Biomedical subjects

T Flohr

Publications and source records attributed to T Flohr.

63 records · Page 4Linked to original sources

PubMed1992

Interferon-gamma regulates expression of a novel keratin class I gene.

Interferon (IFN)-gamma has been implicated in the pathogenesis of several autoimmune disorders and inflammatory skin diseases. To identify novel mediators involved in the IFN-gamma response we have used differential hybridization of a cDNA library prepared from IFN-gamma-treated HeLa cells to isolate a gene that is induced following treatment with IFN-gamma. We report here the molecular cloning and characterization of a cDNA detecting a 1.6-kb mRNA that accumulated in response to IFN-gamma but not in response to IFN-alpha or IFN-beta. The gene is regulated by IFN-gamma in human cell lines of epithelial origin. The mRNA encodes a predicted protein of 432 amino acids and the primary structure of the protein demonstrates that it is a novel member of developmentally regulated keratin class I genes.

Amino Acid Sequence↗

PubMed1992

Molecular cloning and characterization of an interferon induced human cDNA with sequence homology to a mammalian peptide chain release factor.

Here we report the molecular cloning of several related human cDNAs from which a full-length sequence can be determined. The cDNAs encode a 2.8 kb mRNA that is strongly induced by interferon (IFN) gamma and the expression of which is not cell-restricted but observed in fibroblasts, macrophages and epithelial cells. The deduced amino acid sequence predicts a protein of 471 amino acids with high sequence similarity to a previously identified rabbit peptide chain release factor. Functional studies to demonstrate release factor activity showed that the protein encoded by this cDNA inhibited the readthrough activity of a yeast UGA suppressor tRNA in an in vitro translation system. The identification of this novel cDNA implies that translational control by IFN induced proteins may not be restricted to the initial steps of protein synthesis but may also act by regulation of peptide chain termination.

Amino Acid Sequence↗

PubMed1992

Depletion of tryptophan is not involved in expression of tryptophanyl-tRNA synthetase mediated by interferon.

Gamma interferon (IFN-gamma) affects tryptophan metabolism by mediating the expression of indoleamine 2,3-dioxygenase and tryptophanyl-tRNA synthetase. In the present study, we investigated the role of indoleamine 2,3-dioxygenase-mediated tryptophan depletion in the induction of tryptophanyl-tRNA synthetase by IFN-gamma. The addition of excess tryptophan to the culture medium did not affect the induction of tryptophanyl-tRNA synthetase by IFN-gamma, indicating that tryptophan degradation is not directly involved in the IFN-gamma-mediated expression of tryptophanyl-tRNA synthetase.

Humans↗

PubMed1990

Towards a phylogeny and definition of species at the molecular level within the genus Mycobacterium.

16S rRNA sequences from Mycobacterium tuberculosis, M. avium, M. gastri, M. kansasii, M. marinum, M. chelonae, M. smegmatis, M. terrae, M. gordonae, M. scrofulaceum, M. szulgai, M. intracellulare, M. nonchromogenicum, M. xenopi, M. malmoense, M. simiae, M. flavescens, M. fortuitum, and M. paratuberculosis were determined and compared. The sequence data were used to infer a phylogenetic tree, which provided the basis for a systematic phylogenetic analysis of the genus Mycobacterium. The groups of slow- and fast-growing mycobacteria could be differentiated as distinct entities. We found that M. simiae occupies phylogenetically an intermediate position between these two groups. The phylogenetic relatedness within the slow-growing species did not reflect the Runyon classification of photochromogenic, scotchromogenic, and nonchromogenic mycobacteria. In general, the phylogenetic units identified by using rRNA sequences confirmed the validity of phenotypically defined species; an exception was M. gastri, which was indistinguishable from M. kansasii when this kind of analysis was used.

Base Sequence↗

PubMed1990

Differentiation of Mycobacterium species by direct sequencing of amplified DNA.

Nucleotide sequences specific for a range of Mycobacterium species were defined by computer-assisted sequence comparisons of small subunit ribosomal RNA. A polymerase chain reaction-based sequencing strategy was used to demonstrate that the 16S rRNA sequence can be used for the rapid identification of mycobacterial isolates. Identification at the species level can be obtained within 2 d, requiring less than 10,000 bacteria. This procedure reliably differentiates Mycobacterium spp. which are difficult to identify by classical methods, such as M. malmoense, M. szulgai and M. flavescens.

Base Sequence↗

PubMed1990

Detection and identification of mycobacteria by amplification of rRNA.

Oligonucleotides specific at a genus, group, or species level were defined by a systematic comparison of small-subunit rRNA sequences from Mycobacterium tuberculosis, M. bovis, M. africanum, M. bovis BCG, M. avium, M. kansasii, M. marinum, M. gastri, M. chelonae, M. smegmatis, M. terrae, M. nonchromogenicum, M. xenopi, M. malmoense, M. szulgai, M. scrofulaceum, M. fortuitum, M. gordonae, M. intracellulare, M. simiae, M. flavescens, M. paratuberculosis, M. sphagni, M. cookii, M. komossense, M. phlei, and M. farcinica. On the basis of the defined oligonucleotides, the polymerase chain reaction technique was explored to develop a sensitive taxon-specific detection system for mycobacteria. By using M. tuberculosis as a model system, fewer than 10 bacteria could be reliably detected by this kind of assay. These results suggest that amplification of rRNA sequences by the polymerase chain reaction may provide a highly sensitive and specific tool for the direct detection of microorganisms without the need for prior cultivation.

Base Sequence↗

PubMedDate not supplied

Outcome of peripheral blood stem cell mobilization in advanced phases of CML is dependent on the type of chemotherapy applied.

High-dose chemotherapy with autologous transplantation of in vivo purged PBSC is a novel investigational approach to treating chronic myelogenous leukemia (CML) patients not responsive to conventional therapy with interferon-alpha (IFN-alpha) and not eligible for allogeneic transplantation. PBSC mobilization using either '5+2/7+3'-type chemotherapy or 'mini-ICE/ ICE' chemotherapy was investigated in 43 patients with advanced phases of Philadelphia (Ph)-positive CML. Thirty patients were in late chronic phase (>12 months post diagnosis) and 13 patients in accelerated phase (AP) or blast crisis (BC). Contamination with Ph-positive cells was evaluated in harvests from 37/43 patients. The outcome of PBSC mobilization was dependent on the type of chemotherapy administered: a complete or major cytogenetic response (<35% Ph-positive metaphases) in leukapheresis collections was obtained in ten of 15 patients treated with 'mini-ICE/ICE' but in only three of 28 patients treated with '5 + 2/7 + 3' chemotherapy. One patient (1/43) in blast crisis died during mobilization therapy (2%). Twenty-five patients underwent PBSC transplantation and all of them engrafted successfully. Transplantation-related mortality was 0%. The data show that in advanced phases of CML the chance of harvesting Ph-negative peripheral blood stem cells depends on the type of chemotherapy used for mobilization.

Adult↗

PubMedDate not supplied

Accuracy of density measurements within plaques located in artificial coronary arteries by X-ray multislice CT: results of a phantom study.

PURPOSE: Clinical studies indicate that coronary plaque morphology might be differentiated noninvasively using multislice CT by determining tissue density within the lesions. The aim of the present experimental study was to evaluate factors that influence density measurements within small vessels. METHOD: A coronary phantom model was developed, consisting of silicon tubes (lumen diameter 4 mm) with two plaques of known density inside, simulating soft and intermediate lesions (Plaque 1: -39 HU; Plaque 2: 72 HU). Density measurement were conducted in three different contrast medium concentrations (1:30, 1:40, 1:50) and two different slice widths (4 x 2.5 mm, 4 x 1 mm). All scans were performed on a Somatom Volume Zoom (Siemens, Forchheim, Germany). Experimental results were compared with calculated data based on computer simulation. RESULTS: The two plaques could be clearly differentiated from each other on both collimations (4 x 2.5 mm: Plaque 1, 85 +/- 61 HU vs. Plaque 2, 119 +/- 26 HU, p < 0.0001; 4 x 1 mm: Plaque 1, 50 +/- 54 HU vs. Plaque 2, 91 +/- 17 HU, p < 0.0001). Significantly lower and more accurate results were achieved with 1.0 mm collimation (p < 0.0001). Contrast medium concentration contributed significantly to the measurements (p < 0.001). The experimental findings were confirmed by computer simulation, which revealed even more accurate results when using a 0.5 mm collimation (Plaque 1, 0.5 mm: -9 HU vs. 4 x 1 mm: 14 HU, Plaque 2, 4 x 0.5 mm: 83 HU vs. 4 x 1 mm: 93 HU). CONCLUSION: Density measurements were found to be highly dependent on slice width and surrounding contrast enhancement. Our results indicate that standardization of methodology is required before the noninvasive differentiation of human plaque morphology by multislice CT can be applied in the clinical setting as a screening test for coronary soft plaques.

Analysis of Variance↗

PubMedDate not supplied

Heart rate adaptive optimization of spatial and temporal resolution for electrocardiogram-gated multislice spiral CT of the heart.

PURPOSE: We introduce a reconstruction method for electrocardiogram (ECG)-gated multislice spiral computed tomography (CT) examinations of the heart [adaptive cardio volume (ACV) reconstruction]. It is evaluated for a four-slice CT system (Siemens Somatom VolumeZoom). METHOD: State-of-the-art reconstruction techniques for ECG-gated multislice spiral CT use scan data from N consecutive heart cycles for image reconstruction. With increased N, the temporal resolution improves up to t rot /(2 N ) ( t rot is the 360 degrees rotation time of the scanner) but at the expense of insufficient volume coverage or loss of longitudinal resolution, especially at low heart rates. With the ACV technique, the number N of consecutive heart cycles used for image reconstruction is automatically adapted to the momentary heart rate of the patient, ranging from N = 1 at very low heart rates up to N = 3 at high heart rates, to maintain both high z resolution (reconstructed slice width close to the collimated slice width) and adequate temporal resolution. We evaluated slice sensitivity profiles and investigated 10 patients with different heart rates ranging from 55 to 110 beats/min for CT angiography (CTA) studies of the coronary arteries and compared the results with those from a reconstruction with fixed N ( N = 1 and N = 2). Axial images as well as multiplanar reformations were used for an evaluation of image quality. RESULTS: With the ACV approach, the complete heart may be scanned at 1 mm slice width within 25-35 s. A narrow slice sensitivity profile (full width at half-maximum of approximately 1.3 mm) is maintained for all heart rates. Diagnostic results can be obtained for heart rates up to about 95 beats/min by individual patient optimization of the ECG gating parameters. Improved temporal resolution at the expense of reduced longitudinal resolution may degrade the image quality of CTA studies at low heart rates by blurring plaques and stenoses. CONCLUSION: The results indicate the potential of the ACV reconstruction technique for high-resolution coronary CTA in a wide range of heart rates.

Algorithms↗