tbuckley/cabot-search huggingface dataset:
Residence Time of Low-Density Lipoprotein in the Normal and Atherosclerotic Rabbit Aorta
Authors: Eileen Collins Tozer, Thomas E. Carew
Journal: Circulation Research (1997)

Previous results from this laboratory found that the arterial low-density lipoprotein (LDL) residence time in lesion-prone aortic sites was longer in hyperlipidemic rabbits before lesion formation than in the corresponding sites in normolipidemic rabbits. The calculation of residence time in the previous study assumed that the arterial wall was homogeneous; the present study reexamines the issue using a method that does not require such an assumption. The concentration of radiolabeled arterial LDL was measured in New Zealand White rabbits killed at several different times (0.5 to 72 hours) after injection of labeled LDL. Using a stochastic analysis, arterial LDL residence time was calculated from the pooled labeled arterial LDL measurements from these rabbits. In these studies, the arterial LDL residence times in normolipidemic and hyperlipidemic rabbits before lesion formation were similar in both the lesion-prone and -resistant sites. However, immediately upon development of early fatty streak lesions, the arterial LDL residence time increased dramatically. After only 16 days of cholesterol feeding, the residence time was 10 times longer in the lesioned aortic arch compared with similar tissue from normolipidemic rabbits (4 to 45 hours). After 21 days of cholesterol feeding, the residence time of LDL in the lesioned aortic arch increased to > 25-fold that of normolipidemic tissue. Similar results were observed in the lesioned tissue of the abdominal branchings. This early retention of LDL suggests that significant changes are taking place within the arterial wall during this critical stage of early lesion development.
Omalizumab in paediatric asthma: Importance of multi-disciplinary assessment to identify the eligible patients
Authors: Susan Frost, Barrett Lesley, Yasin Lakhani, Satish Rao
Journal: European Respiratory Journal (2011)

Omalizumab is effective treatment for patients with severe asthma. It is reserved for patients with truly severe disease as it is expensive and associated with significant treatment burden. Identifying this small number of patients in problematic severe asthma (PSA) group is challenging. We evaluated the impact of multi-disciplinary severe asthma (SA) protocol on identifying those with severe disease and on potential use of omalizumab.

After initial clinic visit, 19 patients aged between 6-15yrs with PSA underwent specialist nurseled SA protocol which included: assessment of clinical status, lung function, atopy, inhaler technique, asthma control test (ACT), quality of life (QoL); home visit for further assessment of environment, adherence and psychosocial comorbidities; school contact to address impact on education.

Before SA protocol, 17/19 patients met criteria for use of omalizumab. After SA protocol, only 7 (41%) were eligible as modifiable factors were identified in 12 (59%). They included poor adherence (50%), ongoing allergen exposure (42%), hyperventilation (25%), psychology referral (8%). 6/7 patients received omalizumab and 5 (83%) improved. Of other 12 patients, clinical status improved in 7 (58%), unchanged but stable in 4 (33%), worsened in 1 (8%) after assessment.

SA protocol identified modifiable factors in significant proportion of PSA children limiting omalizumab use to those with truly severe disease. Home visit assessment is essential to identify these factors which would otherwise be unrecognized. We hypothesise that proper recognition and management of these factors might not only ensure appropriate use of omalizumab but also improve its effectiveness.
Molecular Evolution of the Ligands of the Insulin-Signaling Pathway: dilp Genes in the Genus Drosophila
Authors: S. Guirao-Rico, M. Aguade
Journal: Molecular Biology and Evolution (2010)

Drosophila melanogaster, unlike mammals, has seven insulin-like peptides (DILPS). In Drosophila, all seven genes (dilp1-7) are single copy in the 12 species studied, except for D. grimshawi with two tandem copies of dilp2. Our comparative analysis revealed that genes dilp1-dilp7 exhibit differential functional constraint, which is indicative of some functional divergence. Species of the subgenera Sophophora and Drosophila differ in some traits likely affected by the insulin-signaling pathway, such as adult body size. It is in the branch connecting the two subgenera that we found the footprint left by positive selection driving nonsynonymous changes at some dilp1 codons to fixation. Finally, the similar rate at which the two dilp2 copies of D. grimshawi have evolved since their duplication and the presence of a putative regulatory region highly conserved between the two paralogs would suggest that both copies were preserved either because of subfunctionalization or dose dependency rather than by the neofunctionalization of one of the two copies.
Altered Gene Expression in the Liver ofγ-Glutamyl Transpeptidase–Deficient Mice
Authors: Geetha M. Habib, Zheng-zheng Shi, Ching-nan Ou, Geeta Kala, Subbarao V. Kala, Michael W. Lieberman
Journal: Hepatology (2000)

We used mice deficient in gamma-glutamyl transpeptidase (GGT) to analyze the effects of GGT deficiency and altered thiol levels on gene expression in liver. GGT-deficient mice have markedly reduced levels of glutathione (GSH), cysteine, methionine, and cysteinylglycine in liver. Steady-state RNA levels of the catalytic subunit of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme in GSH synthesis, are elevated 4-fold in these mice, while those for glutathione synthetase (GSH syn) are elevated 2-fold. RNA levels of cystathionase (cystathionine gamma-lyase), a key enzyme in the synthesis of cysteine from methionine, are elevated approximately 3.5-fold. In contrast, levels of RNA coding for multidrug resistance protein 2 (MRP2), which transports GSH into bile, are half wild-type values. We found no change in RNA levels of enzymes related to oxidative injury (CuZn and Mn superoxide dismutases [SOD], catalase, and glutathione peroxidase). Similarly, RNA levels of glutathione reductase and ribonucleotide reductase were unchanged. Furthermore, in contrast to previous in vitro results, methyl methanesulfonate did not induce stress-activated signal transduction as measured by c-jun phosphorylation in livers of GGT-deficient mice, despite further depletion of GSH by buthionine sulfoximine. Our findings indicate that GGT deficiency itself and/or altered thiol levels regulate expression of genes involved in GSH metabolism, but have no effect on the expression of other antioxidant genes.
Resistances to the Learning Process in Group Dynamics Programs
Authors: IRVING L. BERGER
Journal: American Journal of Psychiatry (1969)

Problems in teaching psychiatry and group psychotherapy in small groups vary with the type of setting, frequency and length of meetings, and specific goals of the group. Problems of dependency, oppositional patterns to the goals of the group, and development of mutual sharing are regularly noted phenomena. It is important that the leader distinguish between blocks in learning related to problems of initial dependency and anxieties about status and role, and those related specifically to learning.
EVALUATING THE COST-EFFECTIVENESS OF CLINICAL AND PUBLIC HEALTH MEASURES
Authors: John D. Graham, Phaedra S. Corso, Jill M. Morris, Maria Segui-Gomez, Milton C. Weinstein
Journal: Annual Review of Public Health (1998)

▪ Abstract Cost-effectiveness analysis, an analytic tool that expresses as a ratio the cost of obtaining an additional unit of health outcome, can help decision makers achieve more health protection for the same or less cost. We characterize the state of the cost-effectiveness analysis literature by reviewing how this technique is applied to various clinical and public health interventions. We describe the results of cost-effectiveness analyses for over 40 interventions to reduce cancer, heart disease, trauma, and infectious disease. The cost-effectiveness ratios for these interventions vary enormously, from interventions that save money to those that cost more than $1 million per year of life gained. The methods used to derive the cost-effectiveness ratios also vary considerably, and we summarize this variation within each health area. Greater uniformity of analytical practice will be necessary if cost-effectiveness analysis is to become a more influential tool in debates about resource allocation.
Effect of BRCA Mutations on the Length of Survival in Epithelial Ovarian Tumors
Authors: Y. Ben David
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To study the role of BRCA mutations in ovarian cancer survival. PATIENTS AND METHODS: Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors. RESULTS: This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v 37.8 months; 3-year survival, 65.8% v 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. CONCLUSION: Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis.
Effects of a drag-reducing polyelectrolyte of microscopic linear dimension (Separan AP-273) on rat hemodynamics.
Authors: P B Coleman, B T Ottenbreit, P I Polimeni
Journal: Circulation Research (1987)

Separan AP-273, a polydisperse, high molecular weight (10(5)-10(7) dalton range), anionic polyacrylamide, demonstrates polymer drag reduction (Toms effect) in the flows of several substances including blood. That is, under appropriate conditions, pipe flow can be increased markedly for a given pressure gradient, sometimes threefold or more, by nanomolar concentrations of linear macropolymers. The effect of intact and degraded Separan was tested in the open-chest, anesthetized rat, and left ventricular and carotid pressures, aortic blood flow (electromagnetic flow probe on ascending aorta), and the electrocardiogram were recorded. The results indicate that aortic flow, which in control animals was about half the flow reported for conscious rats, increases markedly after injection of Separan. The effect on blood pressure after an initial fall was variable, but the slope of arterial diastolic pressure was consistently steepened. Electrocardiographic changes were unremarkable except for a slow decline in heart rate. Although secondary reflexes undoubtedly influenced the results, the primary mechanism of the polymer appears to involve a reduced resistance to flow. The results are compatible with the proposal that the Toms effect, or some variant of it, is operative in vivo under favorable conditions. If this view is correct, then Separan and two other chemically different macropolymers with similar hemodynamic effects and physical attributes, i.e., linearity and molecular lengths approaching 100 micron, might be prototypes of a novel category of cardiovascular drugs.
P112 Association of sputum Pseudomonas aeruginosa (PsA) isolation and length of hospital stay in patients with chronic obstructive pulmonary disease (COPD)
Authors: A. Ali, M. Bhattacharya, J. Corcoran, B. Chakraborty, A. Thomas, M. Raza, R. Mukherjee
Journal: Thorax (2010)

<h3>Introduction and objectives</h3> A lot of effort and investment has been made to improve the length of stay (LOS) in COPD related admissions with variable success. It is known that numbers of hospital admissions and re-admissions have increased. Bacterial infections contribute to acute exacerbation of COPD (AECOPD) in 50% of cases; PsA is a probable pathogenic organism (PPM) causing acute or chronic infection in severe COPD patients. We set out to examine whether PsA in sputum influenced the length of stay as this PPM is not covered by the routinely used first line antibiotics. <h3>Method</h3> A retrospective audit was carried out examining the sputum culture results and LOS in all COPD admissions in an acute hospital from 1 January 2009 to 31 December 2009, patients were identified from coding (ICD: J44). Sputum cultures were attempted (and collected in all sputum producers) by a dedicated respiratory team as a routine for all COPD admissions throughout that period, which was established as part of service improvement well before the audit. Results were obtained from Pathology department database. Patients were divided into sputum producing group and non-producers, Sputum producers were further divided into patients with positive sputum culture of PPM and non-pathogenic organisms. PsA growers were identified. Median LOS was calculated to be 5 days and all groups were compared with this duration as a standard for their LOS. <h3>Results</h3> Total admissions with COPD were 332; 203 were sputum producers and 122 had bacterial isolates. There were 37 PsA growers. LOS was seen to be 5 or more days in: 121 sputum producers vs 47 non-producers, p=0.000046. 79 PPM culture positive patients vs 42 without bacterial growth, p=0.067; PsA growers vs. all admissions, p=0.000744, PsA vs all sputum producers p=0.0126, PsA vs all PPM, p=0.041. <h3>Conclusions</h3> PsA infection is associated with significantly longer LOS in hospital. All COPD patients should possibly be screened for PsA infection (and possibly underlying bronchiectasis) to inform the selection of antibiotics, which is likely to reduce LOS and may reduce re-admission rates.
Decrease in Mitochondrial Complex I Activity in Ischemic/Reperfused Rat Heart
Authors: Giuseppe Paradies, Giuseppe Petrosillo, Marilva Pistolese, Nicola Di Venosa, Antonio Federici, Francesca Maria Ruggiero
Journal: Circulation Research (2003)

Reactive oxygen species (ROS) are considered an important factor in ischemia/reperfusion injury to cardiac myocytes. Mitochondrial respiration is an important source of ROS production and hence a potential contributor to cardiac reperfusion injury. In this study, we have examined the effect of ischemia and ischemia followed by reperfusion of rat hearts on various parameters related to mitochondrial function, such as complex I activity, oxygen consumption, ROS production, and cardiolipin content. The activity of complex I was reduced by 25% and 48% in mitochondria isolated from ischemic and reperfused rat heart, respectively, compared with the controls. These changes in complex I activity were associated with parallel changes in state 3 respiration. The capacity of mitochondria to produce H 2 O 2 increased on reperfusion. The mitochondrial content of cardiolipin, which is required for optimal activity of complex I, decreased by 28% and 50% as function of ischemia and reperfusion, respectively. The lower complex I activity in mitochondria from reperfused rat heart could be completely restored to the level of normal heart by exogenous added cardiolipin. This effect of cardiolipin could not be replaced by other phospholipids nor by peroxidized cardiolipin. It is proposed that the defect in complex I activity in ischemic/reperfused rat heart could be ascribed to a ROS-induced cardiolipin damage. These findings may provide an explanation for some of the factors responsible for myocardial reperfusion injury.
Phase II trial of paclitaxel by three-hour infusion for advanced gastric cancer with short premedication for prophylaxis against paclitaxel-associated hypersensitivity reactions
Authors: Y. Yamada, K. Shirao, A. Ohtsu, N. Boku, I. Hyodo, H. Saitoh, Y. Miyata, T. Taguchi
Journal: Annals of Oncology (2001)
Polymorphisms in the 2 adrenergic receptor and bronchodilator response, bronchial hyperresponsiveness, and rate of decline in lung function in smokers
Authors: L Joos
Journal: Thorax (2003)

<b>Background:</b> Non-specific bronchial hyperresponsiveness (NSBH) is a known predictor of accelerated rate of decline in lung function in smokers. Polymorphisms of the β<sub>2</sub> adrenergic receptor (<i>ADRB2</i>) have previously been associated with NSBH and bronchodilator response (BDR) in asthmatics. Based on these associations, we hypothesised that <i>ADRB2</i> polymorphisms would be associated with NSBH and BDR as well as an accelerated rate of decline in lung function among smokers. <b>Methods:</b> The prevalence of two <i>ADRB2</i> polymorphisms, Arg16→Gly and Gln27→Glu, was examined in 587 smokers chosen from the NHLBI Lung Health Study for having the fastest (n=282) and slowest (n=305) 5 year rate of decline in forced expiratory volume in 1 second (FEV<sub>1</sub>; mean ΔFEV<sub>1</sub> −4.14 and +1.08% predicted/year, respectively). <b>Results:</b> Contrary to our hypothesis, no <i>ADRB2</i> allele or haplotype was associated with NSBH, BDR, or rate of decline in lung function. However, there was a significant negative association between heterozygosity at position 27 and a fast decline in lung function (adjusted odds ratio 0.56, 95% CI 0.40 to 0.78, p=0.0007). <b>Conclusions:</b> Heterozygosity at position 27 may be protective against an accelerated rate of decline in lung function. The polymorphism at position 16 does not contribute to the rate of decline in lung function, measures of NSBH, or BDR in smokers.
Chest wall asynchronies during spontaneous breathing in spinal muscular atrophy (SMA)
Authors: Rita Priori, Antonella Lo Mauro, Marianna Romei, Marianna Laviola, Maria Grazia D'Angelo, Andrea Aliverti
Journal: European Respiratory Journal (2013)

In more severe types of SMA the intercostal muscles are weakened, while the diaphragm is relatively preserved. We studied chest wall asynchronies in SMA type II patients and in a recently proposed sub-classification of SMAIIIA and SMAIIIB to study chest wall distortion and respiratory muscle coordination.  4 SMAII (age 24.0±14.2), 4 SMAIIIA (age 25.0±14.9) and 9 SMAIIIB (age 21.5±10.2) patients and 16 healthy age-matched controls (CTR, age 22.3±11.4) were considered. In each subject pulmonary rib cage, abdominal rib cage and abdominal volumes (V RCp , V RCa  and V AB  respectively) were measured in seated (ST) and supine (SP) positions by opto-electronic plethysmography. Rib cage distortion was quantified as the phase shift between V RCp  and V RCa  (θ RC ) and respiratory muscle coordination between V RCp  and V AB  (θ TA ).  In ST chest wall asynchronies in all SMA were similar to CTR. The major differences were found in SP with SMAII showing highly negative values both in θ RC  and in θ TA  when compared to SMAIIIB and CTR (see fig). The change in posture had an effect on θ RC  and θ TA  in SMAII and SMAIIIA, with more negative values in SP.  In SMAII the diaphragm strongly anticipates intercostal muscles action. This marked direct action of the diaphragm on RCa induces rib cage distortion especially in supine. Changing posture highlights a more similar behavior of SMAIIIA to SMAII confirming the suitability of sub-classification of SMAIII.
Swine flu claims first European death, as cases worldwide rise to 36 000
Authors: A. O'Dowd
Journal: BMJ (2009)

<h3>Summary</h3> Biases, systematic tendencies toward one choice option, are hallmarks of decision-making under uncertainty. In perceptual decision-making, bias can be conceptualized as an internal reference to which incoming sensory evidence is compared. This reference, often called “criterion”, can be flexibly adjusted to match external asymmetries in the payoffs for certain outcomes. Yet, very little is known about how the human brain implements such strategic criterion shifts. Recent studies suggest that spontaneous fluctuations in neural excitability (indexed by suppression of prestimulus alpha-band (8-12 Hz) power in posterior cortex) may impact the criterion. Crucially however, it is currently unknown whether neural excitability and criterion can flexibly and intentionally be adjusted to meet external demands. Here, we experimentally induced criterion shifts in humans through through verbal instruction and assymetric reward contingencies and show for the first time that neural excitability is enhanced when humans adopt a liberal criterion compared to a more conservative criterion. Moreover, we show how increased excitability boosts subsequent stimulus-related visual cortical EEG activity in the gamma (59-100 Hz) range by enhancing sensory response gain. Drift diffusion modeling of choice behaviour further confirms that a liberal criterion is achieved by biasing the sensory evidence accumulation process towards ‘yes’ choices. Together, these findings show that humans are able to intentionally and flexibly adapt neural excitability to current task demands, and that such changes in excitability implement criterion shifts by biasing sensory evidence accumulation.
Tissue-Type Plasminogen Activator Crosses the Intact Blood-Brain Barrier by Low-Density Lipoprotein Receptor–Related Protein-Mediated Transcytosis
Authors: Karim Benchenane, Vincent Berezowski, Carine Ali, Mónica Fernández-Monreal, José P. López-Atalaya, Julien Brillault, Julien Chuquet, André Nouvelot, Eric T. MacKenzie, Guojun Bu, Roméo Cecchelli, Omar Touzani, Denis Vivien
Journal: Circulation (2005)

Background— Accumulating evidence demonstrates a critical involvement of tissue-type plasminogen activator (tPA) in pathological and physiological brain conditions. Determining whether and how vascular tPA can cross the blood-brain barrier (BBB) to enter the brain is thus important, not only during stroke but also in physiological conditions. Methods and Results— In the present work, we provide evidence in vivo that intravenous injection of tPA increases NMDA-induced striatal lesion in the absence of BBB leakage. Accordingly, we show that tPA crosses the BBB both after excitotoxic lesion and in control conditions. Indeed, vascular injected tPA can be detected within the brain parenchyma and in the cerebrospinal fluid. By using an in vitro model of BBB, we have confirmed that tPA can cross the intact BBB. Its passage was blocked at 4°C, was saturable, and was independent of its proteolytic activity. We have shown that tPA crosses the BBB by transcytosis, mediated by a member of the LDL receptor–related protein family. Conclusions— We demonstrate that blood-derived tPA can reach the brain parenchyma without alteration of the BBB. The molecular mechanism of the passage of tPA from blood to brain described here could represent an interesting target to improve thrombolysis in stroke