tbuckley/cabot-search huggingface dataset:
Abstract 4418: Overexpression of PGC-1α in rat cardiomyocytes protects against nucleoside reverse transcriptase inhibitor (NRTI)-induced mitochondrial toxicity.
Authors: Eunwoo Shim, Daniel Liu, Alexander Gibbons, Miriam C. Poirier, Yongmin Liu
Journal: Cancer Research (2013)

Abstract The NRTIs Zidovudine (AZT) and Didanosine (ddI) are components of the antiretroviral combination therapies in widespread use for treatment of HIV-1 infection. However, AZT, a carcinogen in mice, is a DNA replication chain terminator that damages heart, skeletal muscle, brain and liver during long-term clinical use. In addition, both drugs are known to cause treatment-limiting mitochondrial compromise. In order to elucidate the mechanisms resulting in cardiac mitochondrial toxicity in patients using these drugs, we have evaluated rat cardiomyocyte H9c2 cells exposed for &amp;gt;30 passages (P) to 50 μM AZT or 50 μM AZT/50 μM ddI, doses allowing for ≥80% survival. Mitochondrial integrity, evaluated as Oxygen Consumption Rate (OCR, by Seahorse Analyzer) was reduced by ≥50% (p&amp;lt;0.05) in NRTI-exposed cells at most P compared to unexposed controls. Progressive abnormal mitochondrial morphology was observed, with time of exposure, by electron microscopy (EM). In addition, in AZT/ddI-exposed cells there were reductions (about 50%) in protein levels of PGC-1α, a master regulator of mitochondrial function and biogenesis, and its downstream effector NRF-1, compared to unexposed cells. Hypothesizing that up-regulation of PGC-1α might protect cells from AZT/ddI-induced mitochondrial damage, H9c2 cells were infected with lentivirus carrying PGC-1α, and shown by Western blot to overexpress PGC-1α. When both the H9c2 cells and the H9c2/ PGC-1α cells were exposed to 50 μM AZT/50 μM ddI, significantly-increased (20-50%) OCR levels were observed at P 2, 6, 8, 12 and 15 in the H9c2/ PGC-1α cells, compared to the H9c2 cells (p&amp;lt;0.05 for all P). In addition, Western blot showed about 50% higher levels of NRF-1 in AZT/ddI-exposed H9c2/ PGC-1α cells, compared to AZT/ddI-exposed H9c2 cells. These studies support our hypothesis that PGC-1α overexpression protects cardiomyocytes from NRTI-induced mitochondrial compromise, and suggest that the AZT/ddI-induced reduction in protein levels of PGC-1α is a major mechanism contributing to AZT/ddI induced toxicity. We plan to search for natural products that offer similar protection and evaluate their effect on genotoxicity and mitochondrial toxicity of the antiretroviral NRTIs. Citation Format: Eunwoo Shim, Daniel Liu, Alexander Gibbons, Miriam C. Poirier, Yongmin Liu. Overexpression of PGC-1α in rat cardiomyocytes protects against nucleoside reverse transcriptase inhibitor (NRTI)-induced mitochondrial toxicity. [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 4418. doi:10.1158/1538-7445.AM2013-4418
Relationship of serum leptin concentration and other measures of adiposity with gallbladder disease
Authors: Constance E. Ruhl, James E. Everhart
Journal: Hepatology (2001)

Obesity increases the risk of gallstones, especially in women. Most gallbladder disease studies have used body mass index (BMI) as a measure of overall adiposity, although BMI does not distinguish between fat and lean body mass. Central adiposity may also increase gallstone risk, although this is less well studied. Leptin is a peptide whose serum concentration is highly correlated with total body fat mass. We examined the relationship of gallbladder disease with anthropometric measures and serum leptin concentration in a large, national, population-based study. A total of 13,962 adult participants in the Third National Health and Nutrition Examination Survey underwent gallbladder ultrasonography and anthropometric measurements of BMI, body circumferences, and skinfold thicknesses, and a random subgroup of 5,568 had measures of fasting serum leptin concentrations. Gallstone-associated gallbladder disease was defined as ultrasound-documented gallstones or evidence of cholecystectomy. When controlling for BMI and other gallbladder disease risk factors in multivariate analysis, a test for trend for increasing waist-to-hip circumference ratio and risk of gallbladder disease was statistically significant among women (P =.043) and men (P =.007). BMI remained strongly associated with gallbladder disease among women (P <.001), but was unrelated among men (P =.46). Leptin concentration was associated with gallbladder disease in both sexes (P <.001), but not after controlling for BMI and waist-to-hip circumference in either women (P =.29) or men (P =.65). In conclusion, waist-to-hip circumference ratio was related to gallbladder disease among women and men. Serum leptin concentration was not a better predictor of gallbladder disease than anthropometry.
Endoscopic Sphincterotomy in Patients with Difficult Cannulation: Use of an Antegrade Guide
Authors: M. Tanaka, S. Matsumoto, S. Ikeda, K. Miyazaki, S. Yamauchi
Journal: Endoscopy (1986)

Difficulty in introducing a sphincterotome into the common bile duct remains a problem in the technique of endoscopic sphincterotomy. An antegrade guide passed through a percutaneous transhepatic catheter or a choledochal tube was successfully used to help retrograde insertion of the sphincterotome in 6 patients with difficult cannulation. This method is a safer and simpler alternative to precutting, decreasing the risk of acute pancreatitis. Also, when the papilla is located inside a diverticulum and difficult to reach by endoscopy, the antegrade guide is helpful for bringing it out of the diverticulum, allowing one to enter the common bile duct with the cutting probe.
W.H.O. Expert Committee on Biological Standardization
Authors: D. C. Dumonde
Journal: Annals of the Rheumatic Diseases (1974)

This report presents the recommendations of a WHO Expert Committee commissioned to coordinate activities leading to the adoption of international requirements for the production and control of vaccines and other biologicals and the establishment of international biological reference materials. The report starts with a discussion of general issues brought to the Committee's attention and provides information on the status and development of reference materials for various antibodies, antigens, blood products and related substances, cytokines, growth factors, and endocrinological substances. The second part of the report, of particular relevance to manufacturers and national control authorities, contains recommendations for the production and control of oral poliomyelitis vaccine, an amendment to the requirements for meningococcal polysaccharide vaccine, and a decision-tree for setting priorities in the development of reference materials. Also included is an addendum to the guidelines for the preparation, characterization, and establishment of standards and reference reagents for biological substances.
The Histologic Spectrum of Barrett's Esophagus
Authors: Andrew Paull, Jerry S. Trier, M. David Dalton, Roger C. Camp, Peter Loeb, Raj K. Goyal
Journal: New England Journal of Medicine (1976)

To define the histology of the columnarlined esophagus, we obtained esophageal biopsies from various levels with manometric control from 11 patients. There were three types of columnar epithelia above the lower esophageal sphincter: atrophic gastric-fundic-type epithelium with parietal and chief cells; junctional-type epithelium with cardiac mucous glands; and distinctive specialized columnar epithelium with a villiform surface, mucous glands and intestinal-type goblet cells. When present, specialized columnar epithelium was always the most proximal, and gastric fundic epithelium the most distal epithelium. Junctional epithelium was interposed between gastric fundic and specialized columnar or squamous epithelium. Four patients had unequivocal esophagitis in squamous epithelium, but its presence and severity did not correlate with inflammation in or length or type of distal columnar epithelium. Histoligic study of the columnar-lined esophagus demonstrated a spectrum of epithelial patterns. This heterogeneity helps to explain prior discrepant reports.
Depression after Surgery for Breast Cancer
Authors: C. van Heeringen, M. van Moffaert, G. de Cuypere
Journal: Psychotherapy and Psychosomatics (1989)

The impact of the loss of the breast in women undergoing surgical treatment for breast cancer is subordinated to the confrontation with the diagnosis of a malignancy in causing depression. The equal distribution of depression in mastectomy and in lumpectomy patients supports the hypothesis that it is the confrontation with the potentially lethal outcome of the diagnosis which is decisive in causing depression. The grief reaction following mastectomy has two components: a depressive reaction to the loss of the breast and an anticipatory grief for anticipation of the potentially lethal outcome. Psychosocial therapeutic support in breast malignancy must give priority to coping with the diagnosis of cancer over the loss of the breast.
Phase I dose escalation and expansion study to evaluate safety and efficacy of INC280 in patients with advanced MET-dependent solid tumors
Authors: B. Ma, Y.-J. Bang, W.-T. Lim, D.-H. Nam, W.-C. Su, J.H.M. Schellens, A. Azaro, M. Akimov, Y. Zhang, A. Kumar, S. Zhao, M. Schuler
Journal: Annals of Oncology (2015)
Effects of Testosterone Replacement on Response to Sildenafil Citrate
Authors: Steven Smoger
Journal: Annals of Internal Medicine (2013)

Letters2 April 2013Effects of Testosterone Replacement on Response to Sildenafil CitrateSteven Smoger, MDSteven Smoger, MDFrom Robley Rex Veterans Affairs Medical Center, Louisville, Kentucky.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-158-7-201304020-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In Spitzer and colleagues' article (1) about combining testosterone replacement and sildenafil, the authors do not comment on whether the variability of testosterone measurements could explain the ineffectiveness of testosterone replacement. From clinical experience, this seems to be a common occurrence and may influence the decision to consider hormone replacement. In addition, the baseline body mass index was greater than 31 kg/m2 in both groups, raising the question of whether levels of the sex hormone–binding protein could explain the lower average testosterone level.Steven Smoger, MDRobley Rex Veterans Affairs Medical CenterLouisville, KentuckyReference1. Spitzer M, Basaria S, Travison TG, Davda MN, Paley A, Cohen B, et al. Effect of testosterone replacement on response to sildenafil citrate in men with erectile dysfunction: a parallel, randomized trial. Ann Intern Med. 2012;157:681-91. [PMID: 23165659] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Steven Smoger, MDAffiliations: From Robley Rex Veterans Affairs Medical Center, Louisville, Kentucky.Disclosures: Employment: Veterans Affairs. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEffect of Testosterone Replacement on Response to Sildenafil Citrate in Men With Erectile Dysfunction Matthew Spitzer , Shehzad Basaria , Thomas G. Travison , Maithili N. Davda , Amanda Paley , Beth Cohen , Norman A. Mazer , Philip E. Knapp , Samson Hanka , Kishore M. Lakshman , Jagadish Ulloor , Anqi Zhang , Katie Orwoll , Richard Eder , Lauren Collins , Nurahmed Mohammed , Raymond C. Rosen , Leonard DeRogatis , and Shalender Bhasin Effects of Testosterone Replacement on Response to Sildenafil Citrate Allen D. Seftel and Geoffrey Hackett Effects of Testosterone Replacement on Response to Sildenafil Citrate Antonio Aversa , Emmanuele A. Jannini , Mario Maggi , and Andrea Lenzi Effects of Testosterone Replacement on Response to Sildenafil Citrate Matthew Spitzer , Shehzad Basaria , Thomas G. Travison , and Shalender Bhasin Metrics Cited byControversies in Diagnosis and Treatment of Hypogonadism 2 April 2013Volume 158, Issue 7Page: 569KeywordsBody mass indexProteinsTestosterone ePublished: 2 April 2013 Issue Published: 2 April 2013 Copyright & PermissionsCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Letter by Montani et al Regarding Article, “Elevated Levels of Inflammatory Cytokines Predict Survival in Idiopathic and Familial Pulmonary Arterial Hypertension”
Authors: David Montani, Marc Humbert, Rogerio Souza
Journal: Circulation (2011)

We read with great interest the article by Soon et al, 1 in which they demonstrated the importance of dysregulation in inflammatory mediators by conducting a large screening of cytokines in idiopathic and heritable pulmonary arterial hypertension (PAH).These results confirm preliminary data on serum levels of interleukin-1 and interleukin-6 and emphasize the conclusions of the world conference on pulmonary hypertension. 2,3However, the authors' conclusion that cytokine levels impact patient survival seems to overstate their results, and deserves further discussion.First, in this small series of patients, it was striking that levels of cytokines were potent prognostic factors compared with cardiac index and 6-minute walk test, which are classically associated with outcome in PAH.A closer look at the Kaplan-Meier curves raises some points that should be better clarified.The sample size is rather small for the separation into quartiles; it seems that the dichotomizations according to the median level were not presented because they were negative.Moreover, based on visual analyses of the Kaplan-Meier curves, the proportional hazards assumption does not seem to have been respected in order to make possible analyses with the Cox model.Thus, it is difficult to support a strong correlation between inflammatory markers and prognosis of PAH.The study, as an exploratory analysis, may suggest the association but is limited for further speculations.Second, the authors discussed the potential impact of prostanoids on cytokine levels; nevertheless, it would be interesting to have details regarding other PAH therapies, because several studies have suggested a possible impact of endothelin receptor antagonists or phosphodiesterase type 5 inhibitors on inflammatory processes.Finally, no information concerning the distribution of incident and prevalent cases of PAH was reported.It has been demonstrated recently that newly diagnosed cases have a poor prognosis compared with patients with preexisting disease. 4,5If cytokine levels have a relation with the duration of the disease, this could directly impact the observed association with prognosis.Thus, to pool these different subgroups of patients with different prognoses and treatments may bias survival analysis.It would be interesting to know whether the relation between cytokine levels and prognosis was also observed in a more homogeneous group of patients, such as incident cases or specific PAH treatment-naı ¨ve patients.To conclude, even if its conclusions concerning prognosis may be debatable, this study highlights the importance of better understanding the role of inflammation in the pathophysiology of PAH.The French Network for PAH is currently conducting a prospective multicenter study on biomarkers, including cytokines, in a large cohort of patients with incident PAH that will complement the information provided by the study of Soon and coworkers.
CQC lifts conditions on Mid Essex trust after it improves its infection control
Authors: J. Carlowe
Journal: BMJ (2010)

England’s Care Quality Commission has lifted the registration conditions placed on Mid Essex Hospital Services NHS Trust after the organisation showed improvements in cleanliness and infection control.

On Tuesday 13 July the health watchdog announced that it had lifted the condition it had imposed on the trust’s registration on 1 April.

The trust was one of 22 registered with conditions to improve aspects of quality and safety before they could be granted a licence to provide services ( BMJ 2010;340:c1757, 26 Mar, doi:10.1136/bmj.c1757). 

The commission imposed the condition after an inspection in February, in which it was …
Suppressive activity of bronchial macrophages recovered by induced sputum
Authors: E Fireman, A Onn, Y Levo, E Bugolovov, S Kivity
Journal: Allergy (1999)

The immunomodulatory activity of macrophages was shown to be a crucial mechanism in the pathogenesis of asthma.Induced sputum (IS) and methacholine challenge (MC) were carried out in 21 atopic subjects. Suppressive activity (SA) of sputum macrophages (SMO) was investigated on autologous peripheral lymphocytes (APL) proliferation in 12 of these patients and compared to the MC.In 10 of the 21 patients, the FEV1 was >80%; five of these had a nonreactive MC. Eosinophils and metachromatic cells correlated well (r=0.6442; P=0.0029), but not with the MC. The SA of SMO correlated (P=0.0152) with the MC: SMO enhanced APL proliferation in five patients with a positive MC, while SMO showed SA in five with a negative MC. Only two patients with suppressive SMO had a positive MC. Cytokine profiles from five patients showed that two patients with a negative MC had interleukin (IL)-1alpha and beta, IL-6, and transforming growth factor (TGF)-beta transcripts, while two patients with a positive MC transcripted IL-4 and IL-5. One patient with a borderline MC transcripted IL-5, but not IL-4.These data support the theory that patients with reduced suppressive bronchial macrophages display clinical bronchial hyperreactivity.
Fatal Anaphylactic Shock
Authors: B. Hugh Buff
Journal: JAMA (1961)

To the Editor:—  Concerning the letter from Doctor Luton, not only is the type of test used in testing for sensitivity to horse serum controversial—i.e., conjunctival test versus skin test versus history— but also the proper initial dilution of the testing antigen and the amount of solution used for the test also vary according to the investigator. Some authorities advise 0.01 cc. antigen for each intradermal skin test; others advise 0.02, 0.05, and up to 0.1 cc. The latter dosage is that which appears on the instructions for skin testing which come with the antitoxin.  I feel that 0.05 cc. to 0.1 cc., particularly after the catastrophe reported in the article mentioned, is a dosage that is too high. The drug manufacturers should be instructed to revise their directions on horse serum preparation to the effect that no more than 0.01 to 0.02 cc. of any given dilution of the
Abstract 5160: Tumor cells potentiate mesenchymal stem cells-pericytes transition and requirement through PDGF-BB-NRP-1 axis
Authors: Kakali Dhar, Gopal Dhar, Monami Majumder, Inamul Haque, Sushanta K. Banerjee, Smita Mehta, Peter J. Vanveldhuizen, Snigdha Banerjee
Journal: Cancer Research (2010)

Abstract New blood vessel formation or angiogenic switch is an essential event in the development of solid tumors and their metastatic growth. Tumor blood vessel formation and remodeling is a complex and multi-step processes. The differentiation and recruitment of mural cells including vascular smooth muscle cells and pericytes are essential steps in tumor angiogenesis. However, the role of tumor cells in differentiation and recruitment of mural cells is unknown. In this study we focus on the role of tumor cells in governing the differentiation of mesenchymal stem cells (MSCs) to pericytes and their recruitment in tumor angiogenesis process. We show that C3H/10T1/2 mouse embryonic mesenchymal stem cells, under the influence of different tumor cells-derived conditioned media, differentiate into mature pericytes. These differentiated pericytes, in turn, are recruited to bind with capillary-like networks formed by endothelial cells on the matrigel under in vitro condition. The degree of recruitment of pericytes into in vitro neo-angiogenesis is tumor cell phenotype specific. Interestingly, the invasive cells recruit less pericytes as compared to non-invasive cells. We identify tumor cell-secreted platelet derived growth factor (PDGF-BB) as a crucial factor controlling differentiation and recruitment processes through a cross-talk with NRP-1. These new insights into the roles of tumor cell-secreted PDGF in MSCs-fate determination may help in developing new antiangiogenic strategies to prevent the tumor growth and metastasis and also to treat cancers more effectively. 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 5160.
Abstract 401: Gene expression signatures differentiate primary and metastatic uterine leiomyosarcoma.
Authors: Ben Davidson, Vera Maria Abeler, Mette Førsund, Arild Holth, Ie-Ming Shih, Gunnar B. Kristensen, Li Chen, Yanqin Yang, Tian-Li Wang
Journal: Cancer Research (2013)

Abstract Leiomyosarcoma (LMS) is the most common uterine sarcoma, but is a rare cancer. The genetic events related to LMS metastasis are unknown to date. The aim of the present study was to compare the global gene expression patterns of primary uterine LMS and LMS metastases in order to identify potential biological targets. Gene expression profiles of 13 primary uterine LMS and 15 LMS metastases were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry. Unsupervised hierarchical clustering using all 54,675 genes in the array separated primary from metastatic LMS samples. We identified 203 unique probes that were significantly differentially expressed in the two tumor groups by greater than 2-fold with 1% FDR cutoff using one-way ANOVA with Benjamini-Hochberg correction, of which 94 and 109 were overexpressed in primary and metastatic LMS, respectively. Genes overexpressed in primary uterine LMS included OSTN, NLGN4X, NLGN1, SLITRK4, MASP1, XRN2, ASS1, RORB, HRASLS and TSPAN7. Genes overexpressed in LMS metastases included FOLR3, TDO2, CRYM, GJA1, TSPAN10, THBS1, SGK1, SHMT1, EGR2 and AGT. Results for selected genes were validated by quantitative real-time PCR and immunohistochemistry. We present the first study in which gene expression profiling was shown to distinguish between primary uterine LMS and LMS metastases. The molecular signatures unique to primary and metastatic LMS may aid in understanding tumor progression in this cancer and in providing a molecular basis for prognostic studies and therapeutic target discovery. Citation Format: Ben Davidson, Vera Maria Abeler, Mette Førsund, Arild Holth, Ie-Ming Shih, Gunnar B. Kristensen, Li Chen, Yanqin Yang, Tian-Li Wang. Gene expression signatures differentiate primary and metastatic uterine leiomyosarcoma. [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 401. doi:10.1158/1538-7445.AM2013-401
Myelopathy After Duck Embryo Vaccine
Authors: Jack N. Alpert
Journal: JAMA (1973)

To the Editor.—  As a neurologist, I object to the use of the word myelopathy in the article. The case report did not detail any spinal cord signs on neurologic examination. There were depressed deep tendon reflexes, no pathological reflexes, and no sensory abnormalities. Difficulty in swallowing was noted, yet cranial nerves were listed as normal. The examination would indicate a polyradiculopathy such as is seen in a Guillain-Barre syndrome. The spinal fluid examination demonstrated albuminocytologic dissociation with protein level above 60 mg/100 ml and no cells, a common although not a specific finding in polyradiculopathies.