tbuckley/cabot-search huggingface dataset:
Metabolism of Asymmetric Dimethylarginines Is Regulated in the Lung Developmentally and With Pulmonary Hypertension Induced by Hypobaric Hypoxia
Authors: Francesca I. Arrigoni, Patrick Vallance, Sheila G. Haworth, James M. Leiper
Journal: Circulation (2003)

Nitric oxide (NO) plays an important part in lowering pulmonary vascular resistance after birth, and in persistent pulmonary hypertension of the newborn (PPHN), NO-mediated dilation is dysfunctional. The endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) circulates in plasma, and its concentrations are elevated in certain cardiovascular diseases, including pulmonary hypertension. ADMA is metabolized by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), the activity of which regulates ADMA concentrations and provides a mechanism for modulating NO synthase in vivo. We investigated the changes in expression and activity of the 2 isoforms of DDAH in lungs from newborn piglets both during normal development and in PPHN.Using Western blotting, we showed that DDAHI expression did not change in the normal developing lung; however, DDAHII increased after birth and reached a peak at 1 day. This was reflected in an increase in total DDAH activity according to an L-citrulline assay. With pulmonary hypertension, no changes in DDAHI expression were observed, but DDAHII expression was markedly decreased compared with age-matched controls. Total DDAH activity was similarly reduced.These results indicate that each DDAH isoform is differentially regulated during both lung development and PPHN. Suppression of DDAHII isoform expression may be a mechanism underlying PPHN.
Prognostic Relevance of Occult Nodal Micrometastases and Circulating Tumor Cells in Colorectal Cancer in a Prospective Multicenter Trial
Authors: Kazuo Koyanagi, Anton J. Bilchik, Sukamal Saha, Roderick R. Turner, David Wiese, Martin McCarter, Perry Shen, Linda Deacon, David Elashoff, Dave S.B. Hoon
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Nodal micrometastasis and circulating tumor cells detected by multimarker quantitative real-time reverse transcription-PCR (qRT-PCR) may have prognostic importance in patients with colorectal cancer. Experimental Design: Paraffin-embedded sentinel lymph nodes from 67 patients and blood from 34 of these patients were evaluated in a prospective multicenter trial of sentinel lymph node mapping in colorectal cancer. Sentinel lymph nodes were examined by H&amp;E staining and cytokeratin immunohistochemistry. Sentinel lymph nodes and blood were examined by a four-marker qRT-PCR assay (c-MET, melanoma antigen gene-A3 family, β1→4-N-acetylgalactosaminyltransferase, and cytokeratin-20); qRT-PCR results were correlated with disease stage and outcome. Results: In H&amp;E-negative sentinel lymph node patients that recurred, cytokeratin immunohistochemistry and qRT-PCR detected metastasis in 30% and 60% of patients, respectively. Disease-free survival differed significantly by multimarker qRT-PCR upstaged sentinel lymph node (P = 0.014). qRT-PCR analysis of blood for circulating tumor cells correlated with overall survival (P = 0.040). Conclusion: Molecular assessment for micrometastasis in sentinel lymph node and blood specimens may help identify patients at high risk for recurrent colorectal cancer, who could benefit from adjuvant therapy.
The Effect of Granulomatous Pulmonary Disease in Dogs on the Response of the Pulmonary Circulation to Hypoxia
Authors: R. S. Irwin, J. Martinez-Gonzalez-Rio, H. M. Thomas, H. W. Fritts
Journal: Journal of Clinical Investigation (1977)

We studied the effect of diffuse granulomatous pulmonary disease on the reponse of the pulmonary circulation to hypoxia in two series of experiments in intact dogs. First, in animals with unilateral disease, vasoconstriction in the diseased lung was compared to that in the contralateral control lung. Second, in animals with bilateral disease, the vasoconstriction of pulmonary shunt pathways was compared to that of the rest of the pulmonary vasculature. We assessed vasoconstriction in each study by measuring the distribution of pulmonary blood flow between the test and control set of vessels during 21 and 12% oxygen breathing. In the first set of experiments, we measured apportionment of the blood flow between the two lungs by bronchospirometry and the krypton bolus method. In normal dogs, hypoxia did not shift blood flow systematically from one lung to the other. In 10 dogs with unilateral disease, general hypoxia increased the proportion of blood flow to the diseased lung. The mean percent of blood flow to the left lung in eight dogs with disease in that lung rose from 29% during air breathing to 32% (P < 0.001). In the second set of experiments, we measured apportionment of the blood flow between shunt pathways and gas-exchanging pathways by a constant infusion of radio-active krypton and the standard shunt formula. In eight dogs with bilateral disease, hypoxia consistently increased the flow through shunt pathways, from a mean value of 10% of pulmonary blood flow to 14% (P < 0.005).
Elevation of Receptor Tyrosine Kinases by Small Molecule AKT Inhibitors in Prostate Cancer Is Mediated by Pim-1
Authors: Bo Cen, Sandeep Mahajan, Wenxue Wang, Andrew S. Kraft
Journal: Cancer Research (2013)

The PI3K/AKT pathway is hyperactivated in prostate cancer but its effective therapeutic targeting has proven difficult. In particular, the antitumor activity of AKT inhibitors is attenuated by upregulation of receptor tyrosine kinases (RTK) through an uncharacterized feedback mechanism. In this report, we show that RNA interference-mediated silencing or pharmacologic inhibition of Pim-1 activity curtails AKT inhibitor-induced upregulation of RTKs in prostate cancer cells. Although Pim kinases have been implicated in cap-dependent translational control, we find that in the context of AKT inhibition, the expression of RTKs is controlled by Pim-1 in a cap-independent manner by controlling internal ribosome entry. Combination of Pim and AKT inhibitors resulted in synergistic inhibition of prostate tumor growth in vitro and in vivo. Together, our results show that Pim-1 mediates resistance to AKT inhibition and suggest its targeting to improve the efficacy of AKT inhibitors in anticancer therapy.
<i>CCR</i> 20th Anniversary Commentary: Setting the Stage for Nanoparticle Albumin-Bound Paclitaxel—How Far Science Has Come
Authors: Sami I. Bashour, Nuhad K. Ibrahim
Journal: Clinical Cancer Research (2015)

Abstract In this phase I pharmacokinetic study of ABI-007, which was published in the May 1, 2002, issue of Clinical Cancer Research, Ibrahim and colleagues provided the framework needed for subsequent studies to confirm the benefits of ABI-007 over solvent-based formulations. Since the study's publication, experiments have highlighted the importance of drug-delivery systems, the immune system in cancer biology, and immunoregulatory properties of taxane compounds. Clin Cancer Res; 21(9); 1975–7. ©2015 AACR. See related article by Ibrahim et al., Clin Cancer Res 2002;8(5) May 2002;1038–44
Prospective multicentre study on the evaluation of antituberculosis treatment results in Italy: comparison of the culture- versus the smear-based methods
Authors: G.B. Migliori, M. Ambrosetti, G Besozzi, L Casali, None M.C. Raviglione and the National Aipo “tuberculosis” Study Group
Journal: European Respiratory Journal (1999)

Cohort analysis of treatment outcomes is the most informative technique to evaluate the tuberculosis (TB) control programme. The aim of the study was to assess treatment outcomes comparing the smear- versus the culture-based methods, using data on TB patients treated under programme conditions in Italy. This was a prospective monitoring study based on the standardized collection of forms from a representative sample of Italian TB Units. The forms, with individual data, were reviewed and analysed on a quarterly basis according to the principles of cohort analysis, using both the smear- and culture-based methods. The complete bacteriological profile of patients was analysed at diagnosis and at completion of treatment. Nine hundred and ninety-two TB cases were notified. Among 681 pulmonary cases, 368 cases were culture-confirmed at diagnosis (333 new and 35 retreatment cases, 293 being sputum smear positive, 79.6%). At the end of treatment, out of the 333 new culture-confirmed cases, 136 (40.8%) were defined "cured" using the culture-based method and 108 (32.4%) using the smear-based method (p&lt;0.05, chi2 test). The culture-based method is the recommended tool to evaluate pulmonary tuberculosis treatment results. Culture allows a more precise definition of a "cured" patient in both sputum smear positive and negative tuberculosis cases.
Investigating the cellular composition of lymph nodes in preclinical and early inflammatory arthritis: a feasibility study
Authors: L G M van Baarsen, M J H de Hair, T H Ramwadhdoebe, M van de Sande, I J A J Zijlstra, M Maas, D M Gerlag, P P Tak
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease of unknown aetiology. To ultimately cure or prevent this chronic disease, it is critical to understand the earliest changes in the immune system that cause RA. Recent work has shown that systemic autoimmunity precedes inflammation in the synovium of RA patients. Animal models have suggested that changes in the lymph nodes may precede those in the synovial tissue. To provide insight into the immunological mechanisms involved in the pathogenesis of RA, the authors developed a method to obtain lymph node biopsies under local anaesthesia and investigated the lymph node cellular composition and distribution in individuals at risk of developing RA, early arthritis patients and healthy controls. <h3>Materials and methods</h3> Six individuals without any evidence of arthritis upon physical examination who were positive for IgM rheumatoid factor and/or anticitrullinated protein antibodies were included. For comparison 12 early arthritis patients (1× systemic lupus erythematosus, 1× psoriatic arthritis, 1× gout, 5× undifferentiated arthritis and 4× RA; disease duration &lt;1 year, disease-modifying antirheumatic drug naïve), and four autoantibody negative healthy controls without joint complaints were included in the study. All study subjects underwent ultrasound-guided inguinal lymph node biopsy. Different T lymphocyte subsets were analysed by multi-colour flow cytometry using labelled antibodies specific for CD3, CD4, CD8, CD45 and CD69. <h3>Results</h3> The procedure was well tolerated; no complications occurred. Different T cell subsets could be distinguished and differences between autoantibody positive individuals at risk of developing RA, early arthritis patients and healthy controls could be observed. Interim analysis indicate an increase of activated CD69+ T cells in the early arthritis as well as in the at risk group compared to the control group. Interestingly, the CD4/CD8 distribution within the activated T cells was significantly changed in the early arthritis patients compared to healthy controls and the same trend was observed for the at risk group. <h3>Conclusions</h3> Flow cytometry analysis of ultrasound-guided inguinal lymph node biopsies is a feasible method for investigating the cellular composition of lymph nodes in the earliest phases of inflammatory arthritis. These preliminary results suggest increased CD8+ T cell activation within lymph nodes of early arthritis patients as well as in autoantibody positive individuals at risk of developing RA. This method provides a unique tool to investigate the immunological changes in the lymph node compartment in the earliest phases of inflammatory arthritis. These data support the rationale for larger studies using more extensive panels of cellular markers.
Predicting the Optimal Basal Insulin Infusion Pattern in Children and Adolescents on Insulin Pumps
Authors: Paul-Martin Holterhus, Jessica Bokelmann, Felix Riepe, Bettina Heidtmann, Verena Wagner, Birgit Rami-Merhar, Thomas Kapellen, Klemens Raile, Wulf Quester, Reinhard W. Holl
Journal: Diabetes Care (2013)

OBJECTIVE We aimed at developing and cross-validating a mathematical prediction model for an optimal basal insulin infusion pattern for children with type 1 diabetes on continuous subcutaneous insulin infusion therapy (CSII). RESEARCH DESIGN AND METHODS We used the German/Austrian DPV-Wiss database for quality control and scientific surveys in pediatric diabetology and retrieved all CSII patients &amp;lt;20 years of age (November 2009). A total of 1,248 individuals from our previous study were excluded (dataset 1), resulting in 6,063 CSII patients (dataset 2) (mean age 10.6 ± 4.3 years). Only the most recent basal insulin infusion rates (BRs) were considered. BR patterns were identified and corresponding patients sorted by unsupervised clustering. Logistic regression analysis was applied to calculate the probabilities for each BR pattern. Equations were based on both independent datasets separately, and probabilities for BR patterns were cross-validated using typical test patients. RESULTS Of the 6,063 children, 5,903 clustered in one of four major circadian BR patterns, confirming our previous study. The oldest age-group (mean age 12.8 years) was represented by 2,490 patients (42.18%) with a biphasic dawn-dusk pattern (BC). A broad single insulin maximum at 9–10 p.m. (F) was unveiled by 853 patients (14.45%) (mean age 6.3 years). Logistic regression analysis revealed that age, to a lesser extent duration of diabetes, and partly sex predicted BR patterns. Cross-validation revealed almost identical probabilities for BR patterns BC and F in the two datasets but some variation in the remaining two BR patterns. CONCLUSIONS Reconfirmation of four key BR patterns in two very large independent cohorts supports that these patterns are realistic approximations of the circadian distribution of insulin needs in children with type 1 diabetes. Prediction of an optimal pattern a priori can improve initiation and clinical follow-up of CSII in children and adolescents. In addition, these BR patterns represent valuable information for insulin-infusion algorithms in closed-loop CSII.
WHO antenatal care randomised trial for the evaluation of a new model of routine antenatal care
Authors: José Villar, Hassan Ba'aqeel, Gilda Piaggio, Pisake Lumbiganon, José Miguel Belizán, Ubaldo Farnot, Yagob Al-Mazrou, Guillermo Carroli, Alain Pinol, Allan Donner, Ana Langer, Gustavo Nigenda, Miranda Mugford, Julia Fox-Rushby, Guy Hutton, Per Bergsjø, Leiv Bakketeig, Heinz Berendes
Journal: The Lancet (2001)
The Neurophysiological Features of Myoclonus-Dystonia and Differentiation From Other Dystonias
Authors: Traian Popa, Paolo Milani, Aliénor Richard, Cécile Hubsch, Vanessa Brochard, Christine Tranchant, Anna Sadnicka, John Rothwell, Marie Vidailhet, Sabine Meunier, Emmanuel Roze
Journal: JAMA Neurology (2014)

Myoclonus-dystonia (M-D) is a clinical syndrome characterized by a combination of myoclonic jerks and mild to moderate dystonia. The syndrome is related to ε-sarcoglycan (SGCE) gene mutations in about half the typical cases. Whether the M-D phenotype reflects a primary dysfunction of the cerebellothalamocortical pathway or of the striatopallidothalamocortical pathway is unclear. The exact role of an additional cortical dysfunction in the pathogenesis of M-D is also unknown.To clarify the neurophysiological features of M-D and discuss whether M-D due to SGCE deficiency differs from other primary dystonias.We studied a referred sample of 12 patients with M-D (mean [SD] age, 28.8 [6.2] years; age range, 19-38 years; 5 women) belonging to 11 unrelated families with a proven mutation or deletion of the SGCE gene and a group of 12 age- and sex-matched healthy control individuals. Every participant underwent 3 sessions exploring the excitability of the primary motor cortex, the response of the primary motor cortex to a plasticity-inducing protocol, and the cerebellar-dependent eye-blink classic conditioning (EBCC). The clinical evaluation of patients included the Unified Myoclonus Rating Scale and Burke-Fahn-Marsden Dystonia Rating Scale.Myoclonus-dystonia with a proven SGCE mutation.We measured resting and active motor thresholds, and short-interval intracortical inhibition and facilitation. The plasticity of the motor cortex was evaluated before and for 30 minutes after 600 pulses of rapid paired associative stimulation. The cerebellar functioning was evaluated with the number of conditioned responses during the 6 blocks of EBCC and 1 extinction block. All data were compared between the 2 groups. For patients, correlations were explored between electrophysiological data and clinical scores.We found lower membrane excitability of the corticocortical axons and normal intracortical γ-aminobutyric acid inhibition in contrast with what has been described in other forms of primary dystonia. Myoclonus-dystonia patients also shared some common pathophysiological features of dystonia, including enhanced responsiveness of the motor cortex to plasticity induction and abnormal response to cerebellar conditioning as tested by EBCC.Specific underlying dysfunctions are associated with the very particular clinical phenotype of M-D and make it a unique entity that stands apart from other primary dystonias.
Surgical Quality Measurement
Authors: Ryan P. Merkow, Karl Y. Bilimoria, Clifford Y. Ko
Journal: JAMA Surgery (2013)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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 Surgery journal
Safety and efficacy of exercise training in various forms of pulmonary hypertension
Authors: Ekkehard Grünig, Mona Lichtblau, Nicola Ehlken, Hossein A. Ghofrani, Frank Reichenberger, Gerd Staehler, Michael Halank, Christine Fischer, Hans-Jürgen Seyfarth, Hans Klose, Andreas Meyer, Stephan Sorichter, Heinrike Wilkens, Stephan Rosenkranz, Christian Opitz, Hanno Leuchte, Gabriele Karger, Rudolf Speich, Christian Nagel
Journal: European Respiratory Journal (2012)

The objective of this prospective study was to assess safety and efficacy of exercise training in a large cohort of patients with different forms and World Health Organization (WHO) functional classes of chronic pulmonary hypertension (PH). 183 patients with PH (pulmonary arterial hypertension (PAH), chronic thromboembolic PH and PH due to respiratory or left heart diseases received exercise training in hospital for 3 weeks and continued at home. Adverse events have been monitored during the in-hospital training programme. Efficacy parameters were evaluated at baseline, and after 3 and 15 weeks. After 3 and 15 weeks, patients significantly improved the distance walked in 6 min (6MWD) compared to baseline, scores of quality of life, WHO functional class, peak oxygen consumption, oxygen pulse, heart rate and systolic pulmonary artery pressure at rest and maximal workload. The improvement in 6MWD was similar in patients with different PH forms and functional classes. Even in severely affected patients (WHO functional class IV), exercise training was highly effective. Adverse events, such as respiratory infections, syncope or presyncope, occurred in 13% of patients. Exercise training in PH is an effective but not a completely harmless add-on therapy, even in severely diseased patients, and should be closely monitored.
Is there a local renin–angiotensin system in the heart?
Authors: A Danser
Journal: Cardiovascular Research (1999)

The existence of a local renin—angiotensin system in the heart is still a controversial issue. This review discusses the evidence, obtained from studies in cardiac cells, in isolated perfused hearts and in intact animals and humans, both under normal and pathological conditions, for local production of prorenin, renin, angiotensinogen, angiotensin-converting enzyme, angiotensin I and angiotensin II at cardiac tissue sites. In addition, the role of alternative angiotensin-generating enzymes (cathepsin, chymase) and the possibility of (pro)renin uptake from the circulation is evaluated.
Inflammation in Atherosclerosis
Authors: Jun-o Deguchi, Masanori Aikawa, Ching-Hsuan Tung, Elena Aikawa, Dong-Eog Kim, Vasilis Ntziachristos, Ralph Weissleder, Peter Libby
Journal: Circulation (2006)

Background— Matrix metalloproteinases (MMPs) in inflamed atherosclerotic plaques may contribute to extracellular matrix remodeling and the onset of acute thrombotic complications. Methods and Results— To test the hypothesis that optical molecular imaging with the use of an activatable near-infrared fluorescence (NIRF) probe can detect enzymatic action of MMP in atherosclerotic plaques, we used a NIRF substrate for gelatinases (MMP-2/gelatinase-A and MMP-9/gelatinase-B) in apolipoprotein E–deficient (apoE −/− ) mice that consumed a high-cholesterol diet for 12 weeks and age-matched apoE +/+ mice as control. The aortas of apoE −/− mice at 24 hours after probe yielded intense NIRF signals, as detected by NIRF reflectance ex vivo, compared with negligible signals in aortas of apoE +/+ mice with/without probe administration or atherosclerotic apoE −/− aortas without probe. Gelatinase inhibitor treatment abolished NIRF signals in apoE −/− mouse aortas ex vivo. Sites of gelatinase activity visualized by NIRF colocalized with macrophage accumulation, immunoreactive MMP-2 and MMP-9, and gelatinolytic activity detected by in situ zymography. Furthermore, fluorescence molecular tomography indicated in vivo that atherosclerotic aortas of apoE −/− mice produced NIRF signals for gelatinase action, whereas aortas of apoE +/+ mice injected with the probe or apoE −/− aortas with no probe exhibited negligible NIRF signals. Conclusions— These results suggest the feasibility of noninvasively imaging the enzymatic action of MMPs in vivo, an approach that may gauge inflammatory foci in atherosclerosis, assess cardiovascular risk, and evaluate the effects of therapeutic interventions.
Permselectivity of the Glomerular Capillary Wall
Authors: Michael P. Bohrer, Christine Baylis, H. David Humes, Richard J. Glassock, Channing R. Robertson, Barry M. Brenner
Journal: Journal of Clinical Investigation (1978)

To examine the electrostatic effects of fixed negative charges on the glomerular capillary wall, polydisperse [3H]DEAE dextran, a polycationic form of dextran, was infused into 10 Munich-Wistar rats. Fractional clearances of DEAE ranging in radius from 18 to 44Å were determined in these rats, together with direct measurements of the forces and flows governing the glomerular filtration rate of water. These results were compared with data previously obtained in Munich-Wistar rats receiving tritiated neutral dextran (D) and polyanionic dextran sulfate (DS). Measured values for the determinants of the glomerular filtration rate of water in rats given DEAE were found to be essentially identical to those in rats given either D or DS. In addition, DEAE was shown to be neither secreted nor reabsorbed. Fractional clearances of polycationic DEAE were increased relative to both D and DS, the increase relative to D being significant for effective molecular radii ranging from 24 to 44Å.