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T Pabst

Publications and source records attributed to T Pabst.

At least 37 records · Page 2Linked to original sources
PubMed2001

Dichotomy of AML1-ETO functions: growth arrest versus block of differentiation.

The fusion gene AML1-ETO is the product of t(8;21)(q22;q22), one of the most common chromosomal translocations associated with acute myeloid leukemia. To investigate the impact of AML1-ETO on hematopoiesis, tetracycline-inducible AML1-ETO-expressing cell lines were generated using myeloid cells. AML1-ETO is tightly and strongly induced upon tetracycline withdrawal. The proliferation of AML1-ETO(+) cells was markedly reduced, and most of the cells eventually underwent apoptosis. RNase protection assays revealed that the amount of Bcl-2 mRNA was decreased after AML1-ETO induction. Enforced expression of Bcl-2 was able to significantly delay, but not completely overcome, AML1-ETO-induced apoptosis. Prior to the onset of apoptosis, we also studied the ability of AML1-ETO to modulate differentiation. AML1-ETO expression altered granulocytic differentiation of U937T-A/E cells. More significantly, this change of differentiation was associated with the down-regulation of CCAAT/enhancer binding protein alpha (C/EBPalpha), a key regulator of granulocytic differentiation. These observations suggest a dichotomy in the functions of AML1-ETO: (i) reduction of granulocytic differentiation correlated with decreased expression of C/EBPalpha and (ii) growth arrest leading to apoptosis with decreased expression of CDK4, c-myc, and Bcl-2. We predict that the preleukemic AML1-ETO(+) cells must overcome AML1-ETO-induced growth arrest and apoptosis prior to fulfilling their leukemogenic potential.

Apoptosis↗
PubMed2001

Assessment of myocardial infarction in humans with (23)Na MR imaging: comparison with cine MR imaging and delayed contrast enhancement.

PURPOSE: To demonstrate the feasibility of sodium 23 ((23)Na) magnetic resonance (MR) imaging for assessment of subacute and chronic myocardial infarction and compare with cine, late enhancement, and T2-weighted imaging. MATERIALS AND METHODS: Thirty patients underwent MR imaging 8 days +/- 4 (subacute, n = 15) or more than 6 months (chronic, n = 15) after myocardial infarction by using a (23)Na surface coil with a double angulated electrocardiogram-triggered three-dimensional gradient-echo sequence at 1.5 T. In addition, cine, inversion-recovery gradient-echo, and, in the subacute group, T2-weighted images (n = 9) were obtained. Myocardial infarction mass was depicted as elevated signal intensity or wall motion abnormalities and expressed as a percentage of total left ventricular mass for all modalities. Correlations were tested with correlation coefficients. RESULTS: All patients after subacute infarction and 12 of 15 patients with chronic infarction had an area of elevated (23)Na signal intensity that significantly correlated with wall motion abnormalities (subacute; r = 0.96, P <.001, and chronic; r = 0.9, P <.001); three patients had no wall motion abnormalities or elevated (23)Na signal intensity. Only 10 patients in the subacute and nine in the chronic group revealed late enhancement; significant correlation with (23)Na MR imaging occurred only in subacute group (r = 0.68, P <.05). Myocardial edema in subacute infarction correlated (r = 0.71, P <.05) with areas of elevated (23)Na signal intensity but was extensively larger. CONCLUSION: (23)Na MR imaging demonstrates dysfunctional myocardium caused by subacute and chronic myocardial infarction.

Adult↗
PubMed2001

MR angiography of the hand arteries.

The aim of this study was to optimize different magnetic resonance angiography (MRA) techniques and to evaluate MRA of the hand arteries compared to intraarterial digital subtraction angiography (IA-DSA). The MRA examinations were performed on a 1.5-T system equipped with a flexible surface coil. The protocol contained time-of-flight (TOF), rephased/dephased (Re/De), and contrast enhanced (CE) techniques. Maximum intensity projection (MIP) was used for postprocessing. The IA-DSA procedure was performed as pharmaco-angiography (after intraarterial injection of a vasodilatator) via a transbrachial approach. Nine patients suffering from peripheral vascular disease were examined with IA-DSA, TOF-MRA, and Re/De-MRA; six patients were examined with CE-MRA and IA-DSA. Best overall image quality was attained with IA-DSA, followed by TOF-MRA, Re/De-MRA, and CE-MRA. Selective arterial visualization of digital arteries was possible with IA-DSA and TOF-MRA. Rephased/dephased MRA showed venous overlay. Contrast-enhanced MRA was limited by inconstant quality of bolus timing. Appropriate arterial bolus timing was achieved in four of six patients; one examination showed venous overlay, one examination incomplete arterial enhancement. Time-of-flight MRA detected 96% of the digital artery segments that were identified with IA-DSA and revealed 34 segments that were failed on IA-DSA. Rephased/dephased MRA and CE-MRA were inferior to IA-DSA and TOF-MRA regarding detection of digital arteries. Magnetic resonance angiography with optimized protocols is a noninvasive procedure to visualize hand arteries in patients with ischemic disease. With TOF-MRA it is possible to detect angiographically occluded arterial segments of digital arteries.

Adolescent↗
PubMed2000

Hybrid cardiac imaging with MR-CAT scan: a feasibility study.

We demonstrate the feasibility of a new versatile hybrid imaging concept, the combined acquisition technique (CAT), for cardiac imaging. The cardiac CAT approach, which combines new methodology with existing technology, essentially integrates fast low-angle shot (FLASH) and echoplanar imaging (EPI) modules in a sequential fashion, whereby each acquisition module is employed with independently optimized imaging parameters. One important CAT sequence optimization feature is the ability to use different bandwidths for different acquisition modules. Twelve healthy subjects were imaged using three cardiac CAT acquisition strategies: a) CAT was used to reduce breath-hold duration times while maintaining constant spatial resolution; b) CAT was used to increase spatial resolution in a given breath-hold time; and c) single-heart beat CAT imaging was performed. The results obtained demonstrate the feasibility of cardiac imaging using the CAT approach and the potential of this technique to accelerate the imaging process with almost conserved image quality.

Coronary Vessels↗
PubMed2000

Changes in left and right ventricular cardiac function after valve replacement for aortic stenosis determined by cine MR imaging.

The purpose of this study was to determine the changes in function of both the left and the right ventricles (LV, RV) before and after aortic valve replacement (AVR), compared with age-matched healthy volunteers using magnetic resonance (MR) imaging. Fourteen patients with aortic stenosis underwent MR imaging (1.5 T) before and 3 (n = 14) and 12 (n = 9) months after surgical valve replacement. An electrocardiographically triggered two-dimensional cine fast low-angle shot sequence was used for the evaluation of absolute values and indices related to 1 m(2) body surface area for function, mass, and LV wall thickening. Fourteen age-matched healthy volunteers served as controls. Before surgery, all patients showed significant abnormalities of LV mass and function, whereas RV mass and function were not different from those of volunteers and remained mostly unchanged. After surgery, normalization of LV ejection fraction, absolute mass, and end-systolic wall thickness was observed, whereas the LV mass index failed to normalize, and LV volumes remained elevated. Aortic stenosis combined with a significant, but not severe reduction in LV function only affects the LV, whereas the RV remains unaffected at this stage of disease. AVR leads to improved LV function and reduced hypertrophy, but without normalization of LV volumes or the LV mass index within 1 year.

Aged↗
PubMed2000

Deep venous thrombosis and consecutive pulmonary embolism as the first sign of an ovarian cancer: MR angiography using an intravascular contrast agent (CLARISCAN).

We describe a case of progressive deep venous thrombosis and chest pain studied by contrast-enhanced magnetic resonance (MR) angiography with the new intravascular contrast medium CLARISCAN (NC100150 Injection). Combined MR venography and angiography demonstrated pelvic vein thrombosis and consecutive pulmonary embolism caused by a large abdominal tumor, diagnosed as an ovarian cancer after surgery. The potential role of an intravascular contrast medium for studying the vascular system in multiple regions of the body within a single examination without the need for bolus timing is discussed. J. Magn. Reson. Imaging 2000;12:497-500.

Clinical Trials, Phase II as Topic↗
PubMed2000

[Evaluating signal intensity of movement-impaired myocardial segments in MR delayed images after administration of Gd-DTPA. Correlation of regional increase in contraction after revascularization].

PURPOSE: The aim of the study was to correlate delayed contrast enhancement of dysfunctional regions of the myocardium after injection of Gd-DTPA with the improvement of regional contractility 3 months after revascularization. MATERIAL AND METHODS: Eleven patients with coronary artery disease and wall motion abnormalities underwent MR imaging before and 3 months after revascularization therapy (PTCA or CABG). Short-axis images were acquired using a cine gradient echo sequence. After revascularization, a representative slice was analyzed 14 +/- 1 min after injection of 0.1 mmol/kg Gd-DTPA using a T1-weighted turbo fast low-angle shot sequence. Improved systolic wall thickening 3 months after revascularization served as criterion of viability and was correlated with delayed contrast enhancement patterns. RESULTS: After revascularization, 6 patients showed complete recovery of the dysfunctional area, 1 patient partial recovery, and 4 patients remained unchanged. All 4 patients with persisting wall motion abnormalities, 1/6 patients with recovery and the patient with partial recovery revealed a delayed enhancement. CONCLUSIONS: Three months after revascularization, delayed enhancement of dysfunctional myocardium is evident in patients without regional wall motion improvement, while the lack of delayed enhancement correlates with improvement of regional contractility.

Adult↗
PubMed2000

[Cardiac energy metabolism in heart valve diseases with 31P MR spectroscopy].

PURPOSE: Heart valve disease combined with left ventricular hypertrophy leads to derangements in cardiac energy metabolism, which can be detected non-invasively by 31P-MR-spectroscopy. The purpose of the present study was to examine whether the derangements in cardiac metabolism are reversible after surgical valve replacement. PATIENTS AND METHODS: 10 healthy volunteers and 10 patients with aortic stenosis (pressure gradients > 60 mmHg) were included. For assessment of energy metabolism, 31P-MR spectra were obtained with a double oblique 3D-CSI technique (voxel size 25 cm3). In 5 of 10 patients, follow-up examination was performed 3 months after surgical valve replacement (SVR). Left ventricular (LV) function was analyzed by cine MRI. RESULTS: Before SVR the myocardial phosphocreatine to adenosinetriphosphate (PCr-ATP) ratio was significantly (p = 0.0002) reduced to 0.80 +/- 0.25 in patients compared to 1.65 +/- 0.21 in volunteers. 3 months after SVR, LV mass had significantly (p = 0.04) decreased from 238 +/- 33 g to 206 +/- 47 g. At the same time a significant (p = 0.04) increase of the PCr-ATP ratio from 0.80 +/- 0.25 to 1.28 +/- 0.22 was observed. A slight, but not significant, reduction of the phosphodiester ATP ratio was observed before SVR, with a trend towards normalization after SVR. CONCLUSIONS: After SVR, the deranged energy metabolism shows a trend towards normalization. Further follow-up is necessary to determine whether complete normalization of the energetic derangement can be observed over longer periods of time following SVR.

Adult↗
PubMed2000

Altered energy metabolism after myocardial infarction assessed by 31P-MR-spectroscopy in humans.

The value of 31P-magnetic resonance spectroscopy (MRS) as a possible tool to distinguish viable from non-viable tissue after myocardial infarction was analysed in humans. Fifteen patients 3 weeks after anterior myocardial infarction were studied with breath-hold cine MRI and 3D-CSI MRS (1.5 T system). 31P-spectra were obtained from infarcted as well as non-infarcted myocardium (voxel size 25 cm3 each). Gold standard for viability was recovery of regional function, as determined by a control MRI 6 months after revascularization. Ten age-matched healthy volunteers served as control group. No significant difference was found between the phosphocreatine to adenosinetriphosphate (PCr/ ATP) ratio of volunteers (SD 1.72+/-0.31) and non-infarcted septal myocardium of patients. Cine MRI demonstrated recovery of regional function in 10 patients, i. e. 10 patients showed viable and 5 non-viable myocardium. In viable myocardium, the PCr/ATP ratio was 1.47+/-0.38 (non-significant vs volunteers; p>0.05). In the 5 patients with akinetic myocardium, PCr peaks could not be detected. Therefore, calculation of PCr/ATP ratios was not possible. However, a significant reduction of the ATP signal-to-noise ratio (SNR) was observed (2.92+/-0.73 vs 6.68+/-0.80; patients vs volunteers; p<0.05). The SNR of ATP of akinetic regions may predict recovery of function after revascularization in patients with myocardial infarction.

Adenosine Triphosphate↗
PubMed2000

Age- and gender-specific differences in left and right ventricular cardiac function and mass determined by cine magnetic resonance imaging.

We examined possible age- and gender-specific differences in the function and mass of left (LV) and right (RV) ventricles in 36 healthy volunteers using cine gradient-recalled echo magnetic resonance imaging. Subjects were divided into four groups (nine men and nine women in each): men aged under 45 years (32 +/- 7), women aged under 45 (27 +/- 6), men aged over 45 (59 +/- 8), and women aged over 45 (57 +/- 9). Functional analysis of cardiac volume and mass and of LV wall motion was performed by manual segmentation of the endocardial and epicardial borders of the end-diastolic and end-systolic frame; both absolute and normalized (per square meter body surface area) values were evaluated. With age there was a significant decrease in both absolute and normalized LV and RV chamber volumes (EDV, ESV), while LV and RV masses remained unchanged. Gender-specific differences were found in cardiac mass and volume (for men and women, respectively: LV mass, 155 +/- 18 and 110 +/- 16 g; LV EDV, 118 +/- 27 and 96 +/- 21 ml; LV ESV, 40 +/- 13 and 29 +/- 9 ml; RV mass, 52 +/- 10 and 39 +/- 5 g; RV EDV, 131 +/- 28 and 100 +/- 23 ml; RV ESV, 53 +/- 17 and 33 +/- 15 ml). Normalization to body surface area eliminated differences in LV volumes but not those in LV mass, RV mass, or RV function. Functional parameters such as cardiac output and LV ejection fraction showed nonsignificant or only slight differences and were thus largely independent of age and gender. Intra- and interobserver variability ranged between 1.4% and 5.9% for all parameters. Cine magnetic resonance imaging thus shows age- and gender-specific differences in cardiac function, and therefore the evaluation of cardiac function in patients should consider age- and gender-matched normative values.

Adult↗
PubMed2000

[(23)sodium MRI for infarct imaging of the human heart].

PURPOSE: Sodium is elevated in acute/subacute myocardial infarction due to three distinct mechanisms: Breakdown of ion homeostasis with accumulation of intracellular sodium, extracellular edema formation and, during scar formation, increase of extracellular vs. intracellular space as cardiomyocytes are replaced by connective tissue. 23Na MRI has previously been shown to have the potential to demonstrate myocardial infarction in an animal model. Aim of this study was, therefore, to demonstrate myocardial infarction with the use of 23Na-MRI in patients. MATERIAL AND METHODS: 10 patients were examined 14 +/- 7 days after first myocardial infarction using a 23Na surface coil at 1.5 T. Double angulated short axis images of the entire heart were imaged using an ECG-triggered 3d-FLASH-sequence (FOV, 450 mm; matrix, 64 x 128; spatial resolution, 3.5 x 7 mm2; slice thickness, 16 mm; 32 acquisitions). Areas of elevated sodium signal intensity were correlated with infarct-related wall motion abnormalities imaged by Cine MRI in breathhold-technique. RESULTS: All patients showed an area of elevated sodium signal intensity that correlated well with the clinically determined localization of myocardial infarction as well as with regional wall motion abnormalities detected by Cine MRI. CONCLUSIONS: Elevated 23Na MR image signal intensity demonstrates subacute myocardial infarction in patients.

Aged↗
PubMed2000

Analysis of first-pass and delayed contrast-enhancement patterns of dysfunctional myocardium on MR imaging: use in the prediction of myocardial viability.

OBJECTIVE: The purpose of the study was to analyze first-pass and delayed contrast-enhancement patterns of dysfunctional myocardial regions on MR imaging after injection of gadopentetate dimeglumine to predict myocardial viability in patients with coronary artery disease. SUBJECTS AND METHODS: Twelve patients with wall motion abnormalities and related coronary artery disease revealed by conventional coronary angiography underwent MR imaging at 1.5-T before and 3 months after revascularization therapy. Short-axis images were acquired using a cine gradient-echo sequence. Each slice was divided into eight segments. Overall, 73 segments with impaired contractility were imaged during the first-pass and 14 +/- 2 min after injection of 0.05-mmol/kg gadopentetate dimeglumine at a flow of 3 ml/sec using a T1-weighted turbo fast low-angle shot sequence. Improved systolic wall thickening 3 months after revascularization served as the criterion of viability. RESULTS: At study entry, 26 dysfunctional segments showed delayed hyperenhancement compared with the adjacent functional segments within the same slice, and 47 did not reveal hyperenhancement. After revascularization, 25 (96%) of the 26 hyperenhanced segments did not recover function, whereas 39 (83%) of the 47 segments without hyperenhancement showed mechanical improvement. Segment-related sensitivity and specificity for the correlation of lack of delayed hyperenhancement with myocardial viability were 39 (98%) of 40 and 25 (76%) of 33, respectively. Hypoenhancement during first-pass did not serve as a reliable criterion of viability. CONCLUSION: Evidence of delayed hyperenhancement of dysfunctional myocardium may be used to predict lack of mechanical improvement or nonviability, whereas the lack of hyperenhancement can be correlated with improvement of regional contractility or viability after revascularization.

Aged↗
PubMed2000

Divergent expression of cyclin-dependent kinase inhibitors (CKI) and p14ARF/p16 beta in non-Hodgkin's lymphomas and chronic lymphocytic leukemia.

Chronic B-cell lymphocytic leukaemia (CLL) and low-grade B-cell Non Hodgkin's lymphomas (Lg-NHL) are characterized by slow accumulation of neoplastic cells arrested in the G0/G1 phase of the cell cycle. In contrast, proliferation rates are high in aggressive B-cell lymphomas (Hg-NHL). Divergent expression of cyclin-dependent kinase inhibitors (CKI) in the cell cycle may contribute to these differences. We analysed CLL as well as low and high grade B-cell NHL for expression of G1-specific and universal CKI by competitive RT-PCR and immunostaining. p16(INK4A) expression was low in all types of neoplasms. Highest p14(ARF) /p16 beta expression levels were found in normal lymphocytes. Expression of this CKI was significantly lower in CLL, but still higher in CLL than in the lymphomas (median 27 vs. 3 mRNA transcripts x 10(3), p = 0.0001). p14(ARF) /p16 beta immunostaining correlated with mRNA expression. Highest p21 mRNA levels were found in CLL, but three of four CLL with abundant p21 mRNA production were negative on immunostaining. High grade lymphomas showed markedly decreased p21 expression (3.9 in Hg-NHL vs. 12 in Lg-NHL and 29 in CLL; values expressed as mRNA transcripts x 10(3), p < 0.009). mRNA and protein expression of p27 was considerably higher in CLL than in the lymphomas. Differential CKI expression in various B-cell neoplasias may provide important biological markers, if not the molecular underpinning of their different cell cycle kinetics. Targeted interference with such genes governing cell cycle control in lymphoid neoplasia may pave the way towards new treatment strategies.

Adult↗
PubMed1999

Concentrations of human cardiac phosphorus metabolites determined by SLOOP 31P NMR spectroscopy.

Human cardiac 31P nuclear magnetic resonance (NMR) spectra are usually quantified in relative terms, i.e., the ratio of metabolite signals is calculated. If 31P NMR spectroscopy of the heart is to emerge as a clinically relevant diagnostic modality, reliable quantification of absolute concentrations of 31P metabolites is required. We applied spectral localization with optimal point spread function (SLOOP) 31P NMR spectroscopy to measure absolute concentrations of phosphocreatine (PCr) and adenosine triphosphate (ATP) in human myocardium. The accuracy of the quantification was first validated in a phantom study. Seven healthy volunteers (aged 19-29 years) were then examined at 1.5 T using a nominal spatial resolution of 25 mL. SLOOP allowed us to obtain localized spectra from compartments anatomically matched to the left ventricular wall. The a priori knowledge of the anatomical structure was obtained from 1H images. The spatially varying effects of saturation, off-resonance, and sensitivity were considered during the reconstruction process. Metabolites were quantified with reference to an external 31P standard. Concentrations of 9.0 +/- 1.2 and 5.3 +/- 1.2 mmol/kg wet wt (mean +/- SD, n = 9) were determined for PCr and ATP in normal heart, respectively. The influence of nuclear Overhauser enhancement on metabolite quantification is discussed.

Adenosine Triphosphate↗
PubMed1999

Detection of myocardial viability by low-dose dobutamine Cine MR imaging.

The purpose of this work was to test the diagnostic value of dobutamine stress magnetic resonance imaging (MRI) for predicting recovery of regional myocardial contractility after revascularization. Cardiac wall motion abnormalities are due to either non-viable and/or scarred, or viable, but hibernating, myocardial tissue. Dobutamine stress leads to increased systolic wall thickening only in viable myocardium. Twenty-five patients with akinetic or dyskinetic myocardial regions were examined with a Cine FLASH-2D sequence at rest and during dobutamine stress (10 microg/kg/min). Patients were re-examined at rest 3, and in case of persisting wall motion defects, 6 months after revascularization. Criterion of viability was increasing end-systolic wall thickening during stress and/or at follow-up. Akinetic regions related either to the LAD (n = 19) or to the RCA (n = 6) were judged viable if > or = 50% of the affected segments improved. MR studies were completed in all subjects without arrhythmia or need for early terminations due to symptoms. Sensitivity, specificity, and positive predictive value for the prediction of myocardial viability were 61%, 90%, and 87% for the segment-related analysis, and 76%, 100%, and 100% for the patient-related analysis based on coronary artery distribution, respectively. Dobutamine stress MRI allows to predict global functional recovery of akinetic myocardial regions after revascularization with a high positive predictive value and high specificity.

Adult↗
PubMed1999

Cine MR imaging after myocardial infarction--assessment and follow-up of regional and global left ventricular function.

Myocardial infarction often leads to regional wall motion defects and in case of large defects to remodeling of the left ventricle. With this study, changes in regional and global myocardial function of 12 patients 3 weeks after myocardial infarction and after revascularization therapy were determined using MRI. Cine MRI was performed at study entry at rest and during low-dose dobutamine stimulation. All patients were re-examined at rest 3 and 6 months after the revascularization, including analysis of wall thickening and of left ventricular end-diastolic volume index (LVEDVI), end-systolic volume index (LVESVI), ejection fraction (LVEF), and mass index. After revascularization. 6 patients with stress-induced improvement of regional wall thickening recovered, 4 patients without improvement did not, but 2 patients without stress-induced improvement of wall thickening also recovered. Concerning global cardiac function, patients with mainly improved regional wall motion also showed a lower LVESVI and a higher LVEF than patients without improvement of regional contractility 6 months after revascularization in comparison to study entry. In conclusion, improvement of global myocardial function after revascularization is higher in patients with improved contractility in the infarcted region. The extent of the response of regions with wall motion defects to dobutamine stress correlates with the actual improvement after revascularization, and, therefore, dobutamine stress MRI may be helpful in selecting patients that will have a higher benefit from a revascularization therapy.

Adult↗
PubMed1999

[CINE-MRT for the study of the effects of regional left ventricular wall motion disorders on global heart function after a myocardial infarct and revascularization].

PURPOSE: To determine changes in global cardiac function and mass caused by infarct-associated regional wall motion abnormalities and to compare the changes after revascularization in patients with and without improvement of regional contractility. MATERIALS AND METHODS: 21 patients with regional left ventricular wall motion abnormalities and associated coronary artery stenoses requiring revascularization were examined with a Cine FLASH-2D sequence 26 +/- 12 days after their first myocardial infarction and re-examined three months after revascularization. Regional contractility and volumes and masses of both ventricles were determined. RESULTS: After revascularization, regional wall motion improvement led to decreased left ventricular volumes and improved ejection fractions, whereas patients with persisting wall motion defects showed unchanged left ventricular functional parameters. Comparing both groups of patients, the patients with improvement of regional contractility revealed lower end-systolic volumes and higher ejection fractions at follow-up. Cardiac masses and right ventricular parameters were not different, patients with a depressed right ventricular ejection fraction showed improvement at follow-up. DISCUSSION: After myocardial infarction, revascularization of the infarct-related coronary artery leads to an improvement of left ventricular function only if there is also an improvement of regional contractility. An effect on right ventricular function was not observed three months after the first small- or middle-sized myocardial infarction.

Adult↗