tbuckley/cabot-search huggingface dataset:
The electrophysiological basis of MAP recordings
Authors: E VIGMOND
Journal: Cardiovascular Research (2005)

Recently, differing views as to the genesis of monophasic action potential (MAP) recordings have surfaced [1–3]. Kondo et al. [1,3] claim that MAP recordings come about because core conductor theory dictates that the extracellular potential is a scaled version of the transmembrane voltage and that the contact electrode acts as a stationary ground. Franz [2] holds to the view that injury currents at the boundary of the contact electrode zone of influence lead to extracellular potential changes which reflect changes in transmembrane voltage. As a consequence of these divergent views, the importance of one electrode with respect to the other has come into question.

MAP electrodes are similar to potentials recorded with the sucrose gap technique [4]. That is, the technique functions as MAP recordings do, indirectly measuring transmembrane voltage by differencing extracellular potentials. Due to its relative simplicity, this technique warrants further consideration to determine if similar physics concepts are at work, which may shed light on the present issue. The sucrose gap technique separates two portions of an active cable with a perfusion of sucrose solution that serves to stop propagation of any activity across the gap due to the high resistivity of the sucrose region. The intracellular domains are still connected. By taking the difference in extracellular potentials on opposite sides of the sucrose gap, an approximation of the transmembrane voltage is obtained. …
Effect of altitude training on haematological variables in women volleyball players
Authors: B Cueto-Martín, J C de la Cruz-Márquez, J C de la Cruz-Campos, A de la Cruz-Campos
Journal: British Journal of Sports Medicine (2011)

Background Athletes from many endurance disciplines include altitude training in their yearly training programme. In volleyball, it is necessary to clarify the haematological benefits and improvement in sports performance. Objective To investigate the influence of moderate altitude on haematological variables in a women's volleyball team (Honor Division – Spain). Design and setting We assessed 14 elite female volleyball players for two weeks in normoxia (640 m above sea level), two weeks in relative hypoxia (2450 m, at the High Performance Center of Sierra Nevada, Granada, Spain) and two final weeks in normoxia again, during the volleyball preseason (August–September). Participants 14 women (mean age 23±2.8 years; height: 184.9±6.9 cm; weight: 73.1±6.2 kg). All players who started the study completed it. None were taking dietary supplements, vitamins or exogenous iron. During the study, all players menstruated. Interventions The volleyball players trained twice daily (3 h/season). Blood samples were taken at 7-day intervals in normoxia and 72 h in hypoxia. Economy of effort was evaluated by the relationship between oxygen intake (Vo 2 ) and running speed on a treadmill using sport-specific protocols. Blood samples were taken monthly during volleyball season. Independent Variable: Altitude. Dependent Variables: Haematological and VO 2 intake. Results Higher levels of haemoglobin (14.1±1.2 g/dl) and hematocrit (42.7±2.2%) were obtained at normoxia prealtitude, while the lowest levels were obtained in the first week post-altitude (12.9±1.8 g/dl; 38.9±2.3% respectively; p&lt;0.05). After the stay at altitude, oxygen intake was increased (48.1±1.5 to 51.4±2.3 ml/kg/min; p&lt;0.05). Conclusions 2 weeks of moderate hypoxia improved the maximum oxygen intake but not the haemoglobin or hematocrit levels.
Aldosterone Plays a Pivotal Role in the Pathogenesis of Thrombotic Microangiopathy in SHRSP
Authors: Praveen N Chander, Ricardo Rocha, Jeffrey Ranaudo, Gagan Singh, Andrea Zuckerman, Charles T Stier
Journal: Journal of the American Society of Nephrology (2003)

Angiotensin-converting enzyme inhibitors and aldosterone receptor antagonists ameliorate malignant nephrosclerotic lesions of thrombotic microangiopathy in salt-loaded, stroke-prone, spontaneously hypertensive rats (SHRSP) without controlling hypertension. This suggests that angiotensin II (Ang II) and/or aldosterone (ALDO) plays a critical role in renal injury in this model. For evaluating their relative roles in the pathogenesis of thrombotic microangiopathy, SHRSP were adrenalectomized and infused with vehicle, Ang II, or ALDO or were sham-operated for adrenalectomy (SHAM). Saline-drinking rats were assigned to one of four groups: SHAM, adrenalectomy, adrenalectomy + Ang II (25 ng/min, subcutaneously), or adrenalectomy + ALDO (40 micro g/kg per d, subcutaneously). All SHRSP received dexamethasone (12 micro g/kg per d, subcutaneously). Adrenalectomy did not show changes in body weight, plasma creatinine, sodium and potassium, and daily urinary sodium and potassium excretion; did not prevent hypertension but prevented proteinuria (12 +/- 1 versus 49 +/- 3 mg/d; P < 0.01); and abrogated thrombotic microangiopathy and decreased plasma aldosterone (<16 versus 710 +/- 91 pg/ml; P < 0.001) compared with SHAM. Systolic BP in adrenalectomy + Ang II and adrenalectomy + ALDO (238 +/- 8 and 241 +/- 9 mmHg, respectively) was similar to SHAM. Despite Ang II infusion, proteinuria (17 +/- 9 mg/d) and thrombotic microangiopathy and plasma aldosterone (18 +/- 18 pg/ml) remained low but daily urinary excretion of sodium and potassium were not different from adrenalectomy + ALDO. Adrenalectomy + ALDO showed plasma aldosterone levels of 735 +/- 147 pg/ml; plasma potassium was lower; plasma creatinine and proteinuria (78 +/- 7 mg/d) were greater and thrombotic microangiopathy lesions were comparable to SHAM. These results demonstrate a pivotal role for aldosterone in the development of thrombotic microangiopathy, independent of hypertension.
Neonatal lupus erythematosus progressing into systemic lupus erythematosus
Authors: ROBERT JACKSON, MICHAEL GULLIVER
Journal: British Journal of Dermatology (1979)

Journal Article Neonatal lupus erythematosus progressing into systemic lupus erythematosus Get access ROBERT JACKSON, ROBERT JACKSON Department of Medicine, University of Ottawa and Division of Dermatology, Ottawa Civic Hospital, Ottawa, Canada Dr Robert Jackson, 1081 Carling Avenue, Suite 508, Ottawa, Ontario K1Y 4G2, Canada. Search for other works by this author on: Oxford Academic Google Scholar MICHAEL GULLIVER MICHAEL GULLIVER Department of Medicine, University of Ottawa and Division of Dermatology, Ottawa Civic Hospital, Ottawa, Canada Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 101, Issue 1, 1 July 1979, Pages 81–86, https://doi.org/10.1111/j.1365-2133.1979.tb15297.x Published: 01 July 1979
Therapeutic aerosols 2--Drugs available by the inhaled route.
Authors: S W Clarke, S P Newman
Journal: Thorax (1984)

Therapeutic aerosols 2-Drugs available by the inhaled routeInhalation treatment can be said to have stood the test of time, since records can be traced back several thousand years.In ancient Greece, Hippocrates employed the inhalation of vapours distilled in a pot, the lid of which was pierced by a reed;' sulphur and arsenic were said to have been used.The patient breathing these hot vapours needed protection with moistened sponges to avoid scalding.The popularity of these inhalation procedures has waxed and waned, as Miller' writes-at times they have been over praised and unwisely used, and at other times unreasonably condemned and virtually abandoned.The latter phrase still applies to some extent today.Until the middle of the present century, inhalation treatment with volatile aromatic substances with a mild irritant action such as menthol, thymol, and eucalyptus and smokes derived from burning vari- ous types of plant leaf, notably Atropa belladonna and Datura strammonium, was quite commonly recommended for disorders of the upper and lower airways.Several present day pharmaceuticals used for respiratory treatment have been derived from ancient remedies2-for example, khellin was the predecessor of cromoglycate, while burning Datura strammonium leaves form the basis of the asthma cigarette, which is still available from herbalists.These substances have been largely replaced by the range of modern pharmaceuticals available for inhalation either from a metered dose inhaler (MDI), dry powder inhaler, or nebuliser or for the nose by nasal spray.Although the MDI is the most popular method of administering bronchodilator and corticosteroid aerosols, the nebuliser has the great merit of flexibility-virtually any drug solution or suspension can be nebulised.Most drugs are inhaled for topical treatment of the upper and lower respiratory tract, but some may also be given as aerosols for their systemic effect. Beta agonistsBeta agonists are undoubtedly the most common type of drug given by inhalation from an MDI.
Assessment of Coronary Function in Children With a History of Kawasaki Disease Using <sup>15</sup> O-Water Positron Emission Tomography
Authors: Hideto Furuyama, Yasuhisa Odagawa, Chietsugu Katoh, Yasuyoshi Iwado, Keiichiro Yoshinaga, Yoshinori Ito, Kazuyuki Noriyasu, Megumi Mabuchi, Yuji Kuge, Kunihiko Kobayashi, Nagara Tamaki
Journal: Circulation (2002)

Background — Coronary abnormalities after Kawasaki disease (KD) may be associated with endothelial dysfunction due to intimal hypertrophy. The purpose of this study was to evaluate myocardial flow reserve (MFR) and endothelial function in regressed aneurysmal regions after KD. Methods and Results — Subjects were 12 patients aged 16.0±2.6 years who suffered from KD at 1.7±1.5 years and 12 normal subjects aged 26.5±3.4 years. MFR and endothelial function were estimated, respectively, by changes in myocardial blood flow (MBF) during ATP infusion and by that during cold pressor test using 15 O-water positron emission tomography. Data from 24 regressed aneurysmal regions were compared with those from the corresponding regions (n=36) in the control group. Although the MBF at rest in the regressed aneurysmal regions was similar to that in controls, the MBF at a hyperemic state induced by ATP infusion in the regressed aneurysmal regions was significantly lower than that in the control regions. Therefore, the MFR in regressed aneurysmal regions was significantly lower than that in controls (3.53±0.95 versus 4.60±1.14; P &lt;0.05). MBF at rest and during the cold pressor test did not change in the control regions, but it was significantly reduced in regressed aneurysmal regions. The ratio of MBF during the cold pressor test to MBF at rest was significantly lower in regressed aneurysmal regions than in control regions (0.67±0.15 versus 1.00±0.15; P &lt;0.05). Conclusions — MFR and endothelial function are often impaired in regressed aneurysmal regions after KD, and tomography enables the noninvasive evaluation of coronary function.
MMP-9 responsive mesoporous silica nanoparticles for local drug delivery to NSCLC cells
Authors: Deniz Ali Bölükbas, Christian Argyo, Oliver Eickelberg, Thomas Bein, Silke Meiners, Sabine H. Van Rijt
Journal: European Respiratory Journal (2014)

Mesoporous silica nanoparticles (MSNs) offer unique features for drug delivery such as their ability to carry a wide variety of molecules as well as be functionalized by surface coating and/or external functions for controlled drug release.1 Stimuli-responsive drug release may result in a more targeted release of the drugs, and can be achieved by a change in disease specific biological environment. Specifically, MMP-9 is overexpressed during advanced stages of NSCLC, while minimally expressed in healthy tissue, contributing to poor prognosis of lung cancer patients.2, 3

In this study, we report the novel synthesis of MSNs bearing MMP-9 responsive protein caps. The pores of these particles are closed by the caps in the absence of MMP-9, whereas cargo release was observed in a stimuli-responsive manner in the presence of MMP-9 in an in vitro approach. Dose-dependent and stimuli-responsive release was also shown for the model cargo Calcein-AM, as well as for cisplatin, in two different NSCLC cell lines, as determined by cell uptake and cell death assays, respectively. Importantly, the MSNs were non-toxic up to high concentrations as shown by Annexin-V/PI double staining and flow cytometry. Notably, the MSNs which contained non-toxic doses of two chemotherapeutics resulted in increased cell death, indicating that these particles can also be used for combination treatment.

This novel drug delivery system represents a promising platform for controllable site-specific drug delivery with the possibility to deliver multiple drugs, and thus provides a promising approach for new clinical applications to combat NSCLC tumor growth.
SIRT3 Is a Mitochondrial Tumor Suppressor: A Scientific Tale That Connects Aberrant Cellular ROS, the Warburg Effect, and Carcinogenesis
Authors: Marcia C. Haigis, Chu-Xia Deng, Lydia W.S. Finley, Hyun-Seok Kim, David Gius
Journal: Cancer Research (2012)

Abstract Tumors exhibit metabolic reprogramming characterized by increased cellular reactive oxygen species (ROS) and the preferential use of glucose, which is known as the Warburg effect. However, the mechanisms by which these processes are linked remain largely elusive. Murine tumors lacking Sirt3 exhibit abnormally high levels of ROS that directly induce genomic instability and increase hypoxia-inducible factor 1α (HIF-1α) protein levels. The subsequent transcription of HIFα-dependent target genes results in cellular metabolic reprogramming and increased cellular glucose consumption. In addition, agents that scavenge ROS or reverse the Warburg effect prevent the transformation and malignant phenotype observed in cells lacking Sirt3. Thus, mice lacking Sirt3 provide a model that mechanistically connects aberrant ROS, the Warburg effect, and carcinogenesis. Cancer Res; 72(10); 2468–72. ©2012 AACR.
Electronic muscular stimulators: a novel unsuspected cause of rhabdomyolysis
Authors: P Guarascio, E A Lusi, F Soccorsi
Journal: British Journal of Sports Medicine (2004)

We report the first case of rhabdomyolysis following the use of an electronic muscular stimulator for fitness. A 26 year old male student was referred to us in April 2002 suspected of having hepatitis because of severe asthenia and raised levels of transaminases. Over the preceding three months, laboratory tests showed persistent elevation of alanine transaminase and aspartate transaminase activities, reaching values of 125 U/l (normal range 10–60) and 58 U/l (normal range 10–40) respectively. Routine tests, including red blood cell …
Efficacy of Primary Prevention Interventions When Fasting and Postglucose Dysglycemia Coexist
Authors: Ambady Ramachandran, Nanditha Arun, Ananth Samith Shetty, Chamukuttan Snehalatha
Journal: Diabetes Care (2010)

OBJECTIVE Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) have different pathophysiological abnormalities, and their combination may influence the effectiveness of the primary prevention tools. The hypothesis was tested in this analysis, which was done in a pooled sample of two Indian Diabetes Prevention Programmes (IDPP-1 and IDPP-2). RESEARCH DESIGN AND METHODS Researchers analyzed and followed up on the details of 845 of the 869 IGT subjects in the two studies for 3 years. Incidence of diabetes and reversal to normoglycemia (normal glucose tolerance [NGT]) were assessed in group 1 with baseline isolated IGT (iIGT) (n = 667) and in group 2 with IGT + IFG (n = 178). The proportion developing diabetes in the groups were analyzed in the control arm with standard advice (IDPP-1) (n = 125), lifestyle modification (LSM) (297 from both), metformin (n = 125, IDPP-1), and LSM + metformin (n = 121, IDPP-1) and LSM + pioglitazone (n = 298, IDPP-2). Cox regression analysis was used to assess the influence of IGT + IFG versus iIGT on the effectiveness of the interventions. RESULTS Group 2 had a higher proportion developing diabetes in 3 years (56.2 vs. 33.6% in group 1, P = 0.000) and a lower rate of reversal to NGT (18 vs. 32.1%, P = 0.000). Cox regression analysis showed that effectiveness of intervention was not different in the presence of fasting and postglucose glycemia after adjusting for confounding variables. CONCLUSIONS The effectiveness of primary prevention strategies appears to be similar in subjects with iIGT or with combined IGT + IFG. However, the possibility remains that a larger study might show that the effectiveness is lower in those with the combined abnormality.
Risk factors for recurrent venous thromboembolism in the European collaborative paediatric database on cerebral venous thrombosis: a multicentre cohort study
Authors: Gili Kenet, Fenella Kirkham, Thomas Niederstadt, Achim Heinecke, Dawn Saunders, Monika Stoll, Benjamin Brenner, Christoph Bidlingmaier, Christine Heller, Ralf Knöfler, Rosemarie Schobess, Barbara Zieger, Guillaume Sébire, Ulrike Nowak-Göttl
Journal: The Lancet Neurology (2007)

The relative importance of previous diagnosis and hereditary prothrombotic risk factors for cerebral venous thrombosis (CVT) in children in determining risk of a second cerebral or systemic venous thrombosis (VT), compared with other clinical, neuroimaging, and treatment variables, is unknown.We followed up the survivors of 396 consecutively enrolled patients with CVT, aged newborn to 18 years (median 5.2 years) for a median of 36 months (maximum 85 months). In accordance with international treatment guidelines, 250 children (65%) received acute anticoagulation with unfractionated heparin or low-molecular weight heparin, followed by secondary anticoagulation prophylaxis with low-molecular weight heparin or warfarin in 165 (43%).Of 396 children enrolled, 12 died immediately and 22 (6%) had recurrent VT (13 cerebral; 3%) at a median of 6 months (range 0.1-85). Repeat venous imaging was available in 266 children. Recurrent VT only occurred in children whose first CVT was diagnosed after age 2 years; the underlying medical condition had no effect. In Cox regression analyses, non-administration of anticoagulant before relapse (hazard ratio [HR] 11.2 95% CI 3.4-37.0; p<0.0001), persistent occlusion on repeat venous imaging (4.1, 1.1-14.8; p=0.032), and heterozygosity for the G20210A mutation in factor II (4.3, 1.1-16.2; p=0.034) were independently associated with recurrent VT. Among patients who had recurrent VT, 70% (15) occurred within the 6 months after onset.Age at CVT onset, non-administration of anticoagulation, persistent venous occlusion, and presence of G20210A mutation in factor II predict recurrent VT in children. Secondary prophylactic anticoagulation should be given on a patient-to-patient basis in children with newly identified CVT and at high risk of recurrent VT. Factors that affect recanalisation need further research.
Unexpected Rearrangement and Expression of the Immunoglobulin λ1 Locus in Scid Mice
Authors: Norman R. Ruetsch, Gayle C. Bosma, Melvin J. Bosma
Journal: The Journal of Experimental Medicine (1999)

In severe combined immunodeficient (scid) mice, V(D)J recombination is severely impaired due to a recessive mutation (scid). Thus, we were surprised to find in this study that Vλ1–Jλ1 rearrangement is routinely detectable in scid fetal liver, adult bone marrow, and spleen in the apparent absence of completed VH–DJH and Vκ–Jκ rearrangements. Particularly surprising, we found the level of Vλ1–Jλ1 rearrangement in scid fetal liver to be comparable to that in fetal liver of wild-type mice. The majority of scid Vλ1–Jλ1 rearrangements contained abnormal deletions at the VJ junction, consistent with the known effect of scid. However, ∼15% of Vλ1–Jλ1 rearrangements lacked abnormal deletions. Productive λ1 transcripts resulting from in-frame rearrangements were readily detectable in scid adult bone marrow and spleen, consistent with our ability to detect λ1-expressing cells by flow cytometry in the spleens of bcl-2–transgenic scid mice. Strikingly, λ1 transcripts from individual scid mice often showed VJ junctional sequences with the same recurring palindromic (P) additions of three, four, or five nucleotides. To account for these findings, we suggest that (a) nonhomologous end joining of Vλ1 and Jλ1 coding ends in fetal B lineage cells may not be (severely) impaired by scid; (b) recurring P additions in scid λ1 transcripts may reflect certain molecular constraints imposed by scid on the resolution of Vλ1 and Jλ1 hairpin coding ends; and (c), scid lymphocytes with productively rearranged Vλ1 and Jλ1 elements may differentiate into recombinase-inactive cells and emigrate from bone marrow to spleen.
Prediction of response to imatinib by prospective quantitation of BCR-ABL transcript in late chronic phase chronic myeloid leukemia patients
Authors: G. Martinelli, I. Iacobucci, G. Rosti, F. Pane, M. Amabile, F. Castagnetti, D. Cilloni, S. Soverini, N. Testoni, G. Specchia, S. Merante, A. Zaccaria, F. Frassoni, G. Saglio, M. Baccarani
Journal: Annals of Oncology (2006)
Abstract 4480: Preclinical evaluation of the mTOR inhibitor, temsirolimus, in combination with the epothilone B analog, ixabepilone
Authors: Michael E. Menefee, Keith C. Bible, Christina Von Roemeling, John Al Copland
Journal: Cancer Research (2010)

Abstract Introduction: Despite significant progress over the last decade in the development of therapeutics for metastatic cancers including breast cancer (MBC), non small cell lung cancer (NSCLC), and renal cell carcinoma (RCC), most patients will ultimately succumb to their malignancy; more effective therapeutics are sorely needed. The microtubule (MT) is a well-validated target for anti-cancer therapeutics. Ixabepilone (Ixa), a MT stabilizer is approved for MBC and has demonstrated efficacy against other solid tumors. mTOR is another validated target for anti-cancer therapeutics. Temsirolimus (Tem) inhibits mTOR and is approved for advanced RCC. We tested the hypothesis that the addition of Ixa to Tem might augment its anti-tumor activity in vitro. Methods: The cell lines, A498 (RCC), MDA-MB-231 (MBC), and A549 (NSCLC) were treated with Tem alone, Ixa alone, or the combination. All cell lines were also treated with the combination of Tem and Ixa in a fixed ratio of 1:20; Tem doses ranged from 0.125 [nM] to 5 [nM] and Ixa doses ranged from 2.5 [nM] to 100 [nM]. The effects of the treatments were evaluated with clonogenic assays. Synergism was evaluated using CalucSyn 2.0 in accord with the isobologram method of Chou and Talalay. Results: Both Tem and Ixa inhibited cell growth in all tested cell lines as single agents in dose-dependent fashions. Moreover, the combination of Tem and Ixa synergistically enhanced cytotoxicity in all tested lines (see table below).Cell LineED50 [nM]CI (lowest value)A4980.449280.404A5490.285440.263MDA-MB-2310.483550.373 Conclusion: The combination of Ixa and Tem displayed promising activity in all tested cell lines. These findings support the further evaluation of this combination in a phase I clinical trial. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4480.