tbuckley/cabot-search huggingface dataset:
Expiratory flow limitation detected by forced oscillation and negative expiratory pressure
Authors: R. L. Dellacà, N. Duffy, P. P. Pompilio, A. Aliverti, N. G. Koulouris, A. Pedotti, P. M. A. Calverley
Journal: European Respiratory Journal (2006)

The within-breath change in reactance (Δ X̄ rs ) measured by forced oscillation technique (FOT) at 5 Hz reliably detects expiratory flow limitation in chronic obstructive pulmonary disease (COPD). The present study compared this approach to the standard negative expiratory pressure (NEP) method. In total, 21 COPD patients were studied by applying both techniques to the same breath and in 15 patients the measurements were repeated after bronchodilator. For each patient and condition five NEP tests were performed and independently scored by three operators unaware of the FOT results. In 180 tests, FOT classified 53.3% as flow limited. On average, the operators scored 27.6% of tests flow limited and 47.6% non-flow limited, but could not score 24.8%. The methods disagreed in 7.9% of cases; in 78% of these the NEP scores differed between operators. Bronchodilation reduced NEP and Δ X̄ rs scores, with only the latter achieving significance. Averaging the operators′ NEP scores, a threshold between 24.6–30.8% of tidal volume being flow limited by NEP produced 94% agreement between methods. In conclusion, when negative expiratory pressure and forced oscillation technique were both available they showed good agreement. As forced oscillation technique is automatic and can measure multiple breaths over long periods, it is suitable for monitoring expiratory flow limitation continuously and identifying patients′ breathing close to the onset of expiratory flow limitation, where intermittent sampling may be unrepresentative.
Primary Role for GI Protein Signaling in the Regulation of Interleukin 12 Production and the Induction of T Helper Cell Type 1 Responses
Authors: Jianping He, Sanjay Gurunathan, Akiko Iwasaki, Belinda Ash-Shaheed, Brian L. Kelsall
Journal: The Journal of Experimental Medicine (2000)

We explored the role of Gi protein signaling in the regulation of interleukin (IL)-12 production and T helper cell type 1 (Th1) T cell differentiation. In initial studies, we showed that treatment of normal mice with pertussis toxin (PT), which inhibits Gi protein signaling, enhanced the capacity of splenocytes to produce IL-12 in response to both microbial and nonmicrobial stimuli. In addition, PT treatment increased the production of tumor necrosis factor (TNF)-alpha and IL-10 by stimulated cells. These findings were corroborated by the fact that untreated Gi2alpha(2/-) mice exhibited enhanced production of IL-12 and TNF-alpha by splenocytes, and of IL-12 p40 by purified spleen CD8alpha(+) lymphoid dendritic cells. Finally, we showed that while normal BALB/c mice infected with Leishmania major exhibited a nonhealing phenotype, those treated with PT when infection was initiated exhibited a healing phenotype along with an enhancement of leishmania-specific Th1 responses in draining lymph nodes. Further, healing was prevented by coadministration of anti-IL-12 and PT. These data demonstrate that endogenous Gi protein signaling has a primary role in the regulation of IL-12 production and the induction of Th1 responses in vivo.
Association Between Insulin Resistance (Ir) and Pathologic Complete Response (Pcr) to Neoadjuvant Chemotherapy (Nac) Among No Diabetic Women with Localized Infiltrating Breast Cancer (Libc)
Authors: A. Armengol-Alonso, I. Tusquets, S. Servitja, L. Fernández-Morales, M.A. Segui-Palmer, M. Campayo, X. González-Farré, P.L. Fernández, P. Gascón, M. Muñoz
Journal: Annals of Oncology (2014)
Therapy of Digestive Disorders
Authors: R N ALLAN
Journal: Gut (2000)

Therapy of Digestive Disorders . Edited by Wolfe MM, Cohen S, Davis GL, et al . (Pp 881; hardback; illustrated; £85.) Philadelphia: WB Saunders, 1999. ISBN 0 72167 340 6.

This is a substantial book edited by Dr Michael Wolfe with six of his colleagues acting as section editors. Many of the hundred or so contributors are members of the Boston home team. The others are from the key centres in North America with a smattering of contributors from Canada, Europe, Israel, and South America. This is in effect a GI textbook, but stripped largely of pathogenesis, pathophysiology, diagnosis, and differential diagnosis. Five …
Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance
Authors: José F Caro, Jerzy W Kolaczynski, Mark R Nyce, Joanna P Ohannesian, Irina Opentanova, Warren H Goldman, Richard B Lynn, Pei-Li Zhang, Madhur K Sinha, Robert V Considine
Journal: The Lancet (1996)
Histoplasmosis: A review, and account of three patients diagnosed in Great Britain
Authors: W. M. Macleod, I. G. Murray, J. Davidson, D. D. Gibbs
Journal: Thorax (1972)

Active histoplasmosis is rarely diagnosed in Great Britain. We present the illness records of three patients with disseminated histoplasmosis. In two patients the infection was discovered at necropsy and resulted in caseous destruction of the adrenal glands, and in one of these there was also fungal invasion of the liver and wall of the aorta. The third patient had Addison9s disease and also a chronic tongue ulcer from which the fungus was cultured by biopsy. The eight other patients with disseminated histoplasmosis and the six with active localized disease previously reported in Great Britain are reviewed. The natural history of the disease, with emphasis on the prolonged incubation period of up to 18 years, is described. Granulomatous ulceration of the oropharynx and larynx and caseous destruction of the adrenal glands may be characteristic features. Diagnosis usually requires a history of a stay in endemic regions. It is suggested by the clinical picture and positive complement fixation or precipitin tests and it is confirmed by culture of the fungus which may also be recognized in histological preparations. Histoplasmin skin tests are usually negative. Standard treatment is with intravenous amphotericin B, but in our surviving patient a chronic tongue ulcer of nine years9 duration showed considerable healing after 10 months9 oral treatment with trimethoprim-sulphamethoxazole in combination.
Apolipoprotein A-I Mimetic Peptide 4F Rescues Pulmonary Hypertension by Inducing MicroRNA-193-3p
Authors: Salil Sharma, Soban Umar, Francois Potus, Andrea Iorga, Gabriel Wong, David Meriwether, Sandra Breuils-Bonnet, Denise Mai, Kaveh Navab, David Ross, Mohamad Navab, Steeve Provencher, Alan M. Fogelman, Sébastien Bonnet, Srinivasa T. Reddy, Mansoureh Eghbali
Journal: Circulation (2014)

Background— Pulmonary arterial hypertension is a chronic lung disease associated with severe pulmonary vascular changes. A pathogenic role of oxidized lipids such as hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids is well established in vascular disease. Apolipoprotein A-I mimetic peptides, including 4F, have been reported to reduce levels of these oxidized lipids and improve vascular disease. However, the role of oxidized lipids in the progression of pulmonary arterial hypertension and the therapeutic action of 4F in pulmonary arterial hypertension are not well established. Methods and Results— We studied 2 different rodent models of pulmonary hypertension (PH): a monocrotaline rat model and a hypoxia mouse model. Plasma levels of hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids were significantly elevated in PH. 4F treatment reduced these levels and rescued preexisting PH in both models. MicroRNA analysis revealed that microRNA-193-3p (miR193) was significantly downregulated in the lung tissue and serum from both patients with pulmonary arterial hypertension and rodents with PH. In vivo miR193 overexpression in the lungs rescued preexisting PH and resulted in downregulation of lipoxygenases and insulin-like growth factor-1 receptor. 4F restored PH-induced miR193 expression via transcription factor retinoid X receptor α. Conclusions— These studies establish the importance of microRNAs as downstream effectors of an apolipoprotein A-I mimetic peptide in the rescue of PH and suggest that treatment with apolipoprotein A-I mimetic peptides or miR193 may have therapeutic value.
Optimizing Reproductive Outcome in Children and Young People With Cancer
Authors: W. Hamish B. Wallace, Hilary O.D. Critchley, Richard A. Anderson
Journal: Journal of Clinical Oncology (2011)

tomy, but Goodwin et al did not report on the effect of oophorectomy on breast cancer mortality. In summary, limited data are emerging from this article and from others that the treatment choices for women with breast cancer may depend to a significant extent on whether or not they carry a BRCA mutation. This suggests that we might test all patients with breast cancer soon after diagnosis, but the test is currently expensive. For now, perhaps the simplest recommendation is to test women under age 50 years with triple-negative breast cancer and women with a family history of early-onset breast cancer or ovarian cancer. In the future, when costs of genetic sequencing decline, it may be reasonable to test all patients with breast cancer before treatment.
Reperfusion after brief ischemia disrupts the microtubule network in canine hearts.
Authors: H Sato, M Hori, M Kitakaze, K Iwai, S Takashima, H Kurihara, M Inoue, T Kamada
Journal: Circulation Research (1993)

Histological changes in the stunned myocardium are believed to be minimal. This study examined whether cytoskeletal structures of microtubules are disrupted in the stunned myocardium. In 38 dogs, the left anterior descending coronary artery was occluded for 15 minutes and reperfused to produce the stunned myocardium. Microtubules were stained immunohistochemically. In intact myocardium, microtubules appeared as a filamentous network throughout the cytoplasm and encircled the nucleus. This pattern was not affected by 15 minutes of ischemia. One hour of reperfusion, however, disrupted microtubular structure substantially (disruption score in the endocardium, 53.4 +/- 6.0%) although actin filaments remained intact. Microtubular structures were reconstituted 1-3 days after reperfusion, showing supernormal immunoreactivity. Five days after reperfusion, the pattern of microtubular staining was normal. In another protocol, the role of Ca2+ during reperfusion in microtubular disruption was examined. When intracoronary infusion of EDTA (1.67 mumol/kg body wt per minute) was performed during the initial 10 minutes of reperfusion, myocardial stunning was attenuated. The fractional shortening in the perfused area after 1 hour of reperfusion was 20.1 +/- 1.2% versus 11.5 +/- 0.5% in the control condition (p &lt; 0.05), and the microtubular disruption score was lower (12.6 +/- 1.4%). Although intracoronary infusion of calcium chloride (9 mumol/kg body wt per minute) for 10 minutes in nonischemic hearts increased contractile function (fractional shortening, 25.3 +/- 2.0%), it severely disrupted microtubular networks (microtubular disruption score, 64.0 +/- 10.6%). We conclude that microtubules supporting the structural integrity of myofibrils and other organelles are reversibly disrupted by reperfusion after brief ischemia probably through calcium overload.
Impact of Physical Activity on Cancer Recurrence and Survival in Patients With Stage III Colon Cancer: Findings From CALGB 89803
Authors: Jeffrey A. Meyerhardt, Denise Heseltine, Donna Niedzwiecki, Donna Hollis, Leonard B. Saltz, Robert J. Mayer, James Thomas, Heidi Nelson, Renaud Whittom, Alexander Hantel, Richard L. Schilsky, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2006)

Regular physical activity reduces the risk of developing colon cancer, however, its influence on patients with established disease is unknown.We conducted a prospective observational study of 832 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial. Patients reported on various recreational physical activities approximately 6 months after completion of therapy and were observed for recurrence or death. To minimize bias by occult recurrence, we excluded patients who experienced recurrence or died within 90 days of their physical activity assessment.Compared with patients engaged in less than three metabolic equivalent task (MET) -hours per week of physical activity, the adjusted hazard ratio for disease-free survival was 0.51 (95% CI, 0.26 to 0.97) for 18 to 26.9 MET-hours per week and 0.55 (95% CI, 0.33 to 0.91) for 27 or more MET-hours per week. The adjusted P for trend was .01. Postdiagnosis activity was associated with similar improvements in recurrence-free survival (P for trend = .03) and overall survival (P for trend = .01). The benefit associated with physical activity was not significantly modified by sex, body mass index, number of positive lymph nodes, age, baseline performance status, or chemotherapy received. Moreover, the benefit remained unchanged even after excluding participants who developed cancer recurrence or died within 6 months of activity assessment.Beyond surgical resection and postoperative adjuvant chemotherapy for stage III colon cancer, for patients who survive and are recurrence free approximately 6 months after adjuvant chemotherapy, physical activity appears to reduce the risk of cancer recurrence and mortality.
The irrelevance of the psychophysical argument
Authors: Carl Simpson
Journal: Behavioral and Brain Sciences (1997)

The longevity of the Berlin and Kay theses results from the way in which they were formulated, contrasted with extreme relativism. Saunders &amp; van Brakel need not reject colour opponency to reject universal colour categories. Colour opponency does not manifest itself in language, even when dealing directly with spectral colours.
Therapeutic Targeting of TLR9 Inhibits Cell Growth and Induces Apoptosis in Neuroblastoma
Authors: Chiara Brignole, Danilo Marimpietri, Daniela Di Paolo, Patrizia Perri, Fabio Morandi, Fabio Pastorino, Alessia Zorzoli, Gabriella Pagnan, Monica Loi, Irene Caffa, Giovanni Erminio, Riccardo Haupt, Claudio Gambini, Vito Pistoia, Mirco Ponzoni
Journal: Cancer Research (2010)

The Toll-like receptor 9 (TLR9) evolved to cope with pathogens, but it is expressed in a variety of tumors for reasons that are unclear. In this study, we report that neuroblastoma (NB) cells express functional TLR9. Liposome-complexed CpG oligonucleotides inhibited the proliferation of TLR9-expressing NB cells and induced caspase-dependent apoptotic cell death. Inhibitory oligonucleotides (iODNs) abrogated these effects. RNA interference reduced TLR9 expression but not to the level where functional responses to CpG were abolished. Compared with free CpG, liposomal formulations of NB-targeted CpG (TL-CpG) significantly prolonged the survival of mice bearing NB tumor xenografts. While CpG alone lacked antitumor efficacy in NOD/SCID/IL2rg(-/-) mice, TL-CpG retained significant efficacy related to direct effects on tumor cells. TLR9 expression in primary human NB specimens was found to correlate inversely with disease stage. Our findings establish functional expression of TLR9 in NB and suggest that TLR9 may represent a novel theranostic target in this disease.
New directions for protecting the heart against ischaemia–reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway
Authors: D Hausenloy
Journal: Cardiovascular Research (2003)

Reperfusion is a pre-requisite to salvaging viable myocardium, following an acute myocardial infarction. Reperfusion of ischaemic myocardium, however, is not without risk, as the act of reperfusion itself can paradoxically result in myocyte death: a phenomenon termed lethal reperfusion-induced injury. Therapeutic strategies that target and attenuate reperfusion-induced cell death may provide novel pharmacological agents, which can be used as an adjunct to current reperfusion therapy, to limit myocardial infarction. Recent evidence has implicated apoptotic cell death during the phase of reperfusion as an important contributor to lethal reperfusion-induced injury. Targeting anti-apoptotic mechanisms of cellular protection at the time of reperfusion may therefore offer a potential approach to attenuating reperfusion-induced cell death. In this regard, ischaemia–reperfusion has been shown to activate the anti-apoptotic pro-survival kinase signalling cascades, phosphatidylinositol-3-OH kinase (PI3K)–Akt and p42/p44 extra-cellular signal-regulated kinases (Erk 1/2), both of which have been implicated in cellular survival. Activating these pro-survival kinase cascades at the time of reperfusion has been demonstrated to confer protection against reperfusion-induced injury. We and others have shown that insulin, insulin-like growth factor-1 (IGF-1), transforming growth factor-β1 (TGF-β1), cardiotrophin-1 (CT-1), urocortin, atorvastatin and bradykinin protect the heart, by activating the PI3K–Akt and/or Erk 1/2 kinase cascades, when given at the commencement of reperfusion, following a lethal ischaemic insult. Pharmacological manipulation and up-regulation of these pro-survival kinase cascades, which we refer to as the Reperfusion Injury Salvage Kinase (RISK) pathway, as an adjunct to reperfusion may therefore protect the myocardium from lethal reperfusion-induced cell death and provide a novel strategy to salvaging viable myocardium and limiting infarct size.
Effect of left atrial filling pressure on the activity of specific myosin isozymes in rat heart.
Authors: N S Kato, A Weisberg, S Winegrad
Journal: Circulation Research (1991)

One of the fundamental properties of cardiac muscle is the increase in force generated and work performed with a rise in the resting length of the tissue. There are data to indicate that length-dependent responses of electromechanical coupling and calcium binding by troponin are part of the basis for the pressure-volume relation in the heart. In this study, the contribution of changes in the functional properties of the contractile proteins independent of modification in electromechanical coupling has been examined. Isolated working hearts containing either a mixture of myosin heavy chain (MHC) isozymes (alpha[fast] and beta [slow]) or exclusively the fast MHC have been subjected to left atrial filling pressures (LAPs) between 5 and 20 cm H2O. After 40 minutes at a given LAP, the heart was quickly frozen. The relative activities of calcium- and actin-activated ATPase of V1 and V3 myosin, containing alpha- and beta-MHC, were measured in cryostatic sections of the heart by quantitative histochemistry under conditions for which the concentration of calcium would not be limiting. In hearts containing both isozymes of myosin, the relative enzymatic activity of each isozyme of myosin varied with LAP. At low LAP, V1 was primarily responsible for the enzymatic activity, but as LAP increased the relative contribution of V1 decreased and that of V3 increased. The change in the calcium- and actin-activated activities of the enzyme with change in LAP occurred within 5 minutes and was reversible. In spite of the apparent substitution of enzymatic activity of V3 for V1, total myosin ATPase activity did not decline, but instead remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)
Fatty Acid Oxidation and Malonyl-CoA Decarboxylase in the Vascular Remodeling of Pulmonary Hypertension
Authors: Gopinath Sutendra, Sebastien Bonnet, Gael Rochefort, Alois Haromy, Karalyn D. Folmes, Gary D. Lopaschuk, Jason R. B. Dyck, Evangelos D. Michelakis
Journal: Science Translational Medicine (2010)

The overgrowth of vascular cells that causes pulmonary hypertension can be prevented in mice by inhibiting a metabolic shift toward glycolysis.
Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: results of a randomised placebo-controlled trial (ABILITY-1)
Authors: Joachim Sieper, Désirée van der Heijde, Maxime Dougados, Philip J Mease, Walter P Maksymowych, Matthew A Brown, Vipin Arora, Aileen L Pangan
Journal: Annals of the Rheumatic Diseases (2012)

Purpose To evaluate the efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis (nr-axSpA). Methods Patients fulfilled Assessment of Spondyloarthritis international Society (ASAS) criteria for axial spondyloarthritis, had a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥ 4, total back pain score of ≥ 4 (10 cm visual analogue scale) and inadequate response, intolerance or contraindication to non-steroidal anti-inflammatory drugs (NSAIDs); patients fulfilling modified New York criteria for ankylosing spondylitis were excluded. Patients were randomised to adalimumab (N=91) or placebo (N=94). The primary endpoint was the percentage of patients achieving ASAS40 at week 12. Efficacy assessments included BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS). MRI was performed at baseline and week 12 and scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) index. Results Significantly more patients in the adalimumab group achieved ASAS40 at week 12 compared with patients in the placebo group (36% vs 15%, p&lt;0.001). Significant clinical improvements based on other ASAS responses, ASDAS and BASDAI were also detected at week 12 with adalimumab treatment, as were improvements in quality of life measures. Inflammation in the spine and sacroiliac joints on MRI significantly decreased after 12 weeks of adalimumab treatment. Shorter disease duration, younger age, elevated baseline C-reactive protein or higher SPARCC MRI sacroiliac joint scores were associated with better week 12 responses to adalimumab. The safety profile was consistent with what is known for adalimumab in ankylosing spondylitis and other diseases. Conclusions In patients with nr-axSpA, adalimumab treatment resulted in effective control of disease activity, decreased inflammation and improved quality of life compared with placebo. Results from ABILITY-1 suggest that adalimumab has a positive benefit–risk profile in active nr-axSpA patients with inadequate response to NSAIDs.
Insulin infusion in acute illness
Authors: P. Dandona
Journal: Journal of Clinical Investigation (2005)

The discovery of the antiinflammatory effect of insulin and the proinflammatory effect of glucose has not only provided novel insight into the mechanisms underlying several disease states but has also provided a rationale for the treatment of hyperglycemia in several acute clinical conditions. Van den Berghe et al. previously showed the benefits of intensive glycemic control with insulin in patients admitted to intensive care units. In this issue of the JCI, the same group of investigators now demonstrates that infusion of insulin to restore euglycemia in these patients results in a marked reduction in inflammatory indices such as adhesion molecules, hepatic iNOS, and plasma NO metabolites. The reduction in the mediators of inflammation may thus be responsible for the impressive improvement in clinical outcomes following insulin therapy, and the results suggest a new paradigm in which glucose and insulin are related not only through their metabolic actions but also through their opposite effects on inflammatory mechanisms.