tbuckley/cabot-search huggingface dataset:
Chronic dynamic exercise increases apolipoprotein A-I expression in rabbit renal cortex as determined by proteomic technology: Figure 1
Authors: R de Moraes, R H Valente, I R León, M R O Trugilho, A C L Nóbrega, J Perales, E Tibiriçá
Journal: British Journal of Sports Medicine (2007)

We have shown previously that exercise training enhances endothelium-dependent and endothelium-independent vascular relaxation in rabbit kidney. This study aimed to investigate protein expression changes in the rabbit renal cortex induced by chronic dynamic exercise.Kidneys were obtained from New Zealand rabbits either confined to pens (n = 8) or trained on a treadmill (0% grade) for 5 days/week at a speed of 18 m/min for 60-min periods over 12 weeks (n = 8). Expression of proteins in the renal cortex was determined by colloidal Coomassie blue staining after two-dimensional polyacrylamide gel electrophoresis. Differential protein spots were excised and digested with trypsin, and peptides were sequenced by electrospray ionization-ion trap mass spectrometry.Two pairs of matching differentially stained spots displayed an approximate threefold increase in trained compared with sedentary animals. These four spots presented a molecular mass of 23 kDa but different pI values. Mass spectrometric analyses revealed the pairs of matching spots as being rabbit apolipoprotein A-I.Chronic dynamic exercise increases apolipoprotein A-I expression in the rabbit renal cortex. This fact could be involved in the alterations observed in the renal circulation after exercise training.
HRas Signal Transduction Promotes Hepatitis C Virus Cell Entry by Triggering Assembly of the Host Tetraspanin Receptor Complex
Authors: Laetitia Zona, Joachim Lupberger, Nazha Sidahmed-Adrar, Christine Thumann, Helen J. Harris, Amy Barnes, Jonathan Florentin, Rajiv G. Tawar, Fei Xiao, Marine Turek, Sarah C. Durand, François H.T. Duong, Markus H. Heim, François-Loïc Cosset, Ivan Hirsch, Didier Samuel, Laurent Brino, Mirjam B. Zeisel, François Le Naour, Jane A. McKeating, Thomas F. Baumert
Journal: Cell Host & Microbe (2013)
Diabetes in urban African-Americans. XVI. Overcoming clinical inertia improves glycemic control in patients with type 2 diabetes.
Authors: C B Cook, D C Ziemer, I M El-Kebbi, D L Gallina, V G Dunbar, K L Ernst, L S Phillips
Journal: Diabetes Care (1999)

OBJECTIVE: Diabetes care can be limited by clinical inertia-failure of the provider to intensify therapy when glucose levels are high. Although disease management programs have been proposed as a means to improve diabetes care, there are few studies examining their effectiveness in patient populations that have traditionally been underserved. We examined the impact of our management program in the Grady Diabetes Unit, which provides care primarily to urban African-American patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We assessed glycemic outcomes in patients with type 2 diabetes who had an intake evaluation between 1992 and 1996 and who were identified on the basis of compliance with keeping the recommended number of return visits. For 698 patients, we analyzed changes in HbA1c values between baseline and follow-up visits at 6 and 12 months, and the proportion of patients achieving a target value of &amp;lt; or =7.0% at 12 months. Since a greater emphasis on therapeutic intensification began in 1995, we also compared HbA1c values and clinical management in 1995-1996 with that of 1992-1994. RESULTS: HbA1c averaged 9.3% on presentation. After 12 months of care, HbA1c values averaged 8.2, 8.4, 8.5, 7.7, and 7.3% for the 1992-1996 cohorts, respectively, and were significantly lower compared with values on presentation (P &amp;lt; 0.0025); the average fall in HbA1c was 1.4%. The percentage of patients achieving a target HbA1c &amp;lt; or =7.0% improved progressively from 1993 to 1996, with 57% of the patients attaining this goal in 1996. Mean HbA1c after 12 months was 7.6% in 1995-1996, significantly improved over the level of 8.4% in 1992-1994 (P &amp;lt; 0.0001). HbA1c levels after 12 months of care were lower in 1995-1996 versus 1992-1994, whether patients were managed with diet alone, oral agents, or insulin (P &amp;lt; 0.02). Improved HbA1c in 1995-1996 versus 1992-1994 was associated with increased use of pharmacologic therapy CONCLUSIONS: Structured programs can improve glycemic control in urban African-Americans with diabetes. Self-examination of performance focused on overcoming clinical inertia is essential to progressive upgrading of care.
Inpatient Diabetes Control: Rationale
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2004)

Donald Bergman (New York, NY), President of the American Association of Clinical Endocrinologists, suggested the importance of endocrinologists beginning "to partner . . .for practical reasons," perhaps in this one fashion emulating trial lawyers and the National Rifle Association by finding strength in numbers!Nathaniel Clarke, on behalf of the American Diabetes Association, which cospons o r e d t h e m e e t i n g , s t r e s s e d t h e importance of developing common conclusions and guidelines.Representatives of the Endocrine Society, the American Association of Diabetes Educators, the Society of Hospital Medicine, and the American Society of Anesthesiologists agreed on the importance of the topic.Alan Garber (Houston, TX), who moderated the conference, pointed out the frequency of diabetes among hospitalized persons and noted that at his institution, approximately one-third of persons in the coronary care unit have diabetes, with onethird of this group having glucose levels Ն200 mg/dl.There are, he noted, few existing standards for glycemic control of persons with diabetes in hospital.
Low fetuin-A levels are associated with cardiovascular death: Impact of variations in the gene encoding fetuin
Authors: Peter Stenvinkel, Kai Wang, Abdul Rashid Qureshi, Jonas Axelsson, Roberto Pecoits-Filho, Ping Gao, Peter Barany, Bengt Lindholm, Tomas Jogestrand, Olof Heimberger, Clifford Holmes, Martin Schalling, Louise Nordfors
Journal: Kidney International (2005)
Identification of an Integrated SV40 T/t-Antigen Cancer Signature in Aggressive Human Breast, Prostate, and Lung Carcinomas with Poor Prognosis
Authors: Kristin K. Deeb, Aleksandra M. Michalowska, Cheol-yong Yoon, Scott M. Krummey, Mark J. Hoenerhoff, Claudine Kavanaugh, Ming-chung Li, Francesco J. Demayo, Ilona Linnoila, Chu-xia Deng, Eva Y-H.P. Lee, Daniel Medina, Joanna H. Shih, Jeffrey E. Green
Journal: Cancer Research (2007)

Abstract Understanding the genetic architecture of cancer pathways that distinguishes subsets of human cancer is critical to developing new therapies that better target tumors based on their molecular expression profiles. In this study, we identify an integrated gene signature from multiple transgenic models of epithelial cancers intrinsic to the functions of the Simian virus 40 T/t-antigens that is associated with the biological behavior and prognosis for several human epithelial tumors. This genetic signature, composed primarily of genes regulating cell replication, proliferation, DNA repair, and apoptosis, is not a general cancer signature. Rather, it is uniquely activated primarily in tumors with aberrant p53, Rb, or BRCA1 expression but not in tumors initiated through the overexpression of myc, ras, her2/neu, or polyoma middle T oncogenes. Importantly, human breast, lung, and prostate tumors expressing this set of genes represent subsets of tumors with the most aggressive phenotype and with poor prognosis. The T/t-antigen signature is highly predictive of human breast cancer prognosis. Because this class of epithelial tumors is generally intractable to currently existing standard therapies, this genetic signature identifies potential targets for novel therapies directed against these lethal forms of cancer. Because these genetic targets have been discovered using mammary, prostate, and lung T/t-antigen mouse cancer models, these models are rationale candidates for use in preclinical testing of therapies focused on these biologically important targets. [Cancer Res 2007;67(17):8065–80]
Cancer Therapy Meets p53
Authors: H. Peter Rutz
Journal: New England Journal of Medicine (1994)

To the Editor: Kinzler and Vogelstein (July 7 issue)1 eloquently discuss the clinical implications of basic research on the p53 tumor-suppressor gene. In key statements, they suggest that p53 mutations may provide a genetic basis for drug resistance and that the relation between p53 mutations and therapeutic response should be verified. In fact, the field moves rapidly ahead, and a p53-dependent cross-resistance to ionizing radiation and chemotherapeutic agents can now be considered a well-established phenomenon. It occurs not only as a result of p53-dependent apoptosis modulating cytotoxicity,2 but also because of p53-dependent gene amplification,3 p53-dependent expression of the multidrug-resistance gene . . .
Preoperative Plasma HER2 and Epidermal Growth Factor Receptor for Staging and Prognostication in Patients with Clinically Localized Prostate Cancer
Authors: Shahrokh F. Shariat, Karim Bensalah, Jose A. Karam, Claus G. Roehrborn, Andrea Gallina, Yair Lotan, Kevin M. Slawin, Pierre I. Karakiewicz
Journal: Clinical Cancer Research (2007)

Human epidermal growth factor receptor-2 (HER2) and epidermal growth factor receptor (EGFR) expression have been associated with disease progression in patients with prostate cancer. We tested the hypothesis that plasma levels of HER2 and/or EGFR are associated with prostate cancer stage and prognosis in patients with clinically localized disease.We measured preoperative plasma HER2 and EGFR levels using commercially available ELISAs on banked plasma from 227 patients treated with radical prostatectomy and bilateral lymphadenectomy for clinically localized prostate adenocarcinoma.Median preoperative plasma EGFR and HER2 levels were 31.4 ng/mL (interquartile range, 19.2 ng/mL) and 10.0 ng/mL (interquartile range, 2.7 ng/mL), respectively. HER2 was elevated in patients with seminal vesicle invasion (P = 0.033). In separate multivariate analyses that adjusted for the effects of standard preoperative predictors, lower EGFR, higher HER2, and higher HER2/EGFR ratio were associated with prostate-specific antigen (PSA) progression (P = 0.003, P < 0.001, and P < 0.001, respectively). In separate multivariate analyses that adjusted for the effects of standard postoperative predictors, lower EGFR and higher HER2/EGFR ratio were associated with PSA progression (P = 0.027 and P < 0.001, respectively). Among the patients who experienced PSA progression, HER2 was significantly higher (P = 0.023) and EGFR was lower (P = 0.04) in those with features of aggressive disease (i.e., development of metastasis, PSA doubling time <10 months, and/or failure to respond to local salvage radiation therapy).Preoperative plasma HER2 and EGFR were associated with prostate cancer progression after radical prostatectomy. Plasma HER2 and EGFR may provide a tool for predicting long-term recurrence-free survival and early metastasis.
A Phase 1 Study of the Proteasome Inhibitor Bortezomib in Pediatric Patients with Refractory Leukemia: a Children's Oncology Group Study
Authors: Terzah M. Horton, Debananda Pati, Sharon E. Plon, Patrick A. Thompson, Lisa R. Bomgaars, Peter C. Adamson, Ashish M. Ingle, John Wright, Adam H. Brockman, Martin Paton, Susan M. Blaney
Journal: Clinical Cancer Research (2007)

Abstract Purpose: A phase 1 study to determine the maximum-tolerated dose, dose-limiting toxicity, pharmacokinetics, and biological effects of bortezomib in children with recurrent/refractory leukemia. Experimental Design: Bortezomib was administered twice weekly for 2 consecutive weeks at either 1.3 or 1.7 mg/m2 dose followed by a 1-week rest. Bortezomib pharmacokinetics and nuclear factor κB (NF-κB) binding activity were evaluated during the first treatment cycle. Results: Twelve patients (nine with acute lymphoblastic leukemia, three with acute myelogenous leukemia), median age 11 years (range, 1-18 years), were enrolled between May 2004 and November 2005, of whom seven were not fully evaluable for toxicity due to rapidly progressive disease or uncontrolled infection. Dose-limiting toxicities occurred in two patients at the 1.7 mg/m2 dose level. One patient experienced grade 3 confusion and the other patient had grade 4 febrile neutropenia associated with grade 4 hypotension and grade 3 creatinine. Pharmacokinetic analysis at 1.3 mg/m2 revealed a clearance of 11 mL/h/m2, a central volume of distribution of 6.7 L/m2, and a terminal half-life of 12.6 h. NF-κB activity was examined in five patients and was noted to transiently increase and then decrease 4- to 6-fold by 24 h following bortezomib in two patients. There were no objective clinical responses. Conclusions: For children with leukemia, the recommended phase 2 dose of bortezomib, administered twice weekly for 2 weeks followed by a 1-week rest, is 1.3 mg/m2/dose. Although bortezomib treatment inhibited NF-κB activity, bortezomib had little activity as a single agent in this population.
Randomized phase II study of irinotecan, leucovorin and 5-fluorouracil (ILF) versus cisplatin plus ILF (PILF) combination chemotherapy for advanced gastric cancer
Authors: S.H. Park, E. Nam, J. Park, E.K. Cho, D.B. Shin, J.H. Lee, W.K. Lee, M. Chung, S.I. Lee
Journal: Annals of Oncology (2007)
Cancer-specific Survival After Metastasis Following Primary Radical Prostatectomy Compared with Radiation Therapy in Prostate Cancer Patients: Results of a Population-based, Propensity Score–Matched Analysis
Authors: Yu-Hsuan Joni Shao, Sung Kim, Dirk F. Moore, Weichung Shih, Yong Lin, Mark Stein, Isaac Yi Kim, Grace L. Lu-Yao
Journal: European Urology (2013)
Sulforaphane Sensitizes Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL)–Resistant Hepatoma Cells to TRAIL-Induced Apoptosis through Reactive Oxygen Species–Mediated Up-regulation of DR5
Authors: Heesue Kim, Eun Hee Kim, Young Woo Eom, Wook-Hwan Kim, Taeg Kyu Kwon, Soo Jae Lee, Kyeong Sook Choi
Journal: Cancer Research (2006)

Abstract Sulforaphane is a chemopreventive agent present in various cruciferous vegetables, including broccoli. Here, we show that treatment with tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) in combination with subtoxic doses of sulforaphane significantly induces rapid apoptosis in TRAIL-resistant hepatoma cells. Neither TNF-α- nor Fas-mediated apoptosis was sensitized in hepatoma cells by cotreatment with sulforaphane, suggesting that sulforaphane can selectively sensitize cells to TRAIL-induced apoptosis but not to apoptosis mediated by other death receptors. We found that sulforaphane treatment significantly up-regulated mRNA and protein levels of DR5, a death receptor of TRAIL. This was accompanied by an increase in the generation of reactive oxygen species (ROS). Pretreatment with N-acetyl-l-cysteine and overexpression of catalase inhibited sulforaphane-induced up-regulation of DR5 and almost completely blocked the cotreatment-induced apoptosis. Furthermore, the sulforaphane-mediated sensitization to TRAIL was efficiently reduced by administration of a blocking antibody or small interfering RNAs for DR5. These results collectively indicate that sulforaphane-induced generation of ROS and the subsequent up-regulation of DR5 are critical for triggering and amplifying TRAIL-induced apoptotic signaling. We also found that sulforaphane can sensitize both Bcl-xL- and Bcl-2-overexpressing hepatoma cells to TRAIL-induced apoptosis, indicating that treatment with a combination of TRAIL and sulforaphane may be a safe strategy for treating resistant hepatomas. (Cancer Res 2006; 66(3): 1740-50)
In vivo efficacy of a novel histone deacetylase inhibitor in combination with radiation for the treatment of gliomas1
Authors: Michal Entin-Meer, Xiaodong Yang, Scott R. VandenBerg, Kathleen R. Lamborn, Abraham Nudelman, Ada Rephaeli, Daphne Adele Haas-Kogan
Journal: Neuro-Oncology (2007)

Histone modification has emerged as a promising approach to cancer therapy. We explored the in vivo efficacy of a butyric acid derivative, pivaloyloxymethyl butyrate (AN-9), for the treatment of gliomas. Relative to control and single-modality treatments, the combination of AN-9 and radiation significantly inhibited tumor growth and prolonged time to failure in mice bearing glioma xenografts. The enhanced response to radiation was accompanied by inhibition of cellular proliferation and by increased phosphorylation of H2AX, implicating DNA double-strand breaks in the antineoplastic effects of AN-9 and radiation. The data suggest that AN-9 in combination with radiation may be an effective therapy for malignant gliomas.
Physiotherapy in bronchiectasis: we have more patients, we need more evidence
Authors: M. Á. Martínez-García, J. B. Soriano
Journal: European Respiratory Journal (2009)

Beyond any reasonable doubt, one of the greatest achievements of medicine in the last century has been the successful reduction of morbidity and mortality due to infectious disease. In 1938, a landmark paper in the Edinburgh Medical Journal by Cookson and Mason 1 highlighted the high lethality of bronchiectasis even before the fourth decade of life 1, 2. Thanks to improved hygiene measures and antibiotic treatment, what used to be a fatal disease has now become a chronic disease. The major, scattered lung lesions due to cystic bronchiectasis and often associated with outbreaks of infectious diseases, have given way to smaller, cylindrical bronchiectasis as a consequence of dozens of diseases being able to generate lung damage 3. However, far from being an extinct disease, bronchiectasis has emerged with force. The ever increasing lifespan of humans, with more people at risk of developing chronic illnesses with potential to bronchiectasis, and the widespread use of imaging techniques (such as chest high-resolution computed tomography), have increased the burden, particularly in the elderly 4, 5. But the relevance of bronchiectasis goes beyond its mere presence, as bronchiectasis worsens the prognosis of …
Endosonographic features predictive of benign and malignant gastrointestinal stromal cell tumours
Authors: L Palazzo
Journal: Gut (2000)

Some endoscopic ultrasonographic (EUS) features have been reported to be suggestive of malignancy in gastrointestinal stromal cell tumours (SCTs). The aim of this study was to assess the predictive value of these features for malignancy.A total of 56 histologically proven cases of SCT studied by EUS between 1989 and 1996 were reviewed. There were 42 gastric tumours, 12 oesophageal tumours, and two rectal tumours. The tumours were divided into two groups: (a) benign SCT, comprising benign leiomyoma (n = 34); (b) malignant or borderline SCT (n = 22), comprising leiomyosarcoma (n = 9), leiomyoblastoma (n = 9), and leiomyoma of uncertain malignant potential (n = 4). The main EUS features recorded were tumour size, ulceration, echo pattern, cystic spaces, extraluminal margins, and lymph nodes with a malignant pattern. The two groups were compared by univariate and multivariate analysis.Irregular extraluminal margins, cystic spaces, and lymph nodes with a malignant pattern were most predictive of malignant or borderline SCT. Pairwise combinations of the three features had a specificity and positive predictive value of 100% for malignant or borderline SCT, but a sensitivity of only 23%. The presence of at least one of these three criteria had 91% sensitivity, 88% specificity, and 83% predictive positive value. In multivariate analysis, cystic spaces and irregular margins were the only two features independently predictive of malignant potential. The features most predictive of benign SCTs were regular margins, tumour size < or = 30 mm, and a homogeneous echo pattern. When the three features were combined, histology confirmed a benign SCT in all cases.The combined presence of two out of three EUS features (irregular extraluminal margins, cystic spaces, and lymph nodes with a malignant pattern) had a positive predictive value of 100% for malignant or borderline gastrointestinal SCT. Tumours less than 30 mm in diameter with regular margins and a homogeneous echo pattern are usually benign.
IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel
Authors: Vanda A. Lennon, Thomas J. Kryzer, Sean J. Pittock, A.S. Verkman, Shannon R. Hinson
Journal: The Journal of Experimental Medicine (2005)

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ. A serum immunoglobulin G autoantibody (NMO-IgG) serves as a specific marker for NMO. Here we show that NMO-IgG binds selectively to the aquaporin-4 water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier. NMO may represent the first example of a novel class of autoimmune channelopathy.
High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis
Authors: G. Raghu, T. D. Freudenberger, S. Yang, J. R. Curtis, C. Spada, J. Hayes, J. K. Sillery, C. E. Pope, C. A. Pellegrini
Journal: European Respiratory Journal (2005)

The aim of this prospective study was to determine the prevalence and characteristics of acid gastro-oesophageal reflux (GER) in patients with idiopathic pulmonary fibrosis (IPF). Sixty-five consecutive patients with well-defined IPF were subjected to 24-h pH monitoring and oesophageal manometry. A total of 133 consecutive patients with intractable asthma and symptoms of GER were used as comparisons. The prevalence of abnormal acid GER in IPF patients was 87%, with 76% and 63% demonstrating abnormal distal and proximal oesophageal acid exposures, respectively. Abnormal acid GER was significantly more common in IPF patients than asthma patients. Only 47% of IPF patients experienced classic GER symptoms. Despite treatment with standard doses of proton pump inhibitors (PPIs), 12 out of 19 patients receiving PPIs during the 24-h pH monitoring had abnormal oesophageal acid exposures by pH probe. There was no correlation between IPF severity and acid GER severity. In conclusion, abnormal acid gastro-oesophageal reflux is highly prevalent, but often clinically occult in patients with idiopathic pulmonary fibrosis. Standard doses of proton pump inhibitors may not suppress the acid gastro-oesophageal reflux in this population. Therefore, further studies are needed to determine if acid abnormal gastro-oesophageal reflux represents an important risk factor for idiopathic pulmonary fibrosis development or progression, and if optimal suppression of acid gastro-oesophageal reflux slows the progression of idiopathic pulmonary fibrosis and/or decreases episodic exacerbations of idiopathic pulmonary fibrosis.