tbuckley/cabot-search huggingface dataset:
Immunohistochemical Expression of BRCA1 and Lethal Prostate Cancer
Authors: Michelangelo Fiorentino, Gregory Judson, Kathryn Penney, Richard Flavin, Jennifer Stark, Christopher Fiore, Katja Fall, Neil Martin, Jing Ma, Jennifer Sinnott, Edward Giovannucci, Meir Stampfer, Howard D. Sesso, Philip W. Kantoff, Stephen Finn, Massimo Loda, Lorelei Mucci
Journal: Cancer Research (2010)

Abstract BRCA1 functions as a tumor suppressor; recent work suggests that BRCA1 may also induce cell cycle arrest to allow for DNA repair. We hypothesized that BRCA1 expression in prostate tumor tissue may be associated with prostate cancer progression through regulation of the cell cycle. We used immunohistochemistry to evaluate BRCA1 protein expression in archival tumor samples from 393 prostate cancer cases in the Physicians' Health Study. The men were followed prospectively from diagnosis to development of metastases and mortality. Fifteen percent of tumors stained positive for BRCA1. BRCA1-positive tumors had substantially increased tumor proliferation index compared with negative tumors (47.0 Ki67-positive nuclei versus 10.3, P = 0.0016) and were more likely to develop lethal cancer compared with BRCA1-negative tumors (hazard ratio, 4.6; 95% confidence interval, 2.4–8.7). These findings strengthen the hypothesis that BRCA1 plays a role in cell cycle control and show that BRCA1 is a marker of clinical prostate cancer prognosis. Cancer Res; 70(8); 3136–9. ©2010 AACR.
Susceptibility to multiple sclerosis is associated with the proximal immunoglobulin heavy chain variable region.
Authors: M A Walter, W T Gibson, G C Ebers, D W Cox
Journal: Journal of Clinical Investigation (1991)

15 immunoglobulin heavy chain constant (CH) and variable region (VH) polymorphisms were selected to span the entire length of the heavy chain cluster. These polymorphisms were examined in 34 sib pairs concordant for multiple sclerosis (MS) and in 23 sporadic MS patients. Allele frequencies were calculated for the 2 MS patient groups and compared with those found in a control population from the same geographical location and of similar ethnic background. No significant association was found between MS and the 7 CH region polymorphisms examined. However, a significant correlation between the MS phenotype and a VH2 family polymorphism was observed in both MS patient populations (familial MS patients chi 2 = 8.16, P less than 0.005; sporadic MS patients chi 2 = 8.90, P less than 0.005). One allele of the VH2-5 gene segment was found to be over-represented in both MS groups. VH2-5 has recently been physically mapped close to the CH region, between 180 and 360 kb away. These results indicate that a locus near or within the CH-proximal VH region is associated with increased susceptibility to MS.
Clinical performance measurement: part 1--getting the best out of it
Authors: M. Goddard, H. T O Davies, D. Dawson, R. Mannion, F. McInnes
Journal: Journal of the Royal Society of Medicine (2002)

The case for universal measurement of clinical performance now seems unanswerable1. However, as a recent OECD conference has highlighted, the obstacles to implementing an efficient and effective system of performance measurement are formidable2. To get the most out of performance measurement, certain design issues need to be addressed. In this paper we consider two aspects of design: what should a clinical performance measurement system seek to measure? And how should we measure it? In the second and concluding part, we shall look at the pitfalls and how to avoid them.
Multimodality Imaging of Fat-Containing Adrenal Metastasis From Hepatocellular Carcinoma
Authors: Umar Tariq, Liina Poder, David Carlson, Jesse Courtier, Bonnie N. Joe, Fergus V. Coakley
Journal: Clinical Nuclear Medicine (2012)

A biopsy-proven fat-containing metastasis to the adrenal gland in a patient with hepatocellular carcinoma demonstrated low density on nonenhanced CT, heterogeneity on contrast-enhanced CT, and marked signal loss on opposed-phase gradient-echo MRI, mimicking an adrenal adenoma. However, the mass was not present on older studies and showed increased FDG uptake on PET. The possibility of a fat-containing metastasis should be considered for an apparent adrenal adenoma in a patient with a primary hepatocellular carcinoma.
Abstract LB-501: Role of HGF in epithelial-stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ
Authors: Patricia Casbas-Hernandez, Melissa A. Troester, Erick Roman Perez, Rupninder Sandhu, Erin Kirk, Monica D'arcy, Jessica Rein
Journal: Cancer Research (2012)

Abstract Role of HGF in epithelial-stromal cell interactions during progression from benign breast disease to ductal carcinoma in situ. Introduction: Tumor-stroma interactions create a ‘permissive microenvironment’ during cancer progression. Basal and luminal breast cancers (BC) have distinct tumor-stroma interactions, but few studies show how gene expression evolves in premalignant cells. We observed that hepatic fibrosis/HGF signaling is induced in basal-like microenvironments, and previous studies have demonstrated that overexpression of HGF is a predictor of breast cancer recurrence and survival. However it is not known whether HGF signaling is altered in early (premalignant and DCIS) lesions. Methods: To study tumor-stroma interactions during cancer progression, we cocultured breast fibroblasts with a panel of isogenic cell lines, the MCF10 series. The MCF10 series represents different stages of cancer progression (benign, atypical hyperplasia and ductal carcinoma in situ). RNA from cocultures was used to perform gene expression microarrays and proteins secreted into media were analyzed by antibody arrays. Differentially expressed genes were identified using supervised analysis, followed by gene ontology analysis. In addition, a signature of basal-like microenvironment was evaluated to test whether the stroma-epithelial interactions observed in basal-like cancers were also present in premalignant cells. Finally, HGF signaling was inhibited (using an HGF-antibody) to assess effects of this pathway on migration and gene expression. Results: Cocultures with MCF10DCIS express higher levels of RNA involved in immune response processes and connective tissue disorders, as reported previously for basal-like BC. In contrast, premalignant MCF10AT and MCF10A cells showed weak expression of these profiles. In cytokine arrays, striking overexpression of HGF was observed in both MCF10AT1 and MCF10DCIS cocultures relative to cocultures with the benign MCF10A cell line, with corresponding increases in c-MET levels. These changes correlated with increased migration, which was blocked by adding HGF-specific antibodies to the media. Conclusions: Inhibition of HGF alters stromal-epithelial interactions, rendering the premalignant microenvironment more similar to normal microenvironments. HGF signaling is necessary for stroma-induced migratory phenotypes in vitro and is induces widespread gene expression changes. Targeting HGF signaling in early carcinogenesis may have value in preventing progression of basal-like precursor lesions. 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 LB-501. doi:1538-7445.AM2012-LB-501
Diet-Cancer Connection
Authors: HARVEY E. FINKEL
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Diet-Cancer Connection Get access HARVEY E. FINKEL HARVEY E. FINKEL Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 12, 20 June 1990, Page 1070, https://doi.org/10.1093/jnci/82.12.1070-a Published: 20 June 1990
Spectrum of Biventricular Involvement on CMR Among Carriers of ARVD/C-Associated Mutations
Authors: Neda Rastegar, Stefan L. Zimmerman, Anneline S.J.M. Te Riele, Cynthia James, Jeremy R. Burt, Aditya Bhonsale, Brittney Murray, Crystal Tichnell, Daniel Judge, Hugh Calkins, Harikrishna Tandri, David A. Bluemke, Ihab R. Kamel
Journal: JACC. Cardiovascular imaging (2014)
Diagnosis and Follow-up of Hepatic Adenomas
Authors: Mario J. R. Ravry
Journal: JAMA (1976)

<h3>To the Editor.—</h3> Antoniades et al (234:628, 1975) recently described two simultaneous, separate hepatic adenomas in a patient taking oral contraceptives and indicated that liver scans "could be of assistance in evaluating these tumors." Ishak and Rabin<sup>1</sup>reported finding two or more separate nodules in 22 of 75 women who had hepatic adenomas during the reproductive period. Stauffer et al<sup>2</sup>also found multiple nodules of focal nodular hyperplasia in a woman taking oral contraceptives. Thus, the occurrence of multiple synchronous hepatic adenomas in the same patient is probably a frequent phenomenon. Contrary to what Antoniades and colleagues suggest, liver scans lack the accuracy required for the diagnosis and follow-up of these tumors. The following report illustrates the limitations of the liver scan in a patient with multiple adenomas. <h3>Report of a Case.—</h3> A 37-year-old woman complained of indigestion and weakness of one month's duration. She had taken oral
Baldness and Myocardial Infarction
Authors: Samuel M. Lesko
Journal: JAMA (1993)

In Reply.  —There are inaccuracies in Dr Kleinmuntz's letter, and he appears not to understand case-control methods. The 218 men with gastrointestinal disorders were not excluded at all: they were included (as controls). As was stated in the article, men (cases and controls) with a history of rheumatic heart disease, cardiomyopathy, or prior cardiac surgery were not eligible. Only men with a first MI who were under 55 years of age were included as cases; none had preexisting congestive heart failure. In addition, history of angina pectoris was controlled for in the analysis.  Ninety-five percent CIs are commonly used in reporting results of epidemiologic studies and are compatible with the conventional definition of statistical significance (P  With regard to Kleinmuntz's remaining comments, we stated that our nurse-interviewers
Protections for clinical trials in low and middle income countries need strengthening not weakening
Authors: R. Dal-Re, P. Ndebele, E. Higgs, N. Sewankambo, D. Wendler
Journal: BMJ (2014)

The latest revision of the Declaration of Helsinki weakens protections for trial participants in low and middle income countries. <b>Rafael Dal-Ré and colleagues</b> argue that this is a step in the wrong direction
Updates from the British Society for Investigative Dermatology Annual Meeting, 16–18 April 2007, Nottingham, U.K.
Authors: A. Birnie, J.S.C. English
Journal: British Journal of Dermatology (2008)

This is a synopsis of the main research findings presented at the British Society for Investigative Dermatology meeting held during 16-18 April 2007 in Nottingham, U.K. The conference highlighted the recent biological, epidemiological and therapeutic advances that have been made in the field of dermatology. The authors focus on the more important advances or summaries of findings, but this is not meant as a substitute for reading the conference proceedings and related references quoted in this article.
Dehydroepiandrosterone and Cardiac Arrhythmia
Authors: Ray Sahelian
Journal: Annals of Internal Medicine (1998)

Letters1 October 1998Dehydroepiandrosterone and Cardiac ArrhythmiaRay Sahelian, MD and Stuart Borken, MDRay Sahelian, MDMarina Del Rey, CA 90292Abbott Northwestern Hospital; Minneapolis, MN 55424Search for more papers by this author and Stuart Borken, MDMarina Del Rey, CA 90292Abbott Northwestern Hospital; Minneapolis, MN 55424Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-7-199810010-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Dehydroepiandrosterone (DHEA) has been promoted by some members of the alternative medicine community and health food industry as a sexual potency enhancer, energy stimulator, and all around “Fountain of Youth” agent. Recognized androgenic side effects are hirsutism in women and acne in both sexes. Previously unrecognized but a likely additional side effect is cardiac arrhythmia. We report a possible association between DHEA and arrhythmia.A 55-year-old man bought a bottle of 25-mg DHEA tablets at a local retail outlet. He began taking two tablets a day in early June 1997 and noticed palpitations within 2 weeks. He ... Author, Article, and Disclosure InformationAffiliations: Marina Del Rey, CA 90292Abbott Northwestern Hospital; Minneapolis, MN 55424 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byQuantification of BNN27, a novel neuroprotective 17‐spiroepoxy dehydroepiandrosterone derivative in the blood and retina of rodents, after single intraperitoneal administrationDehydroepiandrosterone (DHEA)Heart Toxicity Related to Herbs and Dietary Supplements: Online Table of Case Reports. Part 4 of 5.In Vivo and In Vitro Evidences of Dehydroepiandrosterone Protective Role Cardiovascular SystemDehydroepiandrosterone (DHEA)Thermogenic Supplement Use Does Not Alter Characteristics of Sudden Death in the YoungDoes dehydroepiandrosterone have any benefit in fertility treatment?DHEA as a miracle drug in the treatment of poor responders; hype or hope?Dehydroepiandrosterone sulfate and postmenopausal womenDifferential Manifestation of Cardiovascular Complaints as a Function of Utilization of Ergogenic SupplementsEffect of DHEA on the Hemodynamic Response to Resuscitation in a Porcine Model of Hemorrhagic ShockDehydroepiandrosterone (DHEA)Hormones as Performance-Enhancing DrugsDehydroepiandrosterone and Melatonin: Two NeurohormonesPrasterone 1 October 1998Volume 129, Issue 7Page: 588KeywordsArrhythmiaDehydroepiandrosteroneExerciseFoodHormonesPotassiumPremature atrial contractionPremature ventricular contractionPrevention, policy, and public healthThyroid-stimulating hormone Issue Published: 1 October 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Fc receptor IIIb polymorphism and use of glucocorticoids at baseline are associated with infusion reactions to infliximab in patients with rheumatoid arthritis
Authors: A. Okuyama, H. Nagasawa, K. Suzuki, H. Kameda, H. Kondo, K. Amano, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2010)

Infusion reaction is a major adverse event in patients with rheumatoid arthritis (RA) treated with infliximab. The possible factors including Fcγ receptor (FcγR) polymorphism associated with the development of infusion reactions in patients with RA receiving infliximab were prospectively examined.96 patients with RA were enrolled and scheduled to receive infliximab at a dose of 3 mg/kg at weeks 0, 2 and 6 and every 8 weeks thereafter. Genetic polymorphisms for FcγR were examined in FCGR3A 176F/V and FCGR3B NA1/2 alleles by allele-specific PCR analysis.An infusion reaction was observed in 17 patients (18%) during 52 weeks of treatment with infliximab. The FCGR3B NA1/NA1 genotype was found in 75% of the patients with infusion reactions and in only 37% of those without (p=0.01), whereas the FCGR3A 176F/V genotype was equally distributed in the patients with or without infusion reactions. Glucocorticoids were used in 53% of the patients who developed an infusion reaction and in 80% of those without an infusion reaction (p=0.02). A multivariable logistic regression model showed that the FCGR3B NA1/NA1 genotype and use of glucocorticoids at baseline could be used as independent predictive factors for infusion reactions (OR 6.1 (95% CI 1.9 to 24.3) and OR 0.26 (95% CI 0.08 to 0.84), respectively). The presence of anti-infliximab antibody during infliximab treatment was also associated with infusion reactions.FCGR3B NA1/NA1 genotype, use of glucocorticoids and the presence of anti-infliximab antibody accounted for nearly all patients with RA who developed infusion reactions.
Proliferative lesions in the male reproductive system of F344 rats and B6C3F1 mice: incidence and classification.
Authors: K Mitsumori, M R Elwell
Journal: Environmental Health Perspectives (1988)

The incidences of all primary neoplasms in the testes and accessory reproductive organs of 51,230 male Fischer 344 (F344) rats and 46,752 male B6C3F1 mice were obtained from the pathology data base of more than 300 long-term toxicity/carcinogenicity studies performed for the National Toxicology Program. The overall incidence of reproductive system neoplasms in male F344 rats was 81.5%. The most common neoplasms were interstitial cell adenoma of the testis (76.6%), adenoma/carcinoma of the preputial glands (2.9%), mesothelioma of the tunica vaginalis (1.5%), and adenoma of the prostate gland (0.3%). The combined incidence (0.1%) of 59 other rare neoplasms consisted of 18 different types that occurred with a frequency of 4 or less. In contrast to the rats, male B6C3F1 mice had a low overall incidence (0.6%) of neoplasms in reproductive organs. The most common neoplasm was the interstitial cell adenoma (0.4%). Thirty additional types of neoplasms were identified. Each of these uncommon neoplasms occurred at a frequency of 12 or less with an overall combined incidence of 0.2%. Morphological features are described for neoplasms in the rat and mouse, and criteria are presented for differentiation of testicular interstitial cell adenoma, prostatic adenoma, and mesothelioma from hyperplastic changes.
The Health Transition in Developing Countries: A Role for Internists from the Developed World
Authors: Gerald H. Escovitz
Journal: Annals of Internal Medicine (1992)

Demographic and epidemiologic changes that have occurred in the past five decades in many developing countries provide new opportunities for internists from developed countries to contribute to improvements in international health. These changes, called the "health transition," are characterized by major growth in the number and proportion of middle-aged and elderly persons and in the frequency of the chronic diseases that occur in these age groups. The health transition is the result of concentrated national and international efforts to improve maternal and child health by emphasizing primary care and community-organized outreach services. In many developing countries, such efforts have been responsible for a decrease in the birth rate; reduced maternal mortality; improved preventive services; and a vigorous therapeutic approach to infantile diarrhea and respiratory infection, which, in turn, have resulted in the reduced infant mortality and the increased life expectancy that defines the health transition. These changes, often accompanied by increasing urbanization and industrialization, are creating health problems similar to those seen in the "developed" world but are occurring in countries that have far fewer resources. Internists interested in working in developing countries can therefore bring their skills, experience, and perspective to bear on these problems, primarily by working within well-structured programs, the aim of which is to strengthen the capacity of the organizations and institutions within these countries to cope with the rising tide of chronic adult diseases.
An evidence based approach to individualising treatment
Authors: P. P Glasziou, L. M Irwig
Journal: BMJ (1995)

To which groups of patients can the results of clinical trials be applied? This question is often inappropriately answered by reference to the trial entry criteria. Instead, the benefit and harm (adverse events, discomfort of treatment, etc) of treatment could be assessed separately for individual patients. Patients at greatest risk of a disease will have the greatest net benefit as benefit to patients usually increases with risk while harm remains comparatively fixed. To assess net benefit, the relative risks should come from (a meta-analysis of) randomised trials; the risk in individual patients should come from multivariate risk equations derived from cohort studies. However, before making firm conclusions, the assumptions of fixed adverse effects and constant reduction in relative risk need to be checked.
High Systolic Blood Pressure Increases Prevalence and Severity Of Retinopathy in NIDDM Patients
Authors: Mauro Cignarelli, Maria Luigia De Cicco, Aurelio Damato, Adriano Paternostro, Sergio Pagliarini, Salvatore Santoro, Luigi Cardia, Giovanni De Pergola, Riccardo Giorgino
Journal: Diabetes Care (1992)

To determine whether the severity of retinopathy is higher in a group of NIDDM patients with sBP greater than or equal to 140 mmHg compared with NIDDM patients with sBP less than 140 mmHg.Ophthalmoscopy and FAG were conducted among a group of NIDDM patients with either a sBP above (n = 54) or below (n = 55) 140 mmHg. The groups were matched according to diabetes duration, metabolic control (HbA1c), and AER.Patients with sBP greater than 140 mmHg had a higher prevalence of retinopathy, as established according to a rating scale (4.9 +/- 3.8 vs. 3.2 +/- 3.3, P less than 0.02); furthermore, their BMI values were higher (28.1 +/- 4.5 vs. 24.9 +/- 4.1 kg/m2, P less than 0.001). The group of normotensive subjects showed the highest rate of low grading (0-2) values. However, the highest prevalence rates of 8-10 grading values (proliferative retinopathy) were found in the hypertensive group.These data suggest that sBP values greater than or equal to 140 mmHg favor the onset of retinopathy in NIDDM patients during their 1st 10 yr of disease.
Site-specific alterations in the B oligomer that affect receptor-binding activities and mitogenicity of pertussis toxin.
Authors: Y Lobet, C Feron, G Dequesne, E Simoen, P Hauser, C Locht
Journal: The Journal of Experimental Medicine (1993)

Pertussis toxin plays a major role in the pathogenesis of whooping cough and is considered an important constituent of vaccines against this disease. It is composed of five different subunits associated in a molar ratio 1S1:1S2:1S3:2S4:1S5. The S1 subunit is responsible for the ADP-ribosyltransferase activity of the toxin. The B moiety, composed of S2 through S5, recognizes and binds to the target cell receptors and has some ADP-ribosyltransferase-independent activities such as mitogenicity. Site-directed mutagenesis of subunits S2 and S3 allowed us to identify amino acid residues involved in receptor binding. Of all the modifications generated, the deletion of Asn 105 in S2 and of Lys 105 in S3 resulted in the more drastic reduction of binding to haptoglobin and CHO cells, respectively. A holotoxin carrying both deletions presented a mitogenicity reduced to an undetectable level. The combination of these B oligomer mutations with two substitutions in the S1 subunit led to the production of a toxin analog with reduced ADP-ribosyltransferase-dependent and -independent activities including mitogenicity. As shown by immunoprecipitation with various monoclonal antibodies, the mutant holotoxin was correctly assembled and antigenically similar to the native toxin. This toxin analog induced toxin-neutralizing antibodies at the same level as the holotoxin carrying only mutations in the S1 subunit, and may therefore be considered a useful candidate for the development of a new generation vaccine against whooping cough.
Renal disease. II.
Authors: J. S. Cameron
Journal: BMJ (1966)

Chric Renal Failure In Britain about 7,000 people die every year with unmia.This makes chronic renal failure the major problem facing.nephrologists.Three advances have been mide in the lost few years in coping with the problem-ely, ultaw-proteiu diets, intermittent dialysis, and renal transplantation.