tbuckley/cabot-search huggingface dataset:
United airways disease: therapeutic aspects
Authors: G. Passalacqua
Journal: Thorax (2000)

Objective. This study aimed at investigating: the relationship between WM integrity and processing speed (PS) performance, and the PS-dependent relationship between WM integrity and higher order cognitive functions in patients with SPMS. Background. Secondary progressive multiple sclerosis (SPMS) is a neurodegenerative disease in which patients develop grey and white matter (GM, WM) degeneration and cognitive impairment, including PS deficits. However, the relationship between WM integrity and PS has yet to be clarified. Methods. Thirty one patients with SPMS (mean age, 52.5 years; mean disease duration, 15.5years; mean EDSS, 6.4) had detailed neuropsychological assessment (Trail Making Test A, Stroop test, Digit Cancellation, category and letter fluency). A PS index was computed by combining TMT-A, Stroop speed, and Digit Cancellation. T1-weighted and diffusion weighted MR images were acquired. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) techniques were used to investigate: the correlations between WM/GM measures and cognitive variables; and the differences in WM/GM measures between high (HP) and low performers (LP) divided on the bases of the PS index. Results. VBM analysis showed that only the PS index and timed fluency tasks correlated with left-lateralised WM tracts. Moreover, the HP subgroup had more WM than LP in the same WM tracts. Consistent results were found for fractional anisotropy (FA) in the TBSS analysis: correlations were seen mainly in a wide network of associative tracts only for PS-dependent tests. Furthermore, HP showed higher FA and lower mean diffusivity than LP in similar WM tracts: namely the left superior longitudinal fasciculus and left inferior fronto-occipital fasciculus. Conclusions. In SPMS, PS relies on WM rather than GM integrity as does performance in PS-dependent higher order cognitive functions. WM associative tracts supporting fast integration of information across the brain seem to be crucially involved in tasks requiring effective management of time. <b>Disclosure:</b> Dr. Manca has nothing to disclose. Dr. Stabile has nothing to disclose. Dr. Bevilacqua has nothing to disclose. Dr. Sharrack has nothing to disclose. Dr. Venneri has received personal compensation for activities with Novartis.
Angiotensin II Activates Nuclear Transcription Factor κB Through AT <sub>1</sub> and AT <sub>2</sub> in Vascular Smooth Muscle Cells
Authors: Marta Ruiz-Ortega, Oscar Lorenzo, Mónica Rupérez, Sven König, Burghardt Wittig, Jesús Egido
Journal: Circulation Research (2000)

Abstract —Nuclear factor-κB (NF-κB) regulates many genes involved in vascular physiopathology. We have previously observed in vivo NF-κB activation in injured vessels that diminished by angiotensin-converting enzyme inhibition. In the present work, we investigated the effect of angiotensin II (Ang II) on NF-κB activity in rat vascular smooth muscle cells, evaluating the molecular mechanisms and the specific receptor subtype involved. Ang II increased NF-κB DNA binding (5-fold, 10 − 9 mol/L at 1 hour; electrophoretic mobility shift assay), nuclear translocation of p50/p65 subunits, and cytosolic inhibitor κBα (IκBα) degradation. Ang II elicited NF-κB–mediated transcription (transfection of a reporter gene) and expression of NF-κB–related genes (monocyte chemoattractant protein-1 and angiotensinogen). AT 1 (DUP753) and AT 2 (PD123319 and CGP42112 ) receptor antagonists inhibited Ang II–induced NF-κB DNA binding in a dose-dependent manner (≈85% for each one; 10 − 5 mol/L at 1 hour). The AT 2 agonist p -aminophenylalanine 6 –Ang II augmented NF-κB binding (4.6-fold, 10 − 9 mol/L at 1 hour), p65 nuclear levels, and transcription of an NF-κB reporter gene. AT 1 antagonist markedly inhibited NF-κB–mediated transcription and gene expression. Some differences between AT 1 /AT 2 intracellular signals were found. Antioxidants and ceramide inhibitors, but not protein kinase C inhibitors, diminished NF-κB activation elicited by both Ang II and the AT 2 agonist, while tyrosine kinase inhibitors only decreased Ang II–induced NF-κB activity. Our results demonstrate that Ang II activates NF-κB via AT 1 and AT 2 , although NF-κB–mediated transcription occurred mainly through AT 1 . Both receptors share some signaling pathways (oxygen radicals and ceramide); however, tyrosine kinases only participate in AT 1 /NF-κB responses. These data provide novel insights into Ang II actions, suggesting a potential implication of the AT 2 in the pathobiology of vascular cells.
Antenatal Sildenafil Treatment Attenuates Pulmonary Hypertension in Experimental Congenital Diaphragmatic Hernia
Authors: Christina Luong, Juliana Rey-Perra, Arul Vadivel, Greg Gilmour, Yves Sauve, Debby Koonen, Don Walker, Kathryn G. Todd, Pierre Gressens, Zamaneh Kassiri, Khurram Nadeem, Beverly Morgan, Farah Eaton, Jason R. Dyck, Stephen L. Archer, Bernard Thébaud
Journal: Circulation (2011)

Lung hypoplasia and persistent pulmonary hypertension of the newborn limit survival in congenital diaphragmatic hernia (CDH). Unlike other diseases resulting in persistent pulmonary hypertension of the newborn, infants with CDH are refractory to inhaled nitric oxide (NO). Nitric oxide mediates pulmonary vasodilatation at birth in part via cyclic GMP production. Phosphodiesterase type 5 (PDE5) limits the effects of NO by inactivation of cyclic GMP. Because of the limited success in postnatal management of CDH, we hypothesized that antenatal PDE5 inhibition would attenuate pulmonary artery remodeling in experimental nitrofen-induced CDH.Nitrofen administered at embryonic day 9.5 to pregnant rats resulted in a 60% incidence of CDH in the offspring and recapitulated features seen in human CDH, including structural abnormalities (lung hypoplasia, decreased pulmonary vascular density, pulmonary artery remodeling, right ventricular hypertrophy), and functional abnormalities (decreased pulmonary artery relaxation in response to the NO donor 2-(N,N-diethylamino)-diazenolate-2-oxide). Antenatal sildenafil administered to the pregnant rat from embryonic day 11.5 to embryonic day 20.5 crossed the placenta, increased fetal lung cyclic GMP and decreased active PDE5 expression. Antenatal sildenafil improved lung structure, increased pulmonary vessel density, reduced right ventricular hypertrophy, and improved postnatal NO donor 2-(N,N-diethylamino)-diazenolate-2-oxide-induced pulmonary artery relaxation. This was associated with increased lung endothelial NO synthase and vascular endothelial growth factor protein expression. Antenatal sildenafil had no adverse effect on retinal structure/function and brain development.Antenatal sildenafil improves pathological features of persistent pulmonary hypertension of the newborn in experimental CDH and does not alter the development of other PDE5-expressing organs. Given the high mortality/morbidity of CDH, the potential benefit of prenatal PDE5 inhibition in improving the outcome for infants with CDH warrants further studies.
Leptin Deficiency Shifts Mast Cells toward Anti-Inflammatory Actions and Protects Mice from Obesity and Diabetes by Polarizing M2 Macrophages
Authors: Yi Zhou, Xueqing Yu, Huimei Chen, Sara Sjöberg, Joséphine Roux, Lijun Zhang, Al-Habib Ivoulsou, Farid Bensaid, Cong-Lin Liu, Jian Liu, Joan Tordjman, Karine Clement, Chih-Hao Lee, Gokhan S. Hotamisligil, Peter Libby, Guo-Ping Shi
Journal: Cell Metabolism (2015)
Oral Chemotherapy Program Improves Adherence and Reduces Medication Wastage and Hospital Admissions
Authors: Nikhil Khandelwal, Ian Duncan, Tamim Ahmed, Elan Rubinstein, Cheryl Pegus
Journal: Journal of the National Comprehensive Cancer Network (2012)

Adherence, medication wastage, and reduction in hospital admissions were investigated in a retrospective test-control study design for patients enrolled in the oral chemotherapy cycle management program (CMP), a program that offers clinical support, dose monitoring, and early identification of side effects for patients on select oral chemotherapy. Patients who initiated oral chemotherapy with sorafenib, sunitinib, or erlotinib during June 2008 through December 2009 and who were enrolled in the CMP were included as a test group. Patients who initiated oral chemotherapy with these drugs using Walgreens Specialty Pharmacy during January 2007 through May 2008 and were not part of the CMP were included as control group 1, and patients from a national payor database who initiated therapy with sorafenib, sunitinib, or erlotinib during June 2008 through August 2010 were included as control group 2. Compared with control group 1, patients in the CMP group showed no significant differences with regard to their possession ratios (P > .05), but demonstrated significantly higher persistency rates (P < .05) at the end of 6 months follow-up. For patients in the CMP group who discontinued therapy, approximately 34% could have experienced reduced wastage had they been on a split medication plan. Patients who are monitored closely and able to identify serious side effects early can avoid complications leading to hospitalizations. The study showed potential savings on drug costs because of a split-fill medication plan, and savings from reduced hospitalization associated with timely identification and management of severe side effects. A clinical program, such as CMP, effectively improves adherence and reduces wastage and hospitalizations for oral chemotherapeutic agents, realizing potential cost savings to both payors and patients.
Physical Activity, Physical Fitness, and Insulin and Glucose Concentrations in an Isolated Native Canadian Population Experiencing Rapid Lifestyle Change
Authors: Andrea M. Kriska, Anthony J.G. Hanley, Stewart B. Harris, Bernard Zinman
Journal: Diabetes Care (2001)

OBJECTIVE—Little is known about the relation of physical activity and physical fitness to insulin resistance and glucose intolerance in isolated subarctic Native Canadian populations. The purpose of this effort was to examine the relation between activity and fitness and obesity and glucose concentrations in such a unique population. RESEARCH DESIGN AND METHODS—This study describes 530 men and women from the community of Sandy Lake, Ontario, located in the boreal forest region of central Canada. Fasting blood glucose and insulin concentrations were determined after an overnight fast. Past year physical activity levels were assessed using a modified version of an interviewer-administered questionnaire. Maximal oxygen uptake, a measure of cardiovascular fitness, was estimated using a submaximal step test. RESULTS—Total (leisure and occupational) physical activity and physical fitness were significantly associated with fasting insulin concentrations after adjusting for age, BMI or percent body fat, waist circumference, and fasting glucose concentration in men but not in women. The relations between physical activity, fitness, and fasting glucose concentrations were not as strong or as consistent as they were when fasting insulin concentration was the dependent variable. CONCLUSIONS—In this isolated Native Canadian community, both physical activity and fitness were independently associated with fasting insulin concentrations, suggesting a beneficial role of physical activity/fitness on insulin sensitivity that is separate from any influence of activity on body composition. The fact that this relation was found in men but not in women is most likely explained by issues related to the measurement of activity and fitness in this study and the fact that the women in this population appear to be less active than the men.
Preliminary identification of core domains for outcome studies in psoriatic arthritis using Delphi methods
Authors: W J Taylor
Journal: Annals of the Rheumatic Diseases (2005)

To develop a consensus based set of core domains for outcome studies in psoriatic arthritis.A list of 26 potential domains was prepared through literature review and email discussions amongst the GRAPPA steering committee members and scored by rheumatologists identified through membership of the CASPAR study and the steering committee. Each participant was emailed an up to date review of outcome measures in psoriatic arthritis and asked to distribute 100 points amongst each potential domain. In two subsequent rounds the group median, interquartile range, and earlier responses were emailed to each respondent to provide an opportunity to revise their scoring.Thirty two participants responded to the first round, of whom 30 responded to the third round. For DC-ART, the highest scoring domains were actively inflamed joint count, radiological damage score, patient global assessment, pain, physical function, acute phase response, and quality of life (scores 7 to 12). For SMARD, the highest scoring domains were pain, patient global assessment, physical function, quality of life, and active joint count (scores 10 to 18). For clinical record keeping, three domains scored highly at 10 (pain, patient global assessment, and active joint count). For rehabilitation, the highest scoring domains were physical function, quality of life, pain, patient global assessment, work limitations, and work incapacity (scores 10 to 15).Amongst rheumatologists with an interest in psoriatic arthritis, a reduced list of potential standard outcome domains have been defined by Delphi consensus methods.
Contributions of [Ca2+]i, [Pi]i, and pHi to altered diastolic myocyte tone during partial metabolic inhibition.
Authors: H Ikenouchi, O Kohmoto, M McMillan, W H Barry
Journal: Journal of Clinical Investigation (1991)

Ischemia may cause increased or decreased distensibility of the left ventricle, but the cellular mechanisms involved have not been clarified. We examined the possible contributions of changes in intracellular inorganic phosphate, pH, and Ca2+ concentrations to altered diastolic function in cultured myocytes subjected to partial metabolic inhibition. Paced cultured embryonic chick and adult rabbit ventricular myocytes superfused with 20 mM 2-deoxyglucose (2DG) exhibited an increase in end-diastolic intracellular free calcium concentration ([Ca2+]i) and an upward shift in end-diastolic cell position. These results indicate that glycolytic blockade increases diastolic and systolic calcium in paced ventricular myocytes, and that this elevated diastolic calcium influences the extent of diastolic relaxation. In contrast, paced ventricular myocytes superfused with 1 mM cyanide (CN) exhibited a similar increase in end-diastolic [Ca2+]i but a decrease in end-diastolic cell position and amplitude of motion. Although changes in ATP contents were similar in both groups (2DG, -29.9%; CN, -40.1%), alterations of intracellular pH and inorganic phosphate concentrations were different. In 2DG-treated cells, pHi did not decrease significantly (7.18 +/- 0.04 to 7.12 +/- 0.11, n = 14) but in the CN group it decreased markedly within 6 min (7.18 +/- 0.04 to 6.76 +/- 0.11, n = 11, P less than 0.01). Intracellular inorganic phosphate decreased slightly in the 2DG group (-14.8%, NS) but increased in cells exposed to CN (45.7%, P less than 0.02). We conclude that while a prominent increase in diastolic [Ca2+]i occurs in rapidly paced ventricular myocytes exposed to either inhibitors of glycolysis or oxidative phosphorylation, the effects of this increase in [Ca2+]i on diastolic distensibility may be influenced by intracellular accumulation of metabolites that decrease the sensitivity of myofilament to [Ca2+]i.
New instrument for banding of the pulmonary artery for ventricular septal defect.
Authors: J. S. Bailey
Journal: BMJ (1967)

Role of the Forensic Science Laboratory-Walls MEDICBALJOURNAL 97(3) The part of the body from which a blood sample is taken should be stated.Portal vein blood, for example, will normally contain a higher concentration of the compounds sought than blood from other parts of the body.This fact has the double consequence that blood from another part of the body is preferable, and that calculations based on an unknowing analysis of * .' , . . .
Deletion of the Sphingosine Kinase-1 gene influences cell fate during hypoxia and glucose deprivation in adult mouse cardiomyocytes
Authors: R TAO, J ZHANG, D VESSEY, N HONBO, J KARLINER
Journal: Cardiovascular Research (2007)

Objectives: Activation of sphingosine kinase (SphK), which has two known isoforms, is responsible for the synthesis of sphingosine 1-phosphate (S1P), a cell survival factor. We tested the following hypotheses: 1] cardiac myocytes null for the SphK1 gene are more vulnerable to the stress of hypoxia+glucose deprivation; 2] the monoganglioside GM-1, which activates SphK via protein kinase C ε, is ineffective in SphK1-null myocytes; 3] S1P generated by SphK activation requires cellular export to be cardioprotective. Methods: We cultured adult mouse cardiac myocytes from wildtype and SphK1-null mice (deletion of exons 3–6) and measured cell viability by trypan blue exclusion. Results: In wildtype adult mouse cardiomyocytes subjected to 4 h of hypoxic stress+glucose deprivation, cell viability was significantly higher than in SphK1-null cardiomyocytes. SphK1-null cells also displayed more mitochondrial cytochrome C release. Cell death induced by hypoxia+glucose deprivation was substantially prevented by pretreatment with exogenous S1P in both wildtype and SphK1-null myocytes, but S1P was effective at a lower concentration in wildtype cells. Hence, the absence of the Sphk1 gene did not affect receptor coupling or downstream signal transduction. Pretreatment for 1 h with 1 μM of the monoganglioside GM-1 increased survival in wildtype cells, but not in SphK1-null myocytes. Thus, activation of SphK1 by GM-1 leads to cell survival. In wildtype cells, enhanced survival produced by GM-1 was abrogated by pretreatment either with 300 nM of the S1P1 receptor-selective antagonist VPC23019 or with 100 ng/ml of pertussis toxin for 16 h before exposure to hypoxia+glucose deprivation. Conclusion: As the effect of GM-1 is blocked both at the receptor and the G-protein (Gi) levels, we conclude that S1P generated by GM-1 treatment must be exported from the cell and acts in a paracrine or autocrine manner to couple with its cognate receptor.
The health of UK military personnel who deployed to the 2003 Iraq war: a cohort study
Authors: Matthew Hotopf, Lisa Hull, Nicola T Fear, Tess Browne, Oded Horn, Amy Iversen, Margaret Jones, Dominic Murphy, Duncan Bland, Mark Earnshaw, Neil Greenberg, Jamie Hacker Hughes, A Rosemary Tate, Christopher Dandeker, Roberto Rona, Simon Wessely
Journal: The Lancet (2006)
Cisplatin Excretion in Human Milk
Authors: GILAD BEN-BARUCH, JOSEPH MENCZER, RAN GOSHEN, BELLA KAUFMAN, RALPH GORODETSKY
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Cisplatin Excretion in Human Milk Get access GILAD BEN-BARUCH, GILAD BEN-BARUCH Search for other works by this author on: Oxford Academic PubMed Google Scholar JOSEPH MENCZER, JOSEPH MENCZER Search for other works by this author on: Oxford Academic PubMed Google Scholar RAN GOSHEN, RAN GOSHEN Search for other works by this author on: Oxford Academic PubMed Google Scholar BELLA KAUFMAN, BELLA KAUFMAN Search for other works by this author on: Oxford Academic PubMed Google Scholar RALPH GORODETSKY RALPH GORODETSKY Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 6, 18 March 1992, Pages 451–452, https://doi.org/10.1093/jnci/84.6.451 Published: 18 March 1992
Coamplification of <i>DDX1</i> Correlates With an Improved Survival Probability in Children With <i>MYCN</i>-Amplified Human Neuroblastoma
Authors: Axel Weber, Patricia Imisch, Eckhard Bergmann, Holger Christiansen
Journal: Journal of Clinical Oncology (2004)

Purpose Amplification of the MYCN oncogene at chromosome 2p24-25 identifies an aggressive subtype of human neuroblastoma with a poor clinical outcome. Differences in amplicon structure and coamplification of genes telomeric and centromeric to the MYCN oncogene have previously been described. A relevant role of gene coamplification for neuroblastoma pathogenesis remains elusive. Patients and Methods We analyzed 98 primary neuroblastoma tumors with MYCN amplification for coamplification of seven additional genes at chromosome 2p24-25 (DDX1, NAG, NSE1, LPIN1, EST- AA581763 , SMC6, and SDC1). Two semiquantitative multiplex polymerase chain reactions were used to obtain the amplification status of the target genes in relation to a reference gene on chromosome 2q (Inhibin-beta-b). Furthermore, mRNA expression pattern of coamplified genes in a subset of tumors was analyzed. Results Our results show that the frequency of gene coamplification on 2p24-25 in neuroblastoma is correlated directly to the physical distance to MYCN. Coamplification is correlated to an upregulated gene expression for DDX1 and NAG. Coamplification of the DDX1 gene within 400kb telomeric to MYCN identifies a subgroup of advanced stage neuroblastoma tumors with a more favorable outcome (P = .027, log-rank test). A high expression level of DDX1 is associated with a trend towards a better survival probability (P = .058, log-rank test). Conclusion Our results indicate that DDX1 coamplification correlates with a better prognosis and improved patient survival in MYCN-amplified neurobastoma.
Vascular Calcification
Authors: Rebecca C. Johnson, Jane A. Leopold, Joseph Loscalzo
Journal: Circulation Research (2006)

Once thought to result from passive precipitation of calcium and phosphate, it now appears that vascular calcification is a consequence of tightly regulated processes that culminate in organized extracellular matrix deposition by osteoblast-like cells. These cells may be derived from stem cells (circulating or within the vessel wall) or differentiation of existing cells, such as smooth muscle cells (SMCs) or pericytes. Several factors induce this transition, including bone morphogenetic proteins, oxidant stress, high phosphate levels, parathyroid hormone fragments, and vitamin D. Once the osteogenic phenotype is induced, cells gain a distinctive molecular fingerprint, marked by the transcription factor core binding factor α1. Alternatively, loss of inhibitors of mineralization, such as matrix γ-carboxyglutamic acid Gla protein, fetuin, and osteopontin, also contribute to vascular calcification. The normal balance between promotion and inhibition of calcification becomes dysregulated in chronic kidney disease, diabetes mellitus, atherosclerosis, and as a consequence of aging. Once the physiological determinants of calcification are perturbed, calcification may occur at several sites in the cardiovascular system, including the intima and media of vessels and cardiac valves. Here, calcification may occur through overlapping yet distinct molecular mechanisms, each with different clinical ramifications. A variety of imaging techniques are available to visualize vascular calcification, including fluoroscopy, echocardiography, intravascular ultrasound, and electron beam computed tomography. These imaging modalities vary in sensitivity and specificity, as well as clinical application. Through greater understanding of both the mechanism and clinical consequences of vascular calcification, future therapeutic strategies may be more effectively designed and applied.