tbuckley/cabot-search huggingface dataset:
Tobacco and health. Report of Scottsdale Research Conference
Authors: A. Brass
Journal: JAMA (1970)

The pharmacology of nicotine and other tobacco smoke fractions, and their effects on animal and human tissues, were discussed at the Second Research Conference on Tobacco and Health of the AMA-ERF, held in Scottsdale, Ariz, May 6 and 7, 1970. The majority of the 70 papers presented dealt with animal experiments. Many were concerned with work in progress or projects about to be undertaken. A selection of the findings reported is given below. In studies on the gastrointestinal pharmacology of nicotine, C. C. Hug, Jr., found a dose-dependent inhibition of contractile activity of both circular and longitudinal muscle in the gastric antrum, duodenum, ileum, and colon in intact dogs and monkeys. J. G. Forte reported that low levels of nicotine injected intravenously into rats had no effect on the gastric secretory response to cholinergic mediators, although high levels of nicotine either greatly reduced or completely abolished the hydrochloric acid secretory
Expression of Dog Microdystrophin in Mouse and Dog Muscles by Gene Therapy
Authors: Christophe Pichavant, Pierre Chapdelaine, Daniel G Cerri, Jean-Christophe Dominique, Simon P Quenneville, Daniel Skuk, Joe N Kornegay, João CS Bizario, Xiao Xiao, Jacques P Tremblay
Journal: Molecular Therapy (2010)

Duchenne muscular dystrophy (DMD) is characterized by the absence of dystrophin. Several previous studies demonstrated the feasibility of delivering microdystrophin complementary DNA (cDNA) into mouse and normal nonhuman primate muscles by <i>ex vivo</i> gene therapy. However, these animal models do not reproduce completely the human DMD phenotype, while the dystrophic dog model does. To progress toward the use of the best animal model of DMD, a dog microdystrophin was transduced into human and dystrophic dog muscle precursor cells (MPCs) with a lentivirus before their transplantation into mouse muscles. One month following MPC transplantation, myofibers expressing the dog microdystrophin were observed. We also used another approach to introduce this transgene into myofibers, <i>i.e.</i>, the electrotransfer of a plasmid coding for the dog microdystrophin. The plasmid was injected into mouse and dog muscles, and brief electric pulses were applied in the region of injection. Two weeks later, the transgene was detected in both animals. Therefore, <i>ex vivo</i> gene therapy and electrotransfer are two possible methods to introduce a truncated version of dystrophin into myofibers of animal models and eventually into myofibers of DMD patients.
Plasma C3 and C4 Concentrations in Management of Glomerulonephritis
Authors: J. S. Cameron, R. M. Vick, C. S. Ogg, W. M. Seymour, C. Chantler, D. R. Turner
Journal: BMJ (1973)

As part of a larger study of serial complement profiles in glomerulonephritis plasma C3 and C4 concentrations were measured using commercially available immunodiffusion plates. A total of 303 samples were obtained from 128 patients suffering from forms of nephritis associated with hypocomplementaemia—namely, lupus nephritis, mesangiocapillary glomerulonephritis (M.C.G.N.), and acute glomerulonephritis. These simple measurements of C3 and C4 gave clinically useful information. In lupus nephritis C3 and C4 generally correlated and C4 concentrations were more often and more profoundly depressed than C3 concentrations. Neither C3 nor C4 concentrations alone correlated well with the antinuclear factor titre. In both acute glomerulonephritis and M.C.G.N. the C3 concentrations were frequently lower than 20% of normal (which was never the case in patients with lupus), while the C4 concentration was usually normal and was almost never depressed in the absence of C3 depression. This suggests activation of complement at the C3 level by the "bypass" pathway in acute nephritis as well as in M.C.G.N., though both may be operating in some patients. In acute glomerulonephritis but not in M.C.G.N. C3 concentrations returned to normal within eight to 12 weeks. The two varieties of M.C.G.N. identified by the site of the deposits in the capillary glomerular walls differed in their C3 levels. In 10 patients with intramembranous dense linear deposits the C3 was always low over very long periods of time, rising in three out of four patients only after transplantation and immunosuppression. Other patients with M.C.G.N., in contrast, often showed normal C3 concentrations. Concentrations of C4 did not differ in either group, being normal in 80% of samples from all types.
Active oxygen species play a role in mediating platelet aggregation and cyclic flow variations in severely stenosed and endothelium-injured coronary arteries.
Authors: S K Yao, J C Ober, A Gonenne, F J Clubb, A Krishnaswami, J J Ferguson, H V Anderson, M Gorecki, L M Buja, J T Willerson
Journal: Circulation Research (1993)

A canine model with cyclic flow variations (CFVs) in stenosed and endothelium-injured coronary arteries was used to examine the role of active oxygen species in platelet aggregation in vivo. We studied 90 anesthetized dogs in which the pericardial cavity was opened and the heart was exposed. The velocity of blood flow in the left anterior descending coronary artery (LAD) was monitored by a pulsed Doppler flow probe. In 67 dogs, the LADs were stenosed by applying external constrictors at the site where the endothelium was mechanically injured. CFVs developed in all 67 dogs. Treatment with the antioxidants recombinant human copper-zinc superoxide dismutase (r-h-CuZnSOD), recombinant human manganese superoxide dismutase (r-h-MnSOD), and catalase eliminated platelet aggregation-associated coronary CFVs in 63%, 62%, and 64% of animals, respectively. Intravenous infusion of epinephrine restored CFVs in most dogs. Ketanserin, a serotonin (5-hydroxytryptamine2) receptor antagonist, abolished epinephrine-restored CFVs and eliminated CFVs in dogs in which CFVs had not been eliminated by free radical scavengers. In an additional 23 dogs, the LADs were stenosed but not mechanically injured. For control studies, saline was infused into the LADs of 5 dogs. Xanthine/xanthine oxidase was infused into the LADs of 8 dogs and induced CFVs in 4. Hydrogen peroxide was infused into the other 10 dogs and induced CFVs in 9. Histological analysis of the coronary artery revealed that the intima was significantly injured by the infusion. In ex vivo platelet aggregation studies, the in vivo treatment with r-h-CuZnSOD, r-h-MnSOD, and catalase significantly inhibited platelet aggregation induced by platelet-activating factor. Thus, active oxygen species are involved in mediating platelet aggregation and cyclic flow variations in stenosed and endothelium-injured canine coronary arteries in vivo.
Serum Lipid and Lipoprotein Metabolism After Glucose Ingestion in NIDDM and IGT Patients: Apolipoprotein-containing particles
Authors: Takashi Nagai, Takashi Tomizawa, Seiki Minamide, Katsuyuki Nakajima, Masatomo Mori
Journal: Diabetes Care (1996)

Through analysis of apolipoprotein-containing particles after glucose ingestion, we determined abnormal lipid metabolism in NIDDM patients and subjects with impaired glucose tolerance (IGT) without obesity or hyperlipidemia.Apolipoprotein (apo) AI- or B100-containing particles or remnant-like particles (RLPs) were isolated by immunoaffinity columns prepared with monoclonal antibodies. The cholesterol contents in these particles after glucose ingestion (0, 30, 60, and 120 min) were analyzed in 18 nonobese NIDDM patients, 18 nonobese IGT subjects, and 33 normal control subjects.Changes in cholesterol content in apo B100 particles after oral glucose ingestion decreased significantly in both the NIDDM group and the IGT group; the changes were insignificant in the nondiabetic group. Changes in cholesterol content in the apo AI particles after oral glucose ingestion showed no differences between the three groups. Changes in cholesterol content in RLPs after oral glucose ingestion increased significantly in both the NIDDM group and IGT group; the changes were insignificant in the nondiabetic group. The changes in apo B100 after oral glucose ingestion decreased significantly in the three groups; however, apo AI after oral glucose ingestion showed no change in the three groups.The cholesterol content in apo B100 particles might decrease and the cholesterol content in RLPs might increase after oral glucose ingestion in not only NIDDM patients but also IGT subjects. The changes may be partially due to insulin resistance.
Ventilation Perfusion Mismatch Lung Scan Without Pulmonary Emboli
Authors: HAROLD SIMON
Journal: Clinical Nuclear Medicine (1977)

The accurate diagnosis of pulmonary emboli remains a perplexing problem. Perfusion lung scanning while sensitive is not specific. The addition of ventilation scanning to perfusion scanning has been helpful in increasing the specificity. Yet, the accuracy has varied from 74% to 95%. Most of those patients who had V/Q mismatch without emboli had other abnormalities apparent by chest x-ray. We report two cases with clear chest x-rays and V/Q mismatch without clinical evidence of P.E. We suggest that even if a V/Q mismatch is present and doubt of the diagnosis persists then pulmonary angiography should be considered.
O6 SOFOSBUVIR/LEDIPASVIR FIXED DOSE COMBINATION IS SAFE AND EFFECTIVE IN DIFFICULT-TO-TREAT POPULATIONS INCLUDING GENOTYPE-3 PATIENTS, DECOMPENSATED GENOTYPE-1 PATIENTS, AND GENOTYPE-1 PATIENTS WITH PRIOR SOFOSBUVIR TREATMENT EXPERIENCE
Authors: E.J. Gane, R.H. Hyland, D. An, P.S. Pang, W.T. Symonds, J.G. Mchutchison, C.A. Stedman
Journal: Journal of Hepatology (2014)
Acute lymphoblastic leukemia with myeloperoxidase activity
Authors: Susan Wright, Antoine Chucrallah, Yap Yee Chong, Hagop Kantarjian, Michael Keating, Maher Albitar
Journal: American Journal of Hematology (1996)

The French-American-British (FAB) classification of acute leukemias is based on the light microscopic detection of myeloperoxidase (MPO) activity in blast cells. Cells with MPO activity in > 3% of cells are classified as acute myeloid leukemia (AML) and usually express myeloid cell surface antigens. We describe a case of acute leukemia in which the blast cells have lymphoid morphology, ultrastructure, immunophenotype, and molecular rearrangements, but express significant amounts of MPO. We discuss the incidence, features, and outcome of MPO-positive acute lymphoblastic leukemia (ALL).
Postnatal Recapitulation of Embryonic Hedgehog Pathway in Response to Skeletal Muscle Ischemia
Authors: Roberto Pola, Leona E. Ling, Tamar R. Aprahamian, Elena Barban, Marta Bosch-Marce, Cynthia Curry, Michael Corbley, Marianne Kearney, Jeffrey M. Isner, Douglas W. Losordo
Journal: Circulation (2003)

Hedgehog (Hh) proteins are morphogens regulating epithelial-mesenchymal signaling during several crucial processes of embryonic development, including muscle patterning. Sonic (Shh), Indian (Ihh), and Desert (Dhh) hedgehog constitute the repertoire of Hh genes in humans. The activities of all 3 are transduced via the Patched (Ptc1) receptor. Recent observations indicate that exogenous administration of Shh induces angiogenesis. Here, we studied whether the endogenous Hh pathway, in addition to its functions during embryogenesis, plays a physiological role in muscle regeneration after ischemia in adults.We found that skeletal muscle ischemia induces strong local upregulation of Shh mRNA and protein. In addition, the Ptc1 receptor is activated in interstitial mesenchymal cells within the ischemic area, indicating that these cells respond to Shh and that the Shh pathway is functional. We also found that Shh-responding cells produce vascular endothelial growth factor under ischemic conditions and that systemic treatment with a Shh-blocking antibody inhibits the local angiogenic response and the upregulation of vascular endothelial growth factor.Our study shows that the Hh signaling may be recapitulated postnatally in adult and fully differentiated muscular tissues and has a regulatory role on angiogenesis during muscle regeneration after ischemia. These findings demonstrate a novel biological activity for the Hh pathway with both fundamental and potential therapeutic implications.
Genetic Analysis of 15 STR Loci in Chinese Han Population from West China
Authors: Ya-Jun Deng, Jiang-Wei Yan, Xiao-Guang Yu, Yuan-Zhe Li, Hao-Fang Mu, Yan-Qing Huang, Xiao-Tie Shi, Wei-Min Sun
Journal: Genomics Proteomics & Bioinformatics (2007)

Abstract Allele frequencies for 15 short tandem repeat (STR) loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818, and FGA) were obtained from 7,636 unrelated individuals of Chinese Han population living in Qinghai and Chongqing, China. Totally 206 alleles were observed, with the corresponding allele frequencies ranging from 0.0001–0.4982. Chi-square test showed that all of the STR loci agreed with the Hardy-Weinberg equilibrium. We also compared our data with previously published population data of other ethnics or areas. The results are valuable for human identification and paternity testing in Chinese Han population.
Impedance plethysmography using the occlusive cuff technique in the diagnosis of venous thrombosis.
Authors: R Hull, W G van Aken, J Hirsh, A S Gallus, G Hoicka, A G Turpie, I Walker, M Gent
Journal: Circulation (1976)

Impedance plethysmography using the cuff technique has been compared with venography in 346 consecutive patients with suspected venous thromboembolism. The limbs were classified according to the venographic results as no thrombosis, proximal (popliteal, femoral, or iliac) vein thrombosis, and calf thrombosis. A discriminant analysis was performed. The impedance plethysmographic result was normal in 386 of 397 limbs which were normal on venography, a specificity of 97%, and abnormal in 124 of 133 limbs which showed proximal vein thrombosis, a sensitivity of 93%. Seventy-three of 88 limbs with calf vein thrombi and a normal impedance plethysmographic result. The sensitivity in 29 limbs with asymptomatic proximal vein thrombosis was 83%. Impedance plethysmography is an accurate method for detecting proximal vein thrombosis but has limitations which include the possibility of false positive results due to arterial insufficiency and muscle tension.
Renin-Angiotensin System and Angiotensin Receptor Blockers in the Metabolic Syndrome
Authors: Abhiram Prasad, Arshed A. Quyyumi
Journal: Circulation (2004)

A ctivation of the renin-angiotensin system (RAS) occurs in many cardiovascular disorders, and its modulation with angiotensin-converting enzyme (ACE) inhibitors is now established therapy for hypertension, left ventricular dysfunction, diabetic nephropathy, and atherosclerosis.More recently, angiotensin type 1 receptor blockers (ARBs) have shown similar promise. 1,2Research is currently focused on the role of the RAS in the metabolic syndrome (MetS), a disorder characterized primarily by insulin resistance that has emerged as a major risk factor for cardiovascular disease. 3ere, we review how cross talk between angiotensin II (AII) and insulin signaling contributes to the pathophysiology of the MetS and raises the potential for therapeutic use of angiotensin antagonists in its management.
Effect of prostaglandins I2 (prostacyclin) and F2 on function, energy metabolism, and calcium uptake in ischaemic/reperfused hearts
Authors: M. Karmazyn, M. Tani, J. R Neely
Journal: Cardiovascular Research (1993)

Objective: The aim was to examine the effect on cardiac function, energy metabolism, and calcium uptake of either prostaglandin I2 (PGI2, prostacyclin) or prostaglandin F2α (both 28.6 nM) on the response of isolated rat hearts to 25 min of total global ischaemia with or without 30 min reperfusion. Methods: Rat hearts were perfused by the Langendorff method and function assessed by left ventricular pressure. Energy metabolites were measured using enzymatic techniques and 45Ca2+ uptake determined by radioisotopic analysis. Results: Although there was no effect of either prostaglandin on contractile depression during ischaemia, both compounds accelerated the onset of and increased the magnitude of ischaemic contracture. High energy phosphate content at the end of the ischaemic period was not affected by prostaglandin treatment; however, tissue lactate levels were increased by PGI2, as was tissue calcium content. Under control conditions mean recovery of left ventricular developed pressure ranged from 66% to 83%. In the presence of PGI2 and PGF2α, recovery of developed pressure was reduced to 20% and 38% of preischaemic values, respectively. The reduced recovery in developed pressure was accompanied by an approximately threefold increase in diastolic pressure (p<0.05). The depression of functional recovery in reperfused hearts treated with prostaglandins was associated with various disturbances of cellular metabolism including depressed ATP and creatine phosphate content and increased tissue lactate and calcium following 30 min of reperfusion. A significant correlation was found between the changes in developed pressure and diastolic pressure during reperfusion and the reduction in ATP and creatine phosphate repletion. The deficit in recovery of ventricular function also correlated significantly with increased lactate and calcium accumulation in the reperfused heart. Conclusions: Low concentrations of PGI2 and PGF2α can depress contractile recovery of the globally ischaemic heart through a mechanism associated with altered cellular energy metabolism and increased calcium accumulation. Cardiovascular Research 1993;27:396-402
H1N1 influenza A virus-associated acute lung injury: response to combination oseltamivir and prolonged corticosteroid treatment
Authors: Adolfo Maximo Quispe-Laime, Jonas Daniel Bracco, Patricia Alejandra Barberio, Claudio German Campagne, Verónica Edith Rolfo, Reba Umberger, Gianfranco Umberto Meduri
Journal: Intensive Care Medicine (2009)
Points: Private rest homes
Authors: H M Rhoden
Journal: BMJ (1984)

Mr Richard Earlam has provided us with a clear exposition of the current mismanagement of oesophageal carcinoma in a regional hospital service (23 June, p 1892).Most doctors would agree that at presentation most cases of oesophageal carcinoma are incurable.'The aim of any treatment, therefore, is effective palliation-that is, relief of dysphagia-with consequent low morbidity and mortality.2The treatment statistics detailed by Mr Earlam clearly show that this goal is not being achieved in the North East Thames region.It is likely that the hospital management of oesophageal carcinoma will improve only when all patients with this condition are urgently referred to multidisciplinary teams established in regional specialist centres.
Cardiac Neuronal Nitric Oxide Synthase Isoform Regulates Myocardial Contraction and Calcium Handling
Authors: Claire E. Sears, Simon M. Bryant, Euan A. Ashley, Craig A. Lygate, Stevan Rakovic, Helen L. Wallis, Stefan Neubauer, Derek A. Terrar, B. Casadei
Journal: Circulation Research (2003)

A neuronal isoform of nitric oxide synthase (nNOS) has recently been located to the cardiac sarcoplasmic reticulum (SR). Subcellular localization of a constitutive NOS in the proximity of an activating source of Ca2+ suggests that cardiac nNOS-derived NO may regulate contraction by exerting a highly specific and localized action on ion channels/transporters involved in Ca2+ cycling. To test this hypothesis, we have investigated myocardial Ca2+ handling and contractility in nNOS knockout mice (nNOS-/-) and in control mice (C) after acute nNOS inhibition with 100 micromol/L L-VNIO. nNOS gene disruption or L-VNIO increased basal contraction both in left ventricular (LV) myocytes (steady-state cell shortening 10.3+/-0.6% in nNOS-/- versus 8.1+/-0.5% in C; P<0.05) and in vivo (LV ejection fraction 53.5+/-2.7 in nNOS-/- versus 44.9+/-1.5% in C; P<0.05). nNOS disruption increased ICa density (in pA/pF, at 0 mV, -11.4+/-0.5 in nNOS-/- versus -9.1+/-0.5 in C; P<0.05) and prolonged the slow time constant of inactivation of ICa by 38% (P<0.05), leading to an increased Ca2+ influx and a greater SR load in nNOS-/- myocytes (in pC/pF, 0.78+/-0.04 in nNOS-/- versus 0.64+/-0.03 in C; P<0.05). Consistent with these data, [Ca2+]i transient (indo-1) peak amplitude was greater in nNOS-/- myocytes (410/495 ratio 0.34+/-0.01 in nNOS-/- versus 0.31+/-0.01 in C; P<0.05). These findings have uncovered a novel mechanism by which intracellular Ca2+ is regulated in LV myocytes and indicate that nNOS is an important determinant of basal contractility in the mammalian myocardium. The full text of this article is available at http://www.circresaha.org.
Chinese herbal extract reduces Amyloid-β induced neurotoxicity through inhibiting NF-κB signaling pathway in neuronal cells
Authors: Xuehua Wu, Yan Yu, Liang Zhou, Hecheng Wang, Huan Yang, Kaiyin Zhong, Ximeng Zhang, Hui Zhang, Dongsheng Fan, Dehua Chui
Journal: Molecular Neurodegeneration (2012)

Amyloid-β (Aβ) peptide, which can invoke a cascade of inflammatory responses, is considered to play a causal role in the development and progress of Alzheimer’s disease (AD). Xylocoside G (XG) is an active compound isolated from a traditional Chinese medicinal plant, Itoa orientalis. We have previously reported that XG has neuroprotective effects, with the mechanism yet unknown. In this study, we investigated the possible mechanisms underlying neuroprotection of XG against Aβ-induced toxicity in SH-SY5Y cells and primary neurons. Pretreatment with XG significantly attenuated the cell viability reduction induced by Aβ exposure in a dose dependent manner which was testified by 3-[4, 5-Dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) and Lactate dehydrogenase (LDH) release assay. In addition, pretreatment with XG reversed the effect of Aβ on Bax and Bcl-2 expression and repressed Aβ-induced caspase-3 activation, suggesting that the neuroprotective effect of XG is associated with apoptosis regulation. Neuroinflammation has been implicated in Aβ-induced neuronal death. XG significantly attenuated Aβ-stimulated release of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and prostaglandin E2 (PGE2). It also downregulated the expression of cyclooxygenase-2 (COX-2) in SH-SY5Y cells. Further molecular mechanism studies demonstrated that XG inhibited Aβ-induced NF-κB p65 translocation, which was probably the result of inhibition of JNK phosphorylation but not ERK or p38 MAPK pathway by XG. This is the first study to demonstrate that XG protects SH-SY5Y cells against Aβ-induced inflammation and apoptosis through down-regulating NF-κB signaling pathways.