tbuckley/cabot-search huggingface dataset:
Abstract 1321: Castration-resistant prostate cancer: BAY 1024767 blocks function of mutated androgen receptor.
Authors: Bernard Haendler, Tatsuo Sugawara, Pascale Lejeune, Silke Koehr, Hortensia Faus, Matthias Busemann, Arwed Cleve, Ulrich Luecking, Franz von Nussbaum, Michael Brands, Dominik Mumberg
Journal: Cancer Research (2013)

Abstract Analysis of biopsies from prostate cancer metastases and of circulating tumor cells shows that androgen receptor (AR) mutations are often found in patients developing resistance to antiandrogen therapy, i.e. at the castration-resistant prostate cancer (CRPC) stage. Here we report on preclinical studies with a novel androgen receptor suppressor compound BAY 1024767 that exhibits strong antagonism for wild-type and mutated AR, both in vitro and in vivo. Mutations located in the AR ligand-binding domain (LBD) and potentially involved in the resistance to the standard of care bicalutamide were generated and tested in cell-based transactivation assays, using 0.1 nM R1881 for stimulation. Bicalutamide showed reduced antagonistic activity for AR E709Y and no antagonism up to 10 μM for AR W741C. In comparison, BAY 1024767 exhibited strong antagonism for these mutants. Another mechanism leading to CRPC is the elevation of intratumoral androgen levels. To mimick this situation, the transactivation assays were performed at a higher (1 and 10 nM R1881) androgen concentration. Bicalutamide, and also the novel antiandrogen MDV3100, showed much reduced antagonism for wild-type and W741C or E709Y mutant AR. Conversely, antagonism was still observed for BAY 1024767, especially at 1 nM R1881. The KuCaP-1 model, which is derived from a CRPC patient and harbors the W741C mutation, was obtained from the group of O. Ogawa (Kyoto University). Mice bearing the KuCaP-1 xenograft subcutaneously were treated with bicalutamide (60 mg/kg, PO, qdx20) or BAY 1024767 (50 mg/kg, PO, q2dx10). No effect on tumor growth was observed with bicalutamide (T/C=103%) whereas BAY 1024767 was able to inhibit tumor growth with a T/C of 36% on day 54 post-implantation. In another study we found that MDV 3100 (100 mg/kg, PO) and abiraterone acetate (200 mg/kg, PO) were inactive in the KuCaP-1 model (100% and 73% T/C, respectively). Citation Format: Bernard Haendler, Tatsuo Sugawara, Pascale Lejeune, Silke Koehr, Hortensia Faus, Matthias Busemann, Arwed Cleve, Ulrich Luecking, Franz von Nussbaum, Michael Brands, Dominik Mumberg. Castration-resistant prostate cancer: BAY 1024767 blocks function of mutated androgen receptor. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1321. doi:10.1158/1538-7445.AM2013-1321
Immunopathological abnormalities in the normal skin of patients with rheumatoid arthritis in relation to clinical and serological findings: a one year follow up study.
Authors: M L Westedt, B J Vermeer, C J Meijer, M R Daha, W M Baldwin, A Cats
Journal: Annals of the Rheumatic Diseases (1987)

Fifty two patients with seropositive rheumatoid arthritis (RA) were studied over a period of one year to investigate possible relationships among changes of circulating immune complexes (CIC), deposits of immunoglobulins and complement around the cutaneous blood vessels, clinical activity of the disease, and the presence of extra-articular manifestations (EAM). The presence or absence of IgM and C3 in and around the cutaneous blood vessels correlated significantly with the presence or absence of extra-articular features in cross sectional and longitudinal studies. Patients with evidence of these cutaneous immune deposits also had a greater prevalence of CIC as determined by the Clq binding assay (ClqBA) or polyethylene glycol (PEG) assay for IC containing IgM (IgM IC). Although the degree of perivascular mononuclear cell infiltration around the blood vessels in the papillary dermis was related to the patients9 clinical state at the initial assessment, it did not correlate with the later changes in the activity of the joint disease or the occurrence of EAM. Thus the deposition of immunoglobulin or complement, or both, seems to be independent of cellular infiltration. The meaning of these cellular infiltrates is not yet fully understood. Our study has shown that many patients with RA who appeared to have only joint disease in fact had subclinical systemic disease as reflected by a positive skin biopsy or CIC. Moreover, the disappearance of IgM deposits from the skin correlated with the disappearance of EAM and improvement of joint disease.
Abnormal fibrinolysis in healthy male cigarette smokers: Role of plasminogen activator inhibitors
Authors: William D. Haire, Jonathan C. Goldsmith, Julie Rasmussen
Journal: American Journal of Hematology (1989)

Abstract The extrinsic fibrinolytic system and its response to cigarette smoking was studied in five healthy male smokers 35–45 years old. Tissue plasminogen activator (t‐PA) release in response to venous occlusion was intact both at 8:00 A.M. and 3:00 P.M. Acutely smoking two cigarettes neither stimulated fibrinolysis nor changed levels of t‐PA or plasminogen activator inhibitors. Functional plasminogen activator inhibitor (PA‐I) levels and euglobulin lysis times were higher in the smoking group than in a control group matched for age, sex, and body mass. Antigenic levels of PA‐I 1, the PA‐I derived from vascular endothelial cells and platelets, were similar in both groups. While smoking did not acutely alter fibrinolysis in chronic smokers, these individuals had a high frequency of abnormal fibrinolysis characterized by high levels of PA‐I activity. This abnormality is due to either high specific activity of PA‐I 1 or to the presence of other antigenically distinct plasminogen activator inhibitors. Abnormal firbinolysis may be one mechanism contributing to the thrombotic diathesis of cigarette smokers.
Efficient Delivery of p53 and Cytochrome C by Supramolecular Assembly of a Dendritic Multi‐Domain Delivery System
Authors: David Yuen Wah Ng, Jörg Fahrer, Yuzhou Wu, Klaus Eisele, Seah Ling Kuan, Holger Barth, Tanja Weil
Journal: Advanced Healthcare Materials (2013)

Versatile nanocarrier systems facilitating uptake of exogenous proteins are highly alluring in evaluating these proteins for therapeutic applications. The self-assembly of an efficient nano-sized protein transporter consisting of three different entities is presented: A streptavidin protein core functioning as an adapter, second generation polyamidoamine dendrons for facilitating cell uptake as well as two different therapeutic proteins (tumor suppressor p53 or pro-apoptotic cytochrome c as cargo). Well-defined dendrons containing a biotin core are prepared and display no cytotoxic behavior upon conjugation to streptavidin. The integration of biotinylated human recombinant p53 (B-p53) into the three component system allows excellent internalization into HeLa, A549 and SaOS osteosarcoma cells monitored via confocal microscopy, immunoblot analysis and co-localization studies. In addition, the conjugation of B-p53 to dendronized streptavidin preserves its specific DNA-binding in vitro, and its delivery into SaOS cells impairs cell viability with concomitant activation of caspases 3 and 7. The versatility of this system is further exhibited by the significant enhancement of the pro-apoptotic effects of internalized cytochrome c which is analyzed by flow cytometry and cell viability assays. These results demonstrate that the "bio-click" self-assembly of biotinylated dendrons and proteins on a streptavidin adapter yields a stable supramolecular complex. This efficient bionanotransporter provides an attractive platform for mediating the delivery of functional proteins of interest into living mammalian cells in a facile and rapid way.
Contempo '81. Ophthalmology
Authors: F. C. Blodi
Journal: JAMA (1981)

This year, significant advances have been made in both clinical and experimental ophthalmology. <h3>Treatment of Conjunctival Melanoma</h3> The treatment of diffuse malignant melanoma of the conjunctiva has been enriched by the recent experience of Jakobiec et al,<sup>1</sup>who have had excellent success using cryotherapy for two extensive areas of flat intraepithelial melanosis. They advise surgical excisions of tumefactions and invasive melanomas, but find repeated cryoapplications most suitable for controlling widespread flat disease. This method would be of great benefit because it could avoid exenteration in patients who have widespread melanotic lesions. The conjunctiva treated by cryoapplication recovers quickly after a transient phase of inflammatory reaction. The conjunctival stroma is not damaged, and normal reepithelialization can occur from adjacent zones of conjunctiva. <h3>Surgical Treatment of Myopia</h3> The surgical treatment of myopia has attracted considerable attention in the lay media. A new approach, the radical keratotomy, was introduced into the United
Inadequate Response to Treatment in Coronary Heart Disease
Authors: Johan Denollet, Johan Vaes, Dirk L. Brutsaert
Journal: Circulation (2000)

Improvement in treatment of patients with coronary heart disease (CHD) has caused longer survival but also an increase in the number of patients at risk for subsequent cardiac events and impaired quality of life (QOL). We hypothesized that chronic emotional distress confers an increased risk of poor outcome despite appropriate treatment.This prospective study examined the 5-year prognosis of 319 patients with CHD. Baseline assessment included symptoms of depression/anxiety and distressed personality type (type D-ie, high negative affectivity and social inhibition). The main end points were cardiac death or nonfatal myocardial infarction and impaired QOL. There were 22 cardiac events (16 nonfatal); they were related to left ventricular ejection fraction (LVEF) </=50%, poor exercise tolerance, age </=55 years, symptoms of depression, and type D personality. Multivariate analysis yielded LVEF </=50% (OR, 3.9; P=0.009), type D personality (OR, 8.9; P=0.0001), and age </=55 years (OR, 2.6; P=0.05) as independent predictors of cardiac events. Convergence of these risk factors predicted the absence of the expected therapeutic response that was observed in 10% of the patients. When 2 or 3 risk factors occurred together, the rate of poor outcome was 4-fold higher (P=0. 0001). Estimates of medical costs increased progressively with an increasing number of risk factors. Smoking, symptoms of depression, and type D personality were independent predictors of impaired QOL.Decreased LVEF, type D personality, and younger age increase the risk of cardiac events; convergence of these factors predicts nonresponse to treatment. Emotionally stressed and younger patients with CHD represent high-risk groups deserving of special study.
Systemic Contraceptives and the Liver
Authors: DANIEL M. KNOWLES
Journal: Annals of Internal Medicine (1975)

Comments1 December 1975Systemic Contraceptives and the LiverDANIEL M. KNOWLES, M.D., MARIANNE WOLFF, M.D.DANIEL M. KNOWLES, M.D.Search for more papers by this author, MARIANNE WOLFF, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-83-6-907 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The "pill-associated benign hepatic neoplasms" have evoked considerable interest, as evidenced by still another report, by Stauffer and associates (Ann Intern Med 83:301-306, 1975). We believe that several points raised in that report do, however, require clarification.Stauffer and colleagues consider as a homogeneous group all of the "pill-associated hepatic neoplasms," referring to the occurrence in young women using oral contraceptives as a syndrome. This melée consists of at least two distinct clinicopathologic entities, focal nodular hyperplasia and liver cell adenoma, which unfortunately have not generally been well recognized and accurately diagnosed by pathologists.Critical histopathologic review...References1. MAYSCHRISTOPHERSONBARROW EWG: Focal nodular hyperplasia of the liver: possible relationship to oral contraceptives. Am J Clin Pathol 61:735-746, 1974 CrossrefMedlineGoogle Scholar2. AMERIKSTHOMPSONFREY JNC: Hepatic cell adenomas, spontaneous liver rupture and oral contraceptives. Arch Surg 110:548-557, 1975 CrossrefMedlineGoogle Scholar3. KNOWLESWOLFFCASARELLA DMW: Hepatic cell adenomas (letter). Arch Surg 110:1154-1155, 1975 CrossrefMedlineGoogle Scholar4. KNOWLESWOLFF DM: Focal nodular hyperplasia of the liver: a clinicopathologic study and review of the literature. Hum Pathol, in press Google Scholar5. SÖRENSENBADEN TH: Benign hepatocellular tumors. Scand J Gastroenterol 10:113-119, 1975 MedlineGoogle Scholar1. EDMONDSON H: Tumors of the Liver and Intrahepatic Bile Ducts: Benign Epithelial Tumors. Washington, D.C., Armed Forces Institute of Pathology, 1958, pp. 193-206 Google Scholar2. AMERIKOTHOMPSONFREY JNC: Hepatic cell adenomas, spontaneous liver rupture and oral contraceptives. Arch Surg 110:548-557, 1975 CrossrefMedlineGoogle Scholar3. DAVISSCHENKENZIMMERMAN JJO: Massive hemoperitineum from rupture of benign hepatocellular adenoma. Surgery 73:181-184, 1973 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: DANIEL M. KNOWLES, M.D.; MARIANNE WOLFF, M.D.Affiliations: Department of Pathology College of Physicians and Surgeons Columbia University New York, New York 10032 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDContraceptive steroids and liver lesionsBenign hepatic lesions and orally administered contraceptives 1 December 1975Volume 83, Issue 6Page: 907-908KeywordsAdenomasContraceptivesLiverOral contraceptive therapyPathologists ePublished: 1 December 2008 Issue Published: 1 December 1975 PDF downloadLoading ...
On the Use of Optometers for the Examination of Soldiers and Workmen Employed on the Railroad
Authors: E. Warlomont
Journal: BMJ (1881)

The. cases here narrated, are, of course, too few in number to war- rant 'any confident conclusions; but they are sufficient to show" that thereis a strong probability of benzoate of-soda being a' remedy of considerable efficacy in the treatment of rheumatic fever.In all off them, the symptoms passed off in periods-varying from three
A CASE OF GLOSSOPHARYNGEAL NEURALGIA
Authors: J. P. Martin
Journal: BMJ (1931)

JOURNM~~~d rawing a deep breath.Displacement of the neicgihbouring structures associated with large-accu-imulations of pus in the pleura may also be painful. PAIN IN THE LIMBSPain in the limbs is shown in two ways.: first, the pa-i,inful limb is moved less tha.n the other limbs, and may be motionless and, secondly, any attempts to move the limb provoke crying.When an infant has pain in the
British Regional Heart Study: cardiovascular risk factors in middle-aged men in 24 towns.
Authors: A G Shaper, S J Pocock, M Walker, N M Cohen, C J Wale, A G Thomson
Journal: BMJ (1981)

The British Regional Heart Study seeks to define risk factors for cardiovascular disease, to examine their interrelationships, and to explain the geographic variations in cardiovascular disease in Britain. A clinical survey of men aged 40-59 in 24 British towns was carried out and preliminary data from the survey analysed. On a town basis cardiovascular mortality was associated with mean systolic blood pressure and the prevalence of heavy cigarette smoking and heavy alcohol consumption. No such association was seen for body mass index or mean serum total cholesterol or high-density-lipoprotein cholesterol concentration. Cigarette smoking and alcohol intake and, to a less degree, systolic blood pressure were related to the social class (percentage of manual workers) of a town, and these factors may determine to some extent the increased risk of cardiovascular disease in manual workers. Blood pressure in individual subjects was affected predominantly by age, body mass index, and alcohol intake. Body mass index appeared to affect blood pressure to a greater extent than alcohol intake and did so with a consistent and positive linear trend. Nevertheless, the differences between towns in mean blood pressure readings appeared to be more closely associated with variations in the prevalence of heavy drinking than with variations in body mass index. Alcohol intake and body mass index explained only a part of the striking differences between towns in mean blood pressure readings, and some important "town"factors remained unexplained.
Predictive Biomarkers of Antiangiogenic Therapy for Advanced Hepatocellular Carcinoma: Where Are We?
Authors: Yu-Yun Shao, Chih-Hung Hsu, Ann-Lii Cheng
Journal: Liver Cancer (2013)

Antiangiogenic therapy, especially treatment with sorafenib, is the primary treatment for patients with advanced hepatocellular carcinoma (HCC). However, the efficacy of such therapy is modest, with low objective response rates and limited prolongation of survival times. Several researchers have investigated predictive biomarkers to help identify patients who can benefit most from antiangiogenic therapy. The largest study on this topic to date was based on the pivotal phase III study of sorafenib (the SHARP study) and did not find any plasma markers that could predict the efficacy of sorafenib. Other studies based on single-arm phase II clinical trials found some potential predictive markers, such as early alpha-fetoprotein response, the serum insulin-like growth factor-1 level at baseline, and the volume transfer constants of dynamic contrast-enhanced magnetic resonance imaging. These findings require validation by further studies. Identifying predictive biomarkers of antiangiogenic therapy for HCC remains challenging and warrants further investigations.
Home Care — Who Cares?
Authors: Mary Jane Koren
Journal: New England Journal of Medicine (1986)

Home care is currently one of the most rapidly growing fields in health care, yet it is a subject that the majority of physicians know little about. The purposes of this discussion are, first, to explore the reasons for the general isolation of the medical profession from home care; second, to explain why physicians must acquaint themselves with home care as a system of services to supplement the care they provide to patients in their offices and in institutions; and, third, to demonstrate why medical input is needed to protect patients from becoming pawns of market forces and fiscal policy . . .
Hepatitis B virus X protein (HBx)-related long noncoding RNA (lncRNA) down-regulated expression by HBx (Dreh) inhibits hepatocellular carcinoma metastasis by targeting the intermediate filament protein vimentin
Authors: Jin-feng Huang, Ying-jun Guo, Chen-xi Zhao, Sheng-xian Yuan, Yue Wang, Guan-nan Tang, Wei-ping Zhou, Shu-han Sun
Journal: Hepatology (2012)

The hepatitis B virus X protein (HBx) has been implicated as an oncogene in both epigenetic modifications and genetic regulation during hepatocarcinogenesis, but the underlying mechanisms are not entirely clear. Long noncoding RNAs (lncRNAs), which regulate gene expression with little or no protein-coding capacity, are involved in diverse biological processes and in carcinogenesis. We asked whether HBx could promote hepatocellular carcinoma (HCC) by regulating the expression of lncRNAs. In this study we investigated the alteration in expression of lncRNAs induced by HBx using microarrays and real-time quantitative polymerase chain reaction (PCR). Our results indicate that HBx transgenic mice have a specific profile of liver lncRNAs compared with wildtype mice. We identified an lncRNA, down-regulated expression by HBx (termed lncRNA-Dreh), which can inhibit HCC growth and metastasis in vitro and in vivo, act as a tumor suppressor in the development of hepatitis B virus (HBV)-HCC. LncRNA-Dreh could combine with the intermediate filament protein vimentin and repress its expression, and thus further change the normal cytoskeleton structure to inhibit tumor metastasis. We also identified a human ortholog RNA of Dreh (hDREH) and found that its expression level was frequently down-regulated in HBV-related HCC tissues in comparison with the adjacent noncancerous hepatic tissues, and its decrement significantly correlated with poor survival of HCC patients.These findings support a role of lncRNA-Dreh in tumor suppression and survival prediction in HCC patients. This discovery contributes to a better understanding of the importance of the deregulated lncRNAs by HBx in HCC and provides a rationale for the potential development of lncRNA-based targeted approaches for the treatment of HBV-related HCC.
Individualized Treatment of Alcohol Withdrawal
Authors: John T. Sullivan
Journal: JAMA (1995)

<h3>To the Editor.</h3> —The recent article entitled "Individualized Treatment for Alcohol Withdrawal" by Dr Saitz and colleagues<sup>1</sup>compared "fixed-schedule therapy" (substitution) with "symptom-triggered therapy" (suppression). The conclusions are open to misinterpretation for the following reasons. The dosage chosen for the fixed schedule (400 mg of chlordiazepoxide) may be high for groups of subjects with little evidence of alcohol withdrawal (selection bias). A Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) median score of 9 is barely recognizable as alcohol withdrawal (and some subjects had scores of 0). No entry criterion for alcohol withdrawal was used (presumably it was the expectation of withdrawal). Previous studies using a predominantly white male veteran population have demonstrated that only 13% of these subjects required drug treatment.<sup>2</sup>Other general hospital studies have revealed that a median dose of 50 mg of diazepam (200 mg of chlordiazepoxide) was required using similar criteria for treatment
US academic researchers hold divided views on ties to industry
Authors: B. Roehr
Journal: BMJ (2011)

Academic biomedical researchers in the United States are divided on whether or not ties to industry compromise the integrity of research. The split is largely along the lines of whether the researchers do receive support from industry. But both factions agree that universities’ existing policies on conflicts of interest are “about right.”

The analysis was based on 2168 responses (a 74% response rate) from randomly selected academics in four categories at the 50 universities that received the most research funding from the US National Institutes of Health. The paper survey was conducted in 2007 as part of a regular periodic survey process begun in 1986.

Earlier published analysis from the same survey showed that the industry provides just …
Lithium for Zidovudine-Induced Neutropenia in AIDS-Reply
Authors: Henry H. Balfour
Journal: JAMA (1988)

<h3>In Reply.—</h3> Herbert and colleagues suggest that lithium carbonate, because of its granulopoietic effect, might be used to treat zidovudine-induced neutropenia. Their intriguing postulate merits further study. In addition to the case described in this letter, Roberts et al<sup>1</sup>published an uncontrolled study of five patients with zidovudine-associated neutropenia, four of whom appeared to respond to lithium. However, the relative contribution of reduction in the dose of zidovudine vs lithium therapy to the improved neutrophil counts can be objectively assessed only by a controlled trial, which Herbert et al tell us that they are conducting. We have three specific comments to the speculations raised in this letter. First, reducing the dose of zidovudine to subtherapeutic levels may be harmful because the patient's basic HIV disease then might progress unchecked. However, there is no evidence, as de Gans et al<sup>2</sup>have noted, to substantiate the concept that increased HIV