tbuckley/cabot-search huggingface dataset:
Vascular Distension and Continued Ventilation Are Protective in Lung Ischemia/Reperfusion
Authors: HARTWIG SCHÜTTE, GERD HERMLE, WERNER SEEGER, FRIEDRICH GRIMMINGER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Biophysical factors have been implicated in the development of pulmonary ischemia-reperfusion injury. In isolated rabbit lungs, the impact of vascular and alveolar distension, with and without alveolar oxygen supply, was investigated. With interruption of both perfusion (zero intravascular pressure) and ventilation, reperfusion after 120 min of warm ischemia resulted in transient pulmonary hypertension, with largely unchanged microvascular pressures, followed by a dramatic leakage response with ∼ 10-fold increased capillary filtration coefficients (Kfc) and severe edema. Maintenance of vascular distension during ischemia (intravascular pressure of ∼ 2 to 3 mm Hg) reduced the hypertension and fully suppressed the leakage. Employing ischemic periods of 180 and 240 min, ventilation of the lungs with 21 or 100% oxygen > ventilation with nitrogen during perfusion stop, but not static anoxic inflation, further enhanced the protective effect of vascular distension. At optimal biophysical support (vascular distension and ongoing normoxic ventilation), even 240 min of warm ischemia was tolerated with only moderate Kfc increase. We conclude that biophysical factors exert marked influence on pulmonary ischemia-reperfusion injury. Maintenance of vascular distension possesses strong protective potency, further enhanced by continued ventilation and alveolar oxygen supply during ischemia. These results may have important implications for organ preservation in lung transplantation.
Melatonin in Cancer Management: Progress and Promise
Authors: Brittney Jung, Nihal Ahmad
Journal: Cancer Research (2006)

Abstract Physiologic and pharmacologic concentrations of the pineal hormone melatonin have shown chemopreventive, oncostatic, and tumor inhibitory effects in a variety of in vitro and in vivo experimental models of neoplasia. Multiple mechanisms have been suggested for the biological effects of melatonin. Not only does melatonin seem to control development alone but also has the potential to increase the efficacy and decrease the side effects of chemotherapy when used in adjuvant settings. This review critically evaluates progress in the ability of melatonin to prevent or reverse cancer development and progression. We also discuss future prospects of the possible development of melatonin as a chemopreventive agent. (Cancer Res 2006; 66(20): 9789-93)
Guidelines for management of patients with a short bowel
Authors: J Nightingale
Journal: Gut (2006)

1.1 Aim These guidelines aim to help clinicians manage patients who have had an intestinal resection that leaves a short length (about 2 m or less) of small bowel remaining. DevelopmentThe preliminary guidelines were compiled from the literature and a first document was drafted by Dr J Nightingale and modified by members of the Small Bowel and Nutrition Committee under the chairmanship of Dr B Jones.A section on ''intestinal transplantation'' was written by Dr Woodward and added with the
An arthritogenic lymphokine in the rat.
Authors: S M Helfgott, R Dynesius-Trentham, E Brahn, D E Trentham
Journal: The Journal of Experimental Medicine (1985)

A type II collagen-specific arthritogenic lymphokine has been identified in the rat. Arthritogenic factor (AF) is a 65 kD protein generated in vitro by T cells from rats with collagen arthritis, and it induces an erosive, proliferative synovitis when injected into the knee joint of syngeneic naive recipients. Complement does not appear to be required. These data identify a potential T cell-mediated effector mechanism in this model, and suggest that AF may function in other inflammatory synovial diseases.
Risk:benefit ratio is important in treating atopic dermatitis
Authors: B R. Allen
Journal: BMJ (2002)

EDITOR—Williams acknowledges the efficacy of tacrolimus and pimecrolimus in atopic dermatitis but subsequently his editorial is negative and lacks any patient perspective.1 The issue lies not in clinicians' disembodied comparisons of efficacy but in what treatment provides patients, or their affected children, with the most acceptable benefit : risk ratio.

Only 40% of patients with eczema are reportedly satisfied with their treatment, and work from Williams's own department has shown that in many cases using a topical corticosteroid produces risks, especially of …
Pemetrexed Pathway–Associated Germline Polymorphisms: A Useful Tool for Treatment Individualization?
Authors: Wieneke A. Buikhuisen, Jacobus A. Burgers, Andrew D. Vincent, Jan H.M. Schellens, Jos H. Beijnen, Egbert F. Smit, Markus Joerger
Journal: Journal of Clinical Oncology (2010)

However,pemetrexed is still costly and is considered an expensive drug by theDutch Healthy Authority, as it amounts to a cost of approximately€14,000 per patient and a total of €19 to 24 million per year in theNetherlands. Therefore, every effort should be undertaken to addi-tionally individualize lung cancer treatment with pemetrexed, andpharmacogenetictraitsareprimecandidates.ThestudybyAdjeietal
Abstract 115: S100A6 Regulates Endothelial Cell Cycle Progression via Modulation of the STAT1 Signaling Pathway
Authors: Carolin Lerchenmüller, Julian Heissenberg, Karsten Peppel, Hugo A Katus, Hauke Busch, Melanie Börries, Patrick Most
Journal: Circulation Research (2014)

S100A6, also known as Calcyclin, is a 10.5kDa Ca 2+ -binding protein that belongs to the S100 protein family. We have found S100A6 to be highly expressed throughout all vascular layers during the remodeling process in pig coronary arteries after stenting and rat carotid arteries post balloon dilatation injury. It was the objective of this study to decipher S100A6’s function in vascular cells. Abundant S100A6 expression was confirmed in vitro in human umbilical vein endothelial cells (HUVEC) and human umbilical artery smooth muscle cells (SMC). Upon serum stimulation, a significant increase of S100A6 protein levels was observed in both cell types. S100A6 depletion due to siRNA transfection lead to a profoundly reduced proliferation rate in response to growth factors (e.g. VEGF-A), shown by stagnating cell counts and decreased EdU incorporation in HUVEC and SMC. Of note, S100A6 depletion caused a significant migration deficit of SMC. Also, reduced S100A6 levels in HUVEC lead to an increase in cellular senescence, as measured by the expression of senescence associated β-galactosidase expression. To decipher the molecular mechanisms that lead to the phenotype of S100A6 depleted vascular cells, a time-resolved gene expression analysis was carried out in HUVECs and revealed S100A6 to be in control of antiproliferative signaling pathways, while typical pro-proliferative signaling, e.g. the MAPK pathway, was not disrupted. S100A6 depletion caused increased expression and activation of the STAT1 signaling pathway. With increased STAT1 activity, interferon-inducible protein (e.g. IFITM1) expression was upregulated and lead to stabilization and increased expression of the p53 pathway, specifically p21. We propose that S100A6, found to co-localize with the VEGFR2 in a Ca 2+ -dependent manner, controls antiproliferative signaling by inhibition of the STAT1-phosphorylation by the VEGFR2 and suppression of the STAT1-p53 signaling cascade in human endothelial cells. Endothelialization is a hallmark of vascular healing after stenting and balloon dilatation, for example, while it is of utmost importance to block neointima formation. Understanding these signaling pathways is critical to better direct optimization of interventional therapies.
Anticoagulation Interruptus
Authors: Michael D. Ezekowitz
Journal: Circulation (2004)

he need to withhold anticoagulation in patients requiring elective surgery poses a particularly important challenge when the risk of thrombosis and thromboembolism is high.In spite of the increasing use of prosthetic heart valves and the increasing prevalence of atrial fibrillation in the aging population, Kovacs et al 1 make the important point in this issue of Circulation that there is a paucity of information in the literature to guide the clinician to optimal care.This observation motivated the design of the prospective study they report.Patients' anticoagulation therapy was discontinued before surgery.There were 3 reporting phases: preoperative, intraoperative, and postoperative.
Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Disruptive Behaviors in Children With Subaverage Intelligence
Authors: Michael G. Aman, Goedele De Smedt, Albert Derivan, Ben Lyons, Robert L. Findling, None Risperidone Disruptive Behavior Study Group
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The short-term efficacy and safety of risperidone in the treatment of disruptive behaviors was examined in a well-characterized cohort of children with subaverage intelligence. METHOD: In this 6-week, multicenter, double-blind, parallel-group study of 118 children (aged 5–12 years) with severely disruptive behaviors and subaverage intelligence (IQ between 36 and 84, inclusive), the subjects received 0.02–0.06 mg/kg per day of risperidone oral solution or placebo. The a priori primary efficacy measure was the change in score from baseline to endpoint on the conduct problem subscale of the Nisonger Child Behavior Rating Form. RESULTS: The risperidone group showed significantly greater improvement than did the placebo group on the conduct problem subscale of the Nisonger Child Behavior Rating Form from week 1 through endpoint (change in score of –15.2 and –6.2, respectively). Risperidone was also associated with significantly greater improvement than placebo on all other Nisonger Child Behavior Rating Form subscales at endpoint, as well as on the Aberrant Behavior Checklist subscales for irritability, lethargy/social withdrawal, and hyperactivity; the Behavior Problems Inventory aggressive/destructive behavior subscale; a visual analogue scale of the most troublesome symptom; and the Clinical Global Impression change score. The most common adverse effects reported during risperidone treatment were headache and somnolence. The extrapyramidal symptom profile of risperidone was comparable to that of placebo. Mean weight increases of 2.2 kg. and 0.9 kg occurred in the risperidone and placebo groups, respectively. CONCLUSIONS: Risperidone was effective and well tolerated for the treatment of severely disruptive behaviors in children with subaverage IQ.
A novel chimeric natriuretic peptide reduces cardiomyocyte hypertrophy through the NHE-1–calcineurin pathway
Authors: Ana Kilić, Venkatesh Rajapurohitam, Sharon M. Sandberg, Asad Zeidan, J. Craig Hunter, Nazo Said Faruq, Candace Y. Lee, John C. Burnett, Morris Karmazyn
Journal: Cardiovascular Research (2010)

Natriuretic peptides (NPs) inhibit cardiomyocyte hypertrophy through a cyclic GMP (cGMP)-dependent process, although these effects are associated with substantial vasodilatation. In this study, we used CU-NP, a non-vasodilatating novel NP synthesized from the ring structure of human C-type NP (CNP) and both C- and N-termini of urodilatin, and investigated whether it can directly modulate cardiomyocyte hypertrophy.Experiments were carried out in cultured neonatal rat ventricular myocytes exposed to phenylephrine, angiotensin II, or endothelin-1 in the absence or presence of CU-NP. CU-NP produced a concentration- and time-dependent increase in intracellular cGMP levels. The hypertrophic responses to all agonists were abrogated by 10 nM CU-NP. CU-NP treatment also prevented increased activity, gene and protein expression of sodium-hydrogen exchanger-1 (NHE-1) as well as elevations in intracellular Na(+) concentrations caused by hypertrophic agents. In addition, these effects were associated with a more than two-fold increase in activity of the Ca(2+)-dependent protein phosphatase calcineurin that peaked 6 h after addition of hypertrophic stimuli. Early (1-3 h) calcineurin activation was unaffected by CU-NP, although activation at 6 and 24 h was prevented by CU-NP as was the resultant translocation of the transcriptional factor NFAT into nuclei.Our study demonstrates a direct anti-hypertrophic effect of the chimeric peptide CU-NP via NHE-1 inhibition, thereby preventing calcineurin activation and NFAT nuclear import. Thus, CU-NP represents a novel fusion peptide of CNP and urodilatin that has the potential to be developed into a therapeutic agent to treat cardiac hypertrophy and heart failure.
Bronchorrhoea complicating inflammatory bowel disease
Authors: R Jain, D Scheurich, G M Lindberg, C E Girod
Journal: Thorax (2006)

Bronchorrhoea complicating inflammatory bowel diseaseA 25 year old Hispanic man with a 3 year history of ulcerative colitis presented with 8 months of productive cough with over 200 ml of yellow sputum, fatigue, dyspnoea, diarrhoea, night sweats, and weight loss.At the time of presentation the patient was on a low dose of mesalamine (400 mg three times daily) and azathioprine (25 mg/day).Examination revealed coarse crackles at the lung bases and a prolonged expiratory phase.The white blood cell count was normal.The chest radiograph showed bilateral reticulonodular infiltrates with acinonodular opacities, and a high resolution CT scan showed diffuse bronchiectasis, centrilobular nodules, and a ''tree-in-bud'' pattern (fig 1).Obstruction with air trapping was found on pulmonary function tests.Bronchoscopic examination showed diffuse purulent secretions throughout the major airways (fig 2A).BAL fluid smears and cultures were negative for acid-fast bacilli, fungus, and bacterial pathogens.Transbronchial biopsies revealed dense lymphoplasmacytic inflammation and infiltration of the bronchial mucosa (fig 2B).Rapid resolution of pulmonary and gastrointestinal symptoms occurred after initiation of prednisone 40 mg/day and an increase in azathioprine to 100 mg/day.Pulmonary manifestations of inflammatory bowel disease are uncommon and present as a clinical spectrum including airway disease, interstitial lung disease, parenchymal nodules, and serositis. 1 2Diagnosis is often delayed. 3Our patient presented with a chief complaint of bronchorrhoea due to diffuse bronchiectasis and bronchiolitis which ultimately proved to be due to inflammatory bowel disease.
Transport of Steroid Hormones through the Rat Blood-Brain Barrier
Authors: William M. Pardridge, Lawrence J. Mietus
Journal: Journal of Clinical Investigation (1979)

These studies were undertaken to investigate (a) the permeability properties of the blood-brain barrier (BBB) to the major gonadal and adrenal steroid hormones, and (b) the role of the binding proteins of plasma (albumin and specific globulins) in the regulation of BBB steroid hormone transport.
Temporal associations between coughing or wheezing and acid reflux in asthmatics
Authors: B Avidan
Journal: Gut (2001)

<h3>BACKGROUND AND AIMS</h3> The pulmonary symptoms of patients with lung disease may be ascribed to gastro-oesophageal reflux although a causal relationship between acid reflux and coughing or wheezing has not been proved. Does cough cause reflux or does reflux cause cough? The aim of this study was to evaluate 24 hour oesophageal pH tracings of asthmatics with gastro-oesophageal reflux to determine the temporal association between acid reflux and coughing or wheezing. <h3>METHODS</h3> The oesophageal tracings of 128 asthmatics from the outpatient clinics who underwent oesophagogastroduodenoscopy, oesophageal manometry, and 24 hour oesophageal pH monitoring were analysed. Three possible temporal relationships between the occurrence of acid reflux and the occurrence of coughs or wheezes were evaluated: (1) pulmonary symptoms preceding reflux; (2) reflux preceding pulmonary symptoms; and (3) unrelated occurrence of both events. <h3>RESULTS</h3> Of 128 asthmatics, 53 recorded five or more coughs and 19 recorded three or more wheezes during the 24 hour recording period. Mean acid contact time was similar in asthmatics with and without pulmonary symptoms (12.2 (1.2)% <i>v</i> 10.4 (0.6)%). Of all coughs and wheezes, 46% and 48%, respectively, were associated with acid reflux. For the individual asthmatic, the likelihood of reflux induced coughing increased as the number of coughs increased. <h3>CONCLUSIONS</h3> Half of all coughs and wheezes in asthmatics are associated with acid reflux into the oesophagus. While an occasional coughing episode can lead to reflux, it is rather the reflux episode in the vast majority of instances that leads to cough.
Incomplete mitral leaflet closure in patients with papillary muscle dysfunction.
Authors: R W Godley, L S Wann, E W Rogers, H Feigenbaum, A E Weyman
Journal: Circulation (1981)

Clinical acceptance of an association between papillary muscle dysfunction and mitral regurgitation is widespread, despite the lack of objective support. To evaluate a possible association, we performed echocardiographic examinations on 22 patients with prior myocardial infarction and clinical evidence of papillary muscle dysfunction, 40 patients with prior myocardial infarction and no clinical evidence of papillary muscle dysfunction, and 20 normal subjects. There was a unique pattern of incomplete mitral leaflet closure in a high percentage (91%) of infarct patients with mitral regurgitation. In these patients, one or both leaflets were effectively arrested within the cavity of the left ventricle during ventricular systole. Dyskinetic wall motion in the region immediately surrounding one of the papillary muscles was present in 23 of 24 patients (96%) with demonstrated incomplete closure. This study provides the first objective evidence that de novo mitral regurgitation in patients with prior myocardial infarction is due to dyskinesis involving the left ventricular myocardium beneath one of the papillary muscles, producing increased tension on the mitral leaflets and preventing normal closure.
The rapamycin-regulated gene expression signature determines prognosis for breast cancer
Authors: Argun Akcakanat, Li Zhang, Spiridon Tsavachidis, Funda Meric-Bernstam
Journal: Molecular Cancer (2009)

Mammalian target of rapamycin (mTOR) is a serine/threonine kinase involved in multiple intracellular signaling pathways promoting tumor growth. mTOR is aberrantly activated in a significant portion of breast cancers and is a promising target for treatment. Rapamycin and its analogues are in clinical trials for breast cancer treatment. Patterns of gene expression (metagenes) may also be used to simulate a biologic process or effects of a drug treatment. In this study, we tested the hypothesis that the gene-expression signature regulated by rapamycin could predict disease outcome for patients with breast cancer.Colony formation and sulforhodamine B (IC50 < 1 nM) assays, and xenograft animals showed that MDA-MB-468 cells were sensitive to treatment with rapamycin. The comparison of in vitro and in vivo gene expression data identified a signature, termed rapamycin metagene index (RMI), of 31 genes upregulated by rapamycin treatment in vitro as well as in vivo (false discovery rate of 10%). In the Miller dataset, RMI did not correlate with tumor size or lymph node status. High (>75th percentile) RMI was significantly associated with longer survival (P = 0.015). On multivariate analysis, RMI (P = 0.029), tumor size (P = 0.015) and lymph node status (P = 0.001) were prognostic. In van 't Veer study, RMI was not associated with the time to develop distant metastasis (P = 0.41). In the Wang dataset, RMI predicted time to disease relapse (P = 0.009).Rapamycin-regulated gene expression signature predicts clinical outcome in breast cancer. This supports the central role of mTOR signaling in breast cancer biology and provides further impetus to pursue mTOR-targeted therapies for breast cancer treatment.
Palliation of cyanotic congenital heart disease in infancy with E-type prostaglandins.
Authors: J M Neutze, M B Starling, R B Elliott, B G Barratt-Boyes
Journal: Circulation (1977)

Prostaglandin-E (PGE) infusions have been used in an attempt to increase ductal patency in 11 infants aged one to 99 days with cyanotic heart disease. PGE1 was used in nine infants and PGE2 in two. Five patients had pulmonary atresia, four extreme pulmonary stenosis, one Ebstein's anomaly and one simple transposition of the great arteries. All but the oldest infant showed a satisfactory increase in oxygen saturation (average 36%) attributed to dilatation of the ductus. The failure in one infant may have been due largely to hypoplasia of the left pulmonary artery. The only important side effect was apnea in one infant receiving PGE2. The efficacy of this form of treatment is confirmed in infants dependent on ductal patency for survival. PGE is an important asset in saving the lives of neonates requiring an aorticopulmonary shunt operation. The recommended starting dose is 0.1 mug/kg/min of PGE1 given by constant infusion.
Reference values of arterial oxygen tension in the middle-aged and elderly.
Authors: I Cerveri, M C Zoia, F Fanfulla, L Spagnolatti, L Berrayah, M Grassi, C Tinelli
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The lack of available reference values of arterial PO2, particularly for elderly persons, led us to study a sample of 194 normal nonsmoking subjects, equally distributed over all age ranges from 40 to 90 yr. The radial artery was punctured and blood samples were taken and analyzed on an automated, computerized gas-analyzer. The trend of the mean values of PaO2 in the 5-yr class intervals of age showed a clear decline up to the 70- to 74-yr class, and then an inversion. The two regression lines intersecting at this point provided a better fit to the data than did a single regression line (R22 - R12 = 0.918 - 0.678 = 0.24; F = 20.49, p = 0.0027). The relationship of PaO2 with age was thus subsequently considered for the two subgroups (40 to 74 yr; > or = 75 yr) identified on the basis of this cutoff. Because of the significant influence on Pao2 of age, body-mass index (BMI), and PaCO2 in the group 40 to 74 yr of age, the following reference equation was constructed: Pao2 (mm Hg) = 143.6 - (0.39 . age) - (0.56 . BMI) - (0.57 . PaCO2); R2 = 0.28; SEE = 7.48; p < 0.0001. For subjects > or = 75 yr old, for whom there was no correlation with age, BMI, or PaCO2, only the mean +/- SD and 5th percentile of PaO2 were reported (83.4 +/- 9.15 mm Hg and 68.4 mm Hg, respectively). PaCO2 values were not correlated with either age or BMI; the mean +/- SD was 35.79 +/- 3.87 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacokinetics and Tissue Distribution of Doxorubicin Encapsulated in Stable Liposomes With Long Circulation Times
Authors: A. Gabizon, R. Shiota, D. Papahadjopoulos
Journal: JNCI Journal of the National Cancer Institute (1989)

We have previously reported on liposome formulations with reduced uptake by the reticuloendothelial system, prolonged circulation time, and enhanced accumulation in transplanted tumors. One of these formulations, consisting of hydrogenated phosphatidylinositol (HPI), hydrogenated phosphatidylcholine (HPC), and cholesterol (Chol) (HPI-HPC-Chol), and a control formulation, consisting of phosphatidylglycerol (PG), phosphatidylcholine (PC), and Chol (PG-PC-Chol), were loaded with doxorubicin (DXR) and injected intravenously into BALB/c mice for pharmacokinetic studies. Although both formulations were similar in vesicle size, fraction of negatively charged lipid, and drug-to-lipid ratio, there were striking pharmacokinetic differences. DXR was cleared much faster in PG-containing liposomes than in HPI-containing liposomes. Liposome-associated drug was detectable in plasma up to 5 hours after injection in the case of PG-PC-Chol and as late as 72 hours after injection in the case of HPI-HPC-Chol. In agreement with the plasma clearance curves, peak drug concentrations in the liver were observed at 1/2, 5, and 24 hours after injection for free DXR, DXR in PG-PC-Chol, and DXR in HPI-HPC-Chol, respectively. Both types of liposomes reduced considerably the amount of drug accumulating in the heart compared with that accumulating after injection of free DXR.