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Biomedical subjects

R Franke

Publications and source records attributed to R Franke.

At least 19 recordsLinked to original sources
PubMed2005

The transcription factor profile of human mast cells in comparison with monocytes and granulocytes.

Expression profiles of mRNAs and proteins for various transcription factors were determined for human skin mast cells (sMCs), leukemic HMC-1 MCs, monocytes and granulocytes. By quantitative RT-PCR, sMCs expressed lower levels of c-fos, PU.1, C/EBPalpha, and C/EBPepsilon than monocytes and granulocytes, but higher levels of MITF, SCL, GATA-1 and GATA-2. At the protein level, MITF, SCL, GATA-2, Elf-1 and c-fos were clearly detectable in sMCs. With the exception of c-fos, these proteins were absent or expressed only slightly in monocytes and granulocytes. The expression of NF-E2p45, GATA-1, PU.1, Ets-1, C/EBPalpha and C/EBPepsilon was below the detection limit in sMCs, but detectable in other myelocytes. The high expression of SCL and GATA-2 in sMCs is reminiscent of stem cells. The absence of C/EBPvarepsilon in sMCs, but strong expression in HMC-1, suggests it may impair MC maturation. In summary, mature human MCs can be characterized as C/EBPalpha(low), C/EBPvarepsilon-, PU.1(low), GATA-1(low), GATA-2+, SCL+, MITF(high).

Animals↗
PubMed2004

High-fat diet alters K+-currents in porcine coronary arteries and adenosine sensitivity during metabolic inhibition.

Coronary arteries from animals on normal diets (ND) exhibit well-maintained responses to dilators under ischemic conditions. The reported altered metabolic requirements and K+-currents in blood vessels from hypercholesterolemic animals fed high-fat diets (HF) led us to hypothesize that under metabolically depressed conditions (N2/2-deoxyglucose) coronary arteries from pigs would exhibit significantly decreased responses to adenosine (ADO) as compared with pigs given ND. Diet had no major effect on responses of coronary rings to ET-1, nor on the sensitivity to ADO or 2-chloroadenosine (2-CAD) relaxation under metabolically supported conditions. During metabolic inhibition the response curves for both ADO and 2-CAD were shifted to the right (P < 0.05), with the HF group shifted about 4-fold more than ND (P < 0.05). To determine the involvement of K+-channels, ADO responses were measured in the presence of 4-aminopyridine (4-AP, 1 mM) or glybenclamide (GLYB, 10 microM). The larger shift in the HF group during metabolic inhibition was not affected by GLYB, but disappeared in the presence of 4-AP with ND now behaving similarly to HF. These results indicate that HF diet may have a 4-AP-like effect on voltage-dependent K+-channels (KV). Patch-clamp measures of whole cell K- currents showed the HF cells to have reduced 4-AP sensitive currents (P < 0.02). The 4-AP insensitive currents were similar in both groups. Thus, reduced KV channel activity may play a role in the depressed ADO relaxation associated with metabolic inhibition of HF coronary arteries. These factors may place the coronary circulation of HF at increased risk during an ischemic episode.

Adenosine↗
PubMed2001

Elucidation of new structures in lignins of CAD- and COMT-deficient plants by NMR.

Studying lignin-biosynthetic-pathway mutants and transgenics provides insights into plant responses to perturbations of the lignification system, and enhances our understanding of normal lignification. When enzymes late in the pathway are downregulated, significant changes in the composition and structure of lignin may result. NMR spectroscopy provides powerful diagnostic tools for elucidating structures in the difficult lignin polymer, hinting at the chemical and biochemical changes that have occurred. COMT (caffeic acid O-methyl transferase) downregulation in poplar results in the incorporation of 5-hydroxyconiferyl alcohol into lignins via typical radical coupling reactions, but post-coupling quinone methide internal trapping reactions produce novel benzodioxane units in the lignin. CAD (cinnamyl alcohol dehydrogenase) downregulation results in the incorporation of the hydroxycinnamyl aldehyde monolignol precursors intimately into the polymer. Sinapyl aldehyde cross-couples 8-O-4 with both guaiacyl and syringyl units in the growing polymer, whereas coniferyl aldehyde cross-couples 8-O-4 only with syringyl units, reflecting simple chemical cross-coupling propensities. The incorporation of hydroxycinnamyl aldehyde and 5-hydroxyconiferyl alcohol monomers indicates that these monolignol intermediates are secreted to the cell wall for lignification. The recognition that novel units can incorporate into lignins portends significantly expanded opportunities for engineering the composition and consequent properties of lignin for improved utilization of valuable plant resources.

Alcohol Oxidoreductases↗
PubMed2001

Prediction of rodent carcinogenicity of aromatic amines: a quantitative structure-activity relationships model.

The aromatic amines are widely used industrial chemicals and can be found in tobacco smoke as well as in products generated during cooking. In a previous study, we established quantitative structure-activity relationship (QSAR) models linking the carcinogenic potency of non-heterocyclic carcinogenic aromatic amines to a series of molecular determinants. We also found that QSAR models for carcinogenic potency were inadequate in describing the difference between carcinogenic and non-carcinogenic amines [Benigni,R., Giuliani,A., Franke,R. and Gruska,A. (2000) CHEM: Rev., 100, 3697-3714]. In this paper, we derived specific QSAR models for separating active from inactive amines. It appeared that hydrophobicity (as measured by the octanol/water partition coefficient, logP) played a major role in modulating the potency of the carcinogens, whereas mainly electronic (reactivity) and steric characteristics separated the carcinogens from the non-carcinogens. Interestingly, a similar pattern was previously demonstrated by us regarding their mutagenic activity [Benigni,R., Passerini,L., Gallo,G., Giorgi,F. and Cotta-Ramusino,M. (1998) ENVIRON: Mol. Mutagen., 32, 75-83]. Based on the QSAR models found, the molecular determinants of the mechanisms of action of aromatic amines are discussed in detail. The QSAR models obtained can be used directly for estimating the carcinogenicity of other non-heterocyclic aromatic amines for which experimental data are not available. With the QSARs in Benigni et al. (2000) and the present results, a two-step prediction of carcinogenicity of aromatic amines is possible: (i) step 1, yes/no activity from the discriminant functions; and (ii) step 2, if the answer from step 1 is yes then prediction of the degree of potency from the equations in Benigni et al. (2000). Thus, QSAR models can contribute to the following: the direct synthesis of safer chemicals; the estimation of the risk posed by amines present in the environment; setting priorities for further experimentation, thus also reducing the use of experimental animals. Whereas the quality of in vivo experimental data is often questioned, the robustness and interpretability of the present results strongly support the reliability of the rodent carcinogenicity assay.

Amines↗
PubMed2000

Modified lignin in tobacco and poplar plants over-expressing the Arabidopsis gene encoding ferulate 5-hydroxylase.

Ferulate 5-hydroxylase (F5H) is a cytochrome P450-dependent monooxygenase that catalyses the hydroxylation of ferulic acid, coniferaldehyde and coniferyl alcohol in the pathways leading to sinapic acid and syringyl lignin biosynthesis. Earlier studies in Arabidopsis have demonstrated that F5H over-expression increases lignin syringyl monomer content and abolishes the tissue-specificity of its deposition. To determine whether this enzyme has a similar regulatory role in plants that undergo secondary growth, we over-expressed the F5H gene in tobacco and poplar. In tobacco, over-expression of F5H under the control of the cauliflower mosaic virus 35S promoter increased lignin syringyl monomer content in petioles, but had no detectable effect on lignification in stems. By contrast, when the cinnamate 4-hydroxylase (C4H) promoter was used to drive F5H expression, there was a significant increase in stem lignin syringyl monomer content. Yields of thioglycolic acid and Klason lignin in C4H-F5H lines were lower than in the wild-type, suggesting that F5H over-expression leads to a reduced deposition or an altered extractability of lignin in the transgenic plants. Histochemical analysis suggested that the novel lignin in C4H-F5H transgenic lines was altered in its content of hydroxycinnamyl aldehydes. Transgenic poplar trees carrying the C4H-F5H transgene also displayed enhanced lignin syringyl monomer content. Taken together, these data show that hydroxylation of guaiacyl-substituted lignin precursors controls lignin monomer composition in woody plants, and that F5H over-expression is a viable metabolic engineering strategy for modifying lignin biosynthesis in forest species.

Arabidopsis↗
PubMed2000

Reproducibility of serial intravascular ultrasound measurements in patients with angiographically silent coronary artery disease after heart transplantation.

BACKGROUND: Intracoronary ultrasound (ICUS) imaging is the most sensitive method for the early detection and serial evaluation of vasculopathy of transplants. Both lack of agreement between observers and lack of agreement between serial, independent pullback procedures (repeatability), which can result in a variable intraluminal catheter position may limit the reproducibility of ICUS measurements. OBJECTIVE: To evaluate the reproducibility of serial measurements of standard linear and area cross-sectional coronary dimensions in patients with non-obstructive transplant vasculopathy. METHODS: We performed ICUS imaging of patients without angiographic evidence of obstructive epicardial coronary artery disease after heart transplantation. A 30 MHz phased-array transducer was used. Two independent pullbacks of the left anterior descending coronary artery were performed and recorded on CD-ROM for off-line quantitative analysis of the most severely diseased site. Agreement of observers and repeatability of serial measurements were calculated by the use of linear regression analysis and Bland-Altman plots. RESULTS: Regarding agreement of observers, correlation coefficients for intra-observer agreement ranged from r = 0.98 to r = 0.99; those for interobserver agreement ranged from r = 0.87 to r = 0.98. Serial measurements of the identical coronary artery cross-section within independent catheter pullback procedures were possible for 104 of 112 target lesions (92.90/%). Correlation coefficients ranged from r = 0.91 to r = 0.97 (for lumen diameter r = 0.91, for lumen area r = 0.93, for vessel diameter r = 0.91, for vessel area r = 0.97, for thickness of plaque r = 0.96 and for area of plaque 0.94). The mean difference of measurements was around zero for all parameters with SD from 0.13 to 0.4 mm for linear parameters and from 1.53 to 1.82 mm2 for area parameters. CONCLUSION: Serial intravascular ultrasound measurements are highly reproducible without any evidence of systematic error and a SD of differences of measurements beyond the maximal spatial resolution of currently available intravascular ultrasound catheters.

Coronary Angiography↗
PubMed1999

Model reactor for photocatalytic degradation of persistent chemicals in ponds and waste water.

A laboratory scale flow-through model reactor for the degradation of persistent chemicals using titanium dioxide (TiO2) as photocatalyst immobilized on glass beads is presented. In the test system with a volume of 18 L contaminated water is pumped to the upper part of the floating reactor and flows over the coated beads which are exposed to UV-radiation. The degradation of two dyes of different persistence was investigated. Primary degradation of methylene blue did not fit a first order kinetic due to coincident adsorption onto the photocatalyst and direct photolysis, resulting in a half-life of 6 h. A filtrate of a green algae suspension accelerated the colour removal. In contrast, reactive red 2 was degraded only by photocatalysis; neither adsorption nor direct photolysis led to a colour removal. The course of primary degradation followed a first order kinetic with a half-life of 18 h and a rate constant of 0.04 h-1. Analysis of the degradation products indicated mineralization by detection of NO2- and NO3-, accompanied by a decrease of pH and an increase of conductivity. A successful adaptation of the model reactor (scale 1:10) to dimensions required for surface waters and waste water treatment plants would be a cost-efficient and environmentally sustainable application of photocatalysis for the treatment of industrially polluted water and could be of relevance for third world countries, particularly those favoured by high solar radiation.

Glass↗
PubMed1998

Synthesis, pharmacological characterization, and quantitative structure-activity relationship analyses of 3,7,9,9-tetraalkylbispidines: derivatives with specific bradycardic activity.

A series of 3,7,9,9-tetraalkyl-3,7-diazabicyclo[3.3.1]nonane derivatives (bispidines) was synthesized and identified as potential antiischemic agents. Pharmacological experiments in vitro as well as in vivo are described, and the results are listed. For selection of those compounds fitting best to the desired profile of a specific bradycardic antianginal agent--decrease in heart rate without affecting contractility and blood pressure--these results were scored and ranked. Quantitative structure--activity relationship (QSAR) analyses were performed and discussed a posteriori by means of Hansch, nonelementary discriminant and factor analysis to get insight into the molecular features determining the biological profile. Highly significant equations were obtained, indicating hydrophobic and steric effects. Both pharmacological ranking and QSAR considerations showed compound 6 as the optimum within the structural class under investigation. Compound 6 (tedisamil, KC8857) has been selected as the most promising compound and was chosen for further pharmacological and clinical investigations as an antiischemic drug.

Animals↗
PubMed1996

Mammary derived growth inhibitor is not a distinct protein but a mix of heart-type and adipocyte-type fatty acid-binding protein.

The amino acid sequence of the mammary derived growth inhibitor (MDGI) from bovine mammary gland (Böhmer, F.-D., Kraft, R., Otto, A. , Wernstedt, C., Hellman, U., Kurtz, A., Müller, T., Rohde, K., Etzold, G., Lehmann, W., Langen, P., Heldin, C.-H., and Grosse, R. (1987) J. Biol. Chem. 262, 15137-15143) revealed 95% identity to bovine heart fatty acid-binding protein (H-FABP), explaining the observed immunocross-reactivity. However, a cDNA encoding MDGI has not been found to date. Artificial MDGI cDNA was expressed in an in vitro transcription/translation assay. Analysis by isoelectric focusing of the immunoprecipitated in vitro translation products of lactating bovine mammary gland mRNA did not indicate a protein corresponding to the in vitro translation product of artificial MDGI mRNA. Moreover, two-dimensional electrophoresis of bovine mammary gland proteins confirmed the absence of a protein with the pI of the in vitro translated artificial MDGI mRNA in bovine mammary gland and instead revealed, apart from H-FABP, an unknown protein that was recognized by anti-H-FABP antibodies. From lactating bovine mammary gland the cDNA for adipocyte fatty acid-binding protein (A-FABP) was cloned. The in vitro translation of recombinant mRNA derived from this cDNA yielded a polypeptide that behaved like the unknown immunoreactive protein. Western blotting and immunofluorescence using monospecific antibodies demonstrated the coexistence of H-FABP and A-FABP in the lactating mammary gland. Taking into account that deviations of the MDGI sequence from the bovine H-FABP sequence correspond with A-FABP we attribute the structure originally reported as MDGI to a mix of these proteins.

Adipose Tissue↗
PubMed1996

The determination of local structural units in amorphous SiBN(3)C by means of X-ray photoelectron and X-ray absorption spectroscopy.

X-ray photoelectron spectroscopy (XPS) and X-ray absorption near edge structure (XANES) spectroscopy at the K-edge of Si, N, and B are presented as techniques suited to determine structural units in amorphous SiBN(3)C. The measurements reported give evidence for the presence of tetrahedral (SiN(4))- and planar (BN(3))-groups. It is concluded that these structural elements dominate the atomic surroundings of B and Si, respectively. From the spectroscopic results we conclude that C is mainly bonded to N and is not present as a pure carbide.

Journal Article↗
PubMed1996

X-ray absorption and X-ray photoelectron spectroscopy of a rhodium colloid.

Transition metal colloids are potential precursors of heterogeneous catalysts with application to selective chemical reactions. Sample preparation techniques are described. Experimental details are given of the characterization of these often air-sensitive particles by X-ray photoelectron and X-ray absorption spectroscopy. First results obtained with both techniques for a Rh-colloid show that the metal is mainly present in the zerovalent chemical state. But the spectra indicate further chemical states of Rh which can be assigned to the outermost metal atoms of the colloid interacting with organic ligands or to the educt Rh-halides.

Journal Article↗
PubMed1995

[Biomechanics of the middle ear].

We describe the main biomechanical characteristics of the middle ear in man and in animals. Physical principles of functionment, tympano-ossicular displacements, acoustic reflex, adaptation of impedance, transfer function of the middle ear, middle ear as an acoustic power transformer... are presented. Practical consequences for the hearing sensitivity, the susceptibility to noise and some clinical applications are discussed.

Acoustics↗
PubMed1994

Embryonic chicken gizzard: smooth muscle and non-muscle myosin isoforms.

Antibodies to smooth muscle and non-muscle myosin allow the development of smooth muscle and its capillary system in the embryonic chicken gizzard to be followed by immunofluorescent techniques. Although smooth muscle development proceeds in a serosal to luminal direction, angiogenetic cell clusters develop independently at the luminal side close to the epithelial layer, and the presumptive capillaries invade the developing muscle in a luminal to serosal direction. The smooth muscle and non-muscle myosin heavy chains in this avian system cannot be separated by SDS polyacrylamide gel electrophoresis and do not show isoform specificity in immunoblotting, unlike the system found in mammals. Only two myosin heavy chains with M(r) of 200 and 196 kDa were separable and considerable immunological cross-reactivity was found between the denatured myosin isoform heavy chains.

Animals↗
PubMed1994

Combined factor and QSAR analysis for antibacterial and pharmacokinetic data from parallel biological measurements.

Antibacterial potency data for a variety of bacterial strains and pharmacokinetic parameters of naphthyridines taken from the literature were submitted to factor and QSAR analyses. Factor analysis of antibacterial potencies unraveled a distinct data structure. The information obtained about the internal relatedness of tests can be used in QSAR analyses and reflects itself in the QSAR results. Factor analysis of pharmacokinetic data also led to a clear grouping of measurements with a strong relationship of half life time and urinary recovery, respectively, with log D.

Animals↗
PubMed1994

Classification of serine proteases derived from steric comparisons of their active sites, part II: "Ser, His, Asp arrangements in proteolytic and nonproteolytic proteins".

The assignment of serine proteases to the families of (chymo)trypsins and subtilisins, respectively, is extended by including additional data from the Brookhaven Protein Data Bank. To better understand basic properties connected with this type of assignment the steric situation in the vicinity of the tetrad aminoacyl residues and atomic distances within the tetrads are considered. A new catalytic mechanism is suggested based on differences between tonin and kallikrein with respect to structure and reactivity of the catalytic tetrad. All protein structures available from the Brookhaven Protein Data Bank are analyzed with regard to the occurrence of Asp....His....Ser triads.

Amino Acid Sequence↗
PubMed1993

Signal transduction by immunoglobulin is mediated through Ig alpha and Ig beta.

Immunoglobulin (Ig) antigen receptors are composed of a noncovalently-associated complex of Ig and two other proteins, Ig alpha and Ig beta. The cytoplasmic domain of both of these Ig associated proteins contains a consensus sequence that is shared with the signaling proteins of the T cell and Fc receptor. To test the idea that Ig alpha-Ig beta heterodimers are the signaling components of the Ig receptor, we have studied Ig mutations that interfere with signal transduction. We find that specific mutations in the transmembrane domain of Ig that inactivate Ca2+ and phosphorylation responses also uncouple IgM from Ig alpha-Ig beta. These results define amino acid residues that are essential for the assembly of the Ig receptor. Further, receptor activity can be fully reconstituted in Ca2+ flux and phosphorylation assays by fusing the cytoplasmic domain of Ig alpha with the mutant Igs. In contrast, fusion of the cytoplasmic domain of Ig beta to the inactive Ig reconstitutes only Ca2+ responses. Thus, Ig alpha and Ig beta are both necessary and sufficient to mediate signal transduction by the Ig receptor in B cells. In addition, our results suggest that Ig alpha and Ig beta can activate different signaling pathways.

Amino Acid Sequence↗
PubMed1993

Influence of body position on jugular venous oxygen saturation, intracranial pressure and cerebral perfusion pressure.

Elevation of the head as a common practice to reduce raised intracranial pressure (ICP) has been discussed controversially of late. Some investigators were able to show that besides lowering ICP head elevation may also reduce cerebral perfusion pressure (CPP). For a new evaluation of optimal head position in neurosurgical care it would be of importance to know the influence of body position on cerebral perfusion. We therefore employed continuous jugular venous oximetry, monitoring cerebral oxygenation, to study the effect of 0 degrees, 15 degrees, 30 degrees, and 45 degrees head elevation on ICP, CPP and jugular venous oxygen saturation (SJVO2) in 25 comatose patients with reduced intracranial compliance. As expected, head elevation significantly reduced ICP from 19.8 +/- 1.3 mmHg at 0 degrees to 10.2 +/- 1.2 mmHg at 45 degrees. Already at 30 degrees 92% of the possible effect on ICP was detected. There was no statistically significant change in CPP and SJVO2 associated with varying head position. Individual reactions of CPP to changes in head position, however, were quite unpredictable. The data suggest that an individual approach to head elevation is to be preferred. A moderate head elevation between 15 degrees and 30 degrees significantly reduces ICP and, in general, does not impair cerebral perfusion. Jugular venous oximetry may be used to optimize ICP, CPP and cerebral oxygenation.

Adult↗