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T Müller

Publications and source records attributed to T Müller.

At least 109 records · Page 6Linked to original sources
PubMed2001

Effect of antenatal betamethasone treatment on microtubule-associated proteins MAP1B and MAP2 in fetal sheep.

Betamethasone has been used extensively to accelerate fetal lung maturation, yet little is known of its effects on neuronal morphogenesis in the developing fetus. Microtubule-associated proteins (MAPs) are a diverse family of cytoskeletal proteins that are important for brain development and the maintenance of neuroarchitecture. Vehicle (n = 7) or betamethasone (10 ug h-1, n = 7) was infused I.V. to fetal sheep over 48 h beginning at 0.87 of gestation (128 days of gestation), producing fetal plasma betamethasone concentrations resembling those to which the human fetus is exposed during antenatal glucocorticoid therapy. Paraffin sections of the left hemisphere were stained with monoclonal antibodies against MAP1B and the MAP2 isoforms MAP2a,b,c and MAP2a,b. The level of the juvenile isoform MAP2c was determined by comparison of the two MAP2 immunostainings. We were able to detect MAP1B and MAP2 immunoreactivity (IR) in the fetal sheep brain. MAP2c was the major MAP2, constituting 90.2 % of the total MAPBetamethasone exposure diminished MAP1B IR in the frontal cortex and caudate putamen (P < 0.05) but not in the hippocampus. A decrease of MAP2 IR was found in the frontal cortex, hippocampus and caudate putamen (P < 0.05). Loss of MAP2 IR was mainly due to the loss of MAP2c IR. Haematoxylin-eosin staining did not demonstrate irreversible neuronal damage. Regional cerebral blood flow determined using coloured microspheres was significantly decreased by 28 % in the frontal cortex and by 36 % in the caudate putamen but not in the hippocampus 24 h after the onset of betamethasone exposure (P < 0.05). The loss of MAP1B and MAP2a,b,c IR showed a significant correlation to the cerebral blood flow decrease only in the frontal cortex (P < 0.05). These data suggest that mechanisms other than metabolic insufficiency caused by the decreased cerebral blood flow may contribute to the loss of MAPs. The results suggest that clinical doses of betamethasone may have acute effects on cytoskeletal proteins in the fetal brain.

Animals↗
PubMed2001

Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1.

Male "viable motheaten" (me(v)) mice, with a naturally occurring mutation in the gene of the SH2 domain protein tyrosine phosphatase SHP-1, are sterile. Known defects in sperm maturation in these mice correlate with an impaired differentiation of the epididymis, which has similarities to the phenotype of mice with a targeted inactivation of the Ros receptor tyrosine kinase. Ros and SHP-1 are coexpressed in epididymal epithelium, and elevated phosphorylation of Ros in the epididymis of me(v) mice suggests that Ros signaling is under control of SHP-1 in vivo. Phosphorylated Ros strongly and directly associates with SHP-1 in yeast two-hybrid, glutathione S-transferase pull-down, and coimmunoprecipitation experiments. Strong binding of SHP-1 to Ros is selective compared to six other receptor tyrosine kinases. The interaction is mediated by the SHP-1 NH(2)-terminal SH2 domain and Ros phosphotyrosine 2267. Overexpression of SHP-1 results in Ros dephosphorylation and effectively downregulates Ros-dependent proliferation and transformation. We propose that SHP-1 is an important downstream regulator of Ros signaling.

3T3 Cells↗
PubMed2001

Antenatal betamethasone treatment reduces synaptophysin immunoreactivity in presynaptic terminals in the fetal sheep brain.

Knowledge of morphofunctional effects on the fetal brain induced by exogenous glucocorticoids is limited. Recently, we reported alterations of both the neuronal cytoskeleton and electrocortical function in the ovine fetal brain after antenatal betamethasone treatment in doses used in perinatal medicine. In the present study we examined whether these changes are accompanied by morphological alterations of synapses. Chronically instrumented fetal sheep at 0.87 of gestation were treated either with isotonic saline (n=7) or 10 microg/h betamethasone (n=7) over 48 h administered directly to the fetal jugular vein. Paraffin sections of the frontal neocortex, caudate putamen and hippocampus were stained with a monoclonal antibody against synaptophysin, a specific membrane protein of presynaptic vesicles and quantified morphometrically. Synaptophysin-like immunoreactivity (synaptophysin-LI) showed a widespread granular pattern in the neuropil. Betamethasone exposure reduced synaptophysin-LI in the frontal neocortex, caudate putamen and hippocampus by 46.9, 41.0 and 55.4%, respectively, (P<0.05) that was not accompanied by irreversible neuronal damage. These results suggest that clinical doses of betamethasone have acute effects on presynaptic terminals in the fetal sheep brain that could contribute to the altered complexity of electrocortical function that we have shown previously to occur following fetal exposure to betamethasone.

Animals↗
PubMed2001

Hearing impairment is common in various phenotypes of the mitochondrial DNA A3243G mutation.

OBJECTIVE: To determine whether there are common symptoms within different phenotypes of the mitochondrial DNA A3243G mutation. DESIGN: A series of 52 adults with mitochondrial encephalomyopathies and their symptomatic relatives were screened for the A3243G mutation using restriction enzyme analysis. In addition to clinical examination, patients with the mutation underwent audiometry. RESULTS: The A3243G mutation was identified in 16 patients (10 index patients and 6 symptomatic relatives). Six of these patients presented with strokelike episodes and met the classical criteria of MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes), and one had MELAS/MERRF (myoclonic epilepsy with ragged-red fibers) overlap syndrome. Two patients presented with strokelike episodes but did not meet the classical criteria of MELAS. Predominant features of the 8 other patients were myopathy with hearing loss and diabetes mellitus (n = 1), chronic progressive external ophthalmoplegia (n = 1), diabetes mellitus with hearing loss (n = 1), painful muscle stiffness with hearing loss (n = 1), cardiomyopathy (n = 1), diabetes mellitus (n = 1), and hearing loss (n = 2). In 11 of 16 patients, hearing impairment was obvious on clinical examination. Furthermore, all 5 patients with normal hearing on clinical examination showed subclinical hearing loss; in 4, hearing loss was more pronounced than age-related hearing impairment and in 1, hearing loss can be age related as well. CONCLUSIONS: A variety of phenotypes represent the variable multisystemic involvement of the A3243G mutation. Less than half of the patients presented with MELAS. Hearing impairment, the most common symptom, was clinically or subclinically relevant in 15 (94%) of 16 patients.

Adolescent↗
PubMed2001

GCG repeats and phenotype in oculopharyngeal muscular dystrophy.

Short GCG repeat expansions in the PABP2 gene were recently shown to cause oculopharyngeal muscular dystrophy (OPMD) in French-Canadian and Italian pedigrees. We diagnosed OPMD in 16 German patients by the detection of GCG repeat expansions, confirming genetic homogeneity. Myopathic and neurogenic changes were found in skeletal muscle biopsies. Age of onset and severity of disease were not correlated with the number of repeats.

Age of Onset↗
PubMed2001

A silyl cation with a three-center si-h-si bond.

The unusually high kinetic stability of the silyl cation 1 is due to the presence of a three-center, two-electron Si-H-Si bond. NMR data ((1) H, (2) H, (13) C, (29) Si) are consistent with the static, symmetrical structure shown, which was further corroborated by the results of density functional calculations.

NMR spectroscopy↗
PubMed2001

Combined laser tweezers and dielectric field cage for the analysis of receptor-ligand interactions on single cells.

A new technique based on the combination of optical and chip-based dielectrophoretical trapping was developed and employed to manipulate cells and beads with micrometer precision. The beads were trapped with optical tweezers (OT) and brought into contact for defined times with cells held in the dielectrophoretic field cage (DFC). The well-defined ligand-receptor system biotin-streptavidin was used to study the multiple interaction between biotinylated live cells and streptavidin-coated beads. The biotin density on the cell surface was varied down to a few single bonds (3 +/- 2 bonds/microm2) to control the valency of the binding. The quantitative relationship between the contact area, ligand density and its diffusion rate in the outer membrane of the cell could be demonstrated. The increase of the strength of the cell-bead adhesion was strictly dependent on the increase of individual bond numbers in the contact area. This is in part due to accumulation of ligands (D approxiamtely (0.5 +/- 0.1) 10(-8) cm2/s) in the contact area as seen by confocal laser scanning microscopy. Individual receptor-ligand rupture forces were evaluated and are compatible with values obtained by biomembrane force probe techniques. To summarize, the combination leads to a new powerful microsystem for cell handling and pN-force measurements on the single-cell level.

Animals↗
PubMed2001

Length dependence of variables associated with temporal dispersion in human motor nerves.

Temporal dispersion in motor nerves is associated with changes of amplitude, area, duration, and Fourier spectra of compound muscle action potentials (CMAPs) when comparing responses to proximal and distal stimulation. These changes depend on the length of the nerve segment. To quantitatively assess this dependence, motor conduction studies of nerve segments of various lengths were performed in the median, ulnar, and tibial nerves of 86 test subjects, aged 4 to 73 years. Amplitude, area, duration, and spectral energy above 49 Hz of CMAPs were measured. Values after distal and proximal stimulation of each nerve segment were compared to determine amplitude decay, area decay, protraction, and high-frequency attenuation. A significant length dependence of amplitude decay was found in the tibial and ulnar nerves, of area decay in the median and ulnar nerves, and of CMAP duration in the ulnar and tibial nerves. The length dependence of the high-frequency attenuation was significant in all nerves studied. This report provides normative data for variables associated with temporal dispersion.

Action Potentials↗
PubMed2001

Copper-associated liver disease in North Ronaldsay sheep: a possible animal model for non-Wilsonian hepatic copper toxicosis of infancy and childhood.

Indian childhood cirrhosis (ICC), endemic Tyrolean infantile cirrhosis (ETIC) and idiopathic copper toxicosis (ICT), are clinically and pathologically indistinguishable liver disorders of infants and young children linked with exogenous copper and with increasing evidence for a genetic predisposition. North Ronaldsay sheep are a primitive breed which have adapted to a copper impoverished environment (<5 ppm) and display an abnormal sensitivity to copper poisoning when transferred to a copper replete (11 ppm) habitat. The aetiological parallels prompted a study of copper-associated liver disease in North Ronaldsay sheep (RCT) to see if the pathology could contribute to the understanding of the childhood disorder. A retrospective study was performed in which the livers of 22 mainland-bred North Ronaldsay sheep were compared with three island-bred sheep and categorized for liver copper content and pathomorphology. It was found that all the mainland sheep had accumulated liver copper (>300 microg/g), in contrast to the island sheep, although 10 sheep with increased liver copper (mean 600 SD 270 microg/g) showed no evidence of liver damage. A further 10 sheep with liver copper (mean 1276 SD 508 microg/g) exhibited periportal to panlobular histochemical copper retention, a periportal and/or panlobular pericellular fibrosis, a mixed inflammatory infiltrate and cholangioplasia. Steatosis was absent and regeneration was in abeyance. Finally, two sheep (liver copper >2000 microg/g) had a more active hepatitis with a florid pericellular, panlobular fibrosis and cirrhosis. Electron microscopy identified large numbers of collagen-producing hepatic stellate (Ito) cells in periportal regions. The pathological findings were sufficiently reminiscent of ICC, ETIC and ICT to warrant further exploration of RCT as a putative animal model. The North Ronaldsay sheep liver may be a useful tool for the investigation of copper-induced fibrogenesis.

Animals↗
PubMed2001

[Familial mitochondrial chronic progressive external ophthalmoplegia. Five families with differing genetics].

UNLABELLED: Chronic progressive external ophthalmoplegia (CPEO) is considered the most frequent form of mitochondrial encephalomyopathies. Most cases occur sporadically. We investigated 18 consecutive patients with CPEO. Thirteen cases were sporadic and five cases were familial. In one family with maternal inheritance the mitochondrial point mutation A3243G was identified. In index patients of three other families multiple deletions of mitochondrial DNA were found. One of these families showed autosomal recessive inheritance. In the two other pedigrees a definitive determination of the mode of inheritance was impossible. The fifth family revealed autosomal dominant or maternal inheritance. In their index patient no alteration of mitochondrial DNA could be identified (including sequencing of hot spots for mitochondrial mutations). CONCLUSIONS: CPEO was familial in 28% of our patients. There are three different modes of inheritance: (i) maternal transmission associated with mitochondrial point mutations as it is known for other mitochondrial disorders, (ii) autosomal recessive, and (iii) autosomal dominant inheritance. In contrast to sporadic cases with single mitochondrial deletions autosomal inheritance can be associated with multiple deletions of mitochondrial DNA. They are due to so far unknown nuclear mutations.

Adult↗
PubMed2001

Basic examinations on chemical pre-oxidation by ozone for enhancing bioremediation of phenanthrene contaminated soils.

Biological treatment of polycyclic aromatic hydrocarbons (PAH) has been demonstrated to be a feasible and common remediation technology which has been successfully applied to the clean-up of contaminated soils. Because bioavailability of the contaminants is of great importance for a successful bioremediation, a chemical pre-oxidation step by ozone was tested to enhance the subsequent biodegradation steps. Oxidation of PAH by ozone should result in reaction products that have a better solubility in water and thus a better bioavailability. A major part of this work was done by examinations of the model substance phenanthrene as a typical compound of PAH. After initial ozonation of phenanthrene, analysis by GC-MS showed at least seven identified conversion-products of phenanthrene. In comparison with phenanthrene these conversion products were more efficiently biodegraded by Sphingomonas yanoikuyae or mixed cultures when the ozonation process resulted in monoaromatic compounds. Primary ozonation products with biphenylic structures were found not to be biodegradable. Investigations into the toxicity of contaminated and ozonated soils were carried out by well-established toxicity assays using Bacillus subtilis and garden cress. The ozonated soils surprisingly showed higher toxic or inhibitory effects towards different organisms than the phenanthrene or PAH itself. The microbial degradation of phenanthrene in slurry reactors by S. yanoikuyae was not enhanced significantly by preozonation of the contaminated soil.

Bacillus subtilis↗
PubMed2001

De novo mutation of the connexin 26 gene associated with dominant non-syndromic sensorineural hearing loss.

Mutations of the connexin 26 (Cx26) gene cause isolated recessive or dominant hearing loss or both sensorineural hearing impairment and keratoderma. We have identified the first de novo mutation of the Cx26 gene, R75 W, in a sporadic case of isolated profound hearing loss. R75 W has been previously observed in association with hearing impairment and keratoderma in one family and is thus thought to cause both syndromic and non-syndromic hearing loss. This case illustrates the risk of a possible erroneous diagnosis of autosomal recessive hearing loss in a sporadic case.

Amino Acid Substitution↗
PubMed2001

Low serial serum neopterin does not predict low risk for chronic renal graft rejection.

Research has provided new and potent immunosuppressants which can potentially stop ongoing rejection. Subclinical rejection is a particular problem in the pediatric age group and early identification of children at risk is of the utmost importance. Neopterin has been previously shown to be a non-specific but sensitive marker for immunologic activity. In this study we hypothesized that low serum neopterin in the 1st year after transplantation predicts a low risk of chronic rejection. We retrospectively analyzed serial neopterin data obtained beyond the early postoperative period in 21 children and correlated the peak and average with glomerular filtration rate (GFR) loss during the subsequent years (P = 0.63, NS, r = 0.10). Our results show that serum neopterin did not differ between the majority of children who developed chronic transplant dysfunction and children with stable transplant function beyond the early post-transplant period. Thus serum neopterin failed to delineate a low-risk population who might be spared more invasive diagnostic procedures such as protocol biopsy.

Child↗
PubMed2001

Reduction of delayed renal allograft function using sequential immunosuppression.

Previous data suggested that outcome in small children with cadaveric renal transplantation might be improved with sequential therapy. This protocol combines augmented immunosuppression [by including antibody induction (ATG)] with avoidance of nephrotoxic medication in the immediate postoperative phase (by delayed start of cyclosporin therapy). In this report, we describe effects of this approach in 12 consecutively transplanted small children of less than 5 years of age (mean 3.2 years) who received a cadaveric renal graft at our institution between 1991 and 1998. Up to 1996 triple therapy (prednisolone, azathioprine, cyclosporin) and since 1997 sequential therapy (prednisolone, azathioprine, ATG until serum creatinine <2 mg/dl, then cyclosporin) was used for immunosuppression. Five children had delayed graft function (45.4%), all of whom were treated with triple therapy including cyclosporin from the very beginning, whereas children treated by the sequential protocol gained immediate graft function (P<0.05). There was no statistical difference between the two protocols concerning frequency or severity of rejections (67% vs. 60%, all steroid responsive), difference in the incidence of either bacterial or viral infections, or between the incidence of hypertension. Although not reaching statistical significance, 1-year graft survival rates also increased from 60% for triple therapy to 80% for sequential therapy. In conclusion, our findings confirm previous studies showing that outcome in small children undergoing renal transplantation may be improved by specially tailored treatment protocols such as sequential therapy.

Antibodies↗