tbuckley/cabot-search huggingface dataset:
Carotid Chemoreceptor Modulation of Regional Blood Flow Distribution During Exercise in Health and Chronic Heart Failure
Authors: Michael K. Stickland, Jordan D. Miller, Curtis A. Smith, Jerome A. Dempsey
Journal: Circulation Research (2007)

Previous work has shown sensitization of carotid chemoreceptor (CC) responsiveness during exercise as well as in chronic heart failure (CHF). Accordingly, we hypothesized that the CCs contribute to the sympathetic restraint of skeletal muscle blood flow during exercise and CHF. We examined the effect of transient CC inhibition on total (Con T ) and hindlimb (Con L ) conductance, and blood pressure at rest and during exercise (2.5 miles per hour, 5% grade) in chronically instrumented dogs. Via a carotid arterial catheter, CCs were inhibited using dopamine (5 to 10 μg/kg) or hyperoxic lactated Ringer’s solution. Although vasodilation did not occur with CC inhibition in resting healthy dogs, CC inhibition during exercise caused an immediate vasodilatory response (increase in Con T and Con L and decrease in blood pressure). When comparing the peak Con L response from CC inhibition versus α-adrenergic blockade (phentolamine), we found that the CCs accounted for approximately one-third of the total sympathetic restraint during exercise. CHF was then induced by chronic rapid cardiac pacing and characterized by impaired cardiac function, enhanced chemosensitivity, and greater sympathetic restraint at rest and during exercise. In contrast to healthy dogs, CC inhibition in resting CHF dogs produced vasodilation, whereas a similar vasodilatory response was observed during exercise in CHF as compared with healthy dogs. The vasodilation following CC inhibition during exercise and in CHF was abolished with α-adrenergic blockade and was absent in healthy exercising animals after carotid body denervation. These results establish an important role for the CCs in cardiovascular control in the healthy animal during exercise and in the CHF animal both at rest and during exercise.
THE EVOLUTION OF ADAPTIVE IMMUNITY
Authors: Zeev Pancer, Max D. Cooper
Journal: Annual Review of Immunology (2006)

Approximately 500 mya two types of recombinatorial adaptive immune systems appeared in vertebrates. Jawed vertebrates generate a diverse repertoire of B and T cell antigen receptors through the rearrangement of immunoglobulin V, D, and J gene fragments, whereas jawless fish assemble their variable lymphocyte receptors through recombinatorial usage of leucine-rich repeat (LRR) modular units. Invariant germ line–encoded, LRR-containing proteins are pivotal mediators of microbial recognition throughout the plant and animal kingdoms. Whereas the genomes of plants and deuterostome and chordate invertebrates harbor large arsenals of recognition receptors primarily encoding LRR-containing proteins, relatively few innate pattern recognition receptors suffice for survival of pathogen-infected nematodes, insects, and vertebrates. The appearance of a lymphocyte-based recombinatorial system of anticipatory immunity in the vertebrates may have been driven by a need to facilitate developmental and morphological plasticity in addition to the advantage conferred by the ability to recognize a larger portion of the antigenic world.
The Oncogenic Lung Cancer Fusion Kinase CD74-ROS Activates a Novel Invasiveness Pathway through E-Syt1 Phosphorylation
Authors: Hyun Jung Jun, Hannah Johnson, Roderick T. Bronson, Sebastien de Feraudy, Forest White, Alain Charest
Journal: Cancer Research (2012)

Patients with lung cancer often present with metastatic disease and therefore have a very poor prognosis. The recent discovery of several novel ROS receptor tyrosine kinase molecular alterations in non-small cell lung cancer (NSCLC) presents a therapeutic opportunity for the development of new targeted treatment strategies. Here, we report that the NSCLC-derived fusion CD74-ROS, which accounts for 30% of all ROS fusion kinases in NSCLC, is an active and oncogenic tyrosine kinase. We found that CD74-ROS-expressing cells were highly invasive in vitro and metastatic in vivo. Pharmacologic inhibition of CD74-ROS kinase activity reversed its transforming capacity by attenuating downstream signaling networks. Using quantitative phosphoproteomics, we uncovered a mechanism by which CD74-ROS activates a novel pathway driving cell invasion. Expression of CD74-ROS resulted in the phosphorylation of the extended synaptotagmin-like protein E-Syt1. Elimination of E-Syt1 expression drastically reduced invasiveness both in vitro and in vivo without modifying the oncogenic activity of CD74-ROS. Furthermore, expression of CD74-ROS in noninvasive NSCLC cell lines readily conferred invasive properties that paralleled the acquisition of E-Syt1 phosphorylation. Taken together, our findings indicate that E-Syt1 is a mediator of cancer cell invasion and molecularly define ROS fusion kinases as therapeutic targets in the treatment of NSCLC.
Effects of long term Tai Chi practice and jogging exercise on muscle strength and endurance in older people
Authors: D Q Xu, J X Li, Y Hong
Journal: British Journal of Sports Medicine (2005)

To investigate the influence of regular Tai Chi (TC) practice and jogging on muscle strength and endurance in the lower extremities of older people.Twenty one long term older TC practitioners were compared with 18 regular older joggers and 22 sedentary counterparts. Maximum concentric strength of knee flexors and extensors was tested at angular velocities of 30 degrees/s and 120 degrees/s. Ankle dorsiflexors and plantar flexors were tested at 30 degrees/s and the dynamic endurance of the knee flexors and extensors was assessed at a speed of 180 degrees/s.The differences in the muscle strength of the knee joint amongst the three experimental groups were significant at the higher velocity. The strengths of knee extensors and flexors in the control group were significantly lower than those in the jogging group and marginally lower than those in the TC group. For the ankle joint, the subjects in both the TC and jogging groups generated more torque in their ankle dorsiflexors. In addition, the muscle endurance of knee extensors was more pronounced in TC practitioners than in controls.Regular older TC practitioners and joggers showed better scores than the sedentary controls on most muscle strength and endurance measures. However, the magnitude of the exercise effects on muscles might depend on the characteristics of different types of exercise.
Neurokinin-1 Receptor Antagonists for Chemotherapy-Induced Nausea and Vomiting: A Systematic Review
Authors: L. V. dos Santos, F. H. Souza, A. T. Brunetto, A. D. Sasse, J. P. da Silveira Nogueira Lima
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundThe addition of neurokinin-1 receptor (NK1R) antagonists to antiemetic regimens has substantially reduced chemotherapy-induced nausea and vomiting (CINV). We sought to systematically review the overall impact of NK1R antagonists on CINV prevention.
Monocytes from systemic lupus erythematous patients are severely altered in phenotype and lineage flexibility
Authors: F. Steinbach
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> Cells of the myeloid lineage comprise a very heterogeneous population with many phenotypes and functional activities including macrophages and dendritic cells. To investigate the status, differentiative potential and lineage commitment of monocytic cells in systemic lupus erythematosus (SLE) patients, this study isolated and cultured peripheral blood monocytes from patients and healthy donors. <h3>METHODS</h3> Monocytes were isolated by gradient centrifugation and adherence to plastic dishes. The cells were then cultured for three days, partially supplemented with GM-CSF and interleukin 4 (IL4) to obtain dendritic cells. The differentiation status was monitored by the expression of surface markers using flow cytometry and cytokine secretion. <h3>RESULTS</h3> Monocytes from SLE patients expressed significantly lower numbers of the monocytic marker CD14 and HLA-DR while secreting significantly more tumour necrosis factor α (TNFα) than monocytes from healthy donors. The addition of GM-CSF and IL4 resulted in an inhibition of TNFα secretion, but was not sufficient to generate monocytederived dendritic cells. <h3>CONCLUSION</h3> Monocytes from SLE patients are severely altered in phenotype and function and have a limited differentiation flexibility towards the accessory type of monocytic cells.
Medical treatment of pulmonary hypertension in chronic lung disease
Authors: E Weitzenblum, R Kessler, M Oswald, P Fraisse
Journal: European Respiratory Journal (1994)

In chronic respiratory diseases, especially chronic obstructive pulmonary disease (COPD) pulmonary arterial hypertension is generally mild to moderate and the necessity for treating it can, therefore, be questioned. In fact, pulmonary hypertension, even when modest, may worsen markedly during acute episodes, exercise and sleep. These acute increases in mean pulmonary artery pressure (PAP) could contribute to the development of right heart failure. Therefore, the medical treatment of pulmonary hypertension is justified. There are, at the present time, no selective pulmonary vasodilators, with the exception of inhaled nitric oxide. Indeed, vasodilators appear less effective in COPD compared to primary pulmonary hypertension. Thus, there is, at present, no justification for the long-term use of vasodilators in COPD patients. Long-term oxygen therapy (LTOT) attenuates and sometimes reverses the progression of pulmonary hypertension, although the condition rarely returns to normal. We do not know whether the structural changes of the pulmonary vasculature in COPD patients are potentially reversible with LTOT. The longer the daily duration of LTOT the better are the haemodynamic results. At present, LTOT remains the best treatment for pulmonary hypertension in COPD patient. In the future, treatment of this condition in COPD patients could combine LTOT and specific vasodilators.
Is transbronchial lung biopsy using cryoprobes useful in the management of diffuse lung disease
Authors: Silvia Barril, Virginia Pajares, Carmen Puzo, Diego Castillo, J.M. Rodriguez-Arias, Enrique Lerma, Angeles Montero, M. Angeles Gil de Bernabé, Tomás Franquet, Cristina Burrel, Vicente Plaza, Alfons Torrego
Journal: European Respiratory Journal (2013)

Objectives: Bronchoscopic transbronchial lung biopsy (TBLB) with cryoprobe increases the diagnostic yield in comparison to conventional biopsy forceps in interstitial lung diseases1. The aim of this study is to evaluate the clinical helpfulness of TBLB using cryoprobes compared with conventional technique.  Methods: Randomized clinical trial results post-analysis of patients submitted to a TBLB with conventional forceps (Biopsy Forceps Boston®, Ref: 1556 and Olympus®, Ref: FB-19E) versus cryoprobe (Erbokryo® CA, Ref: 20426-032).  A biopsy was defined as helpful when it allowed a specific clinical or pharmacological decision. Clinical interventions were classified as: (1) drug prescription, (2) diagnostic-based treatment abstention and, (3) removal of allergens or other toxics. TBLB was considered useless if the result did not induced any therapeutic change and/or other sampling procedures, such as surgical biopsy, were required.  Results: The % of patients with a helpful TBLB with cryoprobe was higher (60.5%, n=38) than the conventional forceps group (29,7%, n=37) (p = 0.011).  Conclusion: Diagnostic yield improvement of TBPB using cryoprobe increases the clinical utility of transbronchial biopsies in the study and therapeutic management of patients with interstitial lung diseases.  1Pajares et al. Diagnostic yield of transbronchial cryobiopsy in diffuse lung disease: a randomised trial. ERJ submitted.
Uncoupling Protein-2 Overexpression Inhibits Mitochondrial Death Pathway in Cardiomyocytes
Authors: Yasushi Teshima, Masaharu Akao, Steven P. Jones, Eduardo Marbán
Journal: Circulation Research (2003)

Uncoupling proteins (UCPs) are located in the mitochondrial inner membrane and partially dissipate the transmembrane proton electrochemical gradient. UCP2 is expressed in various human and rodent tissues, including the heart, where its functional role is unknown. In the present study, we tested the hypothesis that UCP2 overexpression could protect cardiomyocytes from oxidative stress-induced cell death by reducing reactive oxygen species (ROS) production in mitochondria. Using an adenoviral vector containing human UCP2, we investigated the effects of UCP2 overexpression on the mitochondrial death pathway induced by oxidative stress (100 micromol/L H2O2) in cultured neonatal cardiomyocytes. UCP2 overexpression significantly suppressed markers of cell death, including TUNEL positivity, phosphatidylserine exposure, propidium iodide uptake, and caspase-3 cleavage. Furthermore, UCP2 remarkably prevented the catastrophic loss of mitochondrial inner membrane potential induced by H2O2, which is a critical early event in cell death. Ca2+ overload and the production of ROS in mitochondria, both of which contribute to mitochondrial inner membrane potential loss, were dramatically attenuated by UCP2 overexpression. Thus, overexpression of UCP2 attenuates ROS generation and prevents mitochondrial Ca2+ overload, revealing a novel mechanism of cardioprotection.
A Multicenter Prospective Cohort Study of Quality of Life and Economic Outcomes after Cataract Surgery in Vietnam
Authors: Beverley M. Essue, Qiang Li, Maree L. Hackett, Lisa Keay, Beatrice Iezzi, Khanh Duong Tran, Huynh Tan Phuc, Stephen Jan
Journal: Ophthalmology (2014)
Effects of the Bcr/abl kinase inhibitors STI571 and adaphostin (NSC 680410) on chronic myelogenous leukemia cells in vitro
Authors: Benjamin M. F. Mow, Joya Chandra, Phyllis A. Svingen, Christopher G. Hallgren, Ellen Weisberg, Timothy J. Kottke, Ven L. Narayanan, Mark R. Litzow, James D. Griffin, Edward A. Sausville, Ayalew Tefferi, Scott H. Kaufmann
Journal: Blood (2002)
Thiazides Reduce Brushite, but not Calcium Oxalate, Supersaturation, and Stone Formation in Genetic Hypercalciuric Stone–Forming Rats
Authors: David A. Bushinsky, John R. Asplin
Journal: Journal of the American Society of Nephrology (2005)

Over 59 generations, a strain of rats has been inbred to maximize urine calcium excretion. The rats now excrete eight to 10 times as much calcium as controls. These rats uniformly form calcium phosphate (apatite) kidney stones and have been termed genetic hypercalciuric stone-forming (GHS) rats. The addition of a common amino acid and oxalate precursor, hydroxyproline, to the diet of the GHS rats leads to formation of calcium oxalate (CaOx) kidney stones. Hydroxyproline-supplemented GHS rats were used to test the hypothesis that the thiazide diuretic chlorthalidone would decrease urine calcium excretion, supersaturation, and perhaps stone formation. All GHS rats received a fixed amount of a standard 1.2% calcium diet with 5% trans-4-hydroxy-l-proline (hydroxyproline) so that the rats would exclusively form CaOx stones. Half of the rats had chlorthalidone (Thz; 4 to 5 mg/kg per d) added to their diets. Urine was collected weekly, and at the conclusion of the study, the kidneys, ureters, and bladders were radiographed for the presence of stones. Compared with control, the addition of Thz led to a significant reduction of urine calcium and phosphorus excretion, whereas urine oxalate excretion increased. Supersaturation with respect to the calcium hydrogen phosphate fell, whereas supersaturation with respect to CaOx was unchanged. Rats that were fed Thz had fewer stones. As calcium phosphate seems to be the preferred initial solid phase in patients with CaOx kidney stones, the reduction in supersaturation with respect to the calcium phosphate solid phase may be the mechanism by which thiazides reduce CaOx stone formation.
THE SEDIMENTATION PROPERTIES OF THE SKIN-SENSITIZING ANTIBODIES OF RAGWEED-SENSITIVE PATIENTS
Authors: Burton R. Andersen, Wilton E. Vannier
Journal: The Journal of Experimental Medicine (1964)

The sedimentation coefficients of the skin-sensitizing antibodies to ragweed were evaluated by the moving partition cell method and the sucrose density gradient method. The most reliable results were obtained by sucrose density gradient ultracentrifugation which showed that the major portion of skin-sensitizing antibodies to ragweed sediment with an average value of 7.7S (7.4 to 7.9S). This is about one S unit faster than gamma-globulins (6.8S). The data from the moving partition cell method are in agreement with these results. Our studies failed to demonstrate heterogeneity of the skin-sensitizing antibodies with regard to sedimentation rate.
Food allergy – accurately identifying clinical reactivity
Authors: H. A. Sampson
Journal: Allergy (2005)

Up to 25% of adults believe that they or their children are afflicted with a food allergy. However, the actual prevalence of food allergy is much lower: approximately 6–8% of children suffer from food allergy during their first 3 years of life, and many children then develop clinical tolerance. Food allergy encompasses a whole spectrum of disorders, with symptoms that may be cutaneous, gastrointestinal or respiratory in nature. Food disorders also differ according to the extent that they are immunoglobulin E (IgE)‐mediated. Skin‐prick testing is often used to identify food sensitization, although double‐blind, placebo‐controlled food challenge (DBPCFC) tests remain the gold standard for diagnosis. Recent evidence suggests that quantitative IgE measurements can predict the outcome of DBPCFC tests and can replace about half of all oral food challenges. When an extensive medical history is obtained in combination with IgE quantification, even fewer patients may require formal food challenges. It has also become possible to map the IgE‐binding regions of many major food allergens. This may help to identify children with persistent food allergy, as opposed to those who may develop clinical tolerance. In future, microarray technology may enable physicians to screen patients for a large number of food proteins and epitopes, using just a few drops of blood.
Changes in the distensibility of the intrapulmonary arteries in the normal newborn and growing pig
Authors: S E GREENWALD, C L BERRY, S G HAWORTH
Journal: Cardiovascular Research (1982)

The static elastic properties and structure of the intra-pulmonary arteries have been studied in pigs from fetal life to 4 months old, by radiographic and histological methods. During this period the average radius of the vessels examined varied from ≈0.9 mm at birth to 3.3 mm at the age of 4 months. The form of the pressure radius curves was similar to that observed in the systemic circulation and was characteristic of the gradual recruitment of collagen fibres with increasing pressure. In vessels near the hilum, wall thickness decreased from ≈180 μm to 100 μm during the first 2 weeks and thereafter increased to ≈250 μm. Throughout the lung and in all age groups there was a linear relationship between the logarithm of pressure strain elastic modulus (used as a measure of functional stiffness) and pressure. In contrast to the systemic arteries there was little change in functional stiffness towards the periphery, although the incremental elastic modulus (structural stiffness) did increase at sites further removed from the heart. During the first two weeks of life there was little change in functional stiffness (Ep ≈ 1.1 × 104 Nm2) although by 4 months Ep had increased by a factor of three. During this period despite fluctuations with age, an overall increase in structural stiffness was also observed (EINC ≈1 × 105 at 4 to 6 h to 2 × 105 Nm−2 at 4 months). The observations suggest that the changes in elasticity observed in early life are a consequence of the adaptation of the circulation to the lower pulmonary arterial pressure of extra-uterine life.
Drug Risks and Free Speech — Can Congress Ban Consumer Drug Ads?
Authors: Miriam Shuchman
Journal: New England Journal of Medicine (2007)

Real-life and longer-term safety studies are often in progress when direct-to-consumer advertising for a new drug begins. The authority to ban direct-to-consumer advertising is included in two drug-safety bills that have been wending their way through the legislative process. Dr. Miriam Shuchman reports.
Impact of self monitoring of blood glucose in the management of patients with non-insulin treated diabetes: open parallel group randomised trial
Authors: Andrew Farmer, Alisha Wade, Elizabeth Goyder, Patricia Yudkin, David French, Anthea Craven, Rury Holman, Ann-Louise Kinmonth, Andrew Neil
Journal: BMJ (2007)

To determine whether self monitoring, alone or with instruction in incorporating the results into self care, is more effective than usual care in improving glycaemic control in non-insulin treated patients with type 2 diabetes.Three arm, open, parallel group randomised trial.48 general practices in Oxfordshire and South Yorkshire.453 patients with non-insulin treated type 2 diabetes (mean age 65.7 years) for a median duration of three years and a mean haemoglobin A1c level of 7.5%.Standardised usual care with measurements of HbA1c every three months as the control group (n=152), blood glucose self monitoring with advice for patients to contact their doctor for interpretation of results, in addition to usual care (n=150), and blood glucose self monitoring with additional training of patients in interpretation and application of the results to enhance motivation and maintain adherence to a healthy lifestyle (n=151).HbA1c level measured at 12 months.At 12 months the differences in HbA1c level between the three groups (adjusted for baseline HbA1c level) were not statistically significant (P=0.12). The difference in unadjusted mean change in HbA1c level from baseline to 12 months between the control and less intensive self monitoring groups was -0.14% (95% confidence interval -0.35% to 0.07%) and between the control and more intensive self monitoring groups was -0.17% (-0.37% to 0.03%).Evidence is not convincing of an effect of self monitoring blood glucose, with or without instruction in incorporating findings into self care, in improving glycaemic control compared with usual care in reasonably well controlled non-insulin treated patients with type 2 diabetes.Current Controlled Trials ISRCTN47464659.
Varied expressions of receptors on the human megakaryoblastic cell line MEG‐01 by monoclonal antibodies
Authors: Nobutaka Imamura, Deodatus M. Mtasiwa, Tominari Inada, Atsushi Kuramoto, Michinori Ogura, Hidehiko Saito
Journal: American Journal of Hematology (1990)

Abstract We herein describe the regulation of specific receptors on the megakaryoblastic cell line MEG‐01 by means of fluorescence‐activated cell sorting (FACS IV) with a panel of monoclonal antibodies (MAbs). MEG‐01 cells expressed GpIIb/IIIa (CD41a) and OKM5 (CD36) antigens on their cell surface, whereas they showed only a little expression of GPIb (CD42b), suggesting that these are megakaryoblastic cells. The up regulation of von Willebrand factor receptor (GPIb) and thrombospondin receptor (GPIV) and the down regulation of fibrinogen receptor (GPIIb/IIIa) and C3bi receptor (CD11b) were found by incubation with MAbs AN51 (CD42b), OKM5 (CD36), J15 (CD41a), and OKM1 (CD11b), respectively. This phenomenon was enhanced in the Ca 2+ containing medium, except for the experiment with OKM5 (CD36) MAb. We thus suggest that several kinds of receptors on the surface of MEG‐01 cells are dexterously regulated through stimulation from outside the cell.