tbuckley/cabot-search huggingface dataset:
Colchicine effects on lysosomal enzyme induction and intracellular degradation in the cultivated macrophage.
Authors: E L Pesanti, S G Axline
Journal: The Journal of Experimental Medicine (1975)

The effects of colchicine on lysosomal fusion and lysosomal enzyme induction in the cultivated mouse peritoneal macrophage have been examined. Colchicine (10- minus 6 M), but not lumicolchicine, inhibited lysosomal enzyme induction by both phagocytic and pinocytic stimuli. In addition, the drug significantly retarded pinocytic uptake of [3-H] sucrose and transport of the amino acids [3-H] alpha aminoisobutyric acid and L-[3-H] leucine. In contrast, lumicolchicine had no effect on pinocytosis or amino acid transport. Thus, a role for intact microtubules in lysosomal enzyme induction, pinocytosis, and amino acid uptake in these cells is suggested. That colchicine inhibited lysosomal enzyme induction by phagocytic stimuli under conditions in which pinocytosis contributed little to the enzyme rise indicated that inhibition of pinocytosis was unlikely to account for colchicine effects on lysosomal enzyme induction. Effects of colchicine on degradation of phagocytized and pinocytized substrates were examined to determine if intact microtubules are required for fusion among lysosomes, pinosomes, and phagosomes. Colchicine did not alter the rate of intracellular digestion of radiolabeled bacteria by the cultivated macrophage. Similarly, it had no effect on enzymatic hydrolysis of intracellular [3-H] sucrose resulting from uptake of exogenous invertase. The finding that colchicine had no effect on the functional consequences of fusion of lysosomes with endosomes suggests that intact microtubules are not required for fusion among these constituents of the vacuolar apparatus.
Hypoxia-Induced Apelin Expression Regulates Endothelial Cell Proliferation and Regenerative Angiogenesis
Authors: Mélanie Eyries, Géraldine Siegfried, Mariana Ciumas, Kevin Montagne, Monique Agrapart, Franck Lebrin, Florent Soubrier
Journal: Circulation Research (2008)

Apelin has been identified as the endogenous ligand of the human orphan G protein–coupled receptor APJ. This peptide exerts a variety of cardiovascular effects and particularly acts as an activator of angiogenesis. Importantly, hypoxia has been reported to regulate apelin expression but the molecular mechanism underlying hypoxia-induced apelin expression and the relationship with the physiological response of the apelin/APJ system are still not established. Here, we demonstrate that apelin expression is induced by hypoxia in cultured endothelial and vascular smooth muscle cells as well as in lung from mice exposed to acute hypoxia. Transient transfection experiments show that hypoxia-inducible transcriptional activation of apelin requires an intact hypoxia-responsive element (+813/+826) located within the first intron of the human apelin gene. Chromatin immunoprecipitation assay reveals that hypoxia-inducible factor-1α binds to the endogenous hypoxia-responsive element site of the apelin gene. Moreover, overexpression of hypoxia-inducible factor-1α increases the transcriptional activity of a reporter construct containing this hypoxia-responsive element, whereas small interfering RNA–mediated hypoxia-inducible factor-1α knockdown abolishes hypoxia-induced apelin expression. Finally, microinterfering RNA-mediated apelin or APJ receptor knockdown inhibits both hypoxia-induced endothelial cell proliferation in vitro and hypoxia-induced vessel regeneration in the caudal fin regeneration of Fli-1 transgenic zebrafish. The hypoxia-induced apelin expression may, thus, provide a new mechanism involved in adaptive physiological and pathophysiological response of vascular cells to low oxygen level.
Safety and efficacy of leflunomide in the treatment of lupus nephritis refractory or intolerant to traditional immunosuppressive therapy: an open label trial
Authors: L-S Tam
Journal: Annals of the Rheumatic Diseases (2006)

We evaluated the safety and efficacy of leflunomide in patients with lupus nephritis in a prospective open label study. Nineteen consecutive patients who fulfilled the revised American College of Rheumatology criteria for systemic lupus erythematosus (SLE)1 and with proteinuria ⩾2 g/day were invited to participate. The patients were chosen because of previous treatment related toxicities (six patients with severe sepsis) or a contraindication to the use of cyclophosphamide (one patient newly diagnosed with lupus nephritis and cryptococcal meningitis) or lack of response to immunosuppressive treatments including cyclophosphamide (mean (SD) cumulative dose 9 (6) g), azathioprine or ciclosporin for at least 6 months with persistent proteinuria ⩾2 g/day for at least 3 months (12 patients). Two patients were excluded because of increased liver enzymes (one patient) and refusal to give consent (one patient). The study protocol was approved by the local ethics committee and consent forms were signed by all 17 subjects.

Previous immunosuppressive drugs were …
Excess recurrent cardiac events in rheumatoid arthritis patients with acute coronary syndrome
Authors: K M J Douglas
Journal: Annals of the Rheumatic Diseases (2005)

Cardiovascular mortality is increased in rheumatoid arthritis. Possible reasons include an increased incidence of ischaemic heart disease or worse outcome after acute coronary syndrome (ACS).To assess the outcome of ACS in rheumatoid arthritis compared with case matched controls in the context of underlying cardiac risk factors, clinical presentation, and subsequent management.40 patients with rheumatoid arthritis and ACS identified from coronary care admission registers between 1990 and 2000 were case matched as closely as possible for age, sex, classical cardiovascular risk factors, type and severity of ACS, and admission date (+/-3 months) with 40 controls. A standardised proforma was used for detailed case note review.Age, sex, other cardiovascular risk factors, and type and severity of presenting ACS were not significantly different between cases and controls. Recurrent cardiac events were commoner in rheumatoid arthritis (23/40, 57.5%) than controls (12/40, 30%) (p = 0.013); there were 16/40 deaths in rheumatoid arthritis (40%) v 6/40 (15%) in controls (p = 0.012). Recurrent events occurred earlier in rheumatoid arthritis (log rank survival, p = 0.05). Presentation with chest pain occurred in all controls compared with 33/40 rheumatoid patients (82%) (p = 0.006); collapse occurred in one control (2.5%) v 7/40 rheumatoid patients (17.5%) (p = 0.025). Treatment during the ACS was not significantly different in the two groups.Recurrent ischaemic events and death occur more often after ACS in rheumatoid arthritis. Atypical presentation is commoner in rheumatoid arthritis. There is an urgent need to develop identification and intervention strategies for ACS specific to this high risk group.
Effect of chronic and acute cigarette smoking on the pharyngo-upper oesophageal sphincter contractile reflex and reflexive pharyngeal swallow
Authors: K Dua, E Bardan, J Ren, Z Sui, R Shaker
Journal: Gut (1998)

Background —Cigarette smoking is known to affect adversely the defence mechanisms against gastro-oesophageal reflux. The effect of smoking on the supraoesophageal reflexes that prevent aspiration of gastric contents has not been previously studied. Aims —To elucidate the effect of cigarette smoking on two of the supraoesophageal reflexes: the pharyngo-upper oesophageal sphincter (UOS) contractile reflex; and the reflexive pharyngeal swallow. Methods —Ten chronic smokers and 10 non-smokers were studied, before and 10 minutes after real or simulated smoking, respectively. UOS pressure and threshold volume for the reflexes were determined using a UOS sleeve assembly. Two modes of fluid delivery into the pharynx were tested: rapid injection and slow injection. Results —For both rapid and slow injections, the threshold volume for triggering the pharyngo-UOS contractile reflex was significantly higher in smokers than in non-smokers (rapid: smokers 0.42 (SE 0.07) ml, non-smokers 0.16 (0.04) ml; slow: smokers 0.86 (0.06) ml, non-smokers 0.38 (0.1) ml; p&lt;0.05). During rapid injection, the threshold volume for reflexive pharyngeal swallow was higher in smokers (smokers 0.94 (0.09) ml, non-smokers 0.46 (0.05) ml; p&lt;0.05). Acute smoking further increased the threshold volume for the pharyngo-UOS contractile reflex and reflexive pharyngeal swallow during rapid injection. Conclusions —Smoking adversely affects stimulation of the pharyngo-UOS contractile reflex and pharyngeal reflexive swallow. These findings may have implications in the development of reflux related respiratory complications among smokers.
TCT-274 Drug-eluting balloon in 001 bifurcated lesions: 1 year clinical and 7-months angiographic outcomes
Authors: Beatriz Vaquerizo, Helena Tizón, Eduard Fernandez-Nofrerias, DARLENE ESTRADA-YÁNEZ, SUÀREZ DE LEZO Javier, Imanol Oategui, Jose R. Rumoroso, Pedro Martin Lorenzo, Faustino Miranda-Guardiola, Marcelo Bettinotti, Antonio Serra
Journal: Journal of the American College of Cardiology (2014)
Tuning Electrical Conduction Along Endothelial Tubes of Resistance Arteries Through Ca <sup>2+</sup> -Activated K <sup>+</sup> Channels
Authors: Erik J. Behringer, Steven S. Segal
Journal: Circulation Research (2012)

Electrical conduction through gap junction channels between endothelial cells of resistance vessels is integral to blood flow control. Small and intermediate-conductance Ca(2+)-activated K(+) channels (SK(Ca)/IK(Ca)) initiate electrical signals in endothelial cells, but it is unknown whether SK(Ca)/IK(Ca) activation alters signal transmission along the endothelium.We tested the hypothesis that SK(Ca)/IK(Ca) activity regulates electrical conduction along the endothelium of resistance vessels.Freshly isolated endothelial cell tubes (60 μm wide; 1-3 mm long; cell length, ≈35 μm) from mouse skeletal muscle feed (superior epigastric) arteries were studied using dual intracellular microelectrodes. Current was injected (±0.1-3 nA) at site 1 while recording membrane potential (V(m)) at site 2 (separation distance=50-2000 μm). SK(Ca)/IK(Ca) activation (NS309, 1 μmol/L) reduced the change in V(m) along endothelial cell tubes by ≥50% and shortened the electrical length constant (λ) from 1380 to 850 μm (P<0.05) while intercellular dye transfer (propidium iodide) was maintained. Activating SK(Ca)/IK(Ca) with acetylcholine or SKA-31 also reduced electrical conduction. These effects of SK(Ca)/IK(Ca) activation persisted when hyperpolarization (>30 mV) was prevented with 60 mmol/L [K(+)](o). Conversely, blocking SK(Ca)/IK(Ca) (apamin+charybdotoxin) depolarized cells by ≈10 mV and enhanced electrical conduction (ie, changes in V(m)) by ≈30% (P<0.05).These findings illustrate a novel role for SK(Ca)/IK(Ca) activity in tuning electrical conduction along the endothelium of resistance vessels by governing signal dissipation through changes in membrane resistance. Voltage-insensitive ion channels can thereby tune intercellular electrical signaling independent from gap junction channels.
Thymidine phosphorylase expression and benefit from capecitabine in patients with advanced breast cancer
Authors: C. Andreetta, C. Puppin, A. Minisini, F. Valent, E. Pegolo, G. Damante, C. Di Loreto, S. Pizzolitto, M. Pandolfi, G. Fasola, A. Piga, F. Puglisi
Journal: Annals of Oncology (2008)
The Acute Antipanic Activity of Aerobic Exercise
Authors: Andreas Ströhle, Christian Feller, Marlies Onken, Frank Godemann, Andreas Heinz, Fernando Dimeo
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Regular physical activity is anxiolytic for both healthy subjects and patients with panic disorder. However, the acute antipanic activity of exercise has not yet been studied systematically. METHOD: The effects of quiet rest or aerobic treadmill exercise (30 minutes at 70% of maximum oxygen consumption) on cholecystokinin tetrapeptide (CCK-4)-induced panic attacks were studied in a crossover design in 15 healthy subjects. The effects were measured with the Acute Panic Inventory. RESULTS: Panic attacks occurred in 12 subjects after rest but in only six subjects after exercise. In both conditions, CCK-4 administration was followed by a significant increase in Acute Panic Inventory scores; however, prior exercise resulted in significantly lower scores than quiet rest. CONCLUSIONS: Aerobic exercise has an acute antipanic activity in healthy subjects. If the authors’ results are confirmed in patients, the optimum intensity and duration of acute exercise for achieving antipanic effects will have to be characterized.
Estrogen levels in childhood determined by an ultrasensitive recombinant cell bioassay.
Authors: K O Klein, J Baron, M J Colli, D P McDonnell, G B Cutler
Journal: Journal of Clinical Investigation (1994)

We hypothesized that estradiol levels are higher in prepubertal girls than in prepubertal boys and that this greater secretion of estradiol might drive the more rapid epiphyseal development and earlier puberty in girls. Since previous estradiol assays have lacked adequate sensitivity to test the hypothesis of higher estradiol levels in girls, we developed a new ultrasensitive assay to measure estrogen levels. The assay uses a strain of Saccharomyces cerevisiae genetically engineered for extreme sensitivity to estrogen. Yeast were transformed with plasmids encoding the human estrogen receptor and an estrogen-responsive promoter fused to the structural gene for beta-galactosidase. Ether extracts of 0.8 ml of serum were incubated with yeast for 8 h and the beta-galactosidase response was used to determine estrogen bioactivity relative to estradiol standards prepared in charcoal-stripped plasma. The assay was highly specific for estradiol with < 3% cross-reactivity with estrone, estriol, or estradiol metabolites. The detection limit was < 0.02 pg/ml estradiol equivalents (100-fold lower than existing assays). Using this assay, we measured estrogen levels in 23 prepubertal boys (9.4 +/- 2.0 yr) and 21 prepubertal girls (7.7 +/- 1.9 [SD] yr). The estrogen level in girls, 0.6 +/- 0.6 pg/ml estradiol equivalents, was significantly greater than the level in boys, 0.08 +/- 0.2 pg/ml estradiol equivalents (P < 0.05). We conclude that the ultrasensitive recombinant cell bioassay for estrogen is approximately 100-fold more sensitive than previous estradiol assays, that estrogen levels are much lower prepubertally, in both sexes, than reported previously, and that prepubertal girls have 8-fold higher estrogen levels than prepubertal boys.
Dieting to win or to be thin? A study of dieting and disordered eating among adolescent elite athletes and non-athlete controls
Authors: M Martinsen, S Bratland-Sanda, A K Eriksson, J Sundgot-Borgen
Journal: British Journal of Sports Medicine (2009)

Objective: To examine the prevalence of dieting, reasons for dieting and prevalence of disordered eating among adolescent elite athletes and age-matched controls, and to examine the differences between athletes competing in leanness and non-leanness sports. Methods: First-year students of 16 different Norwegian Elite Sport High Schools (athlete group, n = 682) and two randomly selected ordinary high schools from a county representative of the general Norwegian population (control group, n = 423) were invited to participate in this cross-sectional study. A total of 606 athletes and 355 controls completed the questionnaire, giving a response rate of 89% and 84%, respectively. The questionnaire contained questions regarding training patterns, menstrual status and history, dieting, use of pathogenic weight control methods and the drive for thinness (DT) and body dissatisfaction (BD) subscales from the Eating Disorders Inventory. Main outcome measure: Disordered eating, defined as meeting one or more of the following criteria: DT score ⩾15 (girls) and ⩾10 (boys), BD score ⩾14 (girls) and ⩾10 (boys), body mass index &lt;17.9 kg/m 2 (girls) and &lt;17.5 kg/m 2 (boys), current and/or ⩾3 previous efforts to lose weight, use of pathogenic weight control methods and self-reported menstrual dysfunction. Results: A higher prevalence of control subjects were dieting and classified with disordered eating compared with the athletes. An improvement of appearance was a more common reason for dieting among controls compared with athletes. No differences in dieting or disordered eating were found between leanness and non-leanness sports athletes. Conclusions: Self-reported disordered eating is more prevalent among controls than adolescent elite athletes, and losing weight to enhance performance is an important reason for dieting among adolescent elite athletes.
Age dependence of myocardial Na+-K+-ATPase activity and digitalis intoxication in the dog and guinea pig.
Authors: A J Marsh, B L Lloyd, R R Taylor
Journal: Circulation Research (1981)

Infants and young animals tolerate higher doses of digitalis glycosides, relative to body weight, than adults. One possible explanation for this could be an age-dependent difference in the myocardial digitalis receptor, the Na+-K+-ATPase. Two functions of this enzyme were studied in adult, 1- and 6-week-old dogs and guinea pigs: in vitro myocardial uptake of rubidium (86Rb) and binding of ouabain. In guinea pigs, rubidium uptake (pmol Rb/mg LV per 15 min) was: 1 week old: 100.9 +/- 7.1 (mean +/- SE); 6 week: 79.8 +/- 6.7 adult: 55.2 +/- 7.9; (1 week: 6 week: P less than 0.025; 1 week: adult, P less than 0.001; 6 week: adult, P less than 0.025). Similarly in dogs, rubidium uptake was significantly greater at 1 week than at 6 weeks (208 +/- 13 vs. 144 +/- 9; P less than 0.001) and the latter greater than in adults (111 +/- 4) (P less than 0.005). Other groups of anesthetized adult and 6-week-old dogs were given digoxin, 0.3 mg/kg, iv. The young dogs took significantly longer to become cardiotoxic (17.3 +/- 3.4 min vs. 9.3 +/- 1.4 min; P less than 0.025), while their myocardial digoxin uptake was at least as great. Rubidium uptake showed an average decrease of 56% after digoxin but residual uptakes were not different in the two groups. Data for ouabain binding showed similar differences between the various groups of dogs studied. Increased myocardial Na+-K+-ATPase activity, reflected in greater active cation transport and specific enzyme binding, has been demonstrated in young animals and may be partly responsible for their greater tolerance to digitalis glycosides.
Comparison of Aerobic Exercise, Clomipramine, and Placebo in the Treatment of Panic Disorder
Authors: Andreas Broocks, Borwin Bandelow, Gunda Pekrun, Annette George, Tim Meyer, Uwe Bartmann, Ursula Hillmer-Vogel, Eckart Rüther
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: The purpose of this study was to compare the therapeutic effect of exercise for patients with panic disorder to a drug treatment of proven efficacy and to placebo. METHOD: Forty-six outpatients suffering from moderate to severe panic disorder with or without agoraphobia (DSM-III-R criteria) were randomly assigned to a 10-week treatment protocol of regular aerobic exercise (running), clomipramine (112.5 mg/day), or placebo pills. RESULTS: The dropout rate was 31% for the exercise group, 27% for the placebo group, and 0% for the clomipramine group. In comparison with placebo, both exercise and clomipramine led to a significant decrease in symptoms according to all main efficacy measures (analysis of variance, last-observation-carried-forward method and completer analysis). A direct comparison of exercise and clomipramine revealed that the drug treatment improved anxiety symptoms significantly earlier and more effectively. Depressive symptoms were also significantly improved by exercise and clomipramine treatment. CONCLUSIONS: These results suggest that regular aerobic exercise alone, in comparison with placebo, is associated with significant clinical improvement in patients suffering from panic disorder, but that it is less effective than treatment with clomipramine.
Immunosuppressive treatment in severe connective tissue diseases: effects of low dose intravenous cyclophosphamide
Authors: I. Martin-Suarez, D. D'Cruz, M. Mansoor, A. P. Fernandes, M. A Khamashta, G. R V Hughes
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To review our experience with low dose intravenous pulse cyclophosphamide in the treatment of patients with severe connective tissue diseases. <h3>PATIENTS</h3> Ninety patients (68F:22M) with severe connective tissue diseases received a total of 883 cyclophosphamide pulses with 78 of 90 patients initially having weekly 500 mg pulses for a median of three (2–10) weeks. Diagnoses included: systemic lupus erythematosus (SLE) (n=43); systemic vasculitides (n=42); idiopathic inflammatory myopathies (n=4); mixed essential cryoglobulinaemic vasculitis (n=1). The median age was 48 (range 22–76) years with a median disease duration of 94 (18–250) months. <h3>RESULTS</h3> Complete or partial remission was noted in 68 of 90 patients (75.5%) after a median follow up of 56 (5–213) months. At follow up significant median changes were noted in SLE patients: erythrocyte sedimentation rate (ESR) from 44 to 22 mm 1st hour; anti-dsDNA antibody concentrations from 81 to 48 IU/ml; proteinuria from 2.5 to 1.5 g/day; serum albumin from 36 to 40 g/l; complement C3 from 0.88 to 0.90 g/l, and C4 from 0.18 to 0.22 g/l. In the vasculitis patients significant median changes were seen in: ESR from 44 to 15 mm 1st hour; C reactive protein (CRP) from 16 to 5 g/dl; neutrophils from 8.55 to 4.3 × 10<sup>9</sup>/l; platelets from 340 to 261 × 10<sup>3</sup>/l, and haemoglobin from 12.6 to 13.2 g/dl. Patients with Churg-Strauss syndrome, Wegener's granulomatosis, and neuropsychiatric lupus showed the best initial response but 58% of Wegener's patients relapsed. Median corticosteroid doses were significantly reduced from 15 (5–60) mg to 10 (3–35) mg daily. Adverse events: infections (7 patients), neutropenia (5), lymphopenia (18), and haemorrhagic cystitis (1 intravenous and 2 oral cyclophosphamide), allergies to mesna (2). None of the women at risk had prolonged amenorrhoea. Five patients doubled their serum creatinine and five died from sepsis (2) or severe disease (3). <h3>CONCLUSION</h3> Treatment of severe connective tissue diseases with 'low dose' intravenous cyclophosphamide pulses compares in efficacy with the higher monthly doses previously advocated. Treatment was well tolerated with fewer adverse effects and most significantly, there were no cases of premature ovarian failure.