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Biomedical subjects

Andreas Schmid

Publications and source records attributed to Andreas Schmid.

At least 37 records · Page 2Linked to original sources

Synthesis of micrometer-sized silica-stabilized polystyrene latex particles.

Micrometer-sized silica-stabilized polystyrene latexes have been readily prepared by alcoholic dispersion polymerization using a 13 or 22 nm commercial alcoholic silica sol as the sole stabilizing agent. These resulting surfactant-free polystyrene particles have relatively narrow particle size distributions and contain surprisingly low levels of silica (</=1.1% by mass), as judged by disk centrifuge photosedimentometry and thermogravimetry, respectively. Transmission electron microscopy studies indicate that the silica sol is located exclusively at the surface of the polystyrene latex particles at submonolayer coverage. The polymerization of styrene in the absence of the silica sol leads to macroscopic precipitation of the polystyrene. Hence, the presence of silica sol is essential for the colloid stability of these latexes, which presumably involves a charge stabilization mechanism.

Letter↗

Low-temperature fabrication of dye-sensitized solar cells by transfer of composite porous layers.

Dye-sensitized solar cells have established themselves as a potential low-cost alternative to conventional solar cells owing to their remarkably high power-conversion efficiency combined with 'low-tech' fabrication processes. As a further advantage, the active layers consisting of nanoporous TiO2 are only some tens of micrometres thick and are therefore in principle suited for flexible applications. However, typical flexible plastic substrates cannot withstand the process temperatures of up to 500 degrees C commonly used for sintering the TiO2 nanoparticles together. Even though some promising routes for low-temperature sintering have been proposed, those layers cannot compete as regards electrical properties with layers obtained with the standard high-temperature process. Here we show that by a lift-off technique, presintered porous layers can be transferred to an arbitrary second substrate, and the original electrical properties of the transferred porous layers are maintained. The transfer process is greatly assisted by the application of composite layers comprising nanoparticles and nanorods.

Journal Article↗

Direct electrochemical regeneration of monooxygenase subunits for biocatalytic asymmetric epoxidation.

We report the first example of direct electrochemical regeneration of a flavin-dependent monooxygenase for asymmetric epoxidation catalysis. It is shown that electrochemical regeneration of the oxygenase subunit of the multicomponent styrene monooxygenase is sufficient to perform enantiospecific S-epoxidation of various styrene derivatives. Kinetic bottlenecks of the novel electroenzymatic reaction are identified. This work opens up new alternatives for asymmetric oxyfunctionalization catalysis.

Catalase↗

Four different subunits are essential for expressing the synaptic glutamate receptor at neuromuscular junctions of Drosophila.

Three ionotropic glutamate receptor subunits, designated GluRIIA, GluRIIB, and GluRIII, have been identified at neuromuscular junctions of Drosophila. Whereas GluRIIA and GluRIIB are redundant for viability, it was shown recently that GluRIII is essential for both the synaptic localization of GluRIIA and GluRIIB and the viability of Drosophila. Here we identify a fourth and a fifth subunit expressed in the neuromuscular system, which we name GluRIID and GluRIIE. Both new subunits we show to be necessary for survival. Moreover, both GluRIID and GluRIIE are required for the synaptic expression of all other glutamate receptor subunits. All five subunits are interdependent for receptor function, synaptic receptor expression, and viability. This indicates that synaptic glutamate receptors incorporate the GluRIII, GluRIID, and GluRIIE subunit together with either GluRIIA or GluRIIB at the Drosophila neuromuscular junction. At this widely used model synapse, the assembly of four different subunits to form an individual glutamate receptor channel may thus be obligatory. This study opens the way for a further characterization of in vivo glutamate receptor assembly and trafficking using the efficient genetics of Drosophila.

Animals↗

Feasibility and early results of interstitial intensity-modulated HDR/PDR brachytherapy (IMBT) with/without complementary external-beam radiotherapy and extended surgery in recurrent pelvic colorectal cancer.

BACKGROUND: A new multimodality treatment concept consisting of extended resection and postoperative fractionated intensity-modulated interstitial brachytherapy (IMBT) was introduced for pelvic recurrence of colorectal carcinoma. PATIENTS AND METHODS: 46 patients received extended resection and single plastic tubes were sutured directly onto the tumor bed. IMBT was started within 2 weeks postoperatively with a median dose of 24.5 Gy (5-35 Gy). Patients were treated either with high-dose-rate brachytherapy (HDR; n = 23) or with pulsed-dose-rate brachytherapy (PDR; n = 23). 25 patients received complementary 45-Gy external-beam irradiation (EBRT) to the pelvic region after explanting the plastic tubes. RESULTS: Median follow-up was 20.6 months (7-107 months) and mean patient survival 25.7 +/- 25.8 months (median 17, range 1-107 months). After 5 years overall survival, disease-free survival and local control rate were 23%, 20% and 33%, significantly influenced by the resectional state. There was a trend in favor of PDR compared to HDR, which reached statistical significance in patients who had not received additional EBRT. CONCLUSION: The combination of extended surgery and postoperative interstitial IMBT is feasible and offers effective interdisciplinary treatment of recurrent colorectal cancer. In this small and inhomogeneous cohort of patients PDR seems to be more effective than HDR, particularly when application of complementary EBRT is not possible. None of the patients who required resection of distant metastasis survived > 2 years in this study.

Brachytherapy↗

Lipid profile in spinal cord-injured women with different injury levels.

Background. In dependence on their injury level, male subjects with spinal cord injury (SCI) exhibit a less favorable lipoprotein profile than control persons. The impairment of the sympathetic nervous system and the fact that persons with spinal cord injury are subject to extreme physical inactivity may have an influence on their lipid profile and lipoprotein(a) concentration. It has been shown that sex-specific differences in hormonal regulation are responsible for differences in lipoprotein levels between nondisabled men and women. However, the role of hormones on lipoprotein levels has not been investigated in female subjects with spinal cord injury. Methods. Therefore, we performed a detailed investigation regarding the lipid profile in 32 premenopausal women with spinal cord injury ranging from tetraplegia to low paraplegia and in 36 control subjects. VO(2max) was determined by a wheelchair ergometry with stepwise increase in work load. Result. VO(2max) was significantly higher in paraplegics than in tetraplegics but significantly lower than in control subjects. Paraplegics had significantly higher low-density lipoprotein levels than both tetraplegics and control persons. The lipid profile of female tetraplegics was characterized by elevated triglycerides. An association between high-density lipoprotein levels and spinal cord injury or the level of the injury was not observed. No significant difference in lipoprotein(a) was found within SCI individuals as well as between SCI individuals and control persons indicating the predominant genetic determination of lipoprotein(a) and the thus related cardiovascular risk. Conclusion. Despite the extreme reduction of VO(2max), the assumed physical inactivity and low serum catecholamine levels due to the impairment of the sympathetic nervous system, female tetraplegic persons did not show an adverse lipoprotein profile with respect to high-density lipoprotein cholesterol levels. If the higher low-density lipoprotein cholesterol concentrations in female with spinal cord injury with low lesion levels or the elevated TG levels in female tetraplegics bare relevance with respect to an increased cardiovascular risk in this population needs to be clarified in further longitudinal investigations.

Adult↗

Glutamate receptor dynamics organizing synapse formation in vivo.

Insight into how glutamatergic synapses form in vivo is important for understanding developmental and experience-triggered changes of excitatory circuits. Here, we imaged postsynaptic densities (PSDs) expressing a functional, GFP-tagged glutamate receptor subunit (GluR-IIA(GFP)) at neuromuscular junctions of Drosophila melanogaster larvae for several days in vivo. New PSDs, associated with functional and structural presynaptic markers, formed independently of existing synapses and grew continuously until reaching a stable size within hours. Both in vivo photoactivation and photobleaching experiments showed that extrasynaptic receptors derived from diffuse, cell-wide pools preferentially entered growing PSDs. After entering PSDs, receptors were largely immobilized. In comparison, other postsynaptic proteins tested (PSD-95, NCAM and PAK homologs) exchanged faster and with no apparent preference for growing synapses. We show here that new glutamatergic synapses form de novo and not by partitioning processes from existing synapses, suggesting that the site-specific entry of particular glutamate receptor complexes directly controls the assembly of individual PSDs.

Animals↗

Prediction of the adaptability of Pseudomonas putida DOT-T1E to a second phase of a solvent for economically sound two-phase biotransformations.

The strain Pseudomonas putida DOT-T1E was tested for its ability to tolerate second phases of different alkanols for their use as solvents in two-liquid-phase biotransformations. Although 1-decanol showed an about 10-fold higher toxicity to the cells than 1-octanol, the cells were able to adapt completely to 1-decanol only and could not be adapted in order to grow stably in the presence of a second phase of 1-octanol. The main explanation for this observation can be seen in the higher water and membrane solubility of 1-octanol. The hydrophobicity (log P) of a substance correlates with a certain partitioning of that compound into the membrane. Combining the log P value with the water solubility, the maximum membrane concentration of a compound can be calculated. With this simple calculation, it is possible to predict the property of an organic chemical for its potential applicability as a solvent for two-liquid-phase biotransformations with solvent-tolerant P. putida strains. Only compounds that show a maximum membrane concentration of less than 400 mM, such as 1-decanol, seem to be tolerated by these bacterial strains when applied in supersaturating concentrations to the medium. Taking into consideration that a solvent for a two-liquid-phase system should possess partitioning properties for potential substrates and products of a fine chemical synthesis, it can be seen that 1-decanol is a suitable solvent for such biotransformation processes. This was also demonstrated in shake cultures, where increasing amounts of a second phase of 1-decanol led to bacteria tolerating higher concentrations of the model substrate 3-nitrotoluene. Transferring this example to a 5-liter-scale bioreactor with 10% (vol/vol) 1-decanol, the amount of 3-nitrotoluene tolerated by the cells is up to 200-fold higher than in pure aqueous medium. The system demonstrates the usefulness of two-phase biotransformations utilizing solvent-tolerant bacteria.

1-Octanol↗

Suitability of recombinant Escherichia coli and Pseudomonas putida strains for selective biotransformation of m-nitrotoluene by xylene monooxygenase.

Escherichia coli JM101(pSPZ3), containing xylene monooxygenase (XMO) from Pseudomonas putida mt-2, catalyzes specific oxidations and reductions of m-nitrotoluene and derivatives thereof. In addition to reactions catalyzed by XMO, we focused on biotransformations by native enzymes of the E. coli host and their effect on overall biocatalyst performance. While m-nitrotoluene was consecutively oxygenated to m-nitrobenzyl alcohol, m-nitrobenzaldehyde, and m-nitrobenzoic acid by XMO, the oxidation was counteracted by an alcohol dehydrogenase(s) from the E. coli host, which reduced m-nitrobenzaldehyde to m-nitrobenzyl alcohol. Furthermore, the enzymatic background of the host reduced the nitro groups of the reactants resulting in the formation of aromatic amines, which were shown to effectively inhibit XMO in a reversible fashion. Host-intrinsic oxidoreductases and their reaction products had a major effect on the activity of XMO during biocatalysis of m-nitrotoluene. P. putida DOT-T1E and P. putida PpS81 were compared to E. coli JM101 as alternative hosts for XMO. These promising strains contained an additional dehydrogenase that oxidized m-nitrobenzaldehyde to the corresponding acid but catalyzed the formation of XMO-inhibiting aromatic amines at a significantly lower level than E. coli JM101.

Biodegradation, Environmental↗

Scientific considerations for physiological evaluations of elite athletes.

This case describes the physiological maturation from ages 21 to 28 yr of the bicyclist who has now become the six-time consecutive Grand Champion of the Tour de France, at ages 27-32 yr. Maximal oxygen uptake (Vo(2max)) in the trained state remained at approximately 6 l/min, lean body weight remained at approximately 70 kg, and maximal heart rate declined from 207 to 200 beats/min. Blood lactate threshold was typical of competitive cyclists in that it occurred at 76-85% Vo(2max), yet maximal blood lactate concentration was remarkably low in the trained state. It appears that an 8% improvement in muscular efficiency and thus power production when cycling at a given oxygen uptake (Vo(2)) is the characteristic that improved most as this athlete matured from ages 21 to 28 yr. It is noteworthy that at age 25 yr, this champion developed advanced cancer, requiring surgeries and chemotherapy. During the months leading up to each of his Tour de France victories, he reduced body weight and body fat by 4-7 kg (i.e., approximately 7%). Therefore, over the 7-yr period, an improvement in muscular efficiency and reduced body fat contributed equally to a remarkable 18% improvement in his steady-state power per kilogram body weight when cycling at a given Vo(2) (e.g., 5 l/min). It is hypothesized that the improved muscular efficiency probably reflects changes in muscle myosin type stimulated from years of training intensely for 3-6 h on most days.

Bicycling↗

Silicone embolism syndrome: a case report, review of the literature, and comparison with fat embolism syndrome.

Liquid silicone is an inert material that is utilized for cosmetic procedures by physicians as well as illegally by nonmedical personnel. We present a case report and collated clinical findings of 32 other patients who were hospitalized after illegal silicone injections. Symptoms and signs of the "silicone syndrome" included dyspnea, fever, cough, hemoptysis, chest pain, hypoxia, alveolar hemorrhage, and altered consciousness. Bilateral patchy alveolar infiltrates were present on the chest radiographs, and silicone pulmonary emboli were detected in all the patients. The patients could be divided into two groups based on the initial presentation and clinical outcome. Twenty-seven patients in group 1 presented predominantly with respiratory symptoms, and 93% of patients were discharged home within 3 weeks. Six patients (group 2) presented with severe neurologic findings, and experienced rapid deterioration and 100% mortality. The clinical findings after silicone embolism are very similar to the published reports of fat embolism, including hypoxemia in 92% of patients with silicone embolism (patients with fat embolism, 56 to 96%), dyspnea in 88% of patients (patients with fat embolism, 56 to 75%), fever in 70% of patients (patients with fat embolism, 23 to 67%), alveolar hemorrhage in 64% of patients (patients with fat embolism, 66%), neurologic symptoms in 33% of patients (patients with fat embolism, 22 to 86%), petechiae in 18% of patients (patients with fat embolism, 20 to 50%), chest pain in 15% of patients (patients with fat embolism, 26%), and mortality in 24% of patients (patients with fat embolism, 5 to 20%). The similarities among the mode of injury to the lung, the clinical findings, and the high incidence of alveolar hemorrhage suggest a common pathogenesis of silicone and fat embolism syndromes. We discuss the possibility that the activation of the coagulation system may be important in the development of these clinical syndromes.

Adult↗

Tyrosine phosphatase PTP1B interacts with TRPV6 in vivo and plays a role in TRPV6-mediated calcium influx in HEK293 cells.

This study investigates the role of tyrosine phosphorylation and dephosphorylation in the regulation of the Ca(2+) permeant TRPV6 channel. HEK293 cells co-transfected with TRPV6 and the tyrosine phosphatase PTP1B show a constitutive Ca(2+) entry which was independent of tyrosine phosphorylation under resting conditions. Following depletion of intracellular Ca(2+) stores, TRPV6-mediated Ca(2+) entry could be increased in the presence of a tyrosine phosphatase inhibitor (bis-(N,N-dimethyl-hydroxamido) hydroxo-vanadate; DMHV). Inhibition of Src-kinases completely abolished DMHV-induced increase in TRPV6-mediated Ca(2+) influx. Co-transfection with Src led to tyrosine phosphorylation of TRPV6 which could be dephosphorylated by PTP1B. In vivo interaction of TRPV6 with PTP1B was visualized using the bimolecular fluorescence complementation (BiFC) method and proved by co-immunoprecipitation of both proteins. These data indicate that tyrosine phosphorylation is involved in the regulation of the TRPV6 channel protein.

Animals↗

Process implementation aspects for biocatalytic hydrocarbon oxyfunctionalization.

Oxidoreductases catalyze a large variety of regio-, stereo-, and chemoselective hydrocarbon oxyfunctionalizations, reactions, which are important in industrial organic synthesis but difficult to achieve by chemical means. This review summarizes process implementation aspects for the in vivo application of the especially versatile enzyme class of oxygenases, capable of specifically introducing oxygen from molecular oxygen into a large range of organic molecules. Critical issues such as reaching high enzyme activity and specificity, product degradation, cofactor recycling, reactant toxicity, and substrate and oxygen mass transfer can be overcome by biochemical process engineering and biocatalyst engineering. Both strategies provide a growing toolset to facilitate process implementation, optimization, and scale-up. Major advances were achieved via heterologous overexpression of oxygenase genes, directed evolution, metabolic engineering, and in situ product removal. Process examples from industry and academia show that the combined use of different concepts enables efficient oxygenase-based whole-cell catalysis of various commercially interesting reactions such as the biosynthesis of chiral compounds, the specific oxyfunctionalization of complex molecules, and also the synthesis of medium-priced chemicals. Better understanding of the cell metabolism and future developments in both biocatalyst and bioprocess engineering are expected to promote the implementation of many and various industrial biooxidation processes.

Biotechnology↗

Palliation of metastatic gastric cancer: impact of preoperative symptoms and the type of operation on survival and quality of life.

Patients with advanced, incurable gastric cancer may present with mild symptoms or require immediate therapeutic intervention. The influence of the intensity of preoperative symptoms on postoperative survival and quality of life (QoL) was evaluated in a palliative setting. In a historical cohort analysis of 492 patients with gastric cancer treated between 1992 and 2001, a total of 169 (34.4%) patients had incurable disease (i.e., pTxNxM1). Patients were classified as having major symptoms if they presented with upper gastrointestinal bleeding (i.e., hematemesis or bloody stools), gastric inlet or outlet obstruction (i.e., symptomatic and endoscopically proven stenosis), or perforation caused by the tumor. All other patients were defined as having minor symptoms. QoL was assessed prospectively using the EORTC questionnaire. The questionnaire was given to the patients before operation, before discharge, and 3 months after operation; and it was analyzed by the Mann-Whitney U-test. Survival, demographic data, and histopathologic characteristics were assessed and analyzed by the log-rank test and the chi(2) test, respectively. Of the 169 patients, 75 (44.3%) presented with major symptoms and 94 (55.7%) with minor symptoms. The distribution of patients undergoing resection or exploration was comparable for the two groups [major: 61 (81.5%)/14 (18.5%); minor: 77 (81.9%)/17 (18.1%)]. Despite comparable demographic and histopathologic characteristics with equal hospital mortality and morbidity (14.6% vs. 8.5%/49.3% vs. 40.4%), the median survival rates in two groups were 4 and 6 months, respectively ( p < 0.05). This was not influenced by the type of operation. QoL was not different in patients with major or minor symptoms before operation or 3 months thereafter. However, preoperative symptoms such as nausea/vomiting and melena were rated significantly higher in patients with major symptoms. In patients with incurable gastric cancer the preoperative intensity of symptoms has a significant impact on survival and QoL, which is not influenced by the operation. The necessity of surgery in patients with minor symptoms requires careful consideration.

Aged↗

Quality of life associated with surgery for esophageal cancer: differences between collar and intrathoracic anastomoses.

Postoperative survival and complication rates have traditionally been the standard parameters of outcome after oncologic surgery. In tumors with poor patient survival, such as esophageal cancer, studies about quality of life are rare. The objectives of this study were to assess outcomes in terms of quality of life in patients with esophageal cancer when investigating differences between two surgical reconstructive procedures: intrathoracic anastomosis and collar anastomosis. A total of 108 patients with esophageal cancer had undergone surgery for esophageal cancer in our department from 1992 to 2000. Median survival was 36 months with no significant differences between patients undergoing collar or intrathoracic anastomosis. After determining the survival status, questionnaires on quality of life were sent to all patients 1 to 2 years after surgery. We received data from 46 patients. The responders were divided into groups of intrathoracic anastomosis ( n = 24) and collar anastomosis ( n = 22). Patients with the collar anastomosis showed significantly better physical and social functioning and global health status. From the viewpoint of postoperative quality of life, reflux-related symptoms were the major problem for patients with an intrathoracic anastomosis. These symptoms cause significant insomnia and impair social and physical function. The study showed that assessing quality of life with specific and general instruments is helpful for determining the differences between surgical procedures where standard parameters such as survival have their limitations.

Adult↗

A glutamate receptor-interacting protein homolog organizes muscle guidance in Drosophila.

During Drosophila embryogenesis, developing muscles extend growth-cone-like structures to navigate toward specific epidermal attachment sites. Here, we show that the homolog of Glutamate Receptor-Interacting Proteins (DGrip) acts as a key component of proper muscle guidance. Mutations in dgrip impair patterning of ventral longitudinal muscles (VLMs), whereas lateral transverse muscles (LTMs) that attach to intrasegmental attachment sites develop normally. Myoblast fusion, stabilization of muscle contacts, and general muscle function are not impaired in the absence of DGrip. Instead, the proper formation of cellular extensions during guidance fails in dgrip mutant VLMs. DGrip protein concentrates at the ends of VLMs while these muscles guide toward segment border attachment sites. Conversely, LTMs overexpressing DGrip form ectopic cellular extensions that can cause attachment of these muscles to other muscles at segment borders. Our data suggest that DGrip participates in the reception of an attractive signal that emanates from the epidermal attachment sites to direct the motility of developing muscles. This dgrip phenotype should be valuable to study mechanistic principles of Grip function.

Animals↗

Biotransformation in double-phase systems: physiological responses of Pseudomonas putida DOT-T1E to a double phase made of aliphatic alcohols and biosynthesis of substituted catechols.

Pseudomonas putida strain DOT-T1E is highly tolerant to organic solvents, with a logP(ow) (the logarithm of the partition coefficient of a solvent in a two-phase water-octanol system of > or =2.5. Solvent tolerant microorganisms can be exploited to develop double-phase (organic solvent and water) biotransformation systems in which toxic substrates or products are kept in the organic phase. We tested P. putida DOT-T1E tolerance to different aliphatic alcohols with a logP(ow) value between 2 and 4, such as decanol, nonanol, and octanol, which are potentially useful in biotransformations in double-phase systems in which compounds with a logP(ow) around 1.5 are produced. P. putida DOT-T1E responds to aliphatic alcohols as the second phase through cis-to-trans isomerization of unsaturated cis fatty acids and through efflux of these aliphatic alcohols via a series of pumps that also extrude aromatic hydrocarbons. These defense mechanisms allow P. putida DOT-T1E to survive well in the presence of high concentrations of the aliphatic alcohols, and growth with nonanol or decanol occurred at a high rate, whereas in the presence of an octanol double-phase growth was compromised. Our results support that the logP(ow) of aliphatic alcohols correlates with their toxic effects, as octanol (logP(ow) = 2.9) has more negative effects in P. putida cells than 1-nonanol (logP(ow) = 3.4) or 1-decanol (logP(ow) = 4). A P. putida DOT-T1E derivative bearing plasmid pWW0-xylE::Km transforms m-xylene (logP(ow) = 3.2) into 3-methylcatechol (logP(ow) = 1.8). The amount of 3-methylcatechol produced in an aliphatic alcohol/water bioreactor was 10- to 20-fold higher than in an aqueous medium, demonstrating the usefulness of double-phase systems for this particular biotransformation.

Biotransformation↗