Identification of a 'genuine' mammalian homolog of nematodal CED-4: is the hunt over or do we need better guns?
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Animals↗
Biomedical subjects
U Maurer
Publications and source records attributed to U Maurer.
[Interstitial brachytherapy--a minimal invasive urological option for treatment of prostate cancer of increasing importance].
As an alternative to a radical prostatectomy with complications reducing the quality of life because of incontinence of urine and erectile dysfunction, the insertion of radioactive sources into the prostate was established in the USA and evaluated by accompanying studies at the beginning of the eighties. The patient has the advantage of minimal-invasive character, the possibility of outpatient treatment and the lower operative morbidity as well as reduced complications. In the locally limited "low-risk" stage (pT1a - pT2c), the American Society for Urology judges it equieffective as a curative treatment as regards the survival period. Although there are long-term studies with a follow-up of 13 years, in Germany we are not able to give our opinion finally, but it can be assumed to be as equally good. Considering the demographic development, one has to expect an increase in this cancer, which today already has the highest cancer rate in men in Germany. The improved diagnosis will lead to an increase in treatments and younger men will be examined. As a result there will be more curable cases and an improvement or even prolongation of the survival period. The trend seen in the USA indicates a rise in this treatment in Germany as well. After a terminological definition of the expression and a presentation of the brachytherapy-technique, the range of actual therapeutical options of prostate cancer and the variations of brachytherapy are shown and compared as far as their efficiency is concerned. Uncertainties in the evaluation of medical necessity are discussed but also contradictions and diversities in the opinions on the mode of accounting.
Adult↗
Minor neurological dysfunction, cognitive development, and somatic development at the age of 3 to 7 years after dexamethasone treatment in very-low birth-weight infants.
The objective of this study was to assess minor neurological dysfunction, cognitive development, and somatic development after dexamethasone therapy in very-low-birthweight infants. Thirty-three children after dexamethasone treatment were matched to 33 children without dexamethasone treatment. Data were assessed at the age of 3-7 years. Dexamethasone was started between the 7th and the 28th day of life over 7 days with a total dose of 2.35 mg/kg/day. Exclusion criteria were asphyxia, malformations, major surgical interventions, small for gestational age, intraventricular haemorrhage grades III and IV, periventricular leukomalacia, and severe psychomotor retardation. Each child was examined by a neuropediatrician for minor neurological dysfunctions and tested by a psychologist for cognitive development with a Kaufman Assessment Battery for Children and a Draw-a-Man Test. There were no differences in demographic data, growth, and socio-economic status between the two groups. Fine motor skills and gross motor function were significantly better in the control group (p<0.01). In the Draw-a-Man Test, the control group showed better results (p<0.001). There were no differences in development of speech, social development, and the Kaufman Assessment Battery for Children. After dexamethasone treatment, children showed a higher rate of minor neurological dysfunctions. Neurological development was affected even without neurological diagnosis. Further long-term follow-up studies will be necessary to fully evaluate the impact of dexamethasone on neurological and cognitive development.
Child↗
Preterm twin gestation and cystic periventricular leucomalacia.
OBJECTIVE: To identify risk factors for the development of cystic periventricular leucomalacia (PVL) in twin gestation. DESIGN: Retrospective case-control study. SETTING: Tertiary care university hospital, Department of Paediatrics, Division of Neonatology, Graz, Austria. PATIENTS: Preterm twin gestations with one sibling having developed cystic PVL, diagnosed by ultrasound scans, compared with their co-twins without PVL, in hospital between 1988 and 2000. MAIN OUTCOME MEASURES: Perinatal and postnatal risk factors for the development of PVL. RESULTS: Eighteen preterm twin gestations were included. Monochorionicity was evident in 47% of the pregnancies, and twin to twin transfusion syndrome occurred in two cases (11%). Fetal distress correlated inversely with PVL (15% v 53%, p = 0.019, relative risk (RR) = 2.057, 95% confidence interval (CI) = 1.067 to 3.968). Hypocarbia with Pco(2) levels below 30 mm Hg (4 kPa) was diagnosed in 29% of the cases compared with 6% of the controls (p = 0.038, RR = 1.944, 95% CI = 1.113 to 3.396). There were no significant differences between groups with regard to premature rupture of the membranes, early onset infection, respiratory distress syndrome, mechanical ventilation, arterial hypotension, persistent ductus arteriosus, and hyperbilirubinaemia. Asphyxia was only evident in three controls. Three infants died and another three were lost to follow up. None of the cases compared with 62% of the controls were diagnosed as having developed normally (p < 0.001), and 14 cases (82%) compared with two controls (15%) developed cerebral palsy (p < 0.001). CONCLUSION: Hypocarbia was the only risk factor strongly associated with cystic PVL. The general outcome of the infants was poor.
Adult↗
p53 triggers apoptosis in oncogene-expressing fibroblasts by the induction of Noxa and mitochondrial Bax translocation.
The mechanism of p53-dependent apoptosis is still only partly defined. Using early-passage embryonic fibroblasts (MEF) from wild-type (wt), p53(-/-) and bax(-/-) mice, we observe a p53-dependent translocation of Bax to the mitochondria and a release of mitochondrial Cytochrome c during stress-induced apoptosis. These events proceed independent of zVAD-inhibitable caspase activation, are not prevented by dominant negative FADD (DN-FADD), but are negatively regulated by Mdm-2. Bcl-x(L) expression prevents the release of mitochondrial Cytochrome c and apoptosis, but not Bax translocation. At a single-cell level, enforced expression of p53 is sufficient to induce Bax translocation and Cytochrome c release. Real-time RT-PCR analysis reveals a significant induction of RNA expression of Noxa and Bax in p53(+/+), but not in p53(-/-) MEF. Noxa protein expression becomes detectable prior to Bax translocation, and downregulation of endogenous Noxa by RNA interference protects wt MEF against p53-dependent apoptosis. Hence, in oncogene-expressing MEF p53 induces apoptosis by BH3 protein-dependent caspase activation.
Adaptor Proteins, Signal Transducing↗
Absent or reversed end-diastolic blood flow in the umbilical artery and abnormal Doppler cerebroplacental ratio--cognitive, neurological and somatic development at 3 to 6 years.
UNLABELLED: The objective of this study was to examine the cognitive, neurological and somatic developments of children who had in utero an absent or reversed end-diastolic blood flow (ARED) in the umbilical artery or an abnormal cerebroplacental ratio (ABF). METHODS: 16 children with ARED blood flow and 15 children with ABF were each matched to children with the same gestational age, appropriate for gestational age, the same sex and born within 4 months. Data were assessed at the age of 3-6 years. Children with asphyxia, neonatal infection, malformation or major surgical interventions in the neonatal period were excluded. Each child underwent a neuropediatrical examination; furthermore, a Kaufman Assessment Battery for Children, a Snijders-Oomen Intelligence Scale for Children and a Man-Drawing Test were used to evaluate cognitive development. The socioeconomic status was also assessed. RESULTS: Children in the ARED group remained lighter and had a higher frequency of microcephaly. In the Kaufman Assessment Battery for Children and the Snijders-Oomen Intelligence Scale for Young Children, cognitive development was impaired in the ARED and the ABF groups compared to the control group. The ARED and the ABF groups, however, showed no differences. The Man-Drawing Test and the Denver Development Test did not show any differences. DISCUSSION: ARED blood flow and ABF showed impaired cognitive development. The degree of impairment was the same in the ARED and the ABF groups. Long-term follow-up studies until adulthood are necessary to see if impaired cognitive development remains significant in these groups of patients.
Adult↗
Death in paradise.
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Adaptor Proteins, Signal Transducing↗
The coexpression of the apoptosis-related genes bcl-2 and wt1 in predicting survival in adult acute myeloid leukemia.
The Wilms tumor gene wt1 and the protooncogene bcl-2 are upregulated in acute myeloid leukemia (AML) and are known to regulate or to inhibit the onset of apoptosis. Since wt1 has been shown to regulate the expression of bcl-2, we investigated the association of the expression of these genes and their prognostic relevance in AML. Leukemic blasts from the bone marrow of 152 patients with newly diagnosed AML were analyzed for bcl-2 and wt1 mRNA expression using RT-PCR and quantitative PCR. Therapy outcome was correlated with the level of bcl-2 and wt1 transcripts. Bcl-2-specific mRNA was detectable in 127/152 (84%) patients and wt1 mRNA in 113/152 (74%) patients with AML. In monocytic subtypes the frequency of bcl-2 and wt1 transcripts was significantly lower. The expression of bcl-2 mRNA was correlated significantly with that of wt1 mRNA (P < 0.0001). In AML patients <60 years, high expression of bcl-2 and wt1 was associated with a reduced rate of continuing complete remission (CCR, P = 0.002 and P = 0.005, respectively) and increased death rate (P = 0.0002 and P = 0.04, respectively) in contrast to patients >60 years, where the expression of bcl-2 or wt1 had no prognostic impact. Based on the coexpression of bcl-2 and wt1, we established a prognostic model defining three risk groups with significant differences in CCR rate (P = 0.01), overall survival (P < 0.04) and disease-free survival (P < 0.03). Thus, bcl-2 and wt1 mRNA expression are associated with response and long-term outcome in AMLs. The coexpression of these genes allows determination of prognostic groups with high predictive value for overall and disease-free survival.
Acute Disease↗
[Small for gestational age - Somatic, neurological and cognitive development until adulthood].
BACKGROUND: The somatic, neurological and cognitive development of children born small for gestational age (SGA) until adulthood was assessed in recent studies. Studies that assessed mortality, morbidity, somatic, neurological and cognitive development of SGA children were compared. MATERIALS AND METHODS: In the studies very low birth weight SGA children were compared to very low birth weight appropriate for age children (AGA, birth weight below 1500 g or 1250 g). Full-term SGA children were compared to full-term appropriate for age children. Growth of SGA children remained under the 10th percentile, if catch up growth did not occur until the end of the second year. Cerebral palsy appeared more often in VLBW-AGA than in VLBW-SGA children. Cognitive development problems appeared in VLBW-SGA and FT-SGA children more often than in VLBW-AGA and FT-AGA children. These cognitive development problems were observed mainly as poor school performance. When reaching adulthood, the differences in cognitive function seem to be less significant. Low socioeconomic status and persistence of microcephaly were associated with problems in neurological and cognitive development. CONCLUSIONS AND DISCUSSION: Growth and cognitive development problems appeared more often in SGA children. More longterm studies are necessary to show, if these cognitive development problems remain significant until adulthood.
Adolescent↗
Is radiotherapy of pelvic lymph nodes successful in prostate cancer?
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Adenocarcinoma↗
The technique of 125I permanent implants.
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Adenocarcinoma↗
Interstitial brachytherapy with permanent seed implants in early prostate cancer.
Excellent clinical results after permanent seed implantation have been reported by various centers in large cohorts of patients. However, all of these had extensive experience in this special field of radiotherapy and the therepy and the follow-up time is too short for definite conclusions. The fact that this option of treatment can be carried out on an outpatient basis and that it allows to get the patient back to normal as far as social environment and work are concerned, has led to wide acceptance of this particular mode of therapy. Therefore, permanent seed implantation is a possible treatment option for localized prostate cancer and can be offered to patients with T1- T2a tumors, PSA levels of < 10 and a Gleason score of < 7. By using permanent seed implantation in these selected patients, it seems possible to achieve results comparable with surgery alone or percutaneous, 3D-planned radiotherapy.
Adenocarcinoma↗
Quantum solution to the Byzantine agreement problem.
We present a solution to an old problem in distributed computing. In its simplest form, a sender has to broadcast some information to two receivers, but they have access only to pairwise communication channels. Unlike quantum key distribution, here the goal is not secrecy but agreement, and the adversary (one of the receivers or the sender himself) is not outside but inside the game. Using only classical channels this problem is provably impossible. The solution uses pairwise quantum channels and entangled qutrits.
Journal Article↗
Ribozyme-mediated cleavage of wt1 transcripts suppresses growth of leukemia cells.
OBJECTIVE: The Wilms' tumor gene product (WT1) was identified as a tumor suppressor in pediatric kidney tumors. Conversely, acute leukemias express WT1 at a high frequency, and leukemias with high levels of WT1 expressed by leukemic blast cells have a significantly worse prognosis, suggesting an oncogenic function of WT1 in leukemic cells. To address this issue, we developed five hammerhead ribozymes (RZ1-RZ5) designed to cleave various wt1-mRNA GUC-recognition sites and thus suppress wt1 expression. METHODS: Using in vitro transcribed ribozymes and truncated wt1 target RNAs as substrates, we performed in vitro cleavage assays. The sequence of two ribozymes was then cloned into the pCDNA3 expression vector containing a self-processing ribozyme cassette. Downregulation of wt1 due to ribozyme expression was analyzed in the human 293 embryonic kidney and the K562 chronic myeloid leukemia cell line by Western blotting and RT-PCR. Growth of stable transfected K562 cells was determined by proliferation analysis and 3H-thymidine incorporation. RESULTS: In vitro, the anti-wt1 ribozymes were able to recognize and cleave the target RNA in a highly sequence-specific and time-dependent manner. The ribozymes showed different catalytic activity. Coexpression of wt1 and the self-processing ribozymes pRZ3 and pRZ5, respectively, resulted in a significantly downregulated WT1 protein level when transiently transfected in 293 cells. Furthermore, stable transfection of pRZ3 and pRZ5 resulted in considerably reduced expression of endogenous wt1 in K562 cells, correlating with the inhibition of cell proliferation and the induction of cell death. CONCLUSION: Our data suggest that anti-wt1 ribozymes are a potent inhibitor of wt1 expression with possible implications for the inhibition of cell proliferation in leukemic cells.
Base Sequence↗
No evidence for mutagenic effects of ribavirin: report of two normal pregnancies.
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Adult↗
Identification of novel polymorphisms in intron 7 of the human p53 gene in acute myeloid leukemia and healthy donors.
Screening for mutations by PCR-SSCP in exons 5 to 9 of the p53 gene in 38 bone marrow or peripheral blood specimens of patients with acute myeloid leukemia (AML) showed abnormal shifts in 9 cases. One reflected a mutation in exon 8, whereas in the other cases there were no exonic mutations identified by sequencing. As PCR primers were chosen annealing in the introns flanking the exon region, following sequencing of the encompassing introns identified 5 base substitutions at various sites in intron 7. Two of them have been described previously [1] and 3 novel polymorphisms could be identified. To determine whether these polymorphisms are linked to the pathogenesis of AML, we screened peripheral blood specimens of 26 healthy controls. We found identical base substitutions in 6 out of 26 controls. Our data suggest that these polymorphisms are not related to the pathogenesis of AML.
Acute Disease↗
The Wilms' tumor gene product (WT1) modulates the response to 1,25-dihydroxyvitamin D3 by induction of the vitamin D receptor.
The Wilms' tumor gene (wt1) encodes a transcription factor involved in urogenital development, in particular in renal differentiation, and in hematopoietic differentiation. Differentiation of a number of solid tumor and leukemic cells lines can be mediated by 1,25-dihydroxyvitamin D(3). This is predominantly mediated by the nuclear receptor for 1,25-dihydroxyvitamin D(3), the vitamin D receptor (VDR). In initial experiments addressing a possible link between WT1 and VDR, we observed a correlated expression of WT1 and VDR mRNA in samples from renal tissues. HT29 colon carcinoma cells, stably transfected to express WT1, exhibited elevated endogenous VDR levels compared with control cells transfected with a control construct. Elevated VDR expression was found in wt1-transfected human embryonic kidney 293 cells, as well. In transient cotransfection experiments, we observed an activation of a vdr promoter reporter by WT1 through a WT1 recognition element, indicating transcriptional regulation of the vdr gene expression by WT1. The responsive sequence element was specifically bound by wild-type, but not by mutated WT1, in electrophoretic mobility shift assays. HT29 colon carcinoma cells, which respond to 1,25-dihydroxyvitamin D(3) with slow induction of growth arrest, were investigated for the influence of WT1 on 1,25-dihydroxyvitamin D(3)-mediated growth suppression. Although HT29 cells transfected with a control construct responded moderately to 1,25-dihydroxyvitamin D(3), the response of HT29 cells expressing WT1 was strikingly enhanced. Stimulation with dihydroxyvitamin D(3) caused an up to 3-fold reduction in the growth rate of different HT29 clones expressing WT1 as compared with control cells lacking WT1 expression. Thus, induction of VDR by WT1 leads to an enhanced response to 1,25-dihydroxyvitamin D(3). We conclude that the vitamin D receptor gene is a target for transcriptional activation by WT1, suggesting a possible physiological role of this regulatory pathway.
Base Sequence↗
Risk factors and determinants of neurodevelopmental outcome in cystic periventricular leucomalacia.
UNLABELLED: The aim of the study was to determine risk factors for the development of cystic periventricular leucomalacia (PVL) and to correlate ultrasound findings with neurodevelopmental outcome. By means of a retrospective case-control study (matched for gestational age, birth weight, sex, and year of birth) and a cohort analysis of all preterm infants with cystic PVL documented by ultrasound scans hospitalised at a local tertiary care centre between 1988 and 1998, 98 preterm infants with a gestational age ranging from 26 to 35 weeks were diagnosed as having cystic PVL. The mean day of diagnosis of periventricular echodensities was 3 +/- 2 days (range 1-11 days), and of cystic PVL 21 +/- 8 days (range 2-47 days). Of 79 infants (1988-1997) eligible for neurodevelopmental follow-up (91%), hemi-, di-, or tetraplegia was diagnosed in 61 (77%), normal mental outcome in 22 (28%), associated visual disorders in 41 (52%) and seizure disorders in 12 (15%) infants. Significant risk factors associated with the development of cystic PVL were premature rupture of membranes, chorioamnionitis, and hyperbilirubinaemia (odds ratios 4.665, 6.026, and 2.460 respectively). Subgroup analysis according to gestational age (26-28, 29-32, 33-35 weeks) revealed similar results despite spontaneous labour (26-28 weeks; odds ratio 4.808) and pre-eclampsia (33-35 weeks; odds ratio 3.517). Multiple pregnancy was associated with a twofold increased risk (odds ratio 2.075). The white matter damage probably accounted for the significantly higher prevalence of apnoeas (P < 0.001) and neonatal seizures (P < 0.001). Cysts located bilateral or parieto-occipital were associated with a higher risk of cerebral palsy (odds ratios 6.933 and 4.327 respectively). Solely anterior located cysts were associated with normal neurological outcome. Increasing size of the cysts was associated with increasing risk of cerebral palsy with a cut-off value of 10 mm (odds ratio 3.300 and above) and all infants with cysts of more than 20 mm diameter had cerebral palsy. CONCLUSION: The high prevalence of premature rupture of the membranes and chorioamnionitis further supports the role of intra-uterine infection in the pathogenesis of periventricular leucomalacia. The overall prognosis of cystic periventricular leucomalacia is poor.
Brain Diseases↗