reversed by P4 treatment, contrary to what is observed in PRcre/+ Mig-6f/f mice. Also, the expression of ERα, as well as its target genes Muc-1, Clca3, Ltf and Birc1, is significantly decreased in the Wnt7acre+ Mig-6f/f mice as compared to the control and PRcre/+ Mig-6f/f after P4 treatment. Concurrently, stromal Mig-6 expression is significantly increased in Wnt7acre+ Mig-6f/f mice indicating that P4-induced stromal Mig-6 can reverse the hyperplasia seen in the Wnt7acre+ Mig-6f/f mice by regulating ERα expression level. These data suggest that epithelial Mig-6 plays an important tumor suppressor role during tumorigenesis in the uterus. (Supported by NIH, R01 HD057873) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2197. doi:10.1158/1538-7445.AM2011-2197
Metabolic Disorders of Bone
Authors: Reginald R. Cooper
Journal: JAMA (1975)

This refreshing, lucid overview of metabolic bone disease represents a welcome newcomer to a rapidly evolving area. Although not encyclopedic in scope, the work summarizes major advances and relates them to traditional views of bone physiology. The author wisely made no attempt to present an in-depth view of normal bone physiology and biology. Instead, a brief review accentuated by an extensive and current bibliography provides the necessary background for understanding the book's main theme—the clinical diagnosis and treatment of metabolic bone problems. Sections on laboratory diagnosis and differential diagnosis should be of particular interest to the clinician. The major portion of the book describes the management of numerous diseases and disorders that alter normal bone dynamics. The discussions adequately describe approaches to care of patients. Perhaps the role of various techniques for evaluating bone turnover in disorders like osteoporosis receives too little attention as the author stresses photon absorptometry. More
Topical liarozole in ichthyosis: a double-blind, left-right comparative study followed by a long-term open maintenance study
Authors: G.P.H. Lucker, C.J. Verfaille, A.M.C. Heremans, F.P. Vanhoutte, J.P.J. Boegheim, P.P.M. Steijlen
Journal: British Journal of Dermatology (2005)

G.P.H.L. and C.J.V. contributed equally to this paper. Sir, Interest in liarozole, a retinoic acid metabolism blocking agent (RAMBA), has received a boost because of its recent orphan drug designation for congenital ichthyosis, approved by the European Commission. Retinoids1 are powerful substances available for modulating keratinocyte proliferation and differentiation. Side‐effects constitute a limit to the chronic use of systemic retinoids. Liarozole is an imidazole derivative developed in the late 1980s by the Janssen Research Foundation in Belgium. Extensive in vitro2–4 and in vivo5–7 pharmacological testing identified liarozole as an inhibitor of several mammalian cytochrome P450 (CYP) isozymes, among which is the one involved in the oxidative metabolism of all‐trans retinoic acid (RA), CYP 26. It represents the first drug in a new class of compounds coined RAMBAs. Oral liarozole seems at least as effective as acitretin in the treatment of hereditary ichthyosis with a rather similar side‐effect profile (1998, unpublished data). To broaden the margin between efficacy and side‐effects, a topical liarozole formulation was developed.
Doctor of Primary Medicine
Authors: Robert D. Gillette
Journal: JAMA (1972)

<h3>To the Editor.—</h3> In view of recent progress in Board Certification for Family physicians and the establishment of numerous Family Practice residencies, the proposal of Dr. Proger to establish separate medical schools for family physicians can only be viewed as a step backward. While family physicians and specialists need different programs of postgraduate medical education, both groups need the basic medical education which is now being provided by undergraduate medical schools. I foresee the following adverse effects of Dr. Proger's proposals. Communications between family physicians and other specialists, never completely satisfactory, would be further impeded. Since history has shown that "separate but equal" programs seldom remain equal in quality very long, it seems likely that the "PMD" programs would not be of first rank. It would follow that the graduates of "PMD" programs would be considered second-class citizens in the medical community.
Effects of alternating cycle lengths on refractoriness of the His-Purkinje system.
Authors: S Denker, M Lehmann, R Mahmud, C Gilbert, M Akhtar
Journal: Journal of Clinical Investigation (1984)

The effects of alternating cycle lengths (bigeminal rhythm) on His-Purkinje system refractoriness were studied in 14 patients using His bundle and right bundle recordings. Programmed atrial stimulation at constant cycle length (method I) was scanned using the atrial extrastimulus technique (A2) and compared with an atrial cycle length of identical duration coupled to A2 on alternate beats (method II). The results showed that (a) despite shorter cycle length of the His-Purkinje system with method II due to effect of A2 on atrioventricular nodal conduction (699 +/- 90 vs. 743 +/- 87 ms, P less than 0.001), the relative refractory period of the His-Purkinje system was always longer with method II (463 +/- 52 vs. 440 +/- 43 ms, P less than 0.001). A similar increase also occurred in effective refractory period of the His-Purkinje system; (b) while functional right bundle branch block occurred in eight patients and functional left bundle branch block in two patients with method I, functional right bundle branch block occurred in all 14 patients and left bundle branch block in seven patients with method II; (c) in two patients where both functional right and left bundle branch block occurred with method I this never was manifest at identical degree of abbreviation of His-Purkinje system cycle length but was manifest at identical abbreviation in each of seven patients with method II; (d) site of conduction delay and/or block during functional right bundle branch block was always proximal, i.e., between the His bundle and right bundle recordings with both methods. During method II this resulted in shortening of the subsequent right bundle cycle length relative to the subsequent His bundle (and of necessity left bundle) cycle length. The finding of increased His-Purkinje system refractoriness despite shorter preceding cycle length of the His-Purkinje system during atrial bigeminy has never been previously described and suggests that classical concepts of His-Purkinje system behavior may require revision in this setting. Secondly, during atrial bigeminy the occurrence of alternating functional bundle branch block cannot be accounted for solely by the degree of abbreviation of His-Purkinje system cycle length, but may be explained by a relative shortening of the next ipsilateral bundle branch cycle length in the bundle manifesting block.
Practical Considerations Arising from the Implementation of Lung Stereotactic Body Radiation Therapy (SBRT) at a Comprehensive Cancer Center
Authors: Max Dahele, Shannon Pearson, Tom Purdie, Jean-Pierre Bissonnette, Kevin Franks, Anthony Brade, John Cho, Alex Sun, Andrew Hope, Andrea Marshall, Jane Higgins, Andrea Bezjak
Journal: Journal of Thoracic Oncology (2008)
Maximum workplace concentration values and carcinogenicity classification for mixtures.
Authors: R Bartsch, S Forderkunz, U Reuter, H Sterzl-Eckert, H Greim
Journal: Environmental Health Perspectives (1998)

In Germany, the Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) generally sets maximum workplace concentration values (i.e., a proposed occupational exposure level [OEL]) for single substances, not for mixtures. For mixtures containing substances with a genotoxic and carcinogenic potential, the commission considered it scientifically inappropriate to establish a safe threshold. This approach is currently under discussion. Carcinogenic mixtures are categorized according to either the carcinogenicity of the mixture or the classification of the carcinogenic substances included. In regulating exposure to mixtures, an approach similar to that used by the American Conference of Governmental Hygienists is proposed: For components with the same target organ and mode of action or interfering metabolism, synergistic effects must be expected and the respective OELs must be lowered. However, if there is proof that the components act independently, the OELs of the individual compounds are not considered to be modified. In the view of the commission, calculating OELs for solvent mixtures according to their liquid phase composition is not justified, and the setting of scientifically based OELs for complex mixtures is not possible.
Access to Drugs for Treatment of Noncommunicable Diseases
Authors: Thomas J. Bollyky
Journal: PLoS Medicine (2013)

Thomas Bollyky explains the emerging controversy over patented medicines for noncommunicable diseases and their affordability in developing countries. Another transformation in global health is required that focuses on low-cost interventions and patient-centered, rather than country-focused, strategies. Please see later in the article for the Editors' Summary
World Tobacco Conference Resolutions Abound
Authors: Andrew A. Skolnick
Journal: JAMA (1992)

MORE THAN 1000 people representing 87 nations attended the Eighth World Conference on Tobacco OR Health. Says Jerie Jordan, editor of the American Cancer Society's<i>World Smoking and Health</i>and a member of the conference organizing committee: "It was the first time an international conference on smoking was held in a developing country. There was also a marked increase in participation by women. We consider these achievements extremely significant because developing countries and women have become major new markets for the tobacco industry." Among the resolutions adopted by the conference was one that calls on the United States to respect the sovereign rights of nations to protect the health of their people through tobacco-control legislation. (Please see accompanying article.) The resolution asks the US government to "give priority to human health over the profits of its tobacco companies in negotiating with Taiwan and other nations." The conference also adopted a
Alexander Campbell Buchan
Authors: Anne B Sutherland
Journal: BMJ (2004)

Consultant plastic surgeon Bangour General Hospital, Edinburgh, 1941-79 (b 1915; q Edinburgh 1940; FRCS Ed, FDS), d 18 November 2003.

Campbell was appointed surgeon to the newly established plastic and maxillofacial surgical unit at Bangour General Hospital in 1941. After the inception of the NHS he was appointed consultant plastic surgeon to the South Eastern Regional Hospital Board. Later he became involved in surgery of the hand, spending some months in Milwaukee, United States, to further his experience. This, with treatment of head and neck malignancy, became his main interests. He was elected president of the British Association of Plastic Surgeons in 1978 and in 1979, the year of his retirement, he was elected president of the British Association for Surgery of the Hand. Predeceased by his wife, Marjorie, he leaves a daughter.
On the Treatment of Puerperal Convulsions
Authors: J. G. Swayne
Journal: BMJ (1868)

Od 7, B tbb m_ewaadcl of the members of this Assocition y be to produce a amukd hIa I an in tue deat arsig from hernit; for the Reports of the Retrar-General must ever cotinue to be the test and sure de.m-oMtrtive evidence of improvement and of advance in the curative re- s of practica surgery.
Abstract 5452: <i>In utero</i> exposure to bisphenol A promotes mammary tumor development in MMTV-erbB-2 transgenic mice
Authors: Zhi-Kun Ma, Xia Cao, XiaoHe Yang
Journal: Cancer Research (2012)

Abstract Increasing evidence indicates that environmental exposure plays a critical role in breast cancer etiology. Bisphenol A (BPA), the building block of polycarbonate plastics with estrogenic activity, is one of the most common chemicals exposed in daily life. Recent studies suggest a link between BPA exposure and increased breast cancer risk. However, specific conditions and the underlying mechanisms of BPA exposure associated breast cancer risk remain unclear. This study aimed to investigate the effects of in utero exposure to BPA on mammary tumor development in MMTV-erbB-2 transgenic mice, which exemplifies a scenario of gene-environmental interaction. Since erbB-2 is amplified/overexpressed in approximately 30% of breast cancer, which has been associated with poor prognosis and therapeutic resistance, use of this clinically relevant mammary tumor model is of high translational value. In this study, pregnant MMTV-erbB-2 mice were subcutaneously injected with 0, 25 ng, 250 ng and 250 µg/Kg body weight BPA daily between day 13 and day 19 of gestation. We found that in utero exposed mice in the low dose (25 and 250 ng) groups, but not the high dose group (250 µg), displayed earlier vaginal opening and prolonged estrous phase, suggesting a dose dependent pro-estrogenic effect of in utero exposure to BPA. Whole mount analysis showed that mammary glands of mice with in utero exposure to low dose BPA had a longer ductal extension at 6 weeks and increased lateral branching/alveolar structures at 10 weeks, which was more significant in the 250 ng group but less evident in the high dose group. Molecular analysis of mammary tissues at 10 weeks indicated that in utero exposure to BPA increased phosphorylation/activation of erbB-2, EGFR, erbB-3 Erk1/2 and Akt, and expression of erbB-3 and EGFR. Signaling of estrogen receptor (ER) pathway was upregulated concomitantly, as reflected by increased expression and phosphorylation of ERα and upregulation of cyclin D1 and c-myc. More importantly, mice in the 250 ng group but not the high dose group, developed tumor earlier than the mice in the control group, suggesting that dose is a critical factor affecting the outcomes. These data demonstrated that in utero exposure to BPA may promote mammary tumor development in erbB-2 transgenic mice in a dose dependent manner. Concomitant activation of the erbB-2 and ER pathways in the premalignant tissues suggests that induction of ER-erbB-2 crosstalk may play a critical role in mammary tumorigenesis promoted by in utero exposure to BPA, which underscores the significance of gene-environment interaction in early exposure to BPA associated breast cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5452. doi:1538-7445.AM2012-5452
The effect of chronic ethanol feeding on ornithine decarboxylase activity and liver regeneration
Authors: Anna Mae Diehl, Marco Chacon, Patrick Wagner
Journal: Hepatology (1988)

The effects of ethanol on liver regeneration are poorly understood. Acute and chronic exposure to ethanol have been found to exert opposite effects on the induction of ornithine decarboxylase, the rate-limiting enzyme for polyamine biosynthesis. Polyamines are necessary for DNA synthesis and liver regeneration after chemical or surgical liver injury. Short-term exposure to ethanol, which inhibits ornithine decarboxylase has been shown to inhibit DNA synthesis and liver regeneration, whereas more chronic exposure to ethanol increases ornithine decarboxylase activity and therefore could conceivably stimulate DNA synthesis and regeneration. To explore this later possibility, the effects of chronic ethanol consumption on ornithine decarboxylase activity, DNA synthesis and liver regeneration were studied in rats after sham laparotomy and partial hepatectomy. Chronic ethanol feeding failed to inhibit the induction of ornithine decarboxylase that occurred after partial hepatectomy and yet significantly inhibited posthepatectomy DNA synthesis and restitution of liver mass. These data suggest that the induction of hepatic polyamine biosynthesis is dissociated from DNA synthesis and liver regeneration after chronic consumption of ethanol.
Diesel Exhaust Activates and Primes Microglia: Air Pollution, Neuroinflammation, and Regulation of Dopaminergic Neurotoxicity
Authors: Shannon Levesque, Thomas Taetzsch, Melinda E. Lull, Urmila Kodavanti, Krisztian Stadler, Alison Wagner, Jo Anne Johnson, Laura Duke, Prasada Kodavanti, Michael J. Surace, Michelle L. Block
Journal: Environmental Health Perspectives (2011)

Air pollution is linked to central nervous system disease, but the mechanisms responsible are poorly understood.Here, we sought to address the brain-region-specific effects of diesel exhaust (DE) and key cellular mechanisms underlying DE-induced microglia activation, neuroinflammation, and dopaminergic (DA) neurotoxicity.Rats were exposed to DE (2.0, 0.5, and 0 mg/m3) by inhalation over 4 weeks or as a single intratracheal administration of DE particles (DEP; 20 mg/kg). Primary neuron-glia cultures and the HAPI (highly aggressively proliferating immortalized) microglial cell line were used to explore cellular mechanisms.Rats exposed to DE by inhalation demonstrated elevated levels of whole-brain IL-6 (interleukin-6) protein, nitrated proteins, and IBA-1 (ionized calcium-binding adaptor molecule 1) protein (microglial marker), indicating generalized neuroinflammation. Analysis by brain region revealed that DE increased TNFα (tumor necrosis factor-α), IL-1β, IL-6, MIP-1α (macrophage inflammatory protein-1α) RAGE (receptor for advanced glycation end products), fractalkine, and the IBA-1 microglial marker in most regions tested, with the midbrain showing the greatest DE response. Intratracheal administration of DEP increased microglial IBA-1 staining in the substantia nigra and elevated both serum and whole-brain TNFα at 6 hr posttreatment. Although DEP alone failed to cause the production of cytokines and chemokines, DEP (5 μg/mL) pretreatment followed by lipopolysaccharide (2.5 ng/mL) in vitro synergistically amplified nitric oxide production, TNFα release, and DA neurotoxicity. Pretreatment with fractalkine (50 pg/mL) in vitro ameliorated DEP (50 μg/mL)-induced microglial hydrogen peroxide production and DA neurotoxicity.Together, these findings reveal complex, interacting mechanisms responsible for how air pollution may cause neuroinflammation and DA neurotoxicity.
P54 * THE USE OF FOLATE TO REDUCE CELL VIABILITY IN GLIOMA CELLS
Authors: M. Rudd, R. Lea, W. Goodwin
Journal: Neuro-Oncology (2014)

INTRODUCTION: Folate is a methylating agent which can reduce the aggressiveness of gliomas by remethylating genes involved in proliferation and apoptosis. Folate is a potential therapeutic treatment for cancer. It can be found naturally as Folinic Acid, or in the synthetic form Folic Acid, and can cross the blood brain barrier. Methylation is a useful target as it is an epigenetic change that can be reversed. METHOD: To begin to investigate the effect of folate on glioma, glioma cell lines U87 and 1321, plus the glial cell line SVG were used. Glioma cell lines were treated for 7 days with Folic and Folinic Acid at 4 and 40 µg/ml with and without an antioxidant. Cell viability was assessed using the PrestoBlue assay and cell cycle and apoptosis were tested using Propidium Iodide and caspase Glo 3/7 respectively. RESULTS: Cells treated with the higher level of Folinic Acid, 40 µg/ml, showed significant reduction in cell viability compared with the control (P < 0.01). Cell cycle analysis showed no difference in the percentages of each different cell cycle phase between the control and treatments on either Day 2 or Day 7. This suggests that the reduction in cell viability may be due to changes in apoptosis. CONCLUSION: These findings suggest that folate has an effect on cell viability in glioma cell lines. Folate could also have a beneficial effect on gliomas, which supports the use of folate for further research on primary glioma tissue.
Adenocarcinoma of the stomach: radiological and pathological correlation of effects of treatment with fast neutrons.
Authors: D Kingsley, A Gad, M Catterall
Journal: Gut (1976)

During the past six years 40 patients have been treated with fast neutrons for inoperable adenocarcinoma of the stomach. A number of these patients have been studied in detail both radiologically and pathologically with regard to the effects of fast neutrons on both the tumour and normal stomach. After treatment there was a constant reduction in size of the stomach capacity when compared with a control group and the motility of the stomach was lost. Mucosal changes, which were noted radiologically, appeared to be dose related. Histologically most of the tumour was destroyed. Small clumps of cells were, however, found in all except one of the patients but only in areas of the stomach which had not received the standard dose. Marked fibrosis occurred and it is our impression that the amount of fibrosis is in excess of that seen with other forms of radiotherapy.
Clonal cytotoxic T cells are expanded in myeloma and reside in the CD8+CD57+CD28− compartment
Authors: Daniel M.-Y. Sze, Gillian Giesajtis, Ross D. Brown, Maria Raitakari, John Gibson, Joy Ho, Alan G. Baxter, Barbara Fazekas de St Groth, Antony Basten, Douglas E. Joshua
Journal: Blood (2001)
Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction
Authors: Connie R Bezzina, Raha Pazoki, Abdennasser Bardai, Roos F Marsman, Jonas S S G de Jong, Marieke T Blom, Brendon P Scicluna, J Wouter Jukema, Navin R Bindraban, Peter Lichtner, Arne Pfeufer, Nanette H Bishopric, Dan M Roden, Thomas Meitinger, Sumeet S Chugh, Robert J Myerburg, Xavier Jouven, Stefan Kääb, Lukas R C Dekker, Hanno L Tan, Michael W T Tanck, Arthur A M Wilde
Journal: Nature Genetics (2010)