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Biomedical subjects

S Schulz

Publications and source records attributed to S Schulz.

At least 127 records · Page 7Linked to original sources
PubMed1998

Opioid withdrawal activates MAP kinase in locus coeruleus neurons in morphine-dependent rats in vivo.

Opioid dependence is widely believed to result from neuroadaptations in specific brain regions. However, the precise molecular mechanisms underlying these adaptations are not yet clear. Our aim was to explore the role of mitogen-activated protein kinase (MAPK) in mu opioid receptor signalling in vivo. Using anti-phospho MAPK antibodies, activated MAPK was detected in cortical neurons (layers II/III), median eminence, amygdaloid and hypothalamic nuclei in untreated animals. Dense nuclear and cytoplasmic staining was observed resulting in full visualization of processes in these cells. Chronic, but not acute, administration of morphine greatly diminished this staining pattern while mu opioid receptor levels and levels of MAP kinase as detected with a phosphorylation state-independent antibody were unchanged. When opioid withdrawal was precipitated with naloxone a dramatic increase in MAP kinase phosphorylation was observed in somata and fibres of locus coeruleus, solitary tract and hypothalamic neurons. Thus, the differential activation state of MAPK could have important implications for understanding the mechanisms underlying opioid tolerance and dependence.

Animals↗
PubMed1998

Immunocytochemical localization of somatostatin receptor sst2A in the rat spinal cord and dorsal root ganglia.

Intrathecal administration of octreotide, a stable somatostatin analogue, provides pain relief in patients, and locally applied somatostatin inhibits firing of nociceptive dorsal horn neurons. In the present study, we have raised polyclonal antibodies that specifically detect the somatostatin receptor sst2A and used these antisera for immunocytochemical localization of the receptor protein in the rat spinal cord and dorsal root ganglia. In the superficial layers of the dorsal horn, sst2A-like immunoreactivity (Li) formed a dense network consisting of neuronal perikarya and dendrites which were often closely apposed by, but not co-contained within, somatostatin-14-immunoreactive nerve fibres and terminals. sst2A-Li was resistant to dorsal rhizotomy and did not colocalize with either substance P or calcitonin gene-related peptide suggesting that sst2A-Li was not located to primary afferents, but rather confined to second-order spinal neurons. The position of sst2A-Li perikarya and dendrites in the dorsal horn appeared to be similar to those containing mu-opioid receptor-Li; however, double labelling experiments revealed no instances of coexistence of these two receptors. sst2A-Li was also observed in the dorsal root ganglia predominantly targeted to the somatic plasmalemma of medium size neurons distinct from those expressing somatostatin-14 or delta-opioid receptors. Thus, the present results not only provide a morphological substrate for spinal octreotide analgesia but also show that somatostatin and opioids are poised to modulate nociceptive transmission by distinct anatomical systems.

Amino Acid Sequence↗
PubMed1998

Quality criteria for electronic publications in medicine.

This paper defines "electronic publications in medicine (EPM)" as computer based training programs, databases, knowledge-based systems, multimedia applications and electronic books running on standard platforms and available by usual distribution channels. A detailed catalogue of quality criteria as a basis for development and evaluation of EPMs is presented. The necessity to raise the quality level of electronic publications is stressed considering aspects of domain knowledge, software engineering, media development, interface design and didactics.

Publishing↗
PubMed1998

Why discourse structures in medical reports matter for the validity of automatically generated text knowledge bases.

The automatic analysis of medical full-texts currently suffers from neglecting text coherence phenomena such as reference relations between discourse units. This has unwarranted effects on the description adequacy of medical knowledge bases automatically generated from texts. The resulting representation bias can be characterized in terms of artificially fragmented, incomplete and invalid knowledge structures. We discuss three types of textual phenomena (pronominal and nominal anaphora, as well as textual ellipsis) and outline basic methodologies how to deal with them.

Artificial Intelligence↗
PubMed1998

[Value and technique of laparoscopic choledochus revision in choledocholithiasis].

Despite a large scale indication to ERCP, 5% of unsuspected stones are shown by principally intraoperative cholangiography in our patients. Praeoperative diagnostic makes it possible to select the individual optimal therapy for each patient, the possibility of saving the Papilla vateri gives the large scale indication to laparoscopic common bile duct exploration. Also suspected stones gets a one-time cure therapy by complete laparoscopic operation. After balloon-dilatation of cysticus duct to 6 mm, the laparoscopic choledochoscopy is possible through the cysticus duct. Little stones are flushed into the duodenum or extracted by Segura-basket through the cysticus duct. Big stones needs a Laser- or electrohydraulic lithotripsy, the stonefragments can be flushed into the duodenum or aspirated through the cysticus duct. Multiple big or proximal incarcerated stones gives the indication for laparoscopic choledochotomy. Effective extraction is possible by big Segura-basket, residual stones are taken out under choledochoscopic control by little Segura-basket. Incarcerated stones needs the lithotripsy. Microdrainage of the common bile duct and only in special indication the T-tube saves the gall-flow to restitution of papilla function, the common bile duct is closed by running suture in Lahodny-technique. After the regular postoperative cholangiography on third day after operation, the microdrainage can be taken out. In 96% of all laparoscopic cholecystectomies the intraoperative cholangiography was successful. Only 3 of 103 patients needs a postoperative EPT because of residual fragments after trans cystic duct exploration. 8 laparoscopic choledochotomies shows the successness of endoscopic techniques, the postoperative complications can be the same then in conventional operation.

Cholecystectomy, Laparoscopic↗
PubMed1998

Immunocytochemical detection of somatostatin receptors sst1, sst2A, sst2B, and sst3 in paraffin-embedded breast cancer tissue using subtype-specific antibodies.

The long-acting somatostatin analogue octreotide (SMS 201-995) inhibits growth of certain breast cancer cell lines in vivo and in vitro. Because the antiproliferative action of octreotide depends on at least the presence of somatostatin receptors, it is crucial to determine the pattern of somatostatin receptor protein expression on the tumor cells. In the present study, we have raised polyclonal antibodies to somatostatin receptor subtypes (ssts) sst1, sst2A, sst2B, and sst3 using peptides corresponding to their COOH-terminal sequences. These antisera were used for immunocytochemical staining of paraffin sections of 33 primary breast cancers. Somatostatin receptor-like immunoreactivity (Li) was predominantly localized to the plasma membrane of the tumor cells. In the vast majority of positively stained tumors, somatostatin receptor-Li was uniformly present on nearly all tumor cells. Both the level and the pattern of expression of ssts varied greatly between individual carcinomas. sst2A-Li and/or sst2B-Li was detectable in 28 tumors (85%); among these, 14 tumors (42%) showed particularly high levels of sst2-Li. sst1-Li was found in 17 (52%) cases and sst3-Li in 16 (48%) cases. The expression of ssts was independent of patient age, menopausal status, diagnosis, histological grade, and levels of estrogen and progesterone receptors. The immunocytochemical determination of somatostatin receptor status allows direct detection of receptor protein on the tumor cells and, hence, may provide more precise information than reverse transcription-PCR for predicting response to octreotide therapy in breast cancer.

Adult↗
PubMed1998

Conversion problems concerning automated mapping from ICD-10 to ICD-9.

The increasing parallel use of ICD-9 and ICD-10 complicates the comparability of coded diagnoses. This is the reason why we developed a symmetric table for interactive conversion between ICD-9 and ICD-10, based on a vector space text-retrieval method that resulted in unambiguous mapping from ICD-9 to ICD-10 in 64%, from ICD-10 to ICD-9 in 87% of all three- and four-character classes of the tabular list. Out of the remaining 13% of multi-valued relations, a table for automated mapping from ICD-10 to ICD-9 was created. In 9% of cases, the selection offered no problems. A compromise between preserving information content and maintaining the logical integrity had to be found in 2.4%; in 1.6% automated mapping was impossible because of newly defined concepts and structural differences between ICD-9 and ICD-10 that are not counterbalanced by a consistent system of residual categories. We recommend that in a future revision of the ICD, compatibility with the then existing classification system should be considered.

Diagnosis, Computer-Assisted↗
PubMed1998

Part-whole reasoning in medical ontologies revisited--introducing SEP triplets into classification-based description logics.

The development of powerful and comprehensive medical ontologies that support formal reasoning on a large scale is one of the key requirements for clinical computing in the next millennium. Taxonomic medical knowledge, a major portion of these ontologies, is mainly characterized by generalization and part-whole relations between concepts. While reasoning in generalization hierarchies is quite well understood, no fully conclusive mechanism as yet exists for part-whole reasoning. The approach we take emulates part-whole reasoning via classification-based reasoning using SEP triplets, a special data structure for encoding part-whole relations that is fully embedded in the formal framework of standard description logics.

Artificial Intelligence↗
PubMed1997

Design of a multiple slice interface chamber and application for resolving the temporal pattern of CREB phosphorylation in hippocampal long-term potentiation.

We describe an improved method for the investigation of time-dependent intracellular events giving rise to long-lasting changes in synaptic efficacy. A new interface chamber for the simultaneous superfusion of approximately 30 rat hippocampal slices was designed. The slice chamber contains an upper and a lower medium reservoir connected by a grooved incubation platform which is mounted at an angle of 7 degrees on a thermoregulation unit. Surface slices placed in the chamber are perfused with oxygenated medium at a rate of 1 ml/min and are maintained synaptically viable for at least 6 h. At different time points after induction of long-term potentiation by stimulation of the Schaffer collateral pathway, slices were either fixed in Zamboni's fixative or the CA1 region was excised and lysed in boiling SDS-sample buffer. Fixed 400 microm hippocampal slices were cut into 30 microm sections and immunocytochemically stained with an anti-serine 133 phosphorylated cAMP-responsive element binding protein (pCREB) antibody. Binding of primary antibody was detected with the avidin-biotinylated peroxidase complex method and enhanced using peroxidase-catalyzed deposition of biotinylated tyramine. Staining was visualized with streptavidin-cyanine 3.18 and observed under a confocal laser scanning microscope. CA1 lysates were electrophoresed and subjected to Western blot analysis. Both pCREB immunocytochemical staining and Western blotting showed that CREB is rapidly and transiently phosphorylated after induction of long-term potentiation. pCREB levels peaked within 30 min and declined back to control after 60 min. Immunocytochemistry also showed that pCREB was localized to the nuclei of CA1 pyramidal cells near the tetanization site.

Animals↗
PubMed1997

Perillic acid inhibits Ras/MAP kinase-driven IL-2 production in human T lymphocytes.

Perillic acid, a major metabolite of d-limonene, substantially suppressed interleukin-2 (IL-2) and IL-10 production in mitogen-activated T lymphocytes. The effects of perillic acid on cytokine secretion were selective: IL-6 and transforming growth factor-beta 1 (TGF-beta 1) generation were unchanged. In H9 T lymphoma cells, exposure to perillic acid resulted in a dose-dependent depletion of membrane-bound Ras proteins. Unlike hydroxymethyl-glutaryl-CoA reductase or protein farnesyltransferase inhibitors, perillic acid did not induce a shift of membrane-bound into cytosolic p21ras but depleted total cellular Ras proteins. Triggering of the T cell receptor (TCR) perturbs the guanine nucleotide binding cycle of p21ras and in turn induces phosphorylation and activation of mitogen-activated protein kinases (MAPK). In perillic acid-treated cells, the levels of phosphorylated but not total MAPK were also decreased in a dose-dependent manner. Taken together, we provide evidence that perillic acid interrupts signalling via the Ras/MAP kinase pathway by depleting farnesylated Ras levels, an effect which may contribute to its inhibition of IL-2 production and T cell activation.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1997

Cytoplasmic domains mediate the ligand-induced affinity shift of guanylyl cyclase C.

Guanylyl cyclase C (GCC), the receptor for the Escherichia coli heat-stable enterotoxin (ST), exhibits multiple binding affinities, including high (RH) and low (RL) affinity sites and a ligand-induced conversion of low-affinity sites from a higher (RL1) to a lower (RL2) affinity state. Occupancy of the lowest affinity state of low-affinity sites is coupled to ligand-induced catalytic activation. In the present studies, ligand binding and catalytic activation properties of a series of intracellular deletion mutants of GCC were examined to identify the structural domains underlying expression of high- and low-affinity sites and the ligand-induced shift in low-affinity sites. These studies demonstrated that the cytoplasmic domains of GCC are not required, but extracellular and transmembrane domains are sufficient, for expression of high-affinity binding sites. In addition, the cytoplasmic juxtamembrane and kinase homology domains are required for expression of the ligand-induced affinity shift in low-affinity sites. Of significance, this shift in affinity was insensitive to adenine nucleotides, in contrast to other members of the receptor guanylyl cyclase family, such as guanylyl cyclase A (GCA). Also, the juxtamembrane and kinase homology domains are critical for coupling ST-receptor binding and guanylyl cyclase catalytic activation. Indeed, deletion of those domains from GCC results in a constitutively inhibited enzyme, suggesting that they function as positive effectors of ligand activation, in contrast to GCA and GCB, in which the kinase homology domain represses basal catalytic activity. These data suggest that the mechanisms regulating different members of the receptor guanylyl cyclase family are overlapping but not identical.

Animals↗
PubMed1997

Disruption of the guanylyl cyclase-C gene leads to a paradoxical phenotype of viable but heat-stable enterotoxin-resistant mice.

Heat-stable enterotoxins (STa), which cause an acute secretory diarrhea, have been suggested to mediate their actions through the guanylyl cyclase-C (GC-C) receptor. The GC-C gene was disrupted by insertion of neo into exon 1 and subsequent homologous recombination. GC-C null mice contained no detectable GC-C protein. Intestine mucosal guanylyl cyclase activity was approximately 16-fold higher in wild-type mice than in the GC-C null mice, and STa-stimulable guanylyl cyclase activity was absent in the null animals. Thus, GC-C is the major cyclase activity present in the intestine, and also completely accounts for the STa-induced elevations of cGMP. Gavage with STa resulted in marked fluid accumulation within the intestine of wild-type and heterozygous suckling mice, but GC-C null animals were resistant. In addition, infection with enterotoxigenic bacteria that produce STa led to diarrhea and death in wild-type and heterozygous mice, while the null mice were protected. Cholera toxin, in contrast, continued to cause diarrhea in GC-C null mice, demonstrating that the cAMP signaling pathway remained intact. Markedly different diets (high carbohydrate, fat, or protein) or the inclusion of high salt (K+, Na+) in the drinking water or diet also did not severely affect the null animals. Given that GC-C is a major intestinal receptor in all mammals, the pressure to retain a functional GC-C in the face of diarrhea-inflicted mortality remains unexplained. Therefore, GC-C likely provides a protective effect against stressors not yet tested, possibly pathogens other than noninvasive enterotoxigenic bacteria.

Animals↗
PubMed1997

Molecular cloning of Drosophila Rh6 rhodopsin: the visual pigment of a subset of R8 photoreceptor cells.

By screening retinal cDNA libraries for photoreceptor-specifically expressed genes we have isolated and sequenced a cDNA clone encoding the rhodopsin (Rh6) of a subset of R8 photoreceptor cells of the Drosophila compound eye. Compared to the other visual pigments of Drosophila, this rhodopsin is equally homologous to Rh1 and Rh2 (51% amino acid identity) but shows only 32% and 33% amino acid identity with Rh3 and Rh4, respectively. The open reading frame codes for a protein of 369 amino acids (MW = 41691). The primary structure of Rh6 displays sites typical for rhodopsin molecules in general, for example, a chromophore binding site in transmembrane domain VII, sequence motifs in the intracellular loops 2 and 3 required for the binding of a heterotrimeric G-protein, and a glycosylation site near the N-terminus which seems to be important for protein transport and maturation. Since R8 cells are founder cells in the developing compound eye, the isolation of a rhodopsin gene expressed in these cells may aid the understanding of terminal differentiation of photoreceptor cells.

Amino Acid Sequence↗
PubMed1997

Immunocytochemistry of endothelial nitric oxide synthase in the rat brain: a light and electron microscopical study using the tyramide signal amplification technique.

There are many inconsistencies in the literature about the cellular and subcellular distribution of the endothelial isoform of nitric oxide synthase (eNOS) in the brain. We have re-investigated its localization by light and electron microscopical (LM, EM) immunocytochemistry and the NADPH-diaphorase reaction. Using bovine aortic tissue as a positive control the protocols for the fixation and staining procedure were optimized. Only cryosections immersion-fixed with aceton and a mixture of aldehydes exhibited a clear-cut immunostaining. In rat brain tissue the endothelium of the entire vasculature showed immunoreactivity and, in addition to that, the epithelial cells of the choroid plexuses, whereas neurons never displayed any signs of immunostaining. EM immunoprecipitates were seen irregularly distributed in the cytosol or attached to endocellular membranes. EM NADPH-diaphorase histochemistry using the tetrazolium salt BSPT provided incoherent pictures in so far as the reaction product was exclusively bound to membranes. The restriction of eNOS within brain tissue to the vasculature may have implications for the differential significance of NOS isoforms in brain function.

Animals↗
PubMed1997

Inhibition by compactin demonstrates a requirement of isoprenoid metabolism for long-term potentiation in rat hippocampal slices.

Hippocampal long-term potentiation of synaptic transmission is the primary experimental model of learning and memory in the vertebrate brain. However, the detailed intracellular mechanisms giving rise to this persistent increase in synaptic efficacy remain incompletely understood. Mevalonic acid constitutes the basic precursor not only for cholesterol, dolichol and ubichinone but also for farnesyl-pyrophosphate and geranylgeranylpyrophosphate, which are required for post-translational modification of proteins. We have used the specific 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, compactin, to examine the role of isoprenoid metabolism for long-term potentiation in rat hippocampal slices. Compactin was applied at a concentration of 25 microM for 70 min before and during tetanization and the orthodromic population spike amplitude and field excitatory postsynaptic potentials were recorded from CA1 pyramidal cells. Compactin had no effect on the initial tetanization. However, compactin-treated slices were not able to maintain long-term potentiation for more than 60 min and population spike as well as field excitatory postsynaptic potentiation returned to basal levels after 120 min. When the slices were retetanized after 180 min, an almost full potentiation of the population spike and an only partial potentiation of the field excitatory postsynaptic potentials were observed. These results suggest an essential role of isoprenoid intermediates for maintenance of hippocampal long-term potentiation.

Animals↗
PubMed1997

Impairment of cation transport in A549 cells and rat alveolar epithelial cells by hypoxia.

A reduced cation reabsorption across the alveolar epithelium decreases water reabsorption from the alveoli and could diminish clearing accumulated fluid. To test whether hypoxia restricts cation transport in alveolar epithelial cells, cation uptake was measured in rat lung alveolar type II pneumocytes (AII cells) in primary culture and in A549 cells exposed to normoxia and hypoxia. In AII and A549 cells, hypoxia caused a PO2-dependent inhibition of the Na-K pump, of Na-K-2Cl cotransport, and of total and amiloride-sensitive 22Na uptake. Nifedipine failed to prevent hypoxia-induced transport inhibition in both cell types. In A549 cells, the inhibition of the Na-K pump and Na-K-2Cl cotransport occurred within approximately 30 min of hypoxia, was stable >20 h, and was reversed by 2 h of reoxygenation. There was also a reduction in cell membrane-associated Na-K-ATPase and a decrease in Na-K-2Cl cotransport flux after full activation with calyculin A, indicating a decreased transport capacity. [14C]serine incorporation into cell proteins was reduced in hypoxic A549 cells, but inhibition of protein synthesis with cycloheximide did not reduce ion transport. In AII and A549 cells, ATP levels decreased slightly, and ADP and the ATP-to-ADP ratio were unchanged after 4 h of hypoxia. In A549 cells, lactate, intracellular Na, and intracellular K were unchanged. These results indicate that hypoxia inhibits apical Na entry pathways and the basolateral Na-K pump in A549 cells and rat AII pneumocytes in culture, indicating a hypoxia-induced reduction of transepithelial Na transport and water reabsorption by alveolar epithelium. If similar changes occur in vivo, the impaired cation transport across alveolar epithelial cells might contribute to the formation of hypoxic pulmonary edema.

Adenosine Diphosphate↗
PubMed1997

Computer-based training and electronic publishing in the health sector: tools and trends.

CBT (computer-based training) applications and hypermedia publications are two different approaches to the utilisation of computers in medical education. Medical CBT software continues to play a minor role in spite of the increasing availability, whereas hypermedia have become very popular through the World Wide Web (WWW). Based on the HTML format they can be designed by non-programmers using inexpensive tools while the production of CBT applications requires programming expertise. HTML documents can be easily developed to be distributed by a web-server or to run as local applications. In developed countries CBT and hypermedia have to compete with an abundance of printed or audio-visual media and a wealth of lectures, conferences, etc., whereas in developing countries these media are scarce and expensive. Here CBT programs, and hypermedia publications in particular, may be a cost-effective way to improve quality of education in the health sector.

Computer Communication Networks↗