tbuckley/cabot-search huggingface dataset:
Effect of Flavone Acetic Acid on Lewis Lung Carcinoma: Evidence for an Indirect Effect1
Authors: G. J. Finlay, G. P. Smith, L. M. Fray, B. C. Baguley
Journal: JNCI Journal of the National Cancer Institute (1988)

Flavone-8-acetic acid (FAA), a new antitumor agent currently undergoing clinical trial, fails to inhibit the growth of early stage Lewis lung (ILL) tumors growing in the lung. However, the growth of advanced subscutaneous tumors, arising from inoculation of either the original in vivo LL line or a tissue culture-adapted cell line (LLTC) derived from the LL line was delayed significantly by FAA treatment. Comparision, by clonogenic survival assays, of the cytotoxic effect of FAA on LLTC cells demonstrated that most cell killing occurred between 2 and 8 hours following in vivo exposure but occurred to a much lesser extent and at later times following in vitro exposure. FAA was inactive against LLTC cells growing in vivo in diffusion chambers, suggesting that a host cellular component was necessay for activity. FAA was found to induce hemorrhagic necrosis in the advanced LL tumors, as well as in a number of human tumor xenografts growing in athymic mice. The human cell lines fom which the xenografts were derviced, as well as the LL tumor lines and P388 leukemia lines, were inhibited by FAA in vitro. However, the ranking of FAA activity in vivo did not parallel that observed in vitro. Together, these observations strongly suggest that FAA has an indirect mode of antitumor action. [J Natl Cancer Inst 1988;80:241–245]
Weight Gain after Lung Reduction Surgery Is Related to Improved Lung Function and Ventilatory Efficiency
Authors: Victor Kim, Dana M. Kretschman, Alice L. Sternberg, Malcolm M. DeCamp, Gerard J. Criner
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Lung volume reduction surgery (LVRS) is associated with weight gain in some patients, but the group that gains weight after LVRS and the mechanisms underlying this phenomenon have not been well characterized.Objectives: To describe the weight change profiles of LVRS patients enrolled in the National Emphysema Treatment Trial (NETT) and to correlate alterations in lung physiological parameters with changes in weight.Methods: We divided 1,077 non–high-risk patients in the NETT into groups according to baseline body mass index (BMI): underweight (<21 kg/m2), normal weight (21–25 kg/m2), overweight (25–30 kg/m2), and obese (>30 kg/m2). We compared BMI groups and LVRS and medical groups within each BMI stratum with respect to baseline characteristics and percent change in BMI (%ΔBMI) from baseline. We examined patients with (ΔBMI ≥ 5%) and without (ΔBMI < 5%) significant weight gain at 6 months and assessed changes in lung function and ventilatory efficiency (V̇e/V̇co2).Measurements and Main Results: The percent change in BMI was greater in the LVRS arm than in the medical arm in the underweight and normal weight groups at all follow-up time points, and at 12 and 24 months in the overweight group. In the LVRS group, patients with ΔBMI ≥ 5% at 6 months had greater improvements in FEV1 (11.53 ± 9.31 vs. 6.58 ± 8.68%; P < 0.0001), FVC (17.51 ± 15.20 vs. 7.55 ± 14.88%; P < 0.0001), residual volume (–66.20 ± 40.26 vs. –47.06 ± 39.87%; P < 0.0001), 6-minute walk distance (38.70 ± 69.57 vs. 7.57 ± 73.37 m; P < 0.0001), maximal expiratory pressures (12.73 ± 49.08 vs. 3.54 ± 32.22; P = 0.0205), and V̇e/V̇co2 (–1.58 ± 6.20 vs. 0.22 ± 8.20; P = 0.0306) at 6 months than patients with ΔBMI < 5% at 6 months.Conclusions: LVRS leads to weight gain in nonobese patients, which is associated with improvement in lung function, exercise capacity, respiratory muscle strength, and ventilatory efficiency. These physiological changes may be partially responsible for weight gain in patients who undergo LVRS.
Bone mass in nodal primary generalised osteoarthrosis.
Authors: D M Reid, N S Kennedy, M A Smith, P Tothill, G Nuki
Journal: Annals of the Rheumatic Diseases (1984)

Previous studies of patients with primary osteoarthrosis of the hip have suggested an increase in bone mass compared with control populations. Nodal primary generalised osteoarthrosis is known to have a strong familial tendency. To test the hypothesis that this tendency might also lead to increased bone mass, total body calcium has been measured by in-vivo neutron activation analysis and cortical area calculated from measurements of metacarpal indices in 15 female patients with primary generalised osteoarthrosis. The results have been compared with those from 12 healthy controls matched for age, menopausal status, and skeletal size. No significant differences were noted in the total body calcium or cortical area measurements between the 2 groups either before or after correction for skeletal size and menopausal status. No relationship was found between the grade of radiological osteoarthrosis in the hand and either bone mass parameter. Bone mass would not appear to be an important factor in the aetiopathogenesis of nodal primary generalised osteoarthrosis.
ST. LOUIS ENCEPHALITIS VIRUS IN THE BLOOD OF EXPERIMENTALLY INOCULATED FOWLS AND MAMMALS
Authors: W. McD. Hammon, W. C. Reeves, E. M. Izumi
Journal: The Journal of Experimental Medicine (1946)

1. Of three species of mammals tested by peripheral inoculation (guinea pig, cat, and horse) none showed viremia under conditions which suggested that any of these species would serve as a frequent source of mosquito infection. 2. Of the birds tested (chicken, duck, and dove) all developed viremia and might readily serve as natural sources of mosquito infection. Chickens were shown to be very highly susceptible to infection by minute amounts of virus inoculated subcutaneously. 3. Virus may appear in the blood of chickens within 16 hours after inoculation and it has persisted till at least the 120th hour. No fowl showed any sign of illness as a result of the infection.
EWS-FLI-1 Expression Triggers a Ewing's Sarcoma Initiation Program in Primary Human Mesenchymal Stem Cells
Authors: Nicolò Riggi, Mario-Luca Suvà, Domizio Suvà, Luisa Cironi, Paolo Provero, Stéphane Tercier, Jean-Marc Joseph, Jean-Christophe Stehle, Karine Baumer, Vincent Kindler, Ivan Stamenkovic
Journal: Cancer Research (2008)

Abstract Ewing's sarcoma family tumors (ESFT) express the EWS-FLI-1 fusion gene generated by the chromosomal translocation t(11;22)(q24;q12). Expression of the EWS-FLI-1 fusion protein in a permissive cellular environment is believed to play a key role in ESFT pathogenesis. However, EWS-FLI-1 induces growth arrest or apoptosis in differentiated primary cells, and the identity of permissive primary human cells that can support its expression and function has until now remained elusive. Here we show that expression of EWS-FLI-1 in human mesenchymal stem cells (hMSC) is not only stably maintained without inhibiting proliferation but also induces a gene expression profile bearing striking similarity to that of ESFT, including genes that are among the highest ESFT discriminators. Expression of EWS-FLI-1 in hMSCs may recapitulate the initial steps of Ewing's sarcoma development, allowing identification of genes that play an important role early in its pathogenesis. Among relevant candidate transcripts induced by EWS-FLI-1 in hMSCs, we found the polycomb group gene EZH2, which we show to play a critical role in Ewing's sarcoma growth. These observations are consistent with our recent findings using mouse mesenchymal progenitor cells and provide compelling evidence that hMSCs are candidate cells of origin of ESFT. [Cancer Res 2008;68(7):2176–85]
Energetics of isometric force development in control and volume-overload human myocardium. Comparison with animal species.
Authors: G Hasenfuss, L A Mulieri, E M Blanchard, C Holubarsch, B J Leavitt, F Ittleman, N R Alpert
Journal: Circulation Research (1991)

Alteration in crossbridge behavior and myocardial performance have been associated with myosin isoenzyme composition in animal models of myocardial hypertrophy or atrophy. In the hypertrophied human heart, myocardial performance is altered without significant changes in myosin isoenzymes. To better understand this discrepancy, isometric heat and force measurements were carried out in 1) control and volume-overload human myocardium, 2) control, pressure-overload, and hyperthyroid rabbit myocardium, and 3) control and hypothyroid rat myocardium. In control human myocardium, peak isometric twitch tension was 44.0 +/- 11.7 mN/mm2, and maximum rate of tension rise was 69.2 +/- 21.0 mN/sec.mm2. In volume-overload human myocardium, peak twitch tension and maximum rate of tension rise were reduced by 55% (p less than 0.05) and 65% (p less than 0.05), respectively. The average force-time integral of the individual crossbridge cycle, calculated by myothermal techniques, was increased by 85% (p less than 0.005) in volume-overload human myocardium. In control and hormonally altered myocardium, both across and within species (control human, control rat, control rabbit, hypothyroid rat, and hyperthyroid rabbit), there was a close relation between the crossbridge force-time integral and the percentage of V3-type myosin isoenzyme in the myocardium. However, hemodynamically altered (volume-overload human and pressure-overload rabbit) myocardium did not follow this relation. Across and within species, there were significant correlations between maximum rate of tension rise and average tension-dependent heat rate (r = 0.97, p less than 0.001) and between maximum rate of tension fall and average tension-independent heat rate (r = 0.82; p less than 0.025). Furthermore, there were close inverse relations between these heat rates and the crossbridge force-time integral. In addition, there was an inverse relation between tension-independent heat and the crossbridge force-time integral. Across and within species total myocardial energy turnover was significantly correlated with the crossbridge force-time integral (relative total heat, r = -0.84, p less than 0.02; relative total-activity related heat, r = -0.88, p less than 0.01). The present findings indicate that 1) factors separate from myosin isoenzymes account for the altered crossbridge cycle in volume-overload human and pressure-overload rabbit myocardium, 2) changes in excitation-contraction coupling processes accompany changes in the crossbridge cycle within and across species, and 3) the force-time integral of the crossbridge cycle is a major determinant of total myocardial energy turnover.
News of Members--Dr. Rex Salisbury Woods' 90th birthday and his paper "Some personal experiences of changing fashions in the treatment of injuries to the knee". Reprinted from BJSM Vol. 4, 1969
Authors: R. Salisbury Woods
Journal: British Journal of Sports Medicine (1981)

The Editor attended two International Conferences -in a private capacity, and reports are included on the 5th Balkan Congress of Sports Medicine, held at Izmir, Turkey, and an interesting interdisciplinary meeting on medicine for horses and their riders at the centre of equestrian activities in France, Saumur, in the Loire valley.BASM's Secretary, Dr. Peter Sperryn, meanwhile attended a meeting in Rome of the International Federation of Sports Medicine together with representatives of national sports medicine bodies and the International Olympic Committee.One main object of this convention was to attempt to standardise rules governing dope control in various sporting events, and to develop detection techniques.The constant battle between dope detection laboratories and unscrupulous "sportsmen" and their advisers resembles the armaments race, where increasingly powerful weapons lead to increasingly effective defence, starting with palaeolithic flints up to the hydrogen bomb.Like the armaments race, we hope that doping would also be controlled by international understanding and agreements, to reinforce legislation.
Role of Oxidant Stress in Endothelial Dysfunction Produced by Experimental Hyperhomocyst(e)inemia in Humans
Authors: Prapti M. Kanani, Christine A. Sinkey, Roger L. Browning, Margaret Allaman, Howard R. Knapp, William G. Haynes
Journal: Circulation (1999)

Background —Moderate elevations in plasma homocyst(e)ine concentrations are associated with atherosclerosis and hypertension. We tested the hypothesis that experimental perturbation of homocysteine levels produces resistance and conduit vessel endothelial dysfunction and that this occurs through increased oxidant stress. Methods and Results —Oral administration of l -methionine (100 mg/kg) was used to induce moderate hyperhomocyst(e)inemia (≈25 μmol/L) in healthy human subjects. Endothelial function of forearm resistance vessels was assessed by use of forearm vasodilatation to brachial artery administration of the endothelium-dependent dilator acetylcholine. Conduit vessel endothelial function was assessed with flow-mediated dilatation of the brachial artery. Forearm resistance vessel dilatation to acetylcholine was significantly impaired 7 hours after methionine (methionine, 477±82%; placebo, 673±110%; P =0.016). Methionine did not alter vasodilatation to nitroprusside and verapamil. Flow-mediated dilatation was significantly impaired 8 hours after methionine loading (0.3±2.7%) compared with placebo (8.2±1.6%, P =0.01). Oral administration of the antioxidant ascorbic acid (2 g) prevented methionine-induced endothelial dysfunction in both conduit and resistance vessels ( P =0.03). Conclusions —Experimentally increasing plasma homocyst(e)ine concentrations by methionine loading rapidly impairs both conduit and resistance vessel endothelial function in healthy humans. Endothelial dysfunction in conduit and resistance vessels may underlie the reported associations between homocysteine and atherosclerosis and hypertension. Increased oxidant stress appears to play a pathophysiological role in the deleterious endothelial effects of homocysteine.
miR-137 and miR-197 Induce Apoptosis and Suppress Tumorigenicity by Targeting MCL-1 in Multiple Myeloma
Authors: Yijun Yang, Fei Li, Manujendra N. Saha, Jahangir Abdi, Lugui Qiu, Hong Chang
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Deregulation of miRNA has been implicated in the pathogenesis of multiple myeloma. We identified miR-137 and miR-197, mapped to the chromosome 1p (12)–(21) deletion region, and examined their antimyeloma activity as tumor suppressors. Experimental Design: The expression of miR-137/197 was examined in multiple myeloma and normal plasma cells by qRT-PCR. Functional effect of miR-137/197 was analyzed by cell viability, apoptosis, clonogenic, and migration assays. Antimyeloma activity of miR-137/197 was further evaluated in vivo by lentiviral-based or lipid-based delivery in a mouse xenograft model of multiple myeloma. Results: miR-137/197 expression was significantly lower in multiple myeloma cell lines and multiple myeloma patient samples compared with normal plasma cells. Transfection of miR-137/197 resulted in reduction of MCL-1 protein expression, as well as alteration of apoptosis-related genes, and induction of apoptosis, inhibition of viability, colony formation, and migration in multiple myeloma cells. MCL-1 was further validated as a direct target of miR-137/197. Conversely, overexpression of MCL-1 partially reverted the effect of miR-137/197. Importantly, in vivo lentiviral-mediated or intratumor delivery of miR-137/197 induced regression of tumors in murine xenograft models of multiple myeloma. Conclusions: Our study reveals a novel role of miR-137/197 as tumor suppressors in mediating apoptosis in multiple myeloma cells by targeting MCL-1. Our findings provide a proof-of-principle that lentivirus-based or formulated synthetic miR-137/197 exerts therapeutic activity in preclinical models, and support a framework for development of miR-137/197-based treatment strategies in patients with multiple myeloma. Clin Cancer Res; 21(10); 2399–411. ©2015 AACR.
Elevated p53 expression is associated with dysregulation of the ubiquitin-proteasome system in dilated cardiomyopathy
Authors: E. J. Birks, N. Latif, K. Enesa, T. Folkvang, L. A. Luong, P. Sarathchandra, M. Khan, H. Ovaa, C. M. Terracciano, P. J.R. Barton, M. H. Yacoub, P. C. Evans
Journal: Cardiovascular Research (2008)

AimsThe molecular mechanisms that regulate cardiomyocyte apoptosis and their role in human heart failure (HF) are uncertain. Expression of the apoptosis regulator p53 is governed by minute double minute 2 (MDM2), an E3 enzyme that targets p53 for ubiquitination and proteasomal processing, and by the deubiquitinating enzyme, herpesvirus-associated ubiquitin-specific protease (HAUSP), which rescues p53 by removing ubiquitin chains from it. Here, we examined whether elevated expression of p53 was associated with dysregulation of ubiquitin-proteasome system (UPS) components and activation of downstream effectors of apoptosis in human dilated cardiomyopathy (DCM).
Atomic Basis for Sialic Acid Specificity by a Transporter that Allows Haemophilus Influenzae to Evade Host Defense by Molecular Mimicry
Authors: N COUSSENS, J JOHNSTON, K TURNER, A ZALESKI, J HOUTMAN, M APICELLA, S RAMASWAMY
Journal: Journal of Allergy and Clinical Immunology (2008)
Experimental Acute Renal Failure Induced by Uranyl Nitrate in the Dog
Authors: WALTER FLAMENBAUM, JAMES S. MCNEIL, THEODORE A. KOTCHEN, ANDREW J. SALADINO
Journal: Circulation Research (1972)

The diminished glomerular filtration rate observed in previous studies of acute renal failure induced by uranyl nitrate has been ascribed to backflow of glomerular filtrate through necrotic tubular epithelium, since renal blood flow was essentially normal. Renal blood flow ( 133 xenon washout) and renal function were studied serially for 96 hours after the administration of uranyl nitrate (10 mg/kg, iv) in unanesthetized dogs with chronic renal artery catheters. Inulin clearance and total renal blood flow decreased to 25% and 52% of control, respectively, by 6 hours and remained depressed. By 3 hours, cortical flow decreased to 330±20 ml/min 100 g -1 (control 507±12 ml/min 100 g -1 ) and outer medullary flow increased to 147±8 ml/min 100 g -1 (control 97±18 ml/min 100 g -1 ), indicating intrarenal blood flow redistribution. From 6 hours on, these flow components were no longer separable. The ratio of flow in the outer two-thirds of the renal cortex to that in the whole cortex, determined using 85 strontium-labeled microspheres (15µ), decreased to 0.34±0.06 and 0.40±0.04 at 6 and 96 hours, respectively (control 2.21±0.12). Plasma renin activity was 1.8±0.6 ng/ml hour -1 at 3 hours and remained elevated (control 0.6±0.2 ng/ml hour -1 ). Histological examination revealed minimal tubular change at 6 hours and widespread disruption at 96 hours. The decrease in renal blood flow prior to any significant tubular pathology suggests that alterations in renal hemodynamics, which may be mediated by the renin-angiotensin system, are responsible for the diminished renal function observed in this model of acute renal failure.
A mutation in the dynein heavy chain gene compensates for energy deficit of mutant SOD1 mice and increases potentially neuroprotective IGF-1
Authors: Anissa Fergani, Judith Eschbach, Hugues Oudart, Yves Larmet, Birgit Schwalenstocker, Albert C Ludolph, Jean-Philippe Loeffler, Luc Dupuis
Journal: Molecular Neurodegeneration (2011)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons. ALS patients, as well as animal models such as mice overexpressing mutant SOD1s, are characterized by increased energy expenditure. In mice, this hypermetabolism leads to energy deficit and precipitates motor neuron degeneration. Recent studies have shown that mutations in the gene encoding the dynein heavy chain protein are able to extend lifespan of mutant SOD1 mice. It remains unknown whether the protection offered by these dynein mutations relies on a compensation of energy metabolism defects.SOD1(G93A) mice were crossbred with mice harboring the dynein mutant Cramping allele (Cra/+ mice). Dynein mutation increased adipose stores in compound transgenic mice through increasing carbohydrate oxidation and sparing lipids. Metabolic changes that occurred in double transgenic mice were accompanied by the normalization of the expression of key mRNAs in the white adipose tissue and liver. Furthermore, Dynein Cra mutation rescued decreased post-prandial plasma triglycerides and decreased non esterified fatty acids upon fasting. In SOD1(G93A) mice, the dynein Cra mutation led to increased expression of IGF-1 in the liver, increased systemic IGF-1 and, most importantly, to increased spinal IGF-1 levels that are potentially neuroprotective.These findings suggest that the protection against SOD1(G93A) offered by the Cramping mutation in the dynein gene is, at least partially, mediated by a reversal in energy deficit and increased IGF-1 availability to motor neurons.
Movement of the Feline Esophagus Associated with Respiration and Peristalsis. AN EVALUATION USING TANTALUM MARKERS
Authors: Wylie J. Dodds, Edward T. Stewart, Donald Hodges, F. Frank Zboralske
Journal: Journal of Clinical Investigation (1973)

The outer, lateral esophageal walls in the distal half of the esophagus in each of five cats were labeled with small tantalum wires. About 8 wk later, esophageal motion associated with respiration and peristalsis, induced by injecting barium boli (5 ml each) into the proximal esophagus, was recorded on cine and serial biplane roentgenograms while recording intraluminal esophageal pressures simultaneously by manometry. Esophageal motion was also evaluated without a manometric tube in place. The coordinates for each marker were digitized and a computer was used to plot marker position against time. During respiration, the markers passively made a shallow, 2-10 mm excursion on the longitudinal esophageal axis. This movement was synchronous with thoracic and diaphragmatic movement and changes in intraluminal esophageal pressure. Immediately after the onset of peristalsis, the markers made a pronounced oral movement of 10 mm or more above their mean respiratory position, as if to engulf the bolus. Markers in opposing esophageal walls approximated one another and commenced an aboral movement as the bolus tail, which was essentially co-incident with onset of the manometric pressure complex, passed the marker sites. The markers returned to their respective rest positions essentially coincident with passage of the pressure complex peak and then moved below their respective rest positions. The aboral excursion occurred predominantly after the bolus had emptied into the stomach. The magnitude and duration of oral excursion was significantly greater for the distal than for the more proximal markers; conversely, the magnitude and duration of aboral excursion was greater for the proximal than for the more distal markers. During the peristaltic sequence, the labeled portion of the esophagus shortened from 26 to 46% of its resting length. No evidence of esophageal torque was shown. These findings suggest that both the longitudinal and circular esophageal musculature play an active and important role during peristaltic transport of a bolus through the esophagus.