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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of nutrition 38 (1999), S. 133-142 
    ISSN: 1436-6215
    Keywords: Key words Flavonoids – cancer-cell lines – proliferation –, cytotoxicity – apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Medicine
    Notes: Summary Flavonoids are polyphenolic compounds that occur ubiquitously in foods of plant origin. Their proposed protective role in tumor development may prevail especially in the intestinal tract due to direct exposure of intestinal epithelia to these dietary ingredients. We have screened more than 30 flavonoids for their effects on cell proliferation and potential cytotoxicity in the human colon cancer cell lines Caco-2, displaying features of small intestinal epithelial cells, and HT-29, resembling colonic crypt cells. In addition, for selected compounds we assessed whether they induce apoptosis by determining caspase-3 activation. Studies on the dose dependent effects of the flavonoids showed antiproliferative activity of all compounds with EC50 values ranging between 39.7 ± 2.3 μM (baicalein) and 203.6 ± 15.5 μM (diosmin). In almost all cases, growth inhibition by the flavonoids occured in the absence of cytotoxicity. There was no obvious structure-activity relationship in the antiproliferative effects either on basis of the subclasses (i.e., isoflavones, flavones, flavonols, flavanones) or with respect to kind or position of substituents within a class. In a subset of experiments we examined the antiproliferative activities of the most potent compound of each flavonoid subgroup in addition in LLC-PK1, a renal tubular cell line, and the human breast cancer cell line MCF-7. Out of four flavonols tested, three displayed almost equal antiproliferative activities in all cell lines but fisetin was less potent in MCF-7 cells. The flavanones bavachinin and flavanone inhibited growth of Caco-2 and HT-29 cells with lower EC50 values than that obtained in LLC-PK1 and MCF-7 cells. The lower susceptibility of LLC-PK1 and MCF-7 cells towards growth arrest was even more pronounced in the case of the flavone baicalein. Half maximal growth-inhibition in LLC-PK1 and MCF-7 required 2.5 and 6.6 fold higher concentrations than that needed in the intestinal cell lines. The flavonoids failed to affect apoptosis in LLC-PK1 and MCF-7, whereas baicalein and myricetin were able to induce apoptosis in HT-29 and Caco-2 cells. In conclusion, flavonoids of the flavone, flavonol, flavanone, and isoflavone classes possess antiproliferative effects in different cancer cell lines. The capability of flavonoids for growth inhibition and induction of apoptosis can not be predicted on the basis of their chemical composition and structure.
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  • 2
    ISSN: 1435-1285
    Keywords: Key words Tissue Doppler echocardiography – diastolic function – pseudonormalization – left ventricular filling pressures – arterial hypertension ; Schlüsselwörter Gewebedopplerechokardiographie – diastolische Funktion – Pseudonormalisierung – linksventrikuläre Füllungsdrücke – arterielle Hypertonie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Hintergrund: Zur Analyse der linksventrikulären Relaxation werden die früh- und spätdiastolischen Geschwindigkeitsmaxima über der Mitralis (E, A) mit dem gepulsten Doppler abgeleitet sowie die Dauer der Dezelerations- und isovolumetrischen Relaxationszeit bestimmt. Alle genannten Parameter ändern sich jedoch in Abhängigkeit von Alter, Herzfrequenz und Lastbedingungen. Die Erfassung der diastolischen Exkursion des Mitralrings mittels Gewebedopplerechokardiographie (TDE) soll eine lastunabhängige Beurteilung der linksventrikulären, diastolischen Funktion ermöglichen. Ziel der Studie: Ziel der vorliegenden Studie war die Erfassung der diagnostischen Wertigkeit der Mitralringexkusion in der Beurteilung der diastolischen, linksventrikulären Funktion. Patienten und Methoden: Drei Gruppen von Patienten mit einer systolischen Ejektionsfraktion 〉 45 % wurden untersucht: 10 Kontrollprobanden (60 ± 10 J., KON-Gruppe), 15 asymptomatische Patienten mit koronarer Herzerkrankung (60 ± 11 J., KHK-Gruppe) und 15 Patienten mit langjähriger, arterieller Hypertonie und Symptomen der Herzinsuffizienz (58 ± 9 J., HYP-Gruppe). Das Mitraleinstromprofil (E, A, E/A) wurde mittels gepulstem Doppler gemessen und die Dezelerations- (DT) sowie isovolumetrische Relaxationszeit (IVRT) bestimmt. Systolische, früh- und spätdiastolische Geschwindigkeiten des medialen Mitralanulus (ST, ET, AT, ET/AT) wurden mittels gepulstem TDE abgeleitet. Bei allen Patienten wurde im Rahmen einer Linksherzkatheteruntersuchung der linksventrikuläre, enddiastolische Füllungsdruck (LVED) bestimmt. Ergebnisse: In der HYP-Gruppe waren ET (6,9 ± 4,8 cm/s) und ET/AT (0,71 ± 0,28) im Vergleich zur KON-Gruppe (11,7 ± 4,7 cm/s bzw. 1,11 ± 0,36, p 〈 0,05) und zur KHK-Gruppe (8,9 ± 5,4 cm/s bzw. 0,85 ± 0,26, p = ns) vermindert. Die drei Gruppen unterschieden sich nicht hinsichtlich der mitralen E/A-Ratio, der Dezelerations- und isovolumetrischen Relaxationszeit. LVED war in der HYP-Gruppe (16 ± 8 mm Hg) höher als in der KON-Gruppe (8 ± 3, p 〈 0,05) und der KHK-Gruppe (12 ± 6 mm Hg, p = ns). Keine Korrelation wurde zwischen ET und LVED gefunden (r = 0,26). Wenn die Kombination aus mitraler E/A-Ratio 〉 1 und einem LVEDP ≥ 15 mm Hg als Pseudonormalisierung klassifiziert wurde, identifizierten eine frühdiastolische Mitralringexkursion (ET) 〈 7 cm/s und eine ET/AT-Ratio 〈 1 eine Pseudonormalisierung mit einer Sensitivität von 77 % und einer Spezifität von 88%. Schlußfolgerung: Das mit TDE gemessene frühdiastolische Geschwindigkeitsmaximum des medialen Mitralanulus (ET) ist ein lastunabhängiger Index der linksventrikulären Relaxation. TDE identifiziert die diastolische Funktionsstörung bei Patienten mit pseudonormalem Mitraleinstromprofil und erhöhten Füllungsdrücken.
    Notes: Summary Background: Mitral inflow velocity, deceleration time, and isovolumic relaxation time recorded by Doppler echocardiography have been widely used to evaluate left ventricular diastolic function but are affected by age, heart rate, loading conditions, and other factors. The diastolic mitral anulus velocity assessed by tissue Doppler echocardiography (TDE) was suggested to provide additional information about LV relaxation less affected by filling pressures. Aim of this study: This study was designed to assess the clinical utility of mitral anulus velocity in the evaluation of left ventricular diastolic function. Patients and methods: Three groups of patients with a systolic ejection fraction 〉 45 % were separated: 10 normal volunteers (60 ± 10 y, CON group), 15 asymptomatic patients with known coronary artery disease (60 ± 11 y, CAD group) and 15 patients with longterm arterial hypertension and heart failure symptoms (58 ± 9 y, HYP group). The mitral inflow profile (E, A, E/A) was measured by pulsed Doppler, and the deceleration time (DT) and the isovolumic relaxation period (IVRT) were calculated. Systolic, early, and late diastolic velocities of the septal mitral anulus (ST, ET, AT, ET/AT) were assessed by pulsed TDE. All study subjects had invasive measurements of left ventricular end diastolic filling pressures during left heart catheterization. Results: In the AH group, ET (6.9 ± 4.8 cm/s) and ET/AT (0.71 ± 0.28) were reduced compared to the CON group (11.7 ± 4.7 cm/s and 1.11 ± 0.36, p 〈 0.05, respectively) and the CAD group (8.9 ± 5.4 cm/s and 0.85 ± 0.26, respectively, p = ns). The groups did not differ with respect to the mitral E/A ratio, the deceleration time and the isovolumic relaxation time. LVED in the HYP group (16 ± 8 mm Hg) was elevated compared to the CON group (8 ± 3, p 〈 0.05) and the CAD group (12 ± 6 mm Hg, p = ns). No correlation was found between ET and LVED (r = 0.26). When the combination of mitral E/A ratio 〉 1 with LVED ≥ 15 mm Hg was classified as pseudonormalization, the pseudonormalization could be identified by a peak early diastolic mitral anulus velocity (ET) 〈 7 cm/s and an ET/AT ratio 〈 1 with a sensitivity of 77 % and a specificity of 88%. Conclusions: The early diastolic mitral anulus velocity assessed by TDE (ET) is a preload-independent index of LV relaxation. TDE permits the detection of diastolic dysfunction in patients with a pseudonormal mitral inflow and elevated filling pressures.
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  • 3
    ISSN: 1435-1285
    Keywords: Key words Dobutamine stress echocardiography — intraventricular obstruction — paradoxic hypotension ; Schlüsselwörter Dobutaminbelastungsechokardiographie — intraventrikuläre Obstruktion — akute Hypotonie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Dobutamine stress echocardiography (DSE) leads to strong hypercontraction, tachycardia, and peripheral vasodilatation. In previous studies systolic obstruction of the left ventricular outflow tract (LVOT) was observed as a result of these factors. To evaluate left ventricular function and morphology in patients (pts) with induced systolic LVOT obstruction, we used continuous wave (CW) doppler registrations in combination with quantitative 2-D-echocardiography in 100 pts during routinely performed DSE (5–40 μg/kg/min). In addition left ventricular wall thickness was measured. Symptoms were registrated using a standardised questionaire and cardiac arrhythmias were counted over a two minute intervall at rest and during the maximal heart rate of each patient. During DSE dynamic flow acceleration with late systolic peak velocity above 2 m/second (s) was considered to represent LVOT obstruction in pts with normal flow profiles in the LVOT before infusion of dobutamine. For invasive studies pts were investigated with femoral catheterisation by the method of Judkins. A greater than 50% stenosis was judged to be significant. Results: Examinations in 73 pts provided data of sufficient quality for echocardiographic and Dopplersonographic evaluations. 39 pts, 26 men, 13 women, mean age 64 ± 8 years, developed late systolic flow velocities above 2 m/s and therefore formed the obstructive group (grp A). Grp B consisted of 34 pts, 26 men and 8 women, mean age 66 ± 10 years, who showed normal time velocity integrals during DSE. In 41 pts invasive data provided information concerning the existence and severity of coronary artery disease. There were no significant differences in the increase of heart rate, the product of maximal systolic blood pressure and maximal heart rate or the percentage of pts, who reached their age corrected submaximal heart rate during DSE. Obstructive pts (group A) showed late systolic dynamic acceleration of systolic flow with a mean maximal speed of 315.4 ± 139.8 cm/s, which peaked 0.12 ± 0.04 s after the R-wave. From the velocities we calculated a mean pressure gradient of 47.5 ± 39.7 mm Hg using the modified Bernoulli equation. Group B patients showed lower and earlier maximal speeds with a mean value of 158.2 ± 37.6 cm/s, 0.09 ± 0.04 s after the R-wave, corresponding to a pressure gradient of 10.6 ± 4.9 mm Hg (p 〈 0.001). Ejection fractions were higher (p 〈 0.001) before the test in grp A: 68.2 ± 8% compared to 55.7 ± 10.4% in B. This difference increased during peak stress: 74.1 ± 7.7% compared to 59.5 ± 12.8%. Enddiastolic (EDVI) and endsystolic volume indexes (ESVI) were lower in grp A (p 〈 0.001). During DSE, the decrease in ESVI was somewhat stronger for pts in grp A. Left ventricular hypertrophy was more often seen with obstruction. Septal thickness was increased in A: 1.45 ± 0.34 cm compared to 1.13 ± 0.27 cm in B (p 〈 0.001). Left ventricular posterior wall measured 1.03 ± 0.28 cm in A and 0.83 ± 0.23 cm in B (p 〈 0.01). 27 pts in grp B and only 9 in grp A had a history of previous myocardial infarction. Showing no difference at rest, wall motion score indexes raised under DSE in both groups and developed significantly higher scores in grp B at peak stress: 1.30 (1.0–1.90) compared to 1.18 (1.0–1.90) compared to 1.18 (1.0–1.75) in A. We observed typical chest pain more often in grp B. Unspecific symptoms and arrhythmogenic complications were not statistically different, with the exception of ventricular bigeminy which was more often observed in grp B. A decline in the diastolic blood pressure was observed in pts with very severe obstruction (〉 3.5 m/s, p 〈 0.05). Sensitivity of DSE was 84%, specificity 79%. No significant differences between pts with and without obstruction were observed. Summary: Intraventricular obstructions during DSE are often observed in pts with normal systolic function at rest and during peak stress, especially in the case of left ventricular hypertrophy. This flow pattern is not regularly correlated to clinical signs, symptoms or complications. It did not impair diagnostic accuracy concerning the detection of significant coronary artery disease in our pts.
    Notes: Zusammenfassung Die Dobutamin-Streßechokardiographie (DSE) führt zu einer starken Hyperkontraktilität des Myokards bei Tachykardie und Vesodilatation. Diese Effekte können zu einer unphysiologischen Abnahme des endsystolischen Volumenindex (ESVI) mit Obstruktion des linksventrikulären Ausflußtraktes (LVOT) führen. Bei 100 Patienten (Pat.), die sich einer DSE (5–40) μg/kg/min) unterzogen, wurde die kontinuierliche Dopplerregistrierung (DW-Doppler) vor Infusion und bei maximaler Herzfrequenz durchgeführt. Eine dynamische, spät-systolische, Flußakzeleration auf mehr als 2 Meter/Sekunde (m/s) unter maximaler Stimulation wurde als systolische Obstruktion des LVOT interpretiert. Manifestationsfaktoren systolischer Flußobstruktionen sollten untersucht werden. Analyseparameter waren die Ejektionsfraktion (EF, 2D-Volumetrie mittels Scheibchensummationsmethode), die Wanddicke des linken Ventrikels, klinische Symptome und das Auftreten von Herzrhythmusstörungen. Zur invasiven Abklärung diente die femorale Katheterisierung nach Judkins mit semiquantitativer Schätzung des Stenosegrades. Stenosen 〉 50% galten als signifikant. Ergebnisse: 73 Pat. waren echokardiographisch und dopplersonographisch auswertbar. 39 Pat., Gruppe A (Grp A), 26 Männer, 13 Frauen, Durchschnittsalter 64 ± 8 Jahre entwickelten eine Obstruktion. Gruppe B (Grp B) 34 Pat., 26 Männern und 8 Frauen, mittleres Alter 66 ± 10 Jahre wiesen auch zum Zeitpunkt der maximalen Herzfrequenz ein parabolisches Geschwindigkeitszeitintegral im LVOT auf. Für 41 Pat. standen die invasiven Vergleichsdaten zur Verfügung. Beide Gruppen unterschieden sich im Testverlauf hinsichtlich Frequenzanstieg, Produkt der Maxima für systolischen Blutdruck und Herzfrequenz sowie Häufigkeit der submaximalen Ausbelastung (220 – Alter × 0,85) nicht signifikant. Pat. in Grp A entwickelten im Mittel 0,12 ± 0,04 Sekunden (s) nach dem Gipfel der R-Zacke eine maximale, spätsystolische und dynamisch akzelerierende Geschwindigkeit von 315,4 ± 139,8 cm/s, entsprechend einem Druckgradienten von 47,5 ± 39,7 mm Hg. In Grp B erreichten die Pat. nach 0,09 ± 0,04 s eine maximale Geschwindigkeit von 158,2 ± 37,6 cm/s. Daraus errechnete sich ein mittlerer Druckgradient von 10,6 ± 4,9 mm Hg (p 〈 0,001). In Grp A war die EF bereits vor Testbeginn höher (68,2 ± 8%) als in Grp B (55,7 ± 10,4%). Unter Belastung fiel dieser signifikante Unterschied (p 〈 0,001) noch deutlicher aus (74,1 ± 7,7% und 59,5 ± 12,8%). Der enddiastolische Volumenindex (EDVI) und der ESVI waren ebenfalls in Grp A signifikant niedriger. Eine Hypertrophie des linken Ventrikels (LV) lag häufiger bei Grp A vor (p 〈 0,001). Die Dicke des Septums betrug 1,45 ± 0,34 cm im Vergleich zu 1,13 ± 0,27 cm bei Grp B. Die entsprechenden Werte an der Hinterwand betrugen für A 1,03 ± 0,28 cm gegenüber 0,83 ± 0,23 cm für B (p 〈 0,01). Ischämische Wandbewegungsstörungen traten häufer in Grp B auf. Der "Score index" berechnete sich bei gleichem Ausgangswert unter maximaler Dobutaminstimulation mit 1,30 (1,0–1,90), verglichen mit 1,18 (1,0–1,75) bei A. Häufiger klagten Pat. der Grp B über Angina pectoris. Bei 27 Pat. in Grp B und 9 Pat. in Grp A bestanden Hinweise auf einen vorangegangenen transmuralen oder intramuralen Myokardinfarkt. Bigeminusartig auftretende ventrikuläre Extrasystolen (VES) waren unter Belastung häufiger in Grp B zu beobachten. Unspezifische Nebenwirkungen (Palpitationen) und andere Herzrhythmusstörungen traten gleich häufig auf. Der diastolische Blutdruck zeigte nur bei schwerer Obstruktion (〉 3,5 m/s) einen signifikanten Abfall (p 〈 0,05). Die Sensitivität der DSE betrug 84%, die Spezifität 79% ohne Unterschied zwischen Grp A und B. Zusammenfassend läßt sich festhalten: Intraventrikuläre Obstruktionen sind gehäuft mit einer guten systolischen Funktion und einer linksventrikulären Hypertrophie verbunden. Komplikationen und Symptome sind nicht regelhaft assoziiert. Die Zuverlässigkeit der DSE hinsichtlich des Ischämienachweises wurde im untersuchten Patientenkollektiv nicht beeinträchtigt.
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  • 4
    Publication Date: 2012-10-02
    Description: Two major transcriptional regulators of Caenorhabditis elegans bodywall muscle (BWM) differentiation, hlh-1 and unc-120 , are expressed in muscle where they are known to bind and regulate several well-studied muscle-specific genes. Simultaneously mutating both factors profoundly inhibits formation of contractile BWM. These observations were consistent with a simple network model in which the muscle regulatory factors drive tissue-specific transcription by binding selectively near muscle-specific targets to activate them. We tested this model by measuring the number, identity, and tissue-specificity of functional regulatory targets for each factor. Some joint regulatory targets (218) are BWM-specific and enriched for nearby HLH-1 binding. However, contrary to the simple model, the majority of genes regulated by one or both muscle factors are also expressed significantly in non-BWM tissues. We also mapped global factor occupancy by HLH-1, and created a genetic interaction map that identifies hlh-1 collaborating transcription factors. HLH-1 binding did not predict proximate regulatory action overall, despite enrichment for binding among BWM-specific positive regulatory targets of hlh-1 . We conclude that these tissue-specific factors contribute much more broadly to the transcriptional output of muscle tissue than previously thought, offering a partial explanation for widespread HLH-1 occupancy. We also identify a novel regulatory connection between the BWM-specific hlh-1 network and the hlh-8/twist nonstriated muscle network. Finally, our results suggest a molecular basis for synthetic lethality in which hlh-1 and unc-120 mutant phenotypes are mutually buffered by joint additive regulation of essential target genes, with additional buffering suggested via newly identified hlh-1 interacting factors.
    Electronic ISSN: 1549-5469
    Topics: Biology , Medicine
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  • 5
    Publication Date: 2016-08-11
    Description: Objectives To discern community attitudes towards research engagement in Libby, Montana, the only Superfund site for which a public health emergency has been declared. Study design Survey study of convenience samples of residents near the Libby, Montana Superfund site. Participants Residents of the Libby, Montana area were recruited from a local retail establishment (N=120, survey 1) or a community event (N=127, survey 2). Measures Two surveys were developed in consultation with a Community Advisory Panel. Results Principal components of survey 1 showed four dimensions of community members' attitudes towards research engagement: (1) researcher communication and contributions to the community, (2) identity and affiliation of the researchers requesting participation, (3) potential personal barriers, including data confidentiality, painful or invasive procedures and effects on health insurance and (4) research benefits for the community, oneself or family. The score on the first factor was positively related to desire to participate in research (r=0.31, p=0.01). Scores on factors 2 and 3 were higher for those with diagnosis of asbestos-related disease (ARD) in the family (Cohen's d=0.41, 0.57). Survey 2 also found more positive attitudes towards research when a family member had ARD (Cohen's d=0.48). Conclusions Principal components analysis shows different dimensions of attitudes towards research engagement. The different dimensions are related to community members' desire to be invited to participate in research, awareness of past research in the community and having been screened or diagnosed with a health condition related to the Superfund contaminant.
    Keywords: Open access, Communication, Occupational and environmental medicine, Public health
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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