tbuckley/cabot-search huggingface dataset:
Induction of Prostaglandin G/H Synthase-2 in a Canine Model of Spontaneous Prostatic Adenocarcinoma
Authors: C. Tremblay, M. Dore, P. N. Bochsler, J. Sirois
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Prostate cancer is the most frequently occurring cancer in men in the United States, with an estimated 179 300 new cases in 1999. The induction of prostaglandin G/H synthase (PGHS), a key rate-limiting enzyme in prostaglandin biosynthesis, has been implicated in various cancers, most notably in colorectal cancers; however, the induction of PGHS expression in prostate cancer in vivo has not been reported for any species. The dog is the only nonhuman species that frequently develops spontaneous cancer of the prostate with increasing age, and the objective of this study was to determine whether PGHS isoenzymes were expressed in canine prostatic adenocarcinomas. METHODS: Four normal canine prostatic tissues and 24 canine prostatic adenocarcinomas were studied by means of immunohistochemistry and immunoblot analysis, using polyclonal antibodies specific for each of the two PGHS isoenzymes, PGHS-1 and PGHS-2. All P values were obtained by use of two-sided Fisher's exact tests. RESULTS: PGHS-1 immunostaining was localized to stromal fibroblasts and vascular endothelium in normal and cancerous prostates. PGHS-2 was not detected in normal prostates, but it was expressed by epithelial tumor cells in 18 (75%) of the 24 adenocarcinomas ( P = .01). Immunoblot analysis confirmed the presence of PGHS-1 (69 000 molecular weight) in normal and cancerous tissues and the expression of PGHS-2 (72 000- to 74 000-molecular-weight doublet) only in prostatic adenocarcinomas. CONCLUSION: To our knowledge, these results demonstrate for the first time that PGHS-2 is induced in the majority of canine spontaneous prostatic adenocarcinomas and suggest that its expression may be involved in prostate cancer.
Long-Term Treatment With Entecavir Induces Reversal of Advanced Fibrosis or Cirrhosis in Patients With Chronic Hepatitis B
Authors: Eugene R. Schiff, Samuel S. Lee, You–Chen Chao, Seung Kew Yoon, Fernando Bessone, Shun–Sheng Wu, Wieslaw Kryczka, Yoav Lurie, Adrian Gadano, George Kitis, Suzanne Beebe, Dong Xu, Hong Tang, Uchenna Iloeje
Journal: Clinical Gastroenterology and Hepatology (2010)

Long-term treatment with entecavir resulted in durable virologic suppression and continued histologic improvement in nucleoside-naive chronic hepatitis B patients. Patients with advanced fibrosis or cirrhosis, who received long-term entecavir treatment, were evaluated for improvement in liver histology.The study included a subset of patients from phase III and long-term rollover studies, who received entecavir for at least 3 years, had advanced fibrosis or cirrhosis, and evaluable biopsies at baseline and after long-term treatment.Ten patients had advanced fibrosis or cirrhosis at baseline (Ishak fibrosis score, ≥ 4). After approximately 6 years of cumulative entecavir therapy (range, 267-297 wk), all 10 patients showed improvement in liver histology and Ishak fibrosis score. The mean change from baseline in Ishak fibrosis and Knodell necroinflammatory scores were -2.2 and -7.6, respectively. A reduction in Ishak fibrosis score to 4 or less was observed for all 4 patients who had cirrhosis at baseline.Chronic hepatitis B patients with advanced fibrosis or cirrhosis demonstrated histologic improvement and reversal of fibrosis and cirrhosis after long-term treatment with entecavir.
Glaucoma in Blacks: Where Do We Go From Here?
Authors: M. Roy Wilson
Journal: JAMA (1989)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Genetic signatures shared in embryonic liver development and liver cancer define prognostically relevant subgroups in HCC
Authors: Diana Becker, Ioannis Sfakianakis, Markus Krupp, Frank Staib, Aslihan Gerhold-Ay, Anja Victor, Harald Binder, Maria Blettner, Thorsten Maass, Snorri Thorgeirsson, Peter R Galle, Andreas Teufel
Journal: Molecular Cancer (2012)

Multiple activations of individual genes during embryonic liver and HCC development have repeatedly prompted speculations about conserved embryonic signatures driving cancer development. Recently, the emerging discussion on cancer stem cells and the appreciation that generally tumors may develop from progenitor cells of diverse stages of cellular differentiation has shed increasing light on the overlapping genetic signatures between embryonic liver development and HCC. However there is still a lack of systematic studies investigating this area. We therefore performed a comprehensive analysis of differentially regulated genetic signaling pathways in embryonic and liver cancer development and investigated their biological relevance.Genetic signaling pathways were investigated on several publically available genome wide microarray experiments on liver development and HCC. Differentially expressed genes were investigated for pathway enrichment or underrepresentation compared to KEGG annotated pathways by Fisher exact evaluation. The comparative analysis of enrichment and under representation of differentially regulated genes in liver development and HCC demonstrated a significant overlap between multiple pathways. Most strikingly we demonstrated a significant overlap not only in pathways expected to be relevant to both conditions such as cell cycle or apoptosis but also metabolic pathways associated with carbohydrate and lipid metabolism. Furthermore, we demonstrated the clinical significance of these findings as unsupervised clustering of HCC patients on the basis of these metabolic pathways displayed significant differences in survival.These results indicate that liver development and liver cancer share similar alterations in multiple genetic signaling pathways. Several pathways with markedly similar patterns of enrichment or underrepresentation of various regulated genes between liver development and HCC are of prognostic relevance in HCC. In particular, the metabolic pathways were identified as novel prognostically relevant players in HCC development.
Strategies Targeting cAMP Signaling in the Treatment of Polycystic Kidney Disease
Authors: Vicente E. Torres, Peter C. Harris
Journal: Journal of the American Society of Nephrology (2013)

Polycystic kidney disease (PKD) is a leading cause of ESRD worldwide. In PKD, excessive cell proliferation and fluid secretion, pathogenic interactions of mutated epithelial cells with an abnormal extracellular matrix and alternatively activated interstitial macrophages, and the disruption of mechanisms controlling tubular diameter contribute to cyst formation. Studies with animal models suggest that several diverse pathophysiologic mechanisms, including dysregulation of intracellular calcium levels and cAMP signaling, mediate these cystogenic mechanisms. This article reviews the evidence implicating calcium and cAMP as central players in a network of signaling pathways underlying the pathogenesis of PKD and considers the therapeutic relevance of treatment strategies targeting cAMP signaling.
Phase II study of a triplet regimen of S-1 combined with irinotecan and oxaliplatin in patients with metastatic gastric cancer: clinical and pharmacogenetic results
Authors: S.R. Park, S.-Y. Kong, J. Rhee, Y.-I. Park, K.W. Ryu, J.H. Lee, Y.-W. Kim, I.J. Choi, C.G. Kim, J.Y. Lee, S.-J. Cho, N.K. Kim
Journal: Annals of Oncology (2010)
AN IMPROVEMENT IN THE METHOD OF ISOLATING AND RECOVERING THE BACILLUS OF CATTLE ABORTION THROUGH GUINEA PIGS
Authors: Ernest W. Smillie
Journal: The Journal of Experimental Medicine (1918)

1. Bacillus abortus Bang can be regularly recovered from guinea pigs inoculated with material containing the bacillus within 3 to 4 weeks. 2. The method is especially useful in recovering the organism from fetal membranes which, as a rule, are obtained after having come in contact with fecal matter, bedding, etc. 3. The spleen is the organ in which the bacteria are regularly present and in largest numbers. Cultures must be made from it to ensure success.
Pulmonary arteriovenous malformations associated with migraine with aura
Authors: M. C. Post, M. W. F. van Gent, H. W. M. Plokker, C. J. J. Westermann, J. C. Kelder, J. J. Mager, T. T. Overtoom, W. J. Schonewille, V. Thijs, R. J. Snijder
Journal: European Respiratory Journal (2009)

Migraine with aura (MA) is associated with cardiac right-to-left shunt. We prospectively studied the association between pulmonary arteriovenous malformations (PAVMs) and MA in hereditary haemorrhagic telangiectasia (HHT). All 220 consecutive HHT patients who underwent high-resolution chest computed tomography for PAVM screening were included prospectively. Prior to screening, a structured validated headache questionnaire was completed by 196 patients (57% female; mean+/-sd age 44.6+/-15.2 yrs). Two neurologists diagnosed migraine according to the International Headache Society Criteria. A PAVM was present in 70 (36%) patients. The prevalence of MA was 24% in the presence of a PAVM compared with 6% in the absence of a PAVM (OR 4.6, 95% CI 1.84-11.2; p = 0.001), and MA was an independent predictor for the presence of PAVM using multivariate analysis (OR 3.6, 95% CI 1.21-10.5; p = 0.02). A PAVM was present in 68% of the patients with MA compared with 32% in the non-migraine controls (OR 4.6, 95% CI 1.84-11.2; p = 0.001), and a PAVM was an independent predictor for MA using multivariate analysis (OR 3.0, 95% CI 1.00-9.20; p = 0.05). In conclusion, PAVMs are associated with MA in HHT patients.
Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides
Authors: Joost P. Schanstra, Petra Zürbig, Alaa Alkhalaf, Angel Argiles, Stephan J.L. Bakker, Joachim Beige, Henk J.G. Bilo, Christos Chatzikyrkou, Mohammed Dakna, Jesse Dawson, Christian Delles, Hermann Haller, Marion Haubitz, Holger Husi, Joachim Jankowski, George Jerums, Nanne Kleefstra, Tatiana Kuznetsova, David M. Maahs, Jan Menne, William Mullen, Alberto Ortiz, Frederik Persson, Peter Rossing, Piero Ruggenenti, Ivan Rychlik, Andreas L. Serra, Justyna Siwy, Janet Snell-Bergeon, Goce Spasovski, Jan A. Staessen, Antonia Vlahou, Harald Mischak, Raymond Vanholder
Journal: Journal of the American Society of Nephrology (2015)

Progressive CKD is generally detected at a late stage by a sustained decline in eGFR and/or the presence of significant albuminuria. With the aim of early and improved risk stratification of patients with CKD, we studied urinary peptides in a large cross-sectional multicenter cohort of 1990 individuals, including 522 with follow-up data, using proteome analysis. We validated that a previously established multipeptide urinary biomarker classifier performed significantly better in detecting and predicting progression of CKD than the current clinical standard, urinary albumin. The classifier was also more sensitive for identifying patients with rapidly progressing CKD. Compared with the combination of baseline eGFR and albuminuria (area under the curve [AUC]=0.758), the addition of the multipeptide biomarker classifier significantly improved CKD risk prediction (AUC=0.831) as assessed by the net reclassification index (0.303±-0.065; P<0.001) and integrated discrimination improvement (0.058±0.014; P<0.001). Correlation of individual urinary peptides with CKD stage and progression showed that the peptides that associated with CKD, irrespective of CKD stage or CKD progression, were either fragments of the major circulating proteins, suggesting failure of the glomerular filtration barrier sieving properties, or different collagen fragments, suggesting accumulation of intrarenal extracellular matrix. Furthermore, protein fragments associated with progression of CKD originated mostly from proteins related to inflammation and tissue repair. Results of this study suggest that urinary proteome analysis might significantly improve the current state of the art of CKD detection and outcome prediction and that identification of the urinary peptides allows insight into various ongoing pathophysiologic processes in CKD.
Long term histological improvement and clearance of intrahepatic hepatitis C virus RNA following sustained response to interferon-ribavirin combination therapy in liver transplanted patients with hepatitis C virus recurrence
Authors: T Bizollon, S N S Ahmed, S Radenne, M Chevallier, P Chevallier, P Parvaz, S Guichard, C Ducerf, J Baulieux, F Zoulim, C Trepo
Journal: Gut (2003)

<b>Background and objective:</b> A proportion of liver transplanted patients with recurrent chronic hepatitis have a sustained virological response to combination therapy with interferon plus ribavirin. However, the long term benefit of antiviral therapy with regard to hepatitis C virus (HCV) RNA clearance remains unknown in patients with HCV recurrence. This study examined the long term biochemical, virological, and histological outcome in transplanted patients with recurrent chronic hepatitis who had a sustained virological response to antiviral therapy. <b>Patients and methods:</b> Fifty four patients with recurrent hepatitis C were treated with antiviral therapy involving induction by combination therapy (interferon (IFN) plus ribavirin) for six months and maintenance ribavirin therapy for 12 months. Fourteen patients who had recurrent chronic hepatitis and sustained virological response to antiviral therapy were followed for three years after the end of antiviral therapy. Serum alanine aminotransferases were assessed every three months during the observation period. Serum hepatitis C RNA detected by polymerase chain reaction was evaluated every six months during follow up, and protocol biopsy procedures were performed routinely every year. Semiquantitative histopathological assessment of allograft hepatitis was performed using the Knodell score and HCV was also detected by polymerase chain reaction on frozen graft tissue samples. <b>Results:</b> At the end of antiviral therapy, the sustained response rate was 26%. A complete response (normal serum alanine aminotransferase level and undetectable serum HCV RNA) was achieved in 13/14 (93%) patients three years after the end of treatment. A comparison of liver histology findings before and after a mean of three years after antiviral therapy showed a clear improvement in 12/14 (86%) patients. In 5/14 (36%) patients, the last biopsy showed normal or near normal histological findings. After three years of follow up, the total Knodell score was 3.2 (range 1–8) versus 8.3 (range 5–12) before treatment (p=0.001). Graft HCV RNA was detectable before treatment in all 14 patients and was undetectable at the end of follow up in 13/14 (93%) patients tested. <b>Conclusion:</b> In patients with biochemical and virological responses induced by ribavirin and interferon, a complete response was sustained in 93% for at least three years after cessation of therapy. This long term response was associated with absence of detectable intrahepatic hepatitis C RNA and marked histological improvement.
Spontaneous and UV Radiation–Induced Multiple Metastatic Melanomas in <i>Cdk4R24C/R24C/TPras</i> Mice
Authors: Elke Hacker, H. Konrad Muller, Nicole Irwin, Brian Gabrielli, Douglas Lincoln, Sandra Pavey, Marianne Broome Powell, Marcos Malumbres, Mariano Barbacid, Nicholas Hayward, Graeme Walker
Journal: Cancer Research (2006)

Abstract Human melanoma susceptibility is often characterized by germ-line inactivating CDKN2A (INK4A/ARF) mutations, or mutations that activate CDK4 by preventing its binding to and inhibition by INK4A. We have previously shown that a single neonatal UV radiation (UVR) dose delivered to mice that carry melanocyte-specific activation of Hras (TPras) increases melanoma penetrance from 0% to 57%. Here, we report that activated Cdk4 cooperates with activated Hras to enhance susceptibility to melanoma in mice. Whereas UVR treatment failed to induce melanomas in Cdk4R24C/R24C mice, it greatly increased the penetrance and decreased the age of onset of melanoma development in Cdk4R24C/R24C/TPras animals compared with TPras alone. This increased penetrance was dependent on the threshold of Cdk4 activation as Cdk4R24C/+/TPras animals did not show an increase in UVR-induced melanoma penetrance compared with TPras alone. In addition, Cdk4R24C/R24C/TPras mice invariably developed multiple lesions, which occurred rarely in TPras mice. These results indicate that germ-line defects abrogating the pRb pathway may enhance UVR-induced melanoma. TPras and Cdk4R24C/R24C/TPras tumors were comparable histopathologically but the latter were larger and more aggressive and cultured cells derived from such melanomas were also larger and had higher levels of nuclear atypia. Moreover, the melanomas in Cdk4R24C/R24C/TPras mice, but not in TPras mice, readily metastasized to regional lymph nodes. Thus, it seems that in the mouse, Hras activation initiates UVR-induced melanoma development whereas the cell cycle defect introduced by mutant Cdk4 contributes to tumor progression, producing more aggressive, metastatic tumors. (Cancer Res 2006; 66(6): 2946-52)
Gemcitabine and cisplatin for inoperable and/or metastatic biliary tree carcinomas: a multicenter phase II study of the Gruppo Oncologico dell'Italia Meridionale (GOIM)
Authors: F. Giuliani, V. Gebbia, E. Maiello, N. Borsellino, E. Bajardi, G. Colucci
Journal: Annals of Oncology (2006)
Intersex and the Olympic Games
Authors: Robert Ritchie, John Reynard, Tom Lewis
Journal: Journal of the Royal Society of Medicine (2008)

The assignment of sex at birth determines the manner in which a child is raised. It determines their appearance and governs their development.1 Sexual ambiguity – intersex – may result in a broad spectrum of physical problems. Certain anomalies may be detectable only by the astute clinician and would otherwise go unnoticed, whereas more profound anomalies may result in considerable developmental and psychological difficulties for both the child and his or her parents and family. Sex determination in individuals with sexual ambiguity has created difficulties in the arena of international sports for many years. While Hitler's Olympic Games in Berlin in 1936 generated much controversy around the issue of racial and religious discrimination, it also brought the complexities of gender verification to the forefront of competitive sport for the first time.

In this paper we review the historical impact of intersex in the area of international sports and discuss current thinking with regard to determination of sex in sports men and women.
CD19 targeting of chronic lymphocytic leukemia with a novel Fc-domain–engineered monoclonal antibody
Authors: Farrukh T. Awan, Rosa Lapalombella, Rossana Trotta, Jonathan P. Butchar, Bo Yu, Don M. Benson, Julie M. Roda, Carolyn Cheney, Xiaokui Mo, Amy Lehman, Jeffrey Jones, Joseph Flynn, David Jarjoura, John R. Desjarlais, Susheela Tridandapani, Michael A. Caligiuri, Natarajan Muthusamy, John C. Byrd
Journal: Blood (2009)

Abstract CD19 is a B cell–specific antigen expressed on chronic lymphocytic leukemia (CLL) cells but to date has not been effectively targeted with therapeutic monoclonal antibodies. XmAb5574 is a novel engineered anti-CD19 monoclonal antibody with a modified constant fragment (Fc)–domain designed to enhance binding of FcγRIIIa. Herein, we demonstrate that XmAb5574 mediates potent antibody-dependent cellular cytotoxicity (ADCC), modest direct cytotoxicity, and antibody-dependent cellular phagocytosis but not complement-mediated cytotoxicity against CLL cells. Interestingly, XmAb5574 mediates significantly higher ADCC compared with both the humanized anti-CD19 nonengineered antibody it is derived from and also rituximab, a therapeutic antibody widely used in the treatment of CLL. The XmAb5574-dependent ADCC is mediated by natural killer (NK) cells through a granzyme B–dependent mechanism. The NK cell–mediated cytolytic and secretory function with XmAb5574 compared with the nonengineered antibody is associated with enhanced NK-cell activation, interferon production, extracellular signal-regulated kinase phosphorylation downstream of Fcγ receptor, and no increased NK-cell apoptosis. Notably, enhanced NK cell–mediated ADCC with XmAb5574 was enhanced further by lenalidomide. These findings provide strong support for further clinical development of XmAb5574 as both a monotherapy and in combination with lenalidomide for the therapy of CLL and related CD19+ B-cell malignancies.
COPD exacerbations {middle dot} 3: Pathophysiology
Authors: D E O'Donnell
Journal: Thorax (2006)

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with increased morbidity and mortality. The effective management of COPD exacerbations awaits a better understanding of the underlying pathophysiological mechanisms that shape its clinical expression. The clinical presentation of exacerbations of COPD is highly variable and ranges from episodic symptomatic deterioration that is poorly responsive to usual treatment, to devastating life threatening events. This underscores the heterogeneous physiological mechanisms of this complex disease, as well as the variation in response to the provoking stimulus. The derangements in ventilatory mechanics, muscle function, and gas exchange that characterise severe COPD exacerbations with respiratory failure are now well understood. Critical expiratory flow limitation and the consequent dynamic lung hyperinflation appear to be the proximate deleterious events. Similar basic mechanisms probably explain the clinical manifestations of less severe exacerbations of COPD, but this needs further scientific validation. In this review we summarise what we have learned about the natural history of COPD exacerbations from clinical studies that have incorporated physiological measurements. We discuss the pathophysiology of clinically stable COPD and examine the impact of acutely increased expiratory flow limitation on the compromised respiratory system. Finally, we review the chain of physiological events that leads to acute ventilatory insufficiency in severe exacerbations.
Airway Inflammation in Chronic Obstructive Pulmonary Disease
Authors: MARINA SAETTA
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

AM J RESPIR CRIT CARE MED 1999;160:S17−S20.Cigarette smoking causes an inflammatory process in the central airways, peripheral airways, and lung parenchyma, even in smokers with normal lung function. The characteristics of this inflammatory process differ between smokers who develop chronic airflow limitation (COPD) and those who do not develop chronic airflow limitation: there is an increased infiltration of CD8-positive T lymphocytes in smokers with COPD. We examine whether airway inflammation alters with increasing severity of disease. When the disease becomes severe, a prominent neutrophilia occurs. The precise roles of the CD8+ T lymphocyte and the neutrophil in the pathogenesis of COPD still remain to be determined. Saetta M. Airway inflammation in chronic obstructive pulmonary disease.