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Biomedical subjects

T Seeger

Publications and source records attributed to T Seeger.

At least 19 recordsLinked to original sources
PubMed2005

Innovative strategies for PBPC mobilization.

Stem cell transplantation, whether autologous or allogeneic, improves the outcome of patients with a number of hematologic malignancies or solid tumors. A relevant proportion of these patients are excluded from this treatment because sufficient numbers of hematopoietic stem cells cannot be obtained by standard cytokine-assisted mobilization. In this article we review the physiology of peripheral blood progenitor cell (PBPC) mobilization and discuss the role of adhesion molecules, such as integrins and selectins, chemokines and their ligands, such as SDF-1alpha and CXCR4, and proteolytic enzymes. Based on this knowledge, several innovative pharmacologic approaches have been proposed to boost the stem cell harvest. Some of them (CTCE, C3a receptor agonist and GrobetaT) are still subject of pre-clinical development, others, such as chemokine receptor ligand AMD3100, have recently been introduced in clinical trials and already deliver promising results. It appears possible to harvest PBPC successfully in poor mobilizers and to cut down the number of collections required in the remaining PBPC donors.

Anti-HIV Agents↗
PubMed2005

[Short communication: ultrasonographic examination of the abomasal position in dairy cows during the peripartal period].

The objective of this study was to document the abomasal position during the peripartal period by ultrasonographic measurement to get more data about the topographic dynamic. In 12 dairy cows the abomasal position was measured daily from the 5th day before calving up to the 5th day after calving by a transabdominal ultrasonographic examination (5 MHz convex transducer). The abomasal position was described by means of 3 measured distances: (a) the distance between the cranial margin of the abomasum and the xiphoid cartilage, (b) the distance between the right margin of the abomasum and the median line and (c) the distance between the left margin of the abomasum and the median line. Prepartal the abomasal position was different from the position during the postpartal period. Its position was more cranially (p < 0.05) and more right laterally (p < 0.05). The left margin was not detectable at the left side of the mid-line ante partum. Directly after calving the left margin of the abomasum was found left of the linea alba (p < 0.05). These results show that there is a great influence of the gravid uterus on the abomasal position. The abomasum is positioned more cranially and more right lateral during the end of pregnancy. This position changes immediately after calving.

Abomasum↗
PubMed2002

Nanotube composites: novel SiO2 coated carbon nanotubes.

A novel route to nanocomposites consisting of multi-walled carbon nanotubes (MWNTs) embedded in amorphous SiOx is reported; the material has been characterised by high resolution transmission electron microscopy (HRTEM) and high resolution electron energy loss spectroscopy (HREELS); for the first time, and based on our observations, we propose theoretical models accounting for stable SiOx/tube interfaces using density functional based tight binding (DFTB).

Journal Article↗
PubMed2001

Muscarinic activation of inwardly rectifying K(+) conductance reduces EPSPs in rat hippocampal CA1 pyramidal cells.

1. To determine how acetylcholine (ACh) modulates the somatodendritic processing of EPSPs, we performed whole-cell recordings from CA1 pyramidal cells of hippocampal slices and examined the effect of the cholinergic agonist, carbachol (CCh), on alpha-amino-3-hydroxy-5-methyl isoxazole-4-propionate (AMPA) EPSPs, miniature EPSPs, and EPSP-like waveforms evoked by brief dendritic glutamate pulses (glutamate-evoked postsynaptic potentials, GPSPs). 2. Although CCh is known to enhance the intrinsic excitability of the neuron in several ways, activation of atropine-sensitive (muscarinic) receptors on the apical dendrite or the soma of CA1 pyramidal cells consistently reduced the amplitude of EPSPs and GPSPs. 3. Cholinergic inhibition of evoked and simulated EPSP waveforms displayed considerable voltage dependence, with the amplitude of the postsynaptic potentials progressively declining with membrane hyperpolarization indicating the involvement of an inwardly rectifying current. 4. Extracellular Ba(2+) (200 microM) and tertiapin (30 nM), a novel and selective blocker of G protein-activated, inwardly rectifying K(+) (GIRK) channels, completely blocked the effect of CCh on GPSP amplitude. 5. Muscarinic reduction of GPSPs was not sensitive to the M1 receptor-preferring antagonist, pirenzepine, but was suppressed by the M2 receptor-preferring antagonist, methoctramine, and by the allosteric M2 receptor antagonist, gallamine. 6. In voltage-clamp recordings, CCh induced an ion current displaying inward rectification in the hyperpolarizing direction, which was identified as a GIRK current based on its sensitivity to low Ba(2+) and tertiapin. Its pharmacological profile paralleled that of the cholinergic GPSP reduction. 7. We link the observed reduction of postsynaptic potentials to the cholinergic activation of a GIRK conductance, which serves to partially shunt excitatory synaptic input.

Animals↗
PubMed2000

Enhancement of persistent Na+ current by sea anemone toxin (ATX II) exerts dual action on hippocampal excitability.

We used anemone toxin II (ATX II) to study how a selective enhancement of persistent Na+ current (INaP) would affect the excitability of CA1 pyramidal neurons in the hippocampal slice. In whole-cell recordings from CA1 cell somata, local application of ATX II (10 microM) into the stratum pyramidale invariably depolarized the neurons and produced sustained burst discharges with depolarizing plateau potentials of variable amplitude and length. However, the strong excitatory action of ATX II, observed on the single cell level, was not mirrored in field potential recordings from the same hippocampal subfield. The amplitude of the electrically evoked population spike declined, reflecting the decreased availability of fast Na+ channels, and the intracellulary recorded burst discharges were not detected by the field electrode. The lacking synchronization of cellular bursting activity was seen during both local and bath application of ATX II, suggesting that the toxin, in addition to promoting burst discharges of individual neurons, simultaneously dampens network excitability. In fact, ATX II reduced afferent fibre volleys (reflecting axonal excitability) and field excitatory postsynaptic potentials (EPSPs) in a similar fashion. As the expression of different Na+ channel subtypes appears to be compartmentalized within hippocampal neurons, we propose that point mutations leading to pathologically enhanced INaP might exert quite opposite effects, depending on the type and location of the Na+ channel affected. Whereas alterations of somatodendritic Na+ channels would give rise to bursting activity, alterations of axonal Na+ channels would primarily decrease network excitability.

Action Potentials↗
PubMed1996

CP-154,526: a potent and selective nonpeptide antagonist of corticotropin releasing factor receptors.

Here we describe the properties of CP-154,526, a potent and selective nonpeptide antagonist of corticotropin (ACTH) releasing factor (CRF) receptors. CP-154,526 binds with high affinity to CRF receptors (Ki < 10 nM) and blocks CRF-stimulated adenylate cyclase activity in membranes prepared from rat cortex and pituitary. Systemically administered CP-154,526 antagonizes the stimulatory effects of exogenous CRF on plasma ACTH, locus coeruleus neuronal firing and startle response amplitude. Potential anxiolytic activity of CP-154,526 was revealed in a fearpotentiated startle paradigm. These data are presented in the context of clinical findings, which suggest that CRF is hypersecreted in certain pathological states. We propose that a CRF antagonist such as CP-154,526 could affirm the role of CRF in certain psychiatric diseases and may be of significant value in the treatment of these disorders.

Acoustic Stimulation↗
PubMed1996

Influence of gelatin matrices cross-linked with transglutaminase on the properties of an enclosed bioactive material using beta-galactosidase as model system.

Transglutaminase (protein-glutamine: amine gamma-glutamyltransferase, EC 2.3.2.13) from Streptoverticillium mobaraense has been used to stabilize immobilisates produced with beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23) from Aspergillus oryzae and acid-processed gelatins of different qualities as support. The isopeptide level of N epsilon-(gamma-L-glutamyl)-L-lysine bonds formed by transglutaminase was determined to estimate their influence on the kinetic properties of the enclosed beta-galactosidase. An HPLC procedure using precolumn derivatization of the gelatin hydrolysates with FMOC-chloride was chosen which permits the analysis of cross-linked lysine with satisfactory precision. Depending on the gelatin quality, the degree of cross-links necessary for the transformation of gelatin into an insoluble protein was in the range 0.3-32.3% of the available lysine residues. beta-Galactosidase was entrapped in the gelatin matrices with a yield of 8-46% of the initial activity. Long reaction times for cross-linking were due to low yields rather than to the number of isopeptide bonds. Repeated use of the immobilisates did not lead to an appreciable loss of activity. The Vmax of beta-galactosidase were diminished by immobilization caused by a tighter package of the protein chains rather than by the extent of cross-links, while the obtained Km values of the free enzyme and the immobilisates were quite similar. Also, the pH and temperature of optima of the free enzyme and the gelatin immobilisates differ only slightly. The data suggest that the immobilization procedure only moderately affects the activity of enzymes catalysing the reaction of a small compound if gelatin with high jelly strength is cross-linked in a 10% solution with transglutaminase.

Aspergillus oryzae↗
PubMed1995

Cocultures of fetal and adult cardiomyocytes yield rhythmically beating rod shaped heart cells from adult rats.

Different models of isolated cardiomyocytes are generally used for biochemical, biophysical, and pharmacological studies. Fetal cardiomyocytes can be easily cultured for several weeks regaining their ability for rhythmical and synchronous contractions. For investigations, differentiated myocytes derived from adult hearts are closer to the in situ situation. Unfortunately, these cells at best exhibit irregular and asynchronous contractions at very low frequencies. Already 1 d after seeding calcium-tolerant rod-shaped adult cardiomyocytes on a suitable substrate, the differentiated cells begin to dedifferentiate forming a confluent monolayer. After 7-10 d their beating activities are like those of fetal cells. Therefore, we tried to combine the advantages of both cell types to achieve fully differentiated cardiomyocytes, rod-shaped and rhythmically beating, isolated from adult hearts. Using contractile fetal cells as a substrate for the adult cardiomyocytes, freshly seeded differentiated adult myocytes are paced by the contraction frequency of the fetal monolayer. As a consequence, the rod-shaped adult cardiomyocytes reach frequencies of more than 140 cycles/min without external electrical stimulation. This model enables us to study cardiomyocytes in a state very similar to the in situ situation with respect to morphology, integrity, and contractile behavior.

Animals↗
PubMed1995

The anti-emetic effects of CP-99,994 in the ferret and the dog: role of the NK1 receptor.

1. The selective NK1 receptor antagonist, CP-99,994, produced dose-related (0.1-1.0 mg kg-1, s.c.) inhibition of vomiting and retching in ferrets challenged with central (loperamide and apomorphine), peripheral (CuSO4) and mixed central and peripheral (ipecac, cisplatin) emetic stimuli. 2. Parallel studies with the enantiomer, CP-100,263 (1 mg kg-1, s.c.), which is > 1,000 fold less potent as a NK1 antagonist, indicated that it was without significant effect against CuSO4, loperamide, cisplatin and apomorphine-induced emesis. Against ipecac, it inhibited both retching and vomiting, expressing approximately 1/10th the potency of CP-99,994. 3. The 5-HT3 receptor antagonist, tropisetron (1 mg kg-1, s.c.) inhibited retching and vomiting to cisplatin and ipecac, but not CuSO4 or loperamide. 4. CP-99,994 (1 mg kg-1, i.v.) blocked retching induced by electrical stimulation of the ventral abdominal vagus without affecting the cardiovascular response, the apnoeic response to central vagal stimulation or the guarding and hypertensive response to stimulation of the greater splanchnic nerves. CP-99,994 (1 mg kg-1, i.v.) did not alter baseline cardiovascular and respiratory parameters and it failed to block the characteristic heart rate, blood pressure and respiratory rate/depth changes in response to i.v. 2-methyl-5-HT challenge (von Bezold-Jarisch reflex). 5. Using in vitro autoradiography, [3H]-substance P was shown to bind to several regions of the ferret brainstem with the density of binding in the nucleus tractus solitarius being much greater than in the area postrema. This binding was displaced by CP-99,994 in a concentration-related manner. 6. In dogs, CP-99,994 (40 micrograms kg-1 bolus and 300 micrograms kg-1 h-1, i.v.) produced statistically significant reductions in vomiting to CuSO4 and apomorphine as well as retching to CuSO4. 7. Together, these studies support the hypothesis that the NK1 receptor antagonist properties of CP-99,994 are responsible for its broad spectrum anti-emetic effects. They also suggest that CP-99,994 acts within the brainstem, most probably within the nucleus tractus solitarius although the involvement of the area postrema could not be excluded.

Animals↗
PubMed1995

[Radioiodine therapy of funcitonal autonomy using the functional autonomous volume].

In order to determine the effective radiation dose to be delivered by 131I in functional autonomy we have used the functional autonomous volume calculated from the global 99mTc thyroid uptake under exogenous or endogenous suppression before and 3 to 7 months after treatment. The radiation dose to the autonomous volume was calculated retrospectively in 131 patients with unifocal, multifocal and disseminated autonomy (75 hyperthyroid, 56 euthyroid) who received 131I treatment of 200-300 Gy to the total volume of the gland. It could be shown that at least 350 Gy to the autonomous volume are required to reach the desired effect of treatment which was dependent only on the radiation dose delivered to the functional autonomous volume.

Follow-Up Studies↗
PubMed1994

[Clinical and radiological results of distal radius fractures].

We report retrospective analysis of results of conservative and operative methods of distal radial fractures, which was carried out to control our treatment methods. Three hundred and ninety-three patients were treated from 1. 7. 1991 to 1. 7. 1992, 361 (91.9%) were followed up to 14 months with average age of 60.1 years (16 to 92 years). Three hundred and twenty-seven patients (90.6%) were treated by conservative methods, 9 (2.5%) by percutaneous pinning, 21 (5.8%) by transfixation through bases of metacarpal bones and 4 (1.1%) by ventral supporting plates. Clinical examination showed 69.6% good, 24.9% fair and 5.5% poor results. Radiological results according to AO-scheme were compared with clinical results, and 70% clinical results correlated with radiological results. Our results show that comminuted and displaced intraarticular fractures AO-classification C 2, C 3 are indications of transfixation and A 3 and some exceptional cases of C 1 are indications of percutaneous pinning.

Adolescent↗
PubMed1993

[Speech perception in children fitted with Nucleus mini system 22 implants].

Currently there are over 380 european children implanted with the Nucleus device. A battery of speech perception tests has been adapted and translated into German, French and English by Cochlear AG to evaluate the benefits of the cochlear implant for european children. The tests evaluate a hierarchy of auditory skills classified into four levels including: detection of speech sounds, speech pattern identification; speech identification and speech recognition. A child's auditory-visual skills are also assessed. Over 100 children randomly selected from participating clinics have been assessed postoperatively with these measures and the results analyzed. These children are representative of the diversity amongst the european child population in terms of etiology of deafness, onset of deafness, duration of deafness and experience with the implant. All children were able to score significantly above chance for the first two perceptual tests. Test results for this group of children suggest that children with a later onset and shorter duration of deafness tend to perform better on some auditory tasks than children deafened earlier in life and for a longer period of time. Furthermore it appears that the children's performance on these tests improves with increasing implant experience.

Age Factors↗
PubMed1990

An initial three-component pharmacophore for specific serotonin-3 receptor ligands.

With computer modeling, an initial three-component pharmacophore for specific 5-HT3 receptor ligands ICS-205-930 (1), ondansetron (2), zacopride (3), and 3-[2-(guanidinylmethyl)-4-thiazolyl]indol (4) has been identified. Two parts represent electrostatic interactions, one as a hydrogen-bond-donating interaction and the other as a hydrogen-bond-accepting interaction. The third part is represented by a plane in which the lipophilic aromatic groups align. The generation of the pharmacophore relies on the interactions of these ligands with probe atoms representative of a possible hydrogen-bond donor or hydrogen-bond acceptor within the receptor. A carboxylate oxygen was used as a hydrogen-bond-accepting probe and a serine-like hydroxyl was utilized as a hydrogen-bond-donating probe.

Animals↗