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Biomedical subjects

H Fischer

Publications and source records attributed to H Fischer.

At least 37 records · Page 2Linked to original sources

[Development of an optical 3-D position measuring system for simultaneous detection of 6 degrees of freedom].

A few years ago it became possible to carry out complicated surgical procedures in humans with the required precision by combining medical imaging (MRI, CT) with minimally invasive surgery. The confined space within these imaging systems and the resulting inaccuracies associated with the manual use of instruments increasingly make necessary the help of aids ranging from positioning systems to robotic devices, which themselves must be position controlled. A position sensor has been developed for a medical robotic system allowing the image-controlled insertion of injection needles and the simultaneous administration of different drugs. The 3D position coordinates are determined by a noncontact optical principle, which also enables simultaneous determination of all 6 basic degrees of freedom of the robotic system (3 translational, 3 rotational). On the basis of an area image sensor and the measurement of a geometrically defined structure in the path of the rays between sensor and light source, the position coordinates are calculated almost real time. Special emphasis was placed on designing the sensor system to cover a sufficiently large workspace to enable it to cover the entire intervention area. The sensor described herein determines the position coordinates in a volume of 10 x 10 x 10 cm at a resolution of up to 1 mm for translations and 1 degree for rotations.

Equipment Design↗

ROBITOM-robot for biopsy and therapy of the mamma.

MR-Mammography reaches a high sensitivity in detecting breast carcinomas of 3 mm in size at least. In cooperation with the Institute of Diagnostic and Interventional Radiology of the Friedrich-Schiller-University of Jena, a manipulator has been developed by the IMB, which combines the advantages of MRM imaging with a minimal invasive biopsy and a possible subsequent therapy. Referring to this ROBITOM I was introduced in November 1999 as worldwide first, precise operating manipulator system in the ISO center of a closed MR, at RSNA in Chicago. Clinical trials started at 22. November 2000. The experiences and results of these tests were brought into the following prototype ROBITOM II, that is currently developed at the IMB. The completion of this Prototype is planned at the end of 2002.

Biopsy↗

Alternative splicing of caspase-8 mRNA during differentiation of human leukocytes.

Caspase-8 is a key initiator of death receptor-induced apoptosis. Here we provide evidence that caspase-8 expression is subject to posttranscriptional regulation in human leukocytes. Resting peripheral blood lymphocytes preferentially use a distant splice donor site at the 3'-end of caspase-8 exon 8 to generate mRNAs with a truncated open reading frame. When lymphocytes were activated, the expression of caspase-8 variants was shifted to caspase-8/a and b which lack the extension of exon 8. The opposite change of the splicing pattern was found in a neutrophil differentiation model. Promyelocytic HL-60 cells mainly expressed caspase-8 mRNAs with the normal exon 8, but the splicing pattern was changed to the distant exon 8 splice site during DMSO-induced differentiation of HL-60 cells. In spite of the presence of these novel mRNAs, the corresponding translation products were not detectable in either cell type. Our findings suggest that leukocyte differentiation and alternative splicing of caspase-8 pre-mRNA are inter-dependent processes.

Alternative Splicing↗

Improvement of the long-term adhesive strength between metal stem and polymethylmethacrylate bone cement by a silica/silane interlayer system.

A loss of adhesive strength between metal stem and bone cement is clinically found to be a serious problem in total hip arthroplasty and causes many operative revisions. The objective of this study was to improve the long-term adhesive strength at this interface. A new silica/silane interlayer coating system is introduced. The layers are designed to bond the metal stem surface to the polymethylmethacrylate bone cement marginally leakage free. In vitro tensile tests were performed on specimens of TiAl6V4 and CoCrMo that were cemented by pairs with different bone cements with and without the new coating system. The specimens were stored in isotonic saline solution up to 150 days. The adhesive strength decreased about 75% within 30 days of storage on specimens of both metal alloys that were conventionally cemented without the new interlayer system. With the new coating, the high initial adhesive strength (40-50 MPa) could be stabilized for TiAl6V4 over 150 days. For the same 150-day storage period, the adhesive strength of the coated CoCrMo alloy still decreased but the decrease was only half that experienced by the uncoated CoCrMo. The loss of adhesive strength on CoCrMo specimens could be reduced if the metal surface was activated by a plasma treatment. The new coating interface system could help to considerably reduce revision operations caused by debonding effects at the interface metal/polymethylmethacrylate bone cement.

Adhesiveness↗

Silica-supported TEMPO catalysts: synthesis and application in the Anelli oxidation of alcohols.

The application of silica-supported TEMPO as a recyclable catalyst in the Anelli oxidation of alcohols is reported. The catalyst is easily obtained in a one-step reductive amination procedure starting from a commercially available aminopropyl-functionalized silica. Details of the synthesis of the supported catalyst and its analysis by MAS NMR are presented. Various alcohol oxidations according to the Anelli protocol have been carried out and the stability of the applied silica-supported TEMPO has been studied.

Journal Article↗

Crystal structure of the dimeric phosphoenolpyruvate carboxykinase (PEPCK) from Trypanosoma cruzi at 2 A resolution.

ATP-dependent phosphoenolpyruvate carboxykinase (PEPCK) (ATP: oxaloacetate carboxylyase (transphosphorylating), EC 4.1.1.49) is a key enzyme involved in the catabolism of glucose and amino acids in the parasite Trypanosoma cruzi, the causative agent of Chagas' disease. Due to the significant differences in the amino acid sequence and substrate specificity of the human enzyme (PEPCK (GTP-dependent), EC 4.1.1.32), the parasite enzyme has been considered a good target for the development of new anti-chagasic drugs. We have solved the crystal structure of the recombinant PEPCK of T. cruzi up to 2.0 A resolution, characterised the dimeric organisation of the enzyme by solution small angle X-ray scattering (SAXS) and compared the enzyme structure with the known crystal structure of the monomeric PEPCK from Escherichia coli. The dimeric structure possesses 2-fold symmetry, with each monomer sharing a high degree of structural similarity with the monomeric structure of the E. coli PEPCK. Each monomer folds into two complex mixed alpha/beta domains, with the active site located in a deep cleft between the domains. The two active sites in the dimer are far apart from each other, in an arrangement that seems to permit an independent access of the substrates to the two active sites. All residues of the E. coli PEPCK structure that had been found to interact with substrates and metal cofactors have been found conserved and in a substantially equivalent spatial disposition in the T. cruzi PEPCK structure. No substrate or metal ion was present in the crystal structure. A sulphate ion from the crystallisation medium has been found bound to the active site. Solution SAXS data suggest that, in solutions with lower sulphate concentration than that used for the crystallisation experiments, the actual enzyme conformation may be slightly different from its conformation in the crystal structure. This could be due to a conformational transition upon sulphate binding, similar to the ATP-induced transition observed in the E. coli PEPCK, or to crystal packing effects. The present structure of the T. cruzi PEPCK will provide a good basis for the modelling of new anti-chagasic drug leads.

Amino Acid Sequence↗

COL11A1 in FAP polyps and in sporadic colorectal tumors.

BACKGROUND: We previously reported that the alpha-1 chain of type 11 collagen (COL11A1), not normally expressed in the colon, was up-regulated in stromal fibroblasts in most sporadic colorectal carcinomas. Patients with germline mutations in the APC gene show, besides colonic polyposis, symptoms of stromal fibroblast involvement, which could be related to COL11A1 expression. Most colorectal carcinomas are suggested to be a result of an activated Wnt- pathway, most often involving an inactivation of the APC gene or activation of beta-catenin. METHODS: We used normal and polyp tissue samples from one FAP patient and a set of 37 sporadic colorectal carcinomas to find out if the up-regulation of COL11A1 was associated with an active APC/beta-catenin pathway. RESULTS: In this study we found a statistically significant difference in COL11A1 expression between normal tissue and adenomas from one FAP patient, and all adenomas gave evidence for an active APC/beta-catenin pathway. An active Wnt pathway has been suggested to involve stromal expression of WISP-1. We found a strong correlation between WISP-1 and COL11A1 expression in sporadic carcinomas. CONCLUSIONS: Our results suggest that expression of COL11A1 in colorectal tumors could be associated with the APC/beta-catenin pathway in FAP and sporadic colorectal cancer.

Adenomatous Polyposis Coli↗

Production of (4)(double Lambda)H hypernuclei.

An experiment demonstrating the production of double-Lambda hypernuclei in (K(-),K(+)) reactions on (9)Be was carried out at the D6 line in the BNL alternating-gradient synchrotron. The technique was the observation of pions produced in sequential mesonic weak decay, each pion associated with one unit of strangeness change. The results indicate the production of a significant number of the double hypernucleus (4)(double Lambda)H and the twin hypernuclei (4)(Lambda)H and (3)(Lambda)H. The relevant decay chains are discussed and a simple model of the production mechanism is presented. An implication of this experiment is that the existence of an S = -2 dibaryon more than a few MeV below the double Lambda mass is unlikely.

Journal Article↗

Dispositional pessimism and amygdala activity: a PET study in healthy volunteers.

The present study used scores from Seligman's Attribution Style Questionnaire and [15O] water positron emission tomographic measurements of regional cerebral blood flow (rCBF) to investigate the relation between individual differences in dispositional pessimism and amygdala activity. During scanning 13 healthy non-snake-phobic females passively viewed a snake videotape. Using one-tailed tests, significant negative correlations were evident between pessimism scores, with low scores reflecting relatively more pessimism, and right (r=-0.60; p=0.014) and left amygdala rCBF (r=-0.53; p=0.032). These results extend previous neuroimaging findings in healthy subjects indicating a role for the amygdala in transient negative emotional states, and suggest that this multimodal brain region also is involved in more durable negative affects such as dispositional pessimism.

Adult↗

Effect of Helicobacter pylori eradication on cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) expression during gastric adaptation to aspirin (ASA) in humans.

Gastric adaptation to aspirin is impaired in Helicobacter pylori infection, but the mechanisms underlying this phenomenon are unclear. In this study, we compared gastric mucosal expression of iNOS and COX-2 during 14 days of aspirin ingestion in the same subjects before and 3 months after eradication of H. pylori. Compared to non-infected controls, mucosal expression of COX-2 and iNOS was enhanced before and 3 months after eradication of H. pylori. During aspirin ingestion, mucosal expression of COX-2 remained unchanged before eradication of H. pylori, but increased gradually after successful antimicrobial treatment. Independent of H. pylori status, expression of iNOS increased at the beginning of aspirin intake, but then returned to initial values. We conclude that COX-2 but not iNOS might be involved in gastric adaptation to aspirin in humans and that this mechanism appears to be impaired in H. pylori infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Entropy control of the cross-reaction between carbon-centered and nitroxide radicals.

Absolute rate constants for the cross-coupling reaction of several carbon-centered radicals with various nitroxides and their temperature dependence have been determined in liquids by kinetic absorption spectroscopy. The rate constants range from <2 x 10(5) M(-)(1) s(-)(1) to 2.3 x 10(9) M(-)(1) s(-)(1) and depend strongly on the structure of the nitroxide and the carbon-centered radical. Grossly, they decrease with increasing rate constant of the cleavage of the corresponding alkoxyamine. In many cases, the temperature dependence shows a non-Arrhenius behavior. A model assuming a short-lived intermediate that is hindered to form the coupling product by an unfavorable activation entropy leads to a satisfactory analytic description. However, the behavior is more likely due to a barrierless single-step reaction with a low exothermicity where the free energy of activation is dominated by a large negative entropy term.

Journal Article↗

C7, a novel nucleolar protein, is the mouse homologue of the Drosophila late puff product L82 and an isoform of human OXR1.

The C7 gene was identified in a project aimed to characterize differential gene expression upon attachment of cells to extracellular matrix proteins in vitro. C7 is the homologue of Drosophila L82, a late puff gene (Stowers et al. (1999) Dev. Biol. 213, 116-130) and human OXR1, a gene, which protects cells against oxidation (Volkert et al. (2000) Proc. Natl. Acad. Sci. USA 97, 14530-14535). All are transcribed into multiple splice forms with a common 3' domain. Additional members of this novel gene family are found in a number of eukaryotic species. In the mouse, the C7 gene is highly and broadly expressed during development in at least 4 splice forms, 3 of which were sequenced. In the adult, the C7 gene is most highly expressed in brain and testis. Antibodies to recombinant C7 protein localized to nucleoli in a variety of cell types, suggesting that C7 may be involved in the formation or function of this important organelle.

Amino Acid Sequence↗

A Fe(x)Mn1-x/Ir(001) multilayer probed by EXAFS and DAFS.

Diffraction Anomalous Fine Structure (DAFS) and EXAFS measurements have been performed on a (Fe0.7Mn0.3)/Ir(100)40 super-lattice at the K-edges of Fe and Mn. Theoretical EXAFS spectra have been refined: a slight difference in the first neighbor distance suggests a non homogeneous distribution of the Mn in the alloy. The smooth features of the DAFS spectra have been modeled to study the composition and the strain profile along the growth axis.

Journal Article↗

Factors influencing the C-O bond homolysis of alkoxyamines: effects of H-bonding and polar substituents.

The synthesis of various new trialkylhydroxylamines is described. The rate constant of the C-O bond cleavage of these new alkoxyamines has been measured. For example, C-O bond homolysis rates in a series of para-substituted TEMPO-styryl compounds TEMPO-CH(CH3)C6H5X 1a (p-MeO), 1b (p-Me), 1d (p-H), 1e (p-Br), and 1f (p-MeO2C) are presented. Furthermore, rate constants for the C-O bond cleavage of alpha-heteroaryl-substituted secondary alkoxyamines are discussed. A correlation by which the rate constant for the C-O bond cleavage of TEMPO-derived alkoxyamines can be predicted from the C-H BDEs of the corresponding alkanes is presented. Solvent effects as well as the effect of camphorsulfonic acid on the rate of the C-O bond homolysis are discussed. Finally, EPR and kinetic evidence show that alkoxyamines derived from nitroxides which are capable of intramolecular H-bonding undergo C-O bond cleavage faster than the corresponding non-H-bond-forming analogues.

Journal Article↗

Differential prefrontal cortex and amygdala habituation to repeatedly presented emotional stimuli.

Repeated presentations of emotional facial expressions were used to assess habituation in the human brain using fMRI. Significant fMRI signal decrement was present in the left dorsolateral prefrontal and premotor cortex, and right amygdala. Within the left prefrontal cortex greater habituation to happy vs fearful stimuli was evident, suggesting devotion of sustained neural resources for processing of threat vs safety signals. In the amygdala, significantly greater habituation was observed on the right compared to the left. In contrast, the left amygdala was significantly more activated than the right to the contrast of fear vs happy. We speculate that the right amygdala is part of a dynamic emotional stimulus detection system, while the left is specialized for sustained stimulus evaluations.

Adult↗

The Indian Ocean experiment: widespread air pollution from South and Southeast Asia.

The Indian Ocean Experiment (INDOEX) was an international, multiplatform field campaign to measure long-range transport of air pollution from South and Southeast Asia toward the Indian Ocean during the dry monsoon season in January to March 1999. Surprisingly high pollution levels were observed over the entire northern Indian Ocean toward the Intertropical Convergence Zone at about 6 degrees S. We show that agricultural burning and especially biofuel use enhance carbon monoxide concentrations. Fossil fuel combustion and biomass burning cause a high aerosol loading. The growing pollution in this region gives rise to extensive air quality degradation with local, regional, and global implications, including a reduction of the oxidizing power of the atmosphere.

Aerosols↗