Biomedical subjects

U Möller

Publications and source records attributed to U Möller.

At least 19 recordsLinked to original sources

PubMed2005

Pilot study: tendency of increasing iodine content in human milk and cow's milk.

The iodine supply in Germany has improved throughout the last decade, albeit with enormous differences between individuals and regions. In the Thuringian city of Jena, analyses of the iodine content of human milk have been undertaken regularly since 1982. Significantly increasing iodine concentrations in human and cow's milk have been found. Therefore, the current situation and the effectiveness of measures to prevent iodine deficiency demands re-evaluation. The iodine content of human milk from 32 lactating mothers was analysed on the 5th day (mean) postpartum and mothers' dietary iodine intake during the last two months of pregnancy was assessed by means of a food frequency questionnaire. To corroborate the assumption that the increasing iodine levels of cow's milk are one of the main reasons for the improved iodine supply, the iodine concentration of 34 cow's milk bulk-samples was also determined. Both human and cow's milk samples were analysed by the ICP-MS method. Twenty women took iodine supplements (mean daily intake = 175 microg). The average daily iodine intake of the 20 supplemented and 12 non-supplemented women was 258 microg and 116 microg, respectively. Daily iodine intake from food and beverages was significantly lower in supplemented women (83 microg/day). The average iodine content of human milk was 169 +/- 88 microg/l with a range of 33 - 348 microg/l. This content is two times higher than levels from 1994 in the same area. There was no difference in the human milk iodine content between mothers taking supplements and those who did not. Cow's milk samples showed a mean iodine concentration of 178 +/- 131 microg/l (range 48 - 661 microg/l).

Adult↗

PubMed2004

Metabolic power of European starlings Sturnus vulgaris during flight in a wind tunnel, estimated from heat transfer modelling, doubly labelled water and mask respirometry.

It is technically demanding to measure the energetic cost of animal flight. Each of the previously available techniques has some disadvantage as well advantages. We compared measurements of the energetic cost of flight in a wind tunnel by four European starlings Sturnus vulgaris made using three independent techniques: heat transfer modelling, doubly labelled water (DLW) and mask respirometry. We based our heat transfer model on thermal images of the surface temperature of the birds and air flow past the body and wings calculated from wing beat kinematics. Metabolic power was not sensitive to uncertainty in the value of efficiency when estimated from heat transfer modelling. A change in the assumed value of whole animal efficiency from 0.19 to 0.07 (the range of estimates in previous studies) only altered metabolic power predicted from heat transfer modelling by 13%. The same change in the assumed value of efficiency would cause a 2.7-fold change in metabolic power if it were predicted from mechanical power. Metabolic power did not differ significantly between measurements made using the three techniques when we assumed an efficiency in the range 0.11-0.19, although the DLW results appeared to form a U-shaped power-speed curve while the heat transfer model and respirometry results increased linearly with speed. This is the first time that techniques for determining metabolic power have been compared using data from the same birds flying under the same conditions. Our data provide reassurance that all the techniques produce similar results and suggest that heat transfer modelling may be a useful method for estimating metabolic rate.

Analysis of Variance↗

PubMed2003

[Cerebral vasospasms with hemodynamic infarctions as a complication of HELLP syndrome].

Sinal thrombosis, intracerebral bleeding, cerebral edema, and cerebral vasospasm are typical neurological complications in pre- and eclampsia. Hemolysis, elevated liver enzyme, and low platelet (HELLP) syndrome is a rare, severe complication of pre-eclampsia. We present the case of a 33-year-old woman with HELLP syndrome. After a cesarean section, generalized epileptic seizure occurred and intubation was necessary due to sustained unconsciousness. Despite magnesium therapy, bilateral hemodynamic ischemic infarctions and narrowing of the circle of Willis were visible on MRI, and vasospasm of all large basal cerebral arteries was confirmed by cerebral angiography and transcranial Doppler sonography. During the following 2 weeks, the cerebral vasospasm resolved with application of high-dose methyl prednisolone and nimodipine. After extubation, the patient initially suffered from mild psychosyndrome and ataxia but recovered completely after 3 months. The HELLP syndrome may be complicated by cerebral vasospasm with subsequent hemodynamic strokes. Combined treatment with magnesium, corticosteroids, and nimodipine can be recommended. In our case, this regimen led to resolution of the cerebral vasospasm and complete clinical recovery.

Adult↗

PubMed2002

[In vitro studies into the influence of ochratoxin A on the production of tumor necrosis factor alpha by the human monocytic cell line THP-1].

The influence of pure OTA and an Aspergillus-ochraceus crude toxin on the intracellular expression and the secretion of tumor necrosis factor (TNF) alpha by the monocytic cell line THP-1 was studied in vitro. After 4 hours exposure, the secretion of TNF alpha was inhibited to 50% by pure OTA in a concentration of 400 ng/ml and by crude toxin in a concentration of 100 ng/ml. The same concentrations of mycotoxins impaired the mitochondrial activity of THP-1 cells only marginally. The intracellular expression of TNF alpha was not disturbed by pure OTA in the concentrations tested, whereas crude toxin showed an inhibitory effect. The possible reasons for these findings are discussed.

Calcium Channel Blockers↗

PubMed2001

Pitfalls in the clustering of neuroimage data and improvements by global optimization strategies.

In this paper, we examined three vector quantization (VQ) methods used for the unsupervised classification (clustering) of functional magnetic resonance imaging (fMRI) data. Classification means that each brain volume element (voxel), according to a given scanning raster, was assigned to one group of voxels based on similarity of the fMRI signal patterns. It was investigated how the VQ methods can isolate a cluster that describes the region involved in a particular brain function. As an example, word processing was stimulated by a word comparison task. VQ analysis methodology was verified using simulated fMRI response patterns. It was demonstrated in detail that VQ based on global rather than local optimization of the objective function yielded a higher performance. Performance was measured in statistically relevant series of VQ attempts using several indices for goodness, reliability and efficiency of VQ solutions. Furthermore, it was shown that a poor local optimization caused either an underestimation or an overestimation of the stimulus-induced brain activation. However, this was not observed if the cluster analysis was based upon a global optimization strategy.

Adult↗

PubMed2001

[HELLP Syndrome as an indication for liver transplantation].

Liver rupture followed by multiorgan failure is perhaps the most catastrophic complication of the HELLP syndrome (hemolysis, elevated liver function, low platelets). Specific treatment options are currently limited and not routinely clarified. Here, we present a patient successfully managed by an innovative surgical approach consisting of combined total hepatectomy, portacaval shunt, and liver transplantation. A 26-year-old primipara (39th week of gestation) who suffered liver rupture as a complication of HELLP syndrome after delivery underwent a portacaval shunt after total hepatectomy. This combination was sufficient until the patient underwent orthotopic liver transplantation. The patient was discharged from the hospital after a dramatic recovery. Bridging portacaval shunt and consecutive orthotopic liver transplantation represented an effective therapy for this patient and should be considered early as a treatment option in patients with liver rupture complicating severe HELLP syndrome.

Adult↗

PubMed2001

Metabolic power, mechanical power and efficiency during wind tunnel flight by the European starling Sturnus vulgaris.

We trained two starlings (Sturnus vulgaris) to fly in a wind tunnel whilst wearing respirometry masks. We measured the metabolic power (P(met)) from the rates of oxygen consumption and carbon dioxide production and calculated the mechanical power (P(mech)) from two aerodynamic models using wingbeat kinematics measured by high-speed cinematography. P(met) increased from 10.4 to 14.9 W as flight speed was increased from 6.3 to 14.4 m s(-1) and was compatible with the U-shaped power/speed curve predicted by the aerodynamic models. Flight muscle efficiency varied between 0.13 and 0.23 depending upon the bird, the flight speed and the aerodynamic model used to calculate P(mech). P(met) during flight is often estimated by extrapolation from the mechanical power predicted by aerodynamic models by dividing P(mech) by a flight muscle efficiency of 0.23 and adding the costs of basal metabolism, circulation and respiration. This method would underestimate measured P(met) by 15-25 % in our birds. The mean discrepancy between measured and predicted P(met) could be reduced to 0.1+/-1.5 % if flight muscle efficiency was altered to a value of 0.18. A flight muscle efficiency of 0.18 rather than 0.23 should be used to calculate the flight costs of birds in the size range of starlings (approximately 0.1 kg) if P(met) is calculated from P(mech) derived from aerodynamic models.

Animals↗

PubMed2000

Structure of the 5'-flanking region of the rat prostaglandin F(2alpha) receptor gene and its transcriptional control functions in hepatocytes.

Prostaglandin F(2alpha) (PGF(2alpha)), modulates hepatocyte functions via a heptahelical G(q)-coupled PGF(2alpha)-receptor (FP-R) which in liver is expressed exclusively in hepatocytes. The aim of the present study was to isolate the 5'-flanking region of the rat FP-R gene and to elucidate its basal and IL-6-modulated transcription control function in rat hepatocytes. The 5'-non-translated region of the rat hepatocyte FP-R mRNA differed from the corresponding region in rat fetal astrocyte or corpus luteum. It was encoded by exons 1a and 2 which were separated by a 1. 4 kb intron containing the exons 1b and 1c coding for the 5'-untranslated region of rat fetal astrocyte and corpus luteum FP-R mRNA, respectively. The transcription initiation site in hepatocytes was localized 263 bp upstream of the start ATG by 5'-RACE. A DNA-fragment covering the 5'-flanking region of the rFP-R gene from -1 of the transcription initiation site to -2590 bp was cloned and sequenced. Its 3'-two thirds had a 65% sequence identity to the mouse FP-R promoter however no homology to the bovine FP-R promoter. In the overlapping sequence most of the putative transcription factor binding sites were conserved between mouse and rat. The rat promoter contained no classical TATA- or CAAT-boxes but putative binding sites for the transcription factors C/EBP, GATA-1, HNF-1, HNF-3beta, SP-1, and USF. Luciferase reporter gene constructs containing portions of the 5'-flanking region were transfected into rat hepatocytes. Luciferase expression ranked -181 >/= -608 < -1418 > -1821 >/= -2590. The strongest transcriptional activity was conferred by the region between -608 and -1418 containing a cluster of potential HNF-1 and HNF-3beta binding sites that might allow the exclusive expression of FP-R mRNA in hepatocytes. The amount of FP-R mRNA and the luciferase expression under control of the -2590 promoter fragment were reduced by IL-6 in hepatocytes.

5' Untranslated Regions↗

PubMed2000

Requirement of N-glycosylation of the prostaglandin E2 receptor EP3beta for correct sorting to the plasma membrane but not for correct folding.

Eight heptahelical receptors have been characterized for prostaglandin (PG) D(2), PGE(2), PGF(2alpha), prostacyclin and thromboxane A(2). They share a sequence identity of 40%. All of them have potential N-glycosylation sites. The current study analysed the role of the two N-glycosylation sites in the rat EP3beta-subtype PGE(2) receptor for protein folding and sorting. The N-glycosylation consensus sequences were eliminated by site-directed mutagenesis and receptors expressed in HEK-293 cells. Both potential N-glycosylation sites were used. Their joint elimination resulted in the synthesis of a receptor protein with full binding competence, biological activity and no reduction of affinity; however, the half-life of the non-glycosylated receptor was slightly reduced. Ligand binding to intact stably transfected cells and confocal laser microscopic immunocytochemistry showed that the glycosylated receptor was correctly inserted into the plasma membrane to a much larger extent than the non-glycosylated receptor, which tended to accumulate in the perinuclear zone of the endoplasmic reticulum. Inhibition of N-glycosylation with tunicamycin resulted in a similar perinuclear distribution of the wild-type receptor. Therefore, glycosylation of the EP3beta receptor seems not to be necessary for correct folding of the receptor protein but for the efficient transport of the receptor protein to the plasma membrane. This contrasts with a previous finding which described a reduction of the affinity for PGE(2) of the EP3alpha receptor by elimination of the distal glycosylation site when the receptor protein was expressed in insect cells.

Animals↗

PubMed1999

Phospholipase D stimulation by receptor tyrosine kinases mediated by protein kinase C and a Ras/Ral signaling cascade.

Stimulation of phospholipase D (PLD) in HEK-293 cells expressing the M(3) muscarinic receptor by phorbol ester-activated protein kinase C (PKC) apparently involves Ral GTPases. We report here that PKC, but not muscarinic receptor-induced PLD stimulation in these cells, is strongly and specifically reduced by expression of dominant-negative RalA, G26A RalA, as well as dominant-negative Ras, S17N Ras. In contrast, overexpression of the Ras-activated Ral-specific guanine nucleotide exchange factor, Ral-GDS, specifically enhanced PKC-induced PLD stimulation. Moreover, recombinant Ral-GDS potentiated Ral-dependent PKC-induced PLD stimulation in membranes. Epidermal growth factor, platelet-derived growth factor, and insulin, ligands for receptor tyrosine kinases (RTKs) endogenously expressed in HEK-293 cells, apparently use the PKC- and Ras/Ral-dependent pathway for PLD stimulation. First, PLD stimulation by the RTK agonists was prevented by PKC inhibition and PKC down-regulation. Second, expression of dominant-negative RalA and Ras mutants strongly reduced RTK-induced PLD stimulation. Third, overexpression of Ral-GDS largely potentiated PLD stimulation by the RTK agonists. Finally, using the Ral binding domain of the Ral effector RLIP as an activation-specific probe for Ral proteins, it is demonstrated that endogenous RalA is activated by phorbol ester and RTK agonists. Taken together, strong evidence is provided that RTK-induced PLD stimulation in HEK-293 cells is mediated by PKC and a Ras/Ral signaling cascade.

Bacterial Proteins↗

PubMed1999

Application of correlation dimension and pointwise dimension for non-linear topographical analysis of focal onset seizures.

For many patients who are candidates for epilepsy surgery, non-invasive evaluation fails to provide sufficient information to permit surgical treatment. Since there are also definite risks and considerable costs associated with invasive procedures, new (non-invasive) techniques are required. This study provides empirical evidence that a non-linear approach applied to ictal surface electroencephalograms (EEGs) can help to delineate the area of seizure onset and may prove useful in complementing visual analysis of the EEG. Multichannel EEGs, recorded from eight patients with different drug-resistant localisation-related epilepsies, were analysed using the concept of correlation dimension and two extensions based on the pointwise dimension. The latter also provided results in cases where assessment of the correlation dimension was not feasible. Comparative values between 2 and 6 were accepted as the result of the algorithms, mostly 3-4 for the EEG channels strongly reflecting epileptic activity, and 4-6 for the other signals. The proportion of accepted pointwise values was usually 200-800% for strong epileptic EEG activity compared to the other data. The approach permitted the characterisation of the scalp area reflecting epileptic activity. The results obtained were in perfect concordance with those obtained during pre-surgical work-up and confirmed by the post-operative outcome.

Adolescent↗

PubMed1999

Agonist-induced phosphorylation by G protein-coupled receptor kinases of the EP4 receptor carboxyl-terminal domain in an EP3/EP4 prostaglandin E(2) receptor hybrid.

Prostaglandin E(2) receptors (EP-Rs) belong to the family of heterotrimeric G protein-coupled ectoreceptors with seven transmembrane domains. They can be subdivided into four subtypes according to their ligand-binding and G protein-coupling specificity: EP1 couple to G(q), EP2 and EP4 to G(s), and EP3 to G(i). The EP4-R, in contrast to the EP3beta-R, shows rapid agonist-induced desensitization. The agonist-induced desensitization depends on the presence of the EP4-R carboxyl-terminal domain, which also confers desensitization in a G(i)-coupled rEP3hEP4 carboxyl-terminal domain receptor hybrid (rEP3hEP4-Ct-R). To elucidate the possible mechanism of this desensitization, in vivo phosphorylation stimulated by activators of second messenger kinases, by prostaglandin E(2), or by the EP3-R agonist M&B28767 was investigated in COS-7 cells expressing FLAG-epitope-tagged rat EP3beta-R (rEP3beta-R), hEP4-R, or rEP3hEP4-Ct-R. Stimulation of protein kinase C with phorbol-12-myristate-13-acetate led to a slight phosphorylation of the FLAG-rEP3beta-R but to a strong phosphorylation of the FLAG-hEP4-R and the FLAG-rEP3hEP4-Ct-R, which was suppressed by the protein kinase A and protein kinase C inhibitor staurosporine. Prostaglandin E(2) stimulated phosphorylation of the FLAG-hEP4-R in its carboxyl-terminal receptor domain. The EP3-R agonist M&B28767 induced a time- and dose-dependent phosphorylation of the FLAG-rEP3hEP4-Ct-R but not of the FLAG-rEP3beta-R. Agonist-induced phosphorylation of the FLAG-hEP4-R and the FLAG-rEP3hEP4-Ct-R were not inhibited by staurosporine, which implies a role of G protein-coupled receptor kinases (GRKs) in agonist-induced receptor phosphorylation. Overexpression of GRKs in FLAG-rEP3hEP4-Ct-R-expressing COS-7 cells augmented the M&B28767-induced receptor phosphorylation and receptor sequestration. These findings indicate that phosphorylation of the carboxyl-terminal hEP4-R domain possibly by GRKs but not by second messenger kinases may be involved in rapid agonist-induced desensitization of the hEP4-R and the rEP3hEP4-Ct-R.

Animals↗

PubMed1998

Nonlinear dynamics of 3 Hz spike-and-wave discharges recorded during typical absence seizures in children.

One-channel routine recordings of the scalp electroencephalogram (EEG) from unmedicated children strictly classified as unprovoked typical (3 c/s) absence seizures were selected. The dynamics of spike-and-wave discharges (SWD) were then examined by means of autocorrelation, correlation dimension, averaged pointwise dimension and largest Lyapunov exponent. For one EEG signal with pronounced spike-and-wave (SW) patterns, these measures were used complementary to a surrogate data method, a nonlinear (SETAR) modeling approach, and a SW simulation procedure providing five types of SW test signals. The SETAR model exhibited stationary SW dynamics, visually very similar to the EEG target signal, and with clear nonlinear structure. According to the results, the EEG episodes investigated represent low-dimensional dynamics, possibly recorded during nonstationary periods. Arguments that justify the assumption of deterministic chaos in our EEG signals were not obtained with the current methods. From the results one may conclude that two global oscillatory modes are present for the model, and three modes are active during the EEG recording period.

Algorithms↗

PubMed1996

Immunochemical detection of CoA-modified mitochondrial matrix proteins.

An in vitro assay mixture consisting of mitochondrial matrix proteins from rat liver and CoA resulted in the formation of CoA-modified proteins. CoA-modified proteins were demonstrated by detection of CoA. CoA was released from the proteins by dithioerythritol treatment under denaturing conditions and was identified by (a) its retention time on HPLC, (b) its absorption spectrum and (c) its activity in a CoA-specific assay. This CoA represents protein-bound CoA and, in addition, protein-bound palmitoyl-CoA when MgATP was also present in the in vitro assay. The detection of immunoreactive proteins using mono-specific anti-CoA antibodies exclusively identifies CoA-modified proteins. The specificity of these antibodies can be used to identify both endogenously occurring CoA-modified proteins and proteins that have been modified in the in vitro assay. An intact thiol group of CoA is an essential precondition for the modification to occur.

Acetyl-CoA C-Acetyltransferase↗

PubMed1995

Non-radioactive detection of oligonucleotide probes by photochemical amplification of dioxetanes.

We describe a new method of non-radioactive labelling and detection of oligonucleotide probes. The approach is based on a simple chemical principle. Oligonucleotides labelled with methylene blue (a photosensitizer) are hybridized on a membrane to immobilized DNA target sequences. After hybridization and stringency washing 2(-)[3-(hydroxyphenyl)methoxymethylene] adamantane is added to the membrane and the membrane is irradiated with a tungsten lamp light source through a cut-off filter. Thermally stable dioxetanes are amplified during irradiation at the positions of the labelled probe. These amplified dioxetanes are detected using chemically triggered chemiluminescent decay. Signals are recorded on commercial X-ray film. Detection is possible immediately after the last washing step and a hard copy of the blot is obtained within 1 h. Dependent on the level of the target sequences, the sensitivity of the method allows detection of 0.3 pg single-stranded M13mp18(+) plasmid DNA in dot blots and 75 pg in Southern blots. Additional immunological reaction steps and washing steps with blocking reagents and buffers are avoided. Furthermore, expensive reagents and equipment for physical detection are not necessary. The method might be particularly useful for fast routine analysis in forensic and medical applications. The synthesis of the olefin, conditions of hybridization and the protocol of detection are described in detail.

Adamantane↗

PubMed1992

Modified cerium-based and Gomori-based cerium methods for light microscopic phosphatase histochemistry: the cerium-perhydroxide-diaminobenzidine-nickel (Ce-H2O2-DAB-Ni and Ce/Ce-H2O2-DAB-Ni) two-step procedures.

Some modified cerium-based and Gomori-based cerium methods for the demonstration of phosphatase activity in cryostat sections were described. Dextrane as stabilizing agent was added to the incubation media for ATPase, 5'-Nase, and TPPase. The oxidation of the CeIII-phosphate primary reaction product in a separate step by H2O2 before the DAB incubation yielded an increase of the intensity of the DAB-based visualization reaction (Ce-H2O2-DAB-Ni two step method). The sensitivity of the histochemical enzyme reaction was remarkably increased if CeIII-ions were employed as amplifying agent (Ce/Ce-H2O2-DAB-Ni two-step method). A new suitable DAB medium consisting of 0.015% DAB, 2.0% Ni-sulphate, 15% methanol, and 0.005% H2O2 in 0.1 mol/l acetate buffer, pH = 5.2, was used. The disadvantage of diffuse background staining has been overcome by addition of 15% methanol to the DAB solution. Electrovalently bound CeIII (cerophilia) was removed by treatment of the incubated sections with CeIII-citrate (CeIII-complexation). In addition, a novel membrane floating incubation for sections is proposed. At present, the modified procedures are some of the most sensitive modes for the demonstration of phosphatases and improve the earlier described cerium-DAB one-step technique (Halbhuber et al. 1988b).

Animals↗

PubMed1991

Identification of the CoA-modified forms of mitochondrial acetyl-CoA acetyltransferase and of glutamate dehydrogenase as nearest-neighbour proteins.

A 52 kDa protein could only be co-purified with the CoA-modified forms of acetyl-CoA acetyltransferase (acetoacetyl-CoA thiolase) (EC 2.3.1.9) from rat liver mitochondria. Immunoprecipitations of these modified forms with anti-(acetyl-CoA acetyltransferase) IgG or anti-(52 kDa protein) IgG yielded, in addition to the appropriate proteins, the 52 kDa protein or the CoA-modified form of acetyl-CoA acetyltransferase (41 kDa) respectively. This was demonstrated by SDS/PAGE and immunoblots. The modified forms containing the 52 kDa protein could be cross-linked by 1,5-difluoro-2,4-dinitrobenzene to a high-molecular-mass complex containing both the 41 kDa and 52 kDa proteins. The 52 kDa protein was identified as mitochondrial glutamate dehydrogenase (EC 1.4.1.3) by amino acid sequence analysis. The results of co-immunoprecipitation and cross-linking characterize the CoA-modified forms of acetyl-CoA acetyltransferase and the glutamate dehydrogenase as nearest-neighbour proteins.

Acetyl-CoA C-Acetyltransferase↗

PubMed1991

Evidence for an in vivo modification of mitochondrial proteins by coenzyme A.

Following denaturation of mitochondrial proteins by sodium dodecyl sulfate, a [1-14C]pantothenic acid-derived radioactivity proved to be acid precipitable in the outer membrane, the intermembrane space, the inner membrane and in the matrix of rat liver mitochondria, where it had the highest specific radioactivity of 541 +/- 29 cpm/100 micrograms protein. This tightly and/or covalently bound protein radioactivity could be released by incubation in the presence of dithioerythreitol; it was identified as [14C]coenzyme A by its HPLC retention time, its absorption spectrum and its radioactivity. This acid-stable and thiol-labile coenzyme A-binding apparently refers to specific protein binding sites. With the purified, homogeneous mitochondrial matrix enzymes acetyl-CoA acetyltransferase (acetoacetyl-CoA thiolase) (EC 2.3.1.9, acetyl-CoA:acetyl-CoA C-acetyltransferase) and 3-oxoacyl-CoA thiolase (EC 2.3.1.16) coenzyme A was found exclusively, e.g., in the modified, partially-active forms A1 und A2 of acetyl-CoA acetyltransferase and not in the unmodified fully-active enzyme. Thus it is evident that this coenzyme A modification is transient. We suggest that coenzyme A-modification is a signal involved in the assembly or the degradation process of distinct mitochondrial matrix proteins.

Acetyl-CoA C-Acetyltransferase↗