tbuckley/cabot-search huggingface dataset:
THE INTRACELLULAR LOCALIZATION OF POLIOMYELITIS VIRUS
Authors: Albert S. Kaplan, Joseph L. Melnick
Journal: The Journal of Experimental Medicine (1953)

A study was made of the intracellular localization of Type 2 poliomyelitis virus, using the technique of Mirsky and Pollister (23) for cellular fractionation. After isotonic saline homogenization of central nervous system tissue from infected mice, and subsequent centrifugation of the suspension, the virus present in the supernatant fluid was held to be of cytoplasmic origin. Upon serial washings of the sediment with physiological saline, the resulting supernates contained progressively less virus until by the seventh washing, virtually none was present. At this point extraction of the washed sediment with molar NaCl, which lyses the nuclei, yielded substantial amounts of virus, and this was assumed to be from nuclear sources. The possibility has not been excluded however that the "nuclear" sediment was contaminated by cytoplasmic particles too large to remain in the supernate. Experiments on the increase of virus during the incubation and acute stages of infection have revealed that it was first detectable in the "cytoplasmic" fraction and subsequently in the "nuclear" fraction. Virus in the "nuclear" fraction from paralyzed mice sometimes reached titers almost as high as those found in the "cytoplasm." Adsorption experiments indicated that the "nuclear" fraction of CNS tissue from normal, uninoculated mice did not adsorb added Type 2 poliomyelitis virus, nor did such fractions adsorb virus procured from the "cytoplasm" or "nuclei" of infected cells. Although individual mice varied in their response after virus injection, the "cytoplasmic" fraction of paralytic mice was found to contain virus regularly, whereas little more than half of the non-paralytic mice yielded it. When virus was present in the "cytoplasm," it could be found in the "nuclear" fraction of paralytic mice with much greater regularity than in that of non-paralytic mice. A comparison between the lines of the MEF1 strain of poliomyelitis virus, "adapted" and "non-adapted" to newborn mice, and the Lansing strain, revealed no differences in their intracellular increase. In both infant and adult mice, the chief difference in the findings with non-paralyzed and paralyzed mice lay in the greater concentration of virus in the "nuclear" fractions of the latter group.
Ionic Current Basis of Electrocardiographic Waveforms
Authors: Kazutaka Gima, Yoram Rudy
Journal: Circulation Research (2002)

Body surface electrocardiograms and electrograms recorded from the surfaces of the heart are the basis for diagnosis and treatment of cardiac electrophysiological disorders and arrhythmias. Given recent advances in understanding the molecular mechanisms of arrhythmia, it is important to relate these electrocardiographic waveforms to cellular electrophysiological processes. This modeling study establishes the following principles: (1) voltage gradients created by heterogeneities of the slow-delayed rectifier ( I Ks ) and transient outward ( I to ) potassium current inscribe the T wave and J wave, respectively; T-wave polarity and width are strongly influenced by the degree of intercellular coupling through gap-junctions. (2) Changes in [K + ] o modulate the T wave through their effect on the rapid-delayed rectifier, I Kr . (3) Alterations of I Ks , I Kr , and I Na (fast sodium current) in long-QT syndrome (LQT1, LQT2, and LQT3, respectively) are reflected in characteristic QT-interval and T-wave changes; LQT1 prolongs QT without widening the T wave. (4) Accelerated inactivation of I Na on the background of large epicardial I to results in ST elevation (Brugada phenotype) that reflects the degree of severity. (5) Activation of the ATP-sensitive potassium current, I K(ATP) , is sufficient to cause ST elevation during acute ischemia. These principles provide a mechanistic cellular basis for interpretation of electrocardiographic waveforms.
Oral and bronchial provocation tests with aspirin for diagnosis of aspirin-induced asthma
Authors: E. Nizankowska, A. Bestynska-Krypel, A Cmiel, A Szczeklik
Journal: European Respiratory Journal (2000)

In 35 asthmatic patients with acetylsalicylic acid (aspirin; ASA) intolerance (AIA) and 15 asthmatics tolerating ASA well, the authors compared the diagnostic value of the placebo-controlled oral ASA versus inhaled L-lysine (L) ASA challenges. All AIA subjects gave a history of asthmatic attacks following ingestion of ASA and in all of them the intolerance was confirmed by oral challenge test over the past 10 yrs. Doses of ASA increasing in geometric progression were used in oral tests 10-312 mg (cumulative dose 500 mg); in bronchial tests 0.18-115 mg (cumulative dose 182 mg). Either challenge was considered as positive, if forced expiratory volume in one second (FEV1) dropped at least 20% from the baseline value and/or strong extrabronchial symptoms of intolerance occurred. Urinary leukotriene E4 excretion was determined at baseline and following the challenges. In 24 out of 35 patients the oral test was positive, based on a 20% decrease in FEV1. When including extrabronchial symptoms this was positive in 31 cases. Bronchial L-ASA challenge led to &gt; or =20% fall FEV1 in 21 out of 35 cases, and in 27 cases when including extrabronchial symptoms. No correlation was observed between ASA provocative dose causing a 20% fall in FEV1, determined by the oral route compared to the inhalation route. Urinary LTE4 increased after both challenges the rise being higher following oral as compared to inhalation provocation (p=0.0001). It is concluded that both tests had similar specificity whilst the oral test showed a tendency to higher sensitivity for the clinical diagnosis of acetylsalicylic acid intolerance. The inclusion of extrabronchial symptoms into the criteria of test positivity enhanced the diagnostic value of both procedures. In both tests the highest leukotriene E4 increases were found in the presence of extrabronchial symptoms, suggesting the participation of tissues other than the lung in aspirin induced leukotriene E4 release to urine.
Diagnosis and management of psoriasis and psoriatic arthritis in adults: summary of SIGN guidance
Authors: A. D. Burden, M. Hilton Boon, J. Leman, H. Wilson, R. Richmond, A. D. Ormerod
Journal: BMJ (2010)

The degree of disability and negative impact on quality of life caused by psoriasis and psoriatic arthritis are comparable to those of ischaemic heart disease, diabetes, depression, and cancer.1 Severe psoriasis and psoriatic arthritis are associated with an increased risk of conditions such as cardiovascular disease, diabetes, and depression.2 3 4 5 Psoriatic arthritis is underdiagnosed; about a fifth of patients with psoriasis also have psoriatic arthritis.6 The management of patients with both conditions may be particularly challenging and require close collaboration among several specialties. This article summarises the most recent recommendations from the Scottish Intercollegiate Guidelines Network (SIGN) on the diagnosis and management of psoriasis and psoriatic arthritis in adults.7 SIGN recommendations are based on systematic reviews of best available evidence. The strength of the evidence is graded as A, B, C, or D (fig 1⇓), but the grading does not reflect the clinical importance of the recommendations. Recommended best practice (“good practice points”), based on the clinical experience of the guideline development group, is also indicated (as GPP). Fig 1 Explanation of SIGN grades of recommendations ### Diagnosis and assessment in primary care
Gallium-67 SPECT scintigraphy may be useful in diagnosis of temporal arteritis
Authors: T Reitblat
Journal: Annals of the Rheumatic Diseases (2003)

Temporal arteritis (TA) is a common syndrome in the elderly, consisting of persistent pain in the temporal area of the skull, jaw claudication, sudden visual loss, high erythrocyte sedimentation rate, and tenderness on palpation in the temporal area. The diagnosis of this condition is relatively straightforward when the typical symptoms and a positive temporal artery biopsy are present. However, only half of the patients have a positive temporal artery biopsy. Other diagnostic procedures, such as colour Doppler sonography or superficial carotid artery angiography which have been proved to be useful for the diagnosis of TA, do not discriminate between inflammatory and non-inflammatory temporal artery disease and may be helpful only in experienced hands. Gallium-67 ((67)Ga) planar scan was reported to be useful in the diagnosis of the disease. Quantitative (67)Ga single photon emission computed tomography (SPECT) may raise the accuracy of the diagnosis.To investigate the effectiveness and usefulness of (67)Ga SPECT scintigraphy in the diagnosis of TA.Nine patients (five male, four female) and six controls were included in the study. All of them received 8-10 mCi (67)Ga intravenously 48 hours before the scan.(67)Ga uptake ratios were calculated on transaxial and coronal slices.All patients showed increased uptake in the temporal area of the skull compared with controls.The data suggest that (67)Ga skull SPECT may be useful in the diagnosis of TA, especially if the uptake ratio in the area of interest is calculated. Further studies are needed to confirm these data.
Effects of inhaled versus intravenous vasodilators in experimental pulmonary hypertension
Authors: D Walmrath, R Schermuly, J Pilch, F Grimminger, W Seeger
Journal: European Respiratory Journal (1997)

Inhaled nitric oxide (NO) causes selective pulmonary vasodilation and improves gas exchange in acute lung failure. In experimental pulmonary hypertension, we compared the influence of the aerosolized vasodilatory prostaglandins (PG) PGI2 and PGE1 on vascular tone and gas exchange to that of infused prostanoids (PGI2, PGE1) and inhaled NO. An increase of pulmonary artery pressure (Ppa) from 8 to approximately 34 mmHg was provoked by continuous infusion of U-46619 (thromboxane A2 (TxA2) analogue) in blood-free perfused rabbit lungs. This was accompanied by formation of moderate lung oedema and severe ventilation-perfusion (V'/Q') mismatch, with predominance of shunt flow (&gt;50%, assessed by the multiple inert gas elimination technique). When standardized to reduce the Pps by approximately 10 mmHg, inhaled NO (200 ppm), aerosolized PGI2 (4 ng x kg(-1) x min(-1)) and nebulized PGE1 (8 ng x kg(-1) x min(-1)) all reduced both pre- and postcapillary vascular resistance, but did not affect formation of lung oedema. All inhalative agents improved the V'/Q' mismatch and reduced shunt flow, the rank order of this capacity being NO &gt; PGI2 &gt; PGE1. In contrast, lowering of Ppa by intravascular administration of PGI2 and PGE1 did not improve gas exchange. "Supratherapeutic" doses of inhaled vasodilators in control lungs (400 ppm NO, 30 ng x kg(-1) x min(-1) of PGI2 or PGE1) did not provoke vascular leakage or affect the physiological V'/Q' matching. We conclude that aerosolization of prostaglandins I2 and E1 is as effective as inhalation of nitric oxide in relieving pulmonary hypertension. When administered via this route instead of being infused intravascularly, the prostanoids are capable of improving ventilation-perfusion matching, suggesting selective vasodilation in well-ventilated lung areas.
Antifungal Prophylaxis for Allogeneic Hematopoietic Cell Transplantation
Authors: Deborah Braccia, Patricia Stone, Heather Taffet Gold
Journal: Journal of Clinical Oncology (2009)

TO THE EDITOR: In the article by Michallet and Ito, the authors provided an excellent comprehensive review of the literature; however, the recommendations for allogeneic hematopoietic cell transplantation prophylaxis outlined in Table 5, “Author Recommendations for Prophylaxis,” are surprising. Three agents are recommended for primary prophylaxis during overlapping time periods. The literature shows that neither micafungin nor voriconazole yield a survival advantage over fluconazole, the standard of care. The authors recommended fluconazole for primary neutropenia through day 75 and voriconazole for neutropenia through day 100. A head-tohead to study between voriconazole and fluconazole reported a decrease in aspergillosis in the voriconazole arm; however, the rates of invasive fungal infection, fungal-free survival, and overall mortality were similar between both groups. The study drugs were administered for 100 days in both arms, which indicates that fluconazole had similar efficacy through day 100. It seems premature to recommend micafungin as primary prophylaxis for “neutropenia through engraftment,” since the standard of care and the authors themselves recommend prophylaxis for 75 to 100 days post-transplant. Although the authors mentioned the possibility of sequencing prophylaxis (micafungin followed by either fluconazole or voriconazole), there are no data to support this approach. In addition, in the trial comparing micafungin to fluconazole, there was not a survival benefit for micafungin as noted by Michallat and Ito, and the other end points were not comparable to the studies reviewed. From the evidence presented, there does not appear to be a strong rationale for the use of voriconazole or micafungin when compared with fluconazole. Furthermore, it should be noted that fluconazole is generic and costs significantly less than voriconazole or micafungin. Based on the evidence and cost considerations, fluconazole seems to be the optimal antifungal agent for prophylaxis in allogeneic hematopoietic stem-cell transplant recipients. Our familiarity with this literature is based on our current work conducting a cost-effectiveness analysis of prophylactic antifungal therapy in patients undergoing allogeneic hematopoietic stem-cell transplant. We presented this work at the annual meeting of the Society for Medical Decision Making, October 18-21, 2009, in Hollywood, CA.
The Translational Repressor Pumilio Regulates Presynaptic Morphology and Controls Postsynaptic Accumulation of Translation Factor eIF-4E
Authors: Kaushiki P. Menon, Subhabrata Sanyal, Yasuaki Habara, Ricardo Sanchez, Robin P. Wharton, Mani Ramaswami, Kai Zinn
Journal: Neuron (2004)
Randomized phase II study of biweekly CHOP anddose-escalated CHOP with prophylactic use of lenograstim (glycosylated G-CSF) in aggressive non-Hodgkin’s lymphoma: Japan Clinical Oncology Group Study 9505
Authors: K. Itoh, T. Ohtsu, H. Fukuda, Y. Sasaki, M. Ogura, Y. Morishima, T. Chou, K. Aikawa, N. Uike, F. Mizorogi, T. Ohno, S. Ikeda, T. Sai, M. Taniwaki, F. Kawano, M. Niimi, T. Hotta, M. Shimoyama, K. Tobinai
Journal: Annals of Oncology (2002)
Biologic and Quality-of-Life Outcomes From the Mediterranean Lifestyle Program
Authors: Deborah J. Toobert, Russell E. Glasgow, Lisa A. Strycker, Manuel Barrera, Janice L. Radcliffe, Rosemary C. Wander, John D. Bagdade
Journal: Diabetes Care (2003)

OBJECTIVE—Few multiple lifestyle behavior change programs have been designed to reduce the risk of coronary heart disease in postmenopausal women with type 2 diabetes. This study tested the effectiveness of the Mediterranean Lifestyle Program (MLP), a comprehensive lifestyle self-management program (Mediterranean low–saturated fat diet, stress management training, exercise, group support, and smoking cessation), in reducing cardiovascular risk factors in postmenopausal women with type 2 diabetes. RESEARCH DESIGN AND METHODS—Postmenopausal women with type 2 diabetes (n = 279) were randomized to either usual care (control) or treatment (MLP) conditions. MLP participants took part in an initial 3-day retreat, followed by 6 months of weekly meetings, to learn and practice program components. Biological end points were changes in HbA1c, lipid profiles, BMI, blood pressure, plasma fatty acids, and flexibility. Impact on quality of life was assessed. RESULTS—Multivariate ANCOVAs revealed significantly greater improvements in the MLP condition compared with the usual care group on HbA1c, BMI, plasma fatty acids, and quality of life at the 6-month follow-up. Patterns favoring intervention were seen in lipids, blood pressure, and flexibility but did not reach statistical significance. CONCLUSIONS—These results demonstrate that postmenopausal women with type 2 diabetes can make comprehensive lifestyle changes that may lead to clinically significant improvements in glycemic control, some coronary heart disease risk factors, and quality of life.
Cancer Network Disruption by a Single Molecule Inhibitor Targeting Both Histone Deacetylase Activity and Phosphatidylinositol 3-Kinase Signaling
Authors: Changgeng Qian, Cheng-Jung Lai, Rudi Bao, Da-Gong Wang, Jing Wang, Guang-Xin Xu, Ruzanna Atoyan, Hui Qu, Ling Yin, Maria Samson, Brian Zifcak, Anna Wai See Ma, Steven DellaRocca, Mylissa Borek, Hai-Xiao Zhai, Xiong Cai, Maurizio Voi
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Given that histone deacetylase (HDAC) inhibitors are known to induce multiple epigenetic modifications affecting signaling networks and act synergistically with phosphatidylinositol 3-kinase (PI3K) inhibitors, we developed a strategy to simultaneously inhibit HDACs and PI3K in cancer cells. Experimental Design: We constructed dual-acting inhibitors by incorporating HDAC inhibitory functionality into a PI3K inhibitor pharmacophore. CUDC-907, a development candidate selected from these dual inhibitors, was evaluated in vitro and in vivo to determine its pharmacologic properties, anticancer activity, and mechanism of action. Results: CUDC-907 potently inhibits class I PI3Ks as well as classes I and II HDAC enzymes. Through its integrated HDAC inhibitory activity, CUDC-907 durably inhibits the PI3K-AKT-mTOR pathway and compensatory signaling molecules such as RAF, MEK, MAPK, and STAT-3, as well as upstream receptor tyrosine kinases. CUDC-907 shows greater growth inhibition and proapoptotic activity than single-target PI3K or HDAC inhibitors in both cultured and implanted cancer cells. Conclusions: CUDC-907 may offer improved therapeutic benefits through simultaneous, sustained disruption of multiple oncogenic signaling networks. Clin Cancer Res; 18(15); 4104–13. ©2012 AACR.
Effects of adenosine on human coronary arterial circulation.
Authors: R F Wilson, K Wyche, B V Christensen, S Zimmer, D D Laxson
Journal: Circulation (1990)

Adenosine is a potent vasodilator used extensively to study the coronary circulation of animals. Its use in humans, however, has been hampered by lack of knowledge about its effects on the human coronary circulation and by concern about its safety. We investigated in humans the effects of adenosine, administered by intracoronary bolus (2-16 micrograms), intracoronary infusion (10-240 micrograms/min), or intravenous infusion (35-140 micrograms/kg/min) on coronary and systemic hemodynamics and the electrocardiogram. Coronary blood flow velocity (CBFV) was measured with a 3F coronary Doppler catheter. The maximal CBFV was determined with intracoronary papaverine (4.5 +/- 0.2.resting CBFV). In normal left coronary arteries (n = 20), 16-micrograms boluses of adenosine caused coronary hyperemia similar to that caused by papaverine (4.6 +/- 0.7.resting CBFV). In the right coronary artery (n = 5), 12-micrograms boluses caused maximal hyperemia (4.4 +/- 1.0.resting CBFV). Intracoronary boluses caused a small, brief decrease in arterial pressure (similar to that caused by papaverine) and no changes in heart rate or in the electrocardiogram. The duration of hyperemia was much shorter after adenosine than after papaverine administration. Intracoronary infusions of 80 micrograms/min or more into the left coronary artery (n = 6) also caused maximal hyperemia (4.4 +/- 0.1.resting CBFV), and doses up to 240 micrograms/min caused a minimal decrease in arterial pressure (-6 +/- 2 mm Hg) and no significant change in heart rate or in electrocardiographic variables. Intravenous infusions in normal patients (n = 25) at 140 micrograms/kg/min caused coronary vasodilation similar to that caused by papaverine in 84% of patients (4.4 +/- 0.9.resting CBFV). At submaximal infusion rates, however, CBFV often fluctuated widely. During the 140-micrograms/kg/min infusion, arterial pressure decreased 6 +/- 7 mm Hg, and heart rate increased 24 +/- 14 beats/min. One patient developed 1 cycle of 2:1 atrioventricular block, but otherwise, the electrocardiogram did not change. In eight patients with microvascular vasodilator dysfunction (delta CBFV, less than 3.5 peak/resting velocity after a maximally vasodilating dose of intracoronary papaverine), the dose-response characteristics to intracoronary boluses and intravenous infusions of adenosine were similar to those found in normal patients.(ABSTRACT TRUNCATED AT 400 WORDS)
Effect of chronic ethanol ingestion on hepatic and intestinal acyl coenzyme A:Cholesterol acyltransferase and 3-hydroxy-3-methylglutaryl coenzyme A reductase in the rat
Authors: F. Jeffrey Field, John S. Boydstun, Douglas R. Labrecque
Journal: Hepatology (1985)

Two groups of rats were pair-fed diets in which 36% of the calories were provided by either ethanol or dextrimaltose. After 60 days on these liquid diets, rats fed ethanol were significantly smaller than control rats fed dextrimaltose. Serum cholesterol levels in ethanol-fed animals were 20% higher than control rats. Cholestasis was not observed histologically, and serum alkaline phosphatase and bilirubin levels were the same in both groups. The livers of animals ingesting ethanol accumulated triglycerides and cholesterol. The increase in cholesterol was due to an increase in cholesteryl esters. The cholesterol content of liver microsomes, however, was unchanged by ethanol feeding. A small increase in unesterified cholesterol was observed in intestinal micro-somes prepared from animals receiving ethanol. Microsomal fatty acids in liver and intestine were unchanged by the ethanol diet. Chronic ingestion of ethanol in these animals failed to change acyl coenzyme A:cholesterol acyltransferase or 3-hydroxy-3-methylglutaryl-coenzyme A reductase activities in the intestine. In contrast, the activities of acyl coenzyme A:cholesterol acyltransferase and 3-hydroxy-3-methylglutaryl-coenzyme A reductase were significantly increased in the livers of rats receiving ethanol. Thus, the chronic ingestion of ethanol caused a marked accumulation of hepatic cholesteryl esters. This was associated with a significant increase in the activities of enzymes that control the rates of both cholesterol synthesis and cholesterol esterification in the liver. These observed changes in enzyme activities may contribute to the lipid accumulation which occurs in these livers. Chronic ethanol consumption did not alter cholesterol metabolism in the intestine.
Suppression of renin secretion in the rat kidney by a nonvascular alpha-adrenergic mechanism.
Authors: R Vandongen, K D Strang, M H Poessè, W H Birkenhäger
Journal: Circulation Research (1979)

We studied the effect of alpha-adrenergic stimulation, using phenylephrine, on basal and isoproterenol-provoked renin secretion in the isolated perfused rat kidney. Infusion of phenylephrine increased renal perfusion pressure and prevented the response in renin secretion to isoproterenol. No suppression of basal secretion was observed. Renal vasoconstriction was abolished, and the response in renin secretion to isoproterenol was restored by alpha-adrenoceptor blockade with phenoxybenzamine. In contrast, when renal vasoconstriction was prevented by dihydralazine, suppression of renin release by phenylephrine still occurred. These observations support an inhibitory effect of a nonvascular alpha-adrenergic mechanism on renin release. We suggest that the alpha receptor mediating this effect is related directly to the juxtaglomerular cell.
Sputum indoleamine-2, 3-dioxygenase activity is increased in asthmatic airways by using inhaled corticosteroids
Authors: Kittipong Maneechotesuwan, Sirinya Supawita, Kanda Kasetsinsombat, Adisak Wongkajornsilp, Peter J. Barnes
Journal: Journal of Allergy and Clinical Immunology (2007)