[Bladder exstrophy--epispadias complex. New goals--new ways?].
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Bladder Exstrophy↗
Biomedical subjects
A Ebert
Publications and source records attributed to A Ebert.
Technique for rapid in vitro single-cell elastography.
Statistically meaningful assays require scanning a large number of cells in a short time. Here we present a technique for rapid in vitro single-cell elastography. The technique is based on atomic force acoustic microscopy but (1) requires only a few minutes of scan time, (2) can be used on live cells briefly removed from most of the nutrient fluid, (3) does negligible harm or damage to the cell, (4) provides semiquantitative information on the distribution of modulus across the cell and (5) yields data with 1- to 10-nm resolution. We describe the new technique in detail, apply it to baby hamster kidney cells, verify the results and calibrate the images with atomic force microscope force-distance measurements. The technique enables rapid assessment of physical/biochemical signals on the cell modulus and contributes to current understanding of cell mechanics.
Animals↗
Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates.
Glial cell line-derived neurotrophic factor (GDNF) has been shown to increase the survival and functioning of dopamine neurons in a variety of animal models and some recent human trials. However, delivery of any protein to the brain remains a challenge due to the blood/brain barrier. Here we show that human neural progenitor cells (hNPC) can be genetically modified to release glycosylated GDNF in vitro under an inducible promoter system. hNPC-GDNF were transplanted into the striatum of rats 10 days following a partial lesion of the dopamine system. At 2 weeks following transplantation, the cells had migrated within the striatum and were releasing physiologically relevant levels of GDNF. This was sufficient to increase host dopamine neuron survival and fiber outgrowth. At 5 weeks following grafting there was a strong trend towards functional improvement in transplanted animals and at 8 weeks the cells had migrated to fill most of the striatum and continued to release GDNF with transport to the substantia nigra. These cells could also survive and release GDNF 3 months following transplantation into the aged monkey brain. No tumors were found in any animal. hNPC can be genetically modified, and thereby represent a safe and powerful option for delivering growth factors to specific targets within the central nervous system for diseases such as Parkinson's.
Animals↗
Differentiated dopaminergic MN9D cells only partially recapitulate the electrophysiological properties of midbrain dopaminergic neurons.
The cell line MN9D, a fusion of embryonic ventral mesencephalic and neuroblastoma cells, is extensively used as a model of dopamine (DA) neurons because it expresses tyrosine hydroxylase and synthesizes and releases DA. These cells are also used to test mechanisms and potential therapeutics relevant to the loss of DA neurons in Parkinson's disease. To date, little work has been done to determine whether MN9D cells electrophysiologically resemble mature DA neurons. We examined sodium, calcium and potassium currents in undifferentiated and differentiated MN9D cells, and compared these to those found in acutely dissociated mouse substantia nigra pars compacta DA neurons. It was observed that undifferentiated MN9D cells bore no resemblance to DA neurons. Upon differentiation with butyric acid with or without a prior treatment with glial cell line-derived neurotrophic factor, differentiated MN9D cells produce an electrophysiological profile that more closely resembles substantia nigra pars compacta DA neurons even though the A-type potassium current remains noticeably absent. These observations demonstrate that undifferentiated MN9D cells are not reasonable models of DA neurons. Although differentiated MN9D cells are closer to the mature DA neuronal phenotype, they do not fully mimic DA neurons and are likely to be of questionable value as a model because of their substantive differences, including the lack of the characteristic A-type potassium current. The future use of one or a combination of growth or other factors to differentiate MN9D cells may yield a more useful model system for Parkinson's disease studies in vitro.
Action Potentials↗
Psychosocial and psychosexual development in childhood and adolescence within the exstrophy-epispadias complex.
PURPOSE: We report the psychosocial and psychosexual development of children and adolescents with the exstrophy-epispadias complex (EEC) after complete functional repair using the Erlangen single stage technique. MATERIALS AND METHODS: In a long-term retrospective followup of an average of 11.1 years 100 patients with EEC (76 boys and 24 girls, mean age 14.5 years) were evaluated with respect to medical history, and received a general questionnaire concerning their social and psychosocial situation. A total of 54 patients who were 15 years or older (mean age 18.5) received an additional questionnaire to assess detailed sexual history. RESULTS: Of the patients 81% returned the general questionnaire within 3 weeks. School education level and social integration were high. In about 25% of the patients impairment of daily life was significant, and in 58.7% peer relations were altered. Of the adolescent group 76% answered the special questionnaire. Genital satisfaction and genital touching were rated low, and avoidance of nudity in public areas was common. All patients expressed heterosexuality and 43.9% had engaged in sexual intercourse but 58.5% displayed anxiety about sexual activity. It is noteworthy that 93.9% expressed an interest in psychological assistance. CONCLUSIONS: Despite a high degree of social integration and adult adaptation, children and adolescents with EEC suffer from psychosocial and psychosexual dysfunction requiring special questionnaires for adequate assessment. Anxiety about genital appearance and sexual activity is a common phenomenon among adolescents with EEC, even when they present with nearly "normal" genitalia and participate with satisfaction in sexual activity. Further studies are needed to understand the exstrophy problem and supply all patients with EEC with the individual care they need.
Activities of Daily Living↗
Cardiac safety of trastuzumab in combination with epirubicin and cyclophosphamide in women with metastatic breast cancer: results of a phase I trial.
This prospective, parallel-group, dose-escalation study evaluated the cardiac safety of trastuzumab (Herceptin) plus epirubicin/cyclophosphamide (EC) in women with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC) and determined an epirubicin dose for further evaluation. HER2-positive patients received standard-dose trastuzumab plus epirubicin (60 or 90 mg/m(2))/cyclophosphamide (600 mg/m(2)) 3-weekly (EC60+H, n=26; EC90+H, n=25), for four to six cycles; 23 HER2-negative patients received EC alone (90/600 mg/m(2)) 3-weekly for six cycles (EC90). All patients underwent thorough cardiac evaluation. Two EC90+H-treated patients experienced symptomatic congestive heart failure 4.5 and 6 months after the end of chemotherapy. One EC60+H-treated patient experienced an asymptomatic decrease in left ventricular ejection fraction (LVEF) to <50% 6 months after the end of chemotherapy. No such events occurred in control patients. Asymptomatic LVEF decreases of >10% points were detected in 12 (48%), 14 (56%) and 5 (24%) patients treated with EC60+H, EC90+H, and EC90. Objective response rates with EC60+H and EC90+H were >60%, and 26% for EC90 alone. These results indicate that trastuzumab may be combined with EC with manageable cardiotoxicity and promising efficacy.
Adult↗
Scalable mobile information system to support the treatment process and the workflow of wastewater facilities.
In order to support the operation of wastewater systems and the workflow of sewage systems an application for demonstration has been developed to show exemplarily how a mobile information system can be transferred into practice and used by the staff. The paper presents a scalable information visualisation system, which can be used with mobile devices. The regarded information data does not only include process data, but also general information about buildings and units, work directions, occupational safety regulations as well as instructions of first aid in case of a work accident. This is particularly appropriate for the use in remote facilities. The implementation is based on but not limited to SQL, JSP and HTML.
Accidents, Occupational↗
[The frequency-doubled double-pulse Neodym:YAG laser lithotripter (FREDDY) in lithotripsy of urinary stones. First clinical experience].
Laser lithotripsy does not play an important role in urinary stone treatment, mostly due to ineffective fragmentation efficiency, and high purchase and maintenance costs. The aim of the following retrospective study was to show the clinical significance and efficiency of an innovative laser lithotripsy system for urinary stone treatment. Between November 1998 and October 1999, 48 patients were treated with the innovative frequency- doubled double-pulse Neodym: YAG laser lithotripter FREDDY. A total of 50 renal units were treated, 43 ureteroscopically, four ureterorenoscopically, three percutaneous-nephroscopically, and one bladder stone cystoscopically. With a median laser operation time of 5 min (range: 1-30 min) and a total procedure duration of 60 min (range: 15-180 min), a stone-free rate of upper ureteral stones of 62%, middle ureteral stones of 91% and distal ureteral stones of 100% were documented on the first day after treatment. In an observation period of 6 months, no complications were seen. In our experience Laser lithotripsy with FREDDY is an effective, simple and reliable method for the treatment of ureteral stones, with low purchase and maintenance costs. The extremely thin and highly flexible quartz fibre may extend the endoscopic spectrum to otherwise poorly accessible upper ureteral stones, the renal pelvis and renal calix stones. Therefore, a prospective validation study for comparison with ballistic lithotriptors is of great interest.
Adolescent↗
[Renal cell carcinoma in childhood. Case report and review].
Renal cell carcinoma (RCC) in childhood is rare and its incidence is estimated to be 3-6% of all kidney cancers in childhood. Thus, clinical experience with renal cell carcinoma in this age group is meager and no consensus between pediatric urologists and pediatric oncologists exists on common treatment strategies. Furthermore, most previous reports included postpubertal patients in whom the biological behavior of the RCC and treatment options are the same as in adults. Based on the literature and a clinical case report of a 12-year-old boy suffering from a papillary renal cell carcinoma stage IV (pT2 N2 MO), the relevance of the biological behavior of different histological subtypes and their treatment options are reviewed and discussed. In adulthood lymph node dissection is still controversial, but in children it seems to have a positive effect on survival. Immunotherapy in childhood is still and experimental option and just a few cases are reported in the literature.
Antineoplastic Combined Chemotherapy Protocols↗
[Effectiveness of syringe shieldings using radionuclides in radiation synovectomy].
AIM: The radiation exposure in radiation synovectomy was investigated for technician and therapist using Erbium-169, Rhenium-186 and Yttrium-90 with and without syringe shieldings. METHODS: Dose rates were measured in relation to the distance of the syringe containing the radionuclide. Measurements were repeated using syringe shieldings which consist of plastic surrounded by a lead layer. RESULTS: The most relevant radiation exposure arises from Yttrium-90. Using syringe shieldings radiation exposure can be reduced by a factor of thousand. CONCLUSION: This kind of radiological protection is completely sufficient for the therapist. Concerning the technician preparing the radiopharmaceutics, the limit of the official German dosimetry service (500 mSv) might be exceeded if no special radiological protection is established. Thus, special dosimetry is recommended.
Humans↗
Foetal lung maturation in 11beta-hydroxysteroid dehydrogenase type 1 knockout mice.
Glucocorticoids (GCs) induce surfactant synthesis in the late foetal lung. Deficient GC action causes respiratory distress syndrome (RDS). 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone), thus amplifying intracellular GC action. Reduction or loss of pulmonary 11beta-HSD1 activity in glycyrrhetinic acid-treated rats substantially impaired foetal lung maturation (Hundertmark et al., Horm Metab Res, this issue). To test these data, we investigated 11beta-HSD1 activity and lung maturity in the late foetal lung using 11beta-HSD1 knockout mice. Control foetal mice showed high 11beta-HSD activity in the late foetal lung and levels of plasma 11-dehydrocorticosterone were high. Lungs from 11beta-HSD1 -/- mice had lower surfactant protein-A (mRNA and protein) levels and significant depletion of lung surfactant according to both light and electron microscopy, and also had reduced amniotic fluid lecithin/sphingomyelin ratios. These results support the previous experiments with glycyrrhetinic acid and emphasize the importance of 11beta-HSD1 in foetal lung maturation.
11-beta-Hydroxysteroid Dehydrogenases↗
Chick CFC controls Lefty1 expression in the embryonic midline and nodal expression in the lateral plate.
Members of the EGF-CFC family of proteins have recently been implicated as essential cofactors for Nodal signaling. Here we report the isolation of chick CFC and describe its expression pattern, which appears to be similar to Cfc1 in mouse. During early gastrulation, chick CFC was asymmetrically expressed on the left side of Hensen's node as well as in the emerging notochord, prechordal plate, and lateral plate mesoderm. Subsequently, its expression became confined to the heart fields, notochord, and posterior mesoderm. Implantation experiments suggest that chick CFC expression in the lateral plate mesoderm is dependent on BMP signaling, while in the midline its expression depends on an Activin-like signal. The asymmetric expression domain within Hensen's node was not affected by application of FGF8, Noggin, or Shh antibody. Implantation of cells expressing human or mouse CFC2, or chick CFC on the right side of Hensen's node randomized heart looping without affecting expression of genes involved in left-right axis formation, including SnR, Nodal, Car, or Pitx2. Application of antisense oligodeoxynucleotides to the midline of Hamburger-Hamilton stage 4-5 embryos also randomized heart looping, but in contrast to the overexpression experiments, antisense oligodeoxynucleotide treatment resulted in bilateral expression of Nodal, Car, Pitx2, and NKX3.2, whereas Lefty1 expression in the midline was transiently lost. Application of the antisense oligodeoxynucleotides to the lateral plate mesoderm abolished Nodal expression. Thus, chick CFC seems to have a dual function in left-right axis formation by maintaining Nodal expression in the lateral plate mesoderm and controlling expression of Lefty1 expression in the midline territory.
Animals↗
Identification of Cripto-1 in human milk.
Cripto-1 (CR-1) is an epidermal growth factor (EGF)-related peptide that plays an important role in normal mammary gland development. CR-1 is expressed in the growing terminal end buds in the virgin mouse mammary gland and its expression increases during pregnancy and lactation. Furthermore, CR-I is involved in the early stages of mouse mammary tumorigenesis and in the pathogenesis of human breast cancer. Since CR-1 is expressed in the mouse mammary gland at high levels during pregnancy and lactation, we have evaluated whether this protein is present in human milk. In the present study we demonstrate that a 28 kDa immunoreactive CR-1 protein is present in 24 human milk samples as assessed by western blot analysis and that by enzyme-linked immunosorbent assay the concentration of CR-1 ranges between 62 and 118 ng/ml. In addition, CR-1 that had been purified from human milk is able to stimulate the phosphorylation of mitogen activated protein kinase in nontransformed NMuMG mouse mammary epithelial cells. These results suggest that CR-1 in human milk may be important in regulating mammary gland development during pregnancy and lactation.
Animals↗
[The impact of pregnancy-prolonging management on maternal and neonatal morbidity in HELLP syndrome].
OBJECTIVE: Until recently, delivery immediately after diagnosing HELLP syndrome was recommended due to the life-threatening risk to mother and child. Prolongation at least until lung maturation is being increasingly considered because of the high rate of premature births characterized by extreme immaturity. We investigated the influence of the time of delivery on maternal and neonatal morbidity at a gestational age of less than 34 + 0 weeks of pregnancy. - MATERIAL AND METHODS: The disease course was reevaluated in 37 patients who developed HELLP syndrome (thrombocytes < 100 000/microl, transaminase > 70 U/l, haptoglobin < 0.5 g/l) between 1994 and 1999. An attempt was made to stabilize the mother's condition under therapeutic volume expansion. Pregnancy was terminated with the onset of a renewed HELLP episode. - RESULTS: HELLP syndrome occurred with an incidence of 1 : 310 births. There were no maternal or neonatal deaths or any severe complications. Prolonging pregnancy until completing drug-induced lung maturity was successful in 16 of 25 patients before the 34(th) week of pregnancy. In the case of immediate delivery with inadequate stabilization, 5 of 9 patients had postpartum complications. A severe RDS occurred in 3 premature babies without drug-induced maturity. - CONCLUSION: If there is no life-threatening risk to the fetus or mother in patients with HELLP syndrome, the objective is the prolongation of pregnancy in a perinatal center until lung maturation. Stabilization is successful in a high percentage of patients under therapeutic volume expansion with optimal monitoring of mother and child.
Adult↗
Current use of HER2 tests.
Reliable detection of HER2 overexpression is important for the success of trastuzumab (Herceptin) therapy. Several methods are available for measuring HER2 expression at the DNA, RNA or protein level. The method most frequently employed is immunohistochemical (IHC) detection of the HER2 receptor in paraffin sections. Advantages include the precise localization of the HER2 protein, the availability of paraffin material and the ease of the procedure. However, IHC can be influenced by the sensitivity/specificity of the antibody, tissue treatment and, in particular, subjective assessment. These disadvantages do not exist in the detection of gene amplification by fluorescence in situ hybridization (FISH) or polymerase chain reaction. However, FISH requires expensive equipment that is not widely available in pathology laboratories. Another approach quantitates shed HER2 antigen in the serum by an enzyme-linked immunosorbent assay. The key advantage of this method is the ease of sampling blood, however, serum HER2 concentrations do not accurately reflect the tumor status. Furthermore, this method does not register single-cell expression, which is important for therapeutic decision making. For routine diagnostics, the combination of IHC and FISH is useful. In addition to improving the accuracy and comparability of HER2 assays, these optimized protocols may further enhance the efficacy of trastuzumab therapy by selecting those patients most likely to respond.
Biomarkers, Tumor↗
Cripto-1 induces apoptosis in HC-11 mouse mammary epithelial cells.
Cripto-1 (CR-1) is an epidermal growth factor (EGF)-related protein. CR-1 can inhibit beta-casein and whey acidic protein expression in mouse mammary epithelial cells. The present study demonstrates that CR-1 can induce apoptosis in HC-11 mouse mammary epithelial cells, as measured by bis-benzimide stained nuclei, TUNEL assay and cell death ELISA. Apoptosis could be observed after 2 days of exposure of confluent HC-11 cells to CR-1 in the absence of the survival factors EGF and insulin, with maximum apoptosis occurring at 3 days. A reduction in poly(ADP-ribose) polymerase (PARP) expression and an increase in beta-catenin cleavage was found after 18 h of exposure to CR-1 suggesting that apoptosis was preceded by the induction of a caspase activity since the caspase inhibitor ZFAD.FMK could block the CR-1-induced reduction in PARP expression and CR-1-induced apoptosis. CR-1 was found to increase the expression of caspase-3-like protease. Although, the levels of p27kip1 and p21Bax did not change after exposure to CR-1 for 18 h, the levels of Bcl-xL became undetectable. These studies suggest that CR-1 promotes apoptosis by mediating the induction of caspase-3-like protease and downregulating the expression of Bcl-xL.
Animals↗
Management of failed bladder exstrophy closure in adolescence and adulthood.
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Adolescent↗
[The clinical importance of keratin 18 in breast cancer].
OBJECTIVE: This study was performed to determine the prognostic significance and the biological function of the structure protein keratin 18 (K18) in a group of patients with breast cancer. MATERIAL AND METHODS: Paraffin sections from the primary tumors in 80 patients with breast cancer were examined for the expression of K18 by immunohistochemical staining with the monoclonal antibody CK2. The intensity of the expression measured by an immune reactive score (IRS) was compared with clinicopathological variables and follow-up data up to 10 years. Additionally K18 expression in different human breast cancer cell lines with well defined metastatic behavior were investigated to confirm the clinical data. RESULTS: A marked positive staining was observed in 13 (16.2%) women. Mortality rate in this group was 7.7% and 46.3% in the group with a low K18 expression. The recurrence rate was with 15.4% significantly lower in the positive group than in the negative group with 56.7%. Irrespective of the morphological tumor stage, almost all patients with strong K18 expression were still free of disease after 10 years. This clinical finding is supported by observations in cell cultures. CONCLUSIONS: In our collective K18 expression was found to be an independent and significant predictor for disease-free and overall survival.
Adult↗