tbuckley/cabot-search huggingface dataset:
Aromatase Inhibition: Translation into a Successful Therapeutic Approach
Authors: Jürgen Geisler, Per Eystein Lønning
Journal: Clinical Cancer Research (2005)

Abstract The development of the novel third-generation aromatase inhibitors and inactivators for breast cancer treatment is one of the most successful contemporary achievements in cancer therapy. Parallel to studies evaluating toxicity and clinical efficacy in metastatic disease, the endocrine effects of multiple compounds were evaluated, leading to the identification of the highly potent third-generation aromatase inhibitors based on estrogen deprivation and aromatase inhibition in vivo. Thus, translational studies have been of vital importance identifying the unique characteristics of these compounds. Whereas first- and second-generation aromatase inhibitors inhibit estrogen synthesis in vivo by up to 90%, the third-generation compounds anastrozole, exemestane, and letrozole were found to cause ≥98% aromatase inhibition. This article summarizes and discusses the “translational research” that provided the background for the implementation of the third-generation aromatase inhibitors and inactivators into large clinical trials. The need for future translational research exploiting the mechanisms of resistance to these compounds for future improvement of endocrine therapy is emphasized.
Abstract 3367: Breast cancer stem cell-like cells are sensitive to ionizing radiation: Role of ATM
Authors: Seog-Young Kim, Edward V. Prochownik, Yong J. Lee
Journal: Cancer Research (2012)

Abstract The aim of this study was to determine the radiosensitivity of cancer stem (tumor-initiating) cells (CSC), which are known to be responsible for tumorogenicity and metastasis. We used breast cancer stem cell (CSC)-like MDA-MB231 and MDA-MB453 cell lines which were established by Dr. Edward V. Prochownik (Sajithlal et al., Stem Cells, 28:1008, 2010). Interestingly, these cells can proliferate without differentiation and have characteristics of tumor-initiating cells. CSC-like cells and their alternate subset non-CSC cells were exposed to α-rays (1.25-8.75Gy) and survival curves were determined by colony formation. A final slope, D0, of the survival curve for each cell line was determined to measure radiosensitivity. D0 of CSC-like MDA-MB453 cells and that of non-CSC MDA-MB453 cells were 1.16 Gy and 1.55 Gy, respectively. Similar results were observed in MDA-MB231 cells. We further examined whether CSC-like cells are relatively radiosensitive owing to different intrinsic factors including cell cycle distribution, free-radical scavengers and DNA repair. We observed that, unlike non-CSC cells, CSC-like cells have little/no sublethal damage repair and a low intracellular level of ATM. These results suggest that low DNA repair capability is responsible for the high radiosensitivity of these CSC-like cells. 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 3367. doi:1538-7445.AM2012-3367
Thrombolysis with recombinant streptokinase in Cuba
Authors: P. A Lopez-Saura
Journal: BMJ (2003)

EDITOR—Analysis of the causes of the low rate (21%) of thrombolysis for acute myocardial infarction in England and Wales described by Mayor would be interesting.1 In Cuba thrombolysis with home manufactured recombinant streptokinase has been widespread since 1993. When this procedure was introduced nationwide, the overall proportion of patients …
Mineral fiber content of lungs in patients with mesothelioma seeking compensation in Québec.
Authors: A Dufresne, R Bégin, A Churg, S Massé
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Asbestos fibers (AF) and ferruginous bodies (FB) in lung parenchyma from 50 workers seeking compensation from the Workers' Compensation Board of Québec for pleural or peritoneal mesothelioma were analyzed using transmission electron microscopy (TEM) equipped with energy-dispersive spectrometer (EDS) and phase-contrast microscopy (PCM). These workers had been occupationally exposed in mining and milling activities (12 were from Asbestos Township and 11 from Thetford Mines) and 27 were from other types of industry (asbestos factory, shipyard, etc.). For comparison, analyses of lung tissue at autopsy were done in a group of 49 subjects from a reference population. A 95% confidence interval upper limit of 540 AF < 5 microns/mg and a 95% confidence interval upper limit of 161 AF > or = 5 microns/mg dried lung tissue were found for the reference population. Similarly, a concentration of FB of 142 FB/g constituted the upper limit of detectable FB in the lungs of the reference population. Forty-eight of the 50 workers with mesothelioma had either a ferruginous body or total asbestos fiber count greater than the 95% confidence interval for the reference population; the remaining two had amosite and/or crocidolite concentrations greater than the 95% confidence interval for the reference population. The fiber types were different in the three groups, with the lungs of workers from Thetford Mines containing only chrysotile and tremolite, those from Asbestos Township containing chrysotile, tremolite, amosite, and crocidolite, and those in other industries containing largely amosite and crocidolite. We conclude that in this population of workers seeking compensation for mesothelioma, fiber analysis confirmed occupational asbestos exposure in every case. The fiber types responsible for the tumors are probably different in the three different groups.
The Promiscuous Receptor — Prostate Cancer Comes of Age
Authors: Jean D. Wilson
Journal: New England Journal of Medicine (1995)

It has been known for almost a century that testosterone and its intracellular mediator, dihydrotestosterone, control the development and function of the prostate gland. Huggins and his colleagues used this knowledge to show that medical or surgical castration can cause regression of prostate cancer. This discovery led to one of the first, if not the first, effective therapies for prostate cancer.1 Unfortunately, prostate cancer continues to be a leading cause of death from cancer in men because the response to castration is usually brief, and few effective alternative therapies are available. Indeed, elucidation of the biology of this tumor lags . . .
Circulating T follicular regulatory and helper cells have memory-like properties
Authors: Peter T. Sage, David Alvarez, Jernej Godec, Ulrich H. von Andrian, Arlene H. Sharpe
Journal: Journal of Clinical Investigation (2014)

Follicular Tregs (Tfr cells) inhibit antibody production, whereas follicular Th cells (Tfh cells) stimulate it. Tfr cells are found in blood; however, relatively little is known about the developmental signals for these cells or their functions. Here we demonstrated that circulating Tfr and Tfh cells share properties of memory cells and are distinct from effector Tfr and Tfh cells found within lymph nodes (LNs). Circulating memory-like Tfh cells were potently reactivated by DCs, homed to germinal centers, and produced more cytokines than did effector LN Tfh cells. Circulating memory-like Tfr cells persisted for long periods of time in vivo and homed to germinal centers after reactivation. Effector LN Tfr cells suppressed Tfh cell activation and production of cytokines, including IL-21, and inhibited class switch recombination and B cell activation. The suppressive function of this population was not dependent on specific antigen. Similar to LN effector Tfr cells, circulating Tfr cells also suppressed B and Tfh cells, but with a much lower capacity. Our data indicate that circulating memory-like Tfr cells are less suppressive than LN Tfr cells and circulating memory-like Tfh cells are more potent than LN effector Tfh cells; therefore, these circulating populations can provide rapid and robust systemic B cell help during secondary antigen exposure.
Frequent Detection of Merkel Cell Polyomavirus in Human Merkel Cell Carcinomas and Identification of a Unique Deletion in the <i>VP1</i> Gene
Authors: Ahmad Kassem, Anja Schöpflin, Carlos Diaz, Wolfgang Weyers, Elmar Stickeler, Martin Werner, Axel zur Hausen
Journal: Cancer Research (2008)

Abstract Merkel cell carcinoma (MCC) is a rare but very aggressive human malignancy of the elderly or immunosuppressed patients. Recently, the clonal integration of a new human polyoma virus, which was termed Merkel cell polyomavirus (MCPyV), has been reported in 8 of 10 MCC patients. In the present study, we studied the formalin-fixed and paraffin-embedded tissue specimens of 39 MCC for the presence of MCPyV by PCR. We applied four different primer sets directed against the large T antigen and the VP1 gene of MCPyV. We were able to detect MCPyV in 77% (n = 30) of MCC as confirmed by sequence analyses of the PCR products. Sequence analyses showed only minor nucleotide changes compared with the previously published MCC sequences. In addition, one patient revealed the amplification of two PCR products using PCR primers directed against the VP1 gene. Sequence analyses confirmed the presence of the expected 351-bp PCR product and in addition a second PCR product of 261 bp containing a unique 90-bp deletion in the VP1 gene, which will lead to a predicted loss of 28 amino acids. The unique 90-bp deletion within the VP1 gene possibly is a result of incomplete viral integration of MCPyV in the MCC. The presence of MCPyV in the majority of MCC tissue specimens in our study strongly underlines a possible role for MCPyV as an etiologic agent in the carcinogenesis of MCC. [Cancer Res 2008;68(13):5009–13]
Mechanistic Target of Rapamycin Complex 2 Protects the Heart From Ischemic Damage
Authors: Mirko Völkers, Mathias H. Konstandin, Shirin Doroudgar, Haruhiro Toko, Pearl Quijada, Shabana Din, Anya Joyo, Luis Ornelas, Kaitleen Samse, Donna J. Thuerauf, Natalie Gude, Christopher C. Glembotski, Mark A. Sussman
Journal: Circulation (2013)

The mechanistic target of rapamycin (mTOR) comprises 2 structurally distinct multiprotein complexes, mTOR complexes 1 and 2 (mTORC1 and mTORC2). Deregulation of mTOR signaling occurs during and contributes to the severity of myocardial damage from ischemic heart disease. However, the relative roles of mTORC1 versus mTORC2 in the pathogenesis of ischemic damage are unknown.Combined pharmacological and molecular approaches were used to alter the balance of mTORC1 and mTORC2 signaling in cultured cardiac myocytes and in mouse hearts subjected to conditions that mimic ischemic heart disease. The importance of mTOR signaling in cardiac protection was demonstrated by pharmacological inhibition of both mTORC1 and mTORC2 with Torin1, which led to increased cardiomyocyte apoptosis and tissue damage after myocardial infarction. Predominant mTORC1 signaling mediated by suppression of mTORC2 with Rictor similarly increased cardiomyocyte apoptosis and tissue damage after myocardial infarction. In comparison, preferentially shifting toward mTORC2 signaling by inhibition of mTORC1 with PRAS40 led to decreased cardiomyocyte apoptosis and tissue damage after myocardial infarction.These results suggest that selectively increasing mTORC2 while concurrently inhibiting mTORC1 signaling is a novel therapeutic approach for the treatment of ischemic heart disease.
Intranasal betamethasone induced acne and adrenal suppression
Authors: J.L. Bong, J.M.C. Connell, R. Lever
Journal: British Journal of Dermatology (2000)

Journal Article Intranasal betamethasone induced acne and adrenal suppression Get access J.L. Bong, J.L. Bong Department of Dermatology, *Department of Medicine and Therapeutics, Western Infirmary, Dunbarton Road, Glasgow, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.M.C. Connell, J.M.C. Connell Department of Dermatology, *Department of Medicine and Therapeutics, Western Infirmary, Dunbarton Road, Glasgow, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. Lever R. Lever Department of Dermatology, *Department of Medicine and Therapeutics, Western Infirmary, Dunbarton Road, Glasgow, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 3, 1 March 2000, Pages 579–580, https://doi.org/10.1046/j.1365-2133.2000.03392.x Published: 01 March 2000
Fine-Needle Aspiration and Cryptococcosis in the Acquired Immunodeficiency Syndrome (AIDS)
Authors: JEAN-MICHEL MOLINA
Journal: Annals of Internal Medicine (1988)

Letters and Corrections1 May 1988Fine-Needle Aspiration and Cryptococcosis in the Acquired Immunodeficiency Syndrome (AIDS)JEAN-MICHEL MOLINA, M.D., ERIC OKSENHENDLER, M.D., MARIE-THERESE DANIEL, M.D., JEAN-PIERRE CLAUVEL, M.D.JEAN-MICHEL MOLINA, M.D.Search for more papers by this author, ERIC OKSENHENDLER, M.D.Search for more papers by this author, MARIE-THERESE DANIEL, M.D.Search for more papers by this author, JEAN-PIERRE CLAUVEL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-108-5-772_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In their evaluation of fine-needle aspiration biopsies of lymph nodes in patients with the acquired immunodeficiency syndrome (AIDS)-related conditions, Bottles and colleagues (1) emphasize the usefulness of this method for diagnosing malignancy, Kaposi sarcoma, and mycobacterial infection. We report a case in which the diagnosis of disseminated cryptococcosis was made on the basis of a routine May-Grünwald-Giemsa-stained lymph node specimen from fine-needle aspiration biopsy.A 33-year-old black patient from Angola had lost weight and had night sweats and fever. Physical examination showed cervical, nontender small lymph nodes (0.5 to 1 cm). Mild splenomegaly was present....References1. BOTTLESMCPHAULVOLBERDING KLP. Fine-needle aspiration biopsy of patients with the acquired immunodeficiency syndrome (AIDS): experience in an outpatient clinic. Ann Intern Med. 1988;108:42-5. LinkGoogle Scholar2. ENGBISHBURGSMITHKAPILA RESR. Cryptococcal infections in patients with acquired immune deficiency syndrome. Am J Med. 1986;81:19-23. CrossrefMedlineGoogle Scholar3. ZUGERLOUIEHOLZMANSIMBERKOFFRAHAL AERMJ. Cryptococcal disease in patients with the acquired immunodeficiency syndrome. Ann Intern Med. 1986;104:234-40. LinkGoogle Scholar4. WITTMCKAYSCHWAMGOLDSTEINGOLD DDLDJ. Acquired immune deficiency syndrome presenting as bone marrow and mediastinal cryptococcosis. Am J Med. 1987;82:149-50. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Hôpital Saint-Louis 75475 Paris cedex 10 France PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByHuman CryptococcosisAtypical Micromorphology and Uncommon Location of Cryptococcosis: A Histopathologic Study Using Special Histochemical Techniques (One Case Report)AIDS and fungal infections 1 May 1988Volume 108, Issue 5Page: 772-772KeywordsAIDSBiopsyCryptococcosisFeversKaposi sarcomaLymph nodesSplenomegalySweat Issue Published: 1 May 1988 PDF DownloadLoading ...
Cultivating a coaching culture
Authors: S. Hutton-Taylor
Journal: BMJ (1999)

There are many formal, well structured mentor schemes in operation - overlapping the roles of educational supervisors, general practitioner trainers, clinical and general practitioner tutors - and many schemes have started and then fallen by the wayside because of lack of funding or time. And there are many informal yet successful mentoring relationships. 

But if this quote is anything to go by there may still be people taking on the role of a mentor without any assessment for suitability or training to perform the duty. Do people being allocated a mentor have any right to expect that they will be talking to someone who has received some instruction in the purpose and methodology of the role? One would certainly like to think that mentors are selected for having demonstrated a basic set of skills or personality attributes. Would Victor Meldrew make a good mentor? 

The word mentoring is bandied about in medical education documents, research into educational support schemes, and workforce reports. It could be argued that many mentoring schemes are merely papering over the cracks. By giving various people the title of mentor and placing others under their guidance, we are solving the need for better support systems - aren't we? However, papering over cracks might give a good cosmetic result, but the underlying structure is still crumbling. The very concept of mentoring assumes a prevailing ethos that promotes and encourages a Merlin-Arthur type relationship, whereas the reality may be far from this. What is needed is not just a handful of allocated or even fully trained mentors but an overall paradigm shift to a culture of coaching, with role models, positive constructive feedback, and good staff management principles. 

### 'Mentoring' survivor speaks out

“Can someone reassure me that mentor appointments (of hospital consultants) are based on some sort of criteria, or does a …
Specific detection of Mycobacterium paratuberculosis by DNA hybridisation with a fragment of the insertion element IS900.
Authors: M T Moss, E P Green, M L Tizard, Z P Malik, J Hermon-Taylor
Journal: Gut (1991)

This paper describes the evaluation of a newly developed DNA probe for Mycobacterium paratuberculosis. DNA probe PCR278 is a 278 bp fragment obtained by polymerase chain reaction (PCR) amplification of the 5'-region of IS900, an insertion element contained in the genome of M paratuberculosis. This DNA probe can specifically distinguish M paratuberculosis from a wide range of other organisms, including members of the M avium-M intracellulare complex. When used in conjunction with the PCR amplification technique DNA probe PCR278 could detect as little as 10 fg (equivalent to two genomes) starting material of M paratuberculosis genomic DNA. Use of PCR amplification assays based on IS900, for the detection of M paratuberculosis, and homologous IS elements found in disease isolates of M avium should greatly help our understanding of the role of these organisms in Crohn's disease and other chronic inflammatory disorders.
Emergence of scarlet fever Streptococcus pyogenes emm12 clones in Hong Kong is associated with toxin acquisition and multidrug resistance
Authors: Mark R Davies, Matthew T Holden, Paul Coupland, Jonathan H K Chen, Carola Venturini, Timothy C Barnett, Nouri L Ben Zakour, Herman Tse, Gordon Dougan, Kwok-Yung Yuen, Mark J Walker
Journal: Nature Genetics (2014)
Fatal Hepatitis after Phenurone Therapy for Epilepsy
Authors: James B. Field, Raymond A. Justi
Journal: New England Journal of Medicine (1954)

IN 1948 Phenurone (phenylacetylurea) was introduced for the treatment of psychomotor epilepsy. Early reports1 2 3 4 5 of its use were favorable, but reports of toxic side effects began to appear and several deaths from liver failure4 , 6 , 7 were attributed to it. Because there has been no recent report on the toxicity of this drug, the following case of fatal hepatitis after treatment with Phenurone is presented.Case ReportMrs. L. S. (M.G.H. 805317), a 39-year-old housewife, was admitted to the Massachusetts General Hospital from an out-of-state hospital on March 18, 1953.In September, 1949, she began having attacks during which she stopped whatever . . .
1049-110 Circulating beta-atrial natriuretic peptide in human coronary artery disease: A new marker for stage A heart failure?
Authors: Fernando L Martin, Alessandro Cataliotti, Shang-Chiun Lee, John A Schirger, Denise M Heublein, Lisa C Costello-Boerrigter, Guido Boerrigter, John C Burnett
Journal: Journal of the American College of Cardiology (2004)
Safety and efficacy of imatinib in CML over a period of 10 years: data from the randomized CML-study IV
Authors: L Kalmanti, S Saussele, M Lauseker, M C Müller, C T Dietz, L Heinrich, B Hanfstein, U Proetel, A Fabarius, S W Krause, S Rinaldetti, J Dengler, C Falge, E Oppliger-Leibundgut, A Burchert, A Neubauer, L Kanz, F Stegelmann, M Pfreundschuh, K Spiekermann, C Scheid, M Pfirrmann, A Hochhaus, J Hasford, R Hehlmann
Journal: Leukemia (2015)
Meeting the health needs of trafficked persons
Authors: C. Zimmerman, S. Oram, R. Borland, C. Watts
Journal: BMJ (2009)

International guidance provides advice on safe and appropriate treatmentIn April 2009, the Council of Europe Convention on Action against Trafficking in Human Beings came into force in the United Kingdom.1 The convention requires the state to provide minimum standards of care, including medical services, to all people identified as "trafficked."Meeting the needs and protecting the safety of such people can be a challenge for doctors.Human trafficking involves the movement of people by force, coercion, or deception into situations of exploitation.2Trafficked persons are often subjected to physical violence, sexual abuse, psychological violence, and severe deprivation.Trafficking of women and girls for sexual exploitation receives the
The effect of storage on allergen and microbial agent levels in frozen house dust
Authors: B. Fahlbusch, A. Koch, J. Douwes, W. Bischof, U. Gehring, K. Richter, H.‐E. Wichmann, J. Heinrich
Journal: Allergy (2003)

Background: House dust samples collected for exposure studies are often stored for variable time periods until analysis. However, there is currently no information on the effects of dust storage on the content of biocontaminants. Therefore, associations were analysed between the levels of mite allergens (Der p 1, Der f 1), cat allergen (Fel d 1) and microbial components (endotoxin, β(1→3)‐glucan) on the one hand and the storage duration of dust samples at −20°C on the other hand. Methods: Within the framework of a study on the influences of INdoor factors and Genetics on Asthma (INGA), dust samples were collected from living room floors between June 1995 and August 1998 and extracted according to a standardized protocol. The concentrations of Der p 1, Der f 1, Fel d 1 and β(1→3)‐glucan were determined with specific enzyme immunoassays. Endotoxin content was quantified using a chromogenic kinetic Limulus amoebocyte lysate (LAL) test. All concentrations were expressed per gram of dust Results: Dust samples ( n = 1236) were obtained from 655 homes in Hamburg, Hettstedt, Zerbst and Bitterfeld. Storage duration (range 8–298 days) was grouped into four categories (≤ 60 d; 61–90 d; 91–120 d; &gt; 120 d). After adjustment for city of residence and season of dust sampling, means ratios comparing categories 2–4 to the first category were not statistically significant for Der p 1, Der f 1, endotoxin and β(1→3 glucan). However, Fel d 1 concentrations significantly declined with increased storage times of dust samples. Conclusions: Storage of house dust at −20°C for up to 10 months has no effect on mite allergen, endotoxin and β(1→3)‐glucan levels. A potential loss of Fel d 1 during storage of frozen dust samples needs further investigations by repeated measurements of allergen in identical dust samples.
Fetal "cardiac mucosa" is not adult cardiac mucosa
Authors: P T Chandrasoma
Journal: Gut (2003)

De Hertogh et al ’s autopsy study of the fetal gastro-oesophageal region provides valuable insight into the development of foregut epithelium in the 13–24 week gestational period ( Gut 2003; 52 :791–6). Coincidentally, two other studies appeared on the same subject in April 2003.1,2 These studies were stimulated by our hypothesis that cardiac mucosa does not exist as a normal structure in humans.3,4

Three columnar epithelial types are reported between squamous epithelium and parietal cell containing gastric mucosa in De Hertogh’s study ( Gut 2003; 52 :791–6). These are called “primitive oesophageal mucosa”, “primitive stomach mucosa”, and “cardiac mucosa”. Careful anatomical correlation place all of these mucosae in the oesophagus, proximal to the gastro-oesophageal junction. “Primitive oesophageal mucosa” is a ciliated epithelium …