tbuckley/cabot-search huggingface dataset:
Hyperreactivity of coronary arterial smooth muscles in response to ergonovine from rabbits with hereditary hyperlipidemia.
Authors: M Yokoyama, H Akita, T Mizutani, H Fukuzaki, Y Watanabe
Journal: Circulation Research (1983)

This study was undertaken to examine the response to ergonovine, an agent used to provoke spastic constriction of large epicardial coronary arteries, to elucidate the responsible underlying mechanism, and to determine the impact of endogenous hyperlipidemia on contractile properties of isolated vessels from different beds. The isolated arteries from both control and Watanabe hereditary hyperlipidemic rabbits (WHHL rabbits) were suspended for recording isometric force in oxygenated Krebs buffer and exposed to agonists and antagonists. In atherosclerotic aortas from WHHL rabbits, the concentration-response relations for ergonovine and serotonin exhibited a marked leftward shift with significantly depressed constrictor threshold concentration and lowered one-half maximally effective concentration values. In coronary arteries with no atherosclerotic lesions detectable macroscopically from WHHL rabbits, the concentration-response relations showed a leftward shift for ergonovine but not serotonin. Coronary contraction evoked by ergonovine was remarkably inhibited by 0.1 microM cyproheptadine and 0.3 microM methysergide, serotonergic antagonists, in both groups. alpha-Adrenergic blockade with 0.1 microM prazosin was effective in inhibiting ergonovine-induced contraction of aortas from control rabbits, but not that of atherosclerotic ones. The constrictor response to ergonovine of atherosclerotic aortas was inhibited by cyproheptadine. The responsiveness to ergonovine of both carotid and femoral arteries from WHHL rabbits with no sclerotic lesions, which was suppressed by prazosin was not different from that of control rabbits. In contrast, the concentration-response relations for phenylephrine in the four different types of arteries did not differ appreciably between the two groups, and the constrictor responses to 20 mM KCl were virtually identical. Thus, aortas and coronary arteries exposed to endogenous hyperlipidemia appear to be hyperreactive to ergonovine mediated by a serotonergic mechanism.
Significance of Ventricular Myocytes and Nonmyocytes Interaction During Cardiocyte Hypertrophy
Authors: Masaki Harada, Hiroshi Itoh, Osamu Nakagawa, Yoshihiro Ogawa, Yoshihiro Miyamoto, Koichiro Kuwahara, Emiko Ogawa, Toshio Igaki, Jun Yamashita, Izuru Masuda, Takaaki Yoshimasa, Issei Tanaka, Yoshihiko Saito, Kazuwa Nakao
Journal: Circulation (1997)

Background In cardiac hypertrophy, both excessive enlargement of cardiac myocytes and progressive interstitial fibrosis are well known to occur simultaneously. In the present study, to investigate the interaction between ventricular myocytes (MCs) and cardiac nonmyocytes (NMCs), mostly fibroblasts, during cardiocytes hypertrophy, we examined the change in cell size and gene expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in cultured MCs as markers for hypertrophy in the neonatal rat ventricular cardiac cell culture system. Methods and Results The size of cultured MCs significantly increased in the MC-NMC coculture. Concomitantly, secretions of ANP and BNP into culture media were significantly increased in the MC-NMC coculture compared with in the MC culture (with the possible contamination of NMC &lt;1% of MC). Moreover, in the MC culture, enlargement of MC and an increase in ANP and BNP secretions were induced by treatment with conditioned media of the NMC culture. A considerable amount of endothelin (ET)-1 production was detected in the NMC-conditioned media. BQ-123, an ET-A receptor antagonist, and bosentan, a nonselective ET receptor antagonist, significantly blocked the hypertrophic response of MCs induced by treatment with NMC-conditioned media. Angiotensin II (Ang II) (10 −10 to 10 −6 mol/L) and transforming growth factor-β1 (TGF-β1) (10 −13 to 10 −9 mol/L), both of which are known to be cardiac hypertrophic factors, did not induce hypertrophy in MC culture, but both Ang II and TGF-β1 increased the size of MCs and augmented ANP and BNP productions in the MC-NMC coculture. This hypertrophic activity of Ang II and TGF-β1 was associated with the potentiation of ET-1 production in the MC-NMC coculture, and the effect of Ang II or TGF-β1 on the secretions of ANP and BNP in the coculture was significantly suppressed by pretreatment with BQ-123. Conclusions These results demonstrate that NMCs regulate MC hypertrophy at least partially via ET-1 secretion and that the interaction between MCs and NMCs plays a critical role during the process of Ang II–or TGF-β1–induced cardiocyte hypertrophy.
Pathology of intestinal tuberculosis and its distinction from Crohn's disease
Authors: H. D. Tandon, A. Prakash
Journal: Gut (1972)

Intestinal lesions of 212 cases presenting with symptoms of intestinal obstruction were studied. Of these, 159 cases were diagnosed as tuberculosis and 10 as Crohn's disease. Forty-three cases could not be classified into any of these entities and are excluded from this account. The amount of chemotherapeutic drugs received by each patient preoperatively was recorded. Cases proved as tuberculosis at the first operation were put on antituberculosis chemotherapy. Thirteen of these cases were operated on a second time, and tissue reactions under the influence of chemotherapy were studied. Fresh diseased tissue was studied for acid-fast organisms by culture and animal inoculation.Morphological features of the tuberculosis group are described in detail. Although the cases were broadly classified into the ulcerative and ulcerohypertrophic varieties, a distinction was not always sharp and the two types of lesions were at times found to coexist. The macroscopic features presented a very wide range, and at times distinction from Crohn's disease, especially in the ulcerohypertrophic variety, was difficult. Microscopically, however, they could be distinguished without much difficulty. Caseation, although a characteristic feature of tuberculous granulomas may, albeit rarely, be absent. Granulomas which are characteristically confluent may be present only in the mesenteric lymph nodes. Acid-fast organisms are not grown consistently from diseased tissues; where grown, they are of human type. Reparative changes during chemotherapy are described in detail; these follow a non-specific pattern. In the group of Crohn's disease, transmural cracks and fissures were consistently observed in all cases. Distinguishing features between the two diseases are discussed in detail.
The Ethics of Using Quality Improvement Methods in Health Care
Authors: Joanne Lynn
Journal: Annals of Internal Medicine (2007)

Quality improvement (QI) activities can improve health care but must be conducted ethically. The Hastings Center convened leaders and scholars to address ethical requirements for QI and their relationship to regulations protecting human subjects of research. The group defined QI as systematic, data-guided activities designed to bring about immediate improvements in health care delivery in particular settings and concluded that QI is an intrinsic part of normal health care operations. Both clinicians and patients have an ethical responsibility to participate in QI, provided that it complies with specified ethical requirements. Most QI activities are not human subjects research and should not undergo review by an institutional review board; rather, appropriately calibrated supervision of QI activities should be part of professional supervision of clinical practice. The group formulated a framework that would use key characteristics of a project and its context to categorize it as QI, human subjects research, or both, with the potential of a customized institutional review board process for the overlap category. The group recommended a period of innovation and evaluation to refine the framework for ethical conduct of QI and to integrate that framework into clinical practice.
Designing Transformative Clinical Trials in the Cancer Genome Era
Authors: Stefan Sleijfer, Jan Bogaerts, Lillian L. Siu
Journal: Journal of Clinical Oncology (2013)

The incorporation of molecular profiling into routine clinical practice has already been adopted in some tumor types, such as human epidermal growth factor receptor 2 (HER2) testing in breast cancer and KRAS genotyping in colorectal cancer, providing a guide to treatment selection that is not afforded by histopathologic diagnosis alone. It is inevitable that over time, with rapid advances in scientific knowledge, bioinformatics, and technology to identify oncogenic drivers, molecular profiling will complement histopathologic data to influence management decisions. Emerging technologies such as multiplexed somatic mutation genotyping and massive parallel genomic sequencing have become increasingly feasible at point-of-care locations to classify cancers into molecular subsets. Because these molecular subsets may differ substantially between each other in terms of sensitivity or resistance to systemic agents, there is consensus that clinical trials should be more stratified for or be performed only in such molecularly defined subsets. This approach, however, poses challenges for clinical trial designs because smaller numbers of patients would be eligible for such trials, while the number of novel anticancer drugs warranting further clinical exploration is rapidly increasing. This article provides an overview of the emerging methodologic challenges in the cancer genome era and offers some potential solutions for transforming clinical trial designs so they can identify new active anticancer regimens in molecularly defined subgroups as efficiently as possible.
Myeloid dendritic cells are primed in allergic asthma for thymic stromal lymphopoietin-mediated induction of Th2 and Th9 responses
Authors: A. Froidure, C. Shen, D. Gras, J. Van Snick, P. Chanez, C. Pilette
Journal: Allergy (2014)

Background Type 1 myeloid dendritic cells (mDCs) contribute to inception of allergic asthma (AA) and are regulated by epithelial-derived cytokines. Objectives To evaluate whether mDCs from AA patients are primed for thymic stromal lymphopoietin (TSLP)-driven responses. Methods mDCs from 18 AA patients and 15 controls were purified using immunomagnetic sorting. Cells were pulsed with TSLP or Dermatophagoides pteronyssinus (Der p) allergen, before FACS phenotyping and co-culture with allogeneic CD4+ T cells. Bronchial biopsies from 15 AA patients and four controls were immunostained for CD1c and TSLP receptor (TSLPR). Results Allergic asthma patients had a higher proportion of TSLPR+ mDCs, in blood and bronchial mucosa. When compared to mDCs from controls, both TSLP- and Der p-pulsed blood mDCs from AA patients induced increased polarization of CD4+ T cells into Th2 cells (IL-5, IL-13, and GATA3+), while only TSLP-mDCs promoted Th9 cells (IL-9 and PU.1+/IRF4+). In addition, OX40L was induced upon TSLP stimulation and was required for the induction of Th2, but not Th9, cells. In contrast, development of Th9 cells in this model depended on TGF-β1. Conclusions Our data indicate overlapping but partially distinct effects of TSLP and Der p allergen pathways, showing that DCs are primed in human asthma for TSLP-driven induction of both Th2 and Th9 cells. This novel TSLP/mDC/Th9 axis operates through a distinct, OX40L-independent pathway. These data further highlight the TSLP pathway as a relevant target in human asthma.
The anxious amygdala: CREB signaling and predisposition to anxiety and alcoholism
Authors: G. Wand
Journal: Journal of Clinical Investigation (2005)

The amygdala is believed to play a key role in assigning emotional significance to specific sensory input, and conditions such as anxiety, autism, stress, and phobias are thought to be linked to its abnormal function. Growing evidence has also implicated the amygdala in mediation of the stress-dampening properties of alcohol. In this issue of the JCI, Pandey and colleagues identify a central amygdaloid signaling pathway involved in anxiety-like and alcohol-drinking behaviors in rats. They report that decreased phosphorylation of cAMP responsive element–binding protein (CREB) resulted in decreased neuropeptide Y (NPY) expression in the central amygdala of alcohol-preferring rats, causing high anxiety-like behavior. Alcohol intake by these animals was shown to increase PKA-dependent CREB phosphorylation and thereby NPY expression, subsequently ameliorating anxiety-like behavior. These provocative data suggest that a CREB-dependent neuromechanism underlies high anxiety-like and excessive alcohol-drinking behavior.
Cell Signaling in Vascular Inflammation
Authors: N.F. Voelkel
Journal: European Respiratory Journal (2006)

Cell Signaling in Vascular Inflammation     Edited by J. Bhattacharya     Published by Humana Press, USA     Pages: 300. Price: £79.50, 115 Euros. ISBN: 1-588-29-525-7    

This book is largely a collection of papers that were presented at an American Heart Association sponsored symposium. Although the title of the book broadly refers to “vascular” inflammation, the objective is to educate the reader in “lung inflammation”. This is stated in the Preface by the editor. For those interested in “lung biology”, this book is relevant. However, it is a collection of articles, such as protein modifications by reactive nitrogen species and signalling by …
Robust Gamma Coherence between Macaque V1 and V2 by Dynamic Frequency Matching
Authors: Mark J. Roberts, Eric Lowet, Nicolas M. Brunet, Marije Ter Wal, Paul Tiesinga, Pascal Fries, Peter De Weerd
Journal: Neuron (2013)

Current theories propose that coherence of oscillatory brain activity in the gamma band (30–80 Hz) constitutes an avenue for communication among remote neural populations. However, reports documenting stimulus dependency and time variability of gamma frequency suggest that distant neuronal populations may, at any one time, operate at different frequencies precluding synchronization. To test this idea, we recorded from macaque V1 and V2 simultaneously while presenting gratings of varying contrast. Although gamma frequency increased with stimulus contrast in V1 and V2 (by ∼25 Hz), V1-V2 gamma coherence was maintained for all contrasts. Moreover, while gamma frequency fluctuated by ∼15 Hz during constant contrast stimulation, this fluctuation was highly correlated between V1 and V2. The strongest coherence connections showed a layer-specific pattern, matching feedforward anatomical connectivity. Hence, gamma coherence among remote populations can occur despite large stimulus-induced and time-dependent changes in gamma frequency, allowing communication through coherence to operate without a stimulus independent, fixed-frequency gamma channel.
Cardiovascular Risk and Inhibition of Cyclooxygenase
Authors: Patricia McGettigan, David Henry
Journal: JAMA (2006)

Evidence that rofecoxib increases the risk of myocardial infarction has led to scrutiny of other nonsteroidal anti-inflammatory drugs (NSAIDs). Regulatory agencies have provided variable advice regarding the cardiovascular risks with older nonselective NSAIDs.To undertake a systematic review and meta-analysis of controlled observational studies to compare the risks of serious cardiovascular events with individual NSAIDs and cyclooxygenase 2 inhibitors.Searches were conducted of electronic databases (1985-2006), scientific meeting proceedings, epidemiological research Web sites, and bibliographies of eligible studies.Eligible studies were of case-control or cohort design, reported on cardiovascular events (predominantly myocardial infarction) with cyclooxygenase 2 inhibitor, NSAID use, or both with nonuse/remote use of the drugs as the reference exposure. Of 7086 potentially eligible titles, 17 case-control and 6 cohort studies were included. Thirteen studies reported on cyclooxygenase 2 inhibitors, 23 on NSAIDs, and 13 on both groups of drugs.Two people independently extracted data and assessed study quality with disagreements resolved by consensus.Data were combined using a random-effects model. A dose-related risk was evident with rofecoxib, summary relative risk with 25 mg/d or less, 1.33 (95% confidence interval [CI], 1.00-1.79) and 2.19 (95% CI, 1.64-2.91) with more than 25 mg/d. The risk was elevated during the first month of treatment. Celecoxib was not associated with an elevated risk of vascular occlusion, summary relative risk 1.06 (95% CI, 0.91-1.23). Among older nonselective drugs, diclofenac had the highest risk with a summary relative risk of 1.40 (95% CI, 1.16-1.70). The other drugs had summary relative risks close to 1: naproxen, 0.97 (95% CI, 0.87-1.07); piroxicam, 1.06 (95% CI, 0.70-1.59); and ibuprofen, 1.07 (95% CI, 0.97-1.18).This review confirms the findings from randomized trials regarding the risk of cardiovascular events with rofecoxib and suggests that celecoxib in commonly used doses may not increase the risk, contradicts claims of a protective effect of naproxen, and raises serious questions about the safety of diclofenac, an older drug.
Comparison of outcomes after hospitalization for worsening heart failure, myocardial infarction, and stroke in patients with heart failure and reduced and preserved ejection fraction
Authors: Søren L. Kristensen, Pardeep S. Jhund, Lars Køber, David Preiss, John Kjekshus, Robert S. McKelvie, Michael R. Zile, Inder S. Anand, John Wikstrand, Hans Wedel, Michel Komajda, Peter E. Carson, John G.F. Cleland, John J.V. McMurray
Journal: European Journal of Heart Failure (2014)
Fever in aspergillus mycetoma
Authors: C. Hilvering, E. A. M. Stevens, N. G. M. Orie
Journal: Thorax (1970)

Two patients with aspergillus mycetoma presenting with fever as a major sign are described. The clinical presentation is correlated with the results of experimental inhalation of <i>Aspergillus fumigatus</i> extract in patients with aspergillus mycetoma. A theory is put forward which tries to explain fever and haemoptysis as belonging to a type III (Gell and Coombs, 1963) antigen-antibody reaction. Therapeutic implications are discussed.
Phase I Trial of Sequential Low-Dose 5-Aza-2′-Deoxycytidine Plus High-Dose Intravenous Bolus Interleukin-2 in Patients with Melanoma or Renal Cell Carcinoma
Authors: Jared A. Gollob, Catherine J. Sciambi, Bercedis L. Peterson, Tina Richmond, Monica Thoreson, Kelly Moran, Holly K. Dressman, Jaroslav Jelinek, Jean-Pierre J. Issa
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The silencing of gene expression through DNA methylation contributes to defects in antigen presentation and apoptosis in melanoma and renal cell cancer. To determine how a hypomethylating agent would modulate the toxicity and antitumor activity of immunotherapy, we initiated a phase I trial of 5-aza-2′-deoxycytidine (decitabine) plus high-dose interleukin 2 (IL-2). Experimental Design: Patients received s.c. decitabine daily × 5 days on weeks 1 and 2 of a 12-week cycle. High-dose IL-2, consisting of two cycles of IL-2 600,000 IU/kg i.v. q8 hours × 14 doses separated by a 2-week break, was administered starting on week 3. Decitabine was escalated from 0.1 to 0.25 mg/kg. The hypomethylating activity of decitabine was assessed during cycle 1 by measuring hemoglobin F levels and changes in DNA methylation in peripheral blood mononuclear cells. Results: Twenty-one patients with melanoma or renal cell cancer were enrolled. Decitabine did not alter the tolerability of IL-2 but caused grade 4 neutropenia in most patients. Grade 4 neutropenia lasting more than 7 days was the only dose-limiting toxicity, with a trend toward a higher incidence with increasing decitabine doses. Infection occurred in only one patient despite the high incidence of neutropenia, and granulocyte colony-stimulating factor use in several patients expedited neutrophil recovery. Decitabine augmented hemoglobin F levels and altered DNA methylation and gene expression in peripheral blood mononuclear cells in a dose-independent manner that overlapped with the administration of IL-2. Objective responses occurred in 31% of melanoma patients. Conclusions: Decitabine can be safely administered with high-dose IL-2 and may enhance the activity of IL-2 in melanoma.
Somatostatin prevents the postoperative increases in plasma amino acid clearance and urea synthesis after elective cholecystectomy.
Authors: H Heindorff, P Billesbolle, S L Pedersen, R Hansen, H Vilstrup
Journal: Gut (1995)

The importance of glucagon on postoperative changes in hepatic amino-nitrogen conversion were investigated in six patients undergoing elective cholecystectomy for uncomplicated gall stones. Patients were given infusions of somatostatin (bolus of 6 micrograms/kg followed by continuous infusion of 6 micrograms/kg/h) from induction of anaesthesia to the end of investigation, the first postoperative day (30 hours). Controls were 16 patients undergoing the same procedures omitting the somatostatin infusion. In all patients blood concentration and plasma clearance of total alpha-amino-nitrogen, and amino acid stimulated rate of urea synthesis were measured. Elective cholecystectomy decreased blood alpha-amino-nitrogen concentration from mean (SEM) 2.9 (0.2) to 2.4 (0.1) mmol/l (p &lt; 0.05), increased the clearance of total alpha-amino-nitrogen from 5.2 (0.3) to 6.6 (0.3) ml/s (p &lt; 0.05), and increased the rate of amino acid stimulated urea synthesis from 27 (1) to 37 (2) mumol/s (p &lt; 0.05) pointing to increased hepatic removal of amino-nitrogen at expense of plasma amino-nitrogen. Infusion of somatostatin prevented increase of glucagon for 24 hours after surgery, and prevented the negative changes in postoperative nitrogen homeostasis resulting from the postoperative changes in hepatic nitrogen conversion, suggesting glucagon as mediator. The exact mechanism remains in doubt, however, because of the multiple effects of somatostatin.