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Biomedical subjects

D Meier

Publications and source records attributed to D Meier.

At least 19 recordsLinked to original sources
PubMed2006

Reactions, characterization and uptake of ammoxidized kraft lignin labeled with 15N.

Ammoxidation of kraft lignin was carried out in a Parr reactor using (15)NH(3) as the main nitrogen source. Reaction parameters were set up until a total nitrogen content of approximately 13 wt.% in lignin was achieved, in accordance with conditions of previous studies. Analytical tools such as FTIR, Py-GC/MS, and solid state NMR were used in this research. The nature of nitrogen bondings is discussed. The incorporation of the (15)N from ammoxidized lignin was followed in pumpkins (Zucchini cucurbita pepo L.) by means of (15)N emission spectroscopy.

Ammonia↗
PubMed2006

Molecular networks orchestrating GALT development.

During evolution, the development of secondary lymphoid organs has evolved as a strategy to promote adaptive immune responses at sites of antigen sequestration. Mesenteric lymph nodes (LNs) and Peyer's patches (PPs) are localized in proximity to mucosal surfaces, and their development is coordinated by a series of temporally and spatially regulated molecular events involving the collaboration between hematopoietic, mesenchymal, and, for PPs, epithelial cells. Transcriptional control of cellular differentiation, production of cytokines as well as adhesion molecules are mandatory for organogenesis, recruitment of mature leukocytes, and lymphoid tissue organization. Similar to fetal and neonatal organogenesis, lymphoid tissue neoformation can occur in adult individuals at sites of chronic stimulation via cytokines and TNF-family member molecules. These molecules represent new therapeutic targets to manipulate the microenvironment during autoimmune diseases.

Animals↗
PubMed2006

Trading spectral separation at 3T for acquisition speed in multi spin-echo spectroscopic imaging.

Fast multiple spin-echo spectroscopic imaging, also called turbo spectroscopic imaging (TSI), may be enhanced in terms of acquisition speed by taking advantage of the higher spectral separation afforded at higher field strength and by further combining it with sensitivity encoding (SENSE). This article demonstrates the possibilities of this approach at 3T, resulting in scan-time reductions of up to a factor of 10. High-resolution, in vivo, single- and multiple-section spectroscopic imaging data are presented.

Aspartic Acid↗
PubMed2005

Parameters affecting the display of antibodies on phage.

Despite the fact that a multitude of antibody phage display libraries has been built, systematic comparisons of critical design parameters are rare. Here we analysed the impact of various factors on the performance of the phage display system. First, we compared several vector designs for the display of Fab fragments of antibodies. Bicistronic as well as monocistronic expression of the antibody/pIII operon and vectors using fd-pIII as well as LC-pIII fusions were tested. Further, we evaluated the influence of glucose on the promoter induction. We compared monovalent versus oligovalent display of the antibody fragments and we used antibody fragments with different folding efficiency to assess the influence of the individual antibody sequences on the performance of the system. Finally, both phage display efficiency and yield of soluble Fab fragments were analysed. The significant differences found for phage yield, display of Fabs on the phage and expression of soluble Fabs suggest to use a bicistronic vector with an fd-fragment-pIII fusion for the construction of future Fab phage display libraries.

Animals↗
PubMed2004

Cortical activation resulting from painless vibrotactile dental stimulation measured by functional magnetic resonance imaging (FMRI).

There have been few investigations on hemodynamic responses in the human cortex resulting from dental stimulation. Identification of cortical areas involved in stimulus perception may offer new targets for pain treatment. This initial study aimed at establishing a cortical map of dental representation, based on non-invasive fMRI measurements. Five right-handed subjects were studied. Eight maxillary and 8 mandibular teeth were stimulated after the vibratory perception threshold was determined for each tooth. Suprathreshold stimulation was repeated thrice per session, in a total of three sessions performed on three consecutive days. Statistical inference on cluster level identified increased blood-oxygen-level-dependent signal during vibratory dental stimulation, primarily in the insular cortex bilaterally and in the supplementary motor cortex. No significant brain activation was observed in the somatosensory cortex with this stimulation protocol. These results agree with previous findings obtained from invasive direct electrical cortical stimulation of the human insula.

Adult↗
PubMed2003

Effects of vigabatrin on brain GABA+/Cr signals in focus-distant and focus-near brain regions monitored by 1H-NMR spectroscopy.

The new antiepileptic drug vigabatrin (VGB) increases gamma-aminobutyric acid (GABA) in the brain. We compared GABA+/Cr signals measured focus-near and focus-distant and correlated it with the degree of response to VGB. Brain GABA+/Cr signals were measured in 17 epileptic patients in structurally normal appearing tissue by nuclear proton magnetic resonance (1H-NMR) spectroscopy using a special editing sequence for GABA. In 11 patients the measurements were done in brain areas distant to focus and in six near to focus. Full-responders (seizure reduction of >or=50% at the end of the treatment phase) and partial-responders (seizure reduction of >or=50% at the end of the first month of treatment but <or=50% at end of treatment) had lower GABA+/Cr signals in the hemisphere with the epileptogenic focus and increases of the GABA+/Cr signals with VGB. Non-responders (seizure reduction of <or=50%) had no side difference in the GABA+/Cr signals before treatment and no increase during treatment. These observations were made in structurally normal appearing tissue near to the focus and distant to the focus. A side difference in brain GABA+/Cr signal between the epileptogenic and non-epileptogenic hemisphere before VGB treatment correlates with an improved seizure control under VGB treatment regardless whether the measurement is done focus-near or focus-distant.

Adolescent↗
PubMed2002

Pramipexole in patients with Parkinson's disease and marked drug resistant tremor: a randomised, double blind, placebo controlled multicentre study.

OBJECTIVE: To compare the tremorlytic properties of pramipexole, a non-ergoline dopamine agonist to those of placebo as add on medication in patients with Parkinson's disease. METHODS: Eighty four patients with early or advanced Parkinson's disease and marked, drug resistant tremor under a stable and optimised antiparkinsonian medication were included in a double blind, randomised, placebo controlled, multicentre study and assigned to add on treatment (7 week dose titration interval, 4 week maintenance period) with either pramipexole (n=44) or placebo (n=40) as adjunct. The primary end point was the absolute change in tremor score, defined as the sum of tremor related items (16, 20, 21) of the unified Parkinson's disease rating scale (UPDRS) in "on" periods. Secondary end points included the percentage change in tremor score, the absolute and percentage changes in long term EMG tremor registration, and the change in tremor self rating scales. Safety and tolerability were assessed on the basis of adverse events, laboratory tests, ECG, and vital signs. RESULTS: Pramipexole was significantly superior to placebo with a difference between treatment groups in the mean absolute change in tremor score of -4.4 (95% confidence interval (95% CI) -6.2 to -2.5) (p<0.0001), corresponding to a difference in the mean percentage change of -34.7% in favour of pramipexole. The secondary end points were consistent with the significant change in tremor score and provided further evidence for the benefit of pramipexole compared with placebo. Long term EMG registration as an objective measure showed a difference in mean absolute change in tremor occurrence of -15.2% (95%CI -21.4 to -9.0) (p<0.0001), and a difference in the mean percentage change of -45.7% in favour of pramipexole. The treatment effects increased during dose titration and remained stable during the 4 week maintenance dose period until the end of the study. The average daily pramipexole dose during maintenance was 4.1 (SD 0.9) mg. Safety analysis showed an increased rate of fatigue, insomnia, nausea, abdominal pain, and headache under pramipexole, comparable with previous studies. CONCLUSION: Pramipexole proved to be an effective agent for patients with Parkinson's disease and drug resistant tremor.

Administration, Oral↗
PubMed2001

Pharmacodynamic profile of the M1 agonist talsaclidine in animals and man.

In functional pharmacological assays, talsaclidine has been described as a functionally preferential M1 agonist with full intrinsic activity, and less pronounced effects at M2- and M3 receptors. In accordance with this, cholinomimetic central activation measured in rabbits by EEG recordings occurred at a 10 fold lower dose than that inducing predominantly M3-mediated side effects. This pharmacological profile is also reflected in the clinical situation: Both in healthy volunteers and in Alzheimer patients--unlike after unspecific receptor stimulation through cholinesterase inhibitors--the mainly M3-mediated gastrointestinal effects (like nausea and vomiting) were not dose-limiting. Rather, sweating and hypersalivation, mediated through muscarinic receptors, occurred dose-dependently and were finally dose-limiting. In contrast to talsaclidine, sabcomeline had a less pronounced functional M1 selectivity in pharmacological assays. This was also shown in anaesthetized guinea pigs where sabcomeline alone induced bronchoconstriction, and in the rabbit EEG where central activation and cholinergic side effects occurred in the same dose range. Neither drug, however, showed convincing improvement of cognitive functions in patients with mild-to-moderate Alzheimer's disease. This asks for a reassessment of the muscarinic hypothesis for the treatment of this disease.

Adrenergic beta-Antagonists↗
PubMed2001

Sensitivity-encoded spectroscopic imaging.

Sensitivity encoding (SENSE) offers a new, highly effective approach to reducing the acquisition time in spectroscopic imaging (SI). In contrast to conventional fast SI techniques, which accelerate k-space sampling, this method permits reducing the number of phase encoding steps in each phase encoding dimension of conventional SI. Using a coil array for data acquisition, the missing encoding information is recovered exploiting knowledge of the distinct spatial sensitivities of the individual coil elements. In this work, SENSE is applied to 2D spectroscopic imaging. Fourfold reduction of scan time is achieved at preserved spectral and spatial resolution, maintaining a reasonable SNR. The basic properties of the proposed method are demonstrated by phantom experiments. The in vivo feasibility of SENSE-SI is verified by metabolic imaging of N-acetylaspartate, creatine, and choline in the human brain. These results are compared to conventional SI, with special attention to the spatial response and the SNR.

Brain↗
PubMed2001

Slow-release effect of N-functionalized kraft lignin tested with Sorghum over two growth periods.

Biomass production of fodder sorghum (Sorghum sp.) has been tested in a field trial over two harvesting periods under natural meteorological conditions using ammoxidized kraft lignin (AKL) as a slow-release fertilizer and urea as conventional reference. In the course of the first growth cycle, plants treated with urea gave higher biomass yields because of the better solubility of urea in the initial phase. However, during the second cycle AKL treated plants performed better than urea treated sorghum, indicating that nitrogen from AKL became readily available.

Biomass↗
PubMed2001

Effects of vigabatrin on brain GABA+/CR signals in patients with epilepsy monitored by 1H-NMR-spectroscopy: responder characteristics.

PURPOSE: Vigabatrin (VGB) is a new antiepileptic drug that increases the human brain gamma-aminobutyric acid (GABA) level by irreversibly inhibiting GABA transaminase. Although some patients respond to VGB with a significant seizure reduction, others do not. The aim of this study was to identify possible responders before or in an early phase of VGB treatment by measuring the GABA and homocarnosine contaminated with macromolecules/creatine and phosphocreatine ratio (GABA+/Cr) signal by means of proton-nuclear magnetic resonance (1H NMR) spectroscopy. METHODS: Measurements were performed immediately before and after a titration period of 1 month (2 g/day during the past 2 weeks). A third measurement followed a maintenance period of 3 months (2 or 3 g/day). In 14 patients with drug-resistant temporal lobe epilepsy and 3 patients with occipital lobe epilepsy, GABA+/Cr was measured in the ipsilateral (i.e., epileptogenic) hemisphere and contralateral (i.e., nonepileptogenic) hemisphere in a volume of 8 cm3. RESULTS: Depending on the therapeutic efficacy of VGB, we defined three groups: (a) full responders (n = 7), (b) nonresponders (n = 7), and (c) partial responders (n = 3). The nonresponders had no significant change in the GABA+/Cr signal during the treatment compared with baseline. The full responders had a significant increase of the GABA+/Cr signal during the whole treatment phase and a lower ipsilateral level at baseline. The partial responders had also a lowered ipsilateral GABA+/Cr signal at baseline and an increase during treatment but a decrease when the seizures started again. CONCLUSIONS: Responders to VGB could be identified by a lower ipsilateral baseline GABA+/Cr signal and a steeper increase during VGB treatment. However, it was not possible to predict the duration of the response (full versus partial responder) with these criteria.

Adolescent↗
PubMed2001

[Corrected normal values for serum ACE by genotyping the deletion-/insertion-polymorphism of the ACE gene].

BACKGROUND: In sarcoidosis, serum ACE is widely recognised as a marker of disease activity. Since 1990 a deletion-/insertion polymorphism of the ACE gene is known and a correlation between the genotypes of this polymorphism and serum ACE levels has been observed. Homzygotes for the deletion allele (DD) have the highest levels and homozygotes for the insertion allele (II) the lowest. Heterozygote (DI) persons show intermediate levels. The extent of this influence varies in populations of different ethnic origin. In a large cohort of healthy individuals from North of Germany, genotype-based normal ranges for serum ACE were determined for the population of Germany for the first time. METHODS: In 262 healthy individuals the genotype of the ACE D/I gene polymorphism was determined from genomic DNA by a PCR method. In addition, in serum samples of all these individuals ACE level was measured with a kinetic test. RESULTS: The genotype DD was found in 29.4 % of the individuals examined, the genotype DI in 49.6 % and the genotype II in 21.0 %, respectively. These results are similar to those found in previous investigations in other populations of Central European origin. The mean serum ACE levels (95 % confidence interval) in individuals with the genotypes DD, DI and II are 59.8 U/l (31.8 - 87.8), 47.7 U/l (18.6 - 76.8) and 32.2 U/l (13.7 - 50.7), respectively. Without taking the genotype into account, the average value is 48.0 U/l (15.0 - 80.9). Differences between all genotype groups are highly significant (p < 0.0001). CONCLUSIONS: In sarcoidosis patients, the determination of this ACE gene polymorphism once in the course of the disease allows a better interpretation of the serum ACE levels measured.

Acetylcholinesterase↗
PubMed2001

Early prediction of irreversible brain damage after ischemic stroke at CT.

PURPOSE: To assess the capability of computed tomography (CT) in the prediction of irreversible ischemic brain damage and its association with the clinical course within 6 hours of stroke onset. MATERIALS AND METHODS: Serial CT scans obtained within 6 hours of stroke onset, at 22-96 hours (median, 1 day), and at 2-36 days (median, 7 days) after symptom onset in 786 patients with ischemic stroke were prospectively studied, and follow-up CT scans were used as the reference. Clinical variables were assessed prospectively and independently of CT evaluation. RESULTS: The specificity and positive predictive value of ischemic edema at baseline CT for brain infarcts were 85% (95% CI: 77%, 91%) and 96% (95% CI: 94%, 98%), respectively. Sensitivity and negative predictive values were 64% (95% CI: 60%, 67%) and 27% (95% CI: 23%, 32%), respectively. Patients without early CT findings were less severely affected (P<.001), developed smaller infarcts (P<.001), had fewer intracranial bleeding events (P<.001), and had a better clinical outcome at 90 days (P<.001) compared with patients with hypoattenuating brain tissue at early CT. CONCLUSION: After ischemic stroke, x-ray hypoattenuation at CT is highly specific for irreversible ischemic brain damage if detection occurs within the first 6 hours. Patients without hypoattenuating brain tissue have a more favorable clinical course.

Adolescent↗
PubMed2001

[Medical-surgical evaluation of living liver donors].

The living related liver segment transplantation is an established procedure in liver transplantation for children and adults. The evaluation of a possible donor should consider the following subjects: (1) Assessment of organ quality by imaging of size and anatomy of the liver and exclusion of the unknown liver diseases by labority analysis and liver biopsy. (2) Risk assessment of the potential organ donor by exclusion of preexisting diseases increasing the risk of surgery, including thromboembolic risk factors. (3) Psychological evaluation. Nevertheless the evaluation procedure should by practicable, convenient for the organ donor and cost effective. This can be realized by a stepwise program.

Adult↗
PubMed2000

Expression of stress protein gp96, a tumor rejection antigen, in human colorectal cancer.

Preparations of stress protein gp96 from tumor cells are active as tumor vaccines by eliciting immune responses against mixtures of individual tumor peptide antigens which are complexed to gp96. Due to the individual antigenicity of tumors, a vaccine consisting of tumor-derived gp96 has to be prepared individually for each patient from autologous tumor tissue. So far, gp96 expression by human tumors has not been analyzed. Here, we report stable and mostly homogenous expression of gp96 by colorectal cancer, which was enhanced compared to surrounding tumor stroma in 70% to 80% of colorectal cancer specimens. Fewer non-metastatic than metastatic primary cancer specimens showed enhanced gp96 expression. Glucose deprivation increased gp96 protein and RNA expression in the human colon cancer cell line HT-29 in accordance with the role of gp96 as a glucose-regulated stress protein. Additionally, TNF-alpha, interferons and other cytokines induced an increase of gp96 RNA expression in HT-29 cells, suggesting that gp96 expression by colorectal cancer cells can be influenced by different methods of immunomodulation. The stable and homogenous expression of gp96 in 19 primary and metastatic colorectal cancer specimens and the up-regulation of gp96 in colon cancer cells by glucose deprivation point to an essential role of this stress protein in colorectal cancer, presumably by protecting against hostile conditions of the tumor micro-environment like glucose deprivation. In view of these results, loss of gp96 expression by colorectal cancer cells as an immune escape mechanism is unlikely.

Colorectal Neoplasms↗
PubMed2000

Genomic alterations in well-differentiated gastrointestinal and bronchial neuroendocrine tumors (carcinoids): marked differences indicating diversity in molecular pathogenesis.

Neuroendocrine tumors (carcinoids) are a heterogeneous group of neoplasms arising from the diffuse neuroendocrine system. Genetic changes underlying their tumorigenesis are primarily unknown. We used comparative genomic hybridization to screen 32 well-differentiated neuroendocrine tumors (21 gastrointestinal and 11 bronchial) and three associated metastases for genomic alterations. There were striking differences of genomic imbalances between the two subgroups of neuroendocrine tumors. Losses of chromosome 18q and 18p were shown in eight (38%) and seven (33%), respectively, out of 21 gastrointestinal tumors and in none of the 11 bronchial tumors. Conversely, deletions of 11q occurred in four of 11 (36%) bronchial tumors but only in one gastrointestinal tumor. These comparative genomic hybridization findings were confirmed by interphase cytogenetics. Our data indicate that neuroendocrine tumors of the two subgroups develop via different molecular pathways. Inactivation of one or several tumor suppressor genes on chromosome 18 may be important for the biological behavior of gastrointestinal tumors, whereas gene inactivation on 11q seems to be associated with tumor development of the bronchi.

Adult↗