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Biomedical subjects

U Maurer

Publications and source records attributed to U Maurer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Simultaneous expression of different immunogenic antigens in acute myeloid leukemia.

Identification of immunogenic leukemia-associated antigens as target structures is mandatory for specific immunotherapy of leukemia. Here, we define acute myeloid leukemia (AML) antigens eliciting a humoral immune response in the autologous host. We applied the method of serologic screening of cDNA expression libraries with autologous serum (SEREX). To date, this technique has been used to characterize antigen structures in solid tumors. The mRNA expression pattern of these newly in AML isolated antigens and previously described leukemia antigens (PRAME, MAGE-1, and Wt-1) was evaluated by reverse transcriptase polymerase chain reaction. For Wt-1, Western blotting also was performed. Screening of a cDNA expression library prepared from a patient with AML FAB M2 using autologous and allogeneic sera, followed by sequencing of positive clones, yielded three autoantigens (Prp1p/Zer1p, L19H1, and one without homology to previously described genes) and two antigens reactive with allogeneic sera (MAZ, PINCH). PRAME mRNA was expressed in 47% of 34 AML patients, but not in 13 CD34(+) cell samples or in peripheral blood mononuclear cells of 13 healthy volunteers. mRNA expression of MAZ was detected in 44% of AML patients, but only in 8% of healthy donors. Humoral responses to MAZ were detected in 35%. More than 80% of the screened AML patients showed simultaneous expression of two or more of these antigens.Differential expression in AML patients vs healthy volunteers suggests that the immunogenic antigens PRAME and MAZ are potential candidates for immunotherapy in AML.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Screening and diagnosis of congenital cytomegalovirus infection: a 5-y study.

Although cytomegalovirus infection is the most common infection transmitted via the placenta, there are no guidelines for routine screening to detect children congenitally infected with cytomegalovirus. From 1993 to 1997, maternal serum and cord vein blood of newborns was screened for HCMV-IgM (n = 21,183). Urine was examined for HCMV-excretion during the first postnatal week to prove HCMV infection in children who expressed HCMV-IgM in cord vein blood (n = 13) or who were born to mothers positive for HCMV-IgM in the serum (n = 234), or when both cord vein blood and maternal serum were positive for HCMV-IgM (n = 6). Congenital HCMV infection was detected in 17 newborns. To determine the incidence of congenital HCMV infection, only those mother/child pairs were selected in whom serum and cord vein blood were investigated (n = 5967 mother/child pairs). In this group 13 newborns were infected. The observed incidence for congenital HCMV infection is 0.21%. It is concluded that that this screening programme will detect those children at risk for congenital HCMV infection. These children have to be examined for virus excretion in the urine. Although the observed incidence is only 0.21%, congenital HCMV infection is a problem that can no longer be neglected because of its long-term sequelae.

Adult↗
PubMed1998

Serial lumbar tapping to prevent posthaemorrhagic hydrocephalus after intracranial haemorrhage in preterm infants.

Posthaemorrhagic ventricular dilation following intraventricular haemorrhage is a serious problem with high morbidity in preterm babies. No consensus exists as to the treatment of intraventricular haemorrhage and as to the treatment or prophylaxis of posthaemorrhagic ventricular dilation. Serial lumbar tapping was already in use to treat existing or being in the offing ventricular dilation. In the present study we evaluated the incidence of posthaemorrhagic hydrocephalus when lumbar tapping was initiated early, i. e. immediately before ventricular dilation had started. Between January 1989 and December 1996 37 preterm infants suffering from intraventricular haemorrhage grade III or grade III plus periventricular haemorrhage were enrolled in this study. Lumbar tapping was started as soon as possible: median (25. percentile-75. percentile) two (0-4) days after onset of haemorrhage. A median of 11 (8-17) punctures was performed in each patient. The outcome was as follows: 6 patients (16.2%) showed complete remission, 24 (64.9%) developed ventriculomegaly and 7 (18.9%) developed posthaemorrhagic hydrocephalus with subsequent need of shunt implantation. With the low incidence of shunt implantations in our study we suggest to reconsider the effectiveness of SLP performed immediately after onset of haemorrhage.

Cerebral Hemorrhage↗
PubMed1998

Neutrophil adhesion and activation during systemic thrombolysis in acute myocardial infarction.

In a pilot study, alterations of polymorphonuclear neutrophil function during systemic thrombolysis in acute myocardial infarction have been investigated in humans. The following parameters of neutrophil function were measured before and at 15 and 45 minutes after initiation of systemic thrombolysis with a recombinant tissue-type plasminogen activator in 20 patients with acute myocardial infarction: (1) neutrophil adhesion and (2) neutrophil activation. During systemic thrombolysis a significant decrease was observed in neutrophil adhesion (5.5+/-6.4 to 3.2+/-3.3; p<0.05), in phagocyting neutrophil activation (39+/-18 to 25+/-14%; p<0.05), and in resting neutrophil activation (9+/-7 to 3+/-4%; p<0.05). Successful reperfusion coincided with a significantly higher reduction of phagocyting neutrophil activation (40+/-14 to 20+/-12% vs. 39+/-24 to 26+/-19% in unsuccessful reperfusion; p<0.05), and of neutrophil adhesion (6.2+/-5.7 to 2.7+/-3.0 vs. 4.1+/-3.8 to 3.5+/-4.0 in unsuccessful reperfusion; p<0.05) during thrombolysis. Systemic thrombolysis in acute myocardial infarction is accompanied by a reduction in neutrophil adhesion and activation dependent on thrombolytic success.

Acute Disease↗
PubMed1998

Glycosphingolipids of skeletal muscle: I. Subcellular distribution of neutral glycosphingolipids and gangliosides in rabbit skeletal muscle.

Membrane vesicles were prepared from rabbit skeletal muscle, separated by sucrose density gradient centrifugation and characterized by their specific marker enzymes, ligand binding, and ion flux activities. The fractions obtained (in the order of increasing density) were sarcolemma (SL), T-tubules (TT), sarcoplasmic reticulum (SR1 and SR2) and triads/mitochondria (Tr/M). Their glycosphingolipid compositions were analyzed by biochemical and immunochemical methods with specific antibodies (TLC immunostaining) and characteristic patterns were obtained from respective membrane fractions, expressed on a protein basis. Glucosylceramide, the main neutral glycosphingolipid of rabbit muscle, was found in SL and TT fractions, whereas SR and Tr/M vesicles lack this compound. Lactosylceramide was selectively recovered in the SR1 fraction. GM3(Neu5Ac), the main ganglioside in rabbit muscle, was found to account for 64% in the SL, 13% in the TT, 7% in the SR1, 3% in the SR2 and 13% in the Tr/M fractions. IV3Neu5Ac-nLcOse4Cer was mostly abundant in SL and decreased in the order SL > TT, Tr/M > SR1, SR2. IV6Neu5Ac-nLcOse4Cer was only detected in the SL and Tr/M fractions in noteworthy quantities. Ganglioseries gangliosides GM1, GD1a, GD1b and GT1b displayed homogeneous distribution patterns in each membrane preparation. They were expressed only in small amounts but mainly in SL, TT and Tr/M vesicles and to less extent in SR1 and SR2 fractions. The presence of GM3(Neu5Ac) in the SL as well as on subcellular level was confirmed in transverse muscle cryosections by means of indirect immunofluorescence microscopy. The SL was brightly stained, but considerable intracellular fluorescence was observed as expected from the biochemical analyses. Thus, the neutral GSL and ganglioside expression of the SL and the intracellular membraneous network is different in skeletal muscle both in terms of quantitative and qualitative GSL composition as demonstrated in details by means of biochemical and immunochemical techniques. The modulatory functions of GM3 and gangliosides of the neolacto- and ganglio-series towards the voltage dependent Ca(2+)-channel, largely preponderant in the triads-containing Tr/M fraction, is the subject of the accompanying paper (J. Müthing, U. Maurer, and S. Weber-Schürholz, Carbohydr. Res., 307 (1998) 147-157).

Animals↗
PubMed1998

Glycosphingolipids of skeletal muscle: II. Modulation of Ca2(+)-flux in triad membranes by gangliosides.

Membrane vesicles of rabbit skeletal muscle were prepared and separated by sucrose density gradient centrifugation. The fractions obtained (in the order of increasing density) were sarcolemma (SL), T-tubules (TT), sarcoplasmic reticulum (SR1 and SR2) and triads/mitochondria (Tr/M) as characterized by their specific marker enzymes, ligand binding, and ion flux activities. The distribution of neutral glycosphingolipids and gangliosides in these membrane preparations has been documented in the preceding paper (J. Müthing, U. Maurer, U. Neumann, B. Kniep, and S. Weber-Schürholz, Carbohydr, Res., (1988) 135-145). GM3(Neu5Ac) is the dominant ganglioside, neolacto-series gangliosides are moderately expressed and ganglio-series gangliosides were found in minor quantities, however, all showing different qualitative and quantitative membrane-type specific patterns. The voltage dependent Ca(2+)-channels of skeletal muscle reside prevalently in the triad enriched membrane fractions deduced from highest binding capacity of 1,4-dihydropyridines. Calcium channel complexes of triads were reconstituted into unilamellar phospholipid vesicles of 400 nm defined size and the active 45Ca(2+)-uptake into intravesicular space was measured after incorporation of muscle specific gangliosides into the outer vesicle lipid bilayer in parallel to control liposomes without gangliosides. GM3(Neu5Ac) strongly increased the uptake of 45Ca2+ (+285%) whereas GM3(Neu5Gc) severely inhibited the ion flux (-61%). Neolacto-series gangliosides evoked miscellaneous effects upon 45Ca(2+)-flux depending on isomeric sialic acid configuration, oligosaccharide size and fatty acid chain length of the ceramide portion. VI3Neu5Ac-nLcOse6Cer (C24-fatty acid), IV3Neu5Ac-nLcOse4Cer (C16-fatty acid) and IV6Neu5Ac-nLcOse4Cer (C16-fatty acid) strongly enhanced the 45Ca(2+)-flux (+208, +162, and +120%, respectively, whereas IV3Neu5Ac-nLcOse4Cer (C24-fatty acid), VI3Neu5Ac-nLcOse6Cer (C16-fatty acid) and IV6Neu5Ac-nLcOse4Cer (C24-fatty acid) slightly reduced 45Ca(2+)-flux (-3, -6, and -17%, respectively). Out of all gangliosides tested in this study, GM1 showed the strongest stimulatory effect (+327%). GD1a and GT1b gave rise to remarkable flux-stimulation of +283 and +255%, respectively, whereas GD1b exhibited only a slightly positive effect (+38%). This data suggest a functional role of gangliosides in subcellular muscle membranes giving strong evidence that gangliosides are capable of modulating the cytosolic calcium level of muscle, which regulates muscle contraction.

Animals↗
PubMed1998

High expression of bcl-2 mRNA as a determinant of poor prognosis in acute myeloid leukemia.

BACKGROUND: The bcl-2 oncoprotein is suggested to be directly involved in the emergence of drug resistance by disrupting or delaying the apoptotic program and promoting tumor survival. PATIENTS AND METHODS: In order to define the clinical relevance of the bcl-2 mRNA expression in acute myeloid leukemia (AML) and its correlation to therapy outcome and prognosis, we analyzed 219 AML bone marrow (BM) samples, including 119 patients with de novo AML at presentation, 37 with AML following myelodysplastic syndrome (MDS), as well as 42 BM samples of AML in relapse and 21 in complete remission (CR) using RT-PCR. For performing quantitative measurements of bcl-2 mRNA, we developed a quantitative RT-PCR. RESULTS: Bcl-2 mRNA was detectable in 133 of 156 (84%) patients at diagnosis and 40 of 42 (95%) at relapse. AML patients with high bcl-2 mRNA expression achieved lower CR rates than those with no or low expression. Concerning the long-term outcome, the overall (OS) and disease-free survival (DFS) was significantly worse in AML patients with high expression levels of bcl-2 mRNA. The three-year OS for all newly diagnosed AML patients was 49% and 10% (P = 0.028), respectively, and 71% and 15% (P = 0.0004) for patients < 60 years. Comparable significant differences were observed for the DFS. In AML following MDS and patients > 60 years, the bcl-2 expression was not associated with remission rate or survival. CONCLUSIONS: The expression of bcl-2 mRNA may serve as a prognostic factor predicting remission outcome and long-term prognosis in AML.

Drug Resistance, Neoplasm↗
PubMed1997

High levels of Wilms' tumor gene (wt1) mRNA in acute myeloid leukemias are associated with a worse long-term outcome.

The tumor suppressor gene wt1 (Wilms' tumor gene) encodes for a zinc finger DNA-binding protein with predominantly transcription repressing properties. Because wt1 has been shown to be expressed in the vast majority of patients with acute myeloid leukemias (AML), we investigated the relevance of wt-1 mRNA expression regarding prognosis and possible prediction of relapse during follow-up. Totally bone marrow-derived blasts of 139 AML patients (129 newly diagnosed AML patients, 22 AML patients again in first relapse, and 10 AML patients analyzed primarily in first relapse) were studied for wt1 mRNA expression. Seventy-seven patients were analyzed for wt1 mRNA expression during follow-up. wt1-specific reverse transcription-polymerase chain reaction (RT-PCR) was performed and the amplification product was visually classified as not, weakly, moderately, or strongly amplified, as described previously. PCR products were quantitated by competitive PCR using a shortened homologous wt1 construct standard in representative cases. The expression of wt1 transcripts was correlated to age, French-American-British (FAB) subtype, phenotype, karyotype, and long-term survival. wt1 mRNA was detectable in 124 of 161 (77%) samples at diagnosis and in first relapse. wt1 expression was independent from age, antecedent myelodysplastic syndrome or FAB subtype, with the exception of a significant difference in M5 leukemias showing wt1 transcripts in only 40% (P = .0025). There was no correlation between the level of wt1 mRNA and response to treatment or the prognostic groups defined by the karyotype. Concerning long-term survival, patients with high levels of wt1 had a significantly worse overall survival (OS) than those with not detectable or low levels. The 3-year OS for all newly diagnosed AMLs was 13% and 38% (P = .038), respectively, and 12% and 43% (P = .014) for de novo AMLs. The difference was more distinct in patients less than 60 years of age. During follow-up, all patients achieving complete remission became wt1 negative. Reoccurrence of wt1 transcripts predicted relapse. The data indicate that high expression of wt1 mRNA is associated with a worse long-term prognosis.

Acute Disease↗
PubMed1997

Assessment of lung function in neonates during extracorporeal membrane oxygenation.

We report our experience with pulmonary function testing in 11 out of 22 full-term neonates with severe respiratory failure, treated at the ECMO center Graz (Austria) during the period from 1990 to 1995. Altogether 17 out of 22 patients survived ECMO and all of them were successfully weaned from ECMO. Pulmonary function was assessed by monitoring expiratory tidal volume on the ventilator and estimating respiratory system compliance from the ratio tidal volume/(PIP-PEEP). In addition, compliance, and functional residual capacity were measured using a computerized pulmonary function system (PEDS). Compliance (mean +/- SD) decreased markedly after 24 hours of ECMO, compared with baseline values (0.20 +/- 0.12 vs 0.12 +/- 0.13 ml/cmH2O/kg) and was significantly higher (0.43 +/- 0.14 ml/cmH2O/kg, p < 0.01) before ECMO stop. When tidal volumes increased continuously ECMO blood flow could be decreased, indicating lung recovery. Most patients had a tidal volume of > 7 ml/kg prior to decannulation. Functional residual capacity and corresponding dynamic compliance, measured in 5 patients, ranged from 18.6 to 29.6 ml/kg and 0.49 to 0.57 ml/cmH2O/kg at this time. Functional residual capacity (mean +/- SD) increased significantly when surfactant was administered to promote weaning from ECMO (8.28 +/- 0.9 vs 19.0 +/- 1.0 ml/kg, p < 0.01). We conclude that the assessment of lung function has improved our understanding of pulmonary recovery during ECMO. Its clinical significance in determining the optimum time of weaning from ECMO needs further evaluation.

Extracorporeal Membrane Oxygenation↗
PubMed1997

Venous thrombosis in and after extracorporeal membrane oxygenation: detection and follow-up by color Doppler sonography.

The purpose of our study was to evaluate thrombosis of venous vessels during and after extracorporeal membrane oxygenation (ECMO) using color Doppler sonography. We prospectively performed serial color Doppler sonography investigations in 30 ECMO patients [age: newborn to 3 years, male:female = 20:10, venoarterial (VA) ECMO = 18, venovenous (VV) ECMO = 12]. During ECMO obstruction and/or thrombosis of the superior vena cava (SVC) was observed in 2 neonates on VA ECMO. Furthermore, a thrombotic clot from an initially open duct of Arantii with partial portal vein thrombosis, reaching into the inferior vena cava (IVC), occurred despite adequate heparinization. After ECMO, late septic SVC thrombus occurred in one neonate. IVC thrombus was observed in two pediatric VV ECMO patients. The overall incidence of venous clots was 20 % (6 of 30). Routine color Doppler sonography monitoring of vessels in children on and after ECMO was found to be useful for early detection of venous thrombosis. It enabled consequent administration of appropriate therapy as well as follow-up after decannulation and reconstruction.

Child, Preschool↗
PubMed1997

Establishment and characterization of a new, factor-independent acute myeloid leukemia line designated Ei501.

We established a factor-independent acute myeloid leukemia cell line, designated Ei501. The line has been growing in RPMI 1640 media for 18 months and can be maintained without addition of growth factors. Ei501 is positive for myeloperoxidase and negative for esterase and PAS. Cytogenetic analysis revealed the FAB M3 associated t(15;17) translocation and a translocation of the chromosomes 7 and 8: 46 XX, -7, +t(7;8)(q32;q13), t(15;17)(q22;q12). This karyotype was confirmed by fluorescence in situ hybridization. Ei501 cells express AML-associated surface markers such as CD13, CD33 and CD38. Although 42% of the patient's blast cells were CD34-positive, the line lacks surface expression of CD34. Furthermore the line has a number of characteristics which are detectable in blasts from AML patients, such as surface adhesion molecules, cytokines such as TGF-beta, cytokine receptors such as the IL-2 receptor beta and gamma chains or the IL-4 receptor and the genes for the transcription factor wt-1 (Wilms' tumor gene) and for the proto-oncogene bcl-2, both shown to be present in the majority of patients with AML. Additionally the line can be used as target in cytotoxicity assays using IL-2 activated cytotoxic lymphocytes as effector cells. In conclusion, besides a rare karyotype the Ei501 cell line has several features common in AML, and may therefore be used as a model to study pathogenetic mechanisms in acute myeloid leukemia.

Adolescent↗
PubMed1997

Wilms tumor gene expression in acute myeloid leukemias.

The Wilms' tumor gene product (WT-1) is suggested to act as a tumor suppressor in childhood malignancies of the kidney and as a transcription factor with regulating activity on a number of growth and differentiation factors. Wt-1 has been shown to be expressed in blast cells of the vast majority of patients with acute myeloid and lymphoblastic leukemias (AL) by a number of workers. High levels of wt-1 mRNA expression in blast cells of newly diagnosed AML patients predict worse prognosis when compared to patients with no or low wt-1 mRNA expression. Patients achieving complete responses after chemotherapy usually lose detectable signals of wt-1. In relapse of the disease reoccurrence of wt-1 mRNA can be determined in almost all patients with initially detectable wt-1 mRNA. Using sensitive techniques such as reverse transcription polymerase chain reaction (RT-PCR) relapses are preceded by wt-1 expression in some cases. Although a subpopulation of normal hematopoietic precursor cells has also been shown to express message for wt-1, detectable levels of wt-1 during follow-ups in AML patients have been shown to be useful as a marker for residual blast populations or even to predict relapse of AML. Whether the high level of wt- expression is a non-specific phenomenon resulting from malignant transformation or whether it has an impact on the pathophysiology of AML or the uncontrolled growth of AML blasts is still controversial. However, there are indicators for an involvement of wt-1 in malignant events of AML blasts such as the downregulation of wt-1 in chemically induced differentiation of AML blast cell lines or the interactions of wt-1 with the protooncogene bcl-2 and the tumor suppressor gene p53. In conclusion, its possible relevance as an AML marker and its role in pathophysiological mechanisms in AML will still have to be defined in the future.

Acute Disease↗
PubMed1997

The Wilms' tumor gene is expressed in a subset of CD34+ progenitors and downregulated early in the course of differentiation in vitro.

The Wilms' tumor gene (wt1) is strongly expressed in malignant blasts of acute myeloid leukemia (AML) in approximately 80% of all cases. However, the role of wt1 expression in non malignant hematopoietic cells remains unclear. To characterize the expression of wt1 in differentiating hematopoietic progenitors, we isolated and cultured CD34+ progenitor cells from four healthy bone marrow donors with stem cell factor (SCF) and granulocyte colony stimulating-factor (G-CSF) to induce differentiation into granulocytes. Four different cultures were carried out for 12 days. During culture, wt1 mRNA expression was analyzed by defining its ratio relative to beta-actin using reverse transcriptase polymerase chain reaction (RT-PCR). To monitor the stage of differentiation, expression of cell surface markers and peroxidase was analyzed daily. The initial purity of CD34+ cells ranged between 80% and 90%; after 12 days, the frequency of neutrophil bands and segmented neutrophils was approximately 60%. Using RT-PCR to determine the ratio of wt1 to beta-actin expression, we reproducibly detected maximum expression of wt1 mRNA at day 0 in two cultures and at day 1 in two other CD34+ cell cultures; at both these time points nearly all cells fulfilled the morphological and immunephenotypical criteria of early hematopoietic blast cells. Wt1 expression dropped rapidly at day 1 and 2, respectively, in these two pairs of cultures, and was accompanied by an increase of cells expressing CD33 surface antigen. Our data suggest that wt1 expression is restricted to a subset of CD34+ progenitors and downregulated in later stages of differentiation in vitro.

Antigens, CD34↗
PubMed1996

Neurodevelopmental outcome of hydrocephalus following intra-/periventricular hemorrhage in preterm infants: short- and long-term results.

Over a 5-year period (1984-1988) intra- and periventricular hemorrhage (IVH/PVH) was observed in 299 preterm infants. Sixty-eight infants developed posthemorrhagic hydrocephalus (PH); of these, 23 infants died and 40 infants could be followed up for assessment of neurological development (5 patients were lost to follow-up). At 1 year of corrected age 15% (25% at 5 year follow-up) of the infants were determined to have developed normally, 35% (25% at 5-year follow-up) showed mild neurological symptoms and/or slight developmental delay, 32.5% (28% at 5-year follow-up) had handicaps and/or moderate mental retardation, and 17.5% (22% at 5-year follow-up) had severe handicaps and/or severe mental retardation. There was a significantly worse outcome in infants with grade 4 IVH/PVH (P < 0.05) and a significantly worse outcome in the group requiring ventriculoperitoneal (VP) shunt (P < 0.05). The results at 1 year of corrected age proved to be a quite realistic predictor of neurological functioning at 5 years of age (80% predicted correctly in the non-shunted-group--one patient lost to follow-up; 95% predicted correctly in the shunted group--four patients lost to follow-up). Cystic periventricular leukomalacia had been diagnosed in 7 (10%) patients and was associated with poor neurodevelopmental outcome. Gestational age, birth weight, time of shunt placement, and peripartum asphyxia had no significant influence on neurodevelopmental outcome. Infants with shunt infections and a high number of shunt revisions were found to have a significantly worse neurodevelopmental outcome (P < 0.01).

Cerebral Hemorrhage↗
PubMed1996

[Intraoperative and percutaneous radiotherapy of pancreatic carcinoma].

Therapeutic strategies in the treatment of pancreatic carcinoma are based on the high number of non-resectable cancers, the high relative radioresistance and the high distant metastases rate. Even in curatively resected carcinomas, a locally effective treatment modality is needed because of the risk of microscopical residual disease in the peripancreatic tissue. The efficacy of radiotherapy is dose dependent. Based on an analysis of published data a dose of more than 50 Gy is recommended, resulting in a high morbidity rate with external beam radiotherapy alone. The use of intraoperative radiotherapy allows locally restricted dose escalation without increased perioperative morbidity. In adjuvant and in primary treatment, local tumor control was improved (70-90%). With palliative intent, pain relief was obtained rapidly in over 60% of patients and led to improved patient performance. As a result of the high distant metastases rate, even in curatively resected carcinomas, the overall prognosis could not be significantly improved. Further dose escalation is limited by the increasing incidence of upper gastrointestinal bleeding (20-30%).

Combined Modality Therapy↗