tbuckley/cabot-search huggingface dataset:
Prognostic Value of Combined “Triple”-Reverse Transcription-PCR Analysis for Prostate-Specific Antigen, Human Kallikrein 2, and Prostate-Specific Membrane Antigen mRNA in Peripheral Blood and Lymph Nodes of Prostate Cancer Patients
Authors: Ralf Kurek, German Nunez, Nikolaos Tselis, Lutz Konrad, Thomas Martin, Sandra Roeddiger, Gerd Aumüller, Nikolaos Zamboglou, Daniel W. Lin, Ulf W. Tunn, Heiner Renneberg
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We present the largest study of both peripheral blood and lymph node samples examining the utility of reverse transcription-polymerase chain reaction (RT-PCR) for established molecular markers as a diagnostic tool in the molecular staging of prostate cancer patients undergoing radical prostatectomy. Experimental Design: Peripheral blood from 358 patients was obtained before radical prostatectomy. Corresponding obturatory lymph node samples were collected from 153 of these patients. Nested RT-PCR for prostate-specific antigen (PSA), human kallikrein 2 (hK2), and prostate-specific membrane antigen (PSMA) were performed on cDNA from peripheral blood. The lymph node cDNA was analyzed for PSA und hK2 expression. Results: RT-PCR in peripheral blood was positive in 124 (34.6%) of 358 samples for PSA, 215 (60.1%) of 358 for PSMA, and 97 (27.1%) of 358 for hK2. Comparison of positive RT-PCR rates of pT2 and pT3 tumors in corresponding peripheral blood for PSA, PSMA, and hK2 were 31.9 and 40.0%, 58.8 and 62.5%, and 26.9 and 27.5%, respectively. Histopathologically, cancer-free lymph node samples were positive in RT-PCR for PSA and hK2 in 70 (49.6%) of 141 and 89 (63.2%) of 141 of cases. All histologically positive lymph node samples (n = 12, pN+) were positive for PSA RT-PCR. PSA RT-PCR alone, as well as combined PSA/PSMA RT-PCR evaluation, in peripheral blood showed a significant association with grading. PSA RT-PCR lymph node-negative samples were significantly less likely positive in their corresponding peripheral blood RT-PCR sample. Conclusions Although the preoperative PSA RT-PCR in peripheral blood correlated with the grading of prostate cancer, no combination of RT-PCR results using “triple” markers (PSA, hK2, PSMA) in peripheral blood and/or lymph nodes yielded additional preoperative staging information.
Pharmacologic Differentiation of Inflammation and Fibrosis in the Rat Bleomycin Model
Authors: Nveed I. Chaudhary, Andreas Schnapp, John E. Park
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: The model most often used to study the pathogenesis of pulmonary fibroses is the bleomycin (BLM)-induced lung fibrosis model. Several treatments have been efficacious in this model, but not in the clinic.Objectives: To describe the time course of inflammation and fibrosis in the BLM model and to study the effect of timing of antiinflammatory and antifibrotic treatments on efficacy.Methods and Measurements: Rats were given single intratracheal injections of BLM on Day 0. At specified time points, 10 rats were killed and their lungs studied for proinflammatory cytokines and for profibrotic growth factor mRNA. After a single intratracheal injection of BLM on Day 0, rats were treated from Day 1 or 10 daily with oral prednisolone (10 mg/kg) or oral imatinib mesylate (50 mg/kg) for 21 d.Results: After BLM administration, the expression of inflammatory cytokines was elevated and returned to background levels at later time points. Profibrotic gene expression peaked between Days 9 and 14 and remained elevated till the end of the experiment, suggesting a “switch” between inflammation and fibrosis in this interval. Antiinflammatory treatment (oral prednisolone) was beneficial when commenced at Day 1, but had no effect if administered from Day 10 onward. However, imatinib mesylate was effective independently of the dosing regime.Conclusions: The response of the BLM model to antifibrotic or antiinflammatory interventions is critically dependent on timing after the initial injury.
Suppressor cells: dependence on assay conditions for functional activity.
Authors: D D Eardley, M O Staskawicz, R K Gershon
Journal: The Journal of Experimental Medicine (1976)

Spleen cells educated in vitro with sheep red blood cells (SRBC) suppressed the plaque-forming cell response of Mishell-Dutton assay cultures challenged with optimal doses of SRBC. Changing conditions in the assay cultures changed the effect educated cells had on the assay culture responses. For example, educated cells helped rather than suppressed assay cultures of suboptimal numbers of spleen cells. Similarly, augmentation resulted upon addition of educated cells to assay cultures challenged with suboptimal doses of SRBC. Such a reversal of regulatory effects was not observed when assay cultures were challenged with supraoptimal antigen doses. Educated cells helped assay cultures of B spleen cells, and the addition of normal T cells reinstated suppression. Furthermore, maintenance of assay cultures under stationary rather than the usual rocking conditions allowed educated cells to help rather than suppress the antibody response of assay cultures. These results show that when the response of the target population (assay cultures) is low, the regulator (educated) cells augment the response, and vice versa, supporting the hypothesis that the effect regulator cells produce depends on the activity of the cells they regulate.
Association Between Depressive Symptoms and Incidence of Crohn's Disease and Ulcerative Colitis: Results From the Nurses' Health Study
Authors: Ashwin N. Ananthakrishnan, Hamed Khalili, An Pan, Leslie M. Higuchi, Punyanganie de Silva, James M. Richter, Charles S. Fuchs, Andrew T. Chan
Journal: Clinical Gastroenterology and Hepatology (2012)
Insulin-like Growth Factor 2 Expression Modulates Taxol Resistance and Is a Candidate Biomarker for Reduced Disease-Free Survival in Ovarian Cancer
Authors: Gloria S. Huang, Jurriaan Brouwer-Visser, Marissa J. Ramirez, Christine H. Kim, Tiffany M. Hebert, Juan Lin, Hugo Arias-Pulido, Clifford R. Qualls, Eric R. Prossnitz, Gary L. Goldberg, Harriet O. Smith, Susan Band Horwitz
Journal: Clinical Cancer Research (2010)

This study was undertaken to examine the role of the insulin-like growth factor (IGF) signaling pathway in the response of ovarian cancer cells to Taxol and to evaluate the significance of this pathway in human epithelial ovarian tumors.The effect of Taxol treatment on AKT activation in A2780 ovarian carcinoma cells was evaluated using antibodies specific for phospho-AKT. To study the drug-resistant phenotype, we developed a Taxol-resistant cell line, HEY-T30, derived from HEY ovarian carcinoma cells. IGF2 expression was measured by real-time PCR. A type 1 IGF receptor (IGF1R) inhibitor, NVP-AEW541, and IGF2 small interfering RNA were used to evaluate the effect of IGF pathway inhibition on proliferation and Taxol sensitivity. IGF2 protein expression was evaluated by immunohistochemistry in 115 epithelial ovarian tumors and analyzed in relation to clinical/pathologic factors using the chi(2) or Fisher's exact tests. The influence of IGF2 expression on survival was studied with Cox regression.Taxol-induced AKT phosphorylation required IGF1R tyrosine kinase activity and was associated with upregulation of IGF2. Resistant cells had higher IGF2 expression compared with sensitive cells, and IGF pathway inhibition restored sensitivity to Taxol. High IGF2 tumor expression correlated with advanced stage (P < 0.001) and tumor grade (P < 0.01) and reduced disease-free survival (P < 0.05).IGF2 modulates Taxol resistance, and tumor IGF2 expression is a candidate prognostic biomarker in epithelial ovarian tumors. IGF pathway inhibition sensitizes drug-resistant ovarian carcinoma cells to Taxol. Such novel findings suggest that IGF2 represents a therapeutic target in ovarian cancer, particularly in the setting of Taxol resistance.
VEGF-A and the Induction of Pathological Angiogenesis
Authors: Janice A. Nagy, Ann M. Dvorak, Harold F. Dvorak
Journal: Annual Review of Pathology Mechanisms of Disease (2007)

Tumors, wounds, and chronic inflammatory disorders generate a new vascular supply by a process known as pathological angiogenesis. Whereas formation of the normal blood vasculature requires the interaction of many different agonists and inhibitors, including vascular endothelial growth factor-A (VEGF-A) and other members of the vascular permeability factor/VEGF family, pathological angiogenesis is a cruder, simpler process that can be replicated by a single VEGF-A isoform, VEGF-A 164/5 . VEGF-A 164/5 induces the formation of several distinctly different types of new blood vessels that differ from normal blood vessels with respect to organization, structure, and function. Elucidating the properties of these new vessels has led to a better understanding of angiogenesis and will hopefully lead to new approaches to antiangiogenic therapy.
NI-27 * SURGICAL TECHNIQUES FOR SAFE AND ACCURATE STEREOTACTIC BIOPSY IN THE ELOQUENT AREAS AND BRAIN STEM
Authors: T. Fujimaki, M. Kobayashi, K. Wakiya, N. Terano, M. Kawashima, R. Nishikawa
Journal: Neuro-Oncology (2014)

BACKGROUND: Stereotactic biopsy (StB) is applied for the deep-seated lesions often located in eloquent structures including brain stem. Preventing no new neurological deficits but obtain enough tumor specimen is important. METHODS: Eighteen patients with brain lesions underwent StB. Age 9–80 years (mean 59), 11 male 8 female. The lesions were 5 in the brainstem, 6 in the thalamus and 6 in the deep white matter. A Leksell stereotactic frame was attached and MR images were acquired with a 1.5T-MRI. Leksell SurgiPlan software were used. Biopsy were performed with following tips: a double-lumen probe with a side-cut window was inserted from the gyrus without passing sulci and ventricles, paths were determined in the reconstructed MR images parallel and orthogonal plains to the probe, a small tubule connected with a 1 ml-syringe was inserted into the probe immediately after biopsy to suck in and irrigate bleeding, not to develop hematoma. RESULTS: Successful diagnosis was achieved in all 18 patients; 12 glial tumors, 3 lymphomas, 1 germ cell tumor, 2 degenerative diseases. No hematoma nor excessive brain damage found in the postoperative CT scans. No new neurological deficits developed. CONCLUSION: Our surgical techniques of StB provide quite safe and successful surgical results.
Application of ’omics technologies to biomarker discovery in inflammatory lung diseases
Authors: Craig E. Wheelock, Victoria M. Goss, David Balgoma, Ben Nicholas, Joost Brandsma, Paul J. Skipp, Stuart Snowden, Dominic Burg, Arnaldo D'Amico, Ildiko Horvath, Amphun Chaiboonchoe, Hassan Ahmed, Stéphane Ballereau, Christos Rossios, Kian Fan Chung, Paolo Montuschi, Stephen J. Fowler, Ian M. Adcock, Anthony D. Postle, Sven-Erik Dahlén, Anthony Rowe, Peter J. Sterk, Charles Auffray, Ratko Djukanović
Journal: European Respiratory Journal (2013)

Inflammatory lung diseases are highly complex in respect of pathogenesis and relationships between inflammation, clinical disease and response to treatment. Sophisticated large-scale analytical methods to quantify gene expression (transcriptomics), proteins (proteomics), lipids (lipidomics) and metabolites (metabolomics) in the lungs, blood and urine are now available to identify biomarkers that define disease in terms of combined clinical, physiological and patho-biological abnormalities. The aspiration is that these approaches will improve diagnosis, i.e. define pathological phenotypes, and facilitate the monitoring of disease and therapy, and also, unravel underlying molecular pathways. Biomarker studies can either select predefined biomarker(s) measured by specific methods or apply an "unbiased" approach involving detection platforms that are indiscriminate in focus. This article reviews the technologies presently available to study biomarkers of lung disease within the 'omics field. The contributions of the individual 'omics analytical platforms to the field of respiratory diseases are summarised, with the goal of providing background on their respective abilities to contribute to systems medicine-based studies of lung disease.
Aldose Reductase in Glucose Toxicity: A Potential Target for the Prevention of Diabetic Complications
Authors: Chihiro Yabe-Nishimura
Journal: Pharmacological Reviews (1998)

Recent data obtained from the Diabetes Control and Complications Trial clearly indicate that intensive insulin treatment effectively delays the onset and slows the progression of longterm diabetic complications in patients with insulin-dependent diabetes mellitus (IDDM)b (Diabetes Control and
Elucidating sodium channel NaV1.5 clustering in cardiac myocytes using super-resolution techniques
Authors: L. Gillet, D. Shy, H. Abriel
Journal: Cardiovascular Research (2014)

This editorial refers to ‘Super-resolution imaging reveals that loss of the C-terminus of connexin43 limits microtubule plus-end capture and NaV1.5 localization at the intercalated disc’ by E. Agullo-Pascual et al. , pp. 371–381, this issue. 

The cardiac voltage-gated sodium channel, NaV1.5, is responsible for conducting the inward sodium current ( I Na), which leads to the fast depolarization of the cardiac cell membrane. Mutations in SCN5A, the gene encoding NaV1.5, that lead to alterations in I Na are linked to many cardiac phenotypes including congenital long QT syndrome type 3, Brugada syndrome, atrial fibrillation, conduction slowing, and dilated cardiomyopathy. Several partner proteins have been described to associate with NaV1.5, and the genes encoding some of these regulatory proteins have also been found to be mutated in patients with inherited forms of cardiac arrhythmias.1

Recent investigations have revealed that the expression level, cellular localization, and activity of NaV1.5 are finely regulated by complex molecular and cellular mechanisms. Multiple pools of NaV1.5 in cardiac cells have been identified,2 depending on where they are targeted and with which partner proteins they interact ( Figure 1A ). Thus, proteins such as SAP97,3 ankyrin-G, plakophilin 2 (PKP2), and connexin43 (Cx43)4,5 have been described to interact with NaV1.5. The importance of these interactions in targeting and stabilizing NaV1.5 at the intercalated disc (ID), where cells are electrically and mechanically coupled, is only partially understood. NaV1.5 is also expressed at the lateral membrane of cardiomyocytes, and its targeting to this compartment is regulated by …
Enhancement of coxsackievirus B3 myocarditis in mice by lobenzarit disodium through inhibition of splenic pan T cells
Authors: C. Kishimoto, H. Takada, Y. Kuroki, I. Matsushita, Y. Hiraoka, M. Kurokawa, H. Ochiai, S. Sasayama
Journal: Cardiovascular Research (1993)

The aim was to test the efficacy of the immune system modulator lobenzarit disodium in the treatment of coxsackievirus B3 myocarditis.Two week old C3H/He mice were inoculated with 10(3) plaque forming units of coxsackievirus B3. Lobenzarit disodium, 25 mg.kg-1.d-1, was given subcutaneously daily on days 0-14 (experiment I; group 2) and days 14-28 (experiment II; group 4). Both treated groups were compared to infected controls for each experiment (groups 1 and 3). For the analysis of splenic lymphocyte subsets, additional mice in untreated and treated groups were killed on d 7, and the percentages of Thy 1.2 (CD3), L3T4 (CD4), Ly 2 (CD8) subsets were analysed by laser flow cytometry (experiment III).In experiment I, the survival rate in the lobenzarit treated group was significantly lower than in the controls (2/11 v 8/11). Cellular infiltration and myocardial necrosis in the lobenzarit group were more severe. Myocardial virus titres and serum neutralising antibody titres did not differ significantly between the two groups. In experiment II, the survival rate (7/9 v 13/13) and cardiac pathology between the two groups did not differ significantly. In experiment III, the percentage of the Thy 1.2 subset (CD3) in the treated group was significantly lower (p < 0.05) than in the control group, at 36.0(SD 2.9)% v 42.8(5.8)%.Lobenzarit disodium decreased splenic pan T cells and aggravated both clinical course and cardiac pathology in acute murine coxsackievirus B3 myocarditis.
The excretion of ibuprofen by the horse - a preliminary report.
Authors: J. A. Evans, M. B. Lambert, J. Miller
Journal: British Journal of Sports Medicine (1976)

The anti-inflammatory drug Ibuprofen [(+/-)-2-(p-isobutylphenyl) propionic acid] was estimated in the blood and urine of a horse using gas-liquid chromatography of the silylated derivative. Levels of the drug in the two body fluids were measured over a period of about 24 hours after administering a 12 gm dose of Ibuprofen. Plasma peak levels were observed within 30 to 60 min, and the drug was no longer detectable in the plasma by 8 hr. Urinary peak levels were observed 200 to 300 min after dosing, and the drug was no longer detectable in the urine by about 28 hr. It was observed that only 2% to 6% of the free unchanged drug was excreted in the urine.
A proteome-wide protein interaction map for Campylobacter jejuni
Authors: Jodi R Parrish, Jingkai Yu, Guozhen Liu, Julie A Hines, Jason E Chan, Bernie A Mangiola, Huamei Zhang, Svetlana Pacifico, Farshad Fotouhi, Victor J DiRita, Trey Ideker, Phillip Andrews, Russell L Finley
Journal: Genome biology (2007)

Data from large-scale protein interaction screens for humans and model eukaryotes have been invaluable for developing systems-level models of biological processes. Despite this value, only a limited amount of interaction data is available for prokaryotes. Here we report the systematic identification of protein interactions for the bacterium Campylobacter jejuni, a food-borne pathogen and a major cause of gastroenteritis worldwide. Using high-throughput yeast two-hybrid screens we detected and reproduced 11,687 interactions. The resulting interaction map includes 80% of the predicted C. jejuni NCTC11168 proteins and places a large number of poorly characterized proteins into networks that provide initial clues about their functions. We used the map to identify a number of conserved subnetworks by comparison to protein networks from Escherichia coli and Saccharomyces cerevisiae. We also demonstrate the value of the interactome data for mapping biological pathways by identifying the C. jejuni chemotaxis pathway. Finally, the interaction map also includes a large subnetwork of putative essential genes that may be used to identify potential new antimicrobial drug targets for C. jejuni and related organisms. The C. jejuni protein interaction map is one of the most comprehensive yet determined for a free-living organism and nearly doubles the binary interactions available for the prokaryotic kingdom. This high level of coverage facilitates pathway mapping and function prediction for a large number of C. jejuni proteins as well as orthologous proteins from other organisms. The broad coverage also facilitates cross-species comparisons for the identification of evolutionarily conserved subnetworks of protein interactions.
NMDA-type glutamate receptors contribute to the development of pulmonary hypertension
Authors: Sébastien J. Dumas, Frédéric Perros, Catherine Rücker-Martin, Ly Tu, Christophe Guignabert, Elodie Gouadon, Peter Dorfmüller, Marc Humbert, Sylvia Cohen-Kaminsky
Journal: European Respiratory Journal (2012)

Background   The NMDA receptor (NMDAR) is present in the three peripheral systems involved in Pulmonary Arterial Hypertension (PAH): immune, vascular systems and heart, but it9s unknown whether it plays a role in the pathophysiology of this disease.   Aims   1) Highlight the presence of NMDARs and its agonist glutamate in the pulmonary vascular wall of PAH patients. 2) Search for deregulations of this signaling pathway in PAH. 3) Test the effect of NMDAR antagonists in a rat model of PAH.   Methods   NMDARs and glutamate were detected by flow cytometry and confocal microscopy. Effects of two NMDAR antagonists (memantine 100mg/kg/day from day 1 to 21 and MK-801 3mg/kg/day from day 14 to 21) were studied in a rat model of monocrotaline-induced PAH. We measured hemodynamic parameters, pulmonary vascular remodeling, right heart hypertrophy, levels of circulating markers of endothelial cell (EC) dysfunction (ICAM-1 and E-selectin) by ELISA and memantine by liquid chromatography and tandem mass spectrometry.   Results   1) GluN1, the obligatory subunit of NMDARs, is expressed in the walls of pulmonary arteries in PAH patients, particularly in ECs that show enhanced proliferation to glutamate. 2) In human and experimental PAH, pulmonary arterial smooth muscle cells accumulate glutamate. 3) Chronic and curative administration of memantine and MK-801 respectively, improve all parameters of PAH in the experimental model, including a reduced EC dysfunction. 4) Improvement of PAH is due to the inhibition of GluN1/GluN2A and/or GluN1/GluN2B NMDARs.   Conclusion   Glutamatergic signaling occurs via NMDARs in the pathophysiology of PAH and may represent an innovative therapeutic target.   Support: Inserm, Paris-Sud, LabEx LERMIT, FRSR.
Use of hospitals, physician visits, and hospice care during last six months of life among cohorts loyal to highly respected hospitals in the United States
Authors: John E Wennberg, Elliott S Fisher, Thérèse A Stukel, Jonathan S Skinner, Sandra M Sharp, Kristen K Bronner
Journal: BMJ (2004)

Abstract Objective To evaluate the use of healthcare resources during the last six months of life among patients of US hospitals with strong reputations for high quality care in managing chronic illness. Design Retrospective cohort study based on claims data from the US Medicare programme. Participants Cohorts receiving most of their hospital care from 77 hospitals that appeared on the 2001 US News and World Report “best hospitals” list for heart and pulmonary disease, cancer, and geriatric services. Main outcome measures Use of healthcare resources in the last six months of life: number of days spent in hospital and in intensive care units; number of physician visits; percentage of patients seeing 10 or more physicians; percentage enrolled in hospice. Terminal care: percentage of deaths occurring in hospital; percentage of deaths occurring in association with a stay in an intensive care unit. Results Extensive variation in each measure existed among the 77 hospital cohorts. Days in hospital per decedent ranged from 9.4 to 27.1 (interquartile range 11.6-16.1); days in intensive care units ranged from 1.6 to 9.5 (2.6-4.5); number of physician visits ranged from 17.6 to 76.2 (25.5-39.5); percentage of patients seeing 10 or more physicians ranged from 16.9% to 58.5% (29.4-43.4%); and hospice enrolment ranged from 10.8% to 43.8% (22.0-32.0%). The percentage of deaths occurring in hospital ranged from 15.9% to 55.6% (35.4-43.1%), and the percentage of deaths associated with a stay in intensive care ranged from 8.4% to 36.8% (20.2-27.1%). Conclusion Striking variation exists in the utilisation of end of life care among US medical centres with strong national reputations for clinical care.
Lack of knowledge about dementia mars home care services, says regulator
Authors: A. O'Dowd
Journal: BMJ (2013)

Some staff who provide home care for older people in England lack important skills and training to enable them to deal with mental health issues such as dementia, finds a new report.

Overall around a quarter of home care providers do not meet all five national standards of quality and safety, concluded the health and social care regulator the Care Quality Commission (CQC) in a report published on 13 February.1

The report gathered findings from inspections of 250 domiciliary care agencies providing at-home support and care to around 26 500 people aged 65 or over in England.

The CQC gathered views from …