tbuckley/cabot-search huggingface dataset:
Changes in pulmonary blood flow affect vascular response to chronic hypoxia in rats.
Authors: M Rabinovitch, M A Konstam, W J Gamble, N Papanicolaou, M J Aronovitz, S Treves, L Reid
Journal: Circulation Research (1983)

We banded the left pulmonary artery in rats to investigate, in the same animal, the effect of both increased and decreased flow on the lung vasculature and to determine how these hemodynamic states modify the structural changes produced by a 2-week exposure to hypobaric hypoxia. In unanesthetized rats, pressures were recorded from the main pulmonary artery and aorta via indwelling catheters, cardiac output was calculated by the Fick principle, and pulmonary and systemic vascular resistance estimated. Technetium-99m macroaggregated albumin was injected and radionuclide activity counted separately over the right and left lungs as a measure of flow. At postmortem, right and left ventricles of the heart were weighed and the lungs injected to permit analysis of arteriograms and morphometric assessment of structural changes in the pulmonary vascular bed. Flow in the left lung was reduced to one-fifth normal in rats with left pulmonary artery bands. In "room air" rats, pressure proximal to the left pulmonary artery band and in the right lung was slightly higher than in nonbanded controls, but not as high as in nonbanded or banded hypoxic rats. Changes in flow and pressure in both lungs of "room air" rats with left pulmonary artery bands were associated with a mild degree of extension of muscle into peripheral pulmonary arteries normally nonmuscular, medial hypertrophy of normally muscular arteries, and reduced arterial density. These three structural changes were present in both lungs of "hypoxic" rats but were much more severe. High flow in the right lungs of "hypoxic rats" with left pulmonary artery bands worsened only the degree of extension. Decreased flow and pressure in the left lungs of these animals prevented both the extension and the medial hypertrophy of hypoxia, but not the severe reduction in arterial density. It seems that the latter may occur as a direct response to low oxygen tension, whereas extension and medial hypertrophy are influenced by altered flow and pressure, respectively.
Phase II study of eribulin mesylate (E7389) in patients with metastatic castration-resistant prostate cancer stratified by prior taxane therapy
Authors: J.S. de Bono, L.R. Molife, G. Sonpavde, J.P. Maroto, E. Calvo, T.H. Cartwright, D.M. Loesch, K. Feit, A. Das, E.A. Zang, J. Wanders, S. Agoulnik, D.P. Petrylak
Journal: Annals of Oncology (2011)
Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial
Authors: Ronald H Gray, Godfrey Kigozi, David Serwadda, Frederick Makumbi, Stephen Watya, Fred Nalugoda, Noah Kiwanuka, Lawrence H Moulton, Mohammad A Chaudhary, Michael Z Chen, Nelson K Sewankambo, Fred Wabwire-Mangen, Melanie C Bacon, Carolyn FM Williams, Pius Opendi, Steven J Reynolds, Oliver Laeyendecker, Thomas C Quinn, Maria J Wawer
Journal: The Lancet (2007)
Early Reduction of Serum-Free Light Chains Associates with Renal Recovery in Myeloma Kidney
Authors: Colin A. Hutchison, Paul Cockwell, Stephanie Stringer, Arthur Bradwell, Mark Cook, Morie A. Gertz, Angela Dispenzieri, Jeffrey L. Winters, Shaji Kumar, S. Vincent Rajkumar, Robert A. Kyle, Nelson Leung
Journal: Journal of the American Society of Nephrology (2011)

Myeloma kidney is the major cause of severe irreversible renal failure in patients with multiple myeloma. This tubulointerstitial injury is a direct consequence of high concentrations of circulating monoclonal free light chains (FLCs) produced by a clonal expansion of plasma cells. Early reduction of serum FLCs associates with renal recovery, but the target threshold of reduction to facilitate renal recovery is unknown. To determine the relationship between the achieved FLC reduction and renal recovery, we identified 39 patients with biopsy-proven myeloma kidney, the majority of whom had severe renal failure at presentation (median estimated GFR 9 ml/min per 1.73 m2). In a multivariable analysis incorporating demographic, hematologic, and renal variables, only the achieved FLC reduction significantly predicted renal recovery (P = 0.003). The relationship between renal recovery and FLC reduction was linear with no absolute threshold for FLC reduction. A 60% reduction in FLCs by day 21 associated with recovery of renal function for 80% of the population. Patient survival strongly associated with renal recovery: the median survival was 42.7 months (range 0 to 80) among those who recovered function compared with 7.8 months (range 0 to 54) among those who did not (P < 0.02). Cox-regression analysis demonstrated that the first presentation of myeloma, the kappa isotype of FLC, and renal recovery were independent predictors of survival. In conclusion, recovery of renal function in myeloma kidney depends on early reduction of serum FLCs, and this recovery associates with a significant survival advantage.
p14ARF induces the relocation of HDM2 and p53 to extranucleolar sites that are targeted by PML bodies and proteasomes.
Authors: Elena Kashuba, Karin Mattsson, George Klein, Laszlo Szekely
Journal: Molecular Cancer (2003)

p14ARF is a protein product of the alternative reading frame of the human INK4a locus. It functions as a tumor suppressor protein. p14ARF suppresses growth through p53-dependent and p53-independent pathways. p14ARF protein localizes primarily to the nucleoli. Here we show that in transfected cells p14ARF also appears in Hsp70 positive extranucleolar inclusions. The formation of p14ARF inclusions induces the parallel re-localization p53 and HDM2 to these sites that are also targeted by PML bodies and proteasomes. Our data show that co-localization between p53, HDM2 and p14ARF occurs at extranucleolar sites. Accumulation of PML and proteasomes at these sites suggest that the components of the nuclear inclusions are targeted for proteasome-mediated degradation.
Complement Activation and Inhibition in Myocardial Ischemia and Reperfusion Injury
Authors: J W Homeister, B R Lucchesi
Journal: The Annual Review of Pharmacology and Toxicology (1994)

The myocardial inflammatory response that occurs as a result of ischemia and reperfusion is similar to that which occurs in other tissues. Activation of the complement system is an integral part of the initiation and maintenance of any inflammatory response. It and other immune system mediators participate in the promotion of neutrophil adherence to endothelium by modulating expression of various adhesion molecules. The complement system also serves an integral role in mediating neutrophil activation, the results of which have been documented in the setting of myocardial ischemia and reperfusion. Another aspect of the complement cascade, which has received little attention with respect to the heart, is the direct effects of complement activation such as endothelial and myocardial cell cytotoxicity mediated by the membrane attack complex. It is likely that this form of tissue injury contributes significantly to myocardial reperfusion injury. Given the numerous contributions of the complement system to the generation of the inflammatory response, and to directly-mediated tissue injury, selective inhibitors of the complement system have great potential to limit reperfusion injury. This has already been demonstrated for the complement inhibitor sCR1. In the future, it is likely that any therapeutic treatment of reperfusion injury will include modulation of the effects of complement activation.
Oxidative damage in selenium deficient hearts on perfusion with adriamycin: protective role of glutathione peroxidase system
Authors: E. NAKANO, K. TAKESHIGE, Y. TOSHIMA, K. TOKUNAGA, S. MINAKAMI
Journal: Cardiovascular Research (1989)

The protective effects of the glutathione peroxidase system against functional damage induced by perfusion of isolated hearts with adriamycin, an anthracycline antibiotic, were studied. We used selenium deficient rats, in which cardiac glutathione peroxidase activity was only 3% of control rats. Both contractile tension and coronary flow decreased during perfusion with the antibiotic. The degree of decline was significantly greater in the selenium deficient hearts than in the control hearts. The increase in malondialdehyde, a product of lipid peroxidation, induced by adriamycin perfusion was more evident in selenium deficient hearts, though the level of reduced glutathione was well maintained. Isolated mitochondrial function also decreased after aerobic adriamycin perfusion and the decrease was greater in selenium deficient rats. These observations indirectly suggest that the decrease in cardiac function induced by adriamycin is protected by the glutathione peroxidase system and that the decrease may be due, at least in part, to damage to the mitochondria caused by oxygen radicals generated by adriamycin.
Epoxyeicosatrienoic Acids Are Released to Mediate Shear Stress–Dependent Hyperpolarization of Arteriolar Smooth Muscle
Authors: An Huang, Dong Sun, Azita Jacobson, Mairead A. Carroll, John R. Falck, Gabor Kaley
Journal: Circulation Research (2005)

We hypothesized that shear stress stimulates the release of epoxyeicosatrienoic acids (EETs) from arteriolar endothelium, which directly hyperpolarize smooth muscle. To test this hypothesis, a perfusion system, consisting of two separate, serially connected chambers (A and B), was used. A donor vessel, isolated from gracilis muscle of female NO-deficient mice and rats, was cannulated in chamber A. In chamber B, an endothelium-denuded detector vessel isolated from mesentery of these animals was cannulated. In the presence of indomethacin, 5, 10, and 20 dyne/cm2 shear stress elicited dilation of donor vessels, followed by dilation of detector vessels. Changes in membrane potential of the detector vessel smooth muscle cells in response to the perfusate from 5 and 10 dyne/cm2 shear stress-stimulated donor vessels was also recorded (by approximately -12 to -15 and -20 to -30 mV, respectively). Exposing detector vessels to 30 mmol/L KCl or pretreating them with iberiotoxin abolished their hyperpolarization and dilation to the flow of perfusate. Pretreatment of donor vessels with PPOH, an inhibitor of cytochrome P-450/epoxygenase, eliminated dilator responses in both donor and detector vessels, as well as the hyperpolarization of detector vessels. GC-MS analysis showed increasing release of EETs into the perfusate collected from 1, 5, and 10 dyne/cm2 shear stress-stimulated arterioles, which was abolished by PPOH. Thus, EETs, released from endothelial cells of donor vessels stimulated with shear stress, hyperpolarize smooth muscle of downstream detector vessels, confirming their identity as endothelium-derived hyperpolarizing factors and suggesting that gap junctional communication may not be necessary for shear stress-stimulated EDHF-mediated vasodilation.
THE ANTIMYCOBACTERIAL ACTIVITY OF VARIOUS AMINES RELATED TO SPERMINE IN CHEMICAL STRUCTURE
Authors: James G. Hirsch
Journal: The Journal of Experimental Medicine (1953)

A final concentration of 3 x 10(-5)M spermine or spermidine inhibited the growth of mammalian tubercle bacilli in a modified Dubos liquid medium. Various related amino compounds, including isolated portions of the spermine molecule and the products of its chemical degradation, did not manifest similar antimycobacterial activity.
Inhaled Nitric Oxide Versus Conventional Therapy
Authors: JOHN R. MICHAEL, RICHARD G. BARTON, JEFFREY R. SAFFLE, MARY MONE, BOAZ A. MARKEWITZ, KAREN HILLIER, MARK R. ELSTAD, EDWARD J. CAMPBELL, BRETT E. TROYER, RALPH E. WHATLEY, THEODORE G. LIOU, WAYNE M. SAMUELSON, HOLLY J. CARVETH, DOUG M. HINSON, STEPHEN E. MORRIS, BYRON L. DAVIS, RONALD W. DAY
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

A randomized, controlled clinical trial was performed with patients with acute respiratory distress syndrome (ARDS) to compare the effect of conventional therapy or inhaled nitric oxide (iNO) on oxygenation. Patients were randomized to either conventional therapy or conventional therapy plus iNO for 72 h. We tested the following hypotheses: (1) that iNO would improve oxygenation during the 72 h after randomization, as compared with conventional therapy; and (2) that iNO would increase the likelihood that patients would improve to the extent that the Fi O2 could be decreased by ⩾ 0.15 within 72 h after randomization. There were two major findings. First, That iNO as compared with conventional therapy increased PaO2 /Fi O2 at 1 h, 12 h, and possibly 24 h. Beyond 24 h, the two groups had an equivalent improvement in PaO2 /Fi O2 . Second, that patients treated with iNO therapy were no more likely to improve so that they could be managed with a persistent decrease in Fi O2 ⩾ 0.15 during the 72 h following randomization (11 of 20 patients with iNO versus 9 of 20 patients with conventional therapy, p = 0.55). In patients with severe ARDS, our results indicate that iNO does not lead to a sustained improvement in oxygenation as compared with conventional therapy.
Risk of progression of advanced adenomas to colorectal cancer by age and sex: estimates based on 840 149 screening colonoscopies
Authors: H. Brenner, M. Hoffmeister, C. Stegmaier, G. Brenner, L. Altenhofen, U. Haug
Journal: Gut (2007)

To derive age and sex specific estimates of transition rates from advanced adenomas to colorectal cancer by combining data of a nationwide screening colonoscopy registry and national data on colorectal cancer (CRC) incidence.Registry based study.National screening colonoscopy programme in Germany.Participants of screening colonoscopy in 2003 and 2004 (n = 840,149).Advanced adenoma prevalence, colorectal cancer incidence, annual and 10 year cumulative risk of developing CRC among carriers of advanced adenomas according to sex and age (range 55-80+ years)The age gradient is much stronger for CRC incidence than for advanced adenoma prevalence. As a result, projected annual transition rates from advanced adenomas to CRC strongly increase with age (from 2.6% in age group 55-59 years to 5.6% in age group >or=80 years among women, and from 2.6% in age group 55-59 years to 5.1% in age group >or=80 years among men). Projections of 10 year cumulative risk increase from 25.4% at age 55 years to 42.9% at age 80 years in women, and from 25.2% at age 55 years to 39.7% at age 80 years in men.Advanced adenoma transition rates are similar in both sexes, but there is a strong age gradient for both sexes. Our estimates of transition rates in older age groups are in line with previous estimates derived from small case series in the pre-colonoscopy era independent of age. However, our projections for younger age groups are considerably lower. These findings may have important implications for the design of CRC screening programmes.
Revenge and forgiveness or betrayal blindness?
Authors: Sasha Johnson-Freyd, Jennifer J. Freyd
Journal: Behavioral and Brain Sciences (2012)

Abstract McCullough et al. hypothesize that evolution has selected mechanisms for revenge to deter harms and for forgiveness to preserve valuable relationships. However, in highly dependent relationships, the more adaptive course of action may be to remain unaware of the initial harm rather than risk alienating a needed other. We present a testable model of possible victim responses to interrelational harm.
Influence of gas density on simulated snoring
Authors: G Liistro, C Veriter, D Stanescu
Journal: European Respiratory Journal (1999)

According to a recent theoretical model, snoring is related to instability of the upper airway (UA). Factors promoting UA instability include increased gas density. The aim of this study was to test the influence of gas density on simulated snoring production and supraglottic resistance. Supraglottic pressure and flow rate (V') were measured in 10 healthy seated subjects during simulated snoring. Subjects breathed three different gas mixtures: Helium-oxygen, He 79%-O2 21% (He-O2); air; and sulphur hexafluoride-oxygen, F6S 79%-O2 21% (F6S-O2) administered in a random order. Supraglottic resistance (Rsg) was measured on its linear range during quiet breathing and V' was measured at the onset and middle of snoring. Linear Rsg increased and V' conversely decreased with gas density. These data are in agreement with predictions of a mathematical model of the upper airway showing that snoring occurs at lower flow rates when gas density is increased.
Hyperinsulinaemia, hyperaminoacidaemia and post-exercise muscle anabolism: the search for the optimal recovery drink
Authors: A H Manninen
Journal: British Journal of Sports Medicine (2006)

Dietary supplements and other ergogenic aids are popular among athletes. Recent studies have shown that nutritional mixtures containing protein hydrolysates, added leucine, and high-glycaemic carbohydrates greatly augment insulin secretion compared with high-glycaemic carbohydrates only. When post-exercise hyperinsulinaemia is supported by hyperaminoacidaemia induced by protein hydrolysate and leucine ingestion, net protein deposition in muscle should occur. Thus, consumption of post-exercise recovery drinks containing these nutrients in conjunction with appropriate resistance training may lead to increased skeletal muscle hypertrophy and strength. However, the long-term effects on body composition and exercise performance remain to be determined.
Practical Application of a Calculator for Conditional Survival in Colon Cancer
Authors: George J. Chang, Chung-Yuan Hu, Cathy Eng, John M. Skibber, Miguel A. Rodriguez-Bigas
Journal: Journal of Clinical Oncology (2009)

Conditional survival (CS) estimates provide important prognostic information for clinicians and patients who have survived a period after diagnosis. In this study we performed a contemporary evaluation of conditional survival among colon cancer patients and created a browser-based tool for real-time determination of conditional survival expectancies.Patients with colon adenocarcinoma diagnosed between 1988 and 2000 were identified from the Surveillance Epidemiology End Results (SEER) registry. Conditional survival estimates were calculated by using the multiplicative law of probability after adjustment for age; sex; ethnicity; grade; and American Joint Commission on Cancer, sixth edition stage. A browser-based calculator was constructed.A total of 83,419 patients were analyzed. As the time alive after initial treatment increased from 0 to 5 years, significant improvements in CS were observed for patients in all stages except stage I, which was associated with good CS even at diagnosis and which reflected the high likelihood of cure. Notably, adjusted 5-year CS rates improved from 42% to 80% for stage IIIC cancers and from 5% to 48% for stage IV cancers during the first 5 years. Differences in cancer-related CS at diagnosis were identified on the basis of age, ethnicity, and grade, but these differences decreased over time. A browser-based CS calculator was implemented by using the multivariate survival model (concordance index, 0.81).For patients with colon cancer who survive over time, 5-year, cancer-specific CS improved dramatically, and the greatest improvements were among patients with poorer initial prognoses. These prognostic data are critical to inform patients for non-treatment-related life decisions and to inform treating physicians for planning of follow-up and surveillance strategies.
Inhibition of Stearoyl-Coenzyme A Desaturase 1 Dissociates Insulin Resistance and Obesity From Atherosclerosis
Authors: J. Mark Brown, Soonkyu Chung, Janet K. Sawyer, Chiara Degirolamo, Heather M. Alger, Tam Nguyen, Xuewei Zhu, My-Ngan Duong, Amanda L. Wibley, Ramesh Shah, Matthew A. Davis, Kathryn Kelley, Martha D. Wilson, Carol Kent, John S. Parks, Lawrence L. Rudel
Journal: Circulation (2008)

Background— Stearoyl-coenzyme A desaturase 1 (SCD1) is a well-known enhancer of the metabolic syndrome. The purpose of the present study was to investigate the role of SCD1 in lipoprotein metabolism and atherosclerosis progression. Methods and Results— Antisense oligonucleotides were used to inhibit SCD1 in a mouse model of hyperlipidemia and atherosclerosis (LDLr −/− Apob 100/100 ). In agreement with previous reports, inhibition of SCD1 protected against diet-induced obesity, insulin resistance, and hepatic steatosis. Unexpectedly, however, SCD1 inhibition strongly promoted aortic atherosclerosis, which could not be reversed by dietary oleate. Further analyses revealed that SCD1 inhibition promoted accumulation of saturated fatty acids in plasma and tissues and reduced plasma triglyceride, yet had little impact on low-density lipoprotein cholesterol. Because dietary saturated fatty acids have been shown to promote inflammation through toll-like receptor 4, we examined macrophage toll-like receptor 4 function. Interestingly, SCD1 inhibition resulted in alterations in macrophage membrane lipid composition and marked hypersensitivity to toll-like receptor 4 agonists. Conclusions— This study demonstrates that atherosclerosis can occur independently of obesity and insulin resistance and argues against SCD1 inhibition as a safe therapeutic target for the metabolic syndrome.
Chest physiotherapy in hospitalized patients with cystic fibrosis: a study of lung function effects and sputum production
Authors: B Oberwaldner, B Theissl, A Rucker, MS Zach
Journal: European Respiratory Journal (1991)

In order to evaluate the short-term lung function effects of high-pressure positive expiratory pressure (PEP)-mask physiotherapy (PT) in relation to PT-assisted sputum production, we studied 18 patients with cystic fibrosis (CF), hospitalized for a pulmonary exacerbation. Lung functions were measured before (a) and after PT (b) on day one (1), five (2), ten (3) and fifteen (4). Five functions improved significantly from a1 to b1, eight from a2 to b2, seven from a3 to b3, and seven from a4 to b4. Baseline (a) measurements improved only slightly, but post-PT (b) values improved more markedly from 1 to 4, and this improvement reached statistical significance for six functions; consequently, a-to-b lung function changes tended to increase from investigation 1 to 4. Eleven PT-induced lung function changes correlated to the weight of sputum produced. High-pressure PEP-mask PT therefore resulted in significant lung function improvements, and not only maintained but increased its effect in the course of the hospitalization.
Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study)
Authors: C. Pinto, F. Di Fabio, S. Siena, S. Cascinu, F.L. Rojas Llimpe, C. Ceccarelli, V. Mutri, L. Giannetta, S. Giaquinta, C. Funaioli, R. Berardi, C. Longobardi, E. Piana, A.A. Martoni
Journal: Annals of Oncology (2006)