tbuckley/cabot-search huggingface dataset:
Abstract 133: Effects of iASPP on paclitaxel-mediated mitotic catastrophe and chemoresistance in ovarian cancers
Authors: Li Li Jiang, Michelle KY Siu, Oscar GW Wong, Kai Fai Tam, Xin Lu, Eric WF Lam, Hextan YS Ngan, Xiao Feng Le, Esther SY Wong, Lara J. Monteiro, Hoi Yan Chan, Annie NY Cheung
Journal: Cancer Research (2010)

Abstract Purpose: In this study, for the first time, we aimed to investigate the expression profile of iASPP in ovarian epithelial tumor in association with clinicopathological parameters. In vitro effect of iASPP on paclitaxel chemosensitivity will also be investigated. Materials and Methods: Expression and amplification status of iASPP was examined in 140 clinical samples and 16 ovarian cell lines using immunohistochemistry, immunoblotting and quantitative real-time PCR, and correlated with clinicopathological parameters. Changes in proliferation, mitotic catastrophe and apoptosis in ovarian cancer cell lines of different p53 status following paclitaxel exposure were also analyzed using TUNEL assay, MTT assay and immunofluorescence. Results: By immunohistochemistry and quantitative PCR, significantly higher protein and mRNA levels of iASPP was found in ovarian cancers when compared with borderline and benign ovarian tumour samples. Higher iASPP expression was also found in ovarian cancer cell lines than normal ovarian epithelial cell lines. Higher iASPP expression was significantly associated with carboplatin and paclitaxel chemoresistance (P=0.04), shorter overall (P=0.003) and disease-free survival (P=0.001). Multivariate analysis confirmed iASPP expression as an independent prognostic factor. Increased iASPP mRNA expression was significantly correlated with its gene amplification (P=0.018), suggesting that gene amplification contributes to overexpression of iASPP in ovarian caner. By in vitro assay, we demonstrated that iASPP overexpression in ovarian cancer cells conferred resistance to paclitaxel by reducing mitotic catastrophe in a p53-independent manner via activation of separase whilst knockdown of iASPP enhanced paclitaxel-mediated mitotic catastrophe through inactivating separase. Both securin and cyclin B1/CDK1complex were involved in regulating separase by iASPP. Conversely, overexpressed iASPP inhibited apoptosis in a p53-dependent mode. Conclusion: Our findings suggested that iASPP may be explored as a potential prognostic marker and a novel molecular target for chemotherapy of ovarian cancers, especially in patients with chemoresistant or recurrent cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 133.
Importance of Renal Artery Stenosis in Normotensive Patients
Authors: Jeffrey M. Rimmer
Journal: Annals of Internal Medicine (1993)

Letters15 November 1993Importance of Renal Artery Stenosis in Normotensive PatientsJeffrey M. Rimmer, MD and F. John Gennari, MDJeffrey M. Rimmer, MDSearch for more papers by this author and F. John Gennari, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-10-199311150-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:To answer Dr. Spital's question with complete confidence would require data that are not currently available. Certainly, individual patients with impaired renal function due to renal artery stenosis can present without hypertension (see case 9 from Messina and coworkers [1]). In our experience, the observed normal or low blood pressure is most likely due to the use of drugs with antihypertensive effects for the treatment of angina or heart failure, although in some cases it appears to be due to severely depressed cardiac output. Most of these patients have a history of hypertension, but some do not.We ...References1. Messina LM, Zelenock GB, Yao KA, Stanley JC. Renal revascularization for recurrent pulmonary edema in patients with poorly controlled hypertension and renal insufficiency. J Vasc Surg. 1992; 15:73-82. Google Scholar2. Harding MB, Smith LR, Himmelstein SI, Harrison K, Phillips HR, Schwab SJ, et al. Renal artery stenosis: prevalence and associated risk factors in patients undergoing routine cardiac catheterization. J Am Soc Nephrol. 1992; 2:1608-16. Google Scholar Author, Article, and Disclosure InformationAuthors: Jeffrey M. Rimmer, MD; F. John Gennari, MD PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 November 1993Volume 119, Issue 10Page: 1054KeywordsEnzyme inhibitorsHeart failureHypertensionHypotensionLesionsRenal arteriesRenal diseasesRenal failureStenosisVascular diseases ePublished: 15 August 2000 Issue Published: 15 November 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Guidelines on appropriate indications for upper gastrointestinal endoscopy
Authors: M. H Wilcox, J. G Cunniffe, C. Tremlett
Journal: BMJ (1995)

EDITOR,--A T R Axon and colleagues review the indications for upper gastrointestinal endoscopy and discuss the serological diagnosis of Helicobacter pylori infection in patients over 45 with dyspepsia.1 They state that serology tests are available in most hospitals. We believe, however, that such tests are not widely available, and we therefore conducted a telephone survey of 65 British microbiology laboratories serving hospitals with 500 beds or more. We asked whether a routine serology service for H pylori was currently offered, whether serum samples were sent elsewhere if a service was …
HIV Treatment as Prevention: Natural Experiments Highlight Limits of Antiretroviral Treatment as HIV Prevention
Authors: David P. Wilson
Journal: PLoS Medicine (2012)

There is growing enthusiasm for increasing coverage of antiretroviral treatment among HIV-infected people for the purposes of preventing ongoing transmission. Treatment as prevention will face a number of barriers when implemented in real world populations, which will likely lead to the effectiveness of this strategy being lower than proposed by optimistic modelling scenarios or ideal clinical trial settings. Some settings, as part of their prevention and treatment strategies, have already attained rates of HIV testing and use of antiretroviral therapy—with high levels of viral suppression—that many countries would aspire to as targets for a treatment-as-prevention strategy. This review examines a number of these "natural experiments", namely, British Columbia, San Francisco, France, and Australia, to provide commentary on whether treatment as prevention has worked in real world populations. This review suggests that the population-level impact of this strategy is likely to be considerably less than as inferred from ideal conditions.
Estimating exposure using kriging: a simulation study.
Authors: D Wartenberg, C Uchrin, P Coogan
Journal: Environmental Health Perspectives (1991)

Retrospective studies of disease often are limited by the resolution of the exposure measurements. For example, in a typical study of adverse health effects from contaminated groundwater, the number of wells sampled may range from only a few to as many as several dozen, while the number of cases and controls may be in the hundreds or more. To derive individual estimates of exposure for wells that were not sampled, investigators must extrapolate. In this study, we compare three methods of extrapolating from a limited number of observations to estimate individual exposures. Using two naive models of groundwater contamination, we compare nearest neighbor interpolation, inverse distance squared weighting, and kriging for estimating exposure based on a limited number of measurements. Our results show that although kriging is a statistically optimal method, it is not markedly better than simpler interpolation algorithms, though it is considerably more complex to use. Aberrant well measurements and discontinuities are problematic for all methods. We provide some guidance in interpolating data and outline a more comprehensive comparison of methodology.
Two- and Three-Dimensional Transesophageal Echocardiography in Patient Selection and Assessment of Atrial Septal Defect Closure by the New DAS–Angel Wings Device
Authors: Giuseppina Magni, Ziyad M. Hijazi, Natesa G. Pandian, Alain Delabays, Lissa Sugeng, Cleo Laskari, Gerald R. Marx
Journal: Circulation (1997)

Background Transcatheter closure of atrial septal defects (ASDs) has been feasible and successful. Two-dimensional echocardiography (2DE) was applied to patients before selection and during device deployment. Three-dimensional echocardiography (3DE) can provide unique anatomic perspectives that might aid in improving device closure of ASDs. Methods and Results Twenty-two consecutive patients were enrolled in an initial protocol for ASD device closure by the new DAS–Angel Wings occluder device. On the basis of transesophageal (TEE) 2DE and 3DE, 13 patients were considered eligible for device closure (9 secundum ASDs and 4 with patent foramen ovale associated with a cerebral vascular accident). Maximal ASD diameter and surrounding rim tissues were compared by TEE 2DE and 3DE and with balloon sizing measurements at catheterization. ASD size measured by TEE 2DE and 3DE correlated well ( y =1.0 x +0.049, r =.95), with good limits of agreement. However, balloon-stretched diameter measurements were systematically larger than echocardiographic measurements. Rim tissue measurements correlated well; however, TEE 3DE could demonstrate the entire shape and perimeter of the defect. Two-dimensional imaging provided reliable information during device deployment and for closure of small ASDs. However, 3DE was superior for imaging the device, especially when abnormally placed. Conclusions Three-dimensional imaging provides unique images and projections that were essential for understanding the spatial relationship of the device to the atrial septum. Three-dimensional echocardiography significantly enhanced our understanding of two-dimensional images and provided an imaging conceptualization that should aid in future development of device closures.
Potentiation of anti-angiogenic activity of heparin by blocking the ATIII-interacting pentasaccharide unit and increasing net anionic charge
Authors: Seung Woo Chung, Myungjin Lee, Sang Mun Bae, Jooho Park, Ok Cheol Jeon, Hui Sun Lee, Han Choe, Han Sung Kim, Beom Suk Lee, Rang-Woon Park, Sang Yoon Kim, Youngro Byun
Journal: Biomaterials (2012)
Lipid Nano-Sphere(LNS), a protein-free analogue of lipoproteins, as a novel drug carrier for parenteral administration. IV
Authors: J. Seki, H. Sasaki, M. Doi, H. Yoshikawa, Y. Takahashi, S. Yamane, H. Fukui, S. Sonoke, H. Yamamoto, M. Hirose, Y. Ezure, T. Ando, K. Ushimaru, M. Sugiyama
Journal: Journal of Controlled Release (1994)
Klebsiella oxytoca as an agent of antibiotic-associated hemorrhagic colitis
Authors: Laurent Beaugerie, Michaela Metz, Frédéric Barbut, Guy Bellaiche, Yoram Bouhnik, Laurent Raskine, Jean-Claude Nicolas, François-Patrick Chatelet, Norbert Lehn, Jean-Claude Petit
Journal: Clinical Gastroenterology and Hepatology (2003)
Sulindac and Jaundice
Authors: PAMELA B. WOLFE
Journal: Annals of Internal Medicine (1979)

Letters1 October 1979Sulindac and JaundicePAMELA B. WOLFE, M.D.PAMELA B. WOLFE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-91-4-656_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I have recently seen a case of jaundice related to sulindac (Clinoril®; Merck Sharp & Dohme, West Point, Pennsylvania) administration.A 46-year-old white man was hospitalized because of jaundice. He had been healthy except for neck pain since an injury in 1975. Four months before admission sulindac had been prescribed. He took the drug irregularly and had taken less than 100 tablets (200 mg) in 15 weeks. Because of increased neck pain he began regular use of 200 mg twice daily. Two weeks later he first noted jaundice. He denied any previous episodes of jaundice, gastrointestinal problems,...Reference1. ANDERSON R. Severe reaction associated with sulindac administration. N Engl J Med. 1979;300:735-6. Letter. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: PAMELA B. WOLFE, M.D.Affiliations: 5714 North 26th Street; Milwaukee, WI 53209 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byIdiosyncratic Liver Toxicity of Nonsteroidal Antiinflammatory Drugs: Molecular Mechanisms and PathologySulindac-associated hepatic injury: Analysis of 91 cases reported to the food and drug administrationTreatmentAcute cholangitis and pancreatitis associated with sulindac (clinoril)SULINDAC HEPATOTOXICITY: EFFECTS OF ACUTE AND CHRONIC EXPOSURESulindac Hepatotoxicity: A Case Report and ReviewSulindac hepatotoxicityClinical associations between arthritis and liver disease.Hepatitis associated with use of sulindac in a childSulindac and PneumonitisMICHAEL FEIN, M.D.Sulindac (Clinoril) hepatitisAnti-inflammatory analgesics and drugs used in rheumatism and goutReaction to SulindacI. JON RUSSELL, M.D. 1 October 1979Volume 91, Issue 4Page: 656-656KeywordsDrugs ePublished: 1 December 2008 Issue Published: 1 October 1979 PDF downloadLoading ...
Comparison of epicardial coronary artery tone and reactivity in Prinzmetal's variant angina and chronic stable angina pectoris
Authors: Juan Carlos Kaski, Dimitris Tousoulis, Stavros Gavrielides, Eugene McFadden, Alfredo R. Galassi, Filippo Crea, Attilio Maseri
Journal: Journal of the American College of Cardiology (1991)
Piecing together the puzzle of cutaneous mosaicism
Authors: Amy S. Paller
Journal: Journal of Clinical Investigation (2004)

Autosomal dominant disorders of the skin may present in a pattern following the lines of embryologic development of the ectoderm. In these cases, the surrounding skin is normal, and molecular studies have shown that the causative mutation is confined to the affected ectodermal tissue (type 1 mosaicism). Rarely, an individual shows skin lesions that follow the pattern of type 1 mosaicism, but the rest of the skin shows a milder form of the disorder (type 2 mosaicism). A new study provides the molecular basis for type 2 mosaicism .
Spi-B is critical for plasmacytoid dendritic cell function and development
Authors: Izumi Sasaki, Katsuaki Hoshino, Takahiro Sugiyama, Chihiro Yamazaki, Takahiro Yano, Akihiko Iizuka, Hiroaki Hemmi, Takashi Tanaka, Masuyoshi Saito, Masanaka Sugiyama, Yuri Fukuda, Tomokazu Ohta, Katsuaki Sato, Akira Ainai, Tadaki Suzuki, Hideki Hasegawa, Noriko Toyama-Sorimachi, Hiroshi Kohara, Takashi Nagasawa, Tsuneyasu Kaisho
Journal: Blood (2012)
Case Number 29: Ochronosis: synovial histopathological characteristics
Authors: E Kruithof
Journal: Annals of the Rheumatic Diseases (2004)

The patient, a 43 year old woman with a 35 year history of alkaptonuria (fig 1A), presented to the orthopaedic clinic for pain in the right shoulder. Clinical examination demonstrated an important reduction of shoulder mobility with, on radiographic evaluation, a greatly destroyed joint (fig 1B). The patient was admitted to hospital to obtain a …
Antibodies against keratinocyte antigens other than desmogleins 1 and 3 can induce pemphigus vulgaris–like lesions
Authors: Vu Thuong Nguyen, Assane Ndoye, Leonard D. Shultz, Mark R. Pittelkow, Sergei A. Grando
Journal: Journal of Clinical Investigation (2000)

Pemphigus is an autoimmune disease of skin adhesion associated with autoantibodies against a number of keratinocyte antigens, such as the adhesion molecules desmoglein (Dsg) 1 and 3 and acetylcholine receptors. The notion that anti-Dsg antibodies alone are responsible for blisters in patients with pemphigus vulgaris (PV) stems from the ability of rDsg1 and rDsg3 to absorb antibodies that cause PV-like skin blisters in neonatal mice. Here, we demonstrate that PV IgGs eluted from rDsg1-Ig-His and rDsg3-Ig-His show similar antigenic profiles, including the 38-, 43-, 115-, and 190-kDa keratinocyte proteins and a non–Dsg 3 130-kDa polypeptide present in keratinocytes from Dsg 3 knockout mouse. We injected into Dsg 3–lacking mice the PV IgGs that did not cross-react with the 160-kDa Dsg 1 or its 45-kDa immunoreactive fragment and that showed no reactivity with recombinant Dsg 1. We used both the Dsg3null mice with a targeted mutation of the Dsg3 gene and the “balding” Dsg3bal/Dsg3bal mice that carry a spontaneous null mutation in Dsg3. These PV IgGs caused gross skin blisters with PV-like suprabasal acantholysis and stained perilesional epidermis in a fishnet-like pattern, indicating that the PV phenotype can be induced without anti–Dsg 3 antibody. The anti–Dsg 1 antibody also was not required, as its presence in PV IgG does not alter the PV-like phenotype in skin organ cultures and because pemphigus foliaceus IgGs produce a distinct phenotype in Dsg3null mice. Therefore, mucocutaneous lesions in PV patients could be caused by non-Dsg antibodies.
Interactions of Abiraterone, Eplerenone, and Prednisolone with Wild-type and Mutant Androgen Receptor: A Rationale for Increasing Abiraterone Exposure or Combining with MDV3100
Authors: Juliet Richards, Ai Chiin Lim, Colin W. Hay, Angela E. Taylor, Anna Wingate, Karolina Nowakowska, Carmel Pezaro, Suzanne Carreira, Jane Goodall, Wiebke Arlt, Iain J. McEwan, Johann S. de Bono, Gerhardt Attard
Journal: Cancer Research (2012)

Prostate cancer progression can be associated with androgen receptor (AR) mutations acquired following treatment with castration and/or an antiandrogen. Abiraterone, a rationally designed inhibitor of CYP17A1 recently approved for the treatment of docetaxel-treated castration-resistant prostate cancer (CRPC), is often effective, but requires coadministration with glucocorticoids to curtail side effects. Here, we hypothesized that progressive disease on abiraterone may occur secondary to glucocorticoid-induced activation of mutated AR. We found that prednisolone plasma levels in patients with CRPC were sufficiently high to activate mutant AR. Mineralocorticoid receptor antagonists, such as spironolactone and eplerenone that are used to treat side effects related to mineralocorticoid excess, can also bind to and activate signaling through wild-type or mutant AR. Abiraterone inhibited in vitro proliferation and AR-regulated gene expression of AR-positive prostate cancer cells, which could be explained by AR antagonism in addition to inhibition of steroidogenesis. In fact, activation of mutant AR by eplerenone was inhibited by MDV3100, bicalutamide, or greater concentrations of abiraterone. Therefore, an increase in abiraterone exposure could reverse resistance secondary to activation of AR by residual ligands or coadministered drugs. Together, our findings provide a strong rationale for clinical evaluation of combined CYP17A1 inhibition and AR antagonism.
Prolactin-like immunoreactivity in human small-intestinal mucosa.
Authors: F M Stevens, C Shaw
Journal: BMJ (1982)

Spinal decompression sickness with delayed onset, delayed treatment, and full recovery Decompression sickness is caused by nitrogen bubbles formed in the body of divers and people working with compressed air who leave a compressed environment too fast.The bubbles most commonly afflict the joints, skin, brain, spinal cord, and lungs.Decompression sickness, if untreated, may cause permanent functional damage and is potentially fatal.We report an unusual case of decompression sickness affecting the brain and spinal cord in which neurological symptoms and signs first appeared five hours after the dive.Symptoms were partially relieved by oxygen, dextran 40, and dexamethasone but disappeared fully only during hyperbaric treatment. Case reportA 20-year-old healthy male diver worked at 20 metres for 40 minutes and ascended with one three-minute decompression stop at three metres.Two hours later he complained of headache, sore throat, and malaise, and five hours later of pain in the left knee and left elbow, headache, and confusion.On examination his temperature was 38 5°C and a mild follicular tonsilitis was found.There were no other abnormalities.Two hours later sensory loss in the right thigh, mild paraparesis, and loss of sensation around the anus developed.He received 20 mg dexamethasone intravenously, 500 ml dextran 40, and sodium lactate (Hartmann's solution); oxygen was given by mask.
Diabetes and Long-Term Risk of Mortality From Coronary and Other Causes in Middle-Aged Swedish Men: A general population study
Authors: Annika M Adlerberth, Annika Rosengren, Lars Wilhelmsen
Journal: Diabetes Care (1998)

OBJECTIVE To assess the relation between cardiovascular risk factors and long-term cause-specific mortality risk in middle-aged diabetic men, compared with men without diabetes. RESEARCH DESIGN AND METHODS This prospective study analyzes a large random population sample of men over a follow-up of 16 years. At baseline in 1974–1977, 249 men with diabetes and 6,851 men without diabetes, all aged 51–59 years, were identified. There were 2,126 deaths, 724 of which were due to coronary heart disease (CHD) and 1,001 deaths were due to any cardiovascular disease (CVD) cause. RESULTS After adjustment for age, serum cholesterol, systolic blood pressure, smoking, BMI, and coronary disease at baseline, the relative risk of dying from any cause was 2.50 (95% CI, 2.11–2.95) in men with diabetes, compared with nondiabetic men, and 2.87 (2.31–3.57) for cardiovascular death. Men with diabetes had no significant excessive risk of dying from cancer or violent causes, but the relative risk of dying from any other noncardiovascular cause was 3.69 (2.55–5.34). Most of these deaths were due to diabetes and its complications. Hypercholesterolemia, smoking, and elevated systolic blood pressure predicted both coronary and allcause mortality in diabetic as well as in nondiabetic men. Men with diabetes and serum cholesterol &amp;gt;7.2 mmol/1 had a risk of dying from coronary disease of 45.3 and from any cause of 76.1 per 1,000 observation-years. In men with diabetes, the relative risk of dying associated with serum cholesterol &amp;gt;7.2 mmol/1, as compared with &amp;lt;5.2 mmol/1, was 1.78 (95% CI, 1.05–3.02). The corresponding risk for nondiabetic men was 1.23 (1.04–1.46), and there was a statistically significant interaction between serum cholesterol and diabetes (P = 0.004). CONCLUSIONS In men with diabetes, hypercholesterolemia, smoking, and hypertension predict coronary mortality risk, as well as mortality risk from all causes. Men with both diabetes and hypercholesterolemia have severely compromised survival and should be targeted for intervention aimed at lowering their lipid levels.
The Stress-Alexithymia Hypothesis: Theoretical and Empirical Considerations
Authors: John B. Martin, R.O. Pihl
Journal: Psychotherapy and Psychosomatics (1985)

An association has been noted between the presence of alexithymic characteristics and psychosomatic/stress-related illness. A hypothesis is presented here outlining the mechanisms through which stress and alexithymic characteristics contribute to the development of stress-related illness. This hypothesis, the stress-alexithymia hypothesis, is considered here in the context of stress research from both theoretical and empirical perspectives. From these considerations, it appears that the stress-alexithymia hypothesis does have a theoretical basis. Additionally, there is indirect empirical evidence supporting the proposed influence of alexithymic characteristics on the physiological stress response. It is suggested that future research should directly examine the influence of alexithymic characteristics on stress responding and use alexithymic characteristics heuristically to explore the role of affect in the illness process.