tbuckley/cabot-search huggingface dataset:
Targeting of a Conformationally Exposed, Tumor-Specific Epitope of EGFR as a Strategy for Cancer Therapy
Authors: Hui K. Gan, Antony W. Burgess, Andrew H. A. Clayton, Andrew M. Scott
Journal: Cancer Research (2012)

Epidermal growth factor receptor (EGFR) and its most common extracellular mutant, EGFRvIII, are important therapeutic targets in multiple cancer types. A number of monoclonal antibodies and small-molecule inhibitors against these receptors are now used for anticancer treatments. New insights into the structure and function of these receptors illustrate how they can be targeted in novel ways, with expected improvements in the therapeutic efficacy. Monoclonal antibody 806 (mAb806) is an antibody that targets a conformationally exposed epitope of wild-type EGFR when it is overexpressed on tumor cells or in the presence of oncogenic mutations such as EGFRvIII. The mechanism of action of mAb806, which allows for EGFR inhibition without normal tissue toxicity, creates opportunities for combination therapy and strongly suggests mAb806 will be a superior targeted delivery system for antitumor agents. Targeting of the epitope for mAb806 also appears to be an improved strategy to inhibit tumors that express EGFRvIII. This concept of conformational epitope targeting by antibodies reflects an underlying interplay between the structure and biology of different conformational forms of the EGFR family.
Angiotensin I and II exert inotropic effects in atrial but not in ventricular human myocardium. An in vitro study under physiological experimental conditions.
Authors: C Holubarsch, G Hasenfuss, S Schmidt-Schweda, A Knorr, B Pieske, T Ruf, R Fasol, H Just
Journal: Circulation (1993)

BACKGROUND The renin-angiotensin system with its renal-humoral and local myocardial components plays an important role in the development and progression of chronic heart failure. Whereas angiotensin receptors have been found in atrial and ventricular myocardium of different species including humans, its influence on myocardial contractility is not yet defined in human failing myocardium and especially in human nonfailing myocardium. METHODS AND RESULTS We measured force development of right atrial and right and left ventricular myocardial preparations of patients with a variety of cardiac diseases. To evaluate the physiological effects of angiotensin, experimental temperature and stimulation rates were 37 degrees C and 60 beats per minute, respectively. Angiotensin I and II increased peak developed force in atrial myocardial preparations obtained from patients without heart failure in a concentration-dependent manner. At optimal concentrations, peak developed force is increased from 10.2 +/- 1.8 to 12.3 +/- 1.9 mN/mm2 by angiotensin I (P &lt; .05) and from 15.4 +/- 2.1 to 20.5 +/- 3.3 mN/mm2 by angiotensin II (P &lt; .05). This effect was not influenced by pretreatment with propranolol (10(-6) mol/L) and prazosin (10(-5) mol/L) but was completely blocked by saralasin (10(-6) mol/L). The positive inotropic effect of angiotensin I could be blocked by enalaprilate (10(-5) mol/L). Neither angiotensin I nor angiotensin II had any effect in preparations of the left ventricle from patients with idiopathic dilated cardiomyopathy, mitral valve stenosis, and incompetence or in patients with no significant heart disease. Additionally, no effect could be seen when angiotensin II was applied to right ventricular preparations from infants undergoing reconstructive heart surgery for tetralogy of Fallot. CONCLUSIONS Angiotensin I and II exert positive inotropic effects via angiotensin receptors in atrial preparations but not in right or left ventricular preparations. Furthermore, the existence of a local myocardial angiotensin converting enzyme with functional importance is shown.
EC produces strategy to reduce harm from alcohol
Authors: Rory Watson
Journal: BMJ (2006)

The European Commission has presented a strategy that sets out ways to tackle alcohol misuse. It highlights the need to deal with underage drinking and drink driving, and it stresses the importance of good practice and cooperation in information campaigns.

The document, which was requested by EU governments from the commission five years ago, has been the target of fierce lobbying behind the scenes. Sections of the alcohol industry, notably German, Austrian, and Czech brewers, have tried to derail the initiative from the start ( BMJ 2006;333:871-2, 28 Oct).

“What was really annoying …
Management of Community-acquired Pneumonia in Adults
Authors: Grant W. Waterer, Jordi Rello, Richard G. Wunderink
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Despite many advances in medical science, the mortality rate from community-acquired pneumonia (CAP) has changed little in the past four decades. Death and adverse outcomes from CAP result from a complex interplay between the pathogen and the host. Newer information about the effect of pneumonia on comorbidity and underlying diseases, especially long term, suggests this is an important additional axis that differs from the traditional triangular concept of pathogen, host defense, and antibiotic treatment. A number of clinical scoring systems have been developed to help physicians identify patients with CAP at risk of adverse outcomes. None of the criteria have been prospectively demonstrated to avoid late intensive care unit transfers or lower mortality, raising interest in the use of biomarkers such as procalcitonin. Quantitative bacterial genomic load represents a potentially important risk stratification. Optimal antibiotic management appears to include use of a macrolide, although the mechanism of benefit remains unclear. Attempts to improve CAP outcomes through setting measurable process of care standards are to be applauded, but making sure that these standards do not become the end in themselves, but rather that the entire process of care is improved, remains critical.
Prisoners' Access to Medications-Reply
Authors: Allen S. Keller
Journal: JAMA (1993)

<h3>In Reply.</h3> —We appreciate Dr Appel's comments about epilepsy, another disease for which recently arrested prisoners may not have access to medication, and we agree with his assertion that prisoners are likely to complain when their medications are confiscated. Diabetic patients usually do not carry their insulin with them, so some method of storing and dispensing medication on-site at the holding areas is essential to prevent continued unnecessary hospitalizations for diabetic ketoacidosis. The quoted statement in Dr Appel's letter describes the current situation, which we agree is unacceptable. The merit of Dr Appel's interesting suggestion for an interim solution should be assessed by public officials responsible for reform; however, we believe a permanent resolution of the problem will require on-site medical care for newly arrested prisoners.
A whole-blood RNA transcript-based prognostic model in men with castration-resistant prostate cancer: a prospective study
Authors: Robert W Ross, Matthew D Galsky, Howard I Scher, Jay Magidson, Karl Wassmann, Gwo-Shu Mary Lee, Leah Katz, Sumit K Subudhi, Aseem Anand, Martin Fleisher, Philip W Kantoff, William K Oh
Journal: The Lancet Oncology (2012)
Perrault Syndrome With Progressive Nervous System Involvement
Authors: Carsten Kobe, Lutz W. Kracht, Lars Timmermann, Juliane Bachmann, Matthias C. Schmidt
Journal: Clinical Nuclear Medicine (2008)

A 21-year-old woman with a Perrault Syndrome (PS) presented with progressive ataxia. PS comprises gonadal dysgenesis and sensorineural deafness in females. More recent studies have asked whether the neurologic signs in some of the patients are a coincidental finding or part of the syndrome. Magnetic resonance imaging in PS patients shows high intensity signals in the periventricular and the subcortical white substance, as well as in the centrum ovale, suggestive for cerebral leucodystrophy, which is one of a wide spectrum of neurologic symptoms found in PS. The fluorodeoxyglucose positron emission tomography (PET) of our patient brought results indicating a progressive heredoataxia. PET is helpful in the early detection of the progressive central nervous involvement of PS.
The Pituitary "Incidentaloma"
Authors: Mark E. Molitch
Journal: Annals of Internal Medicine (1990)

Purpose: To review evidence related to sellar masses that might be found incidentally on various radiologic procedures, including their differential diagnosis and recommendations for their evaluation and treatment. Data Identification: An English-language literature search using bibliographic reviews of textbooks and review articles. Study Selection: Articles were selected on the basis of providing data on the autopsy prevalence of sellar masses, the radiologic and endocrinologic evaluation of such masses, and the prognostic aspects of pituitary adenomas. Data Extraction: Twelve studies relating autopsy findings, 6 studies describing radiologic characteristics, and 26 articles reviewing various endocrine aspects of pituitary adenomas were evaluated. Results of Data Synthesis: Pituitary adenoma is the most common incidental sellar mass. Scanning techniques are of great importance in differentiating the pituitary adenoma from other mass lesions. Autopsy and radiologic studies suggest that microadenomas (<10 mm in diameter) may be present in 10% to 20% of the population but that macroadenomas (>10 mm in diameter) are quite rare. Hormone oversecretion by an adenoma may be asymptomatic but, when present, is very helpful in the differential diagnosis. Conclusions: For adenomas found to be hypersecreting, therapy is as indicated for that specific tumor type. If there is no evidence of hormone oversecretion from microadenomas, we suggest a conservative approach with repeat scanning done at yearly intervals, initially, and subsequently less frequently. Macroadenomas, because they have already indicated some propensity for growth, should either be surgically removed or, if completely asymptomatic, followed closely with repeat scans at 6- to 12-month intervals.
Newcastle-On-Tyne Infirmary: Practice of Sir John Fife
Authors: A. Taylor
Journal: BMJ (1846)

NPWCASTLr-oN-TYNE INFIRMARY.testicle, and so forth, and which more or less tend to impair the health and shorten life, and whose origin is within, from internal catises.Under the first category may be classed Larreys Egyptian cases, the present one, Hoo Loo, auid probably Mr. Liston's case.Under the second, those cases mentioned by John Bell, and the older surgeons,where abscesses, liydroceles, diseased testicles, &c., are spoken of; and also those cases of Mr. Brett publishied in tihe Lancet of the 28th of Febru- uary, 1846, and the more recent case of, the 11th of July.The disease, as described by Dr. Titley, 'in the West Indies, and Mr. Brett in tihe East, appeared to be accomipanied in its origin with acute fever, but less so in the scrotal cases than where the leg is affected, so that after a time the tumour increases, independently of the febrile attacks.(Vide Medico-ChirurgicalReview, February, 1830.)Mr. Brett hIas, however, argued in his account of the last case, in which he operated successfully, and which had its origin from rupture of the urethra, with extravasation of urine, that the pathological condition of all these cases is the samue.This, I think, is carrying generaliza- tion too far, for the peculiar condition of the skin -een in some cases, gives a distinctive chiaracter to the disease, if our pathology is to be based on anatomical structure; for although some of the other conditions may be the same under which these growths occur, and the same size or greater may be attained to,.by the accumulation of deposits in the cellular tissue froin wbatever cause arising, yet, if the commencement, progress, and termination of, and method and, success in operative procedure in, such cases be different, it is evident that on physiological, patio., logical, and surgical grounds, distinction ought to be made.Tbe following are the weiglhts that soine of thlese tumours have arrived at:- M. De ha Croix, operated on by De Lonnes 30 lbs.Chopart, case of a negro on the coast of Guinea 40 lhi.Larrey, in Egypt, fromi - 50 lbs.to 100 ilbs Dr. Titley, in a native of St.
Review: Adding α1-blockers to 5α-reductase inhibitors improves lower urinary tract symptoms in men
Authors: Lionel S. Lim, Brian Sperling
Journal: Annals of Internal Medicine (2014)

ACP Journal Club18 March 2014Review: Adding α1-blockers to 5α-reductase inhibitors improves lower urinary tract symptoms in menLionel S. Lim, MD, MPH, FACP, FACPM, Brian Sperling, DOLionel S. Lim, MD, MPH, FACP, FACPMGriffin Hospital, Derby, Connecticut, USA (L.S.L., B.S.)Search for more papers by this author, Brian Sperling, DOGriffin Hospital, Derby, Connecticut, USA (L.S.L., B.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-160-6-201403180-02002 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationFüllhase C, Chapple C, Cornu JN, et al. Systematic review of combination drug therapy for non-neurogenic male lower urinary tract symptoms. Eur Urol. 2013;64:228-43. https://pubmed.ncbi.nlm.nih.gov/23375241Clinical Impact RatingsGIM/FP/GP: References1 Kaplan SA, Roehrborn CG, McConnell JD, et al; Medical Therapy of Prostatic Symptoms Research Group. Long-term treatment with finasteride results in a clinically significant reduction in total prostate volume compared to placebo over the full range of baseline prostate sizes in men enrolled in the MTOPS trial. J Urol. 2008;180:1030-2. [PMID: 18639298] Google Scholar2 Roehrborn CG, Siami P, Barkin J; CombAT Study Group. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol. 2010;57:123-31. [PMID: 19825505] Google Scholar3 US Food and Drug Administration. FDA Drug Safety Communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer. www.fda.gov/Drugs/DrugSafety/ucm258314.htm (accessed 2 Jan 2014). Google Scholar Author, Article, and Disclosure InformationAffiliations: Griffin Hospital, Derby, Connecticut, USA (L.S.L., B.S.)This article was published at Annals.org on 4 March 2014. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 March 2014Volume 160, Issue 6Page: JC2KeywordsAdverse eventsDrug therapyEpidermal growth factorProstate cancerResearch designSafetySystematic reviewsUrine ePublished: 18 March 2014 Issue Published: 18 March 2014 CopyrightCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Reply to ‘Claimed association of absolute lymphocyte count with therapeutic efficacy of radio-immunotherapy in patients with indolent lymphoma cannot be verified in an independence data set’ by Mark J Bishton et al
Authors: L F Porrata, K Ristow, T E Witzig, N Tuinistra, T M Habermann, D J Inwards, S M Ansell, I N Micallef, P B Johnston, S N Markovic
Journal: Leukemia (2008)
Engineering Cellular Resistance to HIV
Authors: Mark A. Kay, Bruce D. Walker
Journal: New England Journal of Medicine (2014)

A remarkable story of bedside-to-bench-to-bedside research is the discovery of the human immunodeficiency virus (HIV) coreceptor CCR5 and the subsequent therapeutic advances made because of this knowledge. Persons who were heavily exposed to HIV and did not become infected were studied, and a homozygous 32-bp deletion (delta32/delta32) was found in CCR5, the gene encoding this transmembrane protein.1 The deletion did not impair CD4 T-cell function, but it did render cells resistant to infection with the typically transmitted R5 viruses that use the CCR5 receptor together with CD4 to gain entry into cells. This knowledge, in turn, led to the development . . .
The beneficial effects of atrial natriuretic peptide on arrhythmias and myocardial high-energy phosphates after reperfusion
Authors: Y Takata
Journal: Cardiovascular Research (1996)

Objectives: The aim of this investigation was to test whether the administration of atrial natriuretic peptide (ANP) has cardioprotective effects against ischaemic and reperfusion injury. Methods: Thoracotomized dogs underwent a 30 min left circumflex coronary artery occlusion and 60 min of reperfusion (control group; n = 16). The ANP group (n = 9) received a 20 μg bolus injection of synthetic α human ANP (SUN 4936) followed by infusion at a dose of 0.1 μg/kg/min from the beginning of coronary occlusion to the end of the procedure. Results: Administration of exogenous ANP increased plasma ANP immediately and maintained levels at 3000 pg/ml, resulting in an 8-fold increase in plasma cyclic guanosine monophosphate (cGMP) levels. Plasma ANP and plasma cGMP levels did not change at all in controls. There were no significant differences in haemodynamic parameters during ischaemia and reperfusion between the groups. In the ANP group, the prevalence and frequency of ventricular extrasystoles within 10 min after reperfusion decreased markedly [ANP 22% vs. control 100%, P < 0.01, and ANP 1 (1) vs. control 92 (50), P < 0.05, respectively]. No dog in the ANP group had ventricular fibrillation (VF), but the incidence of VF was not statistically significant between the groups [ANP 0% vs. control 25%]. ATP content in the inner layers of the ischaemic myocardium in the ANP group was higher than in controls (P < 0.05) [1.92 (0.28) vs. 1.18 (0.13) μmol/g wet weight]. There was no significant difference in the content of myocardial tissue angiotensin II between the groups. Conclusions: These data show that the infusion of ANP has cardioprotective effects on myocardial ischaemia and reperfusion in this model. These beneficial effects are probably due to direct effects through cGMP rather than haemodynamic changes.
Abstract 144: MicroRNA-190, regulated by estrogen receptor signaling, suppresses expression of the metastasis-promoting gene <i>PAR-1</i> and is associated with breast cancer progression
Authors: Hou-Wei Chu, Chun-Wen Cheng, Wen-Cheng Chou, Ling-Yueh Hu, Hsiao-Wei Wang, Chia-Ni Hsiung, Pei-Ei Wu, Huan-Ming Hsu, Jyh-Cherng Yu, Chen-Yang Shen
Journal: Cancer Research (2012)

Abstract Cancer metastasis contributes to mortality of breast cancer patients. The present study, based on the fundamental concept that dissociation of the extracellular matrix is the driving force for tumor metastasis, was performed to examine the hypothesis that microRNA-190 (miR-190) is important in regulating breast cancer metastasis by decreasing the expression of protease-activated receptor-1 (PAR-1), a gene encoding a receptor for matrix metalloproteinase1 and thrombin that is associated with tumor metastasis. This hypothesis was initially suggested by the observations that the expression of a reporter gene could be regulated by a specific sequence in the 3′-untranslated region of PAR-1 and that miR-190 was complementary to this sequence. Support for our hypothesis came from the findings that (a) PAR-1 expression was directly inhibited by miR-190, (b) increased miR-190 expression suppressed cell migration and invasiveness, and (c) the level of miR-190 expression in primary breast carcinomas correlated with overall survival. Interestingly, we defined the promoter region of miR-190 and noted that it contained half of an estrogen receptor (ER) response element, supporting the breast tumorigenic contribution of miR-190. This was further confirmed by the findings that miR-190 expression was activated by 17β-estradiol and that the ER bound directly to this promoter and regulated miR-190 expression. The findings of the present study may explain why ER-positive patients usually have a favorable progression and how ER regulates cancer metastasis, i.e. ER signaling regulates miR-190 expression, thus causing suppression of PAR-1 expression, resulting in inhibition of breast cancer metastasis. 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 144. doi:1538-7445.AM2012-144
Clinical correlation of the venom-specific IgG antibody level during maintenance venom immunotherapy
Authors: David B.K. Golden, Ira D. Lawrence, Robert H. Hamilton, Anne Kagey-Sobotka, Martin D. Valentine, Lawrence M. Lichtenstein
Journal: Journal of Allergy and Clinical Immunology (1992)

Allergen immunotherapy is associated with a significant increase of specific IgG antibodies that have been suggested as a mechanism of action and as a marker of efficacy for immunotherapy.The value of venom-specific IgG antibody determinations as a measure of clinical protection against sting anaphylaxis has been difficult to prove in individual patients.We performed 211 insect sting challenges in 109 patients over a 4-year period to determine the significance of venom IgG levels 3 tzg/ml or lower.Systemic symptoms occurred in only 1.6% of those with venom IgG more than 3/xg/ml, but in 16% of those with less than 3/zg/ml IgG, and notably in 26% of patients with low venom IgG who had received less than 4 years of treatment.The venom IgG level had no predictive value in patients who had received more than 4 years of therapy.Honeybee sting data were inconclusive because of the small number of subjects.We conclude that low venom-specific lgG levels are associated with an elevated risk of treatment failure during the first 4 years of immunotherapy with yellow jacket or mixed vespid venoms.( J ALLERGY CLIN IMMUNOL 1992;90,'386-93.)