tbuckley/cabot-search huggingface dataset:
Hyperforin Inhibits Cancer Invasion and Metastasis
Authors: Massimo Donà, Isabella Dell’Aica, Elga Pezzato, Luigi Sartor, Fiorella Calabrese, Mila Della Barbera, Arianna Donella-Deana, Giovanni Appendino, Anna Borsarini, Rosy Caniato, Spiridione Garbisa
Journal: Cancer Research (2004)

Abstract Hyperforin (Hyp), the major lipophilic constituent of St. John’s wort, was assayed as a stable dicyclohexylammonium salt (Hyp-DCHA) for cytotoxicity and inhibition of matrix proteinases, tumor invasion, and metastasis. Hyp-DCHA triggered apoptosis-associated cytotoxic effect in both murine (C-26, B16-LU8, and TRAMP-C1) and human (HT-1080 and SK-N-BE) tumor cells; its effect varied, with B16-LU8, HT-1080, and C-26 the most sensitive (IC50 = 5 to 8 μmol/L). At these concentrations, a marked and progressive decline of growth was observed in HT-1080 cells, whereas untransformed endothelial cells were only marginally affected. Hyp-DCHA inhibited in a dose-dependent and noncompetitive manner various proteinases instrumental to extracellular matrix degradation; the activity of leukocyte elastase was inhibited the most (IC50 = 3 μmol/L), followed by cathepsin G and urokinase-type plasminogen activator, whereas that of the matrix metalloproteinases (MMPs) 2 and 9 showed an IC50 &amp;gt; 100 μmol/L. Nevertheless, inhibition of extracellular signal-regulated kinase 1/2 constitutive activity and reduction of MMP-2 and MMP-9 secretion was triggered by 0.5 μmol/L Hyp-DCHA to various degrees in different cell lines, the most in C-26. Inhibition of C-26 and HT-1080 cell chemoinvasion (80 and 54%, respectively) through reconstituted basement membrane was observed at these doses. Finally, in mice that received i.v. injections of C-26 or B16-LU8 cells, daily i.p. administration of Hyp-DCHA—without reaching tumor-cytotoxic blood levels—remarkably reduced inflammatory infiltration, neovascularization, lung weight (−48%), and size of experimental metastases with C-26 (−38%) and number of lung metastases with B16-LU8 (−22%), with preservation of apparently healthy and active behavior. These observations qualify Hyp-DCHA as an interesting lead compound to prevent and contrast cancer spread and metastatic growth.
Reliability of ventilatory parameters during cycle ergometry in multicentre trials in COPD
Authors: D. E. O’Donnell, J. Travers, K. A. Webb, Z. He, Y-M. Lam, A. Hamilton, S. Kesten, F. Maltais, H. Magnussen
Journal: European Respiratory Journal (2009)

We studied the distribution profiles and repeatability of key exercise performance parameters in the first large multicentre trials to include these measurements in chronic obstructive pulmonary disease (COPD). After a screening visit, 463 subjects with COPD (mean± sd forced expiratory volume in 1 s 43±13% predicted) completed two run-in visits before treatment randomisation. At the run-in visits, measurements were conducted at rest, at a standardised time near end-exercise (isotime) and at peak exercise during constant work rate (CWR) cycle tests at 75% of each individual’s maximum work capacity. The intraclass correlation coefficient was used to evaluate the test-retest repeatability of measurements of endurance time (ET), inspiratory capacity (IC), ventilation and dyspnoea intensity (Borg scale) during exercise. IC, ventilation and dyspnoea ratings were normally distributed; ET showed rightward skew (median&lt;mean, skewness of 10.9 (much greater than zero)) with 16% of the sample exceeding 1 sd of the mean. ET was highly repeatable across run-in visits: 7.9±4.8 and 8.4±5.1 min (R = 0.84). IC values at rest, isotime and peak exercise were all highly repeatable (R≥0.87). Ventilation was repeatable over the same time-points (R≥0.92), as was dyspnoea intensity at isotime (R = 0.79) and at peak exercise (R = 0.81). In conclusion, key perceptual and ventilatory parameters can be reliably measured during CWR cycle exercise in multicentre clinical trials in moderate to very severe COPD.
Prostaglandin D <sub>2</sub> Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia
Authors: Luis A. Garza, Yaping Liu, Zaixin Yang, Brinda Alagesan, John A. Lawson, Scott M. Norberg, Dorothy E. Loy, Tailun Zhao, Hanz B. Blatt, David C. Stanton, Lee Carrasco, Gurpreet Ahluwalia, Susan M. Fischer, Garret A. FitzGerald, George Cotsarelis
Journal: Science Translational Medicine (2012)

Prostaglandin D 2 inhibits hair growth through its receptor, GPR44, and this pathway could serve as a new target for developing treatments for male pattern baldness.
Interventricular septal motion in patients with proximal and distal left anterior descending coronary artery lesions.
Authors: M J Gordon, R E Kerber
Journal: Circulation (1977)

In order to evaluate the ability of the echocardiogram to detect and localize left main or left anterior descending (LAD) coronary artery lesions, 43 patients were studied. The systolic excursion of the left side of the septum and the ratio of posterior wall to septal excursion were measured. Seventeen patients had no LAD lesions; all had systolic septal excursion of 3 mm or greater. Twelve patients with septal excursion of 2 mm or less all had left main or LAD lesions, but 14 other patients with LAD lesions had septal excursions of 3 mm or greater. Nine of 16 patients with LAD lesions proximal to the first septal branch had reduced or absent septal excursion, as did three of ten with LAD lesions distal to the first septal branch. In a setting of coronary artery disease reduced or absent septal motion on echocardiography suggests involvement of the left main or left anterior descending coronary. However, the technique is relatively insensitive, with 54% of the LAD patients having normal septal motion.
Contrasting models of promiscuous gene expression by thymic epithelium
Authors: Geoffrey O. Gillard, Andrew G. Farr
Journal: The Journal of Experimental Medicine (2005)

Medullary thymic epithelial cells (mTECs) express a broad spectrum of tissue- restricted self-antigens (TRAs), which are required for the development of central tolerance. A new study suggests that TRA expression is a specialized property of terminally differentiated mTECs. However, as discussed here, an alternative model—whereby TRA expression is regulated by conserved developmental programs active in developing mTECs—may be equally plausible.
Bilateral diaphragmatic paralysis--a rare cause of acute respiratory failure managed with nasal mask bilevel positive airway pressure (BiPAP) ventilation
Authors: MC Lin, MY Liaw, CC Huang, ML Chuang, YH Tsai
Journal: European Respiratory Journal (1997)

A 68 yr old woman presented with acute respiratory failure. She was suspected of having a phrenic-diaphragmatic impairment, without evidence of an intrinsic lung disease or generalized neuromuscular disorder, after 3 weeks of prolonged mechanical ventilation. A series of studies, including fluoroscopy, phrenic nerve stimulation test and diaphragmatic electromyography, was performed before the diagnosis of bilateral diaphragmatic paralysis (BDP) was confirmed. The patient was successfully weaned from the conventional mechanical ventilator, and was placed on nasal mask bi-level positive airway pressure (BiPAP) ventilation. A high degree of clinical suspicion of bilateral diaphragmatic paralysis should always be raised in patients suffering respiratory failure without definite predisposing factors. Weaning with noninvasive nasal mask ventilation should be tried first instead of direct tracheostomy.
The upper limit of alveolar capillary recruitment in a young man with lung growth impairment
Authors: PM Donnelly, BV Daxini, PT Bye
Journal: European Respiratory Journal (1994)

In order to obtain further insight into the adaptive mechanisms relating to gas exchange in anatomically small lungs, tests of mechanical lung function and gas exchange were made in an active young man, whose lung growth had been severely impaired due to pectus excavatum developed in childhood. We found our patient to have small (total lung capacity, 59% of predicted) but mechanically normal lungs. He had a normal cardiac output, a normal single-breath diffusing capacity (100% pred), and a high diffusion coefficient (148% pred) associated with a high pulmonary capillary blood volume (131% pred) at rest. Pulmonary distensibility (K) and elastic recoil were normal. During steady-state exercise he was unable to recruit further reserves of pulmonary capillaries, but this was not reflected in a plateau for oxygen consumption, which was presumably the result of an increased pulmonary capillary blood flow rather than volume. The recruitment of pulmonary capillary reserves in this young man has enabled him to maintain a normal maximum exercise capacity. In addition, the high stroke volume and a haemoglobin level in the high normal range (176 g.l-1) may have maintained his maximal exercise function, despite fewer alveolar units. This study suggests that, contrary to previous findings, loss of a major proportion of lung tissue need not impair exercise capacity. Patients with either small lungs or following pneumonectomy may benefit from physical training sufficient to optimize both an increase in cardiac output and recruitment of their existing alveolar capillary reserves.
More nearly certain
Authors: I. Evans
Journal: Journal of the Royal Society of Medicine (2005)

If you turn to the television comedy archive channel on your multimedia display system you should be able to locate a series of political satires called Yes Prime Minister.Created 20 years ago, they remain hugely popular today.Dear reader in 2055, I'd like to think their linguistic contortions are sufficiently timeless to make you laugh too.In one episode the PM, Jim Hacker, plans to cancel an order for a very expensive nuclear missile.Sir Humphrey Appleby, Civil Service supremo, tries to argue him out of it.The verbal exchange hinges on the concept of uncertainty on the part of those at whom the missile might be directed.Appleby: 'It's a deterrent.'Hacker: 'It's a bluff.I probably wouldn't use it.'Appleby: 'Yes, but they don't know that you probably wouldn't.'Hacker: 'They probably do.' Appleby: 'Yes, they probably know that you probably wouldn't.But they can't certainly know.' Hacker: 'They probably certainly know that I probably wouldn't.'Appleby: 'Yes, but even though they probably certainly know that you probably wouldn't, they don't certainly know that, although you probably wouldn't, there's no probability that you certainly would.
Increased sensitivity to anticancer drugs and decreased inflammatory response in mice lacking the multidrug resistance-associated protein
Authors: Jan Wijnholds, Raymond Evers, Manuel R. van Leusden, Carla A.A.M. Mol, Guido J.R. Zaman, Ulrich Mayer, Jos H. Beijnen, Martin Van Der Valk, Paul Krimpenfort, Piet Borst
Journal: Nature Medicine (1997)
A severe and prolonged case of pemphigoid gestationis successfully treated with combination therapies
Authors: M. Arakawa, C. Ohata, D. Tsuruta, N. Ishii, R. Sogame, T. Nakama, S. Yasumoto, Y. Yokoyama, E. Takeishi, T. Hashimoto
Journal: British Journal of Dermatology (2015)

Journal Article A severe and prolonged case of pemphigoid gestationis successfully treated with combination therapies Get access M. Arakawa, M. Arakawa Department of Dermatology Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology Fukuoka Japan Search for other works by this author on: Oxford Academic Google Scholar C. Ohata, C. Ohata Department of Dermatology Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology Fukuoka Japan Search for other works by this author on: Oxford Academic Google Scholar D. Tsuruta, D. Tsuruta Department of Dermatology Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology Fukuoka Japan Search for other works by this author on: Oxford Academic Google Scholar N. Ishii, N. Ishii Department of Dermatology Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology Fukuoka Japan Search for other works by this author on: Oxford Academic Google Scholar R. Sogame, R. Sogame Department of Dermatology Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology Fukuoka Japan Search for other works by this author on: Oxford Academic Google Scholar T. Nakama, T. Nakama Department of Dermatology Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology Fukuoka Japan Search for other works by this author on: Oxford Academic Google Scholar S. Yasumoto, S. Yasumoto Department of Dermatology Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology Fukuoka Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Yokoyama, Y. Yokoyama Department of Dermatology Sasebo City General Hospital Nagasaki Japan Search for other works by this author on: Oxford Academic Google Scholar E. Takeishi, E. Takeishi Department of Dermatology Sasebo City General Hospital Nagasaki Japan Search for other works by this author on: Oxford Academic Google Scholar T. Hashimoto T. Hashimoto Department of Dermatology Kurume University School of Medicine, and Kurume University Institute of Cutaneous Cell Biology Fukuoka Japan Correspondence: Takashi Hashimoto. E‐mail: hashimot@med.kurume-u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 4, 1 April 2016, Pages 925–927, https://doi.org/10.1111/bjd.14265 Published: 01 April 2016
Derivation and Validation of a Simple Exercise-Based Algorithm for Prediction of Genetic Testing in Relatives of LQTS Probands
Authors: Raymond W. Sy, Christian van der Werf, Ishvinder S. Chattha, Priya Chockalingam, Arnon Adler, Jeffrey S. Healey, Mark Perrin, Michael H. Gollob, Allan C. Skanes, Raymond Yee, Lorne J. Gula, Peter Leong-Sit, Sami Viskin, George J. Klein, Arthur A. Wilde, Andrew D. Krahn
Journal: Circulation (2011)

Background— Genetic testing can diagnose long-QT syndrome (LQTS) in asymptomatic relatives of patients with an identified mutation; however, it is costly and subject to availability. The accuracy of a simple algorithm that incorporates resting and exercise ECG parameters for screening LQTS in asymptomatic relatives was evaluated, with genetic testing as the gold standard. Methods and Results— Asymptomatic first-degree relatives of genetically characterized probands were recruited from 5 centers. QT intervals were measured at rest, during exercise, and during recovery. Receiver operating characteristics were used to establish optimal cutoffs. An algorithm for identifying LQTS carriers was developed in a derivation cohort and validated in an independent cohort. The derivation cohort consisted of 69 relatives (28 with LQT1, 20 with LQT2, and 21 noncarriers). Mean age was 35±18 years, and resting corrected QT interval (QTc) was 466±39 ms. Abnormal resting QTc (females ≥480 ms; males ≥470 ms) was 100% specific for gene carrier status, but was observed in only 48% of patients; however, mutations were observed in 68% and 42% of patients with a borderline or normal resting QTc, respectively. Among these patients, 4-minute recovery QTc ≥445 ms correctly restratified 22 of 25 patients as having LQTS and 19 of 21 patients as being noncarriers. The combination of resting and 4-minute recovery QTc in a screening algorithm yielded a sensitivity of 0.94 and specificity of 0.90 for detecting LQTS carriers. When applied to the validation cohort (n=152; 58 with LQT1, 61 with LQT2, and 33 noncarriers; QTc=443±47 ms), sensitivity was 0.92 and specificity was 0.82. Conclusions— A simple algorithm that incorporates resting and exercise-recovery QTc is useful in identifying LQTS in asymptomatic relatives.
Lymphomatoid granulomatosis--a report on four cases: evidence for B phenotype of the tumoral cells
Authors: P Taniere, F Thivolet-Bejui, D Vitrey, S Isaac, R Loire, JF Cordier, F Berger
Journal: European Respiratory Journal (1998)

Four cases of lymphomatoid granulomatosis are reported, three of them involving the lung. Histological features included a true angiocentric and angiodestructive polymorphic cellular proliferation. This included histiocytes, plasma cells, many reactive T-cells and rare large, atypical cells which were of the B phenotype. Epstein-Barr virus was detected in the atypical cells by in situ hybridization in three cases, with expression of both latent membrane proteins (LMP)-1 and Epstein-Barr nuclear antigen-2 in two cases and expression of only LMP-1 in the third case. Expression of both of these proteins suggests a defect in the T-cell-mediated immunity and that Epstein-Barr virus is not only a silent passenger but may also be involved in the pathogenesis of the disease. This could have implications for therapy.
Inpatient Diabetes Control
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2004)

This is the second of two articles on the Consensus Development Conference on Inpatient Diabetes Control, which was sponsored by the American College of Endocrinology and held in Washington, DC, 14–15 December 2003.

Derek LeRoith (Bethesda, MD) and Irl Hirsch (Seattle, WA) discussed mechanisms by which metabolic control may improve outcomes. Both speakers reviewed physiological and cellular aspects of normal insulin action and glucose homeostasis and molecular aspects of insulin resistance in relation to situations of stress. Insulin has classic actions such as increased glucose uptake, decreased hepatic glucose production (HGP), and antilipolytic effects in skeletal muscle, liver, and adipose tissue, as well as nonclassical vasodilatory effects, proliferative actions on vascular smooth muscle cells (VSMCs), effects on the brain (perhaps related to learning and memory), β-cell actions, and general effects increasing growth and differentiation and decreasing apoptosis. Insulin levels range from <10 to 30–50 μU/ml in the fasting versus fed state. The liver is exposed to portal vein insulin levels triple that in the periphery, with HGP inhibited at levels of 20–25 μU/ml. Lipolysis increases during fasting and is inhibited at levels of 30–50 μU/ml, so that in the fasting state, free fatty acids (FFAs) are available for fuel. A doubling of insulin levels inhibits HGP by 80% and increases glucose utilization by 20%.

The insulin-signaling pathway involves stimulation of cascades of intracellular kinases leading to insulin action. The insulin receptor substrates (IRSs) have metabolic as well as antiapoptotic effects, particularly due to IRS-1 phosphorylation via the phosphatidylinositol-3-hydroxy kinase (PI3K) pathway after activation of the insulin receptor—a process inhibited in situations of insulin resistance. The mitogen-activated protein kinase pathway is involved in gene expression, cell proliferation, and a variety of other anabolic actions. When insulin stimulates glucose uptake, particularly occurring in muscle, which mediates ∼80% of insulin-stimulated glucose uptake, PI3K …
Single Amino Acid Substitution in Aquaporin 11 Causes Renal Failure
Authors: Elena E. Tchekneva, Zaza Khuchua, Linda S. Davis, Veronika Kadkina, Stephen R. Dunn, Sebastian Bachman, Kenichi Ishibashi, Eugene M. Rinchik, Raymond C. Harris, Mikhail M. Dikov, Matthew D. Breyer
Journal: Journal of the American Society of Nephrology (2008)

A screen of recessive mutations generated by the chemical mutagen n-ethyl-n-nitrosourea (ENU) mapped a new mutant locus (5772SB) termed sudden juvenile death syndrome (sjds) to chromosome 7 in mice. These mutant mice, which exhibit severe proximal tubule injury and formation of giant vacuoles in the renal cortex, die from renal failure, a phenotype that resembles aquaporin 11 (Aqp11) knockout mice. In this report, the ENU-induced single-nucleotide variant (sjds mutation) is identified. To determine whether this variant, which causes an amino acid substitution (Cys227Ser) in the predicted E-loop region of aquaporin 11, is responsible for the sjds lethal renal phenotype, Aqp11−/sjds compound heterozygous mice were generated from Aqp11+/sjds and Aqp11+/− intercrosses. The compound heterozygous Aqp11−/sjds offspring exhibited a lethal renal phenotype (renal failure by 2 wk), similar to the Aqp11sjds/sjds and Aqp11−/− phenotypes. These results demonstrate that the identified mutation causes renal failure in Aqp11sjds/sjds mutant mice, providing a model for better understanding of the structure and function of aquaporin 11 in renal physiology.
Development of chronic hepatocerebral degeneration eight years after a distal splenorenal (Warren) shunt.
Authors: A F Bleasel, R C Waugh, G W McCaughan
Journal: Gut (1989)

It is well known that chronic encephalopathy may be a major complication after the establishment of a surgical portal caval shunt for an episode of variceal haemorrhage. In an effort to minimise this problem Warren and colleagues developed the distal splenorenal shunt where the portal and mesenteric blood flow to the liver was left intact. It is now recognised, however, that the longterm incidence of encephalopathy may be no different with this type of shunt compared with conventional surgical portal systemic shunts. Acquired chronic hepatocerebral degeneration has not been reported after such a selective shunt. A patient with primary biliary cirrhosis is reported who developed the clinical features of this syndrome eight years after a successful distal splenorenal shunt.
Use of Generic Antiretroviral Agents and Cost Savings in PEPFAR Treatment Programs
Authors: Charles B. Holmes, William Coggin, David Jamieson, Heidi Mihm, Reuben Granich, Phillip Savio, Michael Hope, Caroline Ryan, Michele Moloney-Kitts, Eric P. Goosby, Mark Dybul
Journal: JAMA (2010)

Context One of the biggest hurdles to the rapid scale-up of antiretroviral therapy in the developing world was the price of antiretroviral drugs (ARVs).Modification of an existing US Food and Drug Administration (FDA) process to expedite review and approval of generic ARVs quickly resulted in a large number of FDA-tentatively approved ARVs available for use by the US President's Emergency Plan for AIDS Relief (PEPFAR).Objective To evaluate the uptake of generic ARVs among PEPFAR-supported programs in Guyana, Haiti, Vietnam, and 13 countries in Africa, and changes over time in ARV use and costs. Design, Setting, and ParticipantsAn annual survey from 2005 to 2008 of ARVs purchased in 16 countries by PEPFAR implementing and procurement partners (organizations using PEPFAR funding to purchase ARVs).Main Outcome Measures Drug expenditures, ARV types and volumes (assessed per pack, a 1-month supply), proportion of generic procurement across years and countries, and cost savings from generic procurement.Results ARV expenditures increased from $116.8 million (2005) to $202.2 million (2008); and procurement increased from 6.2 million to 22.1 million monthly packs.The proportion spent on generic ARVs increased from 9.17% (95% confidence interval [CI], 9.17%-9.18%) in 2005 to 76.41% (95% CI, 76.41%-76.42%) in 2008 (PϽ.001), and the proportion of generic packs procured increased from 14.8% (95% CI, 14.79%-14.84%) in 2005 to 89.33% (95% CI, 89.32%-89.34%) in 2008 (PϽ.001).In 2008, there were 8 PEPFAR programs that procured at least 90.0% of ARV packs in generic form; South Africa had the lowest generic procurement (24.7%; 95% CI, 24.6%-24.8%).Procurement of generic fixed-dose combinations increased from 33.3% (95% CI, 33.24%-33.43%) in 2005 to 42.73% (95% CI, 42.71%-42.75%) in 2008.Estimated yearly savings generated through generic ARV use were $8 108 444 in 2005, $24 940 014 in 2006, $75 645 816 in 2007, and $214 648 982 in 2008, a total estimated savings of $323 343 256. ConclusionAmong PEPFAR-supported programs in 16 countries, availability of generic ARVs was associated with increased ARV procurement and substantial estimated cost savings.