Biomedical subjects

Stefan Schulz

Publications and source records attributed to Stefan Schulz.

At least 73 records · Page 4Linked to original sources

PubMed2004

Two multiarticulated hydraulic hand prostheses.

PURPOSE: Consumers want new prosthetic hand designs that have increased functionality, better cosmetic appearance, and lower weight. METHODS: New lightweight hands that fulfill these demands can be designed by integrating a hydraulic system with small fluidic actuators at the digit joints. RESULTS: Two different designs of lightweight experimental prosthetic hand are presented. The weight of the first hand is reduced by 50% compared to a conventional prosthetic hand, whereas the functionality of the second hand is increased by additional prehension types. Optionally, a tactile feedback system can be integrated. Due to multiple articulated digits and flexible materials, both hands are able to conform to the shape of an object held. This significantly reduces the necessary grip force and results in stable holding of an object. For a natural appearance, the hands are covered with a cosmetic silicone rubber glove.

Artificial Limbs↗

PubMed2004

A description logics approach to CGPS.

We develop a formal framework by which clinical guidelines and protocols (CGPs) can be partially represented as a set of terminological concept definitions using standard description logics. There are two benefits in pursuing such an approach. First, it provides a foundation for logic-based CGP fusion and collision detection. Second, it allows for the checking of clinical treatment episodes from the EPR against CGPs.

Artificial Intelligence↗

PubMed2003

Dufour gland of the digger wasp Liris niger: structure and developmental and biochemical aspects.

The tubiform Dufour gland in the digger wasp species Liris niger is about 1.0 mm long ( 0.15 mm). An alternating arrangement of longitudinal and circumferential bundles of striated muscle fibers surrounds the gland. The Dufour gland, together with the venom gland, enters the sting base and terminates in the sting. The glandular epithelium is monolayered. Glands about 3 day after imaginal ecdysis have an empty lumen but a thick lining epithelium. The gland cells are characterized by a well-developed vesicular smooth endoplasmic reticulum, sparse rough ER and numerous free ribosomes. They also exhibit several electron-lucent vesicles and autophagic vacuoles. Secretion of electron-dense material via the gland cuticle into the gland lumen is apparent. Glands more than 20 days after imaginal ecdysis display a large lumen and a thin epithelium. The cells show signs of degeneration with numerous cytolytic inclusions. Dufour gland liquid contains numerous polypeptides of molecular weights ranging from 14 to about 200 kDa. In addition the secretion consists predominantly of straight-chain hydrocarbons, accompanied by small amounts of esters. The major hydrocarbons are pentadecane and ( Z)-8-heptadecene. Dufour gland secretion may have several functions: (1). the polypeptides might be involved in the gluing process of the eggs, while (2). the hydrocarbon oils may function as lubricants for the lancets and (3). might soften the secretion, thus allowing easier application of the glue. The lipophilic volatile material (4). might also be involved in pheromonal signaling.

Alkanes↗

PubMed2003

Heterodimerization of substance P and mu-opioid receptors regulates receptor trafficking and resensitization.

The micro-opioid receptor (MOR1) and the substance P receptor (NK1) coexist and functionally interact in nociceptive brain regions; however, a molecular basis for this interaction has not been established. Using coimmunoprecipitation and bioluminescence resonance energy transfer (BRET), we show that MOR1 and NK1 can form heterodimers in HEK 293 cells coexpressing the two receptors. Although NK1-MOR1 heterodimerization did not substantially change the ligand binding and signaling properties of these receptors, it dramatically altered their internalization and resensitization profile. Exposure of the NK1-MOR1 heterodimer to the MOR1-selective ligand [D-Ala2,Me-Phe4,Gly5-ol]enkephalin (DAMGO) promoted cross-phosphorylation and cointernalization of the NK1 receptor. Conversely, exposure of the NK1-MOR1 heterodimer to the NK1-selective ligand substance P (SP) promoted cross-phosphorylation and cointernalization of the MOR1 receptor. In cells expressing MOR1 alone, beta-arrestin directs the receptors to clathrin-coated pits, but does not internalize with the receptor. In cells expressing NK1 alone, beta-arrestin internalizes with the receptor into endosomes. Interestingly, in cells coexpressing MOR1 and NK1 both DAMGO and SP induced the recruitment of beta-arrestin to the plasma membrane and cointernalization of NK1-MOR1 heterodimers with beta-arrestin into the same endosomal compartment. Consequently, resensitization of MOR1-dependent receptor functions was severely delayed in coexpressing cells as compared with cells expressing MOR1 alone. Together, our findings indicate that MOR1 by virtue of its physical interaction with NK1 is sequestered via an endocytotic pathway with delayed recycling and resensitization kinetics.

Arrestins↗

PubMed2003

CXCR4 regulates interneuron migration in the developing neocortex.

The chemotactic factors directing interneuron migration during cerebrocortical development are essentially unknown. Here we identify the CXC chemokine receptor 4 (CXCR4) in interneuron precursors migrating from the basal forebrain to the neocortex and demonstrate that stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for isolated striatal precursors. In addition, we show that CXCR4 is present in early generated Cajal-Retzius cells of the cortical marginal zone. In mice with a null mutation in CXCR4 or SDF-1, interneurons were severely underrepresented in the superficial layers and ectopically placed in the deep layers of the neocortex. In contrast, the submeningeal positioning of Cajal-Retzius cells was unaffected. Thus, our findings suggest that SDF-1, which is highly expressed in the embryonic leptomeninx, selectively regulates migration and layer-specific integration of CXCR4-expressing interneurons during neocortical development.

Animals↗

PubMed2003

Inhibitory role of the somatostatin receptor SST2 on the intracrine-regulated cell proliferation induced by the 210-amino acid fibroblast growth factor-2 isoform: implication of JAK2.

The fibroblast growth factor (FGF)-2 isoform of 210 amino acids (HMW FGF-2) contains a nuclear localization sequence (NLS) and is targeted to the nucleus. This FGF-2 isoform allows cells to grow in low serum concentrations through still unknown mechanisms called intracrine regulations. Different peptide hormones and cytokines have been found to be nuclearized through NLS and to induce cell proliferation. The existence of molecules acting as negative regulators of the intracrine-induced cell growth has not been explored. Pancreatic cells AR4-2J were stably transfected to express selectively the HMW FGF-2. We demonstrated that activation of the somatostatin receptor subtype SST2 by the somatostatin analogue RC-160 in serum-deprived medium inhibits the mitogenic effect of the HMW FGF-2, without affecting growth of control cells. The signaling pathway implicates Galphai/JAK2/SHP-1. The Galphai inhibitor pertussis toxin and the JAK2 inhibitor AG490 abrogate the inhibitory effect of RC-160 on HMW FGF-2-induced cell growth. Co-immunoprecipitation studies demonstrate the constitutive association of JAK2 and SHP-1, and RC-160 induces a rapid activation of both proteins followed by the dissociation of the complex. AG490 prevents the RC-160 induced SHP-1 activation indicating the implication of JAK2 in this process. JAK2 and SHP-1 are immunoprecipitated with SST2 in basal conditions indicating the existence of a functional signaling complex at the receptor level. In summary, these data provide the following evidence: 1) the intracrine-induced proliferation can be reversed by extracellular acting polypeptides; 2) SST2 inhibitory signaling may involve the JAK2/SHP-1 pathway.

Animals↗

PubMed2003

ADP-ribosylation factor-dependent phospholipase D2 activation is required for agonist-induced mu-opioid receptor endocytosis.

Agonist exposure of many G protein-coupled receptors induces a rapid receptor phosphorylation and uncoupling from G proteins. Resensitization of these desensitized receptors requires endocytosis and subsequent dephosphorylation. Using a yeast two-hybrid screen, the rat mu-opioid receptor (MOR1, also termed MOP) was found to be associated with phospholipase D2 (PLD2), a phospholipid-specific phosphodiesterase located in the plasma membrane, which has been implicated in the formation of endocytotic vesicles. Coimmunoprecipitation experiments in HEK293 cells coexpressing MOR1 and PLD2 confirmed that MOR1 constitutively interacts with PLD2. Treatment with the mu receptor agonist DAMGO ([d-Ala(2), Me Phe(4), Glyol(5)]enkephalin) led to an increase in PLD2 activity, whereas morphine, which does not induce MOR1 receptor internalization, failed to induce PLD2 activation. The DAMGO-mediated PLD2 activation was inhibited by brefeldin A, an inhibitor of ADP-ribosylation factor (ARF) but not by the protein kinase C (PKC) inhibitor calphostin C indicating that opioid receptor-mediated activation of PLD2 is ARF- but not PKC-dependent. Furthermore, heterologous stimulation of PLD2 by phorbol ester led to an accelerated internalization of the mu-opioid receptor after both DAMGO and morphine exposure. Conversely the inhibition of PLD2-mediated phosphatidic acid formation by 1-butanol or overexpression of a negative mutant of PLD2 prevented agonist-mediated endocytosis of MOR1. Together, these data suggest that PLD2 play a key role in the regulation of agonist-induced endocytosis of the mu-opioid receptor.

1-Butanol↗

PubMed2003

New terpene hydrocarbons from the alligatoridae (crocodylia, reptilia).

The contents of the paracloacal gland secretions of the alligatorids Alligator mississippiensis, A. sinensis, Paleosuchus palpebrosus, and P. trigonatus were investigated. Novel acyclic hydrocarbon terpenes with a rare trisubstituted 2,4-diene system were identified in the secretions of A. sinensis, P. palpebrosus, and P. trigonatus. The structures of the monoterpene (2E,4E)-3,7-dimethyl-2,4-octadiene (9) and the sesquiterpene (2E,4E,7S)-3,7,11-trimethyl-2,4-dodecadiene (14) were proven by synthesis and gas chromatography on a chiral phase. Several other new terpenes (11, 16, 17, 18, 19, and 20) related to these components also were present in the secretions, as well as the known compounds myrcene (6), (E)-beta-farnesene (4), (E)-beta-springene (3), squalene (5), cembrene A (1), and 11,12-dihydrocembren-10-one (2).

Alligators and Crocodiles↗

PubMed2003

Chemical analysis of volatiles emitted by Pinus svlvestris after induction by insect oviposition.

Gas chromatography-mass spectrometry analyses of the headspace volatiles of Scots pine (Pinus sylvestris) induced by egg deposition of the sawfly Diprion pini were conducted. The odor blend of systemically oviposition-induced pine twigs. attractive for the eulophid egg parasitoid Chrysonotomyia ruforum, was compared to volatiles released by damaged pine twigs (control) that are not attractive for the parasitoid. The mechanical damage inflicted to the control twigs mimicked the damage by a sawfly female prior to egg deposition. The odor blend released by oviposition-induced pine twigs consisted of numerous mono- and sesquiterpenes, which all were also present in the headspace of the artificially damaged control twigs. A quantitative comparison of the volatiles from oviposition-induced twigs and controls revealed that only the amounts of (E)-beta-farnesene were significantly higher in the volatile blend of the oviposition-induced twigs. Volatiles from pine twigs treated with jasmonic acid (JA) also attract the egg parasitoid. No qualitative differences were detected when comparing the composition of the headspace of JA-treated pine twigs with the volatile blend of untreated control twigs. JA-treated pine twigs released significantly higher amounts of (E )-beta-farnesene. However, the JA treatment induced a significant increase of the amount of further terpenoid components. The release of terpenoids by pine after wounding, egg deposition, and JA treatment is discussed with special respect to (E)-beta-farnesene.

Adaptation, Physiological↗

PubMed2003

Somatostatin receptor subtypes in human pheochromocytoma: subcellular expression pattern and functional relevance for octreotide scintigraphy.

The stable somatostatin analog octreotide has been successfully used for imaging and treatment of a variety of human tumors. In pheochromocytoma, data on somatostatin receptor subtyping have thus far been sparse. Pheochromocytomas often express more than one somatostatin receptor, and it is uncertain by which receptor subtype the functional responses of octreotide are mediated. Here, we have examined somatostatin receptor protein expression in a panel of 52 pheochromocytomas from 35 randomly selected patients by immunostaining with specific polyclonal anti-sst(1-5) and monoclonal mouse anti-SS-14 antibodies. Staining pattern, distribution and subcellular localization of somatostatin receptor subtypes were investigated. Seventeen patients received (111)In-octreotide scintigraphy. Although the vast majority of tumors (90%) showed positive immunohistochemical staining for sst(3), immunoreactive sst(2A) receptors were only seen in 13 tumors (25%). All other somatostatin receptor subtypes were less frequently detected. Interestingly, among sst(3)-positive tumors strikingly different subcellular distributions of immunoreactive sst(3) receptors were observed. In most cases, immunoreactive sst(3) receptors were distributed throughout the cytosol. Scintigraphic localization of tumors larger than 1 cm in diameter was always successful in the presence of immunoreactive sst(2A) receptors. In the absence of sst(2A), true-positive octreotide scintigraphy was only seen in the presence of membrane-associated sst(3) immunoreactivity. Our findings suggest that selective expression of functional membrane-associated sst(3) receptors is sufficient for high tracer uptake during octreotide scintigraphy in a subgroup of human pheochromocytomas. These tumors may represent a potential target treatment with somatostatin receptor agonists with improved sst(3) activity.

Adrenal Gland Neoplasms↗

PubMed2003

Using cross-lingual information to cope with underspecification in formal ontologies.

Description logics and other formal devices are frequently used as means for preventing or detecting mistakes in ontologies. Some of these devices are also capable of inferring the existence of inter-concept relationships that have not been explicity entered into an ontology. A prerequisite, however, is that this information can be derived from those formal definitions of concepts and relationships which are included within the ontology. In this paper, we present a novel algorithm that is able to suggest relationships among existing concepts in a formal ontology that are not derivable from such formal definitions. The algorithm exploits cross-lingual information that is implicity present in the collection of terms used in various languages to denote the concepts and relationships at tissue. By using a specific experimental design, we are able to quantify the impact of cross-lingual information in coping with underspecification in formal ontologies.

Algorithms↗

PubMed2003

Logic-based remodeling of the Digital Anatomist Foundational Model.

This paper describes a development cycle for the engineering of large knowledge bases: A graphical tool is used for editing and the content is transformed into a logic-based representation language. This representation is used to check the consistency of the knowledge base as well as to facilitate the reviewing process. Showing the usefulness of this approach, aspects of the Digital Anatomist Foundational Model will be transformed into a Description Logics representation. We introduce a special modeling technique to account for the representation of the complex part/whole relationships in the biomedical domain.

Anatomy↗

PubMed2003

Cross-language MeSH indexing using morpho-semantic normalization.

We consider three alternative procedures for the automatic indexing of medical documents using MeSH thesaurus identifiers as target units (document descriptors). Rather than considering complete words as the starting point of the indexing procedure, we here propose morphologically plausible subwords as basic units from which MeSH terms are derived. We describe the morphological segmentation and normalization procedures, as well as the mappings from subwords to MeSH terms, and discuss results from an evaluation carried out on a German-language corpus.

Abstracting and Indexing↗

PubMed2002

Identification of cells expressing somatostatin receptor 2 in the gastrointestinal tract of Sstr2 knockout/lacZ knockin mice.

Somatostatin is found in neurons and endocrine cells in the gastrointestinal tract. The actions of somatostatin are mediated by a family of G-protein-coupled receptors that compose five subtypes (SSTR1-5), each of which is encoded by a separate gene. lacZ "knockin" mice, in which the reporter gene lacZ was engineered into the genomic locus of Sstr2 by gene targeting, were used to examine the expression pattern of Sstr2 and identify potential targets for neurally released and hormonal somatostatin in the gastrointestinal tract. In the body of the stomach, a large proportion of epithelial cells and subpopulations of myenteric neurons expressed Sstr2. Double- or triple-labeling with antisera to H(+)K(+)ATPase (to identify parietal cells) and/or histidine decarboxylase (to identify enterochromaffin-like [ECL] cells) combined with beta-galactosidase staining revealed that both parietal cells and ECL cells expressed Sstr2, and these two cell types accounted for almost all of the Sstr2-expressing epithelial cells. Somatostatin inhibits gastric acid secretion. The presence of SSTR2 on both parietal and ECL cells suggests that somatostatin acting on SSTR2 may reduce acid secretion by both acting directly on parietal cells and by reducing histamine release from ECL cells. In the small and large intestine, subpopulations of neurons in the myenteric and submucosal plexuses expressed Sstr2, and many of the Sstr2-expressing myenteric neurons also showed SSTR2(a) immunostaining. Most of Sstr2-expressing neurons in the myenteric plexus showed nitric oxide synthase (NOS) immunoreactivity. Previous studies have shown that NOS neurons are descending interneurons and anally projecting, inhibitory motor neurons. Thus, somatostatin acting at SSTR2 receptors on NOS neurons might modulate descending relaxation.

Animals↗

PubMed2002

MEDSYNDIKATE--a natural language system for the extraction of medical information from findings reports.

MEDSYNDIKATE is a natural language processor, which automatically acquires medical information from findings reports. In the course of text analysis their contents is transferred to conceptual representation structures, which constitute a corresponding text knowledge base. MEDSYNDIKATE is particularly adapted to deal properly with text structures, such as various forms of anaphoric reference relations spanning several sentences. The strong demands MEDSYNDIKATE poses on the availability of expressive knowledge sources are accounted for by two alternative approaches to acquire medical domain knowledge (semi)automatically. We also present data for the information extraction performance of MEDSYNDIKATE in terms of the semantic interpretation of three major syntactic patterns in medical documents.

Confidence Intervals↗

PubMed2002

Cyclic chiral silyl derivatives for the determination of the absolute configuration of aliphatic diols by gas chromatography.

[reaction: see text] Chiral bidentate silyl reagents have been developed for the GC analysis of aliphatic 1,3- and 1,4-diols. These reagents react with the diols to cyclic siloxanes, which allow the determination of their enantiomeric composition even in complex mixtures. The absolute configuration of 4,6-nonadecanediol 7, occurring in the lipids of sunflower pollen, has been determined to be (4S,6R) by comparison with derivatized synthetic enantiomers.

Chemotactic Factors↗

PubMed2002

A dual role for the SDF-1/CXCR4 chemokine receptor system in adult brain: isoform-selective regulation of SDF-1 expression modulates CXCR4-dependent neuronal plasticity and cerebral leukocyte recruitment after focal ischemia.

The chemoattractant stromal cell-derived factor-1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) are key modulators of immune function. In the developing brain, SDF-1 is crucial for neuronal guidance; however, cerebral functions of SDF-1/CXCR4 in adulthood are unclear. Here, we examine the cellular expression of SDF-1 isoforms and CXCR4 in the brain of mice receiving systemic lipopolysaccharide (LPS) or permanent focal cerebral ischemia. CXCR4 mRNA was constitutively expressed in cortical and hippocampal neurons and ependymal cells. Hippocampal neurons targeted the CXCR4 receptor to their somatodendritic and axonal compartments. In cortex and hippocampus, CXCR4-expressing neurons exhibited an overlapping distribution with neurons expressing SDF-1 transcripts. Although neurons synthesized SDF-1alpha mRNA, the SDF-1beta isoform was selectively expressed by endothelial cells of cerebral microvessels. LPS stimulation dramatically decreased endothelial SDF-1beta mRNA expression throughout the forebrain but did not affect neuronal SDF-1alpha. After focal cerebral ischemia, SDF-1beta expression was selectively increased in endothelial cells of penumbral blood vessels and decreased in endothelial cells of nonlesioned brain areas. In the penumbra, SDF-1beta upregulation was associated with a concomitant infiltration of CXCR4-expressing peripheral blood cells, including macrophages. Neuronal SDF-1alpha was transiently downregulated and neuronal CXCR4 was transiently upregulated in the nonlesioned cerebral cortex in response to ischemia. Although endothelial SDF-1beta may control cerebral infiltration of CXCR4-carrying leukocytes during cerebral ischemia, the neuronal SDF-1alpha/CXCR4 system may contribute to ischemia-induced neuronal plasticity. Thus, the isoform-specific regulation of SDF-1 expression modulates neurotransmission and cerebral infiltration via distinct CXCR4-dependent pathways.

Animals↗

PubMed2002

Expression changes of somatostatin receptor subtypes sst2A, sst2B, sst3 and sst4 after a cortical contusion trauma in rats.

The neuropeptide somatostatin acts as a neuromodulator in the CNS in a predominantly inhibitory manner. In this study, an ipsilateral cortical and hippocampal damage in the brain of adult rats was induced by a cortical contusion trauma in order to examine subsequent changes of expression of different somatostatin receptor subtypes (sst). By using subtype specific antibodies we found a clear decline of expression level for sst2A, sst2B, sst3 and sst4 subtypes in the pyramidal cell layer of the ipsilateral hippocampus. Nissl staining revealed that this decline of expression level is due to cell death of sst expressing neurons within the first 48 h after trauma. Additionally we found a progressive infiltration of sst4 positive cells into regions of cortical and hippocampal damage. The number of these cells increases strikingly within the first 3 days after trauma and it seems that their morphology changes from a round to an astrocyte-like shape. Moreover, sst4 and sst2A positive cells accumulate in the ipsilateral ependym and pyramidal-like cells expressing sst4 were found beneath the damaged CA3 pyramidal layer. Taken together, after trauma we found deterioration of sst positive neurons and an additional activation of sst4 and sst2A expressing cells the final fate of which has to be elucidated further.

Animals↗