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T Pabst

Publications and source records attributed to T Pabst.

At least 55 records · Page 3Linked to original sources
PubMed1999

[The quantification of energy-rich phosphates in healthy and damaged heart muscle by SLOOP 31P-MR spectroscopy. Spatial localization with optimal pointspread function].

PURPOSE: A quantitative 31P-MR-spectroscopic technique was used to assess the energy metabolism in healthy and diseased myocardium. METHODS: 31P spectra were acquired on a 1.5 T scanner using a 3D-chemical shift imaging technique. Based on the anatomical information provided by 1H images, SLOOP (Spatial Localization with Optimal Pointspread Function) allows to obtain spectra from defined compartments. With SLOOP a free voxel shape with adaption to anatomic structures, e.g. the myocardium, is possible. Absolute values for phosphocreatine (PCr) and adenosine triphosphate (ATP) were determined using an external standard. RESULTS: 31P-spectra showed only minimal contamination by surrounding tissue. The standard deviation for the determined values of healthy volunteers was low. Compared to healthy volunteers, reduced PCr and ATP concentrations were seen for dilative cardiomyopathies and coronary artery disease and unchanged concentrations were observed for hypertensive heart disease. CONCLUSION: 31P-MR spectroscopy with SLOOP allows a non-invasive, quantitative analysis of cardiac energy metabolism.

Adenosine Triphosphate↗
PubMed1999

[3-dimensional MR coronary angiography in the navigator technic for the primary diagnosis of coronary heart disease: a comparison with conventional coronary angiography].

PURPOSE: Evaluation of three-dimensional MR coronary angiography with the navigator technique for the primary diagnosis of coronary artery disease (CAD) in patients with chest pain. MATERIALS AND METHODS: In this prospective study 20 patients with chest pain were examined with MR coronary angiography and conventional angiography. The three-dimensional MR coronary angiography was performed using a 1.5 T scanner with an ECG-triggered 3D-FLASH-sequence and retrospective respiratory gating in the navigator technique. The MR coronary angiography was evaluated by two radiologists blinded to the results of the conventional coronary angiography. RESULTS: One patient was excluded from further evaluation due to reduced image quality. Conventional coronary angiography excluded CAD in 8/19 patients, 11/19 patients overall showed 20 stenoses (> 50%) or occlusions. With MR coronary angiography, CAD was correctly excluded in 7 patients, one patient was false positive, one patient was false negative. 14/20 stenoses (> 50%) or occlusions were detected, 5 stenoses were diagnosed false positive. Sensitivity and specificity for primary diagnosis of CAD or detection of coronary artery stenoses were 91% and 88% or 70% and 91%, respectively. DISCUSSION: Using MR coronary angiography with the navigator technique in the primary evaluation of CAD, the diagnosis of stenoses or occlusions of the main coronary arteries is feasible.

Adult↗
PubMed1999

Three-dimensional MR coronary angiography using the navigator technique compared with conventional coronary angiography.

OBJECTIVE: We evaluated the diagnostic accuracy of three-dimensional (3D) MR coronary angiography with the navigator technique for the detection of coronary artery stenoses in comparison with that of conventional radiographic angiography. SUBJECTS AND METHODS: Thirty patients with coronary artery disease were examined with an ECG-triggered 3D fast low-angle shot sequence using retrospective respiratory gating and the navigator technique on a 1.5-T MR scanner. The data set was evaluated as a 3D view with a surface rendering technique. RESULTS: Imaging of the proximal coronary arteries was possible in all patients. The average visualized lengths of the left main, left anterior descending, left circumflex, and right coronary arteries were 1.9+/-0.5 cm (mean +/- SD), 5.2+/-2.3 cm, 4.2+/-1.9 cm, and 5.2+/-2.5 cm, respectively. Irregular breathing reduced image quality in seven of the 30 patients, making diagnosis of stenoses impossible. In the 77% of patients whose examinations resulted in high-quality images, the sensitivity and specificity for detection of significant stenoses and occlusions in all four main coronary arteries were 81% and 89%, respectively. CONCLUSION: The navigator technique allows reproducible imaging of the proximal course of coronary arteries. This technique obviates breath-hold studies, thus allowing more patients to be examined. In patients whose examinations resulted in high-quality images, significant coronary artery lesions could be seen. However, for widespread clinical use, further technical improvement is necessary to increase sensitivity and specificity.

Adult↗
PubMed1998

[3-dimensional MR coronary angiography with navigator technique: imaging of the proximal course of a coronary artery anomaly].

Congenital coronary artery anomalies are found in 0.3 to 1.3% of patients and can cause ischemic heart disease or sudden cardiac death, especially if the anomalous coronary artery courses between the aortic root and the pulmonary artery. Identification of the anatomic course of the anomalous vessel is not always feasible by conventional radiographic coronary angiography. With MR coronary angiography not only flowing blood but also the vessel anatomy can be imaged. In previous studies, a two-dimensional gradient-echo sequence during breathhold was used demanding both cooperation of the patient and operator skill. The navigator technique reduces respiratory artifacts by retrospective respiratory gating on the diaphragm's position, obviating the need for breathhold studies. Furthermore, the three-dimensional MR coronary angiography enables post-processing using the Volume Rendering Technique for evaluation of three-dimensional view. We report on the use of this technique for the identification of the course of anomalous coronary arteries in two patient cases.

Artifacts↗
PubMed1997

Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy.

BACKGROUND: In patients with heart failure due to dilated cardiomyopathy, cardiac energy metabolism is impaired, as indicated by a reduction of the myocardial phosphocreatine-to-ATP ratio, measured noninvasively by 31P-MR spectroscopy. The purpose of this study was to test whether the phosphocreatine-to-ATP ratio also offers prognostic information in terms of mortality prediction as well as how this index compares with well-known mortality predictors such as left ventricular ejection fraction (LVEF) or New York Heart Association (NYHA) class. METHODS AND RESULTS: Thirty-nine patients with dilated cardiomyopathy were followed up for 928+/-85 days (2.5 years). At study entry, LVEF and NYHA class were determined, and the cardiac phosphocreatine-to-ATP ratio was measured by localized 31P-MR spectroscopy of the anterior myocardium. During the study period, total mortality was 26%. Patients were divided into two groups, one with a normal phosphocreatine-to-ATP ratio (>1.60; mean+/-SE, 1.98+/-0.07; n=19; healthy volunteers: 1.94+/-0.11, n=30) and one with a reduced phosphocreatine-to-ATP ratio (<1.60; 1.30+/-0.05; n=20). At re-evaluation (mean, 2.5 years), 8 of 20 patients with reduced phosphocreatine-to-ATP ratios had died, all of cardiovascular causes (total and cardiovascular mortality, 40%). Of the 19 patients with normal phosphocreatine-to-ATP ratios, 2 had died (total mortality, 11%), one of cardiovascular causes (cardiovascular mortality, 5%). Kaplan-Meier analysis showed significantly reduced total (P=.036) and cardiovascular (P=.016) mortality for patients with normal versus patients with low phosphocreatine-to-ATP ratios. A Cox model for multivariate analysis showed that the phosphocreatine-to-ATP ratio and NYHA class offered significant independent prognostic information on cardiovascular mortality. CONCLUSIONS: The myocardial phosphocreatine-to-ATP ratio, measured noninvasively with 31P-MR spectroscopy, is a predictor of both total and cardiovascular mortality in patients with dilated cardiomyopathy.

Adenosine Triphosphate↗
PubMed1997

Up-regulation of p21WAF1 expression in myeloid cells is activated by the protein kinase C pathway.

Phorbol-12-myristate-13-acetate (PMA) induces p21WAF-1 expression in human myeloid leukaemic HL-60 cells. We show that this induction is specifically mediated by protein kinase C (PKC). In addition, the PKC inhibitor Ro 31-8220 with predominant PKC-alpha isoform specificity almost completely inhibited PMA-induced up-regulation of p21WAF1 in HL-60 cells as well as in the myelomonocytic leukaemic U937 cells. Pretreatment of HL-60 cells with Ro 31-8220 also inhibited PMA-induced activation of c-raf-1, a known PKC alpha target. In the phorbol ester-tolerant HL-60 subline (PET) with PKC-beta isoform deficiency PMA or bryostatin-1 induced p21WAF1 expression, but to a lesser extent than in wild-type HL-60 cells. In PET cells, Ro 31-8220 also inhibited PMA and bryostatin-1-induced up-regulation of p21WAF1 expression. Our findings indicate that at least in HL-60 cells up-regulation of p21WAF-1 is specifically activated by PKC. We suggest that PKC isoforms other than beta, presumably the PKC-alpha isoform, are involved in this process.

Cyclin-Dependent Kinase Inhibitor p21↗
PubMed1997

Expression and regulation of G1 cell-cycle inhibitors (p16INK4A, p15INK4B, p18INK4C, p19INK4D) in human acute myeloid leukemia and normal myeloid cells.

In hematological malignancies, structural alterations of genes for G1-specific cyclin-dependent kinases inhibitors (CKIs) have been extensively investigated. G1-CKIs might play an important role not only as tumor suppressor genes but also in cellular differentiation. We examined constitutive and differentiation-induced expression and regulation of the four members of the G1-CKI family p16INK4A, p15INK4B, p18INK4C and p19INK4D in acute myeloid leukemia as well as their expression in normal granulocytes and monocytes. p18INK4C and p19INK4D mRNA were expressed constitutively at high levels in seven myeloid cell lines and 16 AML patient samples, whereas expression of p15INK4B mRNA was very low and only detectable by nested RT-PCR analysis. During phorbol ester-induced monocytic differentiation of leukemic HL-60 cells expression of particular G1-CKIs was disparately regulated. This process was associated with growth arrest of the majority of the cells (> or = 80%) in G1/G0, and in parallel p15INK4B were upregulated whereas p18INK4C and p19INK4D expression was downregulated. In contrast, granulocytic differentiation induced by DMSO was accompanied by an increase of p18INK4C and p19INK4D expression only. PMA treatment of blast cells from two AML patients confirmed these cell line results. Disparate regulation of p15INK4B and p18INK4C mRNA was dependent on intermediary protein synthesis and occurred at the post-transcriptional level as shown by nuclear run-on analysis and mRNA half-life studies. In normal granulocytes and monocytes low constitutive p15INK4B and p18INK4C mRNA expression was detectable by RT-PCR only, but p19INK4D transcripts were noted by Northern blotting in both cell types. Disparate expression of G1-specific cell cycle inhibitors indicates complex and divergent roles of particular CKIs during normal and leukemic myeloid hematopoiesis.

Acute Disease↗
PubMed1997

Comparative detection and quantitation of human CDK inhibitor mRNA expression of p15INK4B, p16INK4A, p16beta, p18INK4C, p19INK4D, p21WAF1, p27KIP1 and p57KIP2 by RT-PCR using a polycompetitive internal standard.

For comparative and quantitative analysis of human cyclin-dependent kinase inhibitor gene expression (CKI; p15INK4B, p16INK4A, p16beta, p18INK4C, p19INK4D, p21WAF1, p27KIP1 and p57KIP2) we set up an RT-PCR assay with a construct termed pCKIquant producing polycompetitive RNA as an internal standard. We demonstrated the reproducibility, accuracy and high sensitivity of the assay in the in vitro model of myeloid leukaemic HL-60 cells. We also showed that the pCKIquant CKI assay is an excellent tool for the assessment of CKI mRNA expression in clinical samples, e.g. single cryostat sections of lymphoma biopsies.

Blotting, Northern↗
PubMed1997

Cardiac high-energy phosphate metabolism in patients with aortic valve disease assessed by 31P-magnetic resonance spectroscopy.

BACKGROUND: The purpose of this work was to determine the clinical and hemodynamic correlates of alterations in cardiac high-energy phosphate metabolism in patients with aortic stenosis and with aortic incompetence. METHODS: Fourteen volunteers, 13 patients with aortic stenosis, and 9 patients with aortic incompetence were included. Patients underwent echocardiography and left and right heart catheterization. 31P-MR spectra from the anterior myocardium were obtained with a 1.5 Tesla clinical MR system. RESULTS: Aortic stenosis and aortic incompetence patients had similar New York Heart Association (NYHA) classes (2.77 +/- 0.12 vs 2.44 +/- 0.18), ejection fractions (normal), left ventricular (LV) end-diastolic pressures, and LV wall thickness. In volunteers, phosphocreatine/adenosine triphosphate (ATP) ratios were 2.02 +/- 0.11. For all patients, phosphocreatine/ATP was significantly reduced (1.64 +/- 0.09; *p = 0.011 vs volunteers). Phosphocreatine/ATP decreased to 1.55 +/- 0.12 (*p = 0.008) in aortic stenosis, while in aortic incompetence, phosphocreatine/ATP only showed a trend for a reduction (1.77 +/- 0.12; p = 0.148). For all patients, phosphocreatine/ATP decreased significantly only with NYHA class III (1.51 +/- 0.09; *p = 0.001), but not with NYHA classes I and II (phosphocreatine/ATP 1.86 +/- 0.18). In aortic stenosis, phosphocreatine/ATP ratios decreased (1.13 +/- 0.03; *p = 0.019) only when LV end-diastolic pressures were > 15 mm Hg or when LV diastolic wall stress was > 20 kdyne cm-2 (1.13 +/- 0.03; *p = 0.024). CONCLUSIONS: For a similar clinical degree of heart failure in human myocardium, volume overload hypertrophy does not, but pressure overload does, induce significant impairment of cardiac high-energy phosphate metabolism. In aortic valve disease, alterations of high-energy phosphate metabolism are related to the degree of heart failure.

Adenosine Triphosphate↗
PubMed1996

Frequent clonal loss of heterozygosity but scarcity of microsatellite instability at chromosomal breakpoint cluster regions in adult leukemias.

Microsatellites are important highly polymorphic genetic markers dispersed in the human genome. Using a panel of 22 (CA)n repeat microsatellite markers mapped to recurrent breakpoint cluster regions specifically involved in leukemia, we investigated 114 adult leukemias (25 acute lymphocytic leukemia [ALL], 32 acute myeloid leukemia [AML], 36 chronic lymphocytic leukemia [CLL], and 21 chronic myeloid leukemia [CML] in chronic phase) for somatic mutations at these loci. In each patient, DNA from fresh leukemia samples was analyzed alongside normal constitutive DNA from buccal epithelium. We detected loss of heterozygosity (LOH) in 81 of 114 patients (ALL 16/25, AML 25/32, CLL 30/36, CML 10/21). Deletions were most often seen in ALL at 11q23 and 19p13; in AML at 8q22 and 11q23; in CLL at 13q14.3, 11q13, and 11q23; and in CML at 3q26. Only six deletions were reported in 74 karyotypes analyzed, whereas in these same cases, 91 LOH events were detected by microsatellites. Of 26 leukemias with a normal karyotype, 16 nevertheless showed at least one LOH by microsatellite analysis. Replication errors were found in 10 of 114 patients (8.8%). Thus, microsatellite instability is rare in leukemia in contrast to many solid tumors. Our findings suggest that in adult leukemia, LOH may be an important genetic event in addition to typical chromosomal translocations. LOH may point to the existence of tumor suppressor genes involved in leukemogenesis to a degree that has hitherto been underestimated.

Adult↗
PubMed1996

Severe neutropenia in T-large granular lymphocyte leukemia corrected by intensive immunosuppression.

Optimum treatment of severe neutropenia, a major factor for morbidity and mortality in T-large granular lymphocyte (LGL) leukemia, is undefined. We observed a rapid improvement of the neutrophil count in a patient with T-LGL leukemia and severe neutropenia after the combined administration of antilymphocyte-globulin (ALG), cyclosporin A, prednisone, and granulocyte colony-stimulating factor (G-CSF). Although G-CSF treatment was terminated after 7 days, the neutrophil count has persisted above 1.0 x 10(9)/1 for up to 6 months now. Oral methotrexate is given continuously as treatment for T-LGL leukemia. The response to this immunosuppressive regimen suggests a T-cell-mediated mechanism as the underlying cause for neutropenia in T-LGL leukemia.

Humans↗
PubMed1996

Detection of microsatellite markers in leukaemia using DNA from archival bone marrow smears.

We describe a simple PCR method to detect highly polymorphic repetitive DNA markers (microsatellites) in leukaemia using DNA from fresh and archival bone marrow smears. Neither the period of storage nor staining of the slides affected microsatellite PCR. Comparison of slide DNA with constitutive DNA from buccal epithelium revealed loss of heterozygosity (LOH) with at least one marker in four of 11 leukaemias. Marrow smears offer an attractive archival source of DNA for the detection of microsatellite markers. Applications include detection of LOH or tracing the origin of cell populations, e.g. in bone marrow transplant recipients.

Bone Marrow↗
PubMed1995

[CA 125--a tumor marker?].

Tumor markers are useful tools in monitoring malignancies postoperatively or under hormone-/chemotherapy. In contrast, they usually lack diagnostic relevance and uncritical use may result in confusing situations. We describe three cases of diagnostic determinations of the tumor marker CA 125 resulting in subsequent partially invasive procedures. Based on these three cases, serum CA 125 levels were examined in 49 patients with abdominal diseases. We found CA 125 to be less a tumor product than an unspecific expression of stimulated mesothelial cells of the peritoneum. CA 125 was a marker for ascites (16 of 16 patients) and an indicator of infra-diaphragmatic involvement in non-Hodgkin's lymphoma (11 of 12 patients). Furthermore, 5 of 6 patients with inflammatory abdominal diseases showed elevated CA 125 levels, as did 13 of 15 patients with solid abdominal tumors of different histology (all non-ovarian cancer, no ascites). In conclusion, CA 125 remains a good marker for follow-up of ovarian cancer, but should not be used for diagnosis of abdominal processes.

Adult↗
PubMed1995

Development of the hippocamposeptal projection in the rat.

We analyzed the development of the hippocamposeptal projection and the morphology of the neurons giving rise to this projection. The fluorescent tracer Dil was injected into the septal region or the hippocampus in fixed brains of embryonic and early postnatal rats. Anterogradely labeled hippocampal axons first reached the septal region at E16. They ran along the midline of the brain, thereby approaching the medial septum. Axons to the lateral septum were first observed around E18/19. The lateral septum is partly innervated by collaterals of axons that travel to the medial septum. The projection to the lateral septal nuclei becomes more massive during early postnatal stages, whereas that to the medial septum becomes smaller. Cells in the medial septum retrogradely labeled by injection into the hippocampus were first observed at E18. Thus, the hippocamposeptal projection is established earlier than the septohippocampal projection. The first hippocampal projection neurons are nonpyramidal neurons that appear to pioneer the pathway to the septum. Pyramidal cell axons follow this first cohort of axons into the medial septum. Pyramidal cells could be retrogradely labeled from the medial septum during the perinatal period but then diminished in number. At P10, only nonpyramidal cells were labeled by medial septal injections. This indicates that the pyramidal component of this projection is transient and is removed shortly after birth. However, as is known from other studies, hippocampal pyramidal cells give rise to a powerful projection to the lateral septum in adult animals. Our results show that there is a considerable remodeling of the projection from the hippocampus to the septum during ontogenetic development.

Animals↗
PubMed1995

Contributions of 31P-magnetic resonance spectroscopy to the understanding of dilated heart muscle disease.

In the present work, we studied clinical and haemodynamic correlates of impaired cardiac high-energy phosphate metabolism in patients with heart failure due to dilated cardiomyopathy (DCM). Myocardial 31P-magnetic resonance (MR) spectra were obtained at 1.5 T in 14 volunteers and 23 patients with DCM (mean ejection fraction 34%) in order to quantify the creatine phosphate (CP)/ATP ratio. In addition, patients underwent cardiac catheterization and echocardiography. Compared to volunteers (2.02 +/- 0.11), CP/ATP ratios were significantly reduced in DCM patients (1.54 +/- 0.10; P < 0.05), indicating impaired high-energy phosphate metabolism. CP/ATP ratios correlated with the clinical severity of heart failure estimated from the NYHA class (r = 0.47, P < 0.01); also, CP/ATP correlated with left ventricular ejection fraction (r = 0.54, P < 0.01) and left ventricular end-diastolic wall thickness (r = 0.51, P < 0.01). Thus, 31P-MR spectroscopy can detect abnormal cardiac high-energy phosphate metabolism in patients with heart failure due to DCM. These abnormalities correlate with clinical and haemodynamic parameters. Future studies will have to determine whether 31P-MR spectroscopy can contribute to the routine clinical evaluation of patients with heart failure.

Adenosine Triphosphate↗