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J Steinbach

Publications and source records attributed to J Steinbach.

At least 19 recordsLinked to original sources

Development of an optical trap for microparticle clouds in dilute gases.

Long-duration experiments with clouds of microparticles are planned for the ICAPS facility on board the International Space Station ISS. The scientific objectives of such experiments are widespread and are ranging from the simulation of aerosol behaviour in Earth's atmosphere to the formation of planets in the early solar system. It is, however, even under microgravity conditions, impossible to sustain a cloud of free-floating, microscopic particles for an extended period of time, due to thermal diffusion and due to unavoidable external accelerations. Therefore, a trap for dust clouds is required which prevents the diffusion of the particles, which provides a source of relative velocities between the dust grains and which can also concentrate the dust to higher number densities that are otherwise not achievable. We are planning to use the photophoretic effect for such a particle trap. First short-duration microgravity experiments on the photophoretic motion of microscopic particles show that such an optical particle-cloud trap is feasible. First tests of a two-dimensional trap were performed in the Bremen drop tower.

Journal Article↗

Investigation of the explosive hazard of mixtures containing hydrogen peroxide and different alcohols.

The explosive properties of mixtures of aqueous hydrogen peroxide (H(2)O(2)) and different alcohols (R-OH) like 2-propanol (2-PropOH), 2-methyl-2-propanol (TBA), 2-methyl-2-butanol (TAA) and 2-methyl-2-pentanol (THA) were investigated. Among others, the potential hazard of such mixtures may be characterized by their ability to react by different mechanisms of an explosion in the condensed phase, e.g. the thermal explosion or the detonation. Accordingly, the mixtures were experimentally investigated either by heating them up under confinement in different autoclaves or by exposing them to a shock wave impact applying the steel tube test. The results are discussed and compared to literature data.

Alcohols↗

Efficient synthesis of the 18F-labelled 3-O-methyl-6-[18F]fluoro-L-DOPA.

The 18F-labelled amino acid derivative 3-O-methyl-6-[18F]fluoro-L-DOPA ([18F]OMFD) is a potential radiotracer for imaging tumour tissue using positron emission tomography. The precursor N-formyl-3-O-methyl-4-O-boc-6-trimethyl-stannyl-L-DOPA-ethyl ester enables direct electrophilic radiofluorination by stereoselective destannylation. After partial hydrolysis, optimized HPLC purification and sterile filtration, the [18F]OMFD obtained with high radiochemical purity and ready for use. The total synthesis time is about 50 min and the radiochemical yield achieved is 20-25% (decay corrected, related to [18F]F(2)). It was demonstrated that [18F]OMFD could be produced routinely and reliably for clinical use. [18F]FDOPA-preparation devices can be used with minor modifications.

Chromatography, High Pressure Liquid↗

In vivo measurement of the serotonin transporter with (S)-([18F]fluoromethyl)-(+)-McN5652.

The radiolabeled serotonin transporter (SERT) ligand [(11)C](+)-McN5652 has recently been used in clinical positron emission tomography (PET) studies for SERT imaging. However, this radioligand offers disadvantages in routine clinical settings because of its short radioisotope half-life (eg PET facilities within hospitals without a cyclotron need to acquire such radioligands from distant cyclotron units for clinical use). S-([(18)F]fluoromethyl)-(+)-McN5652 ([(18)F](+)-FMe-McN5652) is an analogue which has been synthesized newly, and has a significantly longer radioisotope half-life. In the porcine brain, it demonstrates the same characteristic distribution pattern of serotonin-uptake sites like the (11)C-labeled congener with the highest binding in the midbrain and thalamus and the lowest in the cerebellum and occipital cortex. It shows a 30% higher blood-brain transfer and a slower peripheral metabolism than [(11)C](+)-McN5652. Rather uniform brain binding was observed after injection of the pharmacologically inactive radiolabeled enantiomer, or after pretreatment with the highly selective SERT inhibitor citalopram. The norepinephrine uptake inhibitor maprotiline did not show any inhibitory effect. Using a one-tissue compartment model (K(1), k"(2)) or a two-tissue compartment model (K(1) to k(4)) with or without constraints for calculation, the regional binding parameters of [(11)C](+)-McN5652 and [(18)F](+)-FMe-McN5652 are highly correlated among each other and with the SERT density, as determined by in vitro binding of [(3)H]citalopram. Using constraints to correct for the free fraction and nonspecific binding of the radiotracers, a considerable increase of the midbrain-occipital cortex ratios with higher values for [(18)F](+)-FMe-McN5652 compared to [(11)C](+)McN5652 was revealed. It is concluded that [(18)F](+)-FMe-McN5652 has better features than [(11)C](+)McN5652 for SERT imaging with PET.

Animals↗

Distribution of estrone sulfatase in rat brain determined by in vitro autoradiography with 16alpha-[18F]fluoroestradiol-3,17beta-disulfamate.

16Alpha-fluoroestradiol-3,17beta-disulfamate (FESDS) strongly inhibits estrone sulfatase (ES), an enzyme which is also present in the brain. The enzyme is probably involved in important regulatory functions of neurosteroids which may be disturbed in certain brain diseases. In the present study, [18F]FESDS was used to measure the amount of ES in various rat brain regions using quantitative in vitro autoradiography. The obtained values vary between 0.29 pmol (mg protein)(-1) (pons) and 11.5 pmol (mg protein)(-1) (striatum). They are positively correlated with the enzyme activity measured in homogenates of the corresponding regions. Because this radiotracer binds also to carbonic anhydrase in the brain it is only of limited use for in vivo imaging studies.

Adenocarcinoma↗

Distribution of 16alpha-[18F]fluoro-estradiol-3,17beta-disulfamate in rats, tumour-bearing mice and piglets.

Based on a high affinity to the enzyme estrone sulfatase (ES), 16alpha-[18F]fluoroestradiol-3,17beta-disulfamate ([18F]FESDS) has been suggested as a potential PET radiotracer for imaging steroid-dependent breast tumours. The distribution of [18F]FESDS was studied in rats, tumour-bearing nude mice and piglets. In all species evidence for binding to a second target, the enzyme carbonic anhydrase (CA), was obtained. ES and CA inhibitors significantly reduced the radiotracer uptake in various organs but not in tumours. It is concluded that [18F]FESDS binds to ES and CA in vivo but this binding is not strong enough to allow tumour imaging with positron emission tomography (PET).

Animals↗

Aspects of 6-[18F]fluoro-L-DOPA preparation: precursor synthesis, preparative HPLC purification and determination of radiochemical purity.

A modified method for the synthesis of the intermediate product N-Boc-3,4-di(Boc-O)-6-iodo-L-phenylalanine ethyl ester of the [18F]FDOPA precursor preparation was developed. With the application of bis-(trifluoroacetoxy)-iodobenzene for the iodination step with elemental iodine the yield of the intermediate can be increased from 12% to 50-60%. By replacing silica-gel-based RP HPLC column by a polymer-based column for semi-preparative purification of [18F]FDOPA from the reaction mixture the radiochemical purity of the final product can be increased up to >99%. For the determination of the radiochemical impurity [18F]fluoride a HPLC method using a column with polymer-based RP material was introduced.

Chromatography, High Pressure Liquid↗

Automated synthesis of 16alpha-[18F]fluoroestradiol-3,17beta-disulphamate.

After 16alpha-[15F]fluoroestradiol ([18F]FES) has been successfully prepared in an automated module, the synthesis of 16alpha-[18F]fluoroestradiol-3,17beta-disulphamate ([18F]FESDS) is described as a module-assisted one-pot procedure which can provide 10GBq [18F]FESDS with a radiochemical purity better than 99%. The procedure is reliable and reproducible and requires a time of about 90 min. Because of its high sulphatase-inhibitory effect [15F]FESDS is thought to be a new PET tracer to image sites of high sulphatase activity.

Arylsulfatases↗

Synthesis of S-([18F]fluoromethyl)-(+)-McN5652 as a potential PET radioligand for the serotonin transporter.

The present study describes the synthesis of the [18F]fluoromethyl analogue of (+)-McN5652 ([18F]FMe-McN) as a new potential tracer for the serotonin transporter. In vitro binding studies have shown that FMe-McN displays only slightly lower affinity for the serotonin transporter (K(i) = 2.3 +/- 0.1 nM) than (+)-McN5652 (K(i) = 0.72 +/- 0.2 nM). The radiofluorinated tracer [18F]FMe-McN was prepared by reaction of normethyl (+)-McN5652 with the fluoromethylation agent [18F]bromofluoromethane in an overall radiochemical yield of 5 +/- 1% (decay-corrected, related to [18F]fluoride) and with high specific radioactivity (200-2,000 GBq/micromol at the end of synthesis).

Animals↗

Preparation of fluorine-18 labelled sugars and derivatives and their application as tracer for positron-emission-tomography.

The usefulness of 18F-labelled carbohydrates, especially 2-deoxy-2-[18F]fluoro-D-glucose, to study pathophysiological processes in man non-invasively using positron-emission-tomography (PET) led to a widespread investigation of different 18F-labelled sugars and sugar derivatives. In consideration of the short half-life of fluorine-18 (T(1/2) = 110 min) synthetic strategies concerning precursor design, labelling conditions and deprotection of the intermediate compounds were developed to guarantee an efficient high radiochemical yield synthesis for diagnostic purposes. Besides some aspects of medical application of 2-deoxy-2-[18F]fluoro-D-glucose, a few synthetic strategies are described reflecting development work on promising 18F-labelled sugars for diagnostic purposes during the last two decades.

Carbohydrates↗

[Raeder- and Collet-Siccard-Syndrome. Acute pareses of cranial nerves symptomatic of a dissection of internal carotid artery].

Acute cerebral nerve paresis can be caused in many different ways. One of the more rare causes of paresis of one or more neural pathways is dissection of the internal carotid artery. Early diagnosis is important, even with atypical symptoms, since prompt anticoagulative therapy can hinder stroke from embolism due to the dissection. We report on two patients with Raeder's syndrome and Collet-Sicard syndrome resulting from dissection of the internal carotid artery. Besides the cranial and caudal nerves involved in our study, loss of function has also been reported with the sixth to eighth cranial nerves, so that any painful, sudden cranial nerve deficiency can indicate possible carotid dissection.

Acute Disease↗

Relation between brain tissue pO2 and dopamine synthesis of basal ganglia--a 18FDOPA-PET study in newborn piglets.

Perinatal hypoxic-ischemic cerebral injury is a major determinant of neurologic morbidity and mortality in the neonatal period and later in childhood. There is evidence that the dopaminergic system is sensitive to oxygen deprivation. However, the respective enzyme activities have yet not been measured in the living neonatal brain. In this study, we have used 18F-labelled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with positron emission tomography (PET) to estimate the activity of the aromatic amino acid decarboxylase (AADC), the ultimate enzyme in the synthesis of dopamine, in the brain of newborn piglets under normoxic and moderate asphyxial conditions. The study was performed on 8 newborn piglets (2-5 days old). In each piglet PET studies were performed under control conditions and during 2-hour asphyxia. Simultaneously, brain tissue pO2 was recorded, cerebral blood flow (CBF) was measured with colored microspheres and cerebral metabolic rate of oxygen (CMRO2) was determined. Asphyxia was induced by lowering the inspired fraction of oxygen from 0.35 to 0.10 and adding about 6% CO2 to the inspired gas. Asphyxia elicited a more than 3-fold increase of the CBF (p < 0.01) so that CMRO2 remained unchanged throughout the asphyxial period. Despite this, brain tissue pO2 was reduced from 19 +/- 4 mm Hg to 6 +/- 3 mm Hg (p < 0.01). Blood-brain transfer of FDOPA as well as permeability-surface area product (PS) from striatum were unchanged. Striatal synthesis rate of fluoro-dopamine from FDOPA (k3) was, however, significantly increased (p < 0.01). This increase of the AADC activity is associated with reduced brain tissue pO2. Asphyxia-induced CBF increase impedes an alteration of brain oxidative metabolism.

Animals↗

Upregulation of the aromatic amino acid decarboxylase under neonatal asphyxia.

Perinatal hypoxic-ischemic cerebral injury is a major determinant of neurologic morbidity and mortality in the neonatal period and later in childhood. There is evidence that the dopaminergic system is sensitive to asphyxia. However, the respective enzyme activities have not yet been measured in the living neonatal brain. In this study, we have used 18F-labeled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with positron-emission tomography (PET) to estimate the activity of the aromatic amino acid decarboxylase (AADC), the ultimate enzyme in the synthesis of dopamine (DA), in the brain of newborn piglets. Simultaneously, the cerebral blood flow (CBF) was measured with colored microspheres. Asphyxia elicited an up to threefold increase of the CBF. Despite this, the blood-brain transfer of FDOPA as well as the clearance rate constants from brain were unchanged. However, the synthesis rate of FDA from FDOPA was significantly increased in frontal cortex, striatum, and midbrain. This increase of the AADC activity and the decrease of monoamine oxidase activity may contribute to the increase of extracellular DA during asphyxia which is expected to be involved in severe disturbances of neuronal metabolism, e.g., by generating free radicals.

Algorithms↗

Long-distance transport of radionuclides between PET cyclotron and PET radiochemistry.

At the Rossendorf PET Centre the PET cyclotron and the radiochemical laboratories are 500 m away from each other. The distance is bridged by a radionuclide transport system (RATS) whose details such as layout, technical parameters, control system and radiation protection are described along with our experience in long-distance transport of radionuclides.

Carbon Radioisotopes↗

Simultaneous measurement of [18F]FDOPA metabolism and cerebral blood flow in newborn piglets.

Available information on the dopamine (DA) metabolism of the immature brain is rare. In order to establish a useful animal model we have performed PET experiments in anesthetized neonatal pigs using 6-[18F]-fluoro-L-DOPA (FDOPA) as tracer. In this study, we have simultaneously determined the cerebral blood flow and the rate constant of FDOPA conversion by the aromatic amino acid decarboxylase, the ultimate enzyme in the synthesis of dopamine. The estimated values of FDOPA decarboxylation in the basal ganglia were similar to values calculated in adult animals and humans. However, in contrast to those studies a significant decarboxylation was also found in the frontal cortex and the cerebellum. HPLC analysis of brain samples also revealed extensive and rapid metabolism of FDOPA in the five investigated brain regions. At 8 min after tracer injection about 80% of FDOPA was already converted to FDA and its metabolites. Surprisingly, a rather high fraction (16-21%) of [18F]-fluoro-3-methoxytyramine was found which may indicate a low storage capacity of vesicular DA at this perinatal stage. It is suggested that the findings are related to the ontogenetic development of the dopaminergic system. The knowledge of the regulation of the DA metabolism in the immature brain may have implications for the understanding of neurodevelopmental effects of perinatal oxygen deprivation.

Animals↗

Transgenic mice as research tools in neurocarcinogenesis.

Transgenic animal models for neurocarcinogenesis have provided significant insights into the molecular mechanisms underlying carcinogenic processes, including those which affect the nervous system. In view of the very rapid pace of acquisition of knowledge, it is not possible to cover all transgenic mouse models for neural tumors. Instead, this article discusses some of the most important technical innovations for manipulation of the mammalian genome (notably the various methods for targeted genome modifications, as well as the technology for introducing large DNA fragments into the germ line of mice), and presents a selection of the transgenic mouse models which are proving most promising for furthering our understanding of the pathogenetic basis of cancer in the nervous system.

Animals↗

The proto-oncogene c-fos mediates apoptosis in murine T-lymphocytes induced by ionizing radiation and dexamethasone.

Expression of the immediate early response gene c-fos is induced by several cellular and extracellular stress factors including ionizing radiation. We examined the role of c-fos in mediating stress-induced apoptosis of isogenic CD4+ and CD8+ mouse T-lymphocytes differing only in their c-fos status after treatment with ionizing radiation and the synthetic glucocorticoid dexamethasone. The amount of radiation-induced apoptosis was decreased (up to 37%) in the T-lymphocyte population derived from the knockout mice lacking endogenous c-fos compared to the wildtype T-lymphocyte population. The difference in apoptosis induction in T-lymphocytes from wildtype and c-fos knockout mice was even more prominent (up to 55%) after dexamethasone treatment. Comparative experiments were performed with T-lymphocytes from isogenic mouse littermates differing only in the status of the tumor-suppressor gene p53. Whereas p53 plays a primary role in radiation-induced apoptosis, our results suggest that c-fos enhances both p53-dependent radiation- and p53-independent steroid-induced apoptosis in T-lymphocytes.

Animals↗